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Biomedical subjects

R Taylor

Publications and source records attributed to R Taylor.

At least 289 records · Page 16Linked to original sources

Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects.

Intracellular triglyceride (TG) is an important energy source for skeletal muscle. However, recent evidence suggests that if muscle contains abnormally high TG stores its sensitivity to insulin may be reduced, and this could predispose to type II diabetes. To test this hypothesis, we measured muscle lipid content in 27 women aged 47 to 55 years (mean, 52) and related it to their glucose tolerance, insulin resistance, and muscle insulin sensitivity as measured by insulin activation of glycogen synthase, an insulin-regulated enzyme that is rate-limiting for insulin action in muscle. Both muscle TG content and intracellular lipid determined by Oil red O staining of muscle fibers were negatively associated with glycogen synthase activation (r = .43, P = .03 and r = -.47, P = .02, respectively). In addition, intracellular lipid correlated with features of the insulin resistance syndrome, including an increased waist to hip ratio (r = .47, P = .01) and fasting nonesterified fatty acids ([NEFA] r = .44, P = .04). These data demonstrate that increased muscle TG stores are associated with decreased insulin-stimulated glycogen synthase activity. Intracellular fat may underlie a major part of the insulin resistance in normal subjects, as well as type II diabetics.

Body Constitution↗

Prophylactic mastectomy for genetic predisposition to breast cancer: the proband's story.

The identification of the BRCA1 gene may prove a mixed blessing in the short term. First, the demand for testing might outstrip available resources, the ethics of testing are complex and the advice to give someone who tests positive is as yet unclear. Furthermore, the psychological dynamics within such families have not yet been considered seriously. As these families might be widespread, there will inevitably be problems involving clinical genetic centres in different parts of the country, or for that matter, in different areas of the world. In this paper we provide a case report, which might be considered an adumbration of things to come. The proband in this story (a co-author) was known to have inherited a genetic predisposition to cancer. This was because her identical twin had already developed the disease and she came from a kindred with a very high probability for carrying a dominant breast cancer gene in the germ line. We describe the personal reactions of an individual woman faced with these difficult decisions, the impact on her family and the impact on the clinical genetic services in different parts of the country. Our experience could help to provide a template for the development of regional services once genetic testing for predisposition to breast cancer becomes widely available.

Adult↗

A study of infrared thermographic assessment of liquid nitrogen cryotherapy.

OBJECTIVE: To assess whether infrared thermography can accurately predict the area of soft tissue necrosis that results from liquid nitrogen cryoprobe therapy. STUDY DESIGN: Eight rats received cryosurgery on the shaved abdomen with a liquid nitrogen cryoprobe in a triple-freeze technique. The therapy was monitored with infrared thermography and thermocouple probes. The temperature reached was correlated with the area of tissue necrosis found on histologic examination at sacrifice 1 week after the cryotreatment. A parallel study was carried out on pieces on beefsteak to assess the depth and shape of freeze. RESULTS: The -20 degrees C isotherm, which is felt to correspond to the cell lethal zone, occupied the inner 70% of the area of the iceball produced. Histologically, the -20 degrees C isotherm corresponded well to the area of tissue necrosis. In depth, the iceball takes on a semicircular shape. CONCLUSIONS: Infrared tomography is expensive to use clinically and cannot be readily used in the oral cavity. However, this study does show that one can clinically estimate that the inner 70% of the area of an iceball produced by liquid nitrogen on soft tissues will ultimately undergo necrosis.

Animals↗

Properties of complex hallucinations associated with deficits in vision.

Complex visual hallucinations are known to occur in individuals with impaired vision yet whose emotional and intellectual functions are within the normal range. These hallucinations, which were first reported by Charles Bonnet in 1760, have been described in many case studies, but have not been analyzed empirically to determine their major properties. In the present study, sixty complex hallucinators labeled as Charles Bonnet hallucinators were administered a questionnaire to determine the properties of their hallucinations. Combined use of multiple-correspondence analysis and hierarchical cluster analysis reveals a set of features that characterize the 'typical' Charles Bonnet hallucinatory experience: the hallucinators' experience occurs while they are alert and with the eyelids open; a sharply focused image appears suddenly, without any apparent trigger or voluntary control; the hallucination is present for seconds, does not move during this time, then suddenly vanishes. These features are discussed in terms of a 'dimension' of hallucinatory/perceptual experience, which ranges from discrete perceptual experiences to multiple, changing experiences. Possible mechanisms that underlie the Charles Bonnet hallucinations are discussed.

Blindness↗

A noncovalent complex vaccine prepared with detoxified Escherichia coli J5 (Rc chemotype) lipopolysaccharide and Neisseria meningitidis Group B outer membrane protein produces protective antibodies against gram-negative bacteremia.

Earlier studies showed that purified IgG from sera of rabbits immunized with a boiled Escherichia coli J5 (Rc chemotype) whole cell vaccine protected neutropenic rats against gram-negative bacterial sepsis. In the present study, de-O-acylated J5 lipopolysaccharide (J5 DLPS) as a noncovalent complex with Neisseria meningitidis group B outer membrane protein (GBOMP) elicited anti-J5 LPS antibodies in rabbits. IgG prepared from immune rabbit sera protected neutropenic rats against lethal challenge with Pseudomonas aeruginosa 12:4:4 (Fisher Devlin immunotype 6). Sixteen of 26 rats treated with the postimmune serum IgG were protected compared with none of 20 rats treated with the control rabbit serum IgG (P < .001). In vitro binding studies showed binding of anti-J5 IgG to several gram-negative bacteria. These results indicate that a subunit vaccine made of J5 DLPS as a noncovalent complex with GBOMP may protect against gram-negative bacteremia.

Animals↗

Adipocyte insulin action during the normal menstrual cycle.

The relationship between the menstrual cycle and insulin sensitivity is unclear. The aim of this study was to investigate insulin sensitivity during the normal menstrual cycle using the physiological insulin target organ adipose tissue. A total of 23 normal healthy volunteers were studied, nine of whom were in the follicular phase, and 14 of whom were age and body mass index-matched and in the luteal phase of the menstrual cycle. Adipocyte insulin receptor binding was measured and adipocyte insulin action was assessed by measuring initial rates of 3-O-methylglucose uptake and by inhibition of lipolysis. The maximum specific insulin receptor binding was significantly higher in subjects studied during the follicular phase of the menstrual cycle compared to subjects studied during the luteal phase (1.81 +/- 0.13 versus 1.36 +/- 0.15% per 10 cm2 cell surface, P < 0.05). Maximum rates of 3-O-methylglucose transport were 1.70 +/- 0.22 versus 1.75 +/- 0.22 pmol/10 cm2/5 s in the follicular and luteal phase respectively and were not significantly different between the two groups. The maximum percentage lipolysis inhibition observed was 42. 5 +/- 7.5% in the follicular phase and 39.9 +/- 7.4% in the luteal phase (not significant). This study demonstrated that there is a reduction in insulin receptor binding in the luteal phase of the normal ovulatory menstrual cycle. The post-receptor action of insulin is not affected between the two phases of the menstrual cycle.

3-O-Methylglucose↗

Successful management of hyperemesis gravidarum using steroid therapy.

Hyperemesis gravidarum causes uncontrollable vomiting, severe dehydration and muscle wasting in pregnancy and usually requires weeks or months of intravenous fluid therapy. A consecutive series of 7 women with hyperemesis gravidarum were treated with high-dose steroid therapy. Vomiting stopped within 3 h of the first dose of intravenous hydrocortisone in all patients. Maintainence oral prednisolone therapy in doses up to 45 mg/day permitted discharge from hospital within days, resumption of normal eating, reversal of muscle wasting and regain of lost weight (mean loss from prepregnant weight 10.5 +/- 4.3 kg). Prednisolone in doses of 15 mg/day or more was required for 10.6 +/- 4.7 (range 6-20) weeks. High-dose prednisolone therapy is effective in suppressing symptoms of intractable hyperemesis gravidarum and allowing normal maternal nutrition.

Adult↗

Health care expenditure and life expectancy in Australia: how well do we perform?

The Australian health care system consists of mixed public and private financing underpinned by Medicare, a universal government-run insurance scheme paid through taxation (and levy) on income. Australia has improved its ranking for life expectancy (at birth) since 1960, and in 1990 ranked ninth and seventh of 24 countries for females and males respectively; this is ahead of the United States and United Kingdom, and approximately equal to Canada. Australian hospital bed supply and utilisation are average, after deletion of day-only cases. The proportion of gross domestic product (GDP) spent on health, in relation to GDP per capita (adjusted for purchasing power), in Australia in 1990 was average, and the prices for health care from 1975 to 1990 did not increase when adjusted for inflation. Although 68 per cent of health expenditure emanates from public sources in Australia, this is lower than in the majority of European countries and Canada. Some countries are doing poorly (such as the United States, with lower than average life expectancy and higher than predicted health expenditure) and some countries are doing well (with higher than average life expectancy and lower than predicted health expenditure; for example, Japan). Australia has higher than average life expectancy and only slightly higher than predicted health expenditure per capita. Although the Australian system could be improved, there are no indications that radical changes are required. The relatively high life expectancy in Australia can be attributed to favourable social and economic conditions, successful public health programs, and the availability of universal quality health care.

Australia↗

Cervical cancer in New South Wales women: five-year survival, 1972 to 1991.

We analysed five-year relative survival of 6992 cases of cervical cancer incident between 1972 and 1991 in New South Wales (NSW) women, using data from the population-based state Cancer Registry. Follow-up was to 1992. Survival was determined by record linkage to death certificates. Relative survival was derived from absolute survival of cases with expected survival of age- and period-matched NSW women. Proportional hazard regression analysis was used for multivariate analysis. Relative survival at five years improved from 64 per cent in 1972-1976 to 72 per cent in 1987-1991, although the only significant increase occurred between 1972-1976 and 1977-1981 (64 to 70 per cent). Survival was better for the age groups 0-39 years (RR 0.51) and 40-49 years (RR 0.63) and worse for the elderly (> or = 65 years) (RR 1.47) than for the referent group (50-64 years). Excess mortality was much less for those with localised disease (referent group), than for those with regional spread (RR 3.47) or metastatic cancer (RR 10.5) at diagnosis. For the most recent period (1987-1991), relative five-year survival for localised disease was 82 per cent, for regional spread at diagnosis it was 49 per cent, and for metastatic cancer 21 per cent. When adjusted for confounding, excess mortality was significantly higher for adenocarcinoma (RR 1.16) than for squamous cell carcinoma. Five-year relative survival for cervical cancer in NSW women for the most recent period is similar to that in South Australia, and both compare favourably with international statistics. The lack of improvement of five-year survival for cervical cancer over 15 years since 1977-1981 reinforces the importance of prevention through regular screening by cytology.

Adenocarcinoma↗

Socioeconomic differentials in cancer incidence and mortality in urban New South Wales, 1987-1991.

Cancer incidence and mortality in urban residents of New South Wales (NSW), 1987 to 1991, were analyzed according to socioeconomic status (SES) for males (m) and females (f). Incidence rates displaying a negative gradient with SES at P < 0.01 included: cancers of the mouth and pharynx (m), oesophagus (m), stomach (m,f), liver (m), pancreas (m), larynx (m), lung (m,f), cervix, kidney (m,f) and all cancers combined (m). Negative mortality gradients at P < 0.01 were observed for mouth and pharynx (m), stomach (m,f), rectum (m), liver (m), larynx (m), lung (m,f) and cervix, and all cancers (m,f). Those sites for which incidence showed a positive gradient with SES included: colon (m,f), melanoma (m,f), breast (f), prostate and testis. For cancer mortality for specific sites no significant (P < 0.01) positive gradients were observed, although for melanoma (m,f) a positive gradient at P < 0.05 was found. Mortality for all cancers considered together in both sexes was significantly higher in the low SES group compared to the high SES group. This is partly because the more-fatal cancers are more common in the lower SES groups. Diet, tobacco use, reproductive factors, occupational and sun exposures are likely to be associated with the patterns observed but are not investigated in this study. Variations in health care between SES groups may also be partly responsible for some of the differences.

Female↗

Huntington's disease: a molecular genetic and CT comparison.

Huntington's disease is a progressive neurodegenerative disease in which the molecular abnormality has recently been described. Before the availability of this molecular marker diagnosis depended on clinical findings, supported in some instances by neuroimaging using CT or MRI. The imaging modalities may show atrophy of the heads of caudate nuclei in affected people. An attempt was made to validate these imaging findings using the molecular test as "gold standard." Retrospective analysis of cranial CT in 16 patients with Huntington's disease and 16 age and sex matched controls was performed. There was a highly significant difference in caudate head size (P < 0.00001) between patients with Huntington's disease and control subjects. However, the sensitivity of diagnosis based on radiological examination alone was only 87.5% in this study. Thus the sensitivity of CT is insufficient to justify its routine use in the investigation of suspected Huntington's disease, unless genetic tests are negative and other diagnoses need to be excluded.

Adult↗

Improvement in cerebral hemodynamics after carotid angioplasty.

BACKGROUND AND PURPOSE: Carotid percutaneous transluminal angioplasty ( PTA) may offer an alternative treatment to carotid endarterectomy. However, in contrast to carotid endarterectomy, which has been shown to normalize impaired cerebral hemodynamics, the effects of carotid PTA are unknown. Therefore, we prospectively studied the effect of carotid PTA on both perioperative and postoperative cerebral hemodynamics. METHODS: Eleven patients undergoing carotid PTA for symptomatic carotid artery stenosis were prospectively studied. Transcranial Doppler recordings from the ipsilateral middle cerebral artery (MCA) were performed during the procedure. In addition, MCA blood flow velocity and CO2 reactivity were determined before PTA and at 2 days, 1 month, and 6 months after procedure. The results were compared with those in 11 similar patients undergoing carotid endarterectomy in whom measurements were performed before and 1 month after the operation. RESULTS: During carotid PTA, in 2 of 11 patients during passage of the balloon catheter through the stenosis, MCA blood flow velocity fell transiently. In 6 of 11 patients there was a reduction in flow velocity (>50%) during balloon deflation, but this lasted only a few seconds. After the procedure there was a significant improvement in ipsilateral hypercapnic reactivity: preoperative value, 59.8+/-42.2% (mean+/-SD); 2 days, 77.9+/-31.4%; 1 month, 88.7+/-45.0%; 6 months, 89.8+/-33.9%; and (ANOVA P=.003) preoperative value versus 1 month, P<.02; versus 6 months, P<.02. In all cases in which reactivity was significantly impaired preoperatively, it returned to the normal range. Pulsatility index also increased significantly: preoperative value, 0.827+/-0.251 (mean+/-SD); 2 days, 0.992+/-0.262 (P=.002). Contralateral MCA hypercapnic reactivity also improved after carotid PTA. There was a similar improvement in ipsilateral hypercapnic reactivity after carotid endarterectomy. CONCLUSIONS: Carotid PTA results in a normalization of impaired hemodynamics, as assessed by CO2 reactivity. The degree of improvement is similar to that seen after carotid endarterectomy.

Angioplasty, Balloon, Coronary↗

Fat body cells and calcium phosphate spherules induce ice nucleation in the freeze-tolerant larvae of the gall fly Eurosta solidaginis (Diptera, Tephritidae)

During the autumn, the third-instar larvae of the gall fly Eurosta solidaginis acquire freeze tolerance and their crystallization temperatures increase into the -8 to -10 &deg;C range. Despite conflicting reports, efficient endogenous ice nucleators have not been identified in this freeze-tolerant insect. We found large crystalloid spheres within the Malpighian tubules of overwintering larvae. Energy-dispersive X-ray microanalysis and infrared spectroscopy indicated that the spherules were a hydrate of tribasic calcium phosphate. To test for ice-nucleating activity, we placed the calcium phosphate spherules in 10 &micro;l of Schneider's insect medium and cooled them in a refrigerated bath. The addition of spherules increased the crystallization temperature of Schneider's medium by approximately 8 C, from -18.4&plusmn;0.8 &deg;C to -10.1&plusmn;0.9 &deg;C (mean &plusmn; s.e.m., N=20). Ice-nucleating activity (-10.9&plusmn;0.9 &deg;C) was also demonstrated in fat body cells suspended in 10 &micro;l of Schneider's medium. Both calcium phosphate spherules and fat body cells have ice-nucleating activity sufficiently high to explain whole-body crystallization temperatures. Furthermore, other crystalloid deposits, commonly found in diapausing or overwintering insects, also exhibited significant ice-nucleating activity. These endogenous crystalloid deposits represent a new class of heterogeneous ice nucleators that potentially regulate supercooling and promote freeze tolerance in E. solidaginis and possibly in other overwintering insects.

Journal Article↗

Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM.

Inhibition of tumor necrosis factor (TNF)-alpha action has recently been shown to reverse insulin resistance dramatically and to improve glycemic control in obese rodents. This double-blind study was designed to assess the effects of a recombinant-engineered human TNF-alpha-neutralizing antibody (CDP571) on glucose homeostasis in obese NIDDM patients. Glycemic control and insulin sensitivity were monitored in 21 NIDDM subjects for a 2-week run-in and then for 6 weeks after treatment in a randomized fashion with a single intravenous dose of either CDP571 (5 mg/kg) or an equivalent volume of normal saline. The prolonged half-life of the antibody ensured adequate plasma levels as measured throughout the study. Concentrations of fasting glucose (CDP571: 10.0 +/- 0.8, 10.1 +/- 0.8, 10.0 +/- 1.0; placebo: 8.5 +/- 0.6, 8.1 +/- 0.5, 8.7 +/- 0.8 mmol/l at baseline, day 1, and week 4, respectively), fasting serum insulin (CDP571: 21.2 +/- 2.8, 21.0 +/- 2.8, 24.8 +/- 3.3; placebo: 19.0 +/- 2.8, 20.8 +/- 2.9, 17.5 +/- 2.2 pmol/l, respectively), and C-peptide remained unaffected by the type of treatment throughout the study. The percentage rate of glucose clearance per minute (KITT) during intravenous insulin sensitivity tests was identical in the CDP571 and placebo groups at baseline and also at 1 and 4 weeks after treatment (mean +/- SE; CDP571: 1.33 +/- 0.21, 1.44 +/- 0.25, 1.26 +/- 0.18; placebo: 1.38 +/- 0.15, 1.47 +/- 0.20, 1.52 +/- 0.20; P = 0.85, 0.93, and 0.36, respectively). TNF-alpha neutralization over a period of 4 weeks had no effect on insulin sensitivity in obese NIDDM subjects.

Antibodies↗

Does suppression of postprandial blood glucose excursions by the alpha-glucosidase inhibitor miglitol improve insulin sensitivity in diet-treated type II diabetic patients?

OBJECTIVE: Insulin sensitivity is impaired in patients with type II diabetes and is exacerbated by high mean blood glucose (BG). Potentially, large postprandial swings in BG could result in further decrements of insulin sensitivity. Because alpha-glucosidase inhibitors cause a marked reduction in the amplitude of BG changes, the aim of this study was to determine if such a BG-smoothing effect improves insulin sensitivity in well-controlled type II diabetic subjects treated with diet alone. RESEARCH DESIGN AND METHODS: Patients received either miglitol (BAY m 1099) (50 mg three times daily) or placebo for 8 weeks in a randomized double-blind parallel study. The miglitol (9 men, 2 women) and placebo (7 men, 3 women) groups were well matched (mean +/- SD) for age, weight, and blood glucose control (fasting BG, 6.4 +/- 1.0 vs. 6.9 +/- 1.6 mmol/l; HbA1, 7.7 +/- 1.0 vs. 7.9 +/- 0.4%; fructosamine, 0.99 +/- 0.08 vs. 1.07 +/- 0.17 mmol/l). The glucose metabolic clearance rate was calculated during the last 30 min of a 150 min glucose/insulin sensitivity test (glucose, 6 mg . kg-1 . min-1; insulin, 0.5 U . kg-1 . min-1). RESULTS: There was no significant improvement in metabolic clearance rate (0.21 +/- 0.27 vs. 0.16 +/- 0.35 l . kg-1 . min-1) for the miglitol- and placebo-treated groups, respectively. There were no statistically significant differences between miglitol and placebo for changes from baseline in BG (0.1 +/- 0.1 vs. -0.1 +/- 0.2 mmol/l), HbA1 (0.1 +/- 0.1 vs. 0.3 +/- 0.1%), and fructosamine (-0.06 +/- 0.02 vs. -0.03 +/- 0.02 mmol/l). CONCLUSIONS: Alpha-glucosidase-induced improvement in postprandial hyperglycemia does not result in increased insulin sensitivity.

1-Deoxynojirimycin↗

Comparison of four cytokine regimens for mobilization of peripheral blood stem cells: IL-3 alone and combined with GM-CSF or G-CSF.

Improved methods for mobilization may reduce the number of aphereses required to collect adequate numbers of peripheral blood stem cells (PBSC) and hasten engraftment following high-dose therapy. Mobilization with cytokines alone enables engraftment after myeloablative therapy. The optimal cytokine regimen for mobilization has not been established. The study evaluated the effects of four interleukin-3-containing cytokine regimens administered during steady state hematopoiesis on PBSC mobilization in 30 patients with breast cancer or lymphoid malignancies. These regimens included IL-3 alone (Arm 1), sequential IL-3 --> G-GSF (Arm 2), sequential IL-3 --> GM-CSF (Arm 3) and combined IL-3 + G-CSF (Arm 4). Consecutive days of apheresis were performed until a target of 4-6 x 10(8) mononuclear cells/kg were collected. All patients received intravenous GM-CSF after PBSC infusion. Median days to an ANC > or = 500/ microliters in Arm 3(22 days) was significantly slower than for patients in Arm 2 (13 days) but not significantly different from patients in Arm 1 or Arm 4. There was no significant difference in platelet engraftment or days of hospitalization between the study arms. Addition of GM-CSF to IL-3-containing mobilization regimens results in collection of PBSC that lead to delayed engraftment. Further development of Arms 1, 2, and 4 appear warranted.

Adult↗

Restructuring the health care delivery system in the United States.

The article examines some of the drivers and related factors that led to the development of modern health care delivery systems. It assesses the relative successes of different models in today's evolving market and suggests strategies and modifications that are most likely to assure success in our national quest for improved quality and efficiency in the health care delivery systems. The article concludes with a brief look at the changes that may be necessary in health education to support this evolution in health care delivery.

Cost-Benefit Analysis↗