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Biomedical subjects

A Peters

Publications and source records attributed to A Peters.

At least 145 records · Page 8Linked to original sources
PubMed1996

Bacterial virulence antigens and the pathogenesis of autoimmune thyroid diseases (AITD).

There is now substantial evidence that autoimmune thyroid diseases (AITD) coincide with a subclinical persisting infection with Yersinia enterocolitica (YE) which manifests through humoral and cellular immune reactions against YE at the onset of AITD. The humoral and cellular crossreactivities of YE with thyroid autoantigens are exclusively directed against conformational epitopes of YE membrane associated antigens and of YE plasmid encoded virulence proteins (YOPs). Especially, the outer membrane domain of the TSH-Receptor (THSR) appears to have conformational homologies with YE antigens. Immunological- and molecular findings, however, do not allow definite conclusions about a potential role of YE-infection in AITD, although the evidence is suggestive. Recent investigations on the effect of YE-superantigen (Sag) on T-cells from patients with AITD as well as AITD like manifestations in YE immunized mice and rats may yield more conclusive information about the role of YE infection in the pathogenesis of AITD.

Animals↗
PubMed1996

Neurobiological bases of age-related cognitive decline in the rhesus monkey.

The rhesus monkey offers a useful model of normal human aging because when monkeys are tested on a battery of behavioral tasks that can also be used to evaluate cognition in humans, it is found that the monkeys undergo an age-related decline in several domains of cognitive function as do humans. In monkeys these changes begin at about 20 years of age. To determine what gives rise to this cognitive decline, we have examined several parameters in the brains of monkeys. Some parameters do not change with age. Examples of this are the numbers of neurons in the neocortex and hippocampal formation, and the numbers of synapses in the hippocampal formation. Changes in other parameters can be positively correlated with chronological age; examples of this are numbers of neuritic plaques, a decrease in the numbers of neurons in the striatally projecting pars compacta of the substantia nigra, and a decrease in the thickness of layer I in primary visual cortex. But the most interesting changes are those that correlate either with cognitive decline alone, or with both cognitive decline and chronological age. Among these are a breakdown in the integrity of myelin around axons, an overall reduction in the volume of white matter in the cerebral hemispheres, thinning of layer I in area 46 of prefrontal cortex, and decreases in the cell density in cortically projecting brain stem nuclei. To date then, our studies suggest that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer I and in the integrity of myelinated axons, rather than an age-related loss of cortical neurons or synapses, as has long been assumed.

Aging↗
PubMed1996

Nocturnal blood pressure elevation is related to adrenomedullary hyperactivity, but not to hyperinsulinemia, in nonobese normoalbuminuric type 1 diabetes.

We tested the hypothesis that insulin is an independent risk factor for elevated blood pressure. As our model we selected type 1 diabetes with peripheral circulatory hyperinsulinemia induced by sc insulin treatment. In 15 nonobese normoalbuminuric patients with type 1 diabetes (23.7 +/- 0.8 yr old) and in 15 healthy controls matched for age, sex, and body weight, ambulatory blood pressure was recorded over 24 h. The areas under the curve of free insulin (605 +/- 135 vs. 275 +/- 35 pmol/L.h; P = 0.03) and basal plasma epinephrine concentrations were higher (170 +/- 10 vs. 130 +/- 10 pmol/L; P = 0.02), and the basal aldosterone level was lower (220 +/- 40 vs. 410 +/- 50 pmol/L; P = 0.009) in the patients. The nocturnal decline in systolic blood pressure was less pronounced (13 +/- 1 vs. 19 +/- 2 mm Hg; P = 0.007) in the patients. Multivariate adjustment (r2 = 0.75; P = 0.0002) showed an effect of basal plasma epinephrine and norepinephrine levels and body mass index on the mean nocturnal systolic blood pressure, but showed no effect of age, sex, hemoglobin A1c, aldosterone, or, in particular, insulin. We found a blunted nocturnal fall in blood pressure in nonobese, normoalbuminuric type 1 diabetic patients. These patients showed increased adrenomedullary activity, and this predominantly contributed to the blood pressure alterations. We also found hyperinsulinemia in these patients, but, after controlling for covariates, blood pressure was independent of the insulin level.

Adolescent↗
PubMed1996

[Analytic design and clinical application of an intelligent control system for pharmacotherapy with insulin--2].

To determine whether insulin dosage recommendations provided by a computer system are as effective as those given by human experts, we developed an intelligent control system and prospectively studied its use in 42 type-1 diabetics attending a diabetes education center. Control algorithms were based on blood glucose self-monitoring and included parameter estimations to determine glucose metabolism. The algorithms were implemented in a vest pocket-sized system. Over a period of 32 days, 21 patients used the computer to determine the necessary dose of insulin, while a second group of 21 patients followed the recommendations of the diabetes specialists. Baseline HbA1 levels (9.8 +/- 1.6 vs 9.9 +/- 1.6%) were identical in the two groups. The mean serum glucose over the last two weeks of the study was lower in the computer group (151.3 +/- 25.2 vs 165.7 +/- 36.0 mg/dl; p < 0.01) although the rates of hypoglycaemic episodes were equal (1.7 vs 2.3%). Metabolic control, measured by the day-to-day standard deviation of the serum glucose (46.8 +/- 14.4 vs 50.4 +/- 16.2 mg/dl; p < 0.01), was more stable in the computer group. We conclude that metabolic control and safety were comparable in the two groups, and suggest that such an intelligent control system may be of benefit for use at home, when the help of doctors or diabetes educators is not available.

Adult↗
PubMed1996

[Isovolemic hemodilution in coronary heart disease--clinical and hemodynamic effects].

Clinical and hemodynamic effects of isovolemic hemodilution (HD) were evaluated in 12 patients (aged 59 +/- 8 years) with severe multivessel coronary artery disease (CAD) and angina pectoris grade III (Canadian Cardiovascular Society classification) despite high-dose medical treatment. In none of these patients was aortocoronary bypass grafting or percutaneous transluminal coronary angioplasty possible. Prior to HD and after 3 months of HD the incidence of angina pectoris was determined by means of questionnaires; hemodynamic measurements were performed with right heart catheterization at rest and during exercise. After 3 months of HD hematocrit was reduced from 46.2 +/- 1.3% to 38.5 +/- 0.5%. The weekly incidence of angina pectoris was unchanged (19 +/- 7 before, 17 +/- 8 after HD). Cardiac index was 2.5 +/- 0.7 1/min/m2 at rest and 3.9 +/- 1.0 1/min/m2 during exercise before, 2.6 +/- 0.5 1/min/m2 at rest and 3.9 +/- 0.8 1/min/m2 during exercise after HD. Stroke volume index did not increase significantly neither at rest nor during exercise after HD. Initially, systemic vascular resistance decreased from 1659 +/- 603 to 1398 +/- 420 dyns/cm5 during exercise; after HD it was 1522 +/- 551 (rest) and 1283 +/- 348 dyns/cm5 (exercise). Mean pulmonary artery pressure (PAP) and wedge pressure (WP) were unchanged at rest (PAP: 19.9 +/- 6.7 mm Hg before, 19.2 +/- 6.5 mm Hg after HD; WP: 10.8 +/- 5.5 mm Hg before, 10.7 +/- 4.3 mm Hg after HD) and during exercise (PAP: 43.0 +/- 9.9 mm Hg before, 42.8 +/- 8.9 mm Hg after HD; WP: 30.8 +/- 4.6 mm Hg before, 30.6 +/- 6.5 mm Hg after HD). In conclusion, in patients with CAD isovolemic HD does not reduce angina pectoris but also does not induce clinical deterioration. Furthermore, isovolemic HD does not worsen the hemodynamic effects of severe CAD with impaired left ventricular function.

Adult↗
PubMed1995

[45,X/46,XY/47,XXY chromosome mosaicism as a cause of hypergonadotropic hypogonadism diagnosed in late middle age].

UNLABELLED: HISTORY AND FINDINGS ON EXAMINATION: A 62-year-old man complaining of increasingly painful swelling in both breasts over the previous 6 months was admitted to hospital because an endocrine tumour or paraneoplasia was suspected. Unmarried and childless he had always been well except for mild diabetes treated with glibenclamide. On examination both breasts were enlarged with easily palpable glandular tissue; the testes were small and atrophic. Hair growth and distribution were normal. LABORATORY TESTS: Serum testosterone concentration was low (1.3 ng/ml), while luteinizing and follicle-stimulating hormones (27.3 mU/ml and 95 mU/ml, respectively) were raised. Chromosome analysis revealed 45,X/46,XY/47,XYY mosaicism without evidence of structural aberrations. Mammography showed true gynecomastia without signs of malignancy. TREATMENT AND COURSE: Hypergonadotrophic hypogonadism having been diagnosed the patient was given substitution treatment with 250 mg testosterone, 250 mg i.m. every 3 weeks. The concentrations of luteinizing and follicle-stimulating hormones became normal and the gynecomastia regressed over the subsequent 6 months. CONCLUSION: Mosaicism of the sex chromosomes should be considered in the differential diagnosis of late-onset hypogonadism, even in phenotypically unremarkable men.

Age Factors↗
PubMed1995

HIV in injecting drug users in Edinburgh: prevalence and correlates.

A citywide sample of injecting drug users (IDUs) who had injected in the previous 6 months was recruited in Edinburgh. Interviewers administered a questionnaire enquiring about drug use, sharing of injecting equipment, sexual behavior, and imprisonment. A specimen of saliva was assayed for human immunodeficiency virus (HIV) IgG. HIV antibody prevalence in 346 IDUs recruited between June 1992 and October 1993 was 19.7% (95% confidence limits, 15.5 and 23.9%). Univariate analyses indicated that infection was significantly associated with being 27 to 36 years of age, starting to inject between 1975 and 1980, injecting in 1980-1987 and, particularly, 1982-1984, injecting in more than 7 years since 1979, reusing injecting equipment already used by another IDU in 1980-1987, being imprisoned, using equipment used by a fellow prisoner, and residing in north Edinburgh. Multivariate analysis showed that being 27-36 years of age, injecting in 1982-1984, and being imprisoned were independently related to being HIV positive. The risk of being infected increased with the number of times of imprisonment. A quarter of the sample said that they had used injecting equipment already used by another person in the 6 months before interview, and 70% said that they had ever done so. Of IDUs who started injecting after 1986, 4.5% were HIV positive. These findings suggest that the potential for HIV transmission by contaminated equipment still exists in Edinburgh. This is particularly so in prison, where IDUs do not have access to new needles and syringes.

Adolescent↗
PubMed1995

NMR microscopy of single neurons using spin echo and line narrowed 2DFT imaging.

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T2 relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T2 difference between the nucleus and cytoplasm in these cells represents primarily a true T2 relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.

Animals↗
PubMed1995

Perioperative management of the diabetic patient.

Patients with diabetes mellitus are at a higher risk to undergo surgical intervention compared with the non-diabetic population, and additionally, they have an increased perioperative morbidity and mortality. Insulin deficiency and insulin resistance are aggravated by surgery and anaesthesia. The consequences of hyperglycemia are glycosuria, volume depletion from osmotic diuresis, impairment of wound healing and leucocyte function and exacerbation of ischemic brain damage. Depending on the extent of hypoinsulinemia, lipolysis and ketogenesis are enhanced which may result in metabolic acidosis with subsequent electrolyte disturbances. Protein catabolism is increased because of increased breakdown and decreased synthesis. Insulin administration reverts or overcomes most of these disturbances. The preoperative assessment includes the diagnoses of the long-term complications to judge the intraoperative risks. Long-acting insulins, such as ultralente of animal origin should be stopped preoperatively and substituted by protamine and lente insulins. In type-2-diabetic patients, long-acting sulfonylurea drugs such as chlorpropamide should be stopped and substituted by short-acting agents. Metformin must always be stopped. Type-2-diabetic patients with marked hyperglycemia under oral treatment should be switched to insulin before operation. The insulin requirements in diabetic patients during surgery vary from 0.25-0.40 U per gram glucose in normal weight patients, 0.4-0.8 U per gram glucose in case of obesity, liver disease, steroid therapy or sepsis, to 0.8-1.2 U per gram glucose in patients undergoing cardiopulmonary bypass surgery. Therefore, the appropriate dose has to be determined individually. The regimen nowadays preferred by most authors is based on variable rate insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1995

The influence of insulin antibodies on the pharmacokinetics of NPH insulin in patients with type 1 diabetes treated with human insulin.

The influence of insulin binding antibodies on the pharmacokinetics of NPH insulin was studied in Type 1 diabetic patients on human insulin. Insulin-antibody binding (B(o) was measured during a screening procedure in 155 Type 1 diabetic patients. In 36 patients, B(o) was < 1.5%, and in 38 patients B(o) was > 10.0%. Of these, 6 patients, group 1 (B(o) < 1.5%) and 8 patients, group 2 (B(o) > 10.0%), respectively, subsequently participated in a pharmacokinetic study. Free insulin and the glucose infusion rate were measured using a euglycaemic clamp after subcutaneous injection of NPH insulin (0.4 U kg-1). The areas under the curve (AUC) of free insulin concentration were smaller for group 2 (p = 0.01) than for group 1 (212.2 +/- 22.0 vs 316.8 +/- 25.3 mU l-1h). The AUCs of the glucose infusion rate were also smaller for group 2 (p < 0.05) than for group 1 (2.50 +/- 0.32 vs 3.58 +/- 0.36 g kg-1). A significant negative correlation exists between the AUCs for free insulin concentration and insulin-antibody binding B(o) (r = 0.76, p = 0.001). The daily insulin dosage was higher in group 2 (p = 0.02) than in group 1 (0.66 +/- 0.03 vs 0.53 +/- 0.03 U kg-1). We conclude that insulin antibodies influence the pharmacokinetics of NPH human insulin. The demonstrable influence on the kinetics of free insulin and glucose utilization leads to a slight increase in daily total insulin requirements.

Adult↗
PubMed1995

Preserved counterregulatory hormone release and symptoms after short term hypoglycemic episodes in normal men.

To test the hypothesis that subsequent neuroendocrine and symptomatic responses are sustained after short term hypoglycemic episodes of less than 1-h duration, we studied hypoglycemia on 4 consecutive days and after an 8-day pause in 10 nondiabetic men. Highly reproducible decreases in plasma glucose (< 2.8 mmol/L) occurred on study days 1, 2, 3, 4, and 12 after iv insulin boluses (0.04 U/kg). Levels of the counterregulatory hormones rose during the hypoglycemic episodes in all instances, but maximal concentrations on study day 4 were not attenuated: glucagon (peaks on day 1 vs. day 4), 150 +/- 10 vs. 180 +/- 20 ng/L; cortisol, 400 +/- 30 vs. 420 +/- 40 nmol/L; ACTH, 12 +/- 2 vs. 13 +/- 2 pmol/L; GH, 11.1 +/- 1.8 vs. 12.5 +/- 2.2 micrograms/L; norepinephrine, 1.68 +/- 0.17 vs. 1.65 +/- 0.13 nmol/L; and epinephrine, 1370 +/- 440 vs. 1520 +/- 480 pmol. On each study day, symptoms of hypoglycemia were produced after induction of hypoglycemia, and there was no decrease in the degree of symptomatology on subsequent days. The multivariate analysis of variance showed no day to day differences in plasma glucose, counterregulatory hormones, or hypoglycemic symptoms. We conclude, firstly, that after short term hypoglycemic episodes, the neuroendocrine and symptomatic responses remain completely intact in normal individuals and, secondly, that short term periods of hypoglycemia are fundamentally different from prolonged periods, as described previously.

Adrenocorticotropic Hormone↗
PubMed1994

Somatic nonhomologous crossing-over between neuropeptide genes in rat hypothalamic neurons.

Molecular biological and immunocytochemical data demonstrate nonhomologous crossing-over between the closely linked vasopressin (VP) and oxytocin (OT) genes in rat hypothalamic neuroendocrine neurons. Reverse transcription of hypothalamic total RNA from wild-type or homozygous Brattleboro aged rats combined with polymerase chain reaction (PCR) amplifications in the presence of appropriate 5' forward and 3' reverse primers deduced from the VP and OT cDNA sequences yielded PCR products that, upon cloning and sequencing, revealed several hybrid transcripts. They encode the N-terminal part of the VP precursor fused to the C-terminal part of the OT precursor (VP/OT transcripts) and vice versa (OT/VP transcripts). VP/OT hybrid precursor proteins have been identified immunocytochemically in enlarged cisternae of the rough endoplasmic reticulum, yet there is no evidence that the products can be secreted from affected cells. Recombination appears to be a rather frequent genetic event affecting about 0.06-0.1% of the rat vasopressinergic magnocellular neurons in aged rats.

Amino Acid Sequence↗
PubMed1994

Light-activated release of nitric oxide from vascular smooth muscle of normotensive and hypertensive rats.

A porphyrinic sensor was used to monitor nitric oxide release from vascular smooth muscle in response to exposure to ultraviolet light. Aortic rings exposed to UV light relaxed with a time course that parallels this observed NO release. With repeated UV light treatments, the magnitude of the relaxations diminished, suggesting that a store of NO was being exhausted. Photorelaxation in response to UV light was studied in aortic ring from two types of hypertensive rats, genetic (SHRSP) and nitroarginine-induced. These aortic rings showed greater photorelaxation and evidenced less tolerance than did aortic rings from control normotensive rats. Since NO synthase activity is depressed in both types of hypertension, it appears, paradoxically, that the UV light-releasable store of NO is augmented when NO synthase activity is depressed.

Animals↗
PubMed1994

NMR microscopy of hydrating hydrophilic matrix pharmaceutical tablets.

NMR microscopy has been used to monitor the formation of the gel layer in hydrating hydrophilic polymer tablets. Such tablets are used in the controlled delivery of drugs, where it has been found that the rate and extent of the swelling of the outer gel layer critically influences the kinetics of drug release. Tablets were hydrated in distilled water at 37 degrees C and then imaged at discrete time intervals using a 500 MHz microscope. The growth of the gel layer was clearly observed in time sequences of radial and axial sections. Axial images showed some interesting dimensional changes, with the gel at the flat surface of the tablet developing a concave shape. This is probably a reflection of the occurrence of uni-axial stress relaxation as hydration proceeds. Diffusion- and T2-weighted images provided evidence that the water in the gel layer is more strongly bound close to the dry core of the tablet than at the more fully hydrated outer surface. In images of tablets containing diclofenac, disruption of the gel layer was shown to occur primarily from the flat surfaces of the tablet, whilst the distribution of particles could be seen in tablets doped with insoluble calcium phosphate.

Diclofenac↗
PubMed1994

A photoactivable source of relaxing factor in genetic hypertension.

Deendothelialized rings of rabbit aorta relax after exposure to UV light because of release of a relaxing factor that is similar if not identical to nitric oxide. We tested the hypothesis that production of the photo-induced relaxing factor is impaired in a rat model of genetic hypertension. Thoracic aortas were removed from adult Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. The vessels were cut into rings, denuded of endothelium, and placed in a muscle bath for isometric force measurement. Rings were contracted with phenylephrine, and relaxation was measured after exposure to UV light. Aortic rings from stroke-prone spontaneously hypertensive rats relaxed to a greater extent after exposure to UV light than did rings from Wistar-Kyoto rats. An inhibitor of nitric oxide synthase (N omega-nitro-L-arginine) greatly potentiated the relaxation responses to light in both strains, and these enhanced relaxations were attenuated by tetraethylammonium chloride, potassium chloride, ouabain, or inhibitors of guanylate cyclase. These results suggest that UV irradiation induces relaxation in aortic smooth muscle that is greater in hypertensive than normotensive rats and is greatly enhanced after addition of inhibitors of nitric oxide production. Thus, the unidentified photo-induced relaxing factor is not solely nitric oxide but may also represent either a hyperpolarizing factor, because depolarization blocks the responses entirely, or possibly smooth muscle guanylate cyclase that might itself be photoactivable.

Animals↗
PubMed1994

Rapid quantitation of mRNA species in ethidium bromide-stained gels of competitive RT-PCR products.

A rapid method for quantifying the low-abundant mRNAs of the low density lipoprotein receptor and the 3-hydroxy-3-methylglutaryl coenzyme A reductase by competitive polymerase chain reaction is presented. This approach requires neither special labeling nor blotting procedures. For each analysis, a defined amount of total cellular RNA is co-reverse transcribed and co-amplified with a titration series of in vitro synthesized competitor RNA that carries an internal deletion. The equivalence point, which defines the amount of specific RNA in the sample, can be scored in ethidium bromide-stained agarose or polyacrylamide gels of the reaction products. As an example, responses to pravastatin, a competitive inhibitor of the HMG-CoA reductase, in a human tumor cell line were analyzed with this new technique. As a control, the expression of the unregulated gene, glyceraldehyde-3-phosphate dehydrogenase was measured in parallel using the same methodology. The results obtained were compared with those obtained by conventional Northern blotting.

Base Sequence↗