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Biomedical subjects

P Harms

Publications and source records attributed to P Harms.

12 recordsLinked to original sources

The distribution of FSH receptor isoforms is related to basal FSH levels in subfertile women with normal menstrual cycles.

BACKGROUND: Recently a polymorphic variant of the FSH receptor in which amino acid asparagine (Asn) at position 680 is replaced by serine (Ser) was found. This is associated with higher FSH levels in the early follicular phase and an increased FSH requirement to obtain follicular response in IVF patients. The aim of our study was to test the hypothesis that this receptor isoform occurs more often in regularly menstruating subfertility patients with elevated basal FSH than in those with normal early follicular phase FSH. METHODS: A retrospective cohort study of 38 subfertility patients with a regular menstrual cycle and elevated FSH (>10 IU/l) compared to 40 patients with normal early follicular phase FSH was carried out. DNA was analysed to determine the FSH receptor genotype. RESULTS: The N680S variant on one or both alleles of the FSH receptor gene was significantly more prevalent in patients with elevated FSH (P < 0.05). The homozygous Asn/Asn variant at codon 680 was found in 45% of women with normal FSH and in 21% of women with elevated FSH. The homozygous Ser/Ser receptor variant was present in 12.5% of women with normal FSH and in 21% of patients with elevated FSH. Also the heterozygous combination of both variants Asn/Ser occurred more often in women with elevated FSH (58 versus 42.5%). CONCLUSIONS: The N680S sequence variation of the FSH receptor is found in >75% of the cases with elevated basal FSH and suggests a higher FSH threshold.

Adult↗

Socio-cultural factors influencing prevention and treatment of tuberculosis in immigrant and Aboriginal communities in Canada.

This multi-method study used a participatory action research approach to examine the complex net of socio-cultural factors that influenced behaviour related to tuberculosis (TB) prevention and treatment in the 10 highest risk cultural groups consisting of immigrant and Aboriginal populations in the province of Alberta, Canada. Trained community research associates collected qualitative interview data and helped with interpretation and evaluation. A community advisory committee established foundation principles and monitored the ethical and cultural appropriateness of the research process. A key finding is that although patients with active disease learn about TB from health professionals, people in high-risk populations need to learn more about TB transmission and prevention prior to contact. This is particularly important given that lack of knowledge of TB was strongly associated with negative attitudes towards TB and a worse experience of the disease. The study results underline the need for accessible and culturally appropriate health education about TB in the high risk groups. This can be accomplished in collaboration with lay people, particularly those who have recovered from active TB, their family members and health workers from the community.

Antitubercular Agents↗

Paraesthesiae during needle-through-needle combined spinal epidural versus single-shot spinal for elective caesarean section.

The aim of this study was to compare the incidence of paraesthesiae during spinal needle insertion in a needle-through-needle combined spinal-epidural (CSE) versus a single-shot spinal (SSS) technique. Eighty-nine women presenting for elective caesarean section at a tertiary referral obstetric unit were randomized to receive either needle-through-needle CSE or SSS. Equipment used was a 16 gauge/26 gauge combined spinal-epidural kit and a 26 gauge pencil-point spinal needle with introducer (both Sims Portex, Australia) The presence and distribution of paraesthesiae was recorded by an observer at spinal needle insertion and again on day one postoperatively. There were three failures to perform the intended block. One patient was lost to follow-up at postoperative day one. Seventeen of forty-six (37%) women in the needle-through-needle CSE group and four of forty-three (9%) in the SSS group had paraesthesiae upon spinal needle insertion (P < 0.05, Chi-squared test). No patient had persistent neurological symptoms at postoperative day one. We postulate that the higher incidence of paraesthesiae with needle-through-needle CSE may be related to deeper penetration of the subarachnoid space with this technique.

Adult↗

Low-cost microbioreactor for high-throughput bioprocessing.

The design of a microbioreactor is described. An optical sensing system was used for continuous measurements of pH, dissolved oxygen, and optical density in a 2 mL working volume. The K(L)a of the microbioreactor was evaluated under different conditions. An Escherichia coli fermentation in both the microbioreactor and a standard 1 L bioreactor showed similar pH, dissolved oxygen, and optical density profiles.%The low cost of the microbioreactor, detection system, and the small volume of the fermentation broth provide a basis for development of a multiple-bioreactor system for high-throughput bioprocess optimization.

Bioreactors↗

Ratiometric oxygen sensing: detection of dual-emission ratio through a single emission filter.

A new method and device for the ratiometric measurement of oxygen concentration are presented. They are based on the use of a dual-emission oxygen-sensitive dye. The method allows the exclusion of the influence of emission overlap. The detection of the dual-emission ratio is performed using a single long-pass emission filter. The device described is simpler than the widely used lifetime instruments and could easily be a stand-alone low-cost instrument.

Coloring Agents↗

Safety and cost effectiveness of a 10 x 10(9)/L trigger for prophylactic platelet transfusions compared with the traditional 20 x 10(9)/L trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia.

In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 x 10(9)/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 x 10(9)/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 x 10(9)/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.

Acute Disease↗

Pyridinium cross-links in multiple myeloma: correlation with clinical parameters and use for monitoring of intravenous clodronate therapy--a pilot study of the German Myeloma Treatment Group (GMTG).

The relevance of quantitative determinations of urinary deoxypyridinolines (DPY) and pyridinolines (PY), and of serum type I collagen carboxyterminal cross-linked telopeptides (ICTP), has been evaluated for patient monitoring in multiple myeloma (MM). In 178 untreated MM patients, a clear correlation was found between ICTP concentrations, bone destructions and serum calcium levels. Furthermore, serum ICTP, urinary DPY and PY concentrations were estimated before and during treatment in a further 33 MM patients randomly allocated to four groups receiving intravenous melphalan/prednisone (MivP) chemotherapy alone, or MivP in combination with three different doses of i.v. clodronate. 1800 mg of i.v. clodronate combined monthly with MivP induced a rapid and sustained reduction in bone resorption parameters to the normal range, a result not obtained with either MivP alone, or with a lower clodronate dose. While confirming the relevance of determining pyridinium cross-links for estimating bone resorption in MM, our data indicate that measurements of these parameters could be useful for dose finding and monitoring of bisphosphonate therapy.

Adult↗

Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma.

In vitro data have demonstrated autologous T-lymphocytes with anti-tumour activity in multiple myeloma (MM). Therefore a phase I/II trial was conducted to study the feasibility, the effect on several immunological parameters, and the tumour response induction of low-dose recombinant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced stages in progress, who had failed on standard chemotherapy received 9 x 10(6) IU/m2 rIL-2 twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for 5 subsequent days per week subcutaneously from days 3 to 56 (repeated every 12 weeks until progression). Patients were treated for between 8 and 1086 + d (mean 241 d) without serious side-effects. 6/17 patients experienced tumour response (2/17 objective tumour mass reduction, 4/17 long-lasting stable disease following tumour progression before initiation of rIL-2 treatment). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by enhanced CD25 antigen expression, and CD56+ NK cells expanded in the peripheral blood. Furthermore, a diminished pre-treatment ratio of CD4+/CD8+ lymphocytes was normalized during rIL-2 treatment. NK cell activity and lymphokine activated killer (LAK) cell activity was significantly enhanced. Endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations were induced. Low-dose rIL-2 can stimulate immune enhancement in MM despite the characteristic tumour-induced immunodeficiency. The treatment has proven though limited efficacy in advanced MM. Because most of the responders experienced termination of tumour progression rather than tumour regression, rIL-2 maintenance of chemotherapy-induced remissions should be investigated.

Aged↗

Clinical assessment of fetal blood flow velocimetry.

A statistical procedure is presented to analyze the relation between Doppler indices (DIs) such as pulsatility index (PI), resistance index (RI), A/B and clinical data of pregnancy and fetal outcome of three groups: (1) uncomplicated pregnancy, eutrophic fetus (NF), (2) pregnancy-induced hypertension (PIH), and (3) pregnancy and delivery of a dystrophic fetus (IUGR), and the acidity classes according to Saling, respectively. Proceeding and mathematical requirements as well as the possibilities to validate the methodology are introduced, and an application to previously published data is presented. By multivariate analysis of the data a fair prognosis of NF, PIH and IUGR was possible. The variability inherent to the data sampling requires a mathematical postprocessing in the framework of an adequate model before any clinical conclusions can be derived from DIs.

Blood Flow Velocity↗

Effect of substituted benzimidazoles on acid secretion in isolated and enriched guinea pig parietal cells.

The inhibitory effect of the three benzimidazole derivatives timoprazole, picoprazole, and omeprazole on histamine and dbcAMP stimulated 14C-aminopyrine accumulation (= H+ secretion) has been studied in isolated and enriched guinea-pig parietal cells. All compounds tested inhibited H+ secretion in a concentration dependent manner with IC50 values of 8.5 +/- 1.9 mumol/l for timoprazole, 3.9 +/- 0.7 mumol/l for picoprazole, and 0.13 +/- 0.03 mumol/l for omeprazole. The IC50 of timoprazole, when dbcAMP was used as a stimulus, did not differ significantly from that of histamine stimulation. The type of inhibition was of a non-competitive nature. The full acid response to histamine after temporary exposure of the cells to the benzimidazoles could be restored by washing the cells twice; this suggests that the inhibition is reversible. The data - among others - indicate that the properties of the benzimidazoles described here would allow these compounds to be used as effective antisecretagogues.

2-Pyridinylmethylsulfinylbenzimidazoles↗