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Biomedical subjects

K Mann

Publications and source records attributed to K Mann.

At least 127 records · Page 7Linked to original sources

The 2000 Canadian recommendations for the management of hypertension: part two--diagnosis and assessment of people with high blood pressure.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of high blood pressure in adults. OPTIONS: For people with high blood pressure, the assignment of a diagnosis of hypertension depends on the appropriate measurement of blood pressure, the level of the blood pressure elevation, the duration of follow-up and the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases. For people diagnosed with hypertension, defining the overall risk of adverse cardiovascular outcomes requires laboratory testing, a search for target organ damage and an assessment of the modifiable causes of hypertension. Out-of-clinic blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: People at increased risk of adverse cardiovascular outcomes and were identified and quantified. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian recommendations for the management of hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the identification of people at increased risk of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: The identification of people at higher risk of cardiovascular disease will permit counselling for lifestyle manoeuvres and the introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to aspects of the diagnosis and assessment of patients with hypertension, including the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, routine and optional laboratory testing, assessment for renovascular hypertension, home and ambulatory blood pressure monitoring, and the role of echocardiography in hypertension. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only the recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually. ENDORSEMENT: These recommendations are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control of Health Canada.

Adrenal Gland Neoplasms↗

Enhanced epinephrine-induced platelet aggregation in individuals carrying the G protein beta3 subunit 825T allele.

The 825T allele of a common C825T polymorphism in the gene encoding the beta3 subunit of heterotrimeric G proteins is associated with enhanced activation of pertussis toxin (PTX)-sensitive G proteins. We investigated responses of human platelets upon stimulation with epinephrine, which activates PTX-sensitive G proteins, and with agonists which activate additionally, or exclusively PTX-insensitive pathways. Slopes and maximum of the secondary aggregation were significantly enhanced in platelets from 825T allele carriers after epinephrine, and after combined epinephrine/ADP. This effect was more pronounced after inhibition of the cyclooxygenase-2 pathway by acetylsalicylic acid. This phenomenon appeared independent of platelet secretion, or inhibition of the adenylyl cyclase.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Structural and functional analysis of the recombinant G domain of the laminin alpha4 chain and its proteolytic processing in tissues.

The C-terminal G domains of laminin alpha chains have been implicated in various cellular and other interactions. The G domain of the alpha4 chain was now produced in transfected mammalian cells as two tandem arrays of LG modules, alpha4LG1-3 and alpha4LG4-5. The recombinant fragments were shown to fold into globular structures and could be distinguished by specific antibodies. Both fragments were able to bind to heparin, sulfatides, and the microfibrillar fibulin-1 and fibulin-2. They were, however, poor substrates for cell adhesion and had only a low affinity for the alpha-dystroglycan receptor when compared with the G domains of the laminin alpha1 and alpha2 chains. Yet antibodies to alpha4LG1-3 but not to alpha4LG4-5 clearly inhibited alpha(6)beta(1) integrin-mediated cell adhesion to laminin-8, indicating the participation of alpha4LG1-3 in a cell-adhesive structure of higher complexity. Proteolytic processing within a link region between the alpha4LG3 and alpha4LG4 modules was shown to occur during recombinant production and in endothelial and Schwann cell culture. Cleavage could be attributed to three different peptide bonds and is accompanied by the release of the alpha4LG4-5 segment. Immunohistology demonstrated abundant staining of alpha4LG1-3 in vessel walls, adipose, and perineural tissue. No significant staining was found for alpha4LG4-5, indicating their loss from tissues. Immunogold staining demonstrated an association of the alpha4 chain primarily with microfibrillar regions rather than with basement membranes, while laminin alpha2 chains appear primarily associated with various basement membranes.

Adipose Tissue↗

Ligand-inducible interaction of the DRIP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells.

Retinoic acid (RA) signaling is mediated by its nuclear receptors RXR and RAR, which bind to their cognate response elements as a heterodimer, RXR/RAR, and act in concert with coregulatory factors to regulate gene transcription on ligand binding. To identify specific cofactors that interact with the RXR/RAR heterodimer in acute promyelocytic leukemia (APL) cells, a double cistronic construct was used that allowed coexpression of the RXR LBD (ligand binding domain) with the RAR LBD as an affinity matrix to pull down interacting proteins from nuclear extracts prepared from a human APL cell line, NB4. A group of proteins was detected whose interaction with RXR/RAR is ligand inducible. The molecular weight pattern of these proteins is similar to that of a complex of proteins previously identified as DRIP or TRAP, which are ligand-dependent transcription activators of VDR and TR, respectively. The RXR/RAR-interacting proteins from NB4 were confirmed to be identical to the DRIP subunits by comparative electrophoresis, Western blot analysis, and in vitro protein interaction assay. In addition to RXR/RAR, the DRIP component can interact directly with the APL-specific PML-RARalpha fusion protein. The same DRIP complex is present in RA-resistant APL cells and in a variety of cancer cell lines, supporting its global role in transcriptional regulation.

Antineoplastic Agents↗

Patterns of care for patients with primary differentiated carcinoma of the thyroid gland treated in Germany during 1996. U.S. and German Thyroid Cancer Group.

BACKGROUND: To determine current patterns of care and disease characteristics for patients with thyroid carcinoma, a Patient Care Evaluation Study was initiated in 1996 in the U.S. and Germany. This project addresses ongoing concerns with respect to the diagnostic evaluation and treatment of patients diagnosed with thyroid carcinoma and raises questions concerning how physicians are interpreting current standards and acting on the basis of these recommendations. METHODS: Patients with primary thyroid carcinoma were entered into a prospective multicenter observational study with free choice of treatment (no control group) between January 1, 1996 and December 31, 1996 in Germany. This resulted in a total of 2537 cases under observation and analysis; 1685 patients had papillary carcinoma (66.4%), 691 had follicular carcinoma (27.2%), 70 had medullary carcinoma (2.8%), and 91 had anaplastic carcinoma (3.6%). The 2376 patients with carcinoma of either papillary or follicular histology were included in the current analysis. RESULTS: The major symptoms reported for patients with papillary and follicular thyroid carcinoma was neck mass (reported in 76% and 79%, respectively) followed by dysphagia (reported in 25% and 27%, respectively), stridor (reported in 9% and 14%, respectively), and neck pain (reported in 7% and 8%, respectively). Greater than 50% of the patients with papillary thyroid carcinoma were reported to have American Joint Committee on Cancer/International Union Against Cancer Stage I disease. Between 37-39% of the follicular carcinoma patients had Stage I and Stage II disease. Only slight differences in the diagnostic approach to patients with papillary or follicular carcinoma were noted. The majority of patients underwent an ultrasound of the thyroid region (78.1%), which was suggestive of carcinoma in only 39% of the cases. A thyroid scan was performed on 76.6% of patients, and the results were suggestive of carcinoma in 44.8% of the individuals. In contrast, fine-needle aspiration biopsy of the thyroid is highly recommended in the current Clinical Practice Guidelines (CPG) but results were obtained in only 27.4% of the patients. Total thyroidectomy without lymph node dissection was the most commonly used surgical procedure in the treatment of patients with papillary and follicular thyroid carcinoma. Only approximately 2% of patients at low risk in the group with Stage I disease were treated with a lobectomy. In 80% of the patients with Stage I papillary thyroid carcinoma and approximately 90% of those patients diagnosed with Stage II, III, and IV disease treating physicians chose to utilize radioiodine as adjuvant treatment after disease-directed surgery. External beam radiation was added to the treatment regimen for many patients diagnosed with Stage III and IV disease (30% in patients with papillary thyroid carcinoma and 33% in patients with follicular thyroid carcinoma). CONCLUSIONS: To the authors' knowledge no single effective diagnostic test for thyroid carcinoma currently is available and in the majority of cases a combination of ultrasound, thyroid scan, or fine-needle aspiration biopsy together with the clinical findings (e.g., thyroid mass) led to a diagnosis of carcinoma. The authors suspect that the high prevalence of concomitant pathologic findings such as goiter, even in the healthy population in Germany, reduces the accuracy of all diagnostic test methods and may account for the frequent use of imaging techniques. The majority of patients underwent a total or near-total thyroidectomy. Total thyroidectomy with radical lymph node dissection was used very frequently in those patients with papillary thyroid carcinoma (22%). German physicians tend to surgically treat early stage thyroid carcinoma somewhat more radically than recommended in the CPG. With respect to other treatment options employed as part of the first course of treatment, radioiodine appears to play the most important role. [See commentary o

Adenocarcinoma, Follicular↗

Variable zinc coordination in endostatin.

Endostatin is a proteolytic fragment of collagen XVIII that potently inhibits angiogenesis and tumour growth. Human endostatin contains a zinc ion, bound near the N terminus, which was not observed in the original structure of mouse endostatin at pH 5. Controversial data exist on the role of this zinc ion in the anti-tumour activity. We report two new crystal structures of mouse endostatin at pH 8.5 with bound zinc. One crystal form shows a metal ion coordination similar to that in human endostatin (His132, His134, His142, Asp207), but the conformation of the N-terminal segment is different. In the other crystal form, Asp136 replaces His132 as a zinc ligand. Site-directed mutagenesis of zinc-binding residues demonstrates that both coordination geometries occur in solution. The large degree of structural heterogeneity of the zinc-binding site has implications for endostatin function. We conclude that zinc is likely to play a structural rather than a critical functional role in endostatin.

Amino Acid Sequence↗

Purification and characterization of perlucin and perlustrin, two new proteins from the shell of the mollusc Haliotis laevigata.

Two new proteins, named perlucin and perlustrin, with M(r) 17,000 and 13,000, respectively, were isolated from the shell of the mollusc Halotis laevigata (abalone) by ion-exchange chromatography and reversed-phase HPLC after demineralization of the shell in 10% acetic acid. The sequence of the first 32 amino acids of perlucin indicated that this protein belonged to a heterogeneous group of proteins consisting of a single C-type lectin domain. Perlucin increased the precipitation of CaCO(3) from a saturated solution, indicating that it may promote the nucleation and/or the growth of CaCO(3) crystals. With pancreatic stone protein (lithostathine) and the eggshell protein ovocleidin 17, this is the third C-type lectin domain protein isolated from CaCO(3) biominerals. This indicates that this type of protein performs an important but at present unrecognized function in biomineralization. Perlustrin was a minor component of the protein mixture and the sequence of the first 33 amino acids indicated a certain similarity to part of the much larger nacre protein lustrin A.

Amino Acid Sequence↗

Relationship of weight and eating disorders in type 2 diabetic patients: a multicenter study.

OBJECTIVE: Previous work suggested that the degree of psychiatric symptomatology evidenced in overweight individuals was related to the severity of binge eating problems and not related to the severity of overweight. In a multicenter study, we investigated the relationship between weight and eating disorders (EDs) in a sample of type 2 diabetic patients. METHODS: Three hundred twenty-two patients with type 2 diabetes were stratified to various weight categories. Glycemic control, eating and body-related psychological problems, self-esteem, depressive, and general psychopathology of diaetic patients with and without an ED were compared. RESULTS: Eighty-one percent of all type 2 diabetic patients were overweight or obese. Prevalence rates of EDs ranged from 6.5% to 9.0%. Binge eating disorder was the most diagnosed ED. There was a strong relationship between body mass index (BMI) and eating disturbance-related variables and a weak or no relationship between BMI and depression or general psychopathologic variables. Patients with an ED showed a greater psychopathology compared to patients without an ED. The diagnosis of an ED did not seem to have a specific influence on glycemic control. CONCLUSIONS: Our results in a type 2 diabetic sample indicate that weight might have an impact on body and eating-related psychological distress in type 2 diabetic patients, but is of minor or no importance for depressive symptomatology, lower self-esteem, and general psychiatric symptomatology. Type 2 diabetic patients with an ED, however, suffer from considerable psychiatric symptomatology.

Analysis of Variance↗

Bone loss in long-term survivors after transplantation of hematopoietic stem cells: a prospective study.

Organ transplantation is associated with relevant bone loss. Bone loss of up to 20% of pretransplant bone mineral density (BMD) values within the first year after kidney, liver, heart and lung transplantation has been reported. Patients undergoing transplantation of hematopoietic stem cells provide an interesting model to study transplantation-induced bone loss, especially because most patients do not have preexisting bone disease. A longitudinal study was performed in 81 patients undergoing bone marrow or peripheral blood stem cell transplantation. BMD was determined by dual-energy X-ray absorptiometry before transplantation, at discharge from the hospital, and at 6 and 12 months after transplantation in all 81 patients. In 35 patients BMD was re-evaluated 24 months after transplantation. Vitamin D and parathyroid hormone, bone alkaline phosphatase as a marker of bone formation, and N-terminal telopeptide of type I collagen as a marker of bone resorption were assessed before transplantation and in the short-term follow-up 14 and 28 days after transplantation. The majority of patients (72%) showed normal BMD before transplantation. However, lower BMD was observed in patients who had received high-dose cytoreductive chemotherapy before transplantation compared with those who had received no chemotherapy or only hydroxyurea. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (1000 IU/day), the mean rate of bone loss during the first year was 7.2 +/- 6.3% at the lumbar spine, 11.9 +/- 8.1% at the femoral neck and 3.8 +/- 2.5% at the total body compartment. Evaluation of the pattern of bone loss during the first year demonstrated that the amount of bone loss was largest within the first 40 days after transplantation and small during the second half of the first year after transplantation. The majority of patients showed vitamin D deficiency and secondary hyperparathyroidism. Bone formation was normal before and after transplantation, whereas bone resorption was dramatically increased before and after transplantation. Exposure to glucocorticoids was associated with higher bone loss at spine and femoral neck but not at the total body compartment. Our data demonstrate rapid bone loss in patients undergoing transplantation of hematopoietic stem cells. Bone turnover is characterized by biochemical uncoupling of bone resorption and bone formation, changes interestingly pre-existing before transplantation. The observed alterations in bone mass and metabolism emphasize the importance of clinical trials with antiresorptive agents to prevent and treat post-transplantation osteoporosis in this group of patients.

Adolescent↗

Nonlinear analysis of continuous ECG during sleep I. Reconstruction.

In recent years evidence has accumulated that ECG signals are of a nonlinear nature. It has been recognized that strictly periodic cardiac rhythms are not accompanied by healthy conditions but, on the contrary, by pathological states. Therefore, the application of methods from nonlinear system theory for the analysis of ECG signals has gained increasing interest. Crucial for the application of nonlinear methods is the reconstruction (embedding) of the time series in a phase space with appropriate dimension. In this study continuous ECG signals of 12 healthy subjects recorded during different sleep stages were analysed. Proper embedding dimension was determined by application of two techniques the false nearest neighbours method and the saturation of the correlation dimension. Results for the ECG signals were compared with findings for simulated data (quasiperiodic dynamics, Lorenz data, white noise) and for phase randomized surrogates. Findings obtained with the two approaches suggest that embedding dimensions from 6 to 8 may be regarded as suitable for the topologically proper reconstruction of ECG signals.

Adult↗

Nonlinear analysis of continuous ECG during sleep II. Dynamical measures.

The hypothesis that cardiac rhythms are associated with chaotic dynamics implicating a healthy flexibility has motivated the investigation of continuous ECG with methods of nonlinear system theory. Sleep is known to be associated with modulations of the sympathetic and parasympathetic control of cardiac dynamics. Thus, the differentiation of ECG signals recorded during different sleep stages can serve to determine the usefulness of nonlinear measures in discriminating ECG states in general. For this purpose the following six nonlinear measures were implemented: correlation dimension D2, Lyapunov exponent L1. Kolmogorov entropy K2, as well as three measures derived from the analysis of unstable periodic orbits. Results of this study show that continuous ECG signals can be differentiated from linear stochastic surrogates by each of the nonlinear measures. The most significant finding with respect to the sleep-related differentiation of ECG signals is an increase in dominant chaoticity assessed by L1 and a reduction in the degrees of freedom estimated by D2 during REM sleep compared to slow wave sleep. Our findings suggest that the increase in dominant chaoticity during REM sleep with regard to time-continuous nonlinear analysis is comparable to an increased heart rate variability. The reduction in the correlation dimension may be interpreted as an expression of the withdrawal of respiratory influences during REM sleep.

Adult↗

[Alcohol withdrawal syndrome and its treatment].

When alcoholics decrease or interrupt alcohol intake abruptly, they will in general experience alcohol withdrawal symptoms. Clinically in most cases it develops a vegetative syndrome with gastroenteropathy, cardiovascular diseases, neurological and psychopathological symptom. Usually alcohol withdrawal symptoms abate after four to seven days, longer courses are rare. Application of drugs is required in approximately one third to one half of the patients. A variety of drugs was suggested for the treatment of alcohol withdrawal. In the first hours of alcohol detoxification, the sensitivity of epinephrine receptors is reduced, but rises afterwards substantially. The number of NMDA-receptors increases during chronic intoxication with ethanol. The standard therapy in Europe (except of Great Britain) is an oral mono therapy with clomethiazole in a dose which depends on the severity of the symptoms. Severe withdrawal symptoms may require treatment on an intensive care unit with infusion therapy, e.g. in the context of a delirium tremens, which represents a life-threatening status. In this case, benzodiazepines have been used successfully as an alternative to clomethiazole.

Alcohol Withdrawal Delirium↗

Strategic planning in medical education: enhancing the learning environment for students in clinical settings.

BACKGROUND: The 1999 Cambridge Conference was held in Northern Queensland, Australia, on the theme of clinical teaching and learning. It provided an opportunity for groups of academic medical educators to consider some of the challenges posed by recent changes to health care delivery and medical education across a number of countries. PURPOSE: This paper describes the issues raised by the practical challenges posed by the current environment and how they might be addressed in ways that could promote more effective learning in clinical settings. METHOD: A SWOT analysis is a tool that can help in forward planning by identifying the strengths, weaknesses, opportunities and threats presented by any situation. Our SWOT analysis was used to generate a list of items, from which we chose those most feasible and most likely to promote positive change. RESULTS: Twenty different issues were identified, with four of them chosen by consensus for further elaboration. The discussion gave rise to four main recommended strategies: ensuring that clinical teachers thoroughly understand the purpose and process of learning in clinical settings; equipping learners with 'survival skills'; making the best use of learning resources within different clinical environments and making judicious use of information technology to enhance learning efficiency. CONCLUSIONS: The four strategies were selected not only because of their inherent importance, but also because of their feasibility. Modest changes can motivate students to feel part of a clinical team and a 'community of practice' and enhance their capacity for self-regulated practice.

Clinical Clerkship↗

The amino-acid sequence of the abalone (Haliotis laevigata) nacre protein perlucin. Detection of a functional C-type lectin domain with galactose/mannose specificity.

Perlucin isolated from abalone nacre consists of 155 amino acids including a glycosylated asparagine. The sequence of the first 130 amino acids shows a high similarity to the C-type carbohydrate-recognition domains of asialoglycoprotein receptors and other members of the group of C-type lectins but also a weaker similarity to related proteins without carbohydrate-binding activity. This C-type module is followed by a short C-terminal domain containing two almost identical sequence repeats with a length of 10 amino acids. Solid phase assays show a divalent metal ion-dependent binding of perlucin to (neo)glycoproteins containing D-galactose or D-mannose/D-glucose indicating that perlucin is a functional C-type lectin with broad carbohydrate-binding specificity. Our results also indicate that it may be difficult to predict carbohydrate-binding specificity and the occurrence of alternative binding configurations by amino-acid sequence comparisons and homology modeling.

Amino Acid Sequence↗

Expression and proteolysis of vascular endothelial growth factor is increased in chronic wounds.

Degradation of angiogenic mediators might be an underlying cause of chronic wounds. To test this hypothesis, we evaluated the expression and integrity of vascular endothelial growth factor, a potent angiogenic mediator, and its receptors, Flt-1 and KDR, in chronic venous leg ulcerations. Immunohisto- chemical, in situ hybridization, and semiquantitative reverse transcriptase polymerase chain reaction analyses all indicate that expression of vascular endothelial growth factor is elevated in ulcerative tissue, with vascular endothelial growth factor mRNA being especially pronounced in the hyperplastic epithelium of the wound margin. Flt-1 and KDR protein and mRNA were detected in the papillary vessels in close vicinity to the lesional epithelium of chronic wounds. Although increased expression of vascular endothelial growth factor protein was detected in the epidermis, the intensity of this staining was weak compared with the epidermal staining in psoriatic lesions and compared with the strong vascular endothelial growth factor mRNA signal in chronic wounds and psoriasis. To analyze whether this apparent decrease in immunoreactivity could be the result of degradation of vascular endothelial growth factor by proteolytic activities from the wound environment, we examined the stability of recombinant vascular endothelial growth factor in wound fluid from chronic leg ulcers. As demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, incubation of rVEGF165 with chronic, but not acute, wound fluid resulted in rapid proteolytic degradation of rVEGF165. Protease inhibitor studies indicate that serine proteases, such as plasmin, are involved in this degradation. Together, our data show that, although vascular endothelial growth factor expression is elevated in chronic wounds, increased proteolytic activity in this environment results in its degradation, which may contribute to an impaired wound healing response.

Chronic Disease↗