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Biomedical subjects

D Stevens

Publications and source records attributed to D Stevens.

At least 73 records · Page 4Linked to original sources

Temporal relationship of cytokine release by peripheral blood mononuclear cells stimulated by the streptococcal superantigen pep M5.

We undertook this study to determine the quality, quantity, and temporal relationship of pep M5-induced cytokine release. The ability of pep M5 to stimulate interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) production by a T-cell-depleted, monocyte- and B-cell-enriched cell population was dependent on the presence of T cells. The requirement for T cells could be met by addition of exogenous gamma interferon (IFN-gamma). In the presence of IFN-gamma, pep M5 induced the release of TNF-alpha, IL-1, and IL-6, TNF-alpha levels peaked at 24 h, while IL-1 and IL-6 levels peaked at 48 h. pep M5 induced T cells to produce IFN-gamma, which may have accounted for the ability of the super antigen to induce the production of IL-1, IL-6, TNF-alpha, and TNF-beta by peripheral blood mononuclear cells (PBMC). The addition of excess IFN-gamma to cultures of pep M5 and PBMC did not further increase the release of these cytokines at 24 and 48 h but resulted in sustained higher levels at 72 h. Interestingly, TNF-beta production occurred only in the presence of pep M5 and exogenous IFN-gamma. The ability of pep M5 to induce cytokine production was compared with that of a potent super antigen, staphylococcal enterotoxin B (SEB). SEB was a 2- to 14-fold-more-potent inducer of IFN-gamma production. Furthermore, the profile of cytokine released by PBMC in response to this super antigen mimicked that seen with pep M5 in the presence of exogenous IFN-gamma. In conclusion, pep M5 induces the production of cytokines that are involved in immune regulation and inflammation. These cytokines also play a major role in human T-cell responses to this super antigen.

Adult↗

Trauma on the Isle of Man.

The Isle of Man Tourist Trophy motorcycle races remain one of the most popular venues for motorcycle races. This is despite the reduced status of the event. The reason for the loss of world championship and formula one status is the nature of the road racing circuit itself. The twisting narrow roads are only closed to the public at certain times during the practice and race weeks. Motorcycling visitors to the event attempt to emulate their heroes on machines capable of high speeds. Casualties from both visitors and racers are dealt with efficiently by an expanded medical service. This includes the use of an aeromedical evacuation helicopter. Casualties from the visitors exceeded those from the racers themselves during the period reported.

Accidents, Traffic↗

Purification and characterization of the lethal toxin (alpha-toxin) of Clostridium septicum.

Clostridium septicum lethal (alpha-toxin) was purified and found to be a basic protein (pI 8.4) of approximately 48 kDa that is both lethal and hemolytic. The alpha-toxin had a hemolytic activity of approximately 2 x 10(7) hemolytic units per mg and a 50% lethal dose of approximately 10 micrograms/kg of body weight for mice. The alpha-toxin formed concentration-dependent, sodium dodecyl sulfate-resistant aggregates of approximately 230 kDa. Mice immunized with alpha-toxin showed a significant increase in survival time over mock-immunized mice when challenged with C. septicum. Rabbit polyclonal antibody was generated against the purified toxin and was used to confirm that toxin with the same molecular weight was present in seven different C. septicum isolates. No proteins in the supernatants from cultures of Clostridium perfringens, Clostridium histolyticum, Clostridium chauvoei, or Clostridium difficile were found to react with the C. septicum alpha-toxin-specific antibody.

Animals↗

Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome.

To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P less than .001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P less than .001) and other pulmonary air leaks (11.5% vs 25.9%, P less than .001). We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity.

Administration, Inhalation↗

Pilot study on the feasibility of a computerized speech recognition charting system.

The objective of this study was to determine the feasibility of developing and using a voice recognition computerized charting system to record dental clinical examination data. More specifically, the study was designed to analyze the time and error differential between the traditional examiner/recorder method (ASSISTANT) and computerized voice recognition method (VOICE). DMFS examinations were performed twice on 20 patients using the traditional ASSISTANT and the VOICE charting system. A statistically significant difference was found when comparing the mean ASSISTANT time of 2.69 min to the VOICE time of 3.72 min (P less than 0.001). No statistically significant difference was found when comparing the mean ASSISTANT recording errors of 0.1 to VOICE recording errors of 0.6 (P = 0.059). 90% of the patients indicated they felt comfortable with the dentist talking to a computer and only 5% of the sample indicated they opposed VOICE. Results from this pilot study indicate that a charting system utilizing voice recognition technology could be considered a viable alternative to traditional examiner/recorder methods of clinical charting.

Artificial Intelligence↗

Effect of prolonged glucose infusion into fetal sheep on body growth, fat deposition and gestation length.

Eleven Merino sheep fetuses were supplemented with glucose by direct continuous intravenous infusion of 50% dextrose into the fetus from day 115 of gestation until spontaneous delivery. Infusion rates of 15 or 25 g/day per kg were used and equivalent volumes of saline were infused into 11 control fetuses. Infusion periods approximated 27 days in both groups. Fetal plasma glucose concentrations were significantly (P less than 0.001) elevated throughout glucose infusion and resulted in variable but consistently higher plasma insulin concentrations in the glucose than in the saline-infused fetuses. Glucose-infused fetuses were significantly heavier than controls (mean +/- SEM; 3.86 +/- 0.16 vs 3.28 +/- 0.24 kg, P less than 0.05) and body fat depots (in g/kg body wt.) were larger in glucose-infused than control fetuses (9.91 +/- 0.65 vs 6.73 +/- 0.37, P less than 0.005, for internal brown fat depots; 1.25 +/- 0.44 vs 0.27 + 0.13, P less than 0.05, for subcutaneous white adipose tissue). The results indicate that growth and lipid deposition in the sheep fetus are responsive to increased glucose supply, an effect which may be mediated through the actions of insulin. Mean gestation length was 146.60 +/- 1.45 days for controls and 144.18 +/- 1.23 days for glucose-infused animals (normal term 150 days).

Adipose Tissue↗

Umbilical artery flow velocity waveform analysis in normal ovine pregnancy and after carunculectomy.

Twenty fetal lambs were studied in utero using continuous wave Doppler ultrasound to analyse the fetal umbilical artery flow velocity waveforms. Satisfactory waveforms were obtained. Prepregnancy surgical removal of uterine caruncles was used to produce intrauterine fetal growth retardation in 14 of these ovine pregnancies of whom 8 delivered a small for gestational age fetus. In only one fetus was the umbilical artery flow velocity waveform abnormal with a high systolic diastolic ratio. We conclude that the growth restriction occurring in the ovine fetus following a reduction of placental implantation sites is not related to a restriction in the fetoplacental circulation and this is different from the most frequently observed human fetal growth retardation.

Animals↗

Interleukin 3 binds to a 140-kDa phosphotyrosine-containing cell surface protein.

Interleukin 3 (IL-3) is a hematopoietic growth factor that supports the proliferation and differentiation of early hematopoietic-lineage progenitors. By using growth factor-dependent cell lines, IL-3 has been shown to induce the appearance of several phosphotyrosine-containing proteins, including a 140-kDa cell surface phosphoprotein. Here we demonstrate that the 140-kDa phosphoprotein binds IL-3 and forms a stable complex with an apparent molecular mass of 170 kDa. The possible relationship of the 140-kDa phosphoprotein to the previously described 65-kDa IL-3-binding protein is discussed.

Affinity Labels↗

Umbilical artery flow velocity waveforms and placental resistance: the effects of embolization of the umbilical circulation.

Embolization of the umbilical placental circulation in fetal lambs was carried out to occlude the small vessels of the placental vascular bed and to observe the effect on the umbilical artery flow and flow velocity waveforms. Thirteen singleton fetuses were studied from day 120 of pregnancy. Embolization was achieved by injecting approximately 9 X 10(6) microspheres of 15 micron diameter into the fetal placental cotyledons along the umbilical arteries over 9 days. Umbilical and uterine flows were measured by radioactive microsphere counting. The umbilical placental resistance was increased (0.25 to 0.35 mm Hg.ml.min-1) by embolization, and there was an increase in the umbilical artery systolic/diastolic ratio. Embolization produced a significant fall in umbilical flow expressed either as total flow (312 to 237 ml.min-1) or when normalized by reference against splanchnic flow (3.36 to 1.53). We conclude that the umbilical artery flow velocity waveform systolic/diastolic ratio measures the reflection coefficient at the peripheral vascular bed (the "resistance vessels") of the placenta.

Animals↗

Effects of acute and prolonged exposure to heat on regional blood flows in pregnant sheep.

This study deals with fetal growth retardation in heat-exposed sheep, and provides information on mechanisms of acclimation to heat. Radioactive microspheres were used to measure regional capillary blood flows in conscious sheep 80-100 days pregnant, at first in a thermoneutral environment, next after 2.5-6 h exposure to a hot environment of 40 degrees C, 25 mmHg water vapour pressure, and then 7 days and 15-20 days later, after spending 9 h daily in the heat. Maternal blood flow in the placental cotyledons was decreased by the first heat exposure, and remained depressed during the period of periodic heating. Reduction in placental blood flow on the maternal side could be part of the mechanism by which fetal development is retarded in heat-stressed sheep. Acclimation to heat was indicated by a decrease in the rate of rise in rectal temperature during the first 2 h of daily exposure to heat. Concomitantly, there was a progressive increase in the blood flow in extremity skin and nasal mucosa, which are tissues concerned with facilitation of heat loss during acute heat stress. However, in respiratory muscles which are also concerned with heat-loss, there was no further increase in flow after the initial response to to acute heat, indicating that heat acclimation is not due to an increased ability to pant. Blood flow in other tissues such as gut, pancreas and adipose tissue progressively decreased. These changes in blood flow have possible adaptive significance.

Acclimatization↗

Failure to vaccinate against whooping cough.

We describe a prospective study in which we investigated why children fail to get vaccinated against whooping cough, including an assessment of the attitudes of parents and professionals and the impact of different views of the contraindications. There was considerable disagreement among the professionals on the interpretation of the contraindications to immunisation, and the commonest reason for omitting pertussis vaccine was advice from the doctor based on dubious contraindications. When faced with parents anxious about the risks of immunisation health professionals are unable to find reassurance in the list of contraindications to immunisation.

Attitude of Health Personnel↗

Lipid deposition after hypophysectomy and growth hormone treatment in the sheep fetus.

Fifteen sheep fetuses hypophysectomized around 115 days gestation (term 150 days) were treated with growth hormone (GH), adrenocorticotrophin (ACTH) or triiodothyronine (T3) by continuous intravenous infusion. At normal or caesarian delivery, about 149 days gestation, body weights and dissectible internal brown fat and subcutaneous white fat depots were compared with seven control hypophysectomized fetuses and four sham-operated controls, the latter groups receiving no hormone infusions. Hypophysectomy caused the appearance of a large persistent depot of subcutaneous fat which was unaffected by ACTH or T3 infusion. Treatment with ovine pituitary GH resulted in the disappearance of this depot which was also absent from the sham-operated controls. Although the GH source was not subjected to extensive purification, there was very little contamination with prolactin or TSH, suggesting that GH itself has a major role in the control of lipid metabolism in the fetus.

Adipose Tissue↗