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Biomedical subjects

J Betts

Publications and source records attributed to J Betts.

At least 19 recordsLinked to original sources

European regulatory issues.

Current EU regulations do not cover all aspects of the manufacture and control of blood products. Recent legislation coming into force on 1 January 1995 has established the European Medicines Evaluation Agency and introduced revised systems for approving pharmaceutical products, including blood products. There remains a need for comprehensive harmonized legislation covering plasma collection and screening, virus validation studies, and batch release.

Biological Factors

Cumulative conception and livebirth rates after in-vitro fertilisation.

Cumulative conception and livebirth rates related to age and cause of infertility provide the most useful estimate of success after in-vitro fertilisation (IVF), but limited data are available. It is also uncertain whether the probability of pregnancy, livebirth, and pregnancy failure changes with repeated treatment cycles. To assess the effects of patients' age and cause of infertility on these outcomes, we studied the results of 5055 consecutive IVF cycles (773 clinical pregnancies, 518 livebirths) undertaken on 2735 patients in a single IVF unit. Cumulative conception and livebirth rates were analysed by the life-table approach and differences in rates between age-groups and between causes of infertility were measured by the log-rank test and logistic regression modelling. Both conception and livebirth rates per cycle declined with age (p less than 0.001), and cumulative conception and livebirth rates after five treatment cycles were about 54% and 45%, respectively, at 20-34 years, compared with 38.7% and 28.9% at 35-39 years and 20.2% and 14.4% at greater than or equal to 40 years. The two rates were significantly different between causal groups (p less than 0.001 and p = 0.02, respectively) and were lowest in patients with male infertility or multiple infertility factors. The pregnancy failure rate was higher (p = 0.006) in women over the age of 34 years and there was a significant decline in the chances of pregnancy and livebirth per cycle with successive treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Woven carbon surface replacement in the knee: independent clinical review.

An independent assessment was performed of the results of woven carbon implants of mesh or rods into articular cartilage defects performed by two surgeons in the knees of 96 patients. Eight had symptomatic osteochondritis, 31 had chondromalacia patellae and 57 had early osteoarthritis. They were reviewed up to 5 yr after operation. Seventy-six patients (79%) experienced an improvement in analogue pain score and similar improvements occurred in a range of functional activities (P = 0.002). No evidence of inflammatory change or deterioration in joint damage was found. It is concluded that this relatively minor procedure is valuable in younger patients with troublesome symptoms due to early articular cartilage damage and does not prejudice further operative treatment.

Adolescent

Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine brain endothelial cells via a serum-dependent cytotoxic pathway.

An in vitro blood-brain barrier (BBB) model consisting of primary cultures of bovine brain microvascular endothelial cells was used to examine the effect of Haemophilus influenzae type b (Hib) on the BBB. Whole bacteria and purified lipopolysaccharide (LPS; greater than 10 ng/ml) caused marked cytotoxicity on the bovine brain endothelial cells. This effect could be completely blocked by polymyxin B. Similar cytotoxic effects were observed with a cultured bovine pulmonary endothelial cell line. Serum was essential for the LPS-mediated cytotoxic effect, and human, horse, bovine, or fetal calf serum all had similar effects. The serum factor was not a complement component. A monoclonal antibody against CD14, a receptor involved in mediating the effect of LPS in monocytes, completely blocked the cytotoxic effect in both brain and pulmonary endothelial cells. These results suggest that Hib LPS disrupts an in vitro BBB model via a serum- and CD14-dependent pathway and that LPS has cytotoxic effects on bovine endothelial cells without the involvement of monocytic cells, an effect that may be important in gram-negative meningitis and in endotoxic shock.

Animals

Identification of Salmonella typhimurium invasiveness loci.

Salmonella typhimurium is capable of entering into (invading) nonphagocytic host cells. To systematically identify the bacterial genes necessary for this process, 15,000 Tn10dCm random transposon mutants of S. typhimurium were individually screened for invasiveness, using the human colonic epithelial Caco-2 cell line. Four hundred and eighty-eight mutants had decreased levels of invasiveness; most were nonmotile. However, five mutants, representing four loci, were completely motile. Further characterization of these five mutants showed that they were also unable to enter the dog kidney epithelial cell line MDCK and the mouse macrophage line J774.A1. In contrast to the parental strain, they were unable to disrupt the transepithelial resistance of polarized epithelial monolayers, nor were they able to penetrate across these epithelial barriers. Three of the four classes of mutants remained virulent in mice. The results confirm several aspects of S. typhimurium invasiveness: (i) intact motility enhances invasiveness of cultured cells; (ii) S. typhimurium invasiveness is multifactorial, and at least six distinct genetic loci are involved; and (iii) invasion loci involved in uptake into epithelial cells are also needed for uptake into cultured phagocytic cells. The results also emphasize that decreased levels of invasiveness eliminate bacterial penetration of polarized epithelial barriers and invasiveness loci mutants are not necessarily avirulent.

Animals

The influence of training-detraining upon the heart, muscle and adipose tissue of female rats.

The purpose of this study was to measure the effects of a 10 week training, 3 week detraining cycle upon heart, muscle and adipose tissue of the rat. Specific pathogen-free female Wistar rats, 175 g at the onset of the experiments, were separated into three treatment groups; Sedentary Control (SC), Trained (T) and Detrained (DT). Animals from the T group were killed at 2, 4, 6, 8 and 10 weeks and animals from the DT group were killed at 7, 14 and 21 days after the last day of training. Unweighted swimming--6 h/day, 5 day/week, was the form of training employed. The animals, after being sacrificed, were anesthetized with nembutal (45 mg/kg body wt.) and muscle samples and heart removed. These tissues were frozen and analyzed at a later date for succinate dehydrogenase (SDH) activity (muscles), total protein (TP), total hydroxylprotein (TH) and wet and dry weight (heart). Adipose tissue was removed last, digested in collagenase (5 mg/ml) and the isolated cells used to measured 2-[3H]deoxyglucose uptake (DOG) and the conversion of D-[1-14C]glucose (C-1) and D-[6-14C]glucose (C-6) to CO2. The results of this study show that 10 weeks of endurance training induced myocardial hypertrophy (P less than 0.05) which involved increases in both TP and TH, the heart of the trained animals having 20.8% more protein and a 28.5% more hydroxlprotein than the sedentary controls. With detraining hypertrophy was lost within 21 days. Training maintained fat cell size at its pre-trained diameter, while inactivity allowed growth in the adipocytes of the control animals. The uptake of DOG and the conversion of glucose C-1 and glucose C-6 to CO2, were significantly (P less than 0.05) higher in the adipocytes of trained animals indicating that they were more responsive to insulin than the sedentary controls, which corresponded to increases in the respiratory enzyme levels of the muscles. During the first 7 days of detraining DOG uptake and both C-1 and C-6 glucose oxidation remained elevated. In conclusion the results of this study clearly demonstrate that there is a direct relationship between adiposity and training that can be related to the insulin responsiveness of the adipose tissue.

Adipose Tissue

Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group.

The perinatal outcome and congenital malformations in children born between 1978 and 1987 in Great Britain after in-vitro fertilization (IVF) at Bourn Hall Clinic and the Hallam Medical Centre are presented. The average maternal age was 34.2 years. Multiple births were frequent, constituting 23% of all deliveries; 19% were twins and 4% triplets. There were no quadruplet or higher order multiple births during that period. Twenty-five per cent of all deliveries were preterm. The mean birth weight was 2793 g and was strongly related to multiplicity of pregnancy and gestational age. Overall, 32% of babies had a low birthweight (less than 2500 g) with 6% having a very low birthweight (less than 1500 g). The overall stillbirth and infant mortality rates were two to three times higher than those of infants born after natural conception in England and Wales; this is attributed to the high incidence of multiple births. The stillbirth rates were 5.07, 20.8 and 24.7 per thousand total births in singletons, twins and triplets respectively. The corresponding figures for perinatal mortality were 13.5, 38.2 and 37 per thousand. Overall, 2.5% of the babies had one or more major congenital malformations diagnosed within one week of life. This was within the range of expected values in the United Kingdom and there was no significant increase in any specific malformation.

Adult

Surgical management of reflux strictures of the esophagus in childhood.

The etiology of gastroesophageal reflux (GER) in infancy is related to developmental factors, and there is a high incidence of associated conditions such as neurologic syndromes and esophageal atresia (60%). This is different from the situation in adults. Experience with 18 consecutive children with peptic esophageal strictures is reviewed to determine if conservative surgical management is effective. Eighteen children 14 months to 13 years (mean 6.3 years) of age took an average of 3.5 years from the time of onset of symptoms of GER to develop tight strictures diagnosed by esophagography and esophagoscopy. The incidence of stricture in patients with GER was approximately 15%. Preoperative dilation or direct surgical management prior to correction of reflux is ineffective. All 18 children were managed by intraoperative dilatation, Nissen fundoplication, and guided dilatation after operation. More aggressive surgical procedures were not required nor were associated operations such as pyloroplasty; they are rarely necessary. An average three-year follow-up indicates that this conservative surgical approach is effective in the management of peptic esophageal strictures in childhood with relief of symptoms and gratifying improvement in growth.

Adolescent

Biosynthesis of amino sugars by Pseudomonas saccharophila.

Pseudomonas saccharophila growing on specifically labeled glucose incorporated isotope into cell wall glucosamine and muramic acid with less than 5% randomization of carbons. Glucosamine contained isotope in both the 1 and 6 positions when cells were grown on either galactose-6-(14)C or gluconate-6-(14)C. With galactose-1-(14)C, only muramic acid was labeled. Specific activities of the carboxyl group of muramic acid obtained from the glucose-grown cells did not indicate whether the origin of the side chain of muramic acid is pyruvate or phosphoenolpyruvate. However, the high specific activity obtained from galactose-1-(14)C suggested that induced cells preferentially incorporate C-1 of galactose into the side chain of muramic acid. Addition of unlabeled glucosamine to growing cultures repressed incorporation of substrate isotope into glucosamine, but muramic acid contained activity in the lactyl side chain.

Amino Sugars