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Biomedical subjects

L Holmes

Publications and source records attributed to L Holmes.

At least 19 recordsLinked to original sources
PubMed1998

Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: the diabetes in early pregnancy study.

Previous studies indicate that fasting plasma glucose decreases during gestation, but the timing and extent are not consistent from study to study. We had an opportunity to examine this question in the normal pregnancy cohort of women studied in the Diabetes in Early Pregnancy Study. Subjects were monitored to identify pregnancy by human chorionic gonadotropin testing, enrolled within 21 days of conception, and screened to rule out gestational diabetes at the juncture of the second and third trimesters. All subjects were instructed to fast overnight for 10 to 12 hours. Three hundred sixty-one women were studied between 6 and 12 weeks of gestation. A median decrease in plasma glucose of 2 mg/dL was observed between weeks 6 and 10 (P=.007). In a smaller group of subjects evaluated through the third trimester, little further glucose reduction was observed. A reduction in glycosylated hemoglobin levels between 10 and 20 weeks (P=.002) followed the earlier reduction in first trimester glucose levels. Analysis by body mass index (BMI) showed a smaller first trimester reduction with increasing BMI, and none among severely obese women (BMI > 29.9 kg/m2). The decline in fasting plasma glucose in pregnancy begins early in the first trimester, well before fetal glucose requirements can contribute to the decline in the glucose level. Thereafter, plasma glucose levels decrease little. These results suggest that in the setting in which this study was performed (an overnight fast) maternal physiologic adjustments account for a reduction in plasma glucose early in the first trimester of pregnancy, and possibly even later in gestation as well.

Adult↗
PubMed1998

The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.

OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women. RESULTS: Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS: The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.

3-Hydroxybutyric Acid↗
PubMed1995

Survival and quality of life in patients with protracted recovery from cardiac surgery. Can we predict poor outcome?

Of all the 2256 adult cardiac surgical patients operated upon during a 12-month period from 1st February 1992 in three units, only 162 (7.2%) spent more than 48 h in the intensive care unit (ICU) (median 6 days, range 3-90). There were 47 deaths in ICU, 7 more before hospital discharge, and a further 10 before the study end-point of one year after surgery. All 98 1-year survivors were at home with 86 of them reporting their quality of life, on formal evaluation, to be within the reference range which we have established for a less complicated cohort of cardiac surgical patients. Prospectively collected physiological measurements were used in a mathematical model to test how well we could predict which patients will die and which of the survivors have a poor quality of life. The algorithm performs well for cardiac surgery patients with a specificity of 98%. If treatment had been withdrawn when death or poor quality of life became predictable, the maximum number of ICU bed days that could be freed was of the order of 2%. The plight of these patients is distressing, but most survive and do well and they are infrequent compared with the large majority who survive to leave hospital after a short ICU stay.

Adult↗
PubMed1994

Which patients will not benefit from further intensive care after cardiac surgery?

In intensive care units, a predictive model that identified patients who are certain to die would spare suffering and free resources for more productive work. In a prospective study to determine factors which might predict the outcome of a protracted stay in intensive care units, information was collected for 162 patients who remained in intensive care longer than 48 hours after cardiac surgery. Of these patients, 21% presented as emergencies, 35% as urgent cases, and 44% as elective cases. They were drawn from 2256 adult patients operated upon during a 12-month period in three UK centres. 115 patients (71%) who were in intensive care for more than 48 hours survived to be discharged. The median duration of stay was 6 days (range 3-90 days) and the median duration of hospital stay was 21 days (7-111 days). An existing algorithm developed and calibrated to predict outcome for general patients in intensive care was applied to forecast outcomes. Contrary to expectations, the algorithm performed well for patients after cardiac surgery. In identifying deaths in intensive care and before hospital discharge, the specificities for death at various intervals after admission were all 97% or more. There is little scope for improving the algorithm's ability to forecast longer term outcome. Furthermore, if it were to be introduced to aid decisions about withdrawal of treatment, the potential saving in intensive care bed-days would be small--less than 3% overall.

APACHE↗
PubMed1994

Theatre nursing (Part 1).

Whilst discussing the need to increase the number of theatre nurses, Professor Roger Dyson claimed that nurses overtly tended to devalue theatre work as not being 'real nursing'. Many nurses who work outside theatre may support this. Sadly, this may be further supported by theatre nurses themselves. Such statements as 'I know I'm a good nurse because I can scrub for anything' is a comment which has been made to this author on more than one occasion. As Casey states, the conventional image of nurses in theatre is less about nursing and more about technical assistance with operating procedures.

Health Knowledge, Attitudes, Practice↗
PubMed1994

Theatre nursing (2).

Lyn Holmes continues her account of how she explored the topic of nursing care in her operating department. She goes on to describe the questionnaire she devised to test theatre nurses attitudes to and knowledge of primary nursing.

Health Knowledge, Attitudes, Practice↗
PubMed1992

Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria.

BACKGROUND: Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy. METHODS: To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis. RESULTS: The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52). CONCLUSIONS: Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria.

Child, Preschool↗
PubMed1991

Human colorectal adenocarcinoma cells: differential nitric oxide synthesis determines their ability to aggregate platelets.

The existence and role of an L-arginine:nitric oxide (NO) pathway in two human colorectal adenocarcinoma cell lines, SW-480 and SW-620, were investigated. Both cell lines, which derive from the same patient, SW-480 from the primary tumor and SW-620 from its metastatic lesion, were shown to have a cytosolic, Ca(2+)-independent, NADPH-dependent NO synthase, the activity of which was lower in the cytosol of SW-620. These cells were more potent inducers of platelet aggregation. In contrast, SW-480, which had more NO synthase activity, were less potent inducers of platelet aggregation. Pretreatment of both cell lines with NG-monomethyl-L-arginine, an inhibitor of NO synthase, potentiated their proaggregating effect and made them equally active. Exogenous L-arginine, NO, and related nitrovasodilators all inhibited platelet aggregation induced by SW-620. The antiaggregating activity of NO was further potentiated by prostacyclin and by M&B22948, a selective inhibitor of cyclic GMP phosphodiesterase. We propose that the generation of NO by tumor cells inversely correlates with their metastatic potential. Furthermore, we show that the lower activity of NO synthase in metastatic cells is due to the presence in these cells of a low molecular weight inhibitor of the NO synthase. In addition, agents which modulate platelet function by a cyclic GMP-dependent mechanism may be useful in the prevention of tumor metastasis.

Adenocarcinoma↗
PubMed1991

Stage I-II low-grade lymphomas: a prospective trial of combination chemotherapy and radiotherapy.

Between 1984-1989, 44 patients with stage I-II low grade lymphoma were treated prospectively with sequential chemotherapy and involved-field radiotherapy. The chemotherapy was cyclophosphamide, vincristine, prednisone, and bleomycin (COP-Bleo); doxorubicin was included (CHOP-Bleo) for patients with adverse prognostic features (high LDH; extranodal sites; bulky nodes). Of the 44 patients, 37 had measurable disease and all have responded. With a median follow-up of 32 months, the 5-year survival and failure-free survival were 89% and 74%, respectively. Compared to past experience with involved-field radiotherapy alone, the failure-free survival is significantly better with COP-Bleo plus radiotherapy. The potentially cured fraction has risen from 40% to 74%.

Adult↗
PubMed1987

Phorbol esters stimulate 2-deoxyglucose uptake in glia, but not neurons.

Activation of protein kinase C by phorbol esters caused a time- and dose-dependent stimulation (270% of control) of glucose uptake in cultured glia, but not in neurons from rat brain. The phorbol ester stimulation of Vmax of glial glucose uptake occurred only in glia despite nearly 2.5-fold greater phorbol ester binding in neurons. These differences in cellular responses to protein kinase C activation may be the key to understanding brain glucose regulation.

Animals↗
PubMed1987

Transcriptional enhancer activity in the variable tandem repeat DNA sequence downstream of the human Ha-ras 1 gene.

A short term transfection technique using the chloramphenicol acetyltransferase gene as an assay system has been employed to examine the presence of transcriptional regulatory sequences within the variable tandem repeat (VTR) DNA sequence located downstream of the human Ha-ras1 gene. Here we find that the VTR sequences possess an endogenous enhancer activity of both the normal and the T24 mutant Ha-ras1 gene.

Animals↗