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Biomedical subjects

S Mohr

Publications and source records attributed to S Mohr.

At least 19 recordsLinked to original sources

Religious beliefs in schizophrenia: their relevance for adherence to treatment.

The study examined how religious beliefs and practices impact upon medication and illness representations in chronic schizophrenia. One hundred three stabilized patients were included in Geneva's outpatient public psychiatric facility in Switzerland. Interviews were conducted to investigate spiritual and religious beliefs and religious practices and religious coping. Medication adherence was assessed through questions to patients and to their psychiatrists and by a systematic blood drug monitoring. Thirty-two percent of patients were partially or totally nonadherent to oral medication. Fifty-eight percent of patients were Christians, 2% Jewish, 3% Muslim, 4% Buddhist, 14% belonged to various minority or syncretic religious movements, and 19% had no religious affiliation. Two thirds of the total sample considered spirituality as very important or even essential in everyday life. Fifty-seven percent of patients had a representation of their illness directly influenced by their spiritual beliefs (positively in 31% and negatively in 26%). Religious representations of illness were prominent in nonadherent patients. Thirty-one percent of nonadherent patients and 27% of partially adherent patients underlined an incompatibility or contradiction between their religion and taking medication, versus 8% of adherent patients. Religion and spirituality contribute to shaping representations of disease and attitudes toward medical treatment in patients with schizophrenia. This dimension should be on the agenda of psychiatrists working with patients with schizophrenia.

Adaptation, Psychological↗

[Spirituality, religious practices and schizophrenia: relevance for the clinician].

Religion (spirituality and religiousness) is salient in the lives of many people suffering from schizophrenia. In order to assess religious coping in schizophrenia, we developed a clinical grid, as no validated questionnaire exists for this population. Religion had a positive effect for 71% and a negative effect for 14% of the 115 patients interviewed. Religion influences the sense of self, symptoms, social functioning, the comorbidity of substance abuse, suicidal attempts and adherence to treatment. Then religion is relevant for treatment and should be evaluated systematically. The forementioned clinical grid is suitable for this purpose. It proved its applicability to a broad diversity of religious beliefs, even pathological ones. Inter-judge reliability and construct validity were high and specific training is not required.

Adult↗

McArdle's disease and anaesthesia: case reports. Review of potential problems and association with malignant hyperthermia.

BACKGROUND: McArdle's disease of isolated deficiency in glycogen degradation in skeletal muscles has the potential of creating perioperative anaesthesiological problems; such as hypoglycaemia, rhabdomyolysis, myoglobinuria, acute renal failure and possibly malignant hyperthermia. METHODS: Eight patients with McArdle's disease were asked about previous surgery, anaesthesia and perioperative problems, and available hospital records were reviewed. Existing literature was reviewed for reports on McArdle's disease and anaesthesia. RESULTS: The eight patients had 35 anaesthesias (23 general anaesthesias, three regional anaesthesias and nine local anaesthesias). Perioperative problems of a non-specific nature were mentioned in three cases of general anaesthesia: two with postoperative nausea/vomiting, and one with an episode of tachycardia and low blood pressure. Three patients were tested for malignant hyperthermia (MH) using the in vitro contracture test (IVCT); two of them with a positive result. The literature search revealed seven case reports of McArdle's disease and anaesthesia. Apart from one report of hyperthermia, pulmonary oedema and rhabdomyolysis; probably not associated with MH, no problems were encountered from the literature search. CONCLUSION: McArdle's disease does not seem to cause severe perioperative problems in routine anaesthetic care. However, measures for preventing muscle ischaemia and rhabdomyolysis should be kept in mind, as well as the potential for these patients to develop postoperative fatigue, myoglobinuria and renal failure. Although no clinical association with malignant hyperthermia has been established, many of these patients can have a positive in vitro contracture test, and simple prophylactic measures, as with malignant hyperthermia, may be recommended if otherwise not contraindicated.

Adolescent↗

Sevoflurane-induced malignant hyperthermia during cardiopulmonary bypass and moderate hypothermia.

A 56-year old man was admitted for elective mitral valve repair and coronary artery bypass surgery due to mitral valve leakage and unstable angina. After induction of anaesthesia he developed a combined metabolic and respiratory acidosis. Different diagnosis were considered and we decided to treat the patient with dantrolene due to suspicion of malignant hyperthermia (MH). The patient received one dose of dantrolene 2,5 mg/kg during cardiopulmonary bypass (CPB) and a second dose of dantrolene 2,5 mg/kg during weaning from CPB. The first arterial blood gas sample taken in the intensive care unit showed relapse of the acidosis and we administered an infusion of 150 mg dantrolene over 3 hours. The patient gradually recovered without sequel and MH was verified by muscle biopsy testing.

Anesthetics, Inhalation↗

Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis.

BACKGROUND: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition. METHODS: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells. RESULTS: Compared with normal cells, CD T cells cycle faster, express increased phosphorylated Rb and decreased phosphorylated p53 levels, display less caspase activity but more telomerase activity, die less, and undergo vigorous cellular expansion. In contrast, UC T cells cycle slower, express normal levels of phosphorylated Rb and p53, display more caspase activity but have no telomerase activity, die more, and have a limited capacity to expand. CONCLUSIONS: T cell cycle abnormalities in CD indicate a state of hyperreactivity compatible with loss of tolerance, but a hyporeactive state compatible with anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie the pathogenesis of the two main forms of inflammatory bowel disease.

Adolescent↗

Pharmacogenomics and drug response in cardiovascular disorders.

There are a total of 17 families of drugs that are used for treating the heterogeneous group of cardiovascular diseases. We propose a comprehensive pharmacogenomic approach in the field of cardiovascular therapy that considers the five following sources of variability: the genetics of pharmacokinetics, the genetics of pharmacodynamics (drug targets), genetics linked to a defined pathology and its corresponding drug therapies, the genetics of physiologic regulation, and environmental-genetic interactions. Examples of the genetics of pharmacokinetics are presented for phase I (cytochromes P450) and phase II (conjugating enzymes) drug-metabolizing enzymes and for phase III drug transporters. The example used to explain the genetics of pharmacodynamics is glycoprotein IIIa and the response to antiplatelet effects of aspirin. Genetics linked to a defined pathology and its corresponding drug therapies is exemplified by ADRB1, ACE, CETP and APOE and drug response in metabolic syndrome. The examples of cytochrome P450s, APOE and ADRB2 in relation to ethnicity, age and gender are presented to describe genetics of physiologic regulation. Finally, environmental-genetic interactions are exemplified by CYP7A1 and the effects of diet on plasma lipid levels, and by APOE and the effects of smoking in cardiovascular disease. We illustrate this five-tiered approach using examples of cardiovascular drugs in relation to genetic polymorphism.

Animals↗

Is executive function associated with symptom severity in schizophrenia?

This paper reports on a study that was designed to investigate the relationship between psychopathology and executive functions in schizophrenia. Correlations were sparse and mostly weak. The most robust finding was the association between letter fluency and negative symptoms; however, most other applied tasks were not associated with symptom level. Our results support previous findings of differential relationships between impaired executive functions and symptom level.

Adolescent↗

Factors and motives associated with drop-out in an ambulatory service for patients with psychotic disorders.

The aim is to study motives and factors associated with treatment drop-out in an ambulatory psychiatric service, which integrates medical, social, familial and rehabilitation treatments. Only 9% of the psychotic patients dropped out, whose motives were non-compliance with medication and unawareness of illness, and the associated factors were comorbidity of substance abuse, social isolation and male gender.

Adult↗

Comparison of transcutaneous and endtidal CO2-monitoring for rigid bronchoscopy during high-frequency jet ventilation.

OBJECTIVE: To compare endtidal and transcutaneous respiratory monitoring of high-frequency jet ventilation (HFJV) in rigid bronchoscopy. Both techniques provide a noninvasive measurement of pCO2. METHODS: High-frequency jet ventilation was applied via a rigid bronchoscope. Driving pressure (DP) was initially adapted to ensure normal ventilation. It was then changed twice by +/- 30% from the initial value. Endtidal and transcutaneous data were compared with arterial blood gas monitoring (ABG). RESULTS: Results were analyzed separately for the time just after changing the driving pressure (10 min) and the remaining time until the next change of the driving pressure (4 min). The first part was called the dynamic phase, and the second part the steady-state phase. Correlation coefficient between endtidal capnography and ABG was 0.96 for the steady state and 0.94 for the dynamic phase, respectively. Bland-Altman analysis revealed a bias of -0.21 kPa with limits of agreement (LOA) 1.63 kPa for the steady state and -0.25 kPa, 2.08 kPa for the dynamic phase, respectively. Correlation coefficient between transcutaneous monitoring and ABG for the steady state phase was 0.83, and was 0.72 for the dynamic phase. Bland-Altman analysis resulted in a bias of -0.89 kPa with LOA - 3.84 kPa during steady state and 0.92 kPa, 4.06 kPa for the dynamic phase, respectively. CONCLUSION: Endtidal capnography offers accurate respiratory monitoring of HFJV. Transcutaneous monitoring showed a good correlation to ABG only during steady-state conditions. For the dynamic phase the accuracy was significantly lower. Thus, we cannot recommend transcutaneous respiratory monitoring for the specific indication of rigid bronchoscopy using HFJV.

Adult↗

Non-uniform distribution of lesions and biochemical abnormalities within the retina of diabetic humans.

OBJECTIVE: Microaneurysms, acellular capillaries, pericyte ghosts, and thickening of retinal capillary basement membrane are characteristic of diabetic retinopathy, and are believed to be sequelae of excessive blood glucose. Previous studies by us in dogs demonstrated that lesions of diabetic retinopathy were not uniformly distributed across the retina, but were significantly more numerous in the superior/temporal areas of the retina. In the present study, the distribution of these lesions and the biochemical abnormalities postulated to play a role in their pathogenesis have been evaluated in retinas collected at autopsy from diabetic patients. METHODS: Retinas were divided into quadrants (nasal, temporal, superior, inferior), the vasculature exposed by the trypsin-digest method, and the frequency of the lesions compared among the quadrants. Homogenates taken from the mid-retina of nasal and temporal quadrants of retina were used to explore regional differences in expression of Glut1, PKCbeta, and iNOS (Western blots) and caspases (enzymatic activity). RESULTS: Microaneurysms, acellular capillaries and pericyte ghosts were not uniformly distributed across the retina, and were significantly more numerous in the temporal retina than in the nasal retina (P < 0.05). In contrast, the thickness of retinal capillary basement membrane was not found to differ significantly across the retina. In our limited study, activity of the pro-inflammatory protease, caspase 1, was the only biochemical abnormality where there was both a significant diabetes-induced alteration in activity and also a significant difference between retinal quadrants. Expression of the glucose transporter, Glut1, was significanlty decreased in diabetes, but there was no significant difference in expression between the quadrants. Expression of iNOS was increased only in temporal retina in diabetes (but no significant difference between quadrants), and PKCbeta tended to be greater than normal in both temporal and nasal retina. CONCLUSIONS: Retinal microvascular disease does not develop uniformly across the retina of diabetic patients, even though the different regions are exposed to the same level of hyperglycemia.

Aged↗

The human type 2 iodothyronine deiodinase is a selenoprotein highly expressed in a mesothelioma cell line.

Types 1 and 3 iodothyronine deiodinases are known to be selenocysteine-containing enzymes. Although a putative human type 2 iodothyronine deiodinase (D2) gene (hDio2) encoding a similar selenoprotein has been identified, basal D2 activity is not selenium (Se)-dependent nor has D2 been labeled with (75)Se. A human mesothelioma cell line (MSTO-211H) has recently been shown to have approximately 40-fold higher levels of hDio2 mRNA than mesothelial cells. Mesothelioma cell lysates activate thyroxine (T(4)) to 3,5,3'-triiodothyronine with typical characteristics of D2 such as low K(m) (T(4)), 1.3 nm, resistance to propylthiouracil, and a short half-life ( approximately 30 min). D2 activity is approximately 30-fold higher in Se-supplemented than in Se-depleted medium. An antiserum prepared against a peptide deduced from the Dio2 mRNA sequence precipitates a (75)Se protein of the predicted 31-kDa size from (75)Se-labeled mesothelioma cells. Bromoadenosine 3'5' cyclic monophosphate increases D2 activity and (75)Se-p31 approximately 2.5-fold whereas substrate (T(4)) reduces both D2 activity and (75)Se-p31 approximately 2-3-fold. MG132 or lactacystin (10 microm), inhibitors of the proteasome pathway by which D2 is degraded, increase both D2 activity and (75)Se-p31 3-4-fold and prevent the loss of D2 activity during cycloheximide or substrate (T(4)) exposure. Immunocytochemical studies with affinity-purified anti-hD2 antibody show a Se-dependent increase in immunofluorescence. Thus, human D2 is encoded by hDio2 and is a member of the selenodeiodinase family accounting for its highly catalytic efficiency in T(4) activation.

Acetylcysteine↗

TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme.

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.

Adult↗

Are African-American nuclear workers at lower mortality risk than Caucasians?

This study investigated disparities in worker mortality across race at the Savannah River site (SRS) nuclear facility in Aiken, South Carolina. Standardized mortality ratios were calculated stratified by race (Caucasian, African-American) and gender for specific causes of death, and by race, gender, duration of employment, and follow-up for overall mortality. Race-specific standardized mortality ratios for African-American male workers generally were lower than those for Caucasian male workers, although both groups showed strong healthy worker effects. Nevertheless, African-American male workers generally had higher absolute mortality rates. Understanding why SRS African-American male workers are substantially healthier than their reference population as compared with Caucasian male workers but are less healthy in absolute terms than the SRS Caucasian male workers may provide clues for prevention or intervention. Further, the standardized mortality ratios at the SRS were lower than at the Hanford and Oak Ridge nuclear facilities, which warrants investigation.

Adult↗

Mania resulting from continuous positive airways pressure in a depressed man with sleep apnea syndrome.

The authors report the case of a 50-year-old man, with no previous history of bipolar illness, hospitalized with a very severe depression and who was resistant to a 7-weeks treatment of venlafaxine and trazodone (the respective daily doses were 300 and 50 mg which were stable during the last 4 weeks). A diagnosis of sleep apnea syndrome led to the use of the continuous positive airways pressure technique (CPAP). A few days after starting CPAP, he presented a mood switch, first hypomanic, then mixed. The authors discuss the contribution of the sleep apnea syndrome to the appearance and the maintenance of the depressive disorder.

Bipolar Disorder↗

Protein thiol modification of glyceraldehyde-3-phosphate dehydrogenase and caspase-3 by nitric oxide.

The regulation of enzyme activity function is a major factor in the cellular response to a changing environment. One mechanism of enzyme activity regulation includes post-translational protein thiol modification by nitric oxide (NO) or its redox species. Major routs used by NO to modify cysteine residues of proteins include S-nitrosation, oxidation, mixed disulfide formation with glutathione, and the covalent attachment of nucleotide cofactors, i.e NAD(+)/NADH. Critical thiol centers serve as recognition sites for NO, thus channeling the NO signal through post-translational modifications and oxidation into cellular functions. Here, we summarize current knowledge on active site thiol modification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and caspase-3 by nitric oxide. Although very different in their cellular function, both enzymes contain highly reactive cysteines which represent sensitive targets for NO. Our studies are supportive of a potential role of S-nitrosation and mixed disulfide formation as a general signaling mechanism that allows sensing of nitrosative stress. At the same time, modification of GAPDH and caspase-3 by NO show the diversity of mechanisms (S-nitrosation versus oxidations) that we are confronted with as a result of NO delivery, especially comparing in vitro studies with cellular systems. In the future it will be challenging to dissect how nitrosative and oxidative signaling mechanisms overlap and how intracellular communication systems allow their activation in a selective way.

Caspase 3↗

[Gene expression profiling in human mesothelioma cells using DNA microarray and high-density filter array technologies].

Although the use of asbestos has been banned in most industrialized countries, it is still a major public health concern. Asbestos fibers are mutagenic and carcinogenic for humans, classified as "carcinogen category 1 (T, R45: can cause the cancer)" in the 25th adaptation of the directive 67/548/EEC. In France, asbestos is thought to be responsible each year for many pulmonary diseases: pleural plaque, bronchogenic carcinoma and mesothelioma (malignant tumor of pleura). In order to better understand the transformation process of pleural cells, we compared the gene expression of mesothelium cells (Met-5A) and mesothelioma cells (MSTO-211H) using high-density filter array (588 genes) and microarray (6.969 genes). Results of both technologies were compared and expression levels of several genes were confirmed by quantitative RT-PCR. Data analysis with GemtoolsTM 2.4 software allows us hierarchical classification of genes of known functions by enzyme, function and pathway clusters and leads to characterize both malignant and normal phenotypes. Finally, the comparison between the two cell lines provides new markers of mesothelioma and pleura. They could be useful for diagnostic, prognostic and therapeutic.

Cell Adhesion↗

Differential gene expression in mesothelioma.

To investigate the molecular events controlling malignant transformation of human pleural cells, we compared constitutive gene expression of mesothelioma cells to that of pleural cells. Using cDNA microarray and high-density filter array, we assessed expression levels of > 6500 genes. Most of the highly expressed transcripts were common to both cell lines and included genes associated with stress response and DNA repair, outcomes consistent with the radio- and chemo-resistance of mesothelioma. Interestingly, of the fewer than 300 genes that differed between cell lines, most functioned in (i) macromolecule stability, (ii) cell adhesion and recognition, (iii) cell migration (invasiveness), and (iv) extended cell division. Expression levels of several of these genes were confirmed by RT-PCR and could be useful as diagnostic markers of human mesothelioma.

Cell Adhesion↗

Characterization of an unusual tRNA-like sequence found inserted in a Neurospora retroplasmid.

We characterized an unusual tRNA-like sequence that had been found inserted in suppressive variants of the mitochondrial retroplasmid of Neurospora intermedia strain Varkud. We previously identified two forms of the tRNA-like sequence, one of 64 nt (TRL-64)and the other of 78 nt (TRL-78) containing a 14-nt internal insertion in the anticodon stem at a position expected for a nuclear tRNA intron. Here, we show that TRL-78 is encoded in Varkud mitochondrial (mt)DNA within a 7 kb sequence that is not present in Neurospora crassa wild-type 74A mtDNA. This 7-kb insertion also contains a perfectly duplicated tRNA(Trp)gene, segments of several mitochondrial plasmids and numerous GC-rich pallindromic sequences that are repeated elsewhere in the mtDNA. The mtDNA-encoded copy of TRL-78 is transcribed and apparently undergoes 5'- and 3'-end processing and 3' nucleotide addition by tRNA nucleotidyl transferase to yield a discrete tRNA-sized molecule. However, the 14 nt intron-like sequence in TRL-78, which is missing in the TRL-64 form, is not spliced detectably in vivo or in vitro. Our results show that TRL-78 is an unusual tRNA-like species that could be incorporated into suppressive retroplasmids by the same reverse transcription mechanism used to incorporate mt tRNAs. The tRNA-like sequence may have been derived from an intron-containing nuclear tRNA gene or it may serve some function, like tmRNA. Our results suggest that mtRNAs or tRNA-like species may be integrated into mtDNA via reverse transcription, analogous to SINE elements in animal cells.

Base Sequence↗