Welcome to a New Medicine Website!

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This is a new medicine website that critically reviews all aspects of medicine on an ongoing basis, provides basic and important information for the public and experts. This is not a website, just repeating the current knowledge in different disciplines of medicine, but critically reviews the shortcomings with proposals for revisions in the medical diagnostics, treatment, prevention and suggestions for the future research in each topic. Unfortunately medicine that has been in existence since the antiquity, it has not evolved as much a the other field of science, perhaps for not being profitable for capitalism to invest sufficiently in the health of their people as much as other industries. Hopefully this website along others as such would open the path to the future of medicine, where prevention of diseases will be the primary agenda so humans can enjoy the best of health and not being the subjects of profit making for entrepreneurs, hence fulfill the Hippocratic oath “preserve the purity of my life and my arts.”!

Throughout the history, humans have been able to discover and invent mainly through right questioning and critic, that is the purpose of this website.  Whenever we have followed an idea or belief rigidly, then we were stuck in dogma and any progress had stagnated,like many centuries of dark ages before the scientific revolution.  Through right questioning and critic of our current knowledge in medicine, this site will revisit the field and will attempt to bring on new perspectives on different medical conditions. 

Dr. Mostafa Showraki, MD, FRCPC                                                                       Lecturer, School of Medicine, University of Toronto                                        Author: ADHD:Revisited Book Adhdrevisited.com/medicinerevisited.com       

*All the contents of this website is copyright protected under the international law and registered with the Canadian intellectual property office and cannot be copied, including many new ideas, concepts, proposals and terminologies used throughout its articles, without the author’s permission and mentioning the references.

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You care about the demise of our being before we extinct not by our wars or earth collision by asteroids or else, but by microbial invasions who have ruled the earth for billions of years!                          Mostafa Showraki

The only good is knowledge and the only evil is ignorance. Socrates

 All truths are easy to understand once they are discovered; the point is to discover them. Galileo Galilei

Perfect as the wing of a bird may be, it will never enable the bird to fly if unsupported by the air. Facts are the air of science. Without them a man of science can never rise. Ivan Pavlov

Synopses:                                                                                                                           Summary and easy read of lengthy articles that you can find under “Synopses” above in the home menu bar

Coming soon:

Longevity:  Could we determine how long one will live?

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COVID: Denial, Protest, Depression, acceptance and Resolution

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Introduction:

The above title refers to the mental stages of loss, or any interruption in one’s wellbeing that could be any illness. This that could relate also to COVID at a global level, starts with “denial” that the whole world tried at the start to deny it, though some group still do for not believing in the existence of the virus or other conspiracy theories. The second stage of any loss or illness (that’s loss of health) is “protest” against the situation as someone who gets upset and angry when is informed to have a cancer. This stage for COVID appeared more in the form of anxiety and panic at a global and governmental level. The third stage is “depression” when the individual gives up his denial, protests and indeed gives in and becomes depressed and panicky as he sees the end of the tunnel, as it happened globally over the current pandemic. The fourth stage is “acceptance” when the person accepts the loss or the illness and seeks help and treatment. The final stage is “resolution” when the individual even if there is not much hope for survival or treatment as for example in the case of cancers and terminal and grave diseases, comes to acceptance of the fact and the vulnerability and fragility of us as living beings. Not every individual or groups will pass through every five stages normally, but some would get fixated or stuck on one stage and cannot move on to the final stages of acceptance and resolution (1). The final two stages have not yet happened globally to us humans, due to our ignorance and foolish grandiosity thinking that we are able even to defeat the nature. This sad fact was well manifested itself in grandiose and ignorant speech of the former US president, Donald Trump who at the onset of the pandemic, thought the corona virus is like his states’ enemies, for true or false whom he could mass murder with his mighty military power.

As already detailed in this site from the start of the pandemic that we as humans should know better than the rest of un-intelligent animal world about “symbiosis” and living together with other species including viruses and other microbes. After over a year of panic, pandemic, misery and lockdowns, even if we succeed in vaccinating almost everyone globally, the coronavirus on its own or mutant variants may still invade us and causes casualties. The past century and at least with one well know example of Influenza virus with several epidemics of its different mutant variants, and our futile defense efforts in vaccinations, should have thought us better to come to terms with the unstoppable force of symbiosis and endosymbiosis and live in peace with the microbial world for a better ecosystem of our beloved planet. In the following to spell the facts more clearly for the fools and ignorant specially the governments, our past century lesson experience from Influenza virus will be summarized.

The Influenza Virus Lesson:

The three types of Influenza viruses A, B, and C, and D were first isolated in 1933, 1940, 1947 and 2011 respectively (2-5). Influenza A viruses that are the most common pathogens in humans with a wide variety of mutations and subtypes will be the centerpiece of discussion here. Influenza B is exclusively a human pathogen and share with only another animal, seal, but since it is less common and less virulent, so far it is not a subject of attention. Influenza C infests humans and pigs and can cause severe illness and local epidemics with mild diseases in children. Influenza D, the new discovery and addition to the class of influenza viruses in 2011, has been around for several hundreds years when diverged from influenza C (2-7).

Influenza virus A, the most common and virulent of influenza viruses in humans has been subtyped according to the antigenic and genetic nature of their surface glycoproteins; 15 hemagglutinin (HA) and 9 neuraminidase (NA) subtypes have been identified to date. Only viruses of the H1N1, H2N2, and H3N2 subtypes have been associated with widespread epidemics in humans. The successful virulence of influenza viruses is primarily due to antigenic variation that takes place in the two surface glycoproteins of the virus, the HA and NA. Antigenic variation through point mutations in the HA and NA genes (antigenic drift) renders an individual susceptible to new strains despite previous infection by influenza viruses or previous vaccination (8).

With a few notable exceptions, influenza infections in avian hosts are asymptomatic and limited to the gastrointestinal and/or the respiratory tract (9). Influenza viruses infecting these hosts appear to be in evolutionary stasis compared with those infecting humans (10). In contrast with COVID that its mortality is mostly in elderly, the influenza-related deaths hold a 20-fold increase in younger population under age 65 during its epidemics and pandemics. Global influenza surveillance indicates that influenza viruses are isolated every month from humans somewhere in the world. In temperate regions, its peaks during the winter months, while in the northern hemisphere, it typically occurs between November and March, whereas in the southern hemisphere, between April and September and in tropical regions, it can occur throughout the year (11). The constant antigenic variations or mutations of influenza virus keep replacing its predecessor such that the co-circulation of distinct antigenic variants of a given subtype occurs for relatively short periods (12-13).

During an epidemic, overall attack rates of the influenza virus has been estimated to be 10–20%, but in certain susceptible populations such as schoolchildren or nursing home residents, attack rates could reach as high as 40–50%. Studies conducted during both pandemic years and interpandemic periods demonstrate that age-specific attack rates are often highest among schoolchildren (14-15). The Spanish Influenza virus type A H1N1 of 1918-1919, reached nearly 40% attack rated among schoolchildren in the United States and a mortality rate of about 40%, among all age groups including young age ranges (16-17). The Spanish flu infected 500 million people globally, about a third of the world’s population at the time in four successive waves with a death toll between 20 to 50 million, although there are estimates of up to 100 millions, and is knows as the deadliest pandemic of all time (18).

The Asian influenza pandemic of 1957-1958 in China spread province to province, then to Singapore and Hong Kong (19). The causative agent, an influenza A H2N2 virus, was first isolated in Japan in May 1957. This pandemic later on through a second wave in the summer and fall of 1957 spread to the United Kingdom and the United States, followed by a third wave in January 1958 and caused high mortality. The highest attack rates during this pandemic of 50%, occurred in children aged 5–19 (14). The 1968 Hong Kong Influenza pandemic of type A H3N2 soon spread to the United States during the winter of 1968–1969, but in some other countries, including the United Kingdom, an epidemic did not occur until the winter of 1969–1970, with an attack rates as high as 40% among 10- to 14- year-old children. Though not considered a true pandemic, the reemergence of influenza A H1N1 viruses in 1977, started from China soon spread to other parts of Asia and reached Russia by November 1977, then spread to Europe, North America, and the Southern Hemisphere with an attack rates of over 50% among school aged children and young population under age 20 (19).

 In May 1997, a new strain H5N1 of influenza A virus was isolated from the tracheal aspirate of a three-year-old child in Hong Kong that first could not be subtyped using the World Health Organization (WHO) reagents prepared against circulating strains of influenza A H1N1 and H3N2 viruses, but was subsequently identified as an H5N1 virus by the National Influenza Center in Rotterdam, The Netherlands (20). Six months later, 17 additional human H5N1 infections were identified in hospitalized patients in Hong Kong over a seven-week period with an age range of 1 to 60 years with 1/3 mortality rate. This incident established for the first time that the virus from was hosted in chickens could cause an outbreak of disease in humans without passing through an intermediate host (21-22). Two years later in March 1999, another new strain of the influenza A virus that later on was subtyped as H9N2 was again isolated in Hong Kong from two children with self-limiting febrile upper respiratory infections. This new strain was shown again to have spread from chickens to humans (23-24).

Conclusion:

Influenza type A has already been identified with the following major subtypes:

  • H1N1 as the cause of Spanish flu pandemic and 2009 swine flu pandemic
  • H1N2 as endemic in pigs and a few human cases.
  • H2N2 as the cause of Asian flu of 1957-58.
  • H3N2 the cause of Hong Kong flu in of 1968-69.
  • H5N1 as the cause of the global pandemic in mid-2000s.
  • H5N2 as the cause of infecting a few farmers in Japan in 2006.
  • H5N9 as a highly pathogenic strain of a minor flu outbreak in 1966 in Ontario and Manitoba in turkeys.
  • H5N2 as the cause of infecting a few farmers in Japan in 2006.
  • H7N2 as the cause of infection of two individuals Virginia and New York in 2002 and 2003.
  • H7N3 identified in several poultry farms in British Columbia in 2004 with two cases of human infections.
  • H7N7 with an unusual zoonotic potential was identified in several poultry farms in Netherlands with infections in 89 people in 2003.
  • H7N9 with the greatest potential for an influenza pandemic among all other subtypes has been identified in Hong Kong in 2013 with three infected cases.
  • H9N2 a low pathogenic variant identified first in 1999 in China and Hong Kong infecting two children and one in 2003.
  • H7N9 with the greatest potential for an influenza pandemic among all other subtypes has been identified in Hong Kong in 2013 with three infected cases.
  • H10N7 a subtype reported the first time in Egypt infecting two infants in 2004.
  • H10N3was identified most recently in May 2021 in china, infecting one individual (25-26).

 As we see the influenza virus type A in comparison with COVID is a “bad virus” due to its higher mortality rate and fatalities across life span and young age groups. If we also pay attention, influenza virus A infections over a century has mainly caused local epidemics and in case of pandemics such as Spanish flu, it only affected Europe mostly with a thin spread to the North America. In the case of Spanish flu that before COVID has been labeled the deadliest humans’ pandemic, it spread across Europe at the time of the first world war, due to poor hygiene and sanitation in the trenches and war fields, otherwise its mortality could have been much less. Nevertheless as discussed, the mortality rate of influenza A is much higher than COVID, while this coronavirus has a much higher virulence rate, infecting more population but killing less. Still influenza A and COVID are less lethal that “ugly viruses” such as AIDS and HPV with minimum mortality rate of over 50% up to 100%.

The other major lesson to learn from the influenza over a century of infecting humans for application to the case of the current COVID pandemic is the fact and rate of the mutations that all viruses do that make fighting against them and vaccinations futile. Moreover it is good to know that the nature and evolution is an upward process for the survival of living beings on our planet. As a rule the ugly and bad viruses even if they invade us, since they are going against uptrend of evolution and survival, they will be localized in their spread in the numbers and geographical locations. The bad and ugly viruses also down the road will be destroyed by our immune system for the evolutionary survival purposes. In a better word, the nature takes care of itself and the good viruses such as COVID enter in our system for fostering our immune armamentarium. In biology and virology this fact has been known for decades that our immune system apparatus and even our cellular organelles such as interferon and our genome are basically made of good viral insertions.      

 Lastly a lesson if to be learned, it is learnt once as repetition does not make fools understood at all.

Dr.Mostafa Showraki, MD, FRCPC

Lecturer, School of Medicine, University of Toronto

References:

  1. Kübler-Ross E (1969). On Death and Dying. Routledge. ISBN 0-415-04015-9.
  2. Cox NJ, Subbarao K. Global epidemiology of influenza: past and present. Annu Rev Med. 2000;51:407-21. 
  3. Smith W, Andrewes CH, Laidlaw PP. 1933. A virus obtained from influenza patients. Lancet ii:66–88 2.
  4. Francis TJ. 1940. New type of virus from epidemic influenza. Science 91:405–8.
  5. Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. 2004. Isolation of a novel swine influenza virus from Oklahoma in 2011 which is distantly related to influenza C viruses. PLOS Pathogens. 9(2):e1003176.
  6. Matsuzaki Y, Sugawara K, Mizuta K, Tsuchiya E, Muraki Y, Hongo S, Suzuki H, Nakamura K 2002. Antigenic and genetic charachterization of influenza C viruses which caused two outbreaks in Yamagata City, Japan in 1996 and 1998. I Clin Microbiol. 40(2):422-29.
  7. Collin EA, Sheng Z, Lang Y, Ma W, Hause BM, Li F. 2015. Cocirculation of two distinct genetic and antigenic lineages of proposed influenza D virus in cattle. J Virol. 89(2):1036-1042.
  8. Fitch WM, Bush RM, Bender CA, et al. 1997. Long term trends in the evolution of H(3) HA1 human influenza type A. Proc. Natl. Acad. Sci. USA 94:7712–18.
  9. Webster RG, Yakhno M, Hinshaw VS, et al. 1978. Intestinal influenza: replication and characterization of influenza viruses in ducks. Virology 84:268–78 6.
  10. Bean WJ, Schell M, Katz J, et al. 1992. Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts. J. Virol. 66:1129–38.
  11. Simonsen L, Clarke MJ, Schonberger LB, et al. 1998. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J. Infect. Dis. 178:53–60.
  12. Cox NJ, Brammer TL, Regnery HL. 1994. Influenza: global surveillance for epidemic and pandemic variants. Eur. J. Epidemiol. 10:467–70 29.
  13. Cox NJ, Regnery HL. 1996. Global influenza surveillance: tracking a moving target in a rapidly changing world. In Options for the Control of Influenza III, Cairns, Australia, ed. LE Brown, AW Hampson, RG Webster, pp. 591–98. Amsterdam: Elsevier.
  14. Glezen WP. 1982. Serious morbidity and mortality associated with influenza epidemics. Epidemiol. Rev. 4:25–44 32.
  15. Glezen WP. 1996. Emerging infections: pandemic influenza. Epidemiol. Rev. 18:64–76.
  16. Frost WH. 1919. The epidemiology of influenza. JAMA 73:313–18 37.
  17. Walker OJ. 1919. Pathology of influenza pneumonia. J. Lab. Clin. Med. 5:154–75.
  18. Spreeuwenberg P, Kroneman M, Paget J. 2018. Reassessing the global mortality burden of the 1918 Influenza pandemic. American Journal of Epidemiology. 187 (12): 2561-2567. 
  19. Stuart-Harris CH, Schild GC, Oxford JS. 1985. Influenza. The Viruses and the Disease, pp. 118–38. Victoria, Can.: Edward Arnold. 2nd ed.
  20. de Jong JC, Claas EC, Osterhaus AD, et al. 1997. A pandemic warning? [letter]. Nature 389:554.
  21. Subbarao K, Klimov A, Katz J, et al. 1998. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279:393–96.
  22. Mounts AW, Kwong H, Izurieta HS, et al. 1999. Case-control study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997. J. Infect. Dis. 180:505–8.
  23. Periris M, Yuen KY, Leung CW, et al. 1999. Human infection with influenza H9N2. Lancet 354:916–17 53.
  24. Guan Y, Shortridge KF, Krauss S, Webster RG. 1999. Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong? Proc. Natl. Acad. Sci. 96:9363–67.
  25. Komadina N, McVernon J, Hall R, Leder K. 2014. A historical perspective of influenza A H1N2 virus. Emerg Infect Dis. 20(1): 6–12. 
  26. Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. 2004. Mapping the antigenic and genetic evolution of influenza virus. Science. 305 (5682):371-6. 
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Unconscious: Revisited

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Introduction:

Unconscious, the bread and butter of Psychoanalysis, that has widely believed to have been started its inception in the literature by Sigmund Freud at the end of 19th century, it has been indeed coined by the German philosopher Friedrich Scheeling in 18th century. Probing into the history, in fact, unconscious has been known in the scientific arena long ago and in the written materials, as early as 16th century by Paracelsus, a Swiss physician. William Shakespeare has also explored the unconscious in some of his plays very well, and other philosophers such as Schopenhauer, Spinoza, Leibniz, Hegel, Kierkegaard and Nietzsche have discussed the subject.   Indeed Nietzsche in his “Thus Spake Zarathustra” who wrote between 1882 to 1885, not just describes the unconscious (soul/spirit), but the ego and the Self while making a clear distinction between them. “body am I entirely, and nothing more; and soulis only the name of some thing in the body…Ego, sayest thou, and are proud of that word. But the greater thing in which thou art unwilling to believe is thy body with its big sagacity…Instruments and playthings are sense and spirit; behind them there is still the Self. The Self seeketh with the eyes of the senses, it hearkenth also with the ears of the spirit…It ruleth, and is also the ego’s ruler. Behind the thoughts and feelings, my brother, there is a mighty lord, an uknown sage, it is called Self…” He even goes beyond what a century later Freud, the inventor of psychoanalysis discussed, and talks about self-esteem that’s a significant psychological core nowadays. “The creating Self created for itself esteeming and despising, it created for itself joy and woe”.    

 In psychology even Freud has not been the first one to address the topic, but the American psychology and philosopher, William James in his treatise, “The Principles of Psychology” examined the unconscious and subconscious. In fact Freud was influenced by the French Jean-Martin Charcot, a neurologist like Freud, who treated his hysterical patients with hypnosis and reached their unconscious minds. This influence drew Freud from neurology to hypnosis, then the world of unconscious and his following theories of compartmentalization of conscious to “ego”, and unconscious into “id” and “superego”, then “repression” of unacceptable ideas, wishes, traumatic memories and painful emotions by the conscious into unconscious. Freud used his “Interpretation of dreams” at the turn of the 20th century and later on his technique of “Free association” by laying down the patients on his psychoanalytic couch, that became the bread and butter of the future analysts, to reach their patients’ hidden worlds so to cure them.

Freud with all his generalization to expand his theories did not go farther than discussing “neuroses” and treating neurotic and hysterical patients. But the Swiss Carl Gustav Jung, another psychiatrist, who initially had the aspiration of becoming a preacher or minister and later on study archaeology and later on mesmerized by the unconscious, brought his original interest in spirituality and mythology into his psychology. Although psychoanalysis like any other non-scientifically based ideas did not pass the test of time and is almost obsolete in our era, this paper analyzes the Jungian psychology that not for its implication in clinical psychological/psychiatric practice, as it is rarely used nowadays, but for its grandiose generalization beyond the field into culture, philosophy, arts, anthropology and so on. “Man and his Symbols” written by Jung and a few of his immediate associates just before his death that published a few years after, and contains most of his ideas is the subject of this analysis. 

Jungian Psychology: Back to the ancient mythological psychic reading

Read the Full text here:

Unconscious: Revisited

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Living with Coronavirus in Peace and no Panic

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(Hope the authorities across the globe read this paper and change their course of actions)

(Please read and if agreed pass around to the world due to the urgency of the situation)

Introduction:

The new coronavirus that is now popular with the title of COVID-19 around the world and boasting in spreading at a pandemic level, causing more panic than killings, is the seventh in the line of the class of coronaviruses. This family of viruses head by the common cold or flu virus that has lived in symbiosis with humans for long, and had never caused fatalities and created panic in us. Viruses such as Coronaviruses that have lived for billions of years, much longer than any other beings on the earth keep evolving for survival. This is more true for RNA viruses such as Coronaviruses that depend on hosts to survive, due to lack of DNA for independent living. So on the path of their evolution for survival, they evolve in different types invading the hosts like humans. SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) that hit humans’ population a few years ago before COVID-19 are other types of Coronaviruses. In fact the outbreak of Coronaviruses in different forms over the past several years is a good indicator that these viruses are pushing for survival and coevolution now within the human hosts (1-7).

 In this article I discuss the wise option of living with Coronaviruses in peace with no panic and resistance. This contention that might surprise many is not new in the nature as living in peace or “symbiosis” among the living creatures from plants, animals, bacteria and viruses to us humans have been a rule and part of the law of survival than exception. This has been well known in the scientific and medical circle that I will refer to here, though a call for a peace with the microbial invasions have not been forthcoming yet. The symbiosis between two livings could be obligatory or facultative (optional) that could be different on each side of the equation or relationship. For example in the case of microbes and viruses, the symbiosis on their parts is obligatory as they cannot survive without the hosts, but is optional on the hosts part to let them in or fight back and being killed.

Symbiosis and Endosymbiosis:

Symbiosis, a Greek word meaning “living together”, is any type of close and long-term biological relationship, interaction and dependency between two biological organisms in a mutualistic, commensalistic or parasitic manner. Endosymbiosis or living inside of the tissues of the hosts that most microbes, such as bacteria and viruses do, including many bacteria already living in peace within us, e.g. in our digestive system, assists with our normal living. A peaceful and healthy endosymbiosis in fact leads over time to reduction of the genome size and power of the invader or endosymbiont and lower its fatality due to the adaptation with the host. This has been a vital part of “co-evolution” in nature on earth since its living inception. In fact eukaryotes, the origin of plants, fungi and animals like us all have evolved through this symbiogenesis. Mitochondria, chloroplasts and other cellular organelles that divide and replicate independent of the cells in living creatures like us is an obvious example of such evolutionary endosymbiosis. In fact the notion of Darwinism based on competitive survival has been replaced in the modern scientific arena to the cooperative and symbiotic evolutionary survival (8-10).

Read the full text here:

LIVING WITH CORONAVIRUS IN PEACE AND NO PANIC

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Brain Tumors: When our most precious organ is invaded

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Introduction:

Like other cancers, brain tumors could be benign or malignant, primary starting in the brain or secondary, metastasized from elsewhere. The brain tumors also could arise from its outside covering or meninges or from its own brain matter, which consists of grey (neurons) and white (glia cells). Half of the brain tumors are gliomas and about 8% of myelin or nerve sheath, both of white matter, over 20% meningiomas, 15% of Pituitary adenomas and only over 5% from the brain or grey matter tissue. The cause of most brain tumors are yet unknown and the genetic cases such as neurofibromatosis, tuberous sclerosis are very rare (2). This leaves epigenetic factors such as radiation and microbial invasions as the principal causative agents that will be the main focus of this article.

For over a century the medical field has been well aware of infesting cysts throughout the body that anchor in different tissues and organs including the brain, where hydatid cysts have been reported in the brain as primary and secondary target (3-5). Other than hydatid cysts that caused by parasitic tapeworms getting into humans from intermediate hosts (e.g. sheep, goats) and definite hosts (e.g. dogs), other microbial, fungal and viral infections such as tuberculosis and mycosis have been reported as different cysts and cystic tumors in the different parts of the brain since over a half century ago (6-7). Although majority of the microbial brain invasions are limited to the defensive wall (cover) of the brain or meninges or in the viral cases only causing a generalized encephalitis, some aggressive ones rise to create cysts and tumors often malignancies.

In their frontier and heroic study, Schuman, Choi and Gullen showed that the parasitic toxoplasma gondii infection that simply passes to humans from domestic chickens and other fowls could be the causative agents of several brain tumors. Investigating 171 primary central nervous system neoplasms over 18 months period in 1963-1964 from four Minnesota’s hospitals, they traced down the pathogenic routes of several cases of gilomas, acoustic neuromas, neurofibromatosis, mengiomas, pituitary tumors, craniopharyngiomas and miscellaneous brain tumors back to toxoplasmosis infestations (8).    

Finn, Ward and Mattison in 1972 reported previous tuberculosis infection in a quarter of 26 patients with cerebral gliomas (9). This group a year later to replicate their surprised finding, noted previous tuberculosis infection in 21.7% of 92 patients with cerebral gliomas compared with only 7% of 100 controls (10). Such association between previous tuberculosis and cerebral gliomas were replicated later on and in larger samples by others (e.g. 11). Of viral invasion causing brain tumors, Copeland and Bigner in 1977 inoculated an avian sarcoma virus in the brain of rats at different ages and showed 100% causation of brain tumors, with higher such chance at earlier age of inoculation (12). Similar result in rats was published a year later by Roszman, Brooks, Markesbery and Bigner who showed a parallel immunological suppression by the virus between rats and humans (13). Soon other viruses such as Herpes virus were also shown to be causative agents of different brain tumors in animal studies (e.g. 14).

A decade later in 1987, Corallini and colleagues demonstrated the presence of BK virus DNA in 25.6% of human brain tumors of 74 patients and 44.4% in 9 patients with pancreatic islets tumors (15). BK virus that is widespread worldwide except for isolated regions of Brazil, Paraguay, and Malaysia in its primary invasion or infection is mild and unapparent, manifesting generally as mild respiratory or urinary tract infections. During its primary invasion, the virus through blood spreads to several body organs and remains in a dormant state. The reactivation of virus to cause more damages and tumors across different organs occur upon immunological impairment (16-17). While the brain tumors have been reported to be the more common neoplasms caused by this virus (18-21), bone tumors, insulinomas, Hodgkin’s Lymphoma, Kaposic’s Sarcoma and urinary tract tumors have also been reported (e.g. 22-23). Other viruses such as human JC virus and HIV have also been reported causing brain tumors in animal and human studies (e.g. 24-26).

Soon the idea of vaccination therapy for brain tumors such as malignant gliomas started to grow and have an application. Different viral-mediated (Herpes Virus, Rertovirus, Adenoma Virus, and Epstein Barr Virus) gene therapy started to be applied effectively in animal then clinical studies as vaccinations (27-34). In the recent years the gene or vaccination therapy has progressed so that even RNA-binding and other gene proteins instead of viral vectors have been used in the treatment of different brain tumors such as medulloblastomas in children (e.g.35-36). Altogether these gene therapies in the cancer treatment research filed is known as Suicide gene therapy (SGT), as the brain tumor cells are killed and suppressed in growth (37).

Conclusion:

Even our precious brain with its defensive blood-brain barrier that protects our brains from many toxins and invasions, is not immune and exempted from the microbial invasions. From simple and acute brain infections such as meningitis and encephalitis to longer processes of developing tumors in different part and layers of the brain, microbes are the offending agents. From the tinniest viruses such as BK virus with unapparent and mild primary generalized body infection like a flu to the largest such as tapeworms all invade every parts of our being including our precious brain.

 Knowing the microbial invasions underlying brain tumors for almost a century, but calling the cause of these malignancies as idiopathic (unknown) in the official medical textbooks and literature is ignorance. Acknowledging the underlying pathogenesis of brain tumors by microbial invasions holds the vital promise of prevention and early intervention and right treatments. For example monitoring patients with past history of tuberculosis infections, we could identify and save a quarter of them from developing tuberculomas and gliomas. Also identifying and monitoring other viral, bacterial, fungal or even parasitic infections could prevent or early detect development of different brain tumors caused by these insulting agents.

Finally it has been the diligent observations of some medical scientists into the underlying pathogenesis of brain malignancies by microbes that has led to the recent developments of different viral-mediated or RNA- and related protein-mediated vaccines for the treatment of different brain tumors. In fact these novel treatments cleverly have used the microbial invasion strategies at the service of defense and treatment.

Dr.Mostafa Showraki, MD, FRCPC

Lecturer, School of Medicine, University of Toronto

Author: ADHD: Revisited Book, Amazon Kindle Books

www.adhdrevisited.com/www.medicinerevisited.com


Reference:

  1. World Cancer Report (2014). World Health Organization.
  2. Hodgson TS, Nielsen SM, Lesniak MS, Lukas RV (2016). “Neurological Management of Von Hippel-Lindau Disease”. Neurologist (Review). 21 (5): 73–78.
  3. Dew HR (1928). Hydatid Disease. Surg. Gynec. Obstet. 59, 321.
  4. Langmaid C, Rogers L. (1940). Intracranial Hydatids. Brain. 63: 184.
  5. Phillips G. Primary cerebral hydatid cysts. J Neurol Neurosurg Psychiatry. 1948;11(1):44–52.
  6. Iwata K, Wada T. Mycological studies on the strains isolated from a case of chromoblastomycosis with a metastasis in central nervous system. Jpn J Microbiol. 1957 Oct;1(4):355-60.
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  9. Finn R, Ward DW, Mattison ML. Immune suppression, gliomas, and tuberculosis. Br Med J. 1972;1(5792):111.
  10. Ward DW, Mattison ML, Finn R. Association between Previous Tuberculous Infection and Cerebal Glioma. Br Med J. 1973;1(5845):83–84.
  11. Macpherson P. Association between previous tuberculous infection and glioma. Br Med J. 1976;2(6044):1112.
  12. Copeland DD, Bigner DD. Influence of age at inoculation on avian oncornavirus-induced brain tumor incidence, tumor morphology, and postinoculation survival in F344 rats. Cancer Res. 1977 Jun;37(6):1657-61.
  13. Roszman TL, Brooks WH, Markesbery WR, Bigner DD. General immunocompetence of rats bearing avian sarcoma virus-induced intracranial tumors. Cancer Res. 1978 Jan;38(1):74-7.
  14. Adler R, Glorioso JC, Cossman J, Levine M. Possible role of Fc receptors on cells infected and transformed by herpesvirus: escape from immune cytolysis. Infect Immun. 1978 Aug;21(2):442-7.
  15. Corallini A, et al. Association of BK virus with human brain tumors and tumors of pancreatic islets. . Int J Cancer. 1987 Jan 15; 39(1):60-7.
  16. Brown P, Tsai T and Gajdusek DC. (1975). Seroepidemiology of human papovaviruses. Discovery of virgin populations and some unusual patterns of antibody prevalence among remote peoples of the world. Am. J. Epidemiol.,102,331–340.
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  19. Martini F, et al. (1996). SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. Cancer Res.,56,4820–4825.
  20. De Mattei M, et al. (1994). Polyomavirus latency and human tumors.J. Infect. Dis.,169,1175–1176.
  21. De Mattei M, et al. (1995). High incidence of BK virus large-T-antigen-coding sequences in normal human tissues and tumors of different histotypes. Int.J. Cancer,61,756–760.
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  24. Wold WS, Green M, Mackey JK, Martin JD, Padgett BL, Walker DL. (1980) Integration pattern of human JC virus sequences in two clones of a cell line established from a JC virus-induced hamster brain tumor. J Virol. 33(3):1225-8.
  25. Nagashima K, Yasui K, Kimura J, Washizu M, Yamaguchi K, Mori W. (1984). Induction of brain tumors by a newly isolated JC virus (Tokyo-1 strain). Am J Pathol. 116(3):455-63.
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  29. Kramm CM, et al. (1995). Gene therapy for brain tumors. Brain Pathol. 1995 Oct;5(4):345-81.
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Autoimmune Disorders: Relapsing-Remitting Vs. Progressive

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Introduction:

The majority of autoimmune disorders like cancers are progressive and fatal. The exceptions seem to be only autoimmune demyelinating disorders and its most common type, Multiple Sclerosis (MS) that in majority of cases have a relapsing-remitting course and a better prognosis. Although MS at the onset could manifest as a clinically isolated syndrome, it soon takes the form of either relapsing-remitting or progressive (primary). Later on in the course of illness a minority of the relapsing-remitting MS (RRMS) may change its course to progressive and poor prognosis and this group is classified secondary progressive MS (SPMS) against the primary progressive MS (PPMS) that has a progressive course from the onset (1)

 Unfortunately it has not yet been sufficiently questioned and studied why MS and other similar autoimmune demyelinating disorders possess could have a relapsing-remitting course and a better prognosis, while the nature of autoimmune disorders are generally progressive with morbidity and mortality. Autoimmune disorders that like cancers as detailed in other articles on this site are the results of microbial invasions, and no microbes such as bacteria or viruses invade our beings to fool around, remit and relapse. So then why if autoimmune demyelinating disorders such as MS are also the byproducts of microbial invasions such as EBV (Epstein Barr Virus), have a remission and relapse course while the invasion targets our most precious organ, the brain. In fact the answer when probe to it well lies in our brain, not the invaders. It’s the brain that protects itself and fights back against the invasion and strives to undo the damage. This interesting fact that so far seems to happen only in the brain and at least to the myelin sheaths of the brain is a very new discovery in the very recent years. But this has not yet been applied in the explanation of the relapsing-remitting course of autoimmune demyelinating disorders such as MS, and this article could be the first.

The Brain fights back:

While the great majority of brain cells are essentially stable throughout life, oligodendrocyte precursor cells (OPCs) that generate new oligodendrocytes hence new myelin sheaths have been observed widespread in the brain even in adult life (2). The myelin or myelin sheaths that cover the nerve cell axons act as the nervous system wires for the conduction of information from one neuron to the other, or one area of the brain to the other. The white matters or the highways of the brain are basically made of the myelin and myelin sheaths that are the targets of microbial invasions in the autoimmune demyelinating disorders such as MS. Generally the process of myelination or the generation of myelin and myelin sheaths that start early in the third trimester, continues throughout adolescence and early adult life that contribute and correspond to the continuation of the general brain development until mid-20s (3). The reason or need for the long development of the brain through ongoing myelination is building its widespread communication infrastructures for learning, skills developments and other higher cortical functions that create cognitive and skills maturity.  

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Autoimmune Disorders: Relapsing-Remitting Vs. Progressive

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Reactive Depression: Lost in Translation!

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Introduction:

The old classification of depression into Reactive and Endogneous that are still observed in the clinical practice cannot all be accommodated under the current rubric of Major Depression. This is because psychiatric nosology under DSM and its latest 5th edition is still descriptive, and not etiologic. In this article both reactive and endogenous categories of depression are revisited from the perspective of today’s understanding of etiological pathways. From an epigenetic perspective, the old dichotomy of Reactive vs. Endogenous are inter-related through the impact of the environment (e.g. stress). This includes familial or prenatal depression, where the environmental impact is before birth, or childhood depression where the early life stress is the precipitating factor to the genetic susceptibility. In conclusion, searching for both environmental impact (e.g. stressors) and genetic predispositions in depression, even at a clinical level could help clinicians with better therapeutic decisions.

 The differentiation of major depression into ‘reactive (stress-induced)’ vs. ‘endogenous (e.g. genetic)’ dates back to the German psychiatrist, Kurt Schneider (Schneider, 1920) who borrowed the term ‘endogenous’ from Emil Kraepelin. The differentiation was an early attempt at an etiological classification of depression (Mendels & Cochrane C, 1968). Despite the extensive use of these terms and despite the popularity of the catecholamine deficiency hypothesis of depression (Schildkraut, 1965) and the effectiveness of tricyclic antidepressants that began with the introduction of imipramine in the 1950’s, psychiatric nosology then gave up on the attempt of classifying depressions according to etiology.

 Although the aim of DSM-III in 1980 was for psychiatry to do what the rest of medicine does, to classify disease according to cause, this proved impossible and a non-etiological, purely descriptive system was devised that relied on categories based on symptoms and their severity. DSM-III divided the depressions into major and minor (DSM-III, 1980). Almost four decades later, DSM5 continues to be descriptive and non-etiological (DSM5, 2013). This has continued despite research that points to distinguishable pathways leading to the symptoms of major depression (Ghaemi & Vohringer, 2011; Malki et al. 2014; Mizushima et al. 2013; Parker 2000).

In this article an attempt depression is reviewed on a pathophysiological basis through 1) the impact of stressful events and their timing 2) gene-environment interactions and 3) biological circuits affected by different kinds of depression. The generic term of “depression” that has been used in this paper, refers mostly to major or unipolar depression, though it can at times also applies to minor depression and dysthymia. This article also excludes the normal reaction of mood to stress below clinical level of severity and dysfunction.

The timing of the stress onset:

In reference to stress leading to depression, there is a major differentiation between an early childhood adversary or later in life (adulthood) stress. While these two types of depression, one with an early onset in childhood or adolescence, and the other one with a later onset in adulthood, could be referred to as “Reactive Depression”, they are fundamentally different. (Hazel NA., et al., 2008) This differentiation between reactive depression in the past decade has been recognized in the literature as “Juvenile” and “adult” onset with different pathophysiological pathways that perhaps demand different treatment pathways as well. (Jaffee SR, et al., 2002; Weissman MM, 2002)

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Autoimmune Disorders: Relapsing-Remitting Vs. Progressive

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Stem Cell Therapy: Does it work and for what?

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Introduction:

Stem cells are the primordial or original cells that give rise to life and being of a living thing, from animals and humans. Zygote formed from the fusion of sperm and oocyte is the first line of stem cell that is “totipotent” meaning it gives rise to embryonic stem cells and from there to epiblast and embryonic germ stem cells, that are all “pluripotent” meaning they form all the differentiated cell types of a given tissue. These pluripotent stem cells lineage give rise to the primordial germ cells that form all the tissues from skin to bone marrow and all other body tissues. The aim of stem cell therapy over the past half a century has been to induce pluripotent stem cells (IPS) in different body tissues to repair or replace the damaged tissues and cells of specific organ or parts of the body in vitro (in lab) and in vivo (in live beings) (1-2).

 Bone marrow transplant has been the earliest stem cell therapy in the treatment of leukemia and lymphoma and has been widely clinically practiced over almost half of a century all over the world with quite success. Later on umbilical cord blood storage and use for transplants has been clinically practiced, while other forms of stem cell therapy such as the use of induced pluripotent stem cells (IPS) for a wider treatment of cancers and autoimmune disorders of different organs and tissues have been mostly experimental. Another common clinical use of bone marrow transplants has been in chemotherapy of cancers, to introduce the hematopietic stem cells within the bone marrow to replace the destroyed healthy cells by chemotherapy. The most common side-effects of bone marrow and other transplants traditionally has been graft vs. host reaction that rejects the transplant. Another stem cell therapy, “Prochymal” based on allogenic stem cells therapy using mesenchyme stem cells has been used recently in the management of such transplant rejections (3-4).

 While in the past it was thought that the stem cells are basically in bone marrow and umbilical cords and most organs and tissues unlike the epidermis of the skin do not possess the capacity of renewal, in recent years it has become apparent that some other tissues in fact contain stem cells for potential renewal (5). One main reason of the delay in the stem cells therapy has been lack of recognition of different stem cells across different tissues with different potential capacities unlike the progenitor bone marrow and umbilical cord stem cells. As explained above while many of these stem cells are pluripotent, most are multipotent or unipotent, meaning having the capacity of their own specific tissue cells regeneration (6-7). In fact and with a comprehensive perspective, cancer cells could be considered as stem cells for their capacity of turnover and proliferation. This fact has been known and discussed as early as late 80s, but only recently has received widespread attention and acceptance. The cancer stem cell concept is important for opening a new venue to the novel approaches in anti-cancer therapies that instead of killing all or partial cancer cells with the potential of regrowth, to target the cancer stem cells for final cure with no possibility of relapse (8-9).

 The advancement in stem cell research over years has led to the distraction and culture of progenitor or totipotent stem cells in vitro first from the animal models such as mouse, and now from the human’s blastocysts, with the ability of generation all the differentiated cells of a being such as human, hence “cloning” that puts the science in the jeopardy of Frankenstein as it has long been anticipated and infuriated (10-11). Other than blastocysts, the progenitor or embryonic stem cells with capacity of generating differentiated tissues of the whole being, it has been shown that epiblasts first from mouse and now humans could created such pluripotency (12-14). Moreover and morally riskier is the capability of adult stem cells to be reprogrammed to a pluripotent state, through transferring the adult nucleus into an oocyte or by fusion with a pluripotent cell. The most famous example of this cloning has the creation of “Dolly” the sheep by transferring of a somatic nucleus into an oocyte (15-18).

 From a therapeutic not creational standpoint, the ability of regenerating new cells in the damaged and destroyed tissues is the art and science of IPS (induced pluripotent stem cells). Despite knowing for long that some amphibians could naturally regenerate limbs, eye or other injured body parts, therapeutic regeneration or regrowth of damaged or destroyed tissues medically by IPS is quite recent (2, 19-20). Since the original retrovirus-mediated induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by some defined factors in 2006-2007 (21), rapid progress has been made to generate iPS cells from adult human cells (22), a range of tissues that can be reprogrammed (23), and from patients with specific diseases (24). The number of transcription factors required to generate iPS cells has also been reduced (25), and the efficiency of iPS cell generation has increased (26), and techniques have been devised without viral vectors integration (27).

 From Research to the bed side:

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Stem Cell Therapy: Does it work and for what?

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ADHD:Subtypes or one Type?

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Introduction:

The literature on pathophysiology of ADHD is quite inconsistent with mixed results to synthesize all the findings in any domain of neuropsychological, neuroanatomical, neurochemical or genetics to link them to the correspondent clinical phenotypes of the current ADHD subtypes. On a descriptive level, the symptomatology of two distinct ADHD subtypes of hyperactive-impulsive (ADHD-HI) and inattentive (ADHD-I) are quite different and hardly seem to come under the same disease entity as it has long been categorized by DSM classifications with no change in the recent DSM5 (1). While ADHD-I or ADD as it was labeled in the past, it is an “attention-deficit” disorder, ADHD-HI beyond an attention-deficit disorder, it is a behavioural disorder with cardinal symptoms of hyperactivity, impulsivity and behavioural disinhibition (2-4). As a result, the majority of research samples, hence the conclusions of the literature for clinical practice have relied heavily on the “combined subtype” that is an ill-defined combination of both subtypes. This ill-defined combined subtype usually is not consisted of 6 symptoms of either subtypes as required by DSM5, but some of the symptoms of each, in a mixed and arbitrary construct with no clear underlying pathophysiology as either subtypes. This contradicting fact has long caused an intense argument in the literature on the total validity of ADHD as a homogenous or single disorder with a single pathophysiology or two or more heterogeneous disorders with different pathophysiology (5-7), that I will attempt to review and explore in this paper.

 ADHD: Homogenous or Heterogeneous?

In fact throughout the history, ADHD has been a homogeneous condition, first described as “hyperkinetic” or “hyperactive” syndrome or disorder of children, with recognition of “impulsivity” as a component of hyperactivity first by Laufer et al. (8) in 1957. The second edition of DSM, i.e. DSM-II in 1968, (9) published by the APA, that for the first time recognized the condition as a disorder, labeled it as “hyperkinetic reaction of children”. It was not until the third edition of DSM (10) in 1980 that recognized the condition as an attention deficit with hyperactivity and labeled it as such, i.e. ADHD, that we started facing a combined and heterogeneous disorder. Unfortunately since then the research samples have been mostly undifferentiated or of combined subtype with rare comparison between the two subtypes, so to clarify any distinctions between the two if any.

 The few available comparison studies between the subtypes have shown that there is a distinct difference between the two with the conclusion of the most that ADHD is a heterogeneous condition with differences not only in symptomatology and the course of illnesses across the brain development, but differences in cognitive functions and different etiopathophysiology (11-12). Goth-Owens et al. (13) in their comparison study of 572 children and adolescents with pure inattentive subtype (ADD), combined type (ADHD-C) and non-ADHD controls, reported slower cognitive interference speed in the ADD vs. ADHD-C and controls comparisons. A similar result was reported by Carr et al. (14) who reported an attenuated attentional blink versus controls and ADHD-combined addressed in a sample of 145 ADD/ADHD and typically developing comparison adolescents (aged 13-17). A similar result has been reported by Solanto et al. (15 ) that predominantly inattentive subtype show worse performance than combined subtype and control groups on the WISC-III Processing Speed Index. This has made some researchers to question the validity of DSM current diagnostic criteria of ADHD to include two distinct subtypes of inattentive and hyperactive/impulsive under the same diagnostic umbrella. (16) Martel et al. (17) in comparison between the two subtypes, reported “a composite executive function factor was significantly related to inattentive but not hyperactive-impulsive symptoms.” The authors concluded “Executive function weakness in adolescent ADHD is specifically related to symptoms of inattention-disorganization.” Nigg et al. (18) also reported that symptoms of inattention-disorganization were uniquely related to executive functioning when hyperactivity-impulsivity controlled. “Inattention was associated with slower response speed, and hyperactivity-impulsivity with faster output speed. Results were not accounted for by IQ, age, gender, education level, or comorbid disorders.” Also Marshal et al. (19) found academic underachievement in a group of 6-12 years old with ADHD without hyperactivity. Friedman et al. (20) have reported that such cognitive deficits continue until late adolescence and Nigg et al. (21) who report their extensions to adulthood.

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ADHD:Subtypes or one Type?

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Hating Chemicals: Natural Medicines and Vitamins

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Introduction:

Natural medicine or Alternative Medicine or the field of Naturopathy with their widespread health food stores that have filled up the shelves of pharmacies as well is based on the propaganda that medications are chemicals and unsafe and their own products natural and safe. The field of naturopathy and the natural or herbal medicines that have dominated the health products market and sell more than prescription medicines, is solely based on the notion that the prescribed medications are chemicals and theirs are not. The irony is that everything is chemical, the oxygen in the air that we breath (O2), the water that we drink (H2O), and all the food that we eat, and so on.

In fact the prescribed medications that are nowadays synthesized in pharmaceutical factories have been originally made out of plants, e.g. Digoxin for heart attacks, Atropine for pupillary dilatation and else, Codeine for pain relief, L-Dopa for treatment of Parkinson’s, Aspirin, Quinidine an anti-arrhythmic, Reserpine a hypotensive, Theophylline a diuretic, and Yohimbine an aphrodisiac among so many others. Investing and profiting from the popular lack of sufficient knowledge and also the mass suggestibility, the field of alternative medicine has gone so far that simple food items such as garlic, cranberry and fish oils have nowadays been packaged in capsules, tablets and sold to consumers (1-2).

Although the science of Medicine originated from the herbs and plants, it was not until the modern era that the real based evidence medicine as we know it developed a competitor as “alternative medicine” to promote the use of natural medicine and other forms of healings. This alternative medicine or “naturopathy” from the start by the Bavarian priest Sebastian Kneipp in late 19th century to Benedict Lust, the founder of naturopathy in US, started their propaganda against evidence-based or real medicine and medications, including vaccinations even in children and against killing infections such as small pox or chicken pox. Although naturopathy or alternative medicine cover an extensive area and different treatment modalities, e.g. acupuncture, aromatherapy, massage therapy, Chinese medicine, homeopathy, herbology, reflexology, Reiki and chiropractic, the focus here will be on the promotion of the use of natural or herbal medicines, vitamins, minerals and supplements that have become a huge profit making business and available everywhere even on the shelves of pharmacies and grocery stores (3).

 The efficacy and safety of herbal medicines:

In argument against the core of natural or herbal medicine that they are natural and safe while prescription medicines are not, there are numerous studies across the globe demonstrating evidence to the contrary. It is well known even to the lay people that one could get poisoned by food, consuming plants or even coming in touch with them. Mushroom poisoning and contact dermatitis by poison ivy are the two very common examples that almost everyone is aware of. A total of 216 medicinal plants belonging to 77 families in North and Central America and Caribbean have been reported as toxic. These herbal medicines and alike that have been promoted and used for different illnesses such as rheumatism, wound healing, flu, headache, dysentery, gastritis, constipation, diarrhea, body pains, cancer, antiseptic, digestive, diuretic, fever, infections, menopause, dysmenorrhea, postpartum, diabetes, asthma, anemia, inflammation, muscle relaxant, hair loss, seizures, hypertension, anxiety, depression, psychosis, weight loss or simply to purify body and the blood, have been reported to cause many side-effects and toxicities (4).

The list of these untoward effects and toxicities like the claimed positive effects are numerous, e.g. nephrotoxicity (toxicity of kidneys), hepatotoxicity ((toxicity of liver), dermatitis, hypertension, nausea, vomiting, diarrhea, muscle paralysis, cardiotoxicity (toxicity of heart), gastritis, even being carcinogenic, sleepiness, muscle paralysis, respiratory failure, neurotoxicity (toxicity of nerves and central nervous system), causing abortions, hallucinations (hearing voices or seeing visions), edema (swelling), hemorrhage, blurred vision, vertigo, stupor, confusion, being narcotic and addictive among others (5-16).

Other than the above gross and obvious toxicities, the herbal medicines could caused molecular and cellular toxicities (cytotoxicity), even mutagenicity and genotoxicity (causing gene mutations and toxicities). Some herbal medicines could also cause toxicities during pregnancy and reproduction and cause abortions. These facts are only the tip of the iceberg of the possible side-effects and toxicities of the herbal medicines as most people do not report to their physicians and refer to emergency rooms of hospitals when intoxicated. Moreover there are untoward interactions of the herbal or natural medicines with the prescription medications that again many patients do not report to their physicians or pharmacies when use these products in addition to their prescribed medications (17-20).

 The case of naturopathy or homeopathy and their broad advertisements in media, specially in social media, TV, and many journals are beyond control. Nowadays to skip the drug agency controls, many of these products are offered in the common food products such as drinks, teas and even candies and other snacks. Moreover the health benefits of certain herbs, vegetables, plants and food as simple as garlic or fish oil have been exaggerated and they have been produced and released into tablets, capsules and sold in the market at a much higher prices, instead of promoting these basic food items in meals. These propagandas have been at the cost of advertising against the consumption of some food health promoting foods that nowadays are missing from many people’s diet such as dairy products, eggs, lipids, red meat and fruits (21-22).

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Hating Chemicals: Natural Medicines and Vitamins

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Fibromyalgia/Chronic Fatigue Syndrome: Controversy or Truth?

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Introduction:

Fibromyalgia that is diagnosed and labelled by physicians in clinical practice and even research interchangeably with Chronic Fatigue Syndrome is still a controversy by some, while a clear diagnostic entity by others. As the label of fibromyalgia denotes, it is a condition of generalized body (musculoskeletal) and joint pains. The Chronic Fatigue Syndrome label indicates the patient suffering from a general body fatigue. These two labels if they are two conditions may overlap as some patients and present with both generalized symptom clusters. That is why the two conditions are considered by some as one and inter-related. While these conditions were misdiagnosed or under-diagnosed in the past, they may be over-diagnosed in the recent years. Either way the diagnosis of these conditions often is clinical and by history and physical examinations (only if muscle and joint tenderness present) as any lab or imaging tests are often non-conclusive. Therefore the pathophysiology of these conditions is still known by many as idiopathic, without any known aetiology or pathologic pathway(s).

 More than a controversy, Fibromyalgia and Chronic Fatigue Syndrome (FCFS) are elusive and the diagnosis by many could be descriptive and clinical by symptoms counting like major depression. But there is at least one or more types of FCFS that are associated with many other medical conditions, e.g. IBS (Irritable Bowel Syndrome), non-ulcer dyspepsia, esophageal dysmotility, interstitial cystitis, chronic prostatitis, vulvodynia, vulvar vestibulitis, temporomandibular joint syndrome, sickle cell anaemia, osteoarthritis to name a few. The association with some of these comorbidities that are known as autoimmune disorders, could easily classify this type (s) of FCFS as an autoimmune condition(s) (1). The common conception behind the pathogenesis of FCFS is over-focussing on the pain symptoms that could be due to super-sensitivity or hyperalgesia of the nociceptive process in the central nervous system. But here the focus will be more on the type or types of FCFS that have some true underlying pathologies (1-2). This or these pathological condition (s) are inflammatory, systemic throughout the body and associated with one or more inflammatory or autoimmune disorders (e.g. 3-4).

In the Search of a True Pathologic Fibromyalgia & CFS:

A Chronic Pain Syndrome or A Systemic Musculoskeletal Inflammation?

The first thing to reach the truth of FCFS is to separate these two different conditions that currently are diagnosed under the generic umbrella of fibromyalgia and chronic fatigue syndrome. First of all since both a chronic pain syndrome due to hyperalgesia or super-sensitivity of the nociceptive receptors in the central nervous system, and a systemic musculoskeletal inflammation could cause chronic fatigue syndrome, this secondary or post-morbid condition in this article will be excluded and the literature on fibromyalgia is solely explored (5-8).

 Although a systemic musculoskeletal inflammatory condition could cause chronic generalized body pain, but the reason for the pain is not hyperalgesia or hyper-sensitivity of the nociceptive receptors in the central nervous system, but peripheral inflammations. This inflammatory condition is separated and searched for its underpinning pathology as the true pathological fibromyalgia, as pain even a generalized type could be subjective and not a true objective and pathological condition. Even tenderness of the muscles and joints without any proof of underlying pathology such as inflammation could be all subjective. Therefore this subjective condition or Chronic Pain Syndrome that could be due to a hyperalgesia or hyper-sensitivity of the nociceptive receptors of the brain or in a simpler word due to hyper-perception of pain by an individual is separated from a true fibromyalgia in this paper. This sole pain condition that is simply subjective could be perhaps associated more with other subjective conditions such as depression or being influenced by psychosocial processes (9-12).

Fibromyalgia: A Systemic Musculoskeletal Inflammatory Condition  

Unfortunately since most samples of fibromyalgia studies are mixed with chronic pain syndrome and other subjective conditions without any underlying physical pathology, the physical findings of any inflammatory biomarkers are below the real level of the pathological reality of the condition. But despite this limitation, there are studies that have been able to show the presence of an underlying inflammatory process in the true cases of fibromyalgia.

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Fibromyalgia/Chronic Fatigue Syndrome: Controversy or Truth?

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When one is not enough: Multiple Autoimmune Syndrome

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Introduction:

The world even the medical filed are all terrified by the cancers, while the autoimmune disorders are more prevalent across the globe. While the incidence of all cancers world wide is about 17 millions cases in 2018 that makes it .22%, the prevalence of only very common autoimmune disorders is over 3.45% or over 266 millions internationally, making them more than 15 times prevalent than the cancers. (1-2) The common autoimmune disorders that to some including physicians might not be recognized as such diseases in the above estimate of prevalence (with an average prevalence per 100,000 in brackets) are as follow: Diabetes type 1 in all ages (946); Hypo- and Hyper-Thyroidism (691); Rheumatoid Arthritis (381); Ulcerative Colitis (378); Crohn’s Disease (225); Psoriasis (197); Multiple Sclerosis (182); Uveitis (149); Polymyalgia Rheumaica (112), Celiac Disease (50); Sjogren Disease (48); Chronic active Hepatitis (45); SLE (Systmeic Lupus Erythematosus) (32); Vilitigo (29); Systemic Sclerosis (23); Alopecia (21); Addison’s Disease (18); Myasthenia Gravis (18); Primary Billiary Cirrhosis (12); and Systemic Vasculitis (10). (1)

 As discussed in a few articles on different cancers such as breast, prostate, ovarian and endometrial, lung, colorectal, skin cancers and leukemia on this site, cancers are mostly epigenetic than genetic (3-10). Of the epigenetic factors, microbial invasions are the frontiers on the assaults and causation of different cancers. The epigenetic factors such as infections as part of their offensive strategies, weaken the defensive power of the targeted organ, causing dysplasia, polyps or other benign forms of tumours before progressing to malignant cancers that are the killers of the assaulted organs. In a relatively similar process, autoimmune disorders are caused by epigenetic factors including microbial invasions. While cancers are localized assaults, autoimmune disorders are more generalized attacks of epigenetics to our living system.

 

It is not yet very clear to our scientific strive to differentiate at the onset of the invasion which disease will ensue at the end. It seems so far to our limited knowledge that the pathogeneses of either cancers or autoimmune disorders, or the impact of what organ or system of the body are multi-factorial. This depends on the invader, what organ or system it attacks or what is its specialty, and also on the condition of the targeted organ or body system. The control of the invaders is by avoidance (e.g. too much exposure to the sun in skin cancer), prevention (e.g. vaccinations when possible and available), early recognition of he early stages of the attack and recovery (e.g. surgical removal of polyps or benign tumours). But more importantly is the fostering of our body system to be more immune and protective against such invasions that are all around us and often could not be avoided. This strategy is about reinforcing our immune system that is perhaps the major defense against autoimmune disorders (3-15).   

 It is suspected that the incidence of autoimmune disorders are on the rise that could be due more to our less defensive immune system than the stronger environmental factors such as microbial invasions. It also seems that single autoimmune diseases are rising up to multiple autoimmune diseases or syndromes. This makes the hypothesis of increasing the rate of autoimmune disorders due to our poorer immune system seem more right as multiple autoimmune syndromes occur more in the subjects with less defensive or weaker immune system. In this article through a search into our available scarce knowledge data on this growing monster, I will attempt to bring these syndromes and their pathogenesis more to the light of recognition and hope to the arena of prevention (16-18).

 

Humans: More Knowledge, More Tools, More Vulnerable:

For the sake of simplicity and unified terminology with the rest of the field, the term of Multiple Autoimmune Syndrome (MAS) for any multiple autoimmune disorders that occur together in a person. The condition is so on the rise due to our defenseless immune system that the expert consider MAS when there are three or more of autoimmune disorders clamp together in an individual. About 25 percent of patients with autoimmune diseases have a tendency to develop additional autoimmune disorders. Surprisingly for whatever reason, MAS often involves one dermatological or skin condition such as alopecia, vitiligo or psoriasis (19).

 For long and before the discovery of MAS, the medical field was acknowledged of a few systemic autoimmune disorders, spreading to more than one organ of the body, and the most commonly known is SLE (Systemic Lupus Erythematous) that is a progression from skin lupus but spread beyond to the joints and more. Later on in the course of the history of medical knowledge, we recognized more concurrent autoimmune diseases in autoimmune hepatitis autoimmune bowel diseases, e.g. ulcerative colitis and crohn’s disease. Association of skin autoimmune diseases such as vitiligo and alopecia in MAS is another important and significant observation that could one day lead us to more understanding of the pathogenesis of these metastatic autoimmune disorders. Moreover on the epigenetic or the invader’s front, some such as cytomegalovirus by producing multiple autoantibodies are capable of spreading into different organs and causing MAS (20-21).

 

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When one is not enough: Multiple Autoimmune Syndrome

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Sport Injuries: When Young and Healthy Break

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(To: My daughter Tiffany, Mohammad Ali, Rafael Nadal, Milos Raonic and all the injured athletes of the world) 

Introduction:

When my daughter, a junior tennis player, injured her wrist this summer it took her about two months to recover and get back to the game. Having had to retire from a few important tournaments, I realized more of the significance and self-destruction that sport injuries could cause to a person. We all know about the consequences of sport injuries in famous world sport leaders such as Mohammad Ali who developed Parkinson syndrome (not the disease but what’s called in medicine “Punch Drunk Syndrome” with Parkinson-like symptoms). Sport injuries are almost unavoidable in athletes, and in the tennis the fans know how many operations the current world number one, Rafael Nadal has had just on his knees, or Canadian Milos Ranoic broke his hip at age 20 by falling on the grass court in Wimbledon.

Different sports are more prone to injuries and different parts of the body are more common to injuries in different sports. For example tendonitis of the wrist, elbow, shoulders and injuries to the knees, ankles and foot are more common in tennis. But head injuries are more common in boxing and hockey, while foot, legs and knees injuries are more common in soccer. Overall some sports are more prone to injuries due to the nature of the sport and the behavior of the athletes and due to more lenient rules and prohibition executed by the specific sport authorities and the referees in some specific sports such as hockey. While the physical injuries are more obvious and attended to, the mental and emotional injuries due to the stress and expectations of the athlete performance by the athlete, coaches, fans and families should not be ignored(1).

We need not to forget that sport injuries do not occur only in professional athletes that comprise a small population in sports in general, but in many healthy youngsters who engage in sports curricular in schools or extra-curricular sport activities. There are more than 30 millions injuries alone in the United States in teenagers and children. We also need to realize that some sport injuries when befall on the neck and head could lead to permanent disabilities and loss of lives that often happen to the otherwise healthy and young ones. We need not to be scared and avoid the sports for ourselves and our children, as playing sport or exercise is the best that we or they can do as a guarantee for a healthy life, but we need to know how to do it right so to prevent injuries. Although this article is focused on sport injuries in the athletes of all ages and different levels, but ordinary people who engage in harsh and in-calculated exercises could have injuries as well (2).

In this article after classifying the common sport injuries, considering different age groups, in non-professionals and professionals, and across different sports, and also among ordinary people regarding over-use and improper injuries, prevention of such injuries will be discussed.

 Soft-Tissue Injuries:

Soft-tissue injuries are the most common type of injuries that include simple cuts, lacerations and bruises, easily seen by the naked eyes. But deep soft-tissue injuries that could affect tendons, muscles, blood vessels, nerves and could cause more pains, discomfort and longer disability mostly due to deep inflammations, may be ignored. The most common of these deep soft-tissue injuries are tendonitis and neuritis or neuralgic pains that demand longer and more specific treatments.  

  Read the full text here:

https://medicinerevisited.com/sport-injuries-when-young-and-healthy-break/

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Asthma: A Tribute to Ernesto Che Guevara

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(“I went to see an old woman with asthma, a customer at La Gioconda. The poor thing was in a pitiful state, breathing the acrid smell of concentrated sweat and dirty feet that filled her room, mixed with the dust from a couple of armchairs, the only luxury items in her house. On top of her asthma, she had a heart condition. It is at times like this, when a doctor is conscious of his complete powerlessness, that he longs for change: a change to prevent injustice of a system in which only a month ago this poor woman was still earning her living as a waitress, wheezing and panting but facing life with dignity. In circumstances like this, individuals in poor families who can’t pay their way become surrounded by an atmosphere of barely disguised acrimony; they stop being father, mother, sister or brother and become a purely negative factor in the struggle for life and, consequently a source of bitterness for the healthy members of the community who resent their illness as if it were a personal insult to those who have to support them….In those dying eyes there is a submissive appeal for forgiveness and also, often a desperate plea for consolation which is lost to the void, just as their body will be soon lost in the magnitude of mystery surrounding us.”)    

Ernesto Che Guevara,

Motorcycle diaries

Introduction:

Asthma that is the narrowing of the airways of lung, causing difficulty in  breathing with sound of wheeze, is a chronic disease often starts in childhood and is an interaction between the environmental allergens or pathogens and the individual lung’s susceptibility or genetic make up. This early onset asthma that often leads to asthma attacks, frightening the person and the relatives for the fear of inability in total breathing and death, is usually due to an allergic eosinophilic reaction of the lung airways, causing their narrowing due to thickness of their smooth muscle walls and also obstruction caused by reactive sputum (1-3).

 But not all asthma is an allergic eosinophilic reaction of the lung airways and there is a heterogeneity even in the inflammatory asthma known and reported since 1922 by Huber and Koessler (4). It has been shown and reported that any problems with the lung function such as reduced its function even as early as infancy could lead to late on obstructive lung disease such as asthma (5-6). At the same time, having a history of allergy or atopic sensitization as long as not related to such sensitivity in the lung airways, it will not necessarily lead to asthma in childhood. (7) Following an epigenetic model of causation in asthma, the airway hyper-responsiveness or sensitivity or overwhelming the lung airways with too much dust mites, heavy smoking specially at an early age could prolong the childhood asthma into adulthood and also cause exacerbations and further attacks (8).

 Other than the common allergic or eosinophilic asthma with an early onset in life and running a chronic course, microbial invasions of the lungs and respiratory airways, also contribute to asthma. There have been reports on neutrophilic and lymphocytic infiltrations of the lung airways among others causing the narrowing of the airways, hence asthma (9-10). Such infiltrations of other white blood cells even in the airways or sputum of allergic or eosinophilic asthma that for long thought to be due to T helper type 2 disease and as an allergic reaction, has more recently been shown to have an underlying immunologic susceptibility. This is the beginning of a new understanding of asthma and its genetic susceptibility as an immune or perhaps an early autoimmune disease (11-12).

Che Guevara: An Iconic Asthma Sufferer

Ernesto Guevara was an Argentine physician, who later on by his Cuban comrades was popularized as “Che”, meaning comrade or friend, and since then he has been known as Che Guevara. Before joining the Cuban revolution along with Fidel and Raul Castro and other guerillas, since he suffered from a severe asthma with frequent attacks from his childhood, causing him staying home sick often, he spent all his sick time reading a lot of everything from literature, poetry, philosophy, politics and else. He was also in love of photography and travelling, that his trip across South America, that he called one nation, on a motorcycle with his friend Alberto Granado, under the title of “The Motorcycle Diaries”, before his graduation from medical school and becoming a revolutionary, has been a popular book and film. Despite his severe asthma in his continental trip, he swam at night across Amazon river, a considerable distance of 4 kilometers (2.5 miles) when visiting and helping the lepers in a leper colony in Peru. He unlike the doctors and nurses in the colony, did not wear gloves to shake hands and touch the lepers, but bravely did so with his bare hands.

 

Read the full text here:

https://medicinerevisited.com/general-medicine/asthma-tribute-ernesto-che-guevara/

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Sleep: Our yet not well discovered inner world!

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Introduction:

As adults we spend or should if we dont one third of our time in sleep and as children up to half of their time. We all sleep when tired and when have a good sleep, we would feel rested. We therefore know that the sleep function is for restoration of physical tiredness or fatigue. But sleep is not just for restoration of physical fatigue, but for the restoration of the mental or brain fatigue as well. We may think that during the sleep, the body is totally shout down and in rest. But surprisingly the body is quite active in sleep and like a factory, does self-restoration or repair during the hours of sleep. In deep sleep, if we can get any, the physical restoration or repair is done and in REM (Rapid Eye Movement) or dream stage of sleep, the mental or brain restoration or repair is done. More importantly, many hormones such as growth hormone in children are secreted in sleep and mostly in deep sleep.

 In this paper, the architecture or different stages of sleep will be explored. Then the sleep-wake cycle that is a major component of our circadian rhythm and our body homeostasis and health balance will be exposed. Then the importance of sleep hygiene and lack of it and the disorders of sleep will be discussed. The treatment for sleep disorders and the most common one, insomnia or sleeping pills will not be discussed, as majority are of Benzodiazepine class of drugs, addictive and more habit forming and perpetuating the insomnia. The purpose of this article among the others on this site is more to understand the pathophysiologic process of every disease, so hopefully soon move towards the prevention. Finally what is a very dilemma and question for many, the world of dream and its interpretations will be explained.    

 

Stages of sleep:

During a night sleep of about 8 hours that is normal for adults, the body or brain goes through about 5 cycles, starting with the stage 1 that is the drowsiness or falling asleep stage lasting only a few minutes. Then the second stage that comprises about %45-50 of a normal adult sleep, that is still light and the person could be aroused by sounds and noises and it is the usual toss and turn stage of sleep. The second stage lasts about 40-45 minutes in each cycle that lasts normally 90 minutes. Then the deep sleep kicks in that is comprised of stages 3 & 4 and most adults do not get it much nowadays, while they need to have it at least %20 of their sleep. These stages of 3 & 4 or deep sleep is for the restoration of physical fatigue and if the person does not get it enough, he or she would not feel rested in the morning.

The next stage of sleep in the cycle is REM (Rapid Eye Movement) sleep that is the dream stage of sleep when the individual enters the world of his or her dreams. This stage that comprises about 20-25% of a night sleep is very active not just for the eyes that moves fast as its term suggests, but the whole body physiology such as heart beat, respiration and else are active even more than in the waking state.  After the first cycle of sleep and REM, the brain may not start over from stage 1, unless someones sleep is very light and broken and keeps waking up in the middle of the night, or after a nightmare. So in a normal restful sleep, after the first cycle and REM, in the second cycle and thereafter, the brain starts from stage 2 and the rest. If the individuals sleep is light, he or she may not go much or at all through the deep sleep of stages 3 &4 that is very common in the modern era of sleepless nights. Therefore everybody gets mostly stage 2 and REM sleep even if one does not remember having any dreams. REM sleep due to its high brain and physiological activity, has the vital role of restoration of brain fatigue. Thats why people with many mind preoccupation or worries may have lots of dreams and even nightmares. The following figure shows how the body enters the different stages of sleep from a waking state and the repeated sleep cycles throughout a night sleep:

 Now in the following each stage of sleep will be discussed in more detail:

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Training New Physicians:Towards the Future

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Physicians or medical doctors who are in charge of our health and well-being world wide, are the products of different medical training standards around the world. The medical schools training could last from 5 to 8 years to graduate a general practitioner or GP. Many medical schools around the world accept the high school graduates after an entry exam into the medical schools that mostly last about 6 years. This could be true in many developed countries such as in Europe. But in US, Canada and UK that hold higher standards in medical training, the entry into medical school is much more sophisticated, longer and more competitive. The applicants in these countries, mostly need a bachelor degree principally in biological science or alike, passing a medical entry test, MCAT (Medical Colleges Admission Test), voluntary works, references, etc. to be accepted to medical schools that is highly competitive. In these countries, then the medical schools training is four years, all focused on medical sciences, from the basic to the clinical and specialties, concluding general practitioners. But there are no jobs or positions for GPs per se in these countries without any specialties, and the shortest training for these would be family practice that lasts two years that is equivalent of GPs in other countries, only after 6 years of post-graduate studies past high school. Therefore one could easily appreciate the difference in the quality of medical training across the globe that could be translated to the quality of medical care. (1-3)

 In many places in the world after graduation from medical schools, there might not be any final general exams of all the pre-clinical and clinical subjects for licensing to practice general medicine. But in US, Canada and UK there are several step exams during the medical school years and after graduation for licensing to practice medicine. In US there are three step of such exams, step 1, testing basic medical sciences in one-day of 8-hours session, step 2 consisted of two sub-steps of clinical knowledge (one-day of 9-hour test) and clinical skills (one-day of practical clinical skills assessment with mock patients). The final step licensing exam, or step 3 of USMLE (United States Medical Licensing Examination) assesses the capability of the application of basic medical and clinical sciences in a two-day exams, 7-hours the first day and 9-hours the second day including clinical skills assessment of 13 simulation cases across major medical disciplines. (4-5)

In Canada there is a similar licensing exams or MCCQE (Medical Council of Canada Qualifying Examination). The first part of MCCQE in 3.5 hours assesses the general medical knowledge, followed by 4-hours of clinical decision making scenarios assessment. The part 2 of MCCQE consists of an objective structured clinical examination in total simulated clinical sessions with patients, that could be taken after one year past the clinical training graduation.

 In England, unlike US and Canada but like many other parts of the world, entry into medical schools are right after graduation from high schools, though the competition is quite high and the rate of acceptance is not more than 10%. Other than traditional or multiple mini-interview, depending on the university, there is the United Kingdom Clinical Aptitude Test (UKCAT) required by most universities and Biomedical Admission Test (BMAT) required by five universities. The medical courses in English medical schools are “problem-based learning” and “lecture-based learning”, and consist of 2-3 years in pre-clinical and 3 years in clinical. The graduates after these 5-6 years of medical training are recognized as Foundation House officer (FHO) and are only permitted to work in supervised clinics and hospitals for one year before being granted independent license to practice as GP and fully register in the General Medical Council. (6-7)

 

Which system is better?

Is the straight entry from high school to medical school better or an entry after a four years under-grad university education? While entry into medical school in most parts of the world is probably the hardest among any other university courses, when entered most students graduate and there is not much scrutiny and not much failure. A major difference between the two systems is the age and maturity of the applicant. In the straight from high school entry with 6 years course, the applicant is younger and less mature, but in the other system entry after a bachelor degree, the applicant is four years older and more mature. At the same time in the first system of straight six years medical studies, two years basic medical sciences and four years of clinical, the students acquire more knowledge due to studying medicine two years longer. But in the four years course after a bachelor degree, unless those students who have studied four years of basic medical sciences, the rest have only four years to study medicine, including basic and clinical sciences. That is why in countries with this latter system such as US and Canada, there is no GP or licensure to practice after graduation from medical school, unless finishing a specialty training that equivalent to general practice is family practice in these countries that require an additional two years of training. At the end both system in regard with training, education and knowledge could be equivalent, but the only difference will remain age and maturity that the latter system could provide more better health care service due to age and maturity.(8-9)

 Are the licensing examinations well justified?

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Heart Attack: The Killer of all

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(In the memory of my father, a common man, but a poet)

Introduction:

Heart attack that medically known as Myocardial Infarction (MI) is the leading cause of death in the developed countries and the second in the developing world with over 12% of the cause of the death worldwide. The prevalence of such deaths due to heart failure after acute myocardial infarction from the 10% within 30 days and 20% in 5 years in the 70’s, have skyrocketed to 23% and 34%, respectively, in the 90’s. MI usually is a result of Coronary Artery Disease (CAD) of the blood supplies to the heart muscles, that is caused by the occlusion of these arteries by atherosclerotic or lipid plaques that finally rupture and leading to the necrosis or infarction of the cardiac muscles, impeding its pumping function, finally failure and death.

 

The accumulation of the atherosclerotic plaques which is a long or chronic process, after years warns the individual with symptoms of Angina, e.g. chest pain that my feel like heartburn, radiating to left arm, shoulder and other associated symptoms such as nausea and vomiting, shortness of breath, numbness on the left side, faint feeling and cold sweat, etc. While the precipitating process is long, the end result could be sudden and acute, causing sudden death in minutes even at times without warning or chest pain, so called silent MI or heart attack. In certain situations, MI could happen without a precipitating long process, by coronary arteries spasm due to the use of some illicit drugs such as cocaine and extreme cold among others. (1-2)

 

Why a beating heart stops?

A beating heart does not stop incessantly, as it looks in the heart attack or myocardial infarction to be sudden and acute. Underlying a stopping heart or attack that is seemingly acute and sudden, there are chronic or long-standing processes that lead to its standstill. There are more than one factor in the process that ends in the heart attack and understanding of these factors could help to prevent sudden death from heart attacks. Although there are many modern treatment modalities from angioplasty to coronary bypass, saving an infarcted or a partially or more complicated dead heart muscle, hence saving lives, the ultimate goal in this arena needs to be prevention of such fatal accidents, as there are many unfortunate instances such as my father’s that any treatment even advanced ones could be already too late!

 

While to many people, including the patients themselves and their clinicians, heart attack or myocardial infarction is interpreted as coronary arteries (blood supplies to heart itself) occlusion, there is a big and long-standing secret behind it. Moreover the great majority of myocardial infarctions are not fatal, whether treated or untreated, and understanding, prevention and treatment of the precipitating factors are crucial as subsequent attacks may kill the person if not the first one, like in the case of my father. Among many of these factors, there are comorbidities or other illnesses such as diabetes mellitus or hypertension, plus the size and location of the infarct that influence the clinical course, treatment and prevention. The exact anatomic territory infarcted and whether it includes the sinus node or AV node or important neuro-receptors; whether many small arteries are occluded (especially downstream of narrowed main coronary branches) are all important. Also whether the heart is hypertrophied, dilated, infected, or infiltrated; and whether there may be intra-cardiac, extra-cardiac, or intracranial neuro-pathological conditions that could destabilize cardiac electrical activity are needed to be identified. (3)

 

Moreover it is known that apoptosis plays a major role in myocardial infarction or ischemia, but it also occurs within the heart completely and independently of infarction. There is also the vexing dilemma that an effective coronary collateral circulation, which is determined primarily by trans-anastomotic pressure gradient, is made less effective by exactly those treatments that reestablish flow in an occluded coronary artery. Since thrombolysis and angioplasty are automatically considered urgent treatment for an occluded coronary artery, it is prudent to remember the complex causes that determine whether the patient lives or dies. (3)

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Skin Cancer: When our good sun hurts! (In the memory of Bob Marley)

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Introduction:

Skin cancers are divided into three main types of Basal cell carcinoma, Squamous cell carcinoma and Melanoma, based on the abnormal cell development and proliferation of the type of skin cells. While Basal-cell carcinoma grows slowly and is more localized to the skin tissue, Squamous-cell carcinoma is more aggressive and malignant and can lead to metastatic far distance spread to other body tissues and could be fatal. Melanomas that arise from the melanocytes or skin pigment cells, are the most aggressive, malignant and metastatic, that killed Bob Marley.

 

While the sun is the source of life on earth and our own life in different aspects depend on its shinning, such as regulation of our circadian rhythm, sleep-wake cycle, and the color of our skin, its excess could contribute to more than 90% of skin cancers cases. The risk nowadays are higher due to a thinner ozone layer, and also the increase fad of artificial tannings as another common source of ultraviolet radiation. The longer and more intense exposures, such as from childhood and the sensitivity of the skin’s subject, for example the white skins, the living zones, such as regions with intense sunshine like Australia and New Zealand, and also the less defensive immune system, the more risk of cancer. (1-2)

Despite all these, and the skin cancer being the most common of all cancers world wide, the early intervention of the skin cancers, even melanoma through removal of the locus of the cancer such as the mole, radiotherapy and medications, have increased the survival rate of all the skin cancers higher than other cancers, close to 90% recovery rate. That takes us to the sad story of Bob Marley, who due to his religious beliefs, refused the full treatment of his melanoma on his toe from 1977, so the cancer spread to his brain and killed him mercilessly on 11 May 1981, at age only 36 and deprived the whole art of music and his global friends form a longer legendary career. (3-5)

Bob Marley, a musical icon, the father of reggae and an international messenger of love and peace, who started with band “The Wailers” , and a national symbol for Jamaica, with all his spirituality, yet could not survive from a small mole on her toe that finally spread to his brain and killed him. His songs such as “One love”, “Is this Love”, “Redemption Song”, “Waiting in Vain”, “Satisfy my Soul”, “O’Woman don’t cry”, “Buffalo Soldier”, “I shot the Sherriff”, “Jamming” and more has no need for an introduction as he is know and loved still to this day by billions. He could easily be the only human’s messenger and representation in popular music and culture. Unfortunately his religious commitment to Rastafari, not to allow the amputation of his cancerous toe so to prevent the spread of the melanoma, deprived him of such a great life and his fans to enjoy his music years longer.

 

Sunlight: Good, Bad and Ugly

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Anxiety or Depression: Chicken or Egg?!

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Introduction:

In Medicine, the existing of more than one condition or disease is common and it is so called “Comorbidity”. This term by definition refers to the co-existence of two conditions without any relationship such as causal. In other word, comorbidity is the co-existing of two conditions in parallel with no relationship, or different pathophysiology and treatment paths. But in fact that is not the case in many situations, as one condition may give rise to another, or in a better sense, one is primary and the other is secondary. For example hypertension or high blood pressure can lead to stroke and its consequences such as hemiplegia, or diabetes as a primary condition could cause many complications as secondary conditions such as diabetic foot and poor vision, etc. The treatment of the primary condition such as diabetes or osteoporosis could prevent the secondary condition such as diabetic wounds and bone fractures.

 Although some of these co-conditions that are still commonly labeled as “comorbidity” are very obviously primary and secondary to each other with a causal or consequential relationship, some conditions specially in Psychiatry may not look that much related to each other. For example in ADHD, secondary conditions or complications such as depression, oppositional defiant and anti-social behaviours or disorders, substance use disorders, etc. while not much superficially related, they are in fact so, and treatment of ADHD would prevent majority of the others. For the first time, I coined the term “post-morbidity” in ADHD for these secondary conditions or complications that are still in the literature considered loosely “comorbidity” with no apparent causal relationships. (1-2)

 

A similar relationship exists between depression and anxiety that are commonly comorbid in psychiatry and it is still considered with no causal or temporal relationship as simply “comorbid” in the literature and among experts. If two conditions are causally related and not appreciated as such, it will affect their treatments and both conditions could be treated with two treatments, e.g. two or more medications. But if there is a causal relationship, the treatment of the primary condition would prevent and treat the secondary or “post-morbid” condition, while their pathophysiologic relationship is more appreciated and understood. In this paper, I will show for the first time that such a primary and secondary or “post-morbidity” relationship exists between depression and anxiety that has never to this date been recognized.

 

Depression and Anxiety: Are they related?

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Polypharmacy: When too much good is no good!

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Introduction:

While medications from the time of antiquity have saved lives and do so more and more over time, have fostered health and increased longevity, too many medications or polypharmacy, particularly if it is not necessary, could cause more harms than benefits. Polypharmacy is seen in all age ranges and in all countries, but more in patients with comorbidities or more than one medical conditions, specially in the older population that is more risky and cause more harms and is more common in developing countries. Although it is assumed commonly that polypharmacy is used in comorbidity conditions, one would be surprised that it is common as well in single medical conditions, when physicians helplessly add to the number of medications to bring under control a non-responsive medial condition. (1-3)

 

The common and known unfavorable effects or harms of polypharmacy are adverse drug reactions, drug-drug interactions, low adherence to drug therapy and stopping all the medications by the patient, psychological dependency of the patient that only medications could help so not to resort to non-pharmacotherapy modalities if available, also physical dependency if the medication (s) are addictive, and finally the burden of the body tissues and organs by too many medications as foreign objects, specially on liver and kidneys that mostly metabolize the medications. In addition, it is also assumed that polypharmacy causes unnecessary health expenditure, directly due to redundant drug sales and indirectly due to the increased level of hospitalization caused by drug-related problems. Drug-related problems are reported to cause a substantial proportion of all emergency treatment and admissions to hospitals such as in elderly population. (4-7)

 Unfortunately many studies of polypharmacy have primarily been conducted on samples of elderly individuals admitted to hospitals or nursing homes, and only a few have been population-based studies, though some of these again have also been limited to elderly individuals. A recent register study showed that 2/3 of all individuals in a national population who were being prescribed with 5 or more drugs were < 70 years of age, indicating that multiple medication use is not only common in elderly population. A recent Swedish Prescribed Drug Registery in the period of 2005-2008 has shown an 8.2% increase in polypharmacy (>5 medications). (8-9)

In this article, we discuss first polypharmacy in different age groups, elderly, adults, children and adolescents, then across a few common medical disciplines, among comorbidities and single medical conditions.

 

Polypharmacy across life span:

In the above mentioned Swedish study of polypharmacy between 2005-2008, the prevalence of more than one medication in elderly (>70) was 80% on average, with more than 5 drugs averaged 45%, and more than 10 medications was about 13% on average. In adult age group, the prevalence of more than one medication was 30-40% in the age range of 20-49, but that jumped to > 50% in 50’s and to about 65% in 60’s. The use of more than 5 and 10 medications were rare until the 5th and 6th decades of life that was about 10% and 20%, but the use of more than 10 medications was still rare. In children and adolescence surprisingly the use of more than one medication was quite high about 18% in the first decade and 22% in the second decade of life. The number of individuals on polypharmacy and excessive polypharmacy over 5 medications were quite high, >4,500 in the first decade of life, >9,000 in the second, about 18,000 in the third, >35,000 in the fourth, close to 70,000 in the fifth, >138,000 in the sixth, >220,000 in the seventh decade of life, and in the elderly, 70-79 years old it was close to 250,000 and in the 80-89 years age group, it was >210,000. Surprisinlgy in all age groups the prevalance of polypharmacy has been increasing over years from 2005-2008. (9)

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