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Biomedical subjects

A Grant

Publications and source records attributed to A Grant.

At least 127 records · Page 7Linked to original sources

A multicentre randomised controlled trial comparing elective and selective caesarean section for the delivery of the preterm breech infant.

OBJECTIVE: To determine the optimum mode of delivery for women in preterm breech labour at a gestational age of 26 to 32 weeks. DESIGN: A multicentre randomised controlled trial. SETTING: Twenty-six hospitals in England, UK. PARTICIPANTS: Women with a singleton breech fetus in spontaneous preterm labour between 26 and 32 completed weeks of gestation, with no clear indication for a caesarean section or vaginal breech delivery. INTERVENTION: Random allocation to either "intention to delivery vaginally' or "intention to deliver by caesarean section'. MAIN OUTCOME MEASURES: Perinatal mortality, neonatal morbidity, maternal morbidity and gestation at delivery. RESULTS: The trial was closed after 17 months because of low recruitment, by which time substantial numbers of women had been in the eligible gestation period. Thirteen women from six hospitals were recruited. One infant, randomised to and delivered vaginally, was stillborn. Three fetal presentations were cephalic at delivery despite a diagnosis of breech presentation at trial entry. No formal statistical analysis was performed due to the small numbers. CONCLUSIONS: No conclusions about the optimum mode of delivery for women in preterm labour with a fetus presenting by the breech can be drawn from this trial. The low accrual rate was due to clinicians' reluctance to randomise eligible women, reflecting the circumstances and nature of the trial.

Adult↗

Safety concerns affecting delivery of home health care.

Factors influencing the remarkable growth of home health care include increased elderly population, decreased average length of hospital stay, and technological advancements that reduce the need for hospitalization. Societal changes have prompted increasing concern about personal risk to home care providers. The purpose of this pilot study was to: 1) ascertain factors related to perception of risk by home health care administrators and staff and to identify strategies used by home health care administrators to reduce risk to staff; and 2) determine whether quality of care is affected when home-visit situations present risk. A convenience sample of 36 home health care administrators and 62 staff was surveyed about risks and measures provided by the home health care agency to minimize risk. Factors associated with risk are geographic location, high incidence of crime, inappropriate patient or caregiver behavior, infectious diseases, and evening assignments. Strategies used to minimize risk include safety programs, preplanning of visits, personal protective equipment, escorts, and buddy systems. Perceived ability to refuse high-risk assignments, however, is questionable, as 66% of the staff stated that they leave a situation "as soon as possible." These findings will be used to strengthen inservice programs and to provide a basis for future studies.

Adult↗

A pilot trial of continuous infusion 5-fluorouracil with levamisole for adjuvant therapy of colon cancer.

The relatively high response rate demonstrated with the use of continuous infusion 5-Fluorouracil (CIFU) 200 to 300 mg/m2 per day in disseminated colon cancer is the rationale behind a NCI-sponsored intergroup trial (INT 0153) for postoperative adjuvant therapy of stage III colon cancer. Because CIFU necessitates a significant reduction in the dose of the modulator leucovorin compared with bolus 5-FU, a pilot study of continuous infusion 5-FU in several doses with levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of this dose intensive schedule. CIFU, scheduled as two 12-week cycles, was administered at 250 mg/m2 per day. Pending toxicity at the initial dose, CIFU was to be escalated (300 mg/m2) or de-escalated (200 mg/m2). All but one patient entered on this trial completed 24 weeks of adjuvant CIFU+levamisole. Eight patients (57%) completed 24 weeks of therapy with the 2-week scheduled break. One of these 8 patients required a dose reduction without interrupting the schedule. Six patients had toxicity from the CIFU, which obliged us to interrupt the schedule. Limiting toxicities were stomatitis and hand-foot syndrome. No dose-limiting hematologic toxicity was encountered. Three patients (21%) had catheter problems that required replacement. These data suggest that up to 30% of patients started on this regimen may require dose reduction, shorter infusion courses with rest breaks, or both to complete 24 weeks of adjuvant treatment in order to achieve desired dose intensity.

Adult↗

Performance evaluation of automated immunoassays on the Technicon Immuno 1 system.

We performed an immunoassay evaluation for various analytes on a fully automated random-access analyzer, the Technicon Immuno 1 system from Bayer Corp. This system involves latex agglutination, magnetic separation sandwich, and magnetic separation competitive immunoassay configurations. The evaluated analytes were thyrotropin (TSH), triiodothyronine, thyroxine, free thyroxine, follitropin, lutropin, prolactin, beta subunit of human chorionic gonadotropin, cortisol, ferritin, alpha-fetoprotein, carcinoembryonic antigen, and prostate-specific antigen. We tested the assay precision, linearity, and correlation with comparison methods for these analytes. The functional sensitivity of the TSH assay and the sample-to-sample carryover were also studied. Excellent results were obtained for within-run and between-day precision studies, with most assays showing within-run CVs <4% and between-day CVs <6%. The linearity for all assays was acceptable and the correlation between Immuno 1 assays and comparison methods showed satisfactory results. The functional sensitivity of the TSH assay was estimated at 0.04 mU/L. No sample-to-sample carryover was detected.

Autoanalysis↗

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.

Adult↗

Bovine osteodystrophies.

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Animal Nutritional Physiological Phenomena↗

Comparison of obese NIDDM and nondiabetic women: short- and long-term weight loss.

Previous research suggests that overweight patients with diabetes lose less weight than nondiabetics. We compared the response of obese women with NIDDM to nondiabetic controls, matched for age and weight, to a behavior weight loss program. Forty-three overweight women (20 NIDDM, 23 nondiabetic) participated in the study. NIDDM and nondiabetic subjects were treated together and received the same 16-week behavioral weight loss program. Dependent measures included weight, 3-day food records, physical activity, fasting plasma glucose, and questionnaires assessing eating behavior and depressive symptomatology. Weight loss of NIDDM and nondiabetic subjects at posttreatment was comparable (-7.4 +/- 5.3 kg vs. -6.4 +/- 3.8 kg, respectively). Changes in caloric intake, eating behavior, exercise and depressive symptomatology were also similar between the two groups. However, during the 1-year follow-up period, NIDDM subjects regained 5.4 +/- 6.1 kg compared to 1.0 +/- 6.7 kg for nondiabetics (p = .058). These data indicate that NIDDM subjects can lose as much weight as their nondiabetic peers during active treatment. Once treatment terminated, however, NIDDM subjects demonstrated poor weight loss maintenance. Thus the added motivation that comes from having diabetes and seeing improvements in glycemic control with weight loss were not sufficient to improve long term weight loss in diabetic subjects. A continuous care model of weight control may be particularly necessary for overweight patients with type II diabetes.

Analysis of Variance↗

Cyclic-AMP deficient MDCK cells form tubules.

It has been known for many years that MDCK cells form blister-like structures, termed domes. During an examination of the morphology of a large number of MDCK clones, we found that two stable morphotypes exist in an MDCK cell population-namely, dome-forming and tubule-forming clones. When maintained at high cell density, tubule-forming clones displayed large numbers of anastomosing tubules which contained lumens. The frequency of observation of the tubule-forming clones in an MDCK population was 0.7%. Tubule-forming MDCK clones should be useful in studying tubule morphogenesis. While agents that affect protein kinase A activity increased dome formation, the same agents abolished the formation of tubules in all tubule-forming clones. In contrast, drugs that stimulate protein kinase C activity (phorbol esters and staurosporine) decreased dome formation an increased tubule morphogenesis in all MDCK morphotypes. Tubule-forming clones were found to have lower resting levels of cyclic-AMP and to respond to forskolin stimulation of adenylate cyclase less readily. Hence, signals transmitted by the protein kinase C pathway appear to lead to tubule formation in MDCK cells, while signals transmitted through the protein kinase A pathway lead to dome formation.

Ammonium Chloride↗

FTIR and NMR studies on the hydration of a high-M(r) subunit of glutenin.

The hydration behaviour of a purified high-M(r) subunit of glutenin has been studied using Fourier transform infra-red (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The water-insoluble protein was examined in an unalkylated form with intermolecular disulfide bonds, and in a reduced and alkylated (unpolymerized) form. Hydration produced a marked increase in chain mobility, especially above a threshold water content of about 37% w/w. NMR experiments also showed that some parts of the chain were held in a much less mobile state, even at higher water contents. Little difference could be seen between alkylated and unalkylated subunits, implying that NMR is sensitive to localized motions, but not to any restrictions imposed by disulfide bridges close to the chain ends. FTIR spectra of the protein films have shown that increasing hydration enables changes to occur in favour of a more extended and beta-sheet-type structure. The changes in secondary structure are very noticeable at water contents corresponding to the NMR mobility threshold. The behaviour is influenced by intermolecular interactions. beta-sheet formation is enhanced by the presence of disulfide bonds in the unalkylated samples. There is little evidence of beta-structure (sheet or extended chain) either in the dry state, where protein-protein interactions are strongest, or in dilute acetic acid solution, where the interactions are weakest. The balance between protein-protein and protein-water hydrogen-bonding interactions therefore appears to influence the formation of beta-sheet and extended chain structures, and these may in turn affect the elasticity of high M(r) subunits.

Alkylation↗

Controlled trial of dexamethasone in neonatal chronic lung disease: a 3-year follow-up.

OBJECTIVE: We compared the effects of a policy of neonatal steroid administration versus placebo for babies chronically dependent on supplemental oxygen in terms of long-term health and development, judged at 3 years of age. DESIGN: Double-blind randomized controlled trial. SETTING: Thirty-one centers in the United Kingdom, Ireland, Belgium, Germany, Canada, and the United States. PATIENTS: Babies who were chronically dependent on supplemental oxygen between 2 and 12 weeks of age were recruited to the trial between 1986 and 1989. Sixty-two children were known to have died, 23 before discharge from the hospital and 10 afterward in the active group, compared with 25 and 4, respectively, in the placebo group. Information was available for 209 of the 212 eligible for follow-up (99%). INTERVENTIONS: A 1-week course of active dexamethasone phosphate 0.6 mg/kg/d (dexamethasone base 0.5 mg/kg/d) or saline placebo was given intravenously (or orally, if no intravenous line). There was an option to give a second tapering 9-day course if relapse occurred after initial improvement. OUTCOME MEASURES: Information about respiratory problems, growth, neurodevelopment and disability, infection, and health service use when the children were 3 years old was ascertained from questionnaires to general practitioners, health visitors, and parents (and occasionally pediatricians). RESULTS: About half the children in both groups had been admitted to the hospital for respiratory problems, with more in the active than the placebo group having at least five outpatient consultations for these problems over the 3 years. Overall, the children were below average in height, weight, and head circumference. About one fifth had cerebral palsy, 8% some visual loss, and 16% hearing loss; 18% needed or were anticipated to need special schooling. There were no clear differences between the randomized groups. These overall conclusions were not altered by any of the prespecified secondary analyses. CONCLUSIONS: Despite early benefits, there were no clear effects at 3 years of age. As 40% of the placebo group eventually received open steroids, even a trial of this size has limited statistical power to detect a moderate effect of the policy. Regardless of random allocation, overall morbidity was high, confirming that babies with protracted dependence on supplemental oxygen are at high risk of childhood disability and poor health.

Chronic Disease↗

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin-A-stimulated thymocytes. Top-down elasticity analysis and control analysis.

The glucocorticoid methylprednisolone has clinically important anti-inflammatory effects at high concentrations through unknown mechanisms. Methylprednisolone at 0.2 mg/10(7) cells inhibits respiration in Concanavalin-A(ConA)-stimulated thymocytes from rats by about 20%. We have used top-down elasticity analysis to identify the blocks of reactions within oxidative phosphorylation in thymocytes whose kinetics are significantly affected by treatment with methylprednisolone. At this concentration methylprednisolone greatly inhibited the reactions of substrate oxidation and increased mitochondrial proton leak but did not significantly affect the synthesis and and turnover of ATP by the phosphorylating system. Metabolic control analysis showed that oxygen consumption by ConA-treated thymocytes was controlled largely (0.51) by the phosphorylating system but also by proton leak (0.32) and substrate oxidation (0.17); this is similar to the distribution of control in hepatocytes, suggesting that this pattern may be general in cells. Methylprednisolone lowered control by the phosphorylating system to 0.26 and raised control by substrate oxidation to 0.37. From these results we conclude that the inhibition of respiration in ConA-stimulated thymocytes by methylprednisolone at this concentration results from an inhibition of substrate oxidation and a smaller stimulation of mitochondrial proton leak, with only a minor contribution of any effects within the phosphorylating system.

Adenosine Triphosphate↗