Neuropathic arthropathy of the spine in diabetes.
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Adult↗
Biomedical subjects
J R Peters
Publications and source records attributed to J R Peters.
The Eating Pattern Assessment Tool: a simple instrument for assessing dietary fat and cholesterol intake.
OBJECTIVE: This study describes the development of the self-administered Eating Pattern Assessment Tool (EPAT), which is designed to assess dietary fat and cholesterol intake and aid patients and health professionals in achieving control of blood cholesterol levels. DESIGN: Test-retest reliability of the instrument over five visits and concurrent validity testing compared with 4-day food records. SETTING AND SAMPLE: The instrument was tested at multiple sites of a large manufacturing corporation using 436 adult volunteers with approximately equal proportions of men and women from three socioeconomic levels. MAIN OUTCOME MEASURE: Development of the EPAT centered on creating an instrument that was simple and easy to use in a primary-care setting, that would provide a reliable assessment of intake of dietary fat and cholesterol among adults, and that would measure frequency of consumption of foods from high-fat and low-fat categories. ANALYSES: Test-retest reliability for repeated use was estimated by between-visit Pearson product-moment correlations of EPAT section scores. Concurrent validity was assessed by using product-moment correlation between EPAT section scores and mean daily B-scores obtained from 4-day food records. RESULTS: Test-retest reliability estimates were 0.91 between all adjacent pairs of visits and 0.83 between visits 1 and 5 (4 months). Validity was 0.56. APPLICATIONS/CONCLUSIONS: The EPAT is a simple, quick, self-administered tool using an easy scoring method for accurately assessing fat and cholesterol intake. It is a reliable and valid substitute for more time-consuming food records. EPAT also provides an efficient way to monitor eating patterns of patients over time and is arranged to provide an educational message that reinforces the consumption of recommended types and numbers of servings of low-fat foods.
Adult↗
Pituitary stone: two cases of densely calcified thyrotrophin-secreting pituitary adenomas.
Calcification is a well recognized but relatively uncommon feature of prolactin-secreting, growth hormone-secreting and non-functional pituitary tumours. It varies in extent, but rarely exceeds a tiny amount histologically or radiologically. Thyrotroph adenomas are the rarest of the secretory pituitary tumours, accounting for less than 1% of cases, and partial calcification of such lesions has been reported in only three cases. We describe two patients in whom the clinical and biochemical features indicated the presence of a TSH-secreting adenoma and radiology demonstrated a large 'pituitary stone'. One patient, a 59-year-old female, initially presented with hyperthyroidism, aged 18, and was rendered euthyroid by two subtotal thyroidectomies before a pituitary lesion was suspected, over 20 years later. Autonomous secretion of thyrotrophin was demonstrated by dynamic tests, and the failure of exogenous T3 to reduce the serum TSH. In the absence of tumour expansion and compressive symptoms, pituitary surgery was not undertaken. At the age of 56, she developed symptoms of intermittent ataxia and diplopia, culminating in a focal seizure, and was found on CT scan to have, in addition to the pituitary lesion, a parasagittal meningioma. This was successfully removed at craniotomy. In the second patient, a 42-year-old male, the finding of hyperthyroidism in association with an elevated TSH concentration led to the discovery of a pituitary stone which was removed transethmoidally, together with surrounding adenomatous tissue which stained positively for TSH on immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Acute cholinergic blockade with low dose pirenzepine reduces the insulin and glucose responses to a mixed meal in obese women with the polycystic ovary syndrome.
OBJECTIVES: Pirenzepine, a selective muscarinic cholinergic antagonist, reduces plasma insulin and plasma glucose responses to a mixed meal in a dose dependent fashion in normals and in patients with non-insulin dependent diabetes. We have studied the effects of pirenzepine on plasma insulin, plasma glucose, growth hormone (GH), androstenedione, testosterone, insulin-like growth factor-I (IGF-I) and IGF binding protein 1 (IGFBP-1) responses to a mixed meal in obese clinically hyperandrogenic women with the polycystic ovary syndrome. SUBJECTS AND METHODS: Six obese women with polycystic ovary syndrome (BMI range 27.3-39.8 kg/m2) were studied in random sequence, and received either placebo or pirenzepine (single doses of 50, 100, or 200 mg) one hour before a standard test meal. Blood was sampled every 15 minutes for 2 hours after the meal and every 30 minutes thereafter for a total of 4 hours. RESULTS: Mean fasting plasma insulin concentrations were increased. Peak post-prandial plasma insulin concentrations were reduced significantly by all three doses used. Post-prandial integrated plasma insulin concentrations were reduced by the two higher doses. Peak post-prandial plasma glucose concentrations were also reduced. The late post-prandial GH surge was significantly suppressed by all three doses. However, plasma androstenedione, testosterone, IGF-I and IGFBP-1 concentrations were not significantly different when placebo was compared with pirenzepine 200 mg. CONCLUSIONS: Acute cholinergic muscarinic blockade with pirenzepine significantly reduces meal stimulated plasma insulin and plasma glucose concentrations in clinically hyperandrogenic women with polycystic ovary syndrome. The ability of pirenzepine to reduce plasma insulin without worsening glycaemia is a particular advantage and may be therapeutically relevant. Further studies are under way to assess the usefulness of pirenzepine in long-term suppression of plasma insulin in this group of patients.
Adult↗
Urinary growth hormone measurements as a marker of renal tubular function in diabetes mellitus.
Urinary growth hormone (UGH) excretion was assessed in 44 adult subjects (10 control, 21 insulin dependent diabetics (Group I), 13 diabetics in poor glycaemic control (Group II)). UGH was markedly elevated in the diabetic population. The UGH excretion in (1) control subjects ranged from undetectable levels to 0.7 microU/h, mean 0.4, (2) Group I 73-422 microU/h, mean 250 and (3) Group II 10-5,283 microU/h, mean 705. There was a significant correlation between UGH excretion and albumin excretion rate (AER) (r = 0.38, P < 0.05) in the subjects studied although only 50% of patients had an AER of > 20 micrograms/min. A stronger correlation was observed between beta 2-microglobulin and UGH excretion (r = 0.7, P < 0.01). There was no significant change in the 6-h serum GH levels following treatment in the patients in Group II. However a 23-79% decline in UGH excretion was observed following improvement of glycaemic control, although UGH levels failed to revert to normal. We conclude that the major factor responsible for increased UGH excretion in DM appears to be reduced tubular reabsorption of the hormone. This test may therefore prove useful as an additional marker for screening for diabetic nephropathy and may help in the understanding of the contribution of renal tubular abnormalities to the nephropathic process.
Adult↗
Treatment of hyperlipidemia in heart transplant recipients with gemfibrozil +/- lovastatin.
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Female↗
Impact of initial treatment on renal function in newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus.
The impact of improved glycaemic control on renal function in newly-presenting Type 2 (non-insulin-dependent) diabetic patients has not been adequately researched. Consequently, glomerular filtration rate and effective renal plasma flow and urinary albumin excretion rates were determined in 76 subjects (age (mean (SD)): 54 (9.5) years; 50 male) of an original cohort of 110 newly-presenting normotensive non-proteinuric Type 2 diabetic patients following 6 months treatment with diet alone (n = 42) or with oral hypoglycaemic agents (n = 34). Significant reductions were observed in (presentation vs 6 months): body mass index (p < 0.001); fasting plasma glucose (p < 0.001); glycated haemoglobin (HbA1) (p < 0.001); systolic blood pressure (p < 0.01); and diastolic blood pressure (p < 0.001). Glomerular filtration rate declined from 117 (22) to 112 (21) ml.min-1 (p < 0.01), with unchanged effective renal plasma flow (534 (123) vs 523 (113) ml.min-1) and filtration fraction (22.4 (3.0) vs 21.8 (3.4)%). Albumin excretion rate (median (range)) declined from 1.1 (0.1-34.7) to 0.5 (0.1-29.9) micrograms.min-1 (p < 0.01). Changes in glomerular filtration rate (delta values) were inversely correlated with presentation values (p < 0.001), and positive relationships were observed with delta effective renal plasma flow (p < 0.01), and delta glycated haemoglobin (p < 0.05). Type 2 diabetic patients with glomerular filtration rate values at presentation over 120 ml.min-1 demonstrated significant reduction in glomerular filtration rate (n = 31; p < 0.001), whilst those with original values less than 120 ml.min-1 remained unchanged (n = 45).(ABSTRACT TRUNCATED AT 250 WORDS)
Albuminuria↗
Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils.
Several studies have implicated urinary Tamm Horsfall protein (THP) in the aetiology of tubulointerstitial inflammation. Previous research has demonstrated that particulate THP will initiate inflammatory activation of human polymorphonuclear leukocytes (PMN) through a trypsin sensitive mechanism. The present study describes the binding of 125I-monomeric THP to human PMN at 4 degrees C and demonstrates that radiolabeled THP binds to PMN in a saturable, reversible and time dependent manner. The addition of 400 to 600 ng 125I-THP/2 x 10(6) PMN was sufficient to achieve saturable binding. Scatchard analysis of binding data yielded linear plots suggesting a single class of receptors with a mean density of 26218/cell and a dissociation constant (KD) of 4.2 x 10(-9) M. Binding reached steady state by 15 minutes and could be rapidly displaced by the addition of an excess of unlabeled THP. The KD calculated from experimentally derived kinetic rate constants (k1 and k2) was of a similar order of magnitude (0.9 x 10(-9) M) to that generated from Scatchard plots. In addition 125I-THP bound specifically to PMN plasma membrane immobilized on nitrocellulose filters, a process which could be inhibited by unlabeled monomeric THP. Chemical modification of unlabeled THP abolished its capacity to inhibit binding. Specific inhibition studies showed that N-acetylneuraminic (sialic) acid dose dependently displaced the binding of 125I-THP to immobilized PMN membranes at concentrations up to 100 mM. These results indicate that the reported activation of human PMN by THP is mediated through a single class of sialic acid-specific cell surface receptors.
Carbohydrate Metabolism↗
Cholinergic control of growth hormone (GH) responses to GH-releasing hormone in insulin dependent diabetics: evidence for attenuated hypothalamic somatostatinergic tone and decreased GH autofeedback.
OBJECTIVE: We have investigated the effects of cholinergic modulation with pirenzepine and pyridostigmine and of GH pretreatment on the subsequent GH response to a maximal stimulatory dose of GH-releasing hormone (GHRH) in patients with insulin dependent diabetes mellitus (IDDM). We have also investigated the relationship between the differences in metabolic control and other parameters of disease state with the differences in GH responses in IDDM. PATIENTS: Thirteen male subjects with IDDM and no clinical evidence of complications were selected based on HbA1 levels to provide a wide range of metabolic control. Seven normal subjects were also studied. DESIGN: Twelve of the subjects with IDDM and six normal subjects received pirenzepine 200 mg and pyridostigmine 120 mg pretreatment 60 minutes and GH pretreatment 3 hours before an i.v. injection of GHRH (1-44) (80 micrograms) in random order. All subjects underwent a control study with GHRH alone. MEASUREMENTS: Serum GH and plasma glucose were measured at regular intervals throughout the study. Fasting plasma glucose and HbA1 were measured before each study to provide measures of metabolic control. RESULTS: Subjects with IDDM demonstrated exaggerated GH responses to GHRH compared to normals. Pirenzepine significantly reduced GH responses in both normal and diabetic subjects. However, the GH response to GHRH after pirenzepine was higher in subjects with IDDM (mean GH:IDDM vs normals; 8.1 +/- 1.3 vs 2.9 +/- 0.7 mU/l, P < 0.05). Pyridostigmine 120 mg significantly augmented the GH response to GHRH in normal subjects. In diabetic subjects, pyridostigmine failed to increase GH response to GHRH compared to GHRH alone (mean GH: pyridostigmine vs control: 75.7 +/- 12.6 vs 38.9 +/- 5.4 mU/l, P = NS). GH responses to GHRH after pyridostigmine pretreatment in both normal and diabetic subjects did not differ and the GH response to GHRH after pyridostigmine in normal subjects did not differ from the GH response to GHRH alone in diabetic subjects. In normal subjects, GH pretreatment significantly reduced subsequent GH responsiveness to GHRH (delta peak GH 26.4 +/- 5.2 vs 7.7 +/- 5.4 mU/l, P < 0.04). In contrast, GH pretreatment did not cause any significant reduction in GH responsiveness to GHRH in diabetics (delta peak GH 53.6 +/- 9.7 vs 33.4 +/- 11 mU/l, P = NS). No significant correlation was demonstrated between measures of diabetic control and the responses to GHRH alone or after cholinergic modulation and GH pretreatment. CONCLUSION: These data suggest that ambient hypothalamic cholinergic tone in diabetes is high, and of similar degree to the enhanced cholinergic tone in normal subjects pretreated with pyridostigmine. We suggest that in diabetic subjects, the reduced responsiveness to autofeedback may be secondary to the enhanced cholinergic tone demonstrated in these patients. The mechanisms linking the uncontrolled diabetic state to this abnormal neuroregulation of GH remains unknown at present.
Adult↗
Preservation of renal haemodynamic response to an oral protein load in non-insulin-dependent diabetes mellitus.
Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) were determined, for 2 h prior to and 3 h following the ingestion of a 1.2 g kg-1 meat meal, in seven normotensive normoalbuminuric Type 2 diabetic patients exhibiting good glycaemic control (fasting plasma glucose (mean +/- SD): 7.2 +/- 2.0 mmol l-1; glycosylated haemoglobin: 8.1 +/- 1.7%) and in nine normal subjects selected for similar basal GFR values. Baseline GFR and ERPF (corrected to 1.73 m2 surface area) were 83 +/- 10 and 410 +/- 76 ml min-1 for the Type 2 diabetic patients and 86 +/- 11 and 405 +/- 113 ml min-1 for the normals. GFR increased by 38 +/- 8 and 32 +/- 15% in the diabetic patients and normals, to 108 +/- 25 and 105 +/- 26 ml min-1 (p < 0.01 vs baseline). Peak ERPF was 501 +/- 127 and 476 +/- 119 ml min-1 for the two respective groups (p < 0.01 vs baseline). Filtration fractions at peak GFR and EPRF values were unchanged from baseline for either groups. Fractional clearance of albumin for the Type 2 diabetic patients was unaltered by protein ingestion. Therefore, protein ingestion in Type 2 diabetes, as in normals, results in an acute elevation of GFR. Absolute and incremental changes in GFR were identical for the two groups. These data demonstrate a preserved capacity for renal vasodilatation in Type 2 diabetic patients despite their greater chronological age.
Adult↗
Absorption of radiolabelled soluble insulin in type 1 (insulin-dependent) diabetes: influence of subcutaneous blood flow and anthropometry.
The rate of absorption of soluble insulin, and its relationships with subcutaneous blood flow (SCBF) and patients' anthropometry, were investigated in 12 male Type 1 (insulin-dependent) diabetic patients of less than 10 yr disease duration (age range: 23-29 yr; body mass index (BMI): 22.2-30.8 kg m-2). Simultaneous assessment of the absorption of 125I-labelled soluble insulin and SCBF (99mTechnetium clearance) were performed, on separate study days, for the anterior abdominal wall, anterior mid-thigh, and the upper arm injection sites. Absorption of 125I soluble insulin, including during the lag-phase, was determined by the two- and three-parameters biexponential models description of residual radioactivity levels at the injection site. Anthropometric measurements utilized were: BMJ, ultrasonic measurement of the subcutaneous adipose tissue layer, and caliper skinfold thickness at anterior abdominal wall, biceps, triceps, anterior mid-thigh and subscapular sites. Rate-constants for absorption of soluble insulin were positively correlated with SCBF (Spearman rank coefficient (rs) = 0.33-0.55; p < 0.01-0.001). An inverse relationship was observed between the duration of the lag-phase and SCBF (rs = -0.28 - -0.54; p < 0.05-0.001). Patients' degree of adiposity was inversely correlated with the rate of soluble insulin absorption (rs = -0.24 - -0.28; p < 0.05) and SCBF (rs = -0.28 - -0.43; p < 0.05-0.001). Consequently, faster absorption of soluble insulin, with shorter lag-phase duration, was noted for the abdominal and thigh sites for non-obese (BMI > 25 kg m-2) than obese patients (BMI < 27.5 kg m-2) (p < 0.05-0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adsorption↗
The ethics of itemised payment for clinical research procedures.
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Ethics, Professional↗
Factors influencing the development of hypercholesterolemia after cardiac transplantation.
Although hypercholesterolemia is a frequent complication in cardiac transplant recipients, the exact mechanisms contributing to its development are not known. Cholesterol levels in 151 thoracic transplant patients treated with cyclosporine, azathioprine and prednisone were retrospectively examined to evaluate the factors influencing the heterogeneity of changes after the first year after transplantation in patients on a standard 3-drug immunosuppression regimen. Three groups were compared including ischemic heart transplant (n = 72), nonischemic heart transplant (n = 64) and heart-lung/lung transplant (n = 15) recipients. After the first year, 64 patients (43%) developed consistent hypercholesterolemia (greater than 240 mg/dl) for which pharmacologic treatment was initiated. Forty-eight patients (67%) in the ischemic heart transplant group required treatment, significantly (p less than 0.001) greater than both the nonischemic (n = 14; 22%) and heart-lung/lung transplant (n = 2; 13%) group. Univariate and forward stepwise multivariate regression analysis identified 4 factors that were all significantly and independently correlated with follow-up cholesterol including prednisone dose (p less than 0.001), baseline cholesterol (p less than 0.001), glucose (p less than 0.001) and weight gain (p less than 0.01). Changes in triglycerides in the 3 groups of patients were similar to changes in cholesterol. Furthermore, the increase in cholesterol in patients requiring treatment was primarily due to an increase in low-density lipoprotein cholesterol. These data demonstrate that hypercholesterolemia is common in heart transplant recipients treated with standard 3-drug immunosuppression and generally develops within the first 2 years after transplantation. However, this complication is not uniform and appears to be most strongly related to previous coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
5-[3H]hydroxytryptamine and [3H]lysergic acid diethylamide binding to human platelets.
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Binding, Competitive↗
Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus.
Little information is available regarding renal hemodynamics in non-insulin dependent diabetics (NIDDMs), despite their numerical significance to renal support programs. Therefore, simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (expressed to 1.73 m2 surface area) was performed in 110 newly presenting normotensive NIDDMs [mean (SD) age: 52.5 (10.1) years] and compared with 32 normal subjects of similar age range [age: 52.2 (11.3) years]. Mean (SD) GFR, ERPF and filtration fraction (FF) for the NIDDMs were: 117 (22) ml/min (range: 74 to 178), 534 (123) ml/min and 22.4 (3.0)%, and for the normals: 95 (12) ml/min (range: 75 to 119), 472 (70) ml/min and 20.2 (2.2%), respectively. As a group, NIDDMs demonstrated significantly greater GFR (P less than 0.001), ERPF (P less than 0.005) and FF (P less than 0.001). GFR values above 140 ml/min were observed in 16% of the NIDDMs, while 45% had GFRs in excess of mean +/- 2 SD of the normals. NIDDMs demonstrated a positive relationship for GFR with ERPF (P less than 0.001) and an inverse association for both GFR and ERPF with age (P less than 0.001). Multivariable regression analysis revealed ERPF as the strongest explanatory variable for GFR in the NIDDMs (P less than 0.001), followed by age (P less than 0.01). Significant contributions to the regression analysis were not observed for body mass index, systolic or diastolic blood pressures, glycosylated hemoglobin nor fasting levels of plasma glucose, cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides. Urinary albumin excretion rates were not correlated with GFR, ERPF or FF. Microalbuminuria was detected in 7% of the NIDDMs in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Mellitus, Type 2↗
Appropriate days for measuring intake of dietary fat and cholesterol.
Seven consecutive day food records were assessed in 224 free-living adult volunteers to (1) identify the smallest number of days, and which days of the week, would provide most of the information about dietary fat and cholesterol intake (assessed by B score) and (2) whether a complex mathematical formula for weighting certain days was required to achieve reasonable validity. A factor analytic approach was used to identify 3- and 4-day sets. The correlations with the 7-day average B score ranged from 0.95 for the best 4-day (Saturday through Tuesday) average B score to 0.91 for the best 3-day (Sunday through Tuesday) average B score. Simple averaging (no weighting) was found to be adequate to achieve this level of validity.
Adult↗
Relationship between absorption of radiolabeled soluble insulin, subcutaneous blood flow, and anthropometry.
OBJECTIVE: To evaluate the interrelationships between the rate of absorption of soluble insulin, SCBF, and anthropometry in normal subjects. RESEARCH DESIGN AND METHODS: In 12 normal men (age range 23-30 yr, BMI 18.2-41.3 kg/m2), simultaneous assessment of the absorption of 125I-labeled soluble insulin and SCBF (99mTc clearance) was performed, on separate study days, for the anterior abdominal wall, anterior midthigh, and the upper arm sites. Each site was examined in a randomized order on two separate occasions. Absorption of 125I-soluble insulin was determined by external monitoring of residual radioactivity levels at the injection site for 6 h postinjection. Residual radioactivity level-time curves, including the characteristic early phase of slow absorption of soluble insulin (the lag phase), were described using two- and three-parameter biexponential models. Anthropometric measurements included BMI, ultrasonic measurement of the subcutaneous adipose tissue layer, and caliper skin fold thickness at the anterior abdominal wall, biceps, triceps, anterior midthigh, and subscapular sites. RESULTS: A highly significant positive relationship was observed between the rate of absorption of 125I-soluble insulin and SCBF (rS = 0.44-0.52; P < 0.01-0.001). The duration of the lag phase was inversely correlated with SCBF (rS = 0.34 - 0.51; P < 0.01-0.001). Inverse relationships also were observed for the subjects' degree of adiposity with the rate of soluble insulin absorption (rS = -0.43(-)-0.71; P < 0.001) and SCBF (rS = -0.27(-)-0.62; P < 0.05-0.001). Significantly shorter lag phase was observed for the abdominal site compared with thigh and arm injection sites (P < 0.05-0.01). CONCLUSIONS: The rate of absorption of soluble insulin, including during the lag phase, is positively correlated with SCBF. Increasing adiposity prolongs the duration of the early lag phase and reduces the rate of absorption of soluble insulin and SCBF.
Absorption↗
Intense dietary counseling lowers LDL cholesterol in the recruitment phase of a clinical trial of men who had coronary artery bypass grafts.
Intense dietary counseling lowered low-density-lipoprotein (LDL) cholesterol levels during the recruitment phase of a 5-year clinical trial of men who had undergone coronary artery bypass grafts. At visit 1, a 24-hour dietary recall was obtained and analyzed for intakes of total energy; total, saturated, monounsaturated, and polyunsaturated fat; and dietary cholesterol. Participants were then instructed to follow the National Cholesterol Education Program (NCEP) Step I diet. Additional dietary counseling was provided at 1-month intervals during visits 2 and 3. At visit 3, another 24-hour dietary recall was obtained and analyzed similarly. Of 59 men with an LDL cholesterol level greater than 4.5 mmol/L at visit 1, 52 decreased their level to 4.5 mmol/L or less to qualify for the 5-year study. Between visits 1 and 3, mean LDL cholesterol levels decreased significantly from 4.86 +/- 0.04 mmol/L to 4.27 +/- 0.05 mmol/L, which coincided with significant mean decreases in dietary intake of total fat from 33.4 +/- 1.3% to 25.2 +/- 1.4%, saturated fat from 11.1 +/- 0.6% to 7.0 +/- 0.4%, and dietary cholesterol from 122 +/- 6.1 to 90 +/- 6.3 mg/1,000 kcal. Overall, the dietary intake improved to more closely follow the NCEP Step II diet and resulted in a 10.7% decrease in total cholesterol level and a 12.4% decrease in LDL cholesterol level.
Adult↗