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Biomedical subjects

K Peters

Publications and source records attributed to K Peters.

At least 145 records · Page 8Linked to original sources
PubMed2000

A comparison of resident and faculty attitudes toward physician-assisted suicide and active voluntary euthanasia.

PURPOSE: Assisted death practices such as physician-assisted suicide (PAS) and active voluntary euthanasia (AVE) are becoming more acceptable to the public and the medical profession. This study compared the attitudes and practices of resident house staff physicians with the medical staff physicians responsible for teaching them regarding PAS and AVE. METHODS: A convenience sample of 372 medical staff and 105 resident house staff from a multi-residency community teaching hospital were anonymously surveyed. The overall response rate was 47%. The questionnaire consisted of 10 questions that examined the subjects' professional and legal values, willingness to participate in assisted death practices, and personal preferences for assisted death practices. RESULTS: The resident house staff differed significantly from the medical staff in attitudes toward assisted death practices. The resident house staff was less likely to support the traditional prohibitions against PAS and AVE. The resident house staff was also more likely to offer assisted death practices if they were legal. There was no significant difference, however, in the participation of assisted death practices between the groups respectively for PAS and AVE. The residents were more likely to request PAS or AVE for themselves or family members. CONCLUSIONS: There are significant differences in attitudes and practices between resident physicians and medical staff physicians concerning PAS and AVE. These differences could lead to professional conflicts when setting clinical goals for end-of-life care and could compromise patient care.

Attitude of Health Personnel↗
PubMed2000

[Identification of mutations in the arylsulfatase B gene in Russian mucopolysaccharidosis type VI patients].

Molecular genetic analysis of the gene for arylsulfatase B (ASB) was conducted in ten Russian patients with type VI mucopolysaccharidosis (MPS VI) of different severity. Eight exons from the translated region of the ASB gene of each patient were amplified and sequenced using the nonradioactive method. Fourteen mutant alleles were identified in the sample studied by means of DNA analysis; 13 of them had not been described before. All patients except for one, who was an offspring of a consanguineous marriage, were genetic compounds with respect to the mutations found. Polymorphic sites A/G 1072 and A/G 1126, which were earlier revealed in exon 5 of the ASB gene, were found in five out of ten patients studied. The spectrum of mutant alleles of the ASB gene was highly specific and agreed with the characteristics of the population genetic load.

Base Sequence↗
PubMed2000

The effects of repeated optokinetic stimulation on human autonomic function.

Numerous animal studies have suggested that the vestibular system modulates respiratory and cardiovascular function. However, relatively few studies have examined vestibular-autonomic interaction in humans. In this study we investigated the effects of repeated horizontal (clockwise or anticlockwise) optokinetic stimulation on systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse and latency to circularvection (CV) in humans, and compared the effects with those of repeated exposure to a stationary visual stimulus. Although all subjects experienced CV, neither mean SBP, DBP or pulse differed significantly between the clockwise/anticlockwise optokinetic stimulation and no optokinetic stimulation conditions. However, SBP and DBP changed significantly over the 20 trials in each test session, even when there was no optokinetic stimulation (P < 0.001 in each case). These results suggest that while horizontal optokinetic stimulation does not significantly affect SBP, DBP or pulse in humans, changes in these variables can be induced by trial repetition itself, even when no optokinetic stimulation occurs.

Adult↗
PubMed1999

An investigation into the distribution of lecithins in nanosuspension systems using low frequency dielectric spectroscopy.

A range of nanosuspensions comprising a model drug (RMKP 22) with varying concentrations of Phospholipon 90 were prepared using high pressure homogenization and analyzed using low frequency dielectric spectroscopy as a novel means of characterizing the distribution of Phospholipon 90 within the suspensions. A corresponding range of aqueous Phospholipon 90 suspensions were also studied for the purpose of comparison. The dielectric responses were interpreted using a modification of the Maxwell-Wagner approach, whereby the systems were considered to comprise a high frequency response corresponding to the bulk layer serially connected to a lower frequency response corresponding to an electrode barrier layer. The low frequency responses of both the Phospholipon 90 dispersions and the nanosuspensions were found to be essentially independent of phospholipid concentration, indicating the presence of a barrier layer covering the electrode surfaces. In contrast, the high frequency (bulk) loss response was found to increase with Phospholipon 90 concentration for the surfactant suspensions while a maximum in response was seen with Phospholipon 90 concentration for the nanosuspensions; this behaviour was attributed to the presence of impurities within the phospholipids. Based on this investigation, a model is proposed with which the dielectric response may be related to the surface coverage of the suspended drug particles.

Chemistry, Pharmaceutical↗
PubMed1999

Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE-/- mice.

BACKGROUND: The impact of disordered lipid metabolism on collateral vessel development was studied in apolipoprotein (apo)E-/- mice with unilateral hindlimb ischemia. METHODS AND RESULTS: Hindlimb blood flow and capillary density were markedly reduced in apoE-/- mice versus C57 controls. This was associated with reduced expression of vascular endothelial growth factor (VEGF) in the ischemic limbs of apoE-/- mice. Cell-specific immunostaining localized VEGF protein expression to skeletal myocytes and infiltrating T cells in the ischemic limbs of C57 mice; in contrast, T-cell infiltrates in ischemic limbs of apoE-/- mice were severely reduced. The critical contribution of T cells to VEGF expression and collateral vessel growth was reinforced by the finding of accelerated limb necrosis in athymic nude mice with operatively induced hindlimb ischemia. Adenoviral VEGF gene transfer to apoE-/- mice resulted in marked augmentation of hindlimb blood flow and capillary density. CONCLUSIONS: These findings thus underscore the extent to which hyperlipidemia adversely affects native collateral development but does not preclude augmented collateral vessel growth in response to exogenous cytokines. Moreover, results obtained in the apoE-/- and athymic nude mice imply a critical role for infiltrating T cells as a source of VEGF in neovascularization of ischemic tissues.

Adenoviridae↗
PubMed1999

[Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS].

UNLABELLED: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

Anticholesteremic Agents↗
PubMed1999

Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF.

Diabetes is a major risk factor for coronary and peripheral artery diseases. Although diabetic patients often present with advanced forms of these diseases, it is not known whether the compensatory mechanisms to vascular ischemia are affected in this condition. Accordingly, we sought to determine whether diabetes could: 1) impair the development of new collateral vessel formation in response to tissue ischemia and 2) inhibit cytokine-induced therapeutic neovascularization. Hindlimb ischemia was created by femoral artery ligation in nonobese diabetic mice (NOD mice, n = 20) and in control C57 mice (n = 20). Hindlimb perfusion was evaluated by serial laser Doppler studies after the surgery. In NOD mice, measurement of the Doppler flow ratio between the ischemic and the normal limb indicated that restoration of perfusion in the ischemic hindlimb was significantly impaired. At day 14 after surgery, Doppler flow ratio in the NOD mice was 0.49+/-0.04 versus 0.73+/-0.06 for the C57 mice (P< or =0.005). This impairment in blood flow recovery persisted throughout the duration of the study with Doppler flow ratio values at day 35 of 0.50+/-0.05 versus 0.90+/-0.07 in the NOD and C57 mice, respectively (P< or =0.001). CD31 immunostaining confirmed the laser Doppler data by showing a significant reduction in capillary density in the NOD mice at 35 days after surgery (302+/-4 capillaries/mm2 versus 782+/-78 in C57 mice (P< or =0.005). The reduction in neovascularization in the NOD mice was the result of a lower level of vascular endothelial growth factor (VEGF) in the ischemic tissues, as assessed by Northern blot, Western blot and immunohistochemistry. The central role of VEGF was confirmed by showing that normal levels of neovascularization (compared with C57) could be achieved in NOD mice that had been supplemented for this growth factor via intramuscular injection of an adenoviral vector encoding for VEGF. We conclude that 1) diabetes impairs endogenous neovascularization of ischemic tissues; 2) the impairment in new blood vessel formation results from reduced expression of VEGF; and 3) cytokine supplementation achieved by intramuscular adeno-VEGF gene transfer restores neovascularization in a mouse model of diabetes.

Adenoviridae↗
PubMed1999

Academic medicine into the millennium: the UK scene.

Clinical academic medicine has a vital role to play in the introduction and development of new therapies. The clinical scientist is essential in asking for answers to questions that arise from clinical practice. However, clinical academics should not be overburdened with clinical service or teaching commitments as these functions are shared by National Health Service staff. The exciting developments in molecular genetics and the study of the interaction between environmental and genetic factors emphasize the importance of clinical academic medicine and the clinician scientist into the millennium.

Clinical Medicine↗
PubMed1999

An integrated dialysis delivery network in Ontario.

In August 1995, the Ontario Ministry of Health (MOH) issued a request for proposal (RFP) for the establishment of new and expanded dialysis services. London Health Sciences Centre (LHSC) was successful in expanding its integrated dialysis delivery network with satellites in Stratford, Woodstock and Owen Sound. This achievement required collaboration of LHSC and host hospital staff to meet the challenging RFP requirements. With final approval received in January 1997, efforts were required to establish an operational model supporting self-care and full-care patients, to train satellite staff and patients, and to manage the resulting clinical impact. A balanced scorecard (Kaplan & Norton, 1992) evaluation model was developed. Initial outcome data indicate that full-care patients in satellites require more fallback support to London units, experience more hypotensive episodes during dialysis and, in some cases, demonstrate lower levels of dialysis adequacy and nutritional status when compared to satellite self-care patients. Findings from these data will assist in revising patient inclusion criteria and processes to optimize community-based dialysis.

Ambulatory Care↗
PubMed1999

Supportive use of amifostine in patients with head and neck tumors undergoing radio-chemotherapy. Is it possible to limit the duration of the application of amifostine?

BACKGROUND: Amifostine is a new cancer-supporting agent to protect normal tissue in patients receiving radio-chemotherapy. The main question of our study is whether the application of amifostine can be limited on the duration of chemotherapy in patients with advanced head and neck tumors undergoing radio-chemotherapy. PATIENTS AND METHODS: In a randomized study 14 patients were treated with amifostine (500 mg, day 1 to 5 and 29 to 33) during concurrent radio-chemotherapy with carboplatin (70 mg/m2, day 1 to 5 and 29 to 33), 14 patients were treated without amifostine. The analyzed parameters were dermatitis, mucositis, skin temperature, white blood and platelet count, creatinine and scintigram of salivary glands. Median survival of the amifostine group was 19 months, of the control group 10 months. RESULTS: There were no relevant differences in all analyzed parameters between both arms of the study. CONCLUSION: Our form of amifostine application is probably not able to obtain a relevant reduction of the toxicity of radio-chemotherapy.

Adolescent↗
PubMed1999

[Clinical anatomy in the operating room. A model of integrated medical education].

Clinical relevance of theoretical knowledge is advantageous to be demonstrated early during preclinical education in medical schools. We describe a new way for anatomists and surgeons of teaching anatomy together during surgical procedures in the operating theatre, thus demonstrating successfully the need of keen insight in the field of gross anatomy. The students reported to be motivated to learn anatomy. A questionnaire was completely answered by 24 students after having finished the 96/97 course of anatomy in the operating theatre. The students reported that they have learned a lot as well as to be highly motivated to continue their efforts of gaining knowledge on the field of gross anatomy because of its clinical relevance.

Anatomy↗
PubMed1998

Crystal structure of subtilisin DY, a random mutant of subtilisin Carlsberg.

The crystal structure of subtilisin DY inhibited by N-benzyloxycarbonyl-Ala-Pro-Phe-chloromethyl ketone has been solved by molecular replacement with subtilisin Carlsberg as the starting model. The model has been refined to a crystallographic R factor (= sigma absolute value [(absolute value Fo) - (absolute value Fc)] / sigma (absolute value of Fo) of 15.1% using X-ray diffraction data to 0.175 nm resolution. Subtilisin DY is an alkaline proteinase from the X-irradiated Japanese strain DY of Bacillus licheniformis, which normally produces subtilisin Carlsberg. It has very similar properties to subtilisin Carlsberg, with a slightly enhanced resistance to heat and guanidine hydrochloride-induced denaturation, in spite of the fact that the sequences of the two enzymes differ in 31 positions out of 274 residues. The close similarity in overall three-dimensional structure of subtilisins DY and Carlsberg and also their physicochemical properties, such as activity and stability, shows that nature aided by X-irradiation for rapid 'evolution' is able to accommodate considerable changes in sequence without substantial changes in property.

Amino Acid Sequence↗
PubMed1998

[Improvement of aerobic capacity in chronic congestive heart failure. Which training method is appropriate?].

Standardized guidelines for exercise training for patients with chronic congestive heart failure (CHF) have not been established. In the past, CHF patients involved in exercise training studies demonstrated a wide range of cardiac and functional impairment, with an ejection fraction between 18 and 35% and a peak VO2 between 12.2 and 25.4 ml/kg/min on average. For determination of training intensity, a VO2 between 40 and 70% of peak VO2 and/or training heart rate between 60 and 80% of peak heart rate was used. There was also a wide range for frequency (between 3 and 7 times per week) and duration of training (between 20 and 60 min per session). For aerobic exercise training only continuous training methods were applied. We have developed a new interval training method which allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. After only three weeks of training, the improvement in aerobic capacity was similar to that reported after longer training periods using continuous methods. To determine work rate for work phases of interval training, a special steep ramp test was developed. By analysis of acute physical responses to this testing procedure and to the interval training, both were proven to be tolerable in CHF patients, even if their ejection fraction is as low as 13%, or peak cardiac index not greater than 1.61/m2/min, and peak VO2 less than 8.5 ml/kg/min.

Chronic Disease↗
PubMed1998

Evaluation of the RapID CB plus system for identification of coryneform bacteria and Listeria spp.

In a stress test, the recently introduced RapID CB Plus system (Remel Inc. [formerly Innovative Diagnostic Systems], Norcross, Ga.) was challenged with a diverse set of gram-positive rods comprising 345 strains of coryneform bacteria and 33 strains of Listeria spp. representing a total of 49 different taxa. Overall, within 4 h, the system correctly identified 80.9% of the strains on the species level and 12.2% of the strains on the genus level. Only 3.7% strains were misidentified, and for 3.2% of the strains no identification was provided. Difficulties with the system were mainly due to occasional uncertainties in reading reactions for acid production from carbohydrates and, to a lesser extent, aminopeptidase reactions. It is concluded that the system may also perform well under the conditions of a routine clinical laboratory.

Actinomycetales↗
PubMed1998

Immunoglobulin VH genes of high-grade mucosa-associated lymphoid tissue lymphomas show a high load of somatic mutations and evidence of antigen-dependent affinity maturation.

High-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma of the stomach shares several features with its low-grade counterpart. The latter is nearly invariably associated with Helicobacter pylori, and the tumor cells of all MALT lymphomas normally express surface antigen receptors; thus, it is possible that the high-grade type, like the low-grade type, is still influenced by interaction with antigen. In the present study, we analyzed the immunoglobulin heavy chain variable (V)-region genes from eight cases of high-grade MALT lymphoma and one case of Burkitt's lymphoma of the stomach. The V-region genes revealed somatic mutations in all cases, leading to the conclusion that high-grade MALT lymphomas derive from antigen-experienced (post-) germinal center B-cells. Nonrandom distribution of replacement and silent mutations within the gene segments in seven of the eight MALT lymphomas indicated that these V-region genes were selected by antigen, at least for some period of time. Five of the cases showed an unusual mutation pattern that was suggestive of selection by autoantigen or superantigen rather than heterogeneous antigen. Analysis for intraclonal variations revealed evidence of ongoing mutations in two cases. In these cases, the tumor clones probably derived from cells affected by a germinal center B-cell reaction, as the microenvironment of the germinal center is required for maintenance of an active hypermutation mechanism. On the other hand, in another two cases, no evidence of intraclonal variations was found. Thus, either these tumor clones were derived from postgerminal center B-cells, or the hypermutation mechanism in the germinal center ceased after some period of time. Given the mutation pattern, it is possible that high-grade MALT lymphomas emerge from further transformation of low-grade MALT lymphomas with accumulation of additional mutations in the complementarity-determining regions.

Amino Acid Sequence↗