Flow velocity wave forms in the human fetal ductus arteriosus during the normal second half of pregnancy.

Maximum flow velocity wave forms in the ductus arteriosus were studied longitudinally in 40 fetuses from 18 to 38 wk of gestation at 3- to 4-wk intervals. Median maternal age was 29 y (range 18-41 y), median parity was 1 (range 0-6). All flow velocity wave forms were obtained using a mechanical sector scanner with a continuous Doppler system (carrier frequency 3.5 MHz). The flow velocity parameters studied were peak-systolic, peak-diastolic, and time-averaged velocity and acceleration time. There was considerable variability in measurements between fetuses at any particular gestational age. An increase of ductal flow parameters with advancing gestational age was found. They showed no correlation with heart rate. These results suggest that the normal second half of pregnancy is characterized by a reduction in right ventricular afterload. This may be a result of decreased placental vascular resistance or increased pulmonary vascular flow. Acceleration time in ductal flow velocity wave forms was significantly higher than that observed in the pulmonary artery and ascending aorta, suggesting a lower afterload in the ductus arteriosus compared with the other two outflow tract vessels.     

The prevalence of house dust mite (HDM) allergy and the use of HDM-impermeable bed covers in a primary care population of patients with persistent asthma in the Netherlands.

BACKGROUND:: House dust mite (HDM) allergen is one of the most common allergens to which asthma patients are sensitised. Prevalence of HDM allergy varies in the literature. Use of HDM-impermeable bed covers reduces exposure to HDM allergen. The aim of this study was to assess the prevalence of HDM allergy in a primary care population of asthma patients, as well as the use of HDM-impermeable bed covers by these patients. METHODS:: A random sample of asthma patients between 16 and 60 years old was taken from general practices. Allergy was assessed with a radio allegro sorbent test (RAST). A questionnaire was used to identify demographic characteristics and the actual use of bed covers. RESULTS:: 534 patients were invited and 160 patients participated. 53 patients not willing to participate were randomly selected to test the external validity of our findings. The sample was representative for the primary care asthma population. 48.8% of the asthma population was sensitised to HDM allergen. 25.6% of the HDM-allergic asthma patients were using HDM-impermeable bed covers. CONCLUSION:: Almost half of the patients with asthma were sensitised to HDM allergen. Only a minority of the patients used HDM-impermeable bed covers.     

Reproducibility of fetal cardiac flow velocity waveforms at atrioventricular level

Reproducibility of flow velocity waveform recording and analysis was studied at fetal atrioventricular level (mitral and tricuspid valve) in 25 normal pregnancies. The flow velocity parameters studied were peak-E wave velocity, peak-A wave velocity and time-averaged velocity. In each patient, two consecutive measurements were performed (time delay, 15 min) and of each measurement two hardcopies were analyzed. A high reproducibility was achieved for all parameters studied; the coefficients of variation between readings of hardcopies were <2% and the coefficients of variation between tests within patients were -4%.     

Rapid fluorescence-based assay for radiosensitivity and chemosensitivity testing in mammalian cells in vitro

An efficient and rapid cytotoxicity assay has been developed, particularly for radiobiological studies, utilizing 96-well microtiter plates. Several days after treatment, cell numbers per well were measured by fluorescent intensity using an automatic reader after staining with the DNA specific dye Hoechst 33258. For radiobiological applications, a microtiter plate irradiation box was designed and built which allowed a variable number of wells (minimum 4, maximum 16) to be irradiated at one time. In this manner, complete dose-response curves could be obtained from one plate. The assay depends on the growth of surviving and untreated cells, and by appropriate choice of conditions (cell numbers plated, time of assay), cell survival curves for this quick fluorescence assay were in reasonable agreement with those from a clonogenic assay for cisplatin and X-ray-induced cell killing. The assay can span 1.5-2 decades of cell survival and is suitable for any cell line which grows as a monolayer. Radiobiological applications were tested using agents or conditions which modified radiation damage. Firstly, sublethal damage repair could be demonstrated in RIF1 mouse tumor cells by comparing the survival curve for a single X-ray dose with that for two fractions separated by 4 h. Secondly, incorporation of 5-iodo-2'-deoxyuridine into cellular DNA was shown to radiosensitize Chinese Hamster cells, with similar enhancement ratios obtained from the fluorescence and clonogenic assays. Thirdly, radiosensitization by cisplatin and radioprotection by cysteamine could be readily measured using the quick fluorescence assay. The ability to have multiple dose groups per plate makes it an efficient assay for both radiosensitivity and chemosensitivity testing.     

Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo-controlled study

OBJECTIVE: To compare the effects of oral and transdermal hormone therapy (HT) on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in postmenopausal women. DESIGN: In a multicentre, placebo-controlled, double-blind study, 152 hysterectomized healthy women were randomized to receive daily transdermal 17beta-oestradiol (tE2, n = 33), or oral micronized 17beta-oestradiol either unopposed (oE2, n = 37), or continuous combined with gestodene (oE2 + G, n = 33), or placebo (n = 49) for 13, 28-day treatment cycles. Plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured at baseline and in treatment cycles 4 and 13 with a high-performance liquid chromatography method. RESULTS: After 13 cycles all active treatment groups showed a significant reduction in ADMA compared with placebo: tE2, -4.0% (95% CI: -7.5 to -0.6%); oE2, -7.7% (95% CI: -10.9 to -4.4%) and oE2 + G, -7.5% (95% CI: -10.8 to -4.3%). ancova showed a significantly larger reduction in the oral groups compared with the transdermal group (tE2 vs. oE2 and tE2 vs. oE2 + G, both P < 0.01). Oral, but not transdermal treatment, significantly reduced arginine compared with placebo. All active treatments reduced SDMA; however, this was only statistically significant in the oE2 group. CONCLUSION: Reduction of ADMA was more pronounced after oral than after tE2 administration. Adding gestodene to oral 17beta-oestradiol did not alter the reduction of ADMA. The clinical implications of these findings remain uncertain; however, the decrease of ADMA by 17beta-oestradiol could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal HT.     

An observational study on the effect of S(+)‐ketamine on chronic pain versus experimental acute pain in Complex Regional Pain Syndrome type 1 patients

Aims The aim of the study was to explore the analgesic effect of the N‐methyl‐d ‐aspartate receptor (NMDAR) antagonist ketamine in acute experimental versus chronic spontaneous pain in Complex Regional Pain Syndrome type 1 (CRPS‐1) patients. Methods: Ten patients suffering from chronic CRPS‐1 and with a Visual Analogue pain Score (VAS) of >5 were recruited. Seven intravenous 5‐min low‐dose S(+)‐ketamine infusions with increasing doses at 20‐min intervals were applied. Spontaneous pain ratings and VAS responses to experimental heat stimuli were obtained during infusion and for 3‐h following infusion. Results: CRPS pain: Ketamine produced potent analgesia with a significant VAS reduction from 6.2 ± 0.2 to 0.4 ± 0.3 cm at the end of infusion. Analgesia persisted beyond the infusion period (VAS = 2.8 ± 1.0 cm at 5‐h), when measured plasma ketamine concentrations were low (<100 ng/ml). Experimental pain: Ketamine had a dose‐dependent antinociceptive effect on experimental pain that ended immediately upon the termination of infusion. Discussion: The data indicate that while ketamine's effect on acute experimental pain is driven by pharmacokinetics, its effect on CRPS pain persisted beyond the infusion period when drug concentrations were below the analgesia threshold for acute pain. This indicates a disease modulatory role for ketamine in CRPS‐1 pain, possibly via desensitization of NMDAR in the spinal cord or restoration of inhibitory sensory control in the brain.