| 1. |
- Björn, Lars Olof, et al.
(author)
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How does light affect melatonin?
- 2008
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; Jun 4, s. 458-458
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Journal article (other academic/artistic)
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| 2. |
- Bredberg, Anders, et al.
(author)
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Targeting versus tinkering: Explaining why the clinic is frustrated with molecular mapping of disease mechanisms.
- 2013
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 81:4, s. 553-556
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Journal article (peer-reviewed)abstract
- We argue that our common diseases should not necessarily be taken as a sign of physiological error. Regulatory networks developed by evolutionary forces to support reproductive fitness happen to include disease as a side-effect. For example, inflammatory and autoimmune diseases are secondary to a strong defence against infections. An evolutionary perspective can help us understand why many drugs targeted to single molecules or linear signaling pathways fail in clinical trials. We present the hypothesis that a tinkering research strategy, as compared with the prevailing reductionist approach, may be more likely to help us find the tools needed to interfere optimally with disease-generating networks. One application of the hypothesis can be to analyze how manipulation with diet and gut microbial flora influences multiple sclerosis patients, rather than to first map in detail the molecular disease mechanism and then develop targeting drugs.
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| 3. |
- Chourbaji, Sabine, et al.
(author)
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CREB-regulated diurnal activity patterns are not indicative for depression-like symptoms in mice and men.
- 2008
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 70:1, s. 117-21
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Journal article (peer-reviewed)abstract
- Activation of the transcription factor CREB by Ser142 phosphorylation is implicated in synchronizing circadian rhythmicity, which is disturbed in many depressive patients. Hence, one could assume that emotional behaviour and neuroendocrinological markers would be altered in CREB(S142A) mice, in which serine 142 is replaced by alanine, preventing phosphorylation at this residue. Moreover, associations of CREB Ser142 and seasonal affective disorder (SAD) might be detectable by the analysis of single-nucleotide polymorphisms (SNPs) in the CREB gene close to the Ser142 residue in SAD patients. However, neither CREB(S142A) mice demonstrate features of depression, nor there is evidence for an association of SAD with the CREB genotypes. Nevertheless, in humans there is an association of a global seasonality score and circadian rhythmicity with the CREB genotypes in healthy control probands, but not SAD patients. This parallels the phenotype of CREB(S142A) mice, presenting alterations of circadian rhythm and light-induced entrainment. Thus it is reasonable to assume that CREB Ser142 represents a molecular switch in mice and men, which is responsible for the (dys)regulation of circadian rhythms.
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| 4. |
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| 5. |
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| 6. |
- Dutton, Edward, 1980-, et al.
(author)
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Spare the rod and spoil the group’s cultural fitness? : Conditions under which corporal punishment leads to detrimental and beneficial outcomes
- 2020
-
In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 145
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Journal article (peer-reviewed)abstract
- Corporal punishment of children is common across human history, and the specific practice of striking the buttocks, known as spanking, seems to have developed independently across a number of separate cultures. This pattern suggests adaptive value, posing a paradox in view of the many reviews stating that spanking has purely negative outcomes on future mental health, and the recommendation of the American Academy of Pediatrics that it be outlawed. We purport to resolve this paradox by separating this particular type of corporal punishment from less controlled lashing out in anger, and we reanalyze these reviews in terms of psychological and physical health outcomes. We find that spanking is associated with positive mental health outcomes when (1) performed by calm parents in a (2) ritualized, structured fashion and combined with (3) other disciplinary techniques within (4) a loving relationship with the child, typically (5) as part of the practice of moral, collective religiosity, and when (6) controlling for confounding variables. In that spanking is noticeably practiced by conservative religious cultural groups, we hypothesize that it can be a fitness-promoting form of behaviour in line with religiousness being an example of a group-fitness-promoting adaptation.
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| 7. |
- Frisk, G, et al.
(author)
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A unifying hypothesis on the development of type 1 diabetes and celiac disease : Gluten consumption may be a shared causative factor
- 2008
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 70:6, s. 1207-1209
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Journal article (peer-reviewed)abstract
- This paper presents a hypothesis of the aetiology of the increasing incidence of type 1 diabetes (T1D). This together with the global increased incidence of celiac disease (CID) and that these increases cannot be explained by genetic factors suggest a common environmental factor for these two diseases. Even though enterovirus (EV) infections are believed to trigger T1D and gluten is the trigger of CD, the increasing intake of gluten containing products all over the world could be the trigger for both diseases directly and indirectly. It has been shown that the duration of exposure to gluten is related to the prevalence of T1D. It has also been shown that T1D patients at onset have an inflammatory reaction in the gut. Hence, early diagnose of CD followed by elimination of dietary gluten will lead to a decreased incidence of T1D.
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| 8. |
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| 9. |
- Hellmer, Kahl, et al.
(author)
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Infant acetylcholine, dopamine, and melatonin dysregulation : Neonatal biomarkers and causal factors for ASD and ADHD phenotypes
- 2017
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In: Medical Hypotheses. - : CHURCHILL LIVINGSTONE. - 0306-9877 .- 1532-2777. ; 100, s. 64-66
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASD) and ADHD are common neurodevelopmental disorders that benefit from early intervention but currently suffer from late detection and diagnosis: neurochemical dysregulations are extant already at birth but clinical phenotypes are not distinguishable until preschool age or later. The vast heterogeneity between subjects' phenotypes relates to interaction between multiple unknown factors, making research on factor causality insurmountable. To unlock this situation we pose the hypothesis that atypical pupillary light responses from rods, cones, and the recently discovered ipRGC system reflect early acetylcholine, melatonin, and dopamine dysregulation that are sufficient but not necessary factors for developing ASD and/or ADHD disorders. Current technology allows non-invasive cost-efficient assessment already from the first postnatal month. The benefits of the current proposal are: identification of clinical subgroups based on cause rather than phenotypes; facilitation of research on other causal factors; neonatal prediction of later diagnoses; and guidance for targeted therapeutical intervention.
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| 10. |
- Hellmer, Kahl, et al.
(author)
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Pupillometric screening of potential neonatal acetylcholine, dopamine, and melatonin dysregulations in neurodevelopmental disorders
-
In: Medical Hypotheses. - 0306-9877 .- 1532-2777.
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Journal article (other academic/artistic)abstract
- Autism spectrum disorders (ASD) and ADHD are common neurodevelopmental disorders that benefit from early intervention but currently suffer from late detection and diagnosis: neurochemical dysregulations are extant already at birth but clinical phenotypes are not distinguishable until preschool age or later. The vast heterogeneity between subjects’ phenotypes relates to interaction between multiple unknown factors, making research on factor causality insurmountable. To unlock this situation we pose the hypothesis that atypical pupillary light responses from rods, cones, and the recently discovered ipRGC system reflect early acetylcholine, melatonin, and dopamine dysregulation that are sufficient but not necessary factors for developing ASD and/or ADHD disorders. Current technology allows non-invasive cost-efficient assessment already from the first postnatal month. The benefits of the current proposal are: identification of clinical subgroups based on cause rather than phenotypes; facilitation of research on other causal factors; neonatal prediction of later diagnoses; and guidance for targeted therapeutical intervention.
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| 11. |
- Husser, Daniela, et al.
(author)
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Electroatriography - Time-frequency analysis of atrial, fibrillation from modified 12-lead ECG configurations for improved diagnosis and therapy
- 2007
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 68:3, s. 568-573
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Journal article (peer-reviewed)abstract
- Current atrial fibrillation (AF) management guidelines suggest that initially a decision must be made to apply either a rate control or rhythm control strategy in the individual patient. However, patients' selection remains substantially empirical and the strategy initially chosen often proves unsuccessful and alternative therapies must be adopted. Thus, it seems desirable to develop and apply tests that quantify AF disease state and guide AF management. The overall hypothesis of this paper is that time-frequency analysis of AF from modified 12-lead ECG configurations will improve AF management beyond current diagnostic and therapeutic standards. In particular, we present a novel concept in which 12-lead ECG configurations are modified for time-frequency analysis of AF (electroatriography). While five electrodes (VR, VL, VF, V1, V2) are placed in the conventional position, the other four electrodes (V3, V4, V5, V6) are empirically repositioned anterior or posterior over the atria. By applying spatiotemporal QRST cancellation and time-frequency analysis to these recordings in 19 patients with persistent AF, fibrillatory rate dispersion among individual anterior (25 14 fibrillations per minute, fpm) and posterior leads (16 +/- 11 fpm) as well as individual anterior/posterior rate gradients ranging between -24 and +116 fpm could be identified. Consequently, the portrayed techniques may form the conceptual basis for individualized noninvasive characterization of AF. Initiation of further studies using the described techniques in different AF subsets, for comparisons with intracardiac recordings and outcome of different therapies, e.g. cardioversion, antiarrhythmic drug and ablation therapy may be stimulated. (c) 2006 Published by Elsevier Ltd.
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| 12. |
- Håglin, Lena
(author)
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High serum phosphate concentration as the result of smoking might underlie the lower risk of Parkinson's disease
- 2015
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 85:3, s. 287-290
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Journal article (peer-reviewed)abstract
- Epidemiological studies have found a negative association between cigarette smoking and Parkinson's disease (PD): PD patients are approximately 50% less likely to have smoked cigarettes than age- and sex-matched controls. In both women and men, the PD protection effect of smoking may be explained by higher levels of phosphate in serum (S-P) and triglycerides (S-TG) in smokers compared to non-smokers. That is, the protecting effect from smoking could be mediated by either a high S-P or high S-TG levels. I suggest that higher S-P as the result of smoking may be associated with intracellular depletion of Pi in skeletal muscle and that this depletion of Pi is associated with increased availability of phosphate for the brain. This increased phosphate availability would protect against PD, as oxidative phosphorylation in the mitochondria is a central and persistent phenomenon in the pathogenesis cascade of PD. Phosphate is necessary for energy production in the form of creatine phosphate (CP) and adenosine-tri-phosphate (ATP) in the brain and skeletal muscle. As such, hypophosphatemia increases risk of cell death. In some clinical instances, this energy depletion may pre-dispose to dopamine neuron death. Mitochondrial dysfunction is associated with the generation of oxidative stress and mediates the induction of apoptosis. Studies with NMR spectroscopy reveal that an energy deficit in brain cells is a strong mark for PD although this differed for men and women. Compared to women, men had lower serum phosphate and ATP levels in the brain (about 15% lower). In addition to sex differences, age, stress, and malnutrition may cause low serum phosphate levels, a situation that could contribute to the lack of energy available to the brain and the risk of PD. As hypophosphatemia is present in overnutrition and has an inverse relation with a high BMI, both obesity and malnutrition are considered to be presumptive risk factor for PD.
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| 13. |
- Ilbäck, Nils-Gunnar, et al.
(author)
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Do surface-active lipids in food increase the intestinal permeability to toxic substances and allergenic agents?
- 2004
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 63:4, s. 724-30
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Journal article (other academic/artistic)abstract
- The incidence of many common diseases has increased during the last decades. High fat intake is a risk factor for many diseases. We propose that some of the negative effects of fat are caused by lipid-induced damage of the gastrointestinal epithelium, thus compromising the epithelial function as a barrier for passage of toxic substances and allergenic agents to the circulatory system. Monoglycerides (MGs), phospholipids and fatty acids (FAs) are surface-active molecules that in pharmaceutical studies act as permeability enhancers for hydrophilic drugs with low absorption. Three possible mechanisms were proposed: (a) lipid-induced alterations in intracellular events may cause destabilization of tight junctions between the GI epithelial cells, (b) lipids may destabilize cell membranes, (c) lipids cause intestinal cell damage, which increase the permeability of the GI epithelium. These "side effects" of lipids may partly explain the association between fat intake and disease observed in epidemiological studies.
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| 14. |
- Jamshidi, Nima, et al.
(author)
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Design and testing of statistical methods to classify the severity of steppage gait based on center of pressure data
- 2012
-
In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 79:3, s. 334-337
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Journal article (peer-reviewed)abstract
- In this research kinematics parameters derived from ground reaction forces were evaluated to limit differential diagnoses and measure the degree of disabilities during walking among neuropathic subjects. 25 neuropathic subjects affected by drop foot and 20 normal subjects were enrolled in the study. Each subject was tested in average 10 ± 2 times for calculating kinetics parameters derived from ground reaction forces. The results revealed that the center of pressure displacement pattern in sole of foot can be a good index for differential diagnoses and measuring the degree of disabilities. This research can extend the clinical applications of ground reaction force plate and introduce suitable criteria to measure the degree of disability among neuropathic patients. © 2012 Elsevier Ltd.
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| 15. |
- Kerekes, Nora, 1969-, et al.
(author)
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Neuroinflammation as a possible link between attention-deficit/hyperactivity disorder (ADHD) and pain
- 2021
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 157
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Journal article (peer-reviewed)abstract
- Attention-deficit/hyperactivity disorder (ADHD) and pathological pain are two complex syndromes of multifactorial origin. Despite their prevalence and broad impacts, these conditions are seldom recognized and managed simultaneously. The co-existence of neuropsychiatric conditions (such as ADHD) and altered pain perception and chronic pain has been noted in children, and the comorbidity of ADHD and chronic pain is well documented in adults. Pathophysiological studies have suggested dysfunction of the dopaminergic system as a common neurochemical basis for comorbid ADHD and pain. Considerable evidence supports the role of neuroinflammation in the pathophysiology of both. We suggest that central neuroinflammation underlies altered pain perception and pain sensitization in persons with ADHD. Based on our hypothesis, targeting neuroinflammation may serve as a potential new therapeutic intervention to treat ADHD and comorbid pain in children and adolescents and a preventive strategy for the development of chronic pain in adults with ADHD.
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| 16. |
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| 17. |
- Kumar, Arvind, et al.
(author)
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Information homeostasis as a fundamental principle governing the cell division and death
- 2011
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 77:3, s. 318-322
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Journal article (peer-reviewed)abstract
- To express the genetic information with minimal error is one of the key functions of a cell. Here we propose an information theory based, phenomenological model for the expression of genetic information. Based on the model we propose the concept of 'information homeostasis' which ensures that genetic information is expressed with minimal error. We suggest that together with energy homeostasis, information homeostasis is a fundamental working principle of a biological cell. This model proposes a novel explanation of why a cell divides and why it stops to divide and, thus, provides novel insights into oncogenesis and various neuro-degenerative diseases. Moreover, the model suggests a theoretical framework to understand cell division and death, beyond specific biochemical pathways.
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| 18. |
- Landin-Olsson, Mona, et al.
(author)
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Is type 1 diabetes a food-induced disease?
- 2013
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 81:2, s. 338-342
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Journal article (peer-reviewed)abstract
- The incidence of type 1 diabetes among children has almost doubled during the last decades in Sweden. Type 1 diabetes is considered as an autoimmune disease with unknown aetiology. Here we propose that the immune reaction may be initiated by food-derived mechanisms. The incidence of diabetes parallels an increased consumption of pasta, white bread, meat, cheese, low-fat milk, exotic fruits, soda, and snacks. Simultaneously, the consumption of potatoes, butter, high-fat milk, and domestic fruit has decreased. Three categories of food related reaction mechanisms are discussed against the following items (1) proteins from wheat, meat, and milk, (2) fat from processed food, and (3) exotic fruits. The current food consumption is suggested to initiate a pro-inflammatory reaction in the intestine and thereby reduce the intestinal barrier function. This may influence tolerance development and thus pave the way for an autoimmune attack on pancreatic beta cells.
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| 19. |
- Lynoe, Niels, et al.
(author)
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Is there a common denominator for Brief Resolved Unexplained Events, Sudden Infant Death Syndrome, and alleged Shaken Baby Syndrome?
- 2020
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 144
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Journal article (peer-reviewed)abstract
- We propose the medical hypothesis that a common denominator may be the precursor for Brief Resolved Unexplained Events (BRUE), cases of Sudden Infant Death Syndrome (SIDS) as well as to cases of alleged Shaken Baby Syndrome (SBS) without external signs of trauma. Although previous studies have emphasized differences, we have focused on the overarching common denominators of the three conditions in terms of mechanism theories. In consequence, fatal cases with subdural hemorrhage (SDH) classified as SBS could be classified as high risk BRUE with SDH. Fatal cases without SDH could be classified as SIDS. Non-fatal cases with SDH and retinal hemorrhages (RHs), currently classified as SBS, could be classified as BRUE with SDH and RHs, leaving a fourth group of BRUE without SDH and RHs. While both the BRUE and the SIDS diagnoses have been refined and developed, alleged abusive head trauma (AHT) cases with and without external signs of trauma have been indiscriminately combined. This is analogous to indiscriminately grouping together, e.g., headache due to a brain tumor or headache after head trauma. Alleged AHT cases with external signs of trauma and high velocity impact might be explained by the traditional AHT mechanism theories, whereas the one-third of all alleged AHT cases without external signs of trauma could be explained by the hypoxia cascade theory and/or other non-shaking theories.
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| 20. |
- Lynoe, Niels, et al.
(author)
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Is there an association between infantile colic and subdural hemorrhage?
- 2020
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 144
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Journal article (peer-reviewed)abstract
- We present the hypothesis that subdural hemorrhages during childbirth might be associated with so-called three-month colic, whereby an infant cries intensively and repeatedly during its first three months. A traditional interpretation is that this infantile crying is associated with nutrition and is accordingly "a gut issue", but this is probably not the whole explanation. It has also been suggested that infantile crying can trigger a caregiver to shake the baby to make it stop crying, thereby inflicting a subdural hemorrhage. A mechanism-based argument supporting our hypothesis would be that the bilateral film-thin subdural hemorrhage associated with a high percentage of deliveries might cause meningeal irritation and in some cases also symptoms as inconsolable crying. An epidemiological argument is that infantile crying is more frequent among first-born, male and premature babies; these categories have also an increased incidence of subdural hemorrhage. Moreover, preventive programs for managing infantile crying have had no effect on the incidence of alleged shaken baby cases. As infantile crying is currently considered unexplained, it is reasonable to explore the proposed hypothesis and strategies which refute or corroborate it. We suggest that a cohort study of premature, first born and male babies with and without infantile crying are examined with brain MRI scan soon after delivery with clinically and MRI follow up during 3-6 months.
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| 21. |
- Lynøe, Niels, et al.
(author)
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Prolonged unexplained event might change an "unreliable perpetrator" into a "reliable resuscitator"
- 2024
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 189
-
Journal article (peer-reviewed)abstract
- During the 1980′s a sudden life-lessness attack in a very young infant was described as “near-SIDS”, and a caregiver who observed and tried to revive the infant was considered to be reliable and honourable. If, after the later acceptance of the traditional shaken baby theory, bilateral thin subdural hemorrhages (SDH) and retinal hemorrhages (RH) are detected after a lifelessness attack such a reliable caregiver has by default been transformed into an unreliable perpetrator of violent shaking. In 2016, the term “near-SIDS” was – via “apparent life-threatening event” (ALTE) − replaced by “brief resolved unexplained event” (BRUE). We suggest that such a life-threatening event is not always brief, and not always resolved. Based on a neglected hypoxia theory from 2004 we suggest as a hypothesis that a prolonged episode of apnea can result in brain hypoxia, brain edema, SDH, RH and increased intracranial pressure. The new hypothesis includes two new concepts: Prolonged Non-fatal Unexplained Event (PNUE) and Prolonged Fatal Unexplained Event (PFUE) which together with the hypoxia theory might explain why these two separate diagnoses have been conflated into one, viz. shaken baby syndrome (SBS). We suggest a study design that might corroborate or falsify the hypothesis, and if our hypothesis is corroborated, current “unreliable perpetrators” could be re-established as reliable resuscitators.
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| 22. |
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| 23. |
- Lövheim, Hugo
(author)
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A new three-dimensional model for emotions and monoamine neurotransmitters
- 2012
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 78:2, s. 341-348
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Journal article (peer-reviewed)abstract
- The monoamines serotonin, dopamine and noradrenaline have a great impact on mood, emotion and behavior. This article presents a new three-dimensional model for monoamine neurotransmitters and emotions. In the model, the monoamine systems are represented as orthogonal axes and the eight basic emotions, labeled according to Tomkins, are placed at each of the eight possible extreme values, represented as corners of a cube. The model may help in understanding human emotions, psychiatric illness and the effects of psychotropic drugs. However, further empirical studies are needed to establish its validity. (C) 2011 Elsevier Ltd. All rights reserved.
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| 24. |
- Manjer, Jonas, et al.
(author)
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Covariance of breast cancer incidence with smoking-, oestrogen- and diet-related cancers in pre- and postmenopausal women in Sweden
- 1999
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 52:6, s. 561-568
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Journal article (peer-reviewed)abstract
- Effects of smoking on breast cancer risk remains controversial. Tar products have been claimed to increase risk, antioestrogenic effects to reduce risk. Another possibility is that associations to smoking have been confounded by diet. The increasing incidence of breast cancer from 1960 to 1994 in Sweden is parallel to that of lung cancer and the increasing proportion of female smokers. The incidence of endometrial and colon cancer was in premenopausal women negatively and in postmenopausal women positively related to the incidence of breast cancer. Possible explanations and hypotheses to the different co-variance between breast cancer and lung, endometrial and colon cancer in pre- and postmenopausal women are discussed from the perspectives of smoking, sex hormones and diet. It is concluded that the strong and specific positive relationship between breast and lung cancer in premenopausal women is compatible with the hypothesis that aromatic hydrocarbons may be involved in the causation of disease.
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| 25. |
- Nehme, P. A., et al.
(author)
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Reduced melatonin synthesis in pregnant night workers : Metabolic implications for offspring
- 2019
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 132
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Journal article (peer-reviewed)abstract
- Several novel animal studies have shown that intrauterine metabolic programming can be modified in the event of reduced melatonin synthesis during pregnancy, leading to glucose intolerance and insulin resistance in the offspring. It is therefore postulated that female night workers when pregnant may expose the offspring to unwanted health threats. This may be explained by the fact that melatonin is essential for regulating energy metabolism and can influence reproductive activity. Moreover, the circadian misalignment caused by shift work affects fertility and the fetus, increasing the risk of miscarriage, premature birth and low birth weight, phenomena observed in night workers. Thus, we hypothesize that light-induced melatonin suppression as a result of night work may alter intrauterine metabolic programming in pregnant women, potentially leading to metabolic disorders in their offspring.
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| 26. |
- Ott, Michael, et al.
(author)
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Metformin-associated lactic acidosis may be treatable with thiamine
- 2024
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 189
-
Journal article (peer-reviewed)abstract
- Metformin is a biguanide antidiabetic and a first-line therapy for type-2 diabetes mellitus. It is highly effective, cheap, and easily available since taken in tablet form. Metformin-associated lactic acidosis (MALA) is a serious adverse event with high mortality. It is currently treated with bicarbonate and haemodialysis. The mechanism by which metformin can precipitate lactic acidosis remains subject to debate. Lactic acidosis has also been reported in thiamine (vitamin B1) deficiency. Thiamine deficiency results in a switch from aerobic to anaerobic metabolism with accumulation of lactate. MALA and thiamine-associated lactic acidosis are usually considered separate entities. Both, thiamine and metformin are competitive substrates of the organ cation and thiamine transporters. This way, metformin could cause thiamine deficiency in liver cells. We hypothesize that MALA may be treatable with thiamine. High-dose intravenous thiamine treatment is used routinely for the treatment of Wernicke's encephalopathy and is regarded as safe. Thiamine has been reported to have improved MALA in four cases, who had been refractory to haemodialysis. Thiamine is widely available, easy to administer, and cheap. Thiamine could already be given while waiting for dialysis. Above all, thiamine could prove life-saving in the treatment of MALA in clinical settings in which dialysis is not available.
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| 27. |
- Pajediene, Evelina, et al.
(author)
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Subjective and objective features of sleep disorders in patients with acute ischemic or haemorrhagic stroke: It is not only sleep apnoea which is important
- 2020
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In: Medical Hypotheses. - : CHURCHILL LIVINGSTONE. - 0306-9877 .- 1532-2777. ; 136
-
Journal article (peer-reviewed)abstract
- Background: More than half of stroke patients present with a sleep-related breathing disorder including both central and obstructive forms of sleep apnoea. A cerebral infarction in different brain areas can disrupt sleep regulating pathways and cause insomnia, hypersomnia, circadian rhythm disturbances and other sleep disorders. Therefore, there is a need of objective data about various sleep disorders arising after ischemic or haemorrhagic stroke in order to implement practical recommendations how to suspect, diagnose and treat these conditions. Our medical hypothesis is that non-breathing sleep disorders are common among patients with acute ischemic or haemorrhagic stroke. Objective: To investigate the subjective and objective sleep parameters in the patients with an acute ischemic or haemorrhagic stroke. Methods: In the acute period (from 3 to 10 days after the first symptoms) of stroke all the patients completed questionnaires about sleep complaints and symptoms experienced before and after stroke, Epworth Sleepiness Scale (ESS), National Institute of Health Stroke Scale, Hospital Anxiety and Depression Scale and Modified Rankin Scale. Patients were included for further polysomnography (PSG) and sleep electroencephalography according to these criteria: (1) patients expressing severe sleep related complaints and/or symptoms that are new or have exacerbated after the stroke; and/or (2) patients having the ESS score equal or amp;gt;10. Results: 66 patients were examined in the acute period of stroke. 33 (50%) patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mostly related to obstructive sleep apnoea (OSA) and insomnia. Finally, 13 (19.7% of the whole sample) patients were selected for performing PSG. 12 of 13 patients were diagnosed with sleep disorder: 1 patient got the diagnosis of mild OSA, 1 - central sleep apnoea (CSA), 2 - combination of OSA and CSA, 1 - combination of mild OSA, periodic limb movement disorder (PLMD) and REM sleep behaviour disorder (RBD), 1 - combination of mild OSA and PLMD, 3 - combination of PLMD and insomnia, 3 - insomnia. There were no significant relations between type, location or treatment of stroke and various PSG measures, as well as type of a diagnosed sleep disorder. Conclusions: Half of our acute stroke patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mainly related to OSA or insomnia. In the selected PSG group almost all patients were diagnosed with a sleep disorder, half of them having non-breathing sleep disorder, such as PLMD, RBD and insomnia.
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| 28. |
- Persson, Annette, et al.
(author)
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The glioma cell edge - winning by engulfing the enemy?
- 2009
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 73, s. 336-337
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Journal article (peer-reviewed)abstract
- Malignant glioma and glioblastoma multiforme form the largest group of highly malignant brain tumours, for which there is yet no definitive cure. Different approaches to treatment have been tried, in vain or with minimal benefit for the patient. In addition to surgery, radiation and chemotherapy, immunotherapy aiming at evoking an inflammatory reaction against the tumour itself has been tried. Immunotherapy has shown good results in an experimental mouse model, but no convincing efficacy/success in patients. Why are the gliomas always winning, how do they take the lead? The following phenomena lead us to propose an hypothesis about the reason for the glioma lead: the reported findings of phagocytic activity in reactive and neoplastic astrocytes in animal models and humans; the frequently observed ingested "non-self material"/debris in glioma cells; the markedly high contents of tumour cells with phagocytic phenotype in gliomas and the signs of only limited and temporary inflammatory reactions in different immunotherapy attempts. Whether it being a true phagocytosis, an engulfing or comparable activity by the glioma cells, contributing to the tumour's self defense against e.g. antitumoural therapies, it should be beneficial to attempt hampering these self defense properties e.g. by blocking their engulfing capacity.
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| 29. |
- Persson, Mikael
(author)
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Airborne contamination and surgical site infection : Could a thirty-year-old idea help solve the problem?
- 2019
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 132
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Journal article (peer-reviewed)abstract
- Surgical site infection (SSI) is a most serious postoperative complication, associated with increased morbidity and mortality, as well as extended therapy and elevated healthcare costs. In open clean surgery, e.g. orthopedic and cardiothoracic operations, the risk of SSI is strongly correlated with the amount of airborne bacteria being present in the operating room and the surgical field. The source of these bacteria is the surgical team itself, as we all emit thousands of bacteria-carrying skin particles every minute into the air. Although the risk of airborne contamination has decreased over the years, thanks to modern surgical clothing and advanced operating room ventilation, airborne bacteria are still detected and cause SSI. However, during the past thirty years there has been a simple and potentially effective preventive method waiting to be noticed. In 1986 Hall, Mackintosh and Hoffman found in a controlled experimental study that the application of regular unperfumed skin lotion to a person's body reduced the emission of airborne bacteria-carrying particles by approximately 90%. Moreover, the effect lasted at least 4 hours, which corresponds to a major surgical procedure. Thus, in the light of those results the present paper puts forth the hypothesis that this method can decrease the incidence of airborne bacterial contamination and SSI in open clean surgery. The paper also discusses the rationale and advantages of the method, and questions why it has escaped scientific attention for so long. In healthcare, difficult problems rarely have a simple and cheap solution. However, the use of ordinary skin lotion in open surgery may just be one, as it could potentially help prevent surgical site infection, and thereby increase patient safety and reduce healthcare costs.
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| 30. |
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| 31. |
- Pikwer, Andreas
(author)
-
Depersonalization disorder may be related to glutamate receptor activation imbalance.
- 2011
-
In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 77, s. 593-594
-
Journal article (peer-reviewed)abstract
- Low-dose ketamine administration mimics, both clinically and on gross neuroimaging, depersonalization disorder. The perceptual effects of ketamine may be due to secondary stimulation of glutamate release and lamotrigine, possibly by inhibited glutamate release, may reduce some of ketamine's so-called dissociative effects. However, lamotrigine does not seem to be useful in the treatment of depersonalization disorder. Glutamate release in prefrontal cortex is increased by subanaesthetic doses of ketamine, resulting in increased inhibition, possibly via intercalated GABAerg cells, of projections from amygdala, affecting structures critically involved in depersonalization. I speculate that, in depersonalization disorder, the increased glutamate activity in prefrontal cortex is due to intrinsic imbalance, resulting in long-term potentiation, at the postsynaptic glutamate receptors on the GABAerg interneurons while the same receptor abnormality at the synapses on the intercalated GABAerg cells of the amygdala result in long-term depression in the case of either normal or high glutamate release.
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| 32. |
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| 33. |
- Redfors, Björn, et al.
(author)
-
Are the different patterns of stress-induced (Takotsubo) cardiomyopathy explained by regional mechanical overload and demand: Supply mismatch in selected ventricular regions?
- 2013
-
In: Medical hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 81:5, s. 954-960
-
Journal article (peer-reviewed)abstract
- Takotsubo cardiomyopathy (TCM) or stress-induced cardiomyopathy is an increasingly recognized syndrome characterized by severe regional left ventricular dysfunction in the absence of an explanatory coronary lesion. TCM may lead to lethal complications but is completely reversible if the patient survives the acute phase. The pathogenesis of TCM and the mechanism behind this remarkable recovery are unknown. Plasma levels of catecholamine are elevated in many TCM patients and exogenously administered catecholamine induces TCM-like cardiac dysfunction in both humans and rats. A catecholamine excess increases myocardial metabolic demand by increasing the force of contraction as well as the heart rate, and also alters cardiac depolarization patterns. We propose that an altered spatiotemporal pattern of cardiac contraction and excessive force of contraction may lead to a redistribution of wall stresses in the left ventricle. This redistribution of wall stress causes regional mechanical overload of regions where wall tension becomes disproportionately great and renders these cardiomyocytes "metabolically insufficient". In other words, these cardiomyocytes experience a demand: supply mismatch on the basis of excessive metabolic demand. In order to prevent the death of these cardiomyocytes and to prevent excessive wall tension from developing in neighboring regions, a protective metabolic shutdown occurs in the affected cardiomyocytes. This metabolic shutdown, i.e., acute down regulation of non-vital cellular functions, serves to protect the affected regions from necrosis and explains the apparently complete recovery observed in TCM. We propose that this phenomenon may share important characteristics with phenomena such as ischemic conditioning, stunning and hibernation. In this manuscript, we discuss our hypothesis in the context of available knowledge and discuss important experiments that would help to corroborate or refute the hypothesis.
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| 34. |
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| 35. |
- Sandgren, Anna M., et al.
(author)
-
ADHD-originating in the gut? : The emergence of a new explanatory model
- 2018
-
In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 120, s. 135-145
-
Journal article (peer-reviewed)abstract
- The microbiome-gut-brain axis paradigm explains that alterations in the central nervous system and behavior may be secondary to functional changes in the gut in general and more specifically the enteric nervous system. An unfavorable development of the intestinal microbial ecosystem, leading to e.g. a diminished microbial diversity, may play a central role. This paper outlines, and describes the theoretical basis of, a novel integrative model explaining the etiology and pathogenesis of ADHD in a microbiota-gut-brain context, taking into account the complexity of the bi-directional signaling between the gut and the brain.
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| 36. |
- Sodersten, P, et al.
(author)
-
Obesity and the brain
- 2011
-
In: Medical hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 77:3, s. 371-373
-
Journal article (peer-reviewed)
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| 37. |
- Stenberg, Pål, et al.
(author)
-
Zinc is the modulator of the calcium-dependent activation of post-translationally acting thiol-enzymes in autoimmune diseases.
- 2015
-
In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 84:4, s. 331-335
-
Journal article (peer-reviewed)abstract
- Post-translational modifications of proteins can generate antigenic conformations that may cause autoimmune diseases in persons with specific HLA-haplotypes. Monocytes and macrophages, attracted to an inflamed site, can release post-translationally acting enzymes, such as transglutaminases and peptidylarginine deiminases. In vivo, the activation of these enzymes is crucial for the further course of event. Our hypothesis is that zinc modulates the activation of these calcium-dependent thiol-enzymes. Persons with celiac disease carry antibodies against deamidated dietary gluten and against transglutaminase type 2. Similarly, antibodies against citrulline-containing peptides and against peptidylarginine deiminase are detected in patients with rheumatoid arthritis. Thus, in two major autoimmune diseases, antibodies are detected against post-translationally modified proteins and against the thiol-enzymes responsible for catalyzing the modifications. In vitro, physiological concentrations of zinc reversibly inhibit the calcium-dependent activation of transglutaminases. Zinc attenuates the calcium-induced increase in affinity between transglutaminase 2 and serum from patients with celiac disease. Peptidylarginine deiminases are also inhibited by zinc. Moreover, zinc is rapidly redistributed in animals when an infection is induced. This pathway starting with an unspecific inflammation and ending up with an immune reaction against a specific tissue constitutes a theme with variations in other autoimmune diseases, such as dermatitis herpetiformis, multiple sclerosis, and type 1 diabetes. Inhibitors against transglutaminases and peptidylarginine deiminases have a great pharmacological potential. Interestingly, a large portion of the population may have been exposed to such an inhibitor. The primary metabolite of ethanol, acetaldehyde, can probably function as an irreversible inhibitor of these enzymes by forming a hemithioacetal with the thiol group of the active site. Not surprisingly, epidemiological studies have shown that alcohol is beneficial in rheumatoid arthritis. We predict that a similar situation will be observed in multiple sclerosis. The affinity of chelators such as EDTA and EGTA for Zn(2+) is three orders of magnitude greater than that for Ca(2+). This frequently overlooked complication imposes problems in biomedical research since a restoration of the zinc level can never be achieved in a blood sample which has been anti-coagulated by calcium chelators. The new synthetic direct thrombin inhibitors may offer a better way of preventing coagulation in vitro.
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| 38. |
- Stenman, Emelie, et al.
(author)
-
Increased monoaminergic neurotransmission improves compliance with physical activity recommendations in depressed patients with fatigue.
- 2012
-
In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877.
-
Journal article (peer-reviewed)abstract
- Clinical studies have shown that moderately intense physical activity effectively treats various types of depression. Beneficial effects have been reported in the acute phase of the disease as well as in a long-term perspective. In addition, epidemiological studies have shown that inactivity increases the risk of depression and that exercise prevents relapse. Depressed patients are often prescribed antidepressants, with or without psychotherapy. Some studies have, however, suggested that the most frequently used antidepressants, selective serotonin reuptake inhibitors (SSRIs), contribute to fatigue, which is a common residual symptom associated with depression and the target of the proposed study. Profound fatigue may in turn decrease the ability and motivation to perform the beneficial physical activity, e.g. via executive dysfunction. Fatigue and impaired executive function are commonly linked to disturbed cerebral dopaminergic and noradrenergic neurotransmission. This kind of dysfunction is hard to overcome, even when the major symptoms of depression are alleviated. Interestingly, physical activity has been suggested to improve the dopamine and norepinephrine neurotransmission. Furthermore, the favorable effects may be reciprocal; improved dopamine and norepinephrine transmission in the brain may hypothetically increase the ability and motivation to exercise, since some parts of the brain (e.g. the prefrontal cortex, striatum and cerebellum) that control movement and initiative receive dopaminergic and noradrenergic projections. Based on these findings and assumptions, our hypothesis is that increased dopaminergic and noradrenergic neurotransmission, via intake of a dopamine- and norepinephrine-enhancing agent, improves the compliance with prescribed physical activity in patients with depression and residual fatigue. We also believe that the increased physical activity can prevent relapse into depression, even after interruption of medication. Since increased physical activity also has been shown to improve executive cognitive function, we suggest that executive function should be examined as a secondary outcome together with other possibly related variables such as quality of life, sick leave and BMI.
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| 39. |
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| 40. |
- Uvnäs-Moberg, Kerstin, et al.
(author)
-
Oxytocin is a principal hormone that exerts part of its effects by active fragments
- 2019
-
In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 133, s. 1-9
-
Journal article (peer-reviewed)abstract
- Oxytocin is a nonapeptide consisting of a cyclic six amino-acid structure and a tail of three amino acids. It was originally known for its ability to induce milk ejection and to stimulate uterine contractions. More recently, oxytocin has been shown to stimulate social behaviors, and exert pain-relieving, anti-stress/anti-inflammatory and restorative effects. We hypothesize that oxytocin is a principal hormone that, in part, exerts its effects after degradation to active fragments with more specific effect profiles. Experimental findings on rats show that administered oxytocin exerts biphasic effects. For example, after an initial increase in pain threshold, a second more long-lasting increase follows. Blood pressure and cortisol levels initially increase and then reverse into a long-lasting decrease in blood pressure and cortisol. Whereas the initial effects are, the second-phase effects are not blocked by an oxytocin antagonist, but by an opioid mu-antagonist and by an alpha 2-adrenoreceptor antagonist, respectively, suggesting that other receptors are involved. Repeated administration of oxytocin induces multiple anti-stress effects, which are mediated by alpha 2-adrenoreceptors. Repeated administration of linear oxytocin and linear oxytocin fragments with a retained C-terminal reduce spontaneous motor activity, a sedative or anti-stress effect, suggesting that alpha 2-adrenoreceptors have been activated. In contrast, linear mid-fragments stimulate motor activity. Low-intensity stimulation of cutaneous nerves in rats, as well as breastfeeding and skin-to-skin contact between mothers and babies, trigger immediate anti-stress effects. Some of these effects are likely caused by open ring/linear C-terminal fragments activating alpha 2-adrenoreceptors. Oxytocin fragments may be pre-formed and released in the brain or created by metabolic conversion of the principal hormone oxytocin in the central nervous system. Oxytocin and its fragments may also be released from peripheral sites, such as peripheral nerves, the gastrointestinal tract, and blood vessels in response to decreased sympathetic or increased parasympathetic nervous tone. Smaller fragments of oxytocin produced in the periphery may easily pass the blood-brain barrier to induce effects in the brain. In conclusion, oxytocin is linked to many different, sometimes opposite effects. The intact cyclic molecule may act to initiate social interaction and associated psychophysiological effects, whereas linear oxytocin and C-terminal fragments may induce relaxation and anti-stress effects following social interaction. In this way, the principal hormone oxytocin and its fragments may take part in a behavioral sequence, ranging from approach and interaction to calm and relaxation. Linear fragments, with an exposed cysteine-residue, may exert anti-inflammatory and antioxidant effects and thereby contribute to the health-promoting effects of oxytocin.
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| 41. |
- Uvnäs-Moberg, Kerstin
(author)
-
Oxytocin may have a therapeutical potential against cardiovascular disease. Possible pharmaceutical and behavioral approaches
- 2020
-
In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 138
-
Journal article (peer-reviewed)abstract
- Based on the ancient role of oxytocin and its homologues as amplifiers of reproduction we argue for an evolutionary coupling of oxytocin to signaling pathway which support restorative mechanisms of cells and tissue. In particular, the survival and function of different categories of stem cells and primordial cells are enhanced by mitogen-activated protein kinase (MAPK) pathways. Furthermore, oxytocin stimulates the AMP-activated protein kinase pathway (AMPK) in numerous of cell types which promotes the maintenance of different cell structures. This involves autophagic processes and, in particular, may support the renewal of mitochondria. Mitochondrial fitness may protect against oxidative and inflammatory stress - a well-documented effect of oxytocin. The combined specific trophic and protective effects oxytocin may delay several degenerative phenomena including sarcopenia, type-2 diabetes and atherosclerosis. These effects may be exerted both on a central level supporting the function and integrity of the hypothalamus and peripherally acting directly on blood vessels, pancreas, heart, skeletal muscles and adipose tissue etc. Furthermore, in the capacity of being both a hormone and neuromodulator, oxytocin interacts with numerous of regulatory mechanisms particularly the autonomic nervous system and HPA-axis which may reduce blood pressure and affect the immune function. The potential of the oxytocin system as a behavioral and molecular target for the prevention and treatment of cardiovascular disease is discussed. Focus is put on the affiliative and sexual significance and the different options and limitations associated with a pharmaceutical approach.
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| 42. |
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| 43. |
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| 44. |
- Wilder-Smith, Annelies, et al.
(author)
-
Hypothesis : Impregnated school uniforms reduce the incidence of dengue infections in school children
- 2011
-
In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 76:6, s. 861-862
-
Journal article (peer-reviewed)abstract
- Dengue infection causes a significant economic, social and medical burden in affected populations in over 100 countries in the tropics and sub-tropics. Current dengue control efforts have generally focused on vector control but have not shown major impact. School-aged children are especially vulnerable to infection, due to sustained human-vector-human transmission in the close proximity environments of schools. Infection in children has a higher rate of complications, including dengue hemorrhagic fever and shock syndromes, than infections in adults. There is an urgent need for integrated and complementary population-based strategies to protect vulnerable children. We hypothesize that insecticide-treated school uniforms will reduce the incidence of dengue in school-aged children. The hypothesis would need to be tested in a community based randomized trial. If proven to be true, insecticide-treated school uniforms would be a cost-effective and scalable community based strategy to reduce the burden of dengue in children.
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| 45. |
- Yin, D
(author)
-
Is carbonyl detoxification an important anti-aging process during sleep?
- 2000
-
In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 54:4, s. 519-522
-
Journal article (peer-reviewed)abstract
- Organisms living on the earth may undergo inevitable toxification by biological 'garbage', a variety of biometabolites. Such garbage includes a particularly large number of toxic carbonyls, such as a,▀-unsaturated carbonyls created by free radicals, glycation, and other post-translational side-reactions during various stresses and diseases. The accumulation of these toxic substances and their crosslinking products leads to the formation of different age pigments, such as lipofuscin, lens cataracts, and crosslinked collagen. The diurnal fluctuation in the concentration of the pineal gland hormone, melatonin, may be responsible for the 'cleaning activities' that reverse the covalently-bound semi-toxified proteins and nucleic acids. This toxification-cleaning cycle may explain the biochemical necessity for sleep of human and animals during aging. (C) 2000 Harcourt Publishers Ltd.
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| 46. |
- Zhang, Z., et al.
(author)
-
Transdifferentiation of neoplastic cells
- 2001
-
In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 57:5, s. 655-666
-
Journal article (peer-reviewed)abstract
- Transdifferentiation is a process in which a stable cell's phenotype changes to that of a distinctly different cell type. It occurs during certain physiological processes and leads to transition of tumor cell phenotypes. The latter process includes neoplastic epithelial-epithelial transition, neoplastic epithelial-mesenchymal transition, neoplastic mesenchymal-epithelial transition and transition between non-neural and neural neoplastic cell. This phonomenon is exemplified in some origin-debated tumors, such as carcinosarcoma, pleomorphic adenoma, synovial sarcoma, Ewing's/pPNET, and malignant fibrohistiocytoma. We propose that differentiation disturbance of cancer cells should include not only undifferentiation and dedifferentiation, but also transdifferentiation as well. Tumor cell transdifferentiation may be influenced or determined by cellular genetic instabilities, proliferation and apoptosis, as well as by extracellular matrix and growth factors. © 2001 Harcourt Publishers Ltd.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
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