Medical Hypotheses (MED HYPOTHESES )

Publisher: Elsevier


The purpose of Medical Hypotheses is to provide a forum for the presentation and criticism of ideas in medicine and the related biomedical sciences. Most biomedical journals will publish ideas only in papers which also report observations. As the best scientists have repeatedly emphasized, this gives a misleading impression of the process of discovery. The ideas usually come first and they determine what observations should and will be made. Although fully acknowledged in other sciences, this central role of ideas in scientific progress is only now beginning to be widely recognized in medicine. Ideas occur to many people not in a position to test them experimentally. Ideas frequently require much fuller exposition than is allowed in the discussion section of an experimental paper. Ideas should be open to comment by scientists who have not done experimental work in the field. Medical Hypotheses will publish ideas or criticisms of ideas from any person, irrespective of whether any experimental testing of the ideas has been performed by the writer. Medical Hypotheses will also publish letters which comment on articles in the journal. Medical Hypotheses is the only journal fully devoted to the publication of ideas in the biomedical sciences. The justification for its existence is discussed in the editorial printed at the beginning of the first issue (January-February, 1975). If you feel that the aims of Medical Hypotheses are important and worthwhile, please encourage your library to subscribe to it.

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    Medical hypotheses
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    • Publisher last contacted on 18/10/2013
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The inorganic sulfur content of the Western Diet is more than six times greater than the minimal daily requirement. The non-adsorbed organic and inorganic sulfur supports high levels of sulfate reducing bacteria (SRB) in the large intestine. Over time, the combination of elevated dietary inorganic sulfur and high levels of SRB in the gut increases the potential of ultra-exogenous sulfide formation (USF). High levels of SRB in the right colon can sustain USF that overwhelms sulfide oxidation by the colon and sulfide enters into the capillary network of the right colon. White blood cells and platelets in this capillary network are exposed to the elevated sulfide concentration, which induces these cells to generate reactive oxygen species (ROS). An estimated 1.3% of the total cardiac output is impacted by the elevated sulfide every minute. USF for 10 and 78 minutes per day could generate the 12% and 64% of ROS-positive blood cells that were observed in the arterial blood samples of non-hospitalized volunteers and congestive heart failure patients, respectively. More extreme USF is necessary to generate greater percentages of ROS-positive blood cells, since the recirculated blood will provide sulfide oxidation. The dietary inorganic sulfur consumption pattern dictates the abundance of SRB in the gut and therefore, the percent of ROS-positive blood cells. Exposure of blood to a range of sulfide levels may determine the minimum sulfide concentration necessary to generate ROS-positive blood cells. After validation, patients with high levels of ROS-positive blood cells can be evaluated for reduction of oxidative stress by dietary inorganic sulfur control. If USF is confirmed as the source of ROS-positive blood cells, then the problem of oxidative stress becomes manageable through dietary changes, metals supplements, methanogenic probiotics, and antibiotics that target SRB.
    Medical Hypotheses 10/2014;
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    ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by generalized microvascular occlusion. TTP has been related to severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor multimers into less adhesive molecules. However, ADAMTS13 deficiency correlates poorly with severity of thrombocytopenia or microangiopathic hemolysis, with the frequency of neurologic complications or the response to plasma exchange. Also, some patients with severe hereditary ADAMTS13 deficiency consistently relapse every few weeks, whereas others remain asymptomatic into their forties. Taken together, these findings suggest that an additional element is missing in the pathophysiology of TTP. We postulate that both low ADAMTS13 activity and low tissue-plasminogen activator activity are required to trigger TTP attacks. Tissue-plasminogen activator end product, plasmin, extensively degrades von Willebrand factor, breaking-down the bonds between platelets and the blood vessel wall, so that low tissue-plasminogen activator activity prevents a mechanism similar to that of ADAMTS13. The hypothesis that low tissue-plasminogen activator activity plays an important role in TTP pathogenesis is further substantiated by TTP comorbidity. Problems prevalent in patients with TTP attacks or with long-term TTP remission, including increased body mass index, major depression, cognitive abnormalities, hypertension, and premature death, are somehow associated with low tissue-plasminogen activator activity.
    Medical Hypotheses 10/2014; 83:747-750.
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    ABSTRACT: The use of currently available guidelines such as the International Classification of Diseases, 10th Revision (ICD-10) and its clinical modification to assign a principal diagnosis to a patient who has multiple principal diagnoses appears unreliable. This is because these guidelines are complex and uses criteria that are highly subjective. Even when one main diagnosis is selected, the comprehensive list of other diseases that the patient has is often not reported such that the overall clinical condition of the patient is obscured. To address these issues, we have proposed: (i) a simple, potentially reliable and stepwise guide that can be used to assign the single most appropriate main principal diagnosis to each patient and illustrated this with case reports (ii) how to simultaneously report the main and other diagnoses in a scientific paper. It is hoped that our proposal (named NJ model for easy referencing) will help standardize how diagnosis is assigned to patients. � 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 10/2014;
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    ABSTRACT: Castration-resistant prostate cancer (CRPC) is an advanced and incurable stage of the second most frequently diagnosed malignancy in men globally. Current treatment options improve survival modestly but eventually fail due to intrinsic or acquired therapeutic resistance. A hypothesis is presented wherein circulating levels of fibroblast growth factor 23 (FGF23), an endocrine member of the fibroblast growth factor family with phosphaturic properties, are proposed as a prognostic and predictive marker to identify CRPC patients with poor prognosis that are amenable to FGF23 antibody therapy (FGF23i) or treatment with fibroblast growth factor receptor inhibitors (FGFRi). With respect to the latter, FGF23 may also serve as a pharmacodynamic marker enabling individualized FGFRi dosing. We recently discovered that the development of severe and sustained hypophosphatemia in CRPC patients undergoing zoledronic acid therapy for bone metastases was associated with markedly worse prognosis compared to patients without or with only mild and transient hypophosphatemia. Severe hypophosphatemia is a typical manifestation of tumour-induced hypophosphatemic osteomalacia (TIO), a paraneoplastic condition mediated by FGF23 overexpression in most instances. While the postulated tumour-promoting role of FGF23 in CRPC or other malignancies has not yet been studied, several lines of evidence suggest that FGF23 may mediate both severe hypophosphatemia (via its endocrine properties) and aggressive CRPC behaviour (via autocrine and paracrine activities): (i) FGF23 and the necessary signalling machinery (i.e. members of the fibroblast growth factor receptor [FGFR] family and the essential co-receptor α-KLOTHO [KL]) are highly expressed in a sizeable subgroup of CRPC patients; (ii) FGF/FGFR signalling plays important roles in prostate cancer; (iii) FGF23 can induce its own expression via a positive autocrine feedback loop involving FGFR1; and (iv) this positive feedback loop may be triggered by bone-targeted therapies frequently used for the treatment of CRPC-associated bone metastases. While there is a lack of personalized treatment strategies in the management of CRPC to date, FGF23 targeted therapy has the potential to fill this unmet clinical need in the not-so-distant future. In fact, FGFRi are currently in advanced clinical testing for a number of malignancies such as kidney and lung cancer, but there is a lack of conclusive data on FGFRi therapy in patients selected for FGF/FGFR pathway activation.
    Medical Hypotheses 10/2014;
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    ABSTRACT: Meditation is used worldwide by millions of people for relaxation and stress relief. Given sufficient practice, meditators may also experience a variety of altered states of consciousness. These states can lead to a variety of unusual experiences, including physical, emotional and psychic disturbances. This paper highlights the correspondences between brain states associated with these experiences and the symptoms and neurophysiology of epileptic simple partial seizures. Seizures, like meditation practice, can result in both positive and negative experiences. The neurophysiology and chemistry underlying simple partial seizures are characterised by a high degree of excitability and high levels of neuronal synchrony in gamma-band brain activity. Following a survey of the literature that shows that meditation practice is also linked to high power gamma activity, an account of how meditation could cause such activity is provided. This paper discusses the diagnostic challenges for the claim that meditation practices lead to brain states similar to those found in epileptic seizures, and seeks to develop our understanding of the range of pathological and non-pathological states that result from a hyper-excited and hyper-synchronous brain.
    Medical Hypotheses 10/2014;
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    ABSTRACT: An understanding of heart-circulation interaction is crucial to our ability to guide our patients through an episode of septic shock. Our knowledge has advanced greatly in the last one hundred years. There are, however, certain empirical phenomena that may lead us to question the wisdom of our prevailing treatment algorithm. Three extreme but iatrogenically possible haemodynamic states exist. Firstly, inappropriately low venous return; secondly, overzealous arteriolar constriction; and finally, misguided inotropy and chronotropy. Following an unsuccessful fluid challenge, it would be logical to first set the venous tone, then set the cardiac rate and contractility, and finally set the peripheral vascular resistance. It is hypothesized that a combination of dihydroergotamine, milrinone and esmolol should be superior to a combination of noradrenaline and dobutamine for surviving sepsis.
    Medical Hypotheses 09/2014;
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    ABSTRACT: Migraine is a chronic recurring headache for which no complete treatment has been found yet. Therefore, finding new treatment approaches and medicines is important. In this review, we consider the probable mechanism of action of a traditional and ethnic formulary of chamomile extract in sesame oil as a new topical medication for migraine pain relief. Chamomile oil is prepared in traditional Persian medicine by boiling aqueous extract of chamomile in sesame oil. To optimize the procedure, we can use a Clevenger-type apparatus to extract the essential oil and add it to the end product. The preparation includes both essential oils (chamazulene and bisabolol oxide) and polyphenols (a flavonoid such as apigenin and its derivatives). It probably possesses pain relief effects for migraines because of the following properties: 1) chamazulene and apigenin, which inhibit iNOS expression in activated macrophages and can lead to the prohibition of NO release and synthesis; 2) chamomile flavonoids, which have a strong inhibitory effect on endogenous prostaglandin E2 (PGE2) levels in RAW 264.7 macrophages and can play the role of selective COX-2 inhibitor; 3) chamomile polyphenols, which possess anti-inflammatory effects due to the inhibition of pro-inflammatory biomarkers in THP1 macrophages and which can reduce inflammation in neurovascular units (NVU) at the site of migraine pain; 4) chamomile, which has neuroprotective effects because of reduced NO levels; 5) sesamine in sesame oil, which possesses an anti-inflammatory effect. These effects are supported by main pathophysiology theories of migraine such as neural and sensitization theories. Chamomile oil is a traditional formulation still used in Iran as an ethno-medicine. Because of the mentioned mechanisms of action, it can be hypothesized that chamomile oil is a novel medicine for the relief of migraine pain.
    Medical Hypotheses 09/2014;
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    ABSTRACT: Pressure ulcers are one of the most common causes of morbidity, mortality and rehospitalization for those living with Spinal Cord Injury (SCI). Literature examining risk and recurrence of pressure ulcers (PrUs) has primarily focused on the nursing home elderly who do not have SCI. More than 200 factors that increase PrU risk have been identified. Yet unlike the elderly who incur pressure ulcers in nursing homes or when hospitalized, most persons with SCI develop their pressure ulcers as outpatients, while residing in the community. The Veterans Health Administration (VHA) provides medical care for a large number of persons with chronic SCI. Included in the VHA SCI model of chronic disease management is the provision of an annual Comprehensive Preventive Health Evaluation, a tool that has potential to identify individuals at high risk for PrUs. This research was motivated by the clinical observation that some individuals appear to be protected from developing PrUs despite apparently ‘risky’ behaviors while others develop PrUs despite vigilant use of the currently known preventative measures. There is limited literature regarding protective factors and specific risk factors that reduce PrU occurrence in the community dwelling person with chronic SCI have not been delineated. The purpose of this study is to examine the preliminary hypothesis that there are biological and/or psychosocial factors that increase or reduce vulnerability to PrUs among persons with SCI. A limited number of refined hypotheses will be generated for testing in a prospective fashion. A retrospective cross-sectional survey of 119 randomly selected Veterans with SCI undergoing the Comprehensive Health Prevention Evaluation during the year 2009 was performed. Factors that differed between patients with 0, 1 or ⩾ 2 PrUs were identified and stratified, with an emphasis on modifiable risk factors. Three hypotheses generated from this study warrant further investigation: 1) Cumulative smoking history increases the risk of PrUs independent of co-morbidities, 2) Being moderately overweight, BMI>25, with or without spasticity, is a modifiable factor that may be protective and 3) Increased use of a caregiver does not reduce PrU risk. Prospective studies that focus on these hypotheses will lead to evidence-based risk assessment tools and customized interventions to prevent PrUs in persons with SCI in the outpatient setting.
    Medical Hypotheses 09/2014;
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    ABSTRACT: Human stem cells possess memory, and consequently all living human cells must have a memory system. How memory is stored in cells and organisms is an open question. Magnetite is perhaps the best candidate to be a universal memory molecule. Magnetite may give us a clue, because it is the Earth’s most distributed and important magnetic material. It is found in living organisms with no known functions except for involvement in navigation in some organisms. In humans magnetite is found in the brain, heart, liver and spleen. Humans suffer from memory dysfunctions in many cases when iron is out of balance. Anomalous concentrations of magnetite is known to be associated with a neurodegenerative disorder like Alzheimer’s disease. Due to the rapid speed and accuracy of our brain, memory and its functions must be governed by quantum mechanics.
    Medical Hypotheses 09/2014;
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    Medical Hypotheses 09/2014;
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    ABSTRACT: Existing classifications of central nervous system sleep disorders do not often provide tools to diagnose the majority of patients complaining of sleep-related symptoms, nor always guide effective treatment. I present a novel classification system that completely separates clinical syndromes from anatomical localization, pathophysiology, and etiology. The clinical syndrome I present can describe the majority of patients, but can be fractionated into individual subgroups for further study. By then separating the anatomy and physiology from the symptoms, an avenue of research becomes available to study the different possible structures that regulate sleep, that may be damaged and cause syndromes of sleep dysfunction. Some of these may produce symptoms that overlap with narcolepsy and some may be distinct. Because the clinical syndrome should be distinguished from anatomy or physiology, I have proposed the term narcoleptiform syndrome for the clinical syndrome. The model also clearly separates etiology from anatomy in a classical neurological manner. This allows etiology, localization and symptoms to be studied separately. It is likely that different etiologies may produce damage in areas that produce similar syndromes. For example, in this model, different causes of damage to the orexin nucleus would result in the same clinical syndrome. This reinforces the concept of studying anatomy, symptoms and etiology separately. By studying the relationship of syndromes or symptoms to anatomic localization and pathophysiology, it should be possible to test novel approaches to treatment based on different underlying structure or function. For example, patients with lesions in the venerolateral preoptic nucleus or the thalamic intralaminar nuclei may both present with insomnia symptoms but need different treatment; or they might present with symptoms overlapping narcolepsy (a narcoleptiform syndrome) yet need different treatment. In some cases, a single treatment may cross over more than one location, and the best predictor might be symptoms. These are issues that need to undergo careful study on a syndromic, anatomic and physiological bases. This novel model opens up new avenues for understanding central nervous system sleep disorders, providing testable hypotheses regarding diagnosis and treatment.
    Medical Hypotheses 09/2014;
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    ABSTRACT: Mononuclear invasion of Langerhans islet and the ensuing insulitis triggers signal-transduction for the autoimmune mediated pancreatic beta-cell (ß-cell) apoptosis that severely disrupts insulin production resulting in hyperglycemia associated with Type-1 diabetes (T1DM). Today extensive global research is being conducted to eliminate the need for insulin, and even prevent or find a cure for T1DM. The multifactorial combination of autoimmune dysfunction, Langerhans islet hypoxia, and bio-chemical disruption are seen to be contributory factors for ß-cell destruction and the consequential disruption to insulin production. Regeneration of ß-cells back to physiological levels may restore homeostatic insulin levels, reversing T1DM. Evidence suggests that there are still functioning pancreatic ß-cells even in long standing T1DM providing the potential for their regeneration. Although the exact mechanism of ESWT is yet to be fully elucidated, ESWT is seen to influence a complex spectrum of bio-chemical, cellular and neuronal functions (ie. suppression of pro-inflammatory immune response, improved tissue hemodynamics, anti-microbial properties and induction of progenitor cell expression including proangiogenic factors and nitric oxide syntheses). The rationale for the use of extracorporeal shockwaves (ESW) in this instance is attributed to its restorative properties and safety profile demonstrated in cardiology, chronic wounds, osteogenesis, complex pain syndromes, and tendinopathies. ESW may restore autoimmune homeostasis creating a suitable environment for pancreatic ß-cell proliferation that in-turn significantly increases or normalizes endogenous insulin secretion reducing or totally eliminating dependency of exogenous insulin. The devastating complications, morbidity and mortality associated with T1DM warrants the exploration of homeostatic autoimmune restorative treatment (HART) modalities that may partially or fully reverse this disease condition. We present our hypothesis discussing ESW as a potential homeostatic autoimmune restorative treatment (HART) option for T1DM.
    Medical Hypotheses 09/2014;
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    ABSTRACT: Background Hereditary hemorrhagic telangiectasia (HHT) and hepatopulmonary syndrome are disorders characterized by the development of multiple pulmonary arteriovenous malformations (PAVM). Presentation of the hypothesis COX2 may be at the origin of a cascade of pro inflammatory events to favour angiogenesis and PAVM development. Testing the hypothesis HHT and hepatopulmonary syndrome mouse models may be used to show its effects on PAVM formation. Anti COX-2 therapy could also be tested in human individuals, particularly in patients presenting a hepatopulmonary syndrome or HHT twith small PAVM. Implication of the hypothesis PAVMs are one of the main causes of morbidity in patients presenting with HHT disease, owing to the risks of rupture as well as paradoxical embolism exposing to stroke and/or cerebral abscess.. Percutaneous embolization has become the treatment of choice of PAVM. Anti COX2 may prevent from PAVM development and subsequent related complications and avoid either surgery and / or percutaneous embolization and thus subsequent related complication.
    Medical Hypotheses 09/2014;
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    ABSTRACT: Since its introduction in 1960, The Wada test has been considered the gold standard for language lateralization prior to ablative brain surgery. Due to the invasive nature of The Wada test several non-invasive techniques have been alternatively adopted. Recently, it has been suggested that the tongue deviates toward the language dominant cerebral hemisphere on full protraction. This suggestion is based on the important role the tongue plays in articulation and on the close anatomical relationship between the cortical tongue motor area and the motor speech area. It was proposed that this phenomenon could serve as a reliable and simple method for language brain lateralization. However, this hypothesis is still open for verification. In an attempt to correlate tongue deviation and language cerebral dominance we present and discuss in this paper the results of a study conducted on 339 free adult Jordanian volunteers. Tongue deviation and handedness were determined and statistically correlated. Our results showed that 62% of test subjects did not show any tongue deviation on full protrusion. Additionally, 9% of test subjects showed left-sided tongue deviation on full protraction in spite of 90% right handedness with presumed left language dominant cerebral hemisphere. We conclude that, at least in Jordanians, tongue deviation cannot be considered as a reliable indicator for language lateralization.
    Medical Hypotheses 09/2014;