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Biomedical subjects

M Rose

Publications and source records attributed to M Rose.

At least 55 records · Page 3Linked to original sources

[Congenital cystic adenomatoid malformation--clinical spectrum and management].

Congenital cystic adenomatoid malformation (CCAM) is one of the most frequent dysplasias of the lung. Diagnosis is often suspected in utero and urges obstetricians, pediatricians, and pediatric surgeons to make appropriate management decisions as to an optimal management for the affected patients. We report on a preterm baby with a gestational age of 33 weeks, suffering from hydrops fetalis and postnatal respiratory distress syndrome, a two-year old boy with clinical signs of a foreign body aspiration, and a seven-year old boy with a funnel chest. In each case, surgical resection was performed, the histology revealing CCAM. Our case report describes the broad clinical spectrum of CCAM. An algorithm is presented, helping to make diagnostic and therapeutic decisions.

Algorithms↗

Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease.

BACKGROUND: Dipeptidyl peptidase IV (DP IV, CD26), a serine protease with broad tissue distribution and known activity in serum, participates in T cell activation and promotes a Th1 cytokine response, a function in part attributable to its enzymatic activity. We hypothesized that the activity of DP IV in serum and expression of CD26/DP IV in lymphocytes may be altered in patients with inflammatory bowel disease (IBD). METHODS: Serum DP IV activity and CD26 (DP IV)-positive peripheral blood lymphocytes were measured in 110 patients with IBD (Crohn disease (CD): n = 63, ulcerative colitis (UC): n = 47). Additionally, T cell activation antigens (CD25, CD95) and costimulatory molecules (CD28) were evaluated. The same analyses were carried out in healthy volunteers (HC, n = 28). Thirty-nine patients with CD and 28 patients with UC were reassessed 3-6 months after the first visit. RESULTS: In patients with IBD, the DP IV activity in serum was reduced (mean +/- s (standard deviation): 52.8 U/l +/- 16.9 (CD) and 55.7 +/- 15.1 U/l (UC) versus 71.9 +/- 18.4 (HC), P < 0.001). Furthermore, patients with IBD had higher numbers of CD26-positive cells coexpressing CD25 and a higher surface expression of CD26 (DP IV) (mean fluorescence intensity, mean 57.1 (CD) and 59.8 (UC) versus 29.9 (HC), P < 0.001). The DP IV activity in serum showed an inverse correlation with known disease activity scores as well as with the concentrations of orosomucoid in serum. CONCLUSION: The changes of DP IV in patients with IBD highlight alterations at an interface between immune function and metabolism of peptide hormones, with potential importance for the pathophysiology of IBD. Furthermore, these changes may help to refine the assessment of IBD activity.

Adult↗

Studies made to assess risk concerning a 'dioxin' contamination incident near Bolsover, Derbyshire, UK.

During 1990 and 1991, milk samples were collected from farms in Derbyshire, a county in the UK, as part of a study designed to establish background concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) in cows' milk produced in the area. The concentrations found in two samples, both taken from farms near the town of Bolsover, were significantly elevated (40.0-42.0 ng TEQ kg(-1) fat) when compared with the normal range for these compounds in milk from the surrounding area (1.1-7.1 ng TEQ kg(-1) fat). An immediate intensive programme commenced in April 1991 to test milk from a further 27 dairy farms close to those where the original 'high' samples were obtained. A maximum tolerable concentration (MTC) was calculated to be 17.5 ng/TEQ kg(-1) fat. This was derived by using the tolerable daily intake (TDI) for 2,3,7,8-TCDD of 0.01 ng kg(-1) body weight day(-1) set by the World Health Organization in 1990 and accepted by the UK government (this figure has since been revised to 1-4 pg kg(-1) body weight day(-1)). MTC is defined as the amount of PCDD/Fs that could be present and still ensure that high-level (97.5 pecentile) consumers of milk would not exceed the TDI. Milk originating from dairies supplied by these farms and others contained PCDD/F in the range 1.8-3.1 ng TEQ kg(-1) fat, which indicated there was no risk to health for consumers purchasing milk in the normal manner. Milk from the two dairy farms was removed from the food supply until concentrations of PCDD/Fs were consistently below the MTC. The UK Department of Health monitored the blood concentrations of PCDD/Fs in individuals who had consumed milk produced on the affected farms and the Department of the Environment initiated a programme of work to identify and reduce the source of pollution.

Animals↗

Rocuronium: high risk for anaphylaxis?

Patients suspected of anaphylaxis during anaesthesia have been referred to the senior author's clinic since 1974 for investigation. Since release of rocuronium on to the worldwide market, concern has been expressed about its propensity to cause anaphylaxis. We identified 24 patients who met clinical and laboratory (intradermal, mast cell tryptase and morphine radioimmunoassay) criteria for anaphylaxis to rocuronium. The incidence of rocuronium allergy in New South Wales, Australia has risen in parallel with sales, while there has been an associated fall in reactions to other neuromuscular blocking drugs. Data from intradermal testing suggested that rocuronium is intermediate in its propensity to cause allergy in known relaxant reactors compared with low-risk agents (e.g. pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium, succinylcholine).

Anaphylaxis↗

Stress and immune mediators in miscarriage.

BACKGROUND: Stress is thought to be abortogenic and psycho-neuro-immunological pathways have been suggested to be involved in triggering miscarriages. From experiments in pregnant mice exposed to stress some insights into the underlying mechanisms have been gained, delineating immunological imbalances as a cause of pregnancy failure. In order to test the validity of the conclusions drawn from murine experiments and the role of stress in human pregnancy loss, the following study was performed. METHODS: We used an established perceived stress questionnaire and measured the stress score of women with a confirmed diagnosis of first trimester spontaneous abortion (n = 94). Decidual tissue was investigated by immunohistochemistry and in-situ hybridization to detect the presence and distribution of immunocompetent decidual cells [CD56(+) natural killer (NK) cells, CD8(+)and CD3(+) T cells, tryptase(+) mast cells (MCT(+)) and tumour necrosis factor (TNF)-alpha(+) cells]. The patient cohort was divided into women experiencing low or high levels of stress. RESULTS: In the decidua of women with high stress scores we observed significantly higher numbers of MCT(+), CD8(+) T cells and TNF-alpha(+) cells per mm(2) tissue (P < or = 0.05). No significant differences between individuals with lower or higher stress scores could be observed with respect to decidual CD56(+) NK and CD3(+) T cells. CONCLUSIONS: Using a questionnaire to score perceived stress in humans may be a valid approach to assess non-biased stress scores. Stress-triggered abortion in humans, identified by a questionnaire, can be linked to immunological imbalances.

Abortion, Spontaneous↗

Widening the lens on standardized patient assessment: what the encounter can reveal about the development of clinical competence.

The standardized patient (SP) examination is used in a majority of medical schools to test clinical skills. This examination usually yields both numerical ratings of clinical skill and narrative comments by patients or observers, yet most empirical studies of SP assessment focus on the numerical ratings only. This quantitative focus can lead to a narrow conceptualization of the nature and development of clinical competence. The authors suggest that in addition to utilizing SP numerical ratings, medical educators also use the rich qualitative material produced in the SP examination (e.g., patient comments, videotapes of the examination) to explore students' development of clinical competence, which involves the purposive integration of basic science, technical skill, empathy, communication, professional role, and personal history.

Attitude of Health Personnel↗

Pathogenesis and recovery of tetraplegia after electrical injury.

The site of neurological damage causing paralysis after electrical trauma remains to be clarified. A patient is described who developed a flaccid tetraplegia after a high voltage electrical injury. The findings on initial examination and neurophysiological investigation showed a very severe generalised sensory-motor polyneuropathy. His subsequent follow up over 60 months showed a remarkable degree of reinnervation and the unmasking of a myelopathy. The degree of reinnervation noted suggests an axonopathy that left the other elements of the peripheral nerves relatively spared. These findings provide the most convincing evidence to date that a generalised polyneuropathy can follow electrical injury and that it results from non-thermal mechanisms such as electroporation.

Adult↗

Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointestinal motility and sensitivity.

Psychological stress is widely believed to play a major role in functional gastrointestinal (GI) disorders, especially irritable bowel syndrome (IBS), by precipitating exacerbation of symptoms. The available data clearly demonstrate that inhibition of gastric emptying and stimulation of colonic transit is the most consistent pattern in the motility response of the GI tract to acute or short-term stress. Thus, one might propose that these alterations might play a pathophysiological role in dyspeptic symptoms and alterations in stool frequency and consistency in patients with stress-related functional GI disorders. Taken together, the above-mentioned studies suggest that the colonic motor response to stress is exaggerated in IBS. There is evidence that an increased emotional response is associated with this difference in colonic, and perhaps also gastric motor responses to certain stressors. However, almost no valid data are available so far from human studies addressing the question if differences in motility responses to stress between patients with functional GI disorders and healthy subjects are due to an altered stress response associated with an imbalance of the autonomic nervous system or increased stress susceptibility. We can summarize that in experimental animals the most consistent pattern of GI motor alterations induced by various psychological and physical stressors is that of delaying gastric emptying and accelerating colonic transit. Endogenous corticotropin-releasing factor (CRF) in the brain plays a significant role in the central nervous system mediation of stress-induced inhibition of upper GI and stimulation of lower GI motor function through activation of brain CRF receptors. The inhibition of gastric emptying by CRF may be mediated by interaction with the CRF-2 receptor, while CRF-1 receptors are involved in the colonic and anxiogenic responses to stress. Endogenous serotonin, peripherally released in response to stress, seems to be involved in stress- and central CRF-induced stimulation of colonic motility by acting on 5HT-3 receptors. Taken together, the limited data available from investigations in healthy subjects and patients with functional GI disorders provide some evidence that stress affects visceral sensitivity in humans. Acute psychological stress seems to facilitate increased sensitivity to experimental visceral stimuli, if the stressor induces a significant emotional change. In summary, studies in experimental animals suggest that stress-induced visceral hypersensitivity is centrally mediated by endogenous CRF and involvement of structures of the emotional motor system, e.g. the amygdala. Stress-induced activation or sensitization of mucosal mast cells in the GI tract seem to be involved in stress-associated alterations of visceral sensitivity.

Colon↗

ERP correlates of associative learning.

We examined changes of event-related potentials (ERPs) while participants learned stimulus-to-stimulus relations in an S1-S2 task. The design allowed for separating processes of associative learning from nonspecific effects. Participants had to respond to S2 by a left or right key-press dependent on S2 identity (letter W or M). Preparation for S2 could be improved by using the associative information given by S1. The S1 was an arrow pointing to the left or right. In combination with its color, arrow direction was informative about location and identity of S2, but participants were not informed about the relevance of color. Arrows in two of the colors were fully predictive for the S2 whereas the third color gave no valid information. This third stimulus controlled for habituation and procedural learning. Six blocks with 200 trials each and all three S1 colors in random order were presented. Behavioral and ERP differences in each block between "learning" and control trials were used to identify processes of associative learning. Several effects of associative learning were identified indicating the involvement of specific stages of information processing: a continuous increase of P3 amplitude evoked by S1 was accompanied by a decrease of P3 evoked by S2. These changes reflected the modifications of stimulus weights for response selection and the strengthened association between the two stimulus complexes in the time course of learning. The related motor preparation benefited from learning too, expressed in a decrease of CNV amplitude and an increase of LRP amplitude. Finally a decrease of N1 amplitude evoked by S2 indicated the reduced need to allocate spatial attention to the S2 location according to the learned meaning of S1.

Adult↗

Tobacco interventions by oncology nurses in clinical practice: report from a national survey.

BACKGROUND: Tobacco use is an important risk factor in cancer, cancer recurrence, and increased treatment morbidity, but limited information is available about interventions for tobacco cessation used in oncology clinical practice. In 1996, the Agency for Health Care Policy Research (AHCPR) published the first evidence-based smoking cessation guideline for use by health professionals. Using the AHCPR guideline as a framework, the authors describe the frequency of tobacco interventions provided by oncology nurses. METHODS: A questionnaire was mailed to 4000 randomly selected members of the Oncology Nursing Society in winter of 1998. Of those who were mailed questionnaires, 1508 respondents (38%) were available for analysis. RESULTS: The typical respondent was female, 44 years of age, and had practiced as an oncology nurse for 12 years. Seven percent were current smokers, and 30% were former smokers. Most (86%) encountered smokers on a weekly basis, but only 10% had heard of the AHCPR guideline. The majority (64%) assessed and documented tobacco status, 38% assessed readiness to quit. Few went on to provide interventions: 36% provided counseling, 32% provided cessation advice, 24% recommended nicotine replacement, and 16% taught skills to prevent relapse. Common barriers included perceived lack of patient motivation (74%) and the nurse's lack of time (52%) and skills (53%). The majority stated that they wanted to help patients stop smoking (88%) but needed additional training (92%). CONCLUSIONS: Documentation of tobacco status alone is not adequate in assisting patients with smoking cessation. Greater efforts are needed to educate oncology nurses about the range of tobacco interventions available and to facilitate their use in clinical settings.

Adult↗

Ubc8p functions in catabolite degradation of fructose-1, 6-bisphosphatase in yeast.

The key gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) is synthesized when cells of the yeast Saccharomyces cerevisiae are grown on a non-fermentable carbon source. After shifting the cells to glucose-containing medium, in a process called catabolite degradation, FBPase is selectively and rapidly broken down. We have isolated gid mutants, which are defective in this glucose-induced degradation process. When complementing the defect in catabolite degradation of FBPase in gid3-1 mutant cells with a yeast genomic library, we identified the GID3 gene and found it to be identical to UBC8 encoding the ubiquitin-conjugating enzyme Ubc8p. The in vivo function of Ubc8p (Gid3p) has remained a mystery so far. Here we demonstrate the involvement of Ubc8p in the glucose-induced ubiquitylation of FBPase as a prerequisite for catabolite degradation of the enzyme via the proteasome. Like FBPase, Ubc8p is found in the cytoplasmic fraction of the cell. We demonstrate cytoplasmic degradation of FBPase.

Biodegradation, Environmental↗

Progress in Arabidopsis genome sequencing and functional genomics.

Arabidopsis thaliana has a relatively small genome of approximately 130 Mb containing about 10% repetitive DNA. Genome sequencing studies reveal a gene-rich genome, predicted to contain approximately 25000 genes spaced on average every 4.5 kb. Between 10 to 20% of the predicted genes occur as clusters of related genes, indicating that local sequence duplication and subsequent divergence generates a significant proportion of gene families. In addition to gene families, repetitive sequences comprise individual and small clusters of two to three retroelements and other classes of smaller repeats. The clustering of highly repetitive elements is a striking feature of the A. thaliana genome emerging from sequence and other analyses.

Agriculture↗

Dipeptidyl peptidase IV (DPP IV, CD26) in patients with mental eating disorders.

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl Peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leukocyte antigen CD26, is considered to participate in T cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 44 patients (anorexia nervosa (AN): n = 21, bulimia (B): n = 23) in four consecutive weekly analyses. The analysis of CD26-positive cells included the characterization of CD26-bright and CD26-dim positive subsets. Additionally, the expression of CD25 (IL-2 Receptor alpha chain) was evaluated to estimate the degree of T cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD26-positive cells were reduced in patients as compared to healthy controls (mean 40.2% (AN) and 41.1% (B) vs. 47.4% (HC), p < 0.01), while the DPP IV activity in serum was elevated (mean 108.4 U/l (AN) and 91.1 U/l (B) vs. 80.3 U/l (HC), p < 0.01). The potential implications of changes in DPP IV expression and serum activity on--and beyond--immune function are discussed.

Adult↗

Patients' expressions of complaints as a predictor of the course of acute hepatitis A.

OBJECTIVE: Physical complaints, emotional states, liver, and immune parameters were investigated as possible indicators of the course of hepatitis A. METHODS: Forty-seven patients with hepatitis A were studied by means of the Giessen-Complaint-Inventory (GBB) and the Berlin Mood Questionnaire (BSF), as well as by taking into account their typical liver parameters and the following immune parameters: alphaInterferon (alphaIFN), soluble Interleukin 2 receptor (sIL-2R), Interleukin 6 (IL-6), Interleukin 1 receptor antagonist (IL-1Ra), and Immunoglobulin M or G (IgM, IgG). Two hundred twenty-nine medical students and a representative German sample (n = 1557, Braehler et al.) served as controls. RESULTS: We found that the initial degree of change in permeability of the liver cells, complaints about abdominal symptoms, and extent of depressive mood were able to predict the length of hospital stay. Patients with the initial, more pronounced liver damage, as well as patients who articulated less subjective impairment proved to have a longer course of illness. Those patients who needed a significantly longer time for recovery report, at admission, very few complaints-fewer than even the normal population. We were not, however, able to demonstrate a significant difference in the investigated immune parameters. CONCLUSION: A certain denial tendency seems to be harmful with respect to the recovery process and the immunological competence in the course of hepatitis A.

Acute Disease↗

Prevalence and severity of feeding and nutritional problems in children with neurological impairment: Oxford Feeding Study.

The aim of this study was to estimate the prevalence and severity of feeding and nutritional problems in children with neurological impairment within a defined geographical area. In a cross-sectional study, a validated questionnaire was sent to 377 parents of children (aged 4 to 13 years) on the Oxford Register of Early Childhood Impairments with oromotor dysfunction. The return rate was 72%. Of these, 93% had cerebral palsy; 47% were unable to walk; 78% had speech difficulty; and 28% continuous drooling of saliva. Gastrointestinal problems were commonly encountered: 59% were constipated; 22% had significant problems with vomiting, and 31% had suffered at least one chest infection in the previous 6 months. Feeding problems were prevalent: 89% needed help with feeding and 56% choked with food; 20% of parents described feeding as stressful and unenjoyable. Prolonged feeding times (3h/day) were reported by 28%. Only 8% of participants received caloric supplements and 8% were fed via gastrostomy tube. Even though 38% of respondents considered their child to be underweight, 64% of children had never had their feeding and nutrition assessed. The results highlight that feeding problems in children with neurological impairment are common and severe, causing parental concern. Many of these children would benefit from nutritional assessment and management as part of their overall care.

Adolescent↗

The feasibility of high-dose chemotherapy in breast cancer patients with impaired left ventricular function.

Breast cancer patients with cardiac disease are usually excluded from clinical trials of high-dose chemotherapy. We treated 52 patients with inflammatory and/or metastatic disease with sequential high-dose melphalan and stem cell rescue followed by high-dose thiotepa and stem cell rescue. Stem cells were mobilized with cyclophosphamide and/or paclitaxel and filgrastim. Left ventricular ejection fraction (LVEF) was measured by equilibrium radionuclide angiocardiography (ERNA) at baseline, after each course of chemotherapy and 4 weeks after completing both transplants. The mean absolute decrease in LVEF after the two transplants was 3.6% (P = 0. 008 for the comparison with baseline LVEF), and most of this drop (-2.5%, P = 0.007) occurred after mobilization. Unexpectedly, paclitaxel was associated with a mean absolute decrease in LVEF of 3. 4% (P = 0.032, n = 19), cyclophosphamide alone was not associated with a significant change in LVEF (-1.3%, P = 0.23), but mobilization with sequential paclitaxel and cyclophosphamide resulted in a mean absolute drop of 4.9% in LVEF (P = 0.009). Twelve patients were found to have a reduced LVEF (<50%) at least once during treatment and had a mean absolute decrease in LVEF of 10% (P = 0.008) from baseline, compared with a drop of only 1.8% (P = 0. 176) in the patients without impaired LV function. Although two of these 12 patients developed symptomatic heart failure, their cardiac symptoms were easily treated and there were no cardiac deaths. We conclude that our protocol has acceptable cardiac toxicity and breast cancer patients with impaired LV function should not be denied high-dose chemotherapy if otherwise indicated.

Adult↗

Oxidative stress following traumatic brain injury in rats: quantitation of biomarkers and detection of free radical intermediates.

Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8-epi-prostaglandin F(2alpha), was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N:-oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury.

Animals↗