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Biomedical subjects

W Peters

Publications and source records attributed to W Peters.

At least 37 records · Page 2Linked to original sources

Practice parameters for the treatment of sigmoid diverticulitis--supporting documentation. The Standards Task Force. The American Society of Colon and Rectal Surgeons.

It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.

Diverticulitis, Colonic↗

Growth, ageing and death of a photoautotrophic plant cell culture.

Batch cultures of photoautotrophic cell suspensions of Chenopodium rubrum L., growing in an inorganic medium on CO2 under a daily balanced light-dark regime of 16: 8 h could be maintained for approximately 100 d without subcultivation. The long-lived cultures showed an initial cell division phase of 4 weeks, followed by a stationary phase of another 4 weeks, after which ageing and progressive cell death reduced the number of living cells and the cultures usually expired after another 3-4 weeks. These developmental phases of the cell culture were characterised with respect to photosynthetic performance, dark respiration, content of phytohormones and capacity of cell division. Cell division of the majority of the cells finished in the G1- or G0-phase of the cell cycle, caused by a pronounced decline in the endogenous levels of auxin and cytokinins. Supply of these growth factors to resting cells resulted in resumption of cytokinesis, at least by some of the cells. However, responsiveness to the phytohormones declined during the stationary phase, and subcultivation was no longer possible beyond day 60 when the phases of ageing and death commenced. Ageing was characterised by a further decline in the photosynthetic capacity of the cells, by a climacteric enhancement of dark respiration, but also by a slight increase in the level of IAA and cytokinins concomitant with a decrease in ethylene. Similarities and differences between the development of batch-cultured photoautotrophic cells of C. rubrum and that of a leaf are discussed with respect to using the cell culture as a model for a leaf.

Cell Death↗

Analysis of silicon in human tissues with special reference to silicone breast implants.

The increase, in the last two decades, in the application of silicones (polysiloxanes) and inorganic silicon compounds in medicine and the food industry, has exposed the human body to extensive contacts with these substances. Most silicone breast implants contain a gel consisting of a crosslinked silicone elastomer swollen by silicone oil (PDMS). Diffusion of PDMS through the silicone elastomer envelope and rupture of the envelope with release of the gel contents both occur clinically. The amount and distribution of silicone compounds in various tissues are key issues in the assessment of health problems connected with silicone implants. We have measured by GFAAS the Si content of tissues from normal and implant patients and the organic solvent extractable Si levels (assumed to be silicone), using careful control of sample collection and preparation. Whole blood levels were: implant patients mean 38.8 (SD 25.6) (microg/kg), controls mean 24.2 (SD 26.7) (microg/kg) in one study and subsequently 103.8 (SD 112.1) and 74.3 (SD 86.5) (microg/kg) in another study. Capsular tissue levels were: gel implants 25047 (SD 39313) (mg/kg of dry tissue), saline implants 20.0 (SD 27.3) (mg/kg of dry tissue) and controls 0.24 (SD 0.39) (mg/kg of dry tissue). Breast milk levels were: implant patients mean 58.7 (SD 33.8) (microg/kg), controls mean 51.1 (SD 31.0) (microg/kg); infant formula mean was 4.40 (mg/kg). Various precautions were undertaken to avoid Si contamination in this work, the most important being a) the use of a Class 100 laboratory for sample preparation and b) application of strict and elaborate washing procedure for specimen collection tools and laboratory plasticware. This data demonstrated that to properly interpret the importance of these numbers for human health, a larger study of "normal" levels of Si in human tissues should be undertaken and factors such as diet, water, race and geographical location should be considered.

Breast Implants↗

Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer.

We report here the transplantation of extensively purified "mobilized" peripheral blood CD34Thy-1 hematopoietic stem cells from 22 patients with recurrent or metastatic breast cancer. Patients were mobilized with either high-dose granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSE Median purity of the stem cell product at cryopreservation was 95.3% (range, 91.1%-98.3%), and viability was 98.6% (range, 96.5%-100%). After high-dose chemotherapy with carmustine, cisplatin, and cyclophosphamide, CD34+Thy-1 cells at a median dose of 11.3 x 10(5) per kilogram (range, 4.7-163 x 10(5) per kilogram) were infused. No infusion-related toxicity was observed. Neutrophil recovery was prompt, with median absolute neutrophil count >500/microL by day 10 (range, 8-15 days) and >1000/microL by day 11 (range, 8-17 days). Median platelet recovery (>20,000/microL) was observed by day 14 (range, 9-42 days) and >50,000/microL by day 17 (range, 11-49 days). Tumor cell depletion below the limits of detection of a sensitive immunofluorescence-based assay was accomplished in all patients who had detectable tumor cells in apheresis products before processing. Although CD4+ T-cell reconstitution was slow, no unusual infections were observed. Neither early nor late graft failure was observed, and no patient required infusion of unmanipulated backup cells. At a median follow-up of approximately 1.4 years and a maximum follow-up of 2.5 years, 16 of the 22 patients remain alive, with 9 free of disease progression, and have stable blood counts. In summary, highly purified CD34+Thy-1+ cells used as the sole source of the hematopoietic graft result in rapid and sustained hematopoietic engraftment.

Adult↗

Expression of nitric oxide synthase in pleomorphic adenomas of the parotid.

The actions of nitric oxide (NO) in the pathology of solid tumours are complicated and many are poorly understood because NO has both inhibitory and tumour-promoting activities. In the current study we aimed to find out immunohistochemically whether the expression of both the inducible (iNOS) and endothelial (eNOS) forms of the enzyme nitric oxide synthase (NOS) were changed in pleomorphic adenomas of the parotid compared with normal salivary tissue. There was a significant difference in staining for iNOS between the tumour and normal salivary tissue, with tumour epithelial cells being stained in 29 cases of the 30 cases studied (P< 0.0001). The luminal cells of the salivary ducts also stained, but not the normal salivary tissue. Immunohistochemistry for the eNOS isoenzyme showed moderate staining of the tumour epithelium in only three specimens. There was also mild staining in the salivary duct cells of the normal glandular tissue and in endothelium of blood vessels in both tumour and normal glandular tissue in the same 29 cases.

Adenoma, Pleomorphic↗

The chemotherapy of rodent malaria. LVIII. Drug combinations to impede the selection of drug resistance, Part. 2: The new generation--artemisinin or artesunate with long-acting blood schizontocides.

The search for combinations of antimalarial drugs that will impede the selection of drug resistance, especially in Plasmodium falciparum, is currently focused on the use of a member of the artemisinin family, with a short half-life, in association with a relatively long-acting blood schizontocide. Experiments with such 'third-generation' combinations, in mice infected either with chloroquine-sensitive P. berghei or P. chabaudi, or chloroquine-resistant P. yoelii ssp. NS, have produced interesting results. The data collected, using the '2% relapse technique' (2%RT), indicate that a combination of artemisinin with mefloquine can impede to a significant degree, although by no means completely, the selection of resistance to both compounds in P. berghei and in P. yoelii ssp. NS. Similarly, a combination of artesunate with pyronaridine impedes the selection of resistance to these compounds in P. berghei. Parallels are drawn between observations with such combinations in man and in the rodent models which, it is argued, once again demonstrate their value in predicting the protective value of using different types of antimalarials together. Evidence is presented that resistance to single compounds may emerge more rapidly when a high dose is employed in the 2%RT than a lower dose. It is noted also that the rate at which resistance to pyronaridine is selected by a given dose varies with the species of rodent Plasmodium, and the relevance of this to the malarial parasites of human is discussed.

Animals↗

The chemotherapy of rodent malaria. LIX. Drug combinations to impede the selection of drug resistance, Part 3: Observations on cyproheptadine, an antihistaminic agent, with chloroquine.

Several compounds in current clinical use as antihistaminic agents, among them cyproheptadine (CYP), have been shown, in experimental models, to reverse resistance of the asexual, intra-erythrocytic stages of rodent or human malarial parasites to chloroquine (CQ). Although preliminary clinical trials with CYP failed to confirm such activity in subjects with naturally acquired infection with Plasmodium falciparum, Nigerian investigators have reported that another antihistaminic, chlorpheniramine, significantly restores the blood schizontocidal action of CQ in semi-immune patients with CQ-resistant P. falciparum, when the two compounds are administered together. The rates at which resistance to CYP can be produced, in mice infected either with CQ-resistant P. yoelii ssp. NS or CQ-resistant P. yoelii nigeriensis, when drug-selection pressure is exerted with this compound alone have now been compared with the rate and extent to which resistance develops in infected animals that are treated with various combinations of CYP and CQ. The data indicate that, in both parasites, stable resistance develops slowly to CYP alone and that exposure to a combination of CYP plus CQ significantly impedes the selection of resistance to CYP. Although the antimalarial action of CYP is reported to extend to the pre-erythrocytic hepatic stages, there was no evidence of gametocytocidal activity in the present study. The future implications of these observations are discussed in relation to the clinical potential of CYP + CQ and similar combinations and possible future research.

Animals↗

Weight loss is correlated with an improved lipoprotein profile in obese postmenopausal women.

BACKGROUND: Changes in plasma lipid and lipoprotein distributions that occur after menopause increase the risk of cardiovascular disease in women, especially in those who are overweight. OBJECTIVE: The purpose of this study was to evaluate the impact of a nine-month weight reduction program on plasma lipids, dietary intake and abdominal fat obesity. DESIGN: A partial crossover design was used to study a weight loss treatment consisting of Phentermine hydrochloride (Fastin, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) therapy plus a low energy diet (5040 kJ/d). Forty-seven obese, postmenopausal Caucasian women (BMI of 30-38 kg/m2) were randomized into two groups, both of which received drug and diet treatment over six months. However, Group I started the intervention program three months later than Group II. Plasma total, HDL and LDL cholesterol and triacylglycerol were measured, body composition was assessed by anthropometry and dual energy x-ray absorptiometry, and food frequency records were collected at four timepoints. RESULTS: Over nine months, women in Group II reduced body weight (14.4%), lowered plasma concentrations of LDL cholesterol (14% to 26%) and triacylglycerol (15%) and raised plasma HDL cholesterol concentration (15%). These plasma lipid changes decreased the total cholesterol/HDL cholesterol ratio from 4.3 to 3.2. All subjects decreased abdominal fat measurements and energy and cholesterol intakes, as well as percentage of energy derived from total and saturated fat during the study. Most subjects also increased dietary fiber consumption. CONCLUSION: Both weight loss and diet modifications are associated with an improved plasma lipid profile in obese postmenopausal women.

Adult↗

Efficacy and safety of bipolar sensing with high atrial sensitivity in dual chamber pacemakers.

In dual chamber pacemakers, atrial sensing performance is decisive for maintenance of AV synchrony. Particularly, the efficacy of mode switching algorithms during intermittent atrial tachyarrhythmias depends on the sensitive detection of low potential amplitudes. Therefore, a high atrial sensitivity of 0.18 mV, commonly used in single lead VDD pacemakers, was investigated for its efficacy and safety in DDD pacing. Thirty patients received dual chamber pacemakers and bipolar atrial screw-in leads for sinus node syndrome or AV block; 15 patients suffered from intermittent atrial fibrillation. Pace makers were programmed to an atrial sensitivity of 0.18 mV. Two weeks, 3, 9, and 15 months after implantation, P wave sensing threshold and T wave oversensing thresholds for the native and paced T wave were determined. The myopotential oversensing thresholds were evaluated by isometric contraction of the pectoral muscles. Automatic mode switch to DDIR pacing was activated when the mean atrial rate exceeded 180 beats/min. The patients were followed by 24-hour Holter monitoring. Two weeks after implantation, mean atrial sensing threshold was 1.81 +/- 0.85 mV (range 0.25-2.8 mV) without significant differences during further follow-up. Native T wave sensing threshold was < 0.18 mV in all patients. In 13% of patients, paced T waves were perceived in the atrial channel at the highest sensitivity. This T wave sensing could easily be avoided by programming a postventricular atrial refractory period exceeding 300 ms. Myopotential oversensing could not be provoked and Holter records showed no signs of sensing dysfunction. During a 15-month follow-up, 1,191 mode switch events were counted by autodiagnostic pacemaker function. Forty-two of these events occurred during Holter monitoring. Unjustified mode switch was not observed. In DDD pacemakers, bipolar atrial sensing with a very high sensitivity is efficient and safe. Using these sensitivity settings, activation of the mode switch algorithm almost completely avoids fast transmission of atrial rate to the ventricle during atrial fibrillation.

Adult↗

Age dependency of sensing performance and AV synchrony in single lead VDD pacing.

Implantation of single lead VDD pacemakers is an established therapeutic option in patients with AV block and normal sinus node function. However, related to occurrence of sinus node disease and atrial undersensing, there is concern whether VDD devices are appropriate in physically active young patients. Two hundred thirty-two consecutive patients with isolated AV block and VDD pacemakers were investigated. This population was subdivided into quartiles of 58 patients according to age at time of inclusion: 26.2-59.4 years (group A), 59.5-70.1 years (group B), 70.2-81.0 years (group C), and 81.1-92.5 years (group D). Follow-up visits included pacemaker telemetry, Holter monitoring, and exercise testing. Patients were visited at 2 and 12 weeks after implantation thereafter followed by 6-month intervals. Mean follow-up period was 35 +/- 14 months. Three months after implantation, atrial sensing threshold was significantly higher in young patients: 1.18 +/- 0.58 mV (group A) versus 0.79 +/- 0.35 mV (group B), 0.68 +/- 0.33 mV (group C), and 0.60 +/- 0.25 mV (group D), P < 0.001 for comparison of group A to all other groups. Atrial undersensing was observed less frequently in young patients: 6.9% (group A) versus 17.2% (group B), 24.1% (group C), and 27.6% (group D), P = 0.025 for intergroup comparisons. Sinus node dysfunction did not occur in group A. Atrial arrhythmias and loss of AV synchronized pacing mode occurred rarely in young patients: 0.6% (0.4%) per year in group A versus 1.3% (1.3%) in group B, 3.9% (3.4%) in group C, and 5.7% (7.4%) per year in group D, P < 0.01 for intergroup comparisons. Our data show good atrial sensing performance, low incidence of sinus node dysfunction, and few atrial arrhythmias in young patients with VDD pacing for AV block. Thus, single lead VDD pacing can be recommended particularly for young patients with AV block.

Adult↗

Long-term superiority of steroid elution in atrial active fixation platinum leads.

Steroid elution reduces the acute increase in stimulation threshold particularly in active fixation leads. The aim of this study was to investigate the long-term efficacy of steroid elution in atrial screw-in leads compared to conventional lead design. Two different bipolar active fixation platinum lead designs were implanted. Leads were similar except for the presence (group S, n = 66) or absence (group N, n = 68) of steroid elution. Patients received dual chamber pacemakers with the following atrial leads in consecutive order: Medtronic 4058 M (group N, n = 30), Medtronic 4068 (group S, n = 40), Vitatron IMS 13 (identical to 4058 M, group N, n = 38), and Vitatron IMX 13 (identical to 4068, group S, n = 26). The mean follow-up period was 40.7 +/- 16.1 months (range 10 to 84 months). Stimulation thresholds, pacing impedances, P wave potentials, and sensing threshold were assessed for both groups immediately, 10 days, 6 weeks, and 3 months after implantation followed by 6-months intervals. Energy thresholds, chronaxie-rheobase products, and energy consumption of atrial pacing were calculated. Chronic values were deduced from the most recent measurement performed in an individual patient. Within the first 10 days after implantation, atrial voltage threshold at pulse duration of 0.4 ms increased from 0.91 +/- 0.42 to 2.06 +/- 0.45 V in group N (P < 0.001). Less increase was observed in group S (0.83 +/- 0.39 to 1.08 +/- 0.53 V, P = 0.003). Atrial voltage thresholds remained markedly lower in steroid-eluting leads during whole follow-up (1.12 +/- 0.49 V in group S vs 1.58 +/- 0.71 V in group N, P < 0.001). Chronic energy consumption was markedly reduced in group S (4.0 +/- 2.7 microJ) compared to group N (9.8 +/- 7.5 microJ, P < 0.001). An atrial voltage threshold below 1.25 V at 0.4 ms was achieved in 92.3% of patients of group S allowing programming of an output of 2.5 V. Such low outputs were feasible in only 49.3% of patients in group N (P < 0.001). Chronic P wave amplitudes did not differ significantly between groups (3.27 +/- 1.81 mV in group N vs 3.24 +/- 1.18 mV in group S, P = 0.91). Steroid elution diminishes the increase of stimulation thresholds of nonsteroid atrial active fixation platinum leads resulting in a long-term reduction of energy consumption. Thus, use of steroids can be recommended for general use in atrial active fixation lead designs.

Aged↗

Atrial lead placement during atrial fibrillation. Is restitution of sinus rhythm required for proper lead function? Feasibility and 12-month functional analysis.

Unexpected atrial fibrillation (AF) during implantation of an atrial pacemaker lead is sometimes encountered. Intraoperative cardioversion may lengthen and complicate the implantation process. This study prospectively investigates the performance of atrial leads implanted during AF (group A) and compares atrial sensing and pacing properties to an age- and sex-matched control group in which sinus rhythm had been restored before atrial lead placement (group B). Patient groups consisted of 32 patients each. All patients received DDDR pacemakers and bipolar, steroid-eluting, active fixation atrial leads. In patients with AF at the time of implantation (group A), a minimal intracardiac fibrillatory amplitude of at least 1.0 mV was required for acceptable atrial lead placement. In patients with restored sinus rhythm (group B), a voltage threshold < 1.5 V at 0.5 ms and a minimal atrial potential amplitude > 1.5 mV was required. Patients of group A in whom spontaneous conversion to sinus rhythm did not occur within 4 weeks after implantation underwent electrical cardioversion to sinus rhythm. Pacemaker interrogations were performed 3, 6, and 12 months after implantation. In group A, implantation time was significantly shorter as compared to group B (58.7 +/- 8.6 minutes vs 73.0 +/- 17.3 minutes, P < 0.001). Mean atrial potential amplitude during AF was correlated with the telemetered atrial potential during sinus rhythm (r = 0.49, P < 0.001), but not with the atrial stimulation threshold. Twelve months after implantation, sensing thresholds (1.74 +/- 0.52 mV vs 1.78 +/- 0.69 mV, P = 0.98) and stimulation thresholds (1.09 +/- 0.42 V vs 1.01 +/- 0.31 V, P = 0.66) did not differ between groups A and B. However, in three patients of group A, chronic atrial sensing threshold was < or = 1 mV requiring atrial sensitivities of at least 0.35 mV to achieve reliable atrial sensing. Atrial lead placement during AF is feasible and reduces implantation time. However, bipolar atrial leads and the option to program high atrial sensitivities are required.

Aged↗

Mechanisms of artemisinin resistance in the rodent malaria pathogen Plasmodium yoelii.

Artemisinin and its derivatives are important new antimalarials which are now used widely in Southeast Asia. Clinically relevant artemisinin resistance has not yet been reported but is likely to occur. In order to understand how the malaria parasite might become resistant to this drug, we studied artemisinin resistance in the murine malaria parasite Plasmodium yoelii. The artemisinin-resistant strain (ART), which is approximately fourfold less sensitive to artemisinin than the sensitive NS strain, accumulated 43% less radiolabeled drug in vitro (P < 0.01). Within the parasite, the drug appeared to react with the same parasite proteins in both strains. The translationally controlled tumor protein, one of the artemisinin target proteins, did not differ between the strains. No DNA sequence difference was found, but the resistant strain was found to express 2.5-fold-more protein than the sensitive strain (P < 0.01). Thus, the phenotype of artemisinin resistance in P. yoelii appears to be multifactorial.

Amino Acid Sequence↗

Plasmodium berghei: identification of an mdr-like gene associated with drug resistance.

Amplification, mutations, or overexpression of the pfmdr1 gene have been associated with multiple drug resistance in some strains of Plasmodium falciparum. In order to better understand this potential mechanism of drug resistance, we are currently investigating putative mdr homologues in vivo in the rodent malaria Plasmodium berghei. We have identified and partially sequenced a gene that is amplified in a MFQ-resistant (MFQr) line. Using degenerate primers, a 579-bp fragment was amplified by PCR using P. berghei genomic DNA as template. The predicted amino acid sequence shares 66% identity with the previously reported pfmdr1 gene product (Pgh1) of P. falciparum. Southern blots and slot blots of genomic DNA suggest that this gene is amplified two- to threefold in a MFQr line (N/1100), as has been previously reported in some MFQr strains of P. falciparum. The P. berghei gene was mapped to chromosome 12 in all of the lines analyzed. Furthermore, the cloned PCR product also hybridizes to chromosome 5 of the MFQr strain.

ATP-Binding Cassette Transporters↗