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Biomedical subjects

J Compton

Publications and source records attributed to J Compton.

At least 19 recordsLinked to original sources

In vivo assessment of the effects of estrogen on human brain.

There is increasing evidence from animal and in vitro studies to suggest that estrogen might have neuroprotective effects, and several plausible physiological mechanisms have been proposed. However, it is not yet fully understood how estrogen affects the human brain. There are several techniques that are currently employed for in vivo assessment of brain structure and function in humans, including neuropsychological and neuroendocrine testing, computerized tomography, structural and functional magnetic resonance imaging, magnetic resonance spectroscopy, single photon emission spectroscopy and positron emission tomography. Results from studies investigating the effects of estrogen on the female brain using the above techniques are reviewed here. The current data from humans suggest that the use of estrogen hormone-replacement therapy (HRT) in healthy, postmenopausal women might reduce the risk of developing Alzheimer's disease (AD) and preserve certain aspects of cognitive function. The use of HRT in postmenopausal women might also modulate neurotransmitter function and can increase cerebral blood flow in a regionally specific and task-dependent manner. In addition, the neuroprotective effects of HRT might depend on the length of its use. However, there is very little evidence at present that HRT is an effective treatment for established AD.

Brain↗

HRT and its effect on normal ageing of the brain and dementia.

There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD.

Aging↗

The treatment of gastroesophageal reflux disease with proton-pump inhibitors and its implications on managed care--clinical overview of gastroesophageal reflux disease. Roundtable discussion.

The importance of gastroesophageal reflux disease (GERD) to managed health care systems cannot be overestimated. It contributes significantly to the use of health care resources, including doctor's services, medication consumption, and diagnostic testing. A roundtable meeting of 13 managed care experts was convened January 23, 2001 in Dallas, to discuss the implications of GERD on the managed care system. The following proceedings are published in five sections. In the first part, Jeffrey Danzig, MD, a gastroenterologist, provides the clinical foundation for the discussion, based on the existing literature and his personal practice.

Anti-Ulcer Agents↗

Patterns of nucleotide substitution in angiosperm cpDNA trnL (UAA)-trnF (GAA) regions.

Patterns of substitution in chloroplast encoded trnL_F regions were compared between species of Actaea (Ranunculales), Digitalis (Scrophulariales), Drosera (Caryophyllales), Panicoideae (Poales), the small chromosome species clade of Pelargonium (Geraniales), each representing a different order of flowering plants, and Huperzia (Lycopodiales). In total, the study included 265 taxa, each with > 900-bp sequences, totaling 0.24 Mb. Both pairwise and phylogeny-based comparisons were used to assess nucleotide substitution patterns. In all six groups, we found that transition/transversion ratios, as estimated by maximum likelihood on most-parsimonious trees, ranged between 0.8 and 1.0 for ingroups. These values occurred both at low sequence divergences, where substitutional saturation, i.e., multiple substitutions having occurred at the same (homologous) nucleotide position, was not expected, and at higher levels of divergence. This suggests that the angiosperm trnL-F regions evolve in a pattern different from that generally observed for nuclear and animal mtDNA (transitional/transversion ratio > or = 2). Transition/transversion ratios in the intron and the spacer region differed in all alignments compared, yet base compositions between the regions were highly similar in all six groups. A>- C transversions were significantly less frequent than the other four substitution types. This correlates with results from studies on fidelity mechanisms in DNA replication that predict A<->T and G<->C transversions to be least likely to occur. It therefore strengthens confidence in the link between mutation bias at the polymerase level and the actual fixation of substitutions as recorded on evolutionary trees, and concomitantly, in the neutrality of nucleotide substitutions as phylogenetic markers.

DNA, Chloroplast↗

Control of mitotic events by the Cdc42 GTPase, the Clb2 cyclin and a member of the PAK kinase family.

BACKGROUND: Cyclins and cyclin-dependent kinases induce and coordinate the events of the cell cycle, although the mechanisms by which they do so remain largely unknown. In budding yeast, a pathway used by the Clb2 cyclin to control bud growth during mitosis provides a good model system in which to understand how cyclin-dependent kinases control cell-cycle events. In this pathway, Clb2 initiates a series of events that lead to the mitosis-specific activation of the Gin4 protein kinase. A protein called Nap1 is required in vivo for the activation of Gin4, and is able to bind to both Gin4 and Clb2. We have used a simple genetic screen to identify additional proteins that function in this pathway. RESULTS: We have found that the Cdc42 GTPase and a member of the PAK kinase family called Cla4 both function in the pathway used by Clb2 to control bud growth during mitosis. Cdc42 and Cla4 interact genetically with Gin4 and Nap1, and both are required in vivo for the mitosis-specific activation of the Gin4 kinase. Furthermore, Cla4 undergoes a dramatic hyperphosphorylation in response to the combined activity of Nap1, the Clb2-Cdc28 kinase complex, and the GTP-bound form of Cdc42. Evidence is presented which suggests that the hyperphosphorylated form of Cla4 is responsible for relaying the signal to activate Gin4. CONCLUSIONS: Previous studies have suggested that cyclin-dependent kinases control the cell cycle by directly phosphorylating proteins involved in specific events, such as nuclear lamins, microtubule-associated proteins and histones. In contrast, our results demonstrate that the Clb2-Cdc28 cyclin-dependent kinase complex controls specific cell-cycle events through a pathway that involves a GTPase and at least two different kinases. This suggests that cyclin-dependent kinases may control many cell-cycle events through GTPase-linked signaling pathways that resemble the intricate signaling pathways known to control many other cellular events.

Cell Cycle↗

Hyperglycemia in extremely- low-birth-weight infants.

The cause of hyperglycemia in extremely-low-birth-weight (ELBW) infants is not well understood. We studied infants weighing <1,000 g to investigate the relationship of hyperglycemia to blood levels of insulin-like growth factor (IGF)-I and IGF-II. We also compared two methods of treatment for hyperglycemia: continuous insulin infusion and reduction of glucose intake. Fifty-six ELBW infants were enrolled on day 2 of life. Intravenous glucose intake was increased incrementally to a maximum of 12 mg/kg/min on day 6. Infants who developed hyperglycemia were randomly assigned to receive reduced glucose intake (n = 11) or insulin infusion (n = 12). Infants whose blood sugar remained normal served as controls (n = 33). Blood was drawn on days 3, 8 and 15 in all infants, and again when they developed hyperglycemia. Nutritional intake and laboratory results for the treatment groups were compared with controls. Hyperglycemic infants had lower birth weights than controls. Hyperglycemic infants treated with glucose reduction remained <60 kcal/kg/day longer than control or insulin infusion groups (8.6 +/- 1.3 days vs. 4.1 +/- 0.2 and 5.5 +/- 0.6 days). No infants became hypoglycemic during insulin infusion. There was no difference in baseline blood levels of IGF-I or IGF-II among the groups, and these growth factors did not change in response to hyperglycemia. Hyperglycemic infants had baseline levels of insulin which were similar to normal controls, and endogenous insulin increased in response to hyperglycemia in 15 of the 23 infants who developed hyperglycemia. IGF-I and IGF-II are not related to hyperglycemia. In our population, hyperglycemic infants did not have baseline insulin deficiency and most had a normal insulin response to hyperglycemia. Insulin infusion appears safe in these infants and helped to maintain normal caloric intake, whereas glucose reduction was associated with a prolonged caloric deprivation.

Birth Weight↗

Heritability of plasma leptin in a population sample of African-American families.

The aim of this study was to examine familial patterns of plasma leptin levels and the potential association with cardiovascular risk factors in a population sample of African-American families recruited from metropolitan Chicago. The study included 68 mothers, 31 fathers, 143 daughters, and 119 sons, for a total of 361 individuals from 118 families. Leptin levels were adjusted for the effect of age separately for mothers, fathers, daughters, and sons. Residuals were then standardized before estimating familial correlation using the maximum-likelihood method available in SEGPATH. With the exception of height, plasma leptin level was strongly correlated with all measured anthropometric variables. Familial effect (i.e., heritability) of leptin levels was estimated as 39% in this population at high risk for over weight. A significant sex difference was observed, and most of the estimated familial effect may be attributed to genetic influences since the spouse correlation was not statistically different from zero. A strong nonshared environmental effect is also suggested, however.

Anthropometry↗

Malaria in the emergency department.

Malaria can a be serious, life-threatening illness. Data suggest that there are thousands of cases in the United States each year and that infection rates are increasing. Initial patient presentation will often be at the ED triage desk; patients usually have flulike symptoms and a fever. A high index of suspicion for individuals at risk of malaria clarified by a brief but thorough travel history facilitates early identification of presumptive cases and prompt, effective care. Early antibiotic treatment and aggressive supportive care are the mainstays of treatment. Serious P. falciparum infection should always be presumed and treated until proven otherwise.

Adult↗

Using partner hospitals in collaborative benchmarking..

In May 1994 the Physiotherapy Department at John Hunter Hospital received a Commonwealth Best Practice in the Health Sector grant to design a critical pathway for the treatment of stroke. The implementation of the pathway at John Hunter Hospital and the introduction of the methodology to secondary sites (The Alfred Healthcare Group, Melbourne, and Royal Hobart & Repatriation General Hospitals, Hobart) resulted in the development of a Benchmarking Consortium. This paper will discuss the importance of benchmarking in understanding clinical processes, and the methodology employed to ensure that meaningful benchmarks were achieved.

Ancillary Services, Hospital↗

Benchmarking critical pathways--a method for achieving best practice.

This article outlines the processes for the development and implementation of critical pathways to achieve best practice by two health organisations funded under the Commonwealth Government's Best Practice in the Health Sector Program. Each organisation is using a slightly different approach to using benchmarking as a tool to ensure best practice is achieved, however, they are similar in that they each demonstrate customer focus and a multidisciplinary, participative change management style.

Australia↗

Comparative pharmacokinetics and glucodynamics of two human insulin mixtures. 70/30 and 50/50 insulin mixtures.

OBJECTIVE: To compare and contrast the pharmacokinetics and glucodynamics of two insulin mixtures, one of 50% NPH human insulin and 50% Regular human insulin (50/50) and one of 70% NPH human insulin and 30% Regular human insulin (70/30), in healthy male volunteers after subcutaneous administrations of 0.3 U/kg. RESEARCH DESIGN AND METHODS: We administered single doses of 50/50 and 70/30 insulins to 18 volunteers in a randomized crossover fashion. All subjects received 0.3 U/kg of each mixture separated by at least 7 days. Each dose was given after an overnight fast and during a glucose clamp to maintain a euglycemic state. We measured serum insulin and C-peptide concentrations through frequent blood sampling after each treatment. Pharmacokinetic measurements were calculated from insulin data corrected for C-peptide, including maximum insulin concentration (Cmax), time to maximum insulin concentration (tmax), terminal rate constant (beta), area under the curve from 0 to infinity (AUCinfinity0), and mean residence time (MRT). Pharmacodynamic measurements were summarized from C-peptide concentrations (minimum C-peptide concentration [Cmin], time to minimum C-peptide concentration [tmin], area between the C-peptide baseline and the C-peptide suppression curve [AOCc], absolute maximal difference from baseline [Sdiff] and glucose clamp measurements. The glucose clamp measurements included maximum infusion rates (Rmax) and time to Rmax (TRmax) from glucose infusion rate (GIR) documentation, as well as cumulative glucose infused during the first 4 h ((0)4Gtot) and total glucose infused (Gtot) during the study. RESULTS: For the pharmacokinetic assessment, statistically greater values of insulin Cmax and beta were found for the 50/50 mixture, whereas the 70/30 mixture had a greater MRT. Statistical differences were also detected in glucodynamics, with greater values of Rmax and (0)4Gtot found with the 50/50 mixture. Notably, differences were not detected for insulin AUCinfinity0 and Gtot values. CONCLUSIONS: Higher insulin concentrations and a greater initial response were present with the 50/50 mixture, but the two mixtures had equivalent bioavailability and cumulative effects. These results support use of the 50/50 mixture in situations where greater initial glucose control is required.

Adult↗

Nucleic acid sequence-based amplification.

Nucleic acid sequence-based amplification (NASBA) is a primer-dependent technology that can be used for the continuous amplification of nucleic acids in a single mixture at one temperature.

Base Sequence↗

Grading and outcome prediction of cases of aneurysmal subarachnoid haemorrhage by bedside xenon cerebral blood flowmetry.

Ninety-six patients with aneurysmal subarachnoid haemorrhage underwent serial measurement of regional cerebral blood flow throughout the period of their treatment over the period of 5 years (1983 to 1988). A portable bedside xenon cerebral blood flow machine was used in this study and the initial slope index (ISI) values showed a clear relationship between reduction of cerebral blood flow and deteriorating clinical grade. Furthermore, serial measurements showed a statistically significant relationship between drop of cerebral blood flow, at anytime during the course of the disease, and fatal or less than satisfactory outcome.

Adolescent↗

Trigeminal neuroma. A report of eleven cases.

The clinical features, diagnosis, and management of a series of 11 cases of trigeminal neuroma (four men, seven women; mean age 40 years) are summarized. Symptoms at presentation were generally those of cerebellopontine angle and petrous apex space occupying lesions. Computed tomography scanning and magnetic resonance imaging were found to provide the best preoperative localization of these lesions, allowing better planning of the surgical approach and thereby maximizing tumor exposure, an essential for any attempt at total excision, considering the large size (greater than 3 cm) of these tumors when diagnosed. A retromastoid incision and posterior fossa craniectomy or a combined suprainfratentorial approach was used. Total excision was possible in four cases. In seven cases, a macroscopic clearance was effected (operative mortality nil, excellent outcome occurred in ten of the 11 cases). There has been no clinical evidence of recurrence or ongoing tumor growth despite possibly subtotal excision.

Adolescent↗