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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Longevity: Could we determine how long one will live?
The following article of “Living with coronavirus in peace and no panic” that was posted 3 weeks ago with its suggestions based on scientific evidence was not taken seriously and the authorities all around the world continued with their own made-up prevention strategies, and the massacre of the virus continued and is still ongoing. As of 9 AM eastern time this morning of April 5,2020, COVID-19 has managed to kill 65,841 people around the world with diagnosed cases over 1.2 millions. These figures by the time the virus finishes its business, will probably culminate to 2 millions cases and close to 100,000 deaths world-wide.
COVID-19 is a viral pandemic and cannot be like other matters handled by the politicians and not even chief medical officers or even WHO who are all in administrations and not in medical science. Epidemics and pandemics of such scale need to be handled by the most experts in the field, i.e. virologists who have known viruses like coronaviruses for years and studied them in and off their labs while politicians and ordinary people were sleeping or being busy with their usual affairs. If the coronavirus has not concluded its universal entry agenda into the human hosts, it will return in about 5-8 years with more aggressive and killing pandemic. In fact what the world has labeled the virus as COVID-19 and ridiculously a twins have been named after it “COVID” and “Corona”, in the virology field and among such scientists the virus that is of the same family of common cold virus and SARS has been officially named “SARS-COV-2”. We did not manage MERS and SARS in the years before and even did not understand them, so the virus came back most aggressively for universal entry into its human hosts through this COVID-19.
But no panic for now as the coronavirus will leave us soon in 4-6 weeks according to the following timelines of departure in different parts of the world:
Italy: Will depart in 7-10 days
Spain, Germany,Iran, Switzerland, Belgium and Netherland: Will depart in 10-14 days
France, USA, Turkey, Canada, Brazil: 14-21 days
The Coronavirus will leave the world at the latest by early to mid-May, so no panic and get ready to return to your normal lives and enjoy the spring and summer. But do not forget that the virus may come back soon in a few years and if it has not done its universal entry into us, it will be more aggressive and more lethal. So the world needs to be prepared and grant this important management of the epidemics and pandemics to the right generals who are virology scientists in the next invasion.
(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)
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).
One of the most impressive example of endosymbiosis in fact is the microbiota living in the mammalian guts including 100 trillion microbes living in one human’s gut. The gut microbiota is so vital for the maintenance of our immune system in fight against infections and diseases for our survival that when disrupted and not cooperated with, e.g. in the case of slow bowel movements and constipation, they could turn to pathogens and causing diseases such as colon cancers. In endosymbiosis, e.g. our guts microbiota, the relationship is not static but dynamic and plastic or flexible on both sides. Any disruption of this equilibrium takes long and many processes of negotiations, commensalism and mutualism on both parts for the sake of peace and survival, unless the terms of homeostasis is broken repeatedly or continually by one side that is mostly by the hosts. This indeed is a major lesson observed diligently in molecular biology that needs to be expanded to other symbioses and endosymbiosis around and within us. In fact the survival of our ecosystem outward and inward is heavily dependent on a full cooperation between the partners of symbiosis and endosymbiosis that hinges mostly on the hosts part like us (11-16).
Another impressive well know example of endosymbiosis between us and microbes is the bacterial communities present in the vagina of reproductive-aged women as a cornerstone of a multifaceted antimicrobial defense system. The vaginal microbiota play a significant role in the prevention of bacterial vaginosis, yeast and sexually transmitted infections, urinary tract and HIV infections among others. The lactic acid–producing bacteria (mainly Lactobacillus sp.), common colonizing bacteria in the human vagina, are the key players in maintaining homeostasis of this microbiota endosymbiosis. Like the gut, depending on the sexual activity, menstrual cycle, and other environmental factors, there are periods of community-wide stability as well as periods of extreme variability. The stability or healthy symbiosis and instability or dysbiosis in vagina depends heavily on the host and her sexual/hygienic/reproductive behaviours (17-20).
Viruses not antagonistisc but essentials:
While the roles of bacteria have been known for long in endosymbiosis of the hosts well-being like us, the role of viruses traditionally and still out of scientific arena in endosymbiosis has not been appreciated until about a decade ago. Indeed viruses due to their much minute sizes and its cellular structures, particularly RNA or particle viruses that cannot survive independently, have much more endosymbiotic roles not only in the large size beings, but even within bacteria. This mutualistic relationship has been explored in detail recently pointing to the vitality of viral endosymbiosis not for short-term survival but for long-terms and in the hosts’ evolution as they are the major partners in the hosts’ genomes. In fact the viral symbiogenesis seems to be the most important factor in the evolution of all life on earth (21-24).
Viruses that have been until recently associated with diseases and studied as such, are the most abundant and diverse biological entities on the planet. Recent biodiversity surveys in desert, ocean, soil, animals and plants have revealed the vital roles of viruses in every ecosystem. Due to their obligatory existence as endosymbiont within all other beings larger than themselves, the viruses had to possess evolutionary plasticity to form and maintain the most excellent models of symbiotic relationships. Moreover and most importantly the viruses are the main force behind the genome diversities and genetic evolutions across all species. In fact majority of virus-host interactions all around are commensal or friendly. But even in the case of antagonistic interactions, when there is resistance from the host by fighting the virus through its immune armamentarium, the plasticity and obligation of the virus for endosymbiosis living and evolutionary genetic diversification, assists the survival of the host at the end of the arm race, as the end of life of the host would be the end of life of the virus (25-34)
A great example of such co-evolution and assistance in survival is the “interferon”, a master regulator of the immune system and cell metabolism found in nearly all cell types that has evolved within lives through viral interactions. Another impressive example observed in the interaction between a bacterium and lytic virus and also in the killer viruses of yeast by the virus protection against the lytic phage (virus fighting against its own killing machine) for the survival of the host, ultimately leading to the endosymbiosis or dependency of the host onto the virus for living. Studies on plants that were first to appreciate the importance of viral interactions and symbiosis in ecosystem, diversity and evolution of the plants, have also shown how viruses assist the plants in coping with their adverse environments such as drought, thermal tolerance and adversarial invasions (34-43).
In human studies, GB virus C has been shown to fight against HIV through down-regulation of cell receptors for entry, reduced replication, promoting interferon and interactions with interleukin immune pathways. Latent herpes virus and cytomegalovirus have also been shown to enhance the T cells immune response to influenza and other fatal microbial invasions. Endogenous retroviruses that make up at least 8% of human genomes and non-retroviral endogenous viruses have been revealed in recent years that have been contributing for million of years to the genetic evolution and diversities of all living forms on earth. This so-called endogenization of viral elements has sculpted the evolution of extant genomes in all domains of life. The significance of the contribution of viral interactions in the evolution of their hosts’ genetic make-up, diversity and survival became possible only since the sequencing and analysis of hosts genomes such as humans in the recent years. In brief, viruses that have until recently been considered fatal and antagonistic to life, at least in the field of virology, genetics, evolution, ecosystem and biodiversity, have been appreciated as the most important vital elements of life on the planet (44-63).
What about the aggressive viruses?
As early as mid-80s it has been argued that the virulence of a microbial invasion such as viral infections could be favored by the natural selection and lead more to co-evolution, when pathology enhances genetic transmission, better adaptation and evolution (64). This has also been shown in the case of coronavirus as early as mid-90s, when it was shown that mouse hepatitis virus strain A59 (MHV-A59) a member of the family of coronaviruses, containing a single-stranded positive-polarity RNA genome, similar to other coronaviruses, e.g. SARS and COVID-19, that the co-evolution between the mouse and the virus favors virulence. In a vitro (lab study), Wan Chen and Ralph Baric in 1996 showed the resistant host cells of the mouse that impede the vertical transmission of the virus created a genetic bottleneck for the subsequent selection of a more virulent variants viruses (65).
The virulent coronaviruses such as SARS, MERS and now COVID-19 that once long ago were circumlocated to the wild life mostly bats and one genu have rapidly spread intra-species (e.g. between different genu of bats) and recently inter-species even to humans. This rapid spread of this class of virus with its high virulence is a hallmark of the coronavirus rapid evolution (66). Most recently Letko and colleagues in 2018 have shown that how MERS-CoV by altering the surface charge of its spike (or crown where the name of Corona derives from) surpasses the host cell receptor resistance for entry (67). Koonpaew et al. (68) in 2019 have also shown another coronavirus, Enteropathogenic porcine epidemic diarrhea virus (PEDV) and porcine delta coronavirus (PDCoV) that cause diarrhea in neonatal pigs in the past decade, how circumvent or subvert the host’s first line of defense for entry.
The Evolutionary Pathway of Coronavirus:
Most impressive Wertheim and colleagues in 2013 argued and showed that coronaviruses infecting mammals (alpha-and-beta coronaviruses) and gamma-and-delta coronaviruses infecting birds have co-existed and evolved with these ancient species between 190 to 489 million years ago (69). By analysis of the nucleotide sequences of these coronaviruses at the non-recombinant regions of their genomes and estimation of the branch length of the inferred maximum likelihood of their phylogenies, these researchers were able to extrapolate the lineage of Coronaviruses being as ancient as their hosts, back to an average of 300 million years ago. More recently it has also been shown that the human coronavirus OC43 involved in the common cold or flu, that’s a beta coronavirus type 1, similar to the one infecting cattle (BCoV) has been spilled over from bovine to our homo sapiens ancestor after the first contact with their respiratory tracts (70).
The coronavirus spillover once again has emerged in the recent years with full force of the new types of beta coronavirus infections such as SARS, MERS and now COVID-19. Such pathogen emergence is driven by ecological, genetic factors and codon usage at the service of adaptation of the viruse to the hosts, through natural selection based on translation efficiency and drift according to the genomic mutation pressure. On the path of its evolution and adaptation to its host and breaking any resistance, the human coronavirus OC43 has evolved and changed to many genotypes and variants that had already been shown in the human samples in France and China among other places. What we have seen and suffered by the novel coronaviruses of SARS, MERS and now COVID-19 in the recent years are all the tips of an iceberg of biodiversity and power of co-evolution of the coronaviruses deep down in the ocean of a universal ecosystem on earth (71-81).
An Enemy that was never:
The human coronaviruses that evolved almost a million year ago with our homo sapiens ancestor and lived with us since as a peaceful common cold or flu in our respiratory system has been striking back in the recent years. Our current knowledge despite the vast and fast progress in the field of virology and bridging with genetics, evolution and ecosystem, is still in it infancy, lest to resist the entry of our own coronavirus with its diversity and unbreakable armamentarium. Despite our current and ongoing all global panic over COVID-19, the virus has been fatal only in the elderly and persons with underlying severe medical conditions with poor immune system to adapt to the virus. According to the WHO data, almost 20% of the fatalities have been in the age group of over 80 years old with decreasing drastically by decade down the ladder of life, so 10% in the age group of 70-79, less than 5% in the age group of 60-69 and just over 1% in the age group of 50-59 with rare to almost no mortality in any age group under 50 years old (less than 1% in all age groups of 0-49).
The above factual data is an evidence that the virus is not antagonistic and against our survival, but an endosymbiont and a part of the co-evolution and ecosystem that needs to be with us. While the interaction or invasion of the coronavirus on the surface seems to be unilateral and opportunist with no benefit for us, our scarce knowledge in the very field cautions us to the contrary. Unlike the antagonistic and destructive viruses such as HIV and HPV, the cornoviruses like many so other good viruses have never caused the extinction of their other bovine and avian hosts and not even our own human CoV-OC43 over million years of cohabitation has not harmed us seriously. Therefore it is obvious that our human coronavirus in its different variants, even the current ongoing COVID-19 is a mutual partner that most probably is on the mission of evolving us or helping us to adapt to the current and the future environment. The virulence of the new variants of the human coronavirus as detailed in other viral cases is not a sign against mutual cohabitation or symbiosis and co-evolution but it speaks of the urgency for the need of entry at the service of genomic diversity and evolution. The fatalities of elderly and immune compromised population not withstanding this entry and adaptation for a healthier future is not the fault of the virus. Any resistance to the virus entry, specially at the current time of its utmost urgent virulence for entry will lead to another later more aggressive entry through another more fatal pandemic outbreak.
The current universal panic about the COVID-19 has been so far the worst pandemic event befalling on the humans globally. Although there have been epidemics and pandemics across the human history such as plague and Spanish Flu, none has been this extensive crossing all the waters and lands. While at the onset, all the blames were on China and its Wuhan province where the outbreak started, there has been rarely any place on the face of earth to have skipped this microbial invasion. This universal entry of the coronavirus, this time after the recent SARS and MERS with its powerful virulence is a strong evidence of the natural selection obligation that the virus has for maintenance of our longer-term survival.
Our lack of knowledge and ignorance about the significance of symbiosis with other beings such as viruses that have been the backbones of life like other vital elements making this planet, has been the cause of our world-wide panic never seen before. While even in the scientific arena viruses until recently were thought as antagonistic and pathogens, we need to come to the realization and appreciation of the role of viruses in every single life form from plants to bacteria and larger animals like us. Symbiosis and endosymbiosis is a vital part of life and has existed from the inception of life on the planet with no exceptions, even for us. Our brains and logic that makes us different from the other forms of livings, and was evolved to understand our environment has obviously failed us by our greed and panic.
To get to the point hastily for the urgency of the situation world-wide if there are any common sense and understanding left, the human coronavirus OC43 that has spilled over almost a million year ago from bovines to our homo sapience ancestor has been living with us in peaceful endosymbiosis causing only a mild flu or common cold since. The recent aggressive invasion of the virulent variants of the virus, e.g. SARS, MERS and now COVID-19 does not mean that the virus agenda has changed from a peaceful cohabitation and co-evolution to wipe us out! In fact the current understanding and appreciation in the scientific field is that the virulence and aggression of the virus for entry is not antagonistic to life, but at the service of an urgent entry for maintaining survival, natural selection and evolution on both sides of the equation, the virus and the host. Any resistance and fighting back would lead to the future more aggressive and fatal entry of the virus as history has repeated itself with the outbreak of the current and ongoing COVID-19 that has been much more virulent and lethal than his sisters SARS & MERS.
First and most of all the current coronavirus invasion is not an invasion of an enemy to panic and put us in a defensive mode to fight it back foolishly with our weapons and economic power. The virus has obviously defeated us financially, mentally and physically and has been still proceeding with full force causing more morbidities and mortalities. The fear and damage will not end by COVID-19 that its course as like other coronaviruses will end as a winter virus by the end of season. But more future outbreaks of its more virulent and aggressive type will be our upcoming nightmares. Therefore it is imperative for our survival and maintenance of the balance in our ecosystem, if wish to be a part, and also for our future evolution and survival, to step back and proceed with the following recommendations:
1-Since the COVID-19 has obviously killed the elderly and compromised immune populations, we need to protect this population all over the world with quarantine, vaccination and fostering their immunity.
2- Since the COVID-19 has not and will not kill the younger age groups and immune healthy populations, these age groups do not need at any rate to panic and be quarantined or isolated. If we look well around, the virus has caused no to mild and tolerable symptoms in our young and healthy population that after the infection will leave them a future immunity from the next more virulent outbreaks.
3-Since the majority of the population will be safe even by exposure to the virus and being infected with a future natural immunization that is better than any man-made vaccinations, we need to stop running away from the virus and insulting it with sanitations and isolations.
4-Therefore it is very urgent to return to our normal manners of life as soon as possible and open what have been closed and start running whatever have been halted and welcome the virus in a friendly manner and in peace.
5-Since the universal spread of the COVID-19 is an obvious sign of the urgency of the virus for a global entry into the human race, the welcoming of the virus has to be a world-wide effort with no resistance.
Hope the above recommendations will be appreciated and put in place urgently before the worse future outbreaks befall on us.
Dr.Mostafa Showraki, MD, FRCPC Lecturer, School of Medicine, University of Toronto
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It was not long ago that the human world was attacked by MERS, Ebola, Zika and Noroviruses and just few years ago with the mass killings of SARS. The new year of 2020 just before starting has brought another killing viral attack with it in China in last December, soon spread all across the globe. The new virus that is similar to MERS and SARS is a type of Coronavirus, that is a group of virus causing from common cold to the new killer, novel coronavirus and since it started in 2019 as 2019-nCoV or Wuhan Coronavirus since it started from the Wuhan province in China. Most of these viruses are zoonotic, meaning spread from animals to humans and passed on between humans easily air-borne. Most of the recent case in Wuhan province arose from the famous Huanan Seafood Market from infected live animal meats.
This frightening scenario has stricken the whole globe more than any ongoing man-made wars, costing numerous lives and downfall of the financial and stock markets worldwide that are heavily dependent on China. More haunting than the current mass murdering scene of this new virus is the alarming sign of how viruses like their other microbial counterparts continue in their evolutions and arsenals, more advanced and fatal than any human’s best weaponry. The new coronavirus is the seventh in the line of such type of virus after 229E (one of the causes of common cold), NL63 causing bronchitis and respiratory infection discovered in 2004, OC43 causing pneumonia in immune vulnerable individuals such as infants and elderly discovered in 2004, HKU1 causing acute respiratory infection discovered in 2005, MERS-CoV (Middle East Respiratory Syndrome-related Corona Virus) discovered in 2012, and SARS-CoV (Severe Acute Respiratory Syndrome-related Corona Virus) discovered in 2003.
Another fascinating power of this novel Coronavirus is its capability to create several gnomes so to survive and endure its invasion. From January 12 to January 26, 2020 in only two weeks the virus has more than doubled its genomes from 12 to 28. More frightening about the novel Coronavirus is that it is only a single stranded RNA (not even double stranded or with no DNA as most beings) that in addition to its progressive genomes, acts like a messenger RNA and uses the host cells and organelles for further replication and survival. Novel Coronavirus like SARS uses ACE2 (Angiotensin Converting Enzyme) that has direct effect on cardiac function, as an entry point into human cells.
As we speak a number of countries other than China are hardly working on producing vaccines against the novel Coronavirus by mimicking the virus own protease. But by the time any of these vaccines being first tested on animal models before their clinical applications on infected patients, the novel Coronavirus will boast with its daily increased mass massacre. Microbial invasion such as the novel Coronavirus is like a Trojan Horse and while after the acute attack and relief of the world, since they have already resided in the host bodies, waiting for their next insidious attacks and damage to the body organs, causing malignancies and autoimmune disorders among many other chronic and hardly treatable human diseases.
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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).
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
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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.
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)
Struggling with Anxiety more than usual so that causes dysfunctions in one or more areas of life seems to be very common and more than the current statistics in DSM5 (Diagnostics and Statistics of Manual of Mental Disorders) 5th edition. Please take a few minutes and answer the following survey as an attempt to identify the true rate or prevalence of the common anxiety disorder that’s medically known as GAD (Generalized Anxiety Disorder). To a get close estimate of the prevalence of this condition, we ask everyone who visits this site to fill out the survey even if you don’t have no history of anxiety or depression.
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).
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.
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).
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.
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).
(To: My daughter Tiffany, Mohammad Ali, Rafael Nadal, Milos Raonic and all the injured athletes of the world)
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 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.
(“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,
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.
As adults we spend or should if we don’t 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 someone’s 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 individual’s 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. That’s 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:
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)
(In the memory of my father, a common man, but a poet)
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)
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.
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.