Recruitment and retention of volunteers in a dietary methodology study.
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Adult↗
Biomedical subjects
J R Peters
Publications and source records attributed to J R Peters.
Hyperinsulinaemia and microvascular angina ("syndrome X")
Glucose and insulin responses to a glucose load in 11 patients with angina attributed to microvascular coronary dysfunction were compared with those in 11 healthy subjects matched for age, sex, and body mass. Stimulated hyperinsulinaemia was demonstrated in the microvascular angina group. The findings suggest a role for increased concentrations of insulin in coronary microvascular dysfunction.
Adult↗
Biofeedback-assisted relaxation training for the aging chronic pain patient.
The older segments of the U.S. population are expanding rapidly and account for a disproportionate amount of health care, including treatment for pain-related musculoskeletal disorders. In a prospective study with objective measures and one-year follow-up, Middaugh et al. (1988) found that older patients (55-78 yr; N = 17, 76% success) treated in a multidisciplinary chronic pain rehabilitation program enjoyed a success rate equal to that of younger patients (29-48 yr, N = 20, 70% success). The current study presents additional data on these two groups of patients to compare their ability to learn the physiological self-regulation skills taught in the biofeedback/relaxation component of the multimodal program. This component included progressive muscle relaxation training, diaphragmatic breathing instruction, and EMG biofeedback. Repeated measures ANOVA showed significant increases in digital skin temperature (peripheral vasodilation) and decreases in respiration rate both within and across training sessions (p values = .04 to .0001) with no differences between age groups (p greater than .05). EMG measures for the upper trapezius ms in patients with cervical pain showed similar deficits in muscle control at evaluation and similar improvements with biofeedback training for the two age groups. These findings indicate that older pain patients responded well to the biofeedback/relaxation training component of the multimodal pain program.
Adult↗
Simultaneous determination of glomerular filtration rate and effective renal plasma flow.
A method is described for the simultaneous determination of GFR and ERPF within the normal range using a single injection of 51Cr-EDTA and 125I-OIH. Reference values of GFR (range 59-176 ml min-1) and ERPF (268-810 ml min-1) were calculated from bi-exponential analysis of curves based on multiple plasma samples. A subset of the samples (44, 120, 180 and 240 min) was used to estimate GFR by fitting a bi-exponential curve. Regression analysis demonstrated that the reference GFR value could be predicted from this four-sample estimate with a standard error of estimate (SEE) of 2.9 ml min-1, which compared favourably with methods based on mono-exponential analysis (minimum SEE = 6.3 ml min-1) or single samples (minimum SEE = 7.7 ml min-1). The effective volume of distribution of 125I-OIH calculated from the 44 min sample was used to estimate ERPF using a published equation with a SEE of 52 ml min-1. The improved precision of this simplified method for the simultaneous measurement of GFR and ERPF in the normal range will facilitate longitudinal studies in large patient groups in the evaluation of the causative factors of renal disease.
Chromium Radioisotopes↗
Effects of ambient glycaemic state on growth hormone responsiveness in insulin-dependent diabetes.
OBJECTIVE: We wished to examine the effects of ambient glycaemia on hypothalamic somatostatinergic tone in insulin-dependent diabetes mellitus. DESIGN: After 6-hour periods of either euglycaemia (5 mmol/l) or hyperglycaemia (15 mmol/l), exercise-induced GH secretion was measured. PATIENTS: Seven insulin dependent diabetics with no evidence of complications were recruited. RESULTS: There was no significant difference between basal GH levels during euglycaemia and hyperglycaemia (5.50 vs 5.53 mU/l). Nor was there a significant difference when mean delta GH levels (33.9 vs 27.4 mU/l) or mean area under GH curve (2331 vs 4038 mU min/l) during euglycaemia or hyperglycaemia were compared. CONCLUSIONS: We find no evidence therefore to support short-term effects of ambient glucose concentration on GH responsiveness, and by inference no direct effect of short-term changes in glycaemic control on hypothalamic release of somatostatin in the aetiology of GH hypersecretion in insulin-dependent diabetes mellitus.
Adult↗
Cholinergic blockade with pirenzepine induces dose-related reduction in glucose and insulin responses to a mixed meal in normal subjects and non-insulin dependent diabetics.
OBJECTIVE: The aim of the study was to assess the effects of cholinergic blockade with pirenzepine on glucose and insulin responses to a mixed meal in normal subjects and patients with non-insulin dependent diabetes (NIDDM). Further, to assess in normal subjects the relative importance of nocturnal GH suppression by pirenzepine. DESIGN: Placebo, 100 or 200 mg pirenzepine were given to the normal subjects 1 hour before a standard mixed meal. The effects of placebo or 200 mg pirenzepine at night on nocturnal GH secretion and subsequent breakfast carbohydrate tolerance were also studied. NIDDMs were given placebo or 200 mg pirenzepine before the meal. SUBJECTS: We studied six healthy male volunteers (ages 20-22, body mass indices 20.3-23.3) and ten NIDDMs (eight men, ages 42-74); five obese (BMI 25.5-31.8) and five non-obese (BMI 21.2-24.8). MEASUREMENTS: Serial plasma glucose and insulin concentrations were measured for 3 hours after a standard mixed meal. RESULTS: Acute pretreatment of normal male volunteers with pirenzepine produced a dose-related improvement in carbohydrate tolerance. Peak post-prandial plasma glucose levels were delayed and significantly reduced following 200 mg orally (6.5 +/- 0.1 mmol/l), but not following 100 mg (7.3 +/- 0.3), compared with placebo (7.6 +/- 0.3). Peak insulin levels were similarly delayed and reduced by the 200 mg dose only (36.5 +/- 6.1 mU/l, compared with 49.8 +/- 8.7). Suppression of nocturnal GH by 200 mg pirenzepine at night produced a small reduction in fasting plasma glucose (5.0 +/- 0.1 mmol/l, compared with 5.3 +/- 0.1, P less than 0.02) but did not improve subsequent breakfast carbohydrate tolerance. Peak plasma glucose in NIDDMs was reduced following pirenzepine (12.4 +/- 0.9 mmol/l) compared with placebo (14.3 +/- 1.0, P less than 0.01). This reduction was equally significant in obese and non-obese groups. Peak plasma insulin was also reduced by pirenzepine (22.4 +/- 3.9 mU/l) compared with placebo (42.4 +/- 5.3, P less than 0.01). Insulin suppression was quantitatively greater in obese than in non-obese patients. CONCLUSIONS: Improvement in carbohydrate tolerance after pirenzepine in normal subjects is dose related and largely independent of GH suppression. Cholinergic blockade can also improve meal carbohydrate tolerance with simultaneous reduction in plasma insulin concentrations in non-insulin dependent diabetics, particularly those with obesity.
Adult↗
Ketorolac in acute headache management.
Twelve patients presenting to an emergency department in headache crisis were treated with Ketorolac tromethamine 60 mg. intramuscularly. All improved sufficiently to require no further emergent treatment. There was statistically significant improvement on all segments of the short form McGill Pain Questionnaire. This open label trial suggests that Ketorolac Tromethamine may be a useful agent in the treatment of headache crisis, and a controlled study to examine this is warranted.
Acute Disease↗
Papilloedema and cranial nerve palsies complicating apparent benign aseptic meningitis.
Three patients who presented with apparently uncomplicated aseptic meningitis subsequently developed papilloedema and sixth cranial nerve palsies between 11 and 16 days after the onset of the illness. All three patients recovered completely without treatment. Raised intracranial pressure is a poorly recognized complication of aseptic meningitis that may represent a post-infective or 'allergic' response to an enteroviral infection. While clinicians should be aware of this possible complication of aseptic meningitis, differentiation from tuberculous meningitis may be difficult necessitating empirical treatment with anti-TB drugs.
Abducens Nerve↗
Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.
OBJECTIVE: To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). RESEARCH DESIGN AND METHODS: Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. RESULTS: Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). CONCLUSIONS: Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.
Adult↗
Allelic variants at insulin-receptor and insulin gene loci and susceptibility to NIDDM in Welsh population.
A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to the insulin gene. There was no significant difference in RFLP frequencies between the NIDDM subjects and a group of 87 matched White control subjects. Paired haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I. Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas, another haplotype was associated with the control group (P less than 0.02). Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM subjects with the differing IRG haplotypes to a standard meal tolerance test. Both groups showed equivalent basal and postprandial glucose excursions, but one group revealed a significantly exaggerated plasma insulin response compared with the other (P less than 0.05). This may reflect the influence of genetic variation at the IRG locus on insulin sensitivity in patients with NIDDM.
Adult↗
Needle aspiration of nonfunctioning parathyroid cysts.
Until recently, nonfunctioning parathyroid cysts were usually identified at operation for a presumed thyroid mass. Thyroid needle biopsy now allows their preoperative diagnosis and potential definitive treatment. This study reviews four patients with nonfunctioning parathyroid cysts treated during a two-year period. Three women and one man range in age from 28 to 70 years. Each presented with an asymptomatic thyroid mass ranging from 3 to 5 cm in length. None had symptoms of primary hyperparathyroidism. Serum calciums were from 9.2 to 10.7 mg/dl and serum phosphoruses were 3.2 to 4.4 mg/dl. Needle aspiration revealed 5 to 85 cc of water-clear fluid. C-terminal parathyroid hormone in three patients was 12,600, 6,500 and 61,200 pg/ml and N-terminal PTH was 1,700 pg/ml in one. All four had normal serum calcium and phosphorus on follow-up ranging from six months to two years. Two patients had resolution of their cysts with a single aspiration. One patient had recurrence but has no evidence of recurrence six months after injection with tetracycline. Another patient had a recurrence but remains well one year following reaspiration. Nonfunctioning parathyroid cysts present as a thyroid mass. Needle aspiration of water-clear fluid high in parathormone is diagnostic and, in most patients, is the therapeutic modality of choice.
Adult↗
Cholinergic blockade with pirenzepine improves carbohydrate tolerance and abolishes the GH response to meals in normal subjects.
Pretreatment of normal male volunteers with the cholinergic muscarinic receptor-blocking drug pirenzepine (200 mg p.o.) abolishes the delayed GH response to a meal stimulus. In addition, the glycaemic and insulin responses to meals are significantly reduced following this dose of pirenzepine. The data suggest that the effect of pirenzepine on the glucose response to meals is at least partly independent of the inhibition of GH release. Our findings are of relevance to the further investigation of cholinergic muscarinic antagonist in diabetes mellitus.
Adult↗
Development of an invasive macroprolactinoma: a possible consequence of prolonged oestrogen replacement. Case report.
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Adult↗
Early morning hyperglycemia in insulin-dependent diabetes: acute and sustained effects of cholinergic blockade.
Nocturnal release of GH has been shown to be related to the early morning rise in plasma glucose (PG) seen in insulin-dependent diabetes mellitus (IDDM). We have studied the effects of suppression of nocturnal GH release during a single night (acute study) and after nightly suppression for 1 week (chronic study). Changes in plasma glucose and counter-regulatory hormone concentrations were monitored in six IDDM patients during a constant overnight insulin infusion alone, after addition of the anticholinergic agent pirenzepine to cause acute GH suppression, and again on the seventh night of such treatment. In control experiments (infusion of insulin alone; 0.075 mU/kg.min) PG increased from (mean +/- SEM) 5.6 +/- 0.6 mmol/L at 2400 h to 11.1 +/- 1.3 mmol/L at 0900 h (P = 0.0024). Addition of pirenzepine (100 mg at 2200 h and again at 2400 h) in the acute study resulted in a PG change from 5.6 +/- 0.3 mmol/L at 2400 h to 8.4 +/- 1.4 mmol/L at 0900 h (P = 0.17). After pirenzepine administration at the same dose for 7 nights, PG increased from 4.7 +/- 0.6 mmol/L at 2400 h to 6.8 +/- 1.2 mmol/L at 0900 h (P = 0.11). Increases in PG during the study period were significantly less after chronic treatment than after acute treatment compared with changes on control nights. The nocturnal release of GH, which was demonstrated in all patients during the control nights, was suppressed in all patients during the acute study and in four of six patients during the chronic studies. We conclude that initial reduction of the early morning rise of PG in IDDM is associated with acute suppression of nocturnal GH release, and that the more significant sustained effect of anticholinergic GH suppression on the rise of PG may be associated with additional indirect effects on insulin clearance.
Adult↗
Evidence that growth hormone depletion and uncoupling of the regulatory protein of adenylate cyclase (Ns) both contribute to the desensitization of growth hormone responses to growth hormone-releasing factor.
Recent data suggest that the response of GH to GH-releasing factor (GRF) is reduced following prior exposure to high concentrations of GRF. However, it is unknown whether this is due to alterations in GRF receptors, adenylate cyclase activity or the size of a GRF-releasable storage pool of GH. In order to clarify these questions we have compared the effects of pretreatment with GRF (10 nmol/l every 2 h for 12 h) with those of pretreatment with somatostatin (SRIF; 1 mumol/l), forskolin (10 mumol/l) and GRF plus SRIF (10 nmol/l and 1 mumol/l added together) on the subsequent responses of GH to GRF (1 pmol/l-10 nmol/l), cholera toxin (10 nmol/l), 3-isobutyl-l-methylxanthine (IBMX) (100 mumol/l) and forskolin (10 mumol/l). Experiments were performed on 4-day monolayer cultures of rat anterior pituitary cells. The cells were pretreated with test substances every 2 h for 12 h and incubated with GRF or forskolin for 3 h. Per cent maximal (Bmax) GH responses to GRF (10 nmol/l) were reduced after pretreatment with both GRF (control, 173% of basal; GRF, 25% of basal; P less than 0.001) and forskolin (98% of basal; P less than 0.001), but were increased after pretreatment with SRIF (246% of basal; P less than 0.02). However, GH responses after pretreatment with GRF plus SRIF were not significantly different from those of the control.(ABSTRACT TRUNCATED AT 250 WORDS)
1-Methyl-3-isobutylxanthine↗
Growth hormone and its modulation.
Our knowledge of the mechanisms involved in the regulation of somatotroph cell growth is scanty and much work is still needed to elucidate the role of different growth factors and the mechanisms involved in oncogene activation in both normal and tumour cell growth. However, there are several recent, important clinical ramifications from our improved understanding of GH neuroregulation. The use of long-acting SS analogues is valuable in the treatment of acromegaly, probably in acute variceal haemorrhage and it also produces symptomatic improvement in patients with vipomas and glucagonomas. GHRH may be of value in the treatment of short stature due to hypothalamic GHRH deficiency but further definitive studies are now required to provide convincing evidence that this line of treatment is of greater benefit than the use of synthetic recombinant human GH. Inhibition of GH release may be of value in prevention of both acute and chronic complications of insulin-dependent diabetes mellitus. The use of cholinergic muscarinic receptor blockade in this context may be particularly useful because of a probably sparing of the counter-regulatory GH response to hypoglycaemia. In view of the relative ease with which nocturnal GH secretion can be abolished, we think it reasonable to consider the possible existence of a permissive or mediating role of GH in other disease states, either directly or by maintaining production of either local tissue or circulating growth factors or both.
Acromegaly↗
Effect of fibric acid derivatives on blood lipid and lipoprotein levels.
The literature for the last seven years was reviewed in terms of the effect of the various fibric acid derivatives on blood lipid and lipoprotein levels. The criteria for review resulted in a greater focus on three of the newer fibric acid derivatives: bezafibrate, ciprofibrate, fenofibrate. In type II A hyperlipoproteinemia, all fibric acid derivatives produce modest reductions in total plasma cholesterol and low-density lipoprotein cholesterol. The evidence suggests that bezafibrate, ciprofibrate, and fenofibrate may produce greater reductions in low-density lipoprotein cholesterol than those usually observed with clofibrate and gemfibrozil. All fibric acid derivatives produce modest reductions in triglycerides and modest increases in high-density lipoprotein cholesterol in type II A hyperlipoproteinemia. In type II B hyperlipoproteinemia, the low-density lipoprotein cholesterol lowering effect of fibric acid derivatives is generally less than that observed in type II A hyperlipoproteinemia. In type II B hyperlipoproteinemia, there is a mean decrease in low-density lipoprotein cholesterol for all patients studied. However, there is a considerable interpatient variation ranging from significant decreases to significant increases in low-density lipoprotein cholesterol. Further studies are required to assess whether the low-density lipoprotein cholesterol lowering effect is greater with the newer fibric acid derivatives. All fibric acid derivatives produce clinically significant decreases in triglyceride levels in type II B. There is also an associated increase in high-density lipoprotein cholesterol. In type IV hyperlipoproteinemia, all fibric acid derivatives produce clinically significant reductions in triglyceride. There is also an associated increase in high-density lipoprotein cholesterol and generally also an increase in low-density lipoprotein cholesterol levels. The available data do not suggest a clinically significant difference in the hypotriglyceridemic effect of the various fibric acid derivatives in type IV hyperlipoproteinemia. The lipid-altering effects of the various fibric acid derivatives were usually less in those studies that contained placebo and dietary controls. Additional controlled clinical trials are needed to accurately discriminate the relative lipid-and lipoprotein-altering effects of the various fibric acid derivatives.
Anticholesteremic Agents↗
Cholinergic muscarinic receptor blockade with pirenzepine abolishes slow wave sleep-related growth hormone release in young patients with insulin-dependent diabetes mellitus.
Cholinergic receptor blockade has been shown to abolish GH secretion in a variety of physiological and pharmacological situations in normal subjects. We have investigated the effect of pirenzepine on nocturnal GH secretion in young adult patients with Type I insulin-dependent diabetes mellitus. Five patients (three male, two female; aged 20-27 years) were studied in a randomized order on two days separated by at least 1 week. All patients showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 6-115 mU/l). In contrast, cholinergic muscarinic receptor blockade with pirenzepine (100 mg orally at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. Mean plasma glucose levels at each sampling time between each study did not differ significantly. The ability to abolish nocturnal GH secretion may be important in the field of diabetes, since excess GH secretion is implicated in several acute metabolic and chronic microvascular complications of the disease.
Adult↗