Biomedical subjects

S Cataland

Publications and source records attributed to S Cataland.

At least 19 recordsLinked to original sources

PubMed2006

A rapid test for the diagnosis of thrombotic thrombocytopenic purpura using surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF)-mass spectrometry.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a life-threatening thrombotic microangiopathy, requires immediate diagnosis and plasma exchange therapy. Development of TTP is related to functional deficiency of ADAMTS-13 protease that leads to the accumulation of ultra large von Willebrand factor (VWF) and subsequent platelet thrombosis. Currently no clinical test is available for the rapid detection of ADAMTS-13 activity. OBJECTIVES: The goal is to devise a novel method to rapidly detect functional activity of ADAMTS-13 and improve clinical outcome. METHODS AND RESULTS: A recombinant VWF substrate containing the ADAMTS-13 cleavage site and a 6X Histidine tag was cleaved by ADAMTS-13 in a dose-dependent manner, generating approximately 7739 Da peptide containing a 6X Histidine tag. This cleaved peptide, bound to an IMAC/Nickel ProteinChip, was quantified using Surface Enhanced Laser Desorption/Ionization Time-of-flight Mass Spectrometry (SELDI-TOF-MS). The assay is capable of quantifying ADAMTS-13 activity as low as 2.5% in plasma within 4 h. When the cleaved peptide was quantified as a ratio of an internal control peptide, the test displayed good reproducibility, with an average inter-assay coefficient of variation (CV) of < 33%. Further validation revealed a mean ADAMTS-13 activity of 92.5% +/- 16.6% in 39 healthy donors. Sixteen patients with idiopathic TTP displayed mean ADAMTS-13 activity of 1.73% +/- 3.62%. Further utility of this novel method includes determining the inhibitory titer of ADAMTS-13 antibody in cases of acquired TTP. CONCLUSIONS: We have devised a novel SELDI-TOF-MS assay that offers a rapid, cost-effective, and functionally relevant test for timely diagnosis and management of TTP.

ADAM Proteins↗

PubMed1995

The Semmes-Weinstein monofilament as a potential predictor of foot ulceration in patients with noninsulin-dependent diabetes.

The objective was to evaluate the Semmes-Weinstein monofilament as a potential predictor of foot ulceration. A case-control study was carried out in a teaching hospital clinic specializing in diabetes and hyperlipidemic disorders. Two groups of patients with noninsulin-dependent diabetes mellitus were studied: 168 with no history of foot lesions (No-Ulcer group, aged 58.1 +/- 9.7 years, duration 11.5 +/- 7.8 years) and 14 who had at least one foot ulceration during the last year (foot ulcer group, aged 60.8 +/- 7.8 years', duration 17.1 +/- 10.5 years). The authors defined and measured a "monofilament index" using a size 5.07 Semmes-Weinstein monofilament on three locations on each foot and then measured peroneal nerve current perception thresholds using the Neurometer at three frequencies: 5 Hz, 250 Hz, and 2,000 Hz. The monofilament index score was lower in patients in the foot ulcer group than in patients in the No-Ulcer group (1.71 +/- 2.36 vs 5.21 +/- 1.81, P < 0.001). A cutoff point at an index of 5 out of 6 yielded a sensitivity rate of 85.71% and a false-positive rate of 16.07%. The peroneal nerve current perception threshold was higher (P < 0.005) in patients in the foot ulcer group than in patients in the No-Ulcer group for all frequencies (605.8 +/- 414.6 vs 181.5 +/- 272.3 for 5 Hz; 743.2 +/- 361.7 vs 251.6 +/- 283.7 for 250 Hz; 859.4 +/- 220.2 vs 423.3 +/- 252.6 for 2,000 Hz). (ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Continuous subcutaneous octreotide infusion: dose-response relationships between metabolic effects and octreotide clearance in patients with insulin-dependent (type 1) diabetes.

Octreotide (Sandostatin), a potent and long-acting octapeptide analogue of somatostatin, exhibits variable metabolic effects in type 1 diabetes. We have postulated that interindividual variability in octreotide metabolism could be responsible in part for the differences in metabolic responses reported in previous clinical studies. To this end, we determined plasma levels and MCR of octreotide during 24-hour continuous SC infusion (low dose, 200 micrograms; high dose, 400 micrograms) in nine female, C peptide-negative patients with type 1 diabetes. The metabolic effects of the analogue were assessed by measuring serum glucose, free insulin, glucagon, GH, and PP levels before and at 1- to 2-hour intervals during each dose of the analogue or control (0.9% saline solution) infusion in a single-blind randomized manner. Mean daytime (0800-0000 hours) and bedtime (0000-0800 hours) serum glucose levels decreased significantly (p less than 0.05 to 0.02) during analogue therapy compared with control. Mean serum free insulin levels were significantly (p less than 0.02) greater during octreotide infusion compared with control, despite the similar daily insulin requirements. Both doses of the analogue effectively suppressed 24-hour GH by 50%, glucagon by 50%, and PP by 80%. Steady-state octreotide levels varied considerably among patients (low, mean +/- SEM), 1000 +/- 101, range 638 to 1375 pg/ml; high, mean 1940 +/- 147, range 1032 to 2462 pg/ml). Although mean MCR values were similar with both doses, we observed greater interindividual variability (low, mean 2.45 +/- 0.30, range 1.31 to 3.78 ml/kg/min; high, mean 2.36 +/- 0.19, range 1.68 to 3.48 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1989

Metabolic effects of long-acting somatostatin analogue (sandostatin) in type I diabetic patients on conventional therapy.

We evaluated the effectiveness of a more potent and longer-acting somatostatin analogue (SMS 201-995) as an adjunct to insulin therapy, in a double-blind placebo-controlled randomized study of 26 C-peptide-negative type I (insulin-dependent) diabetic patients (20 women, 6 men, aged 22-40 yr) on their conventional drug regimens for 12 wk. Eight patients received a low dose (10 micrograms) of the analogue, 9 received a high dose (50 micrograms) of the analogue, and 9 received placebo subcutaneously before breakfast and dinner. Twenty-four-hour serum glucose, free insulin, plasma growth hormone (GH), and glucagon profiles were obtained before and during treatment at 4-wk intervals. The mean age, duration of diabetes, daily insulin dose, and body weight were not significantly different among the groups. The mean weekly capillary blood glucose values and exogenous insulin requirements were not changed by the SMS 201-995 therapy. Mean glycosylated hemoglobin A1 levels were unchanged in both the analogue- and placebo-treated groups at wk 12. Basal and postprandial glucose, free insulin, GH, and glucagon profiles were not influenced by the SMS 201-995 therapy throughout the study. Nocturnal glucose turnover rates (D-[3-3H]glucose technique) remained unaltered by the analogue therapy. Dose-dependent gastrointestinal (GI) adverse effects (e.g., diarrhea) were documented in the analogue-treated patients. Visual acuity and fundic photomicrographs of our patients were not changed by the analogue therapy. In conclusion, the prominent adverse GI effects our patients experienced preclude the use of larger doses of the analogue that may be necessary to suppress GH and glucagon and improve glucose control in type I diabetic patients.

Adult↗

PubMed1987

Absence of hepatic extraction of gastric inhibitory polypeptide in conscious dogs.

Fractional hepatic extraction of gastric inhibitory polypeptide was examined in conscious unrestrained dogs with catheters in the portal vein, hepatic vein, and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. Following a control period, endogenous gastric inhibitory polypeptide was stimulated by oral administration of glucose with and without prior infusion of atropine. In other experiments, gastric inhibitory polypeptide (20 ng/kg/min) was infused into the portal system in association with peripheral infusion of glucose. In none of these experiments was it possible to demonstrate any significant fractional hepatic extraction of gastric inhibitory polypeptide.

Animals↗

PubMed1987

Comparison of the effects of continuous subcutaneous infusion and split-mixed injection of insulin on nerve function in type I diabetes mellitus.

Comparable groups of type I diabetic patients (n = 19) were matched for age, duration of diabetes, mean HbA1 values, insulin requirements, degree of neuropathy, and the mean of nerve conduction velocities (CV) in median, ulnar, and peroneal motor and median, ulnar, and sural sensory nerves. One group (n = 9) was managed with continuous subcutaneous infusion of (regular) insulin (CSII); the other (n = 10) with split-mixed injections of (intermediate and regular) insulin (SMII). After 12 months, glucose regulation was equally and significantly improved in both groups (P less than 0.005), although it was not sufficiently intense to normalize mean total glycosylated hemoglobin values in either group. Furthermore treatment produced no difference between groups in the values for mean amplitude of glycemic excursions, 12 month average of consecutive M-values or in clinical evaluation. However, in the CSII group, mean CV had increased 6.4% (2.75 + 0.56 m/s; mean +/- SEM) versus 1.3% (0.57 +/- 0.54 m/s) in the SMII group (P less than 0.005). Multivariate analysis on a nerve-by-nerve basis found significantly improved conduction in 2/6 nerves (median motor; ulnar sensory) in the CSII group compared to the SMII group. These results suggest that CSII may provide a more favorable microenvironment for nerve repair.

Adult↗

PubMed1986

Exercise adaptation responses for gastric inhibitory polypeptide (GIP) and insulin in obese children. Possible extra-pancreatic effects.

Thirteen obese children and matched controls were fed a mixed meal, and responses were evaluated at fixed intervals for glucose, insulin, and gastric inhibitory polypeptide (GIP). The obese children were evaluated before and within 48 h after completion of a 5-mo exercise training program (ETP). The ETP included three aerobic exercise sessions per week and modest diet restrictions. Caloric expenditure was increased by approximately 300 kcal/exercise session. Weight gain was minimal over the 5 mo. An unexpected increase in GIP response and improved insulin tolerance were recorded for the obese children post-ETP. GIP values were higher (P less than 0.05) at 30 and 60 min and led to a highly significant elevation (P less than 0.01) of the integrated GIP response for post-ETP obese versus both pre-ETP and normal-weight controls. Insulin values were lower (P less than 0.05) at 30 and 60 min and led to a lower integrated insulin response (P less than 0.0585) for post-ETP obese children. However, the obese children continued to secrete more insulin (P less than 0.05) than normal-weight controls. Glucose tolerance, similar for pre-ETP obese subjects and controls, did not change in post-ETP children. Exercise-induced improvement in glucose utilization in these obese children was associated with an increase in GIP secretion. This contrasts with reports that calorie restriction will improve glucose utilization with decreased insulin and GIP secretion. The study demonstrates a previously unreported uncoupling of GIP and insulin secretion and suggests shifts in peripheral tissue sensitivity to insulin-induced glucose uptake. These shifts may, in part, be influenced by GIP.

Adolescent↗

PubMed1985

Abnormal retinal artery responses to stress in patients with type I diabetes.

The brachial artery pressure and retinal artery pressure responses to a one-minute cold pressor test were evaluated simultaneously in 14 patients with type I diabetes mellitus (six with and eight without diabetic retinopathy) and 10 age-matched control subjects. Five patients with type I diabetes had autonomic neuropathy. Mean baseline brachial artery pressure and retinal artery pressure were similar in patients with type I diabetes and control subjects. After cold pressor testing, the brachial artery pressure increased significantly (p less than 0.01) compared with baseline values in both groups. Retinal mean arterial pressures increased significantly (p less than 0.001) after cold pressor testing compared with the baseline values only in patients with type I diabetes. Positive correlation was found between the brachial and retinal mean arterial pressures after cold pressor testing (r = 0.48; p less than 0.05) in the diabetic patients but not in the control subjects (r = 0.10; p = NS). No correlation was found between the retinal artery pressure and age of onset of diabetes, duration of diabetes, the presence or absence of diabetic retinopathy, and glycemic control. Four patients with autonomic neuropathy and low retinal artery pressures, which remained unchanged after cold pressor testing, had no diabetic retinopathy. The fifth patient with autonomic neuropathy and exaggerated systolic brachial artery pressure (175 mm Hg) and retinal artery pressure (more than 80 mm Hg) responses had severe background diabetic retinopathy. In conclusion, abnormal retinal artery responses to stress are present in patients with type I diabetes. This may be modified by the presence or absence of both autonomic neuropathy and hypertension. The biologic significance of these findings is yet to be determined.

Adult↗

PubMed1985

Theoretical basis for a new in vivo radioreceptor assay for polypeptide hormones.

To date the in vivo identification and quantitation of specific hormone receptors has been difficult, time consuming, and lacking in sensitivity. We present the theory underlying a new in vivo radioreceptor assay for polypeptide hormones based on receptor theory derived from in vitro investigations and in vivo kinetic and autoradiographic studies. The assay was developed from a tissue model and a theory of hormone distribution. Measuring the labeled hormone distributed between the plasma and interstitial space in the presence or absence of excess unlabeled hormone permits the accurate determination of hormone specifically bound to receptors. This approach eliminates the problem of nonspecific binding due to free tracer, hormone degradation products, or labeled non-hormone molecules. A receptor compartment and specific binding of hormone are calculated from only four measured parameters: total tissue labeled hormone, tissue albumin, plasma labeled hormone, and plasma albumin. The method is applicable to most tissues and hormones under a variety of conditions and permits simultaneous comparison of multiple tissues in the same animal under identical conditions.

Albumins↗

PubMed1985

Identification of tissue insulin receptors: use of a unique in vivo radioreceptor assay.

An in vivo radioreceptor assay for polypeptide hormones has been developed and applied to the identification of tissue insulin receptors. The theoretical basis for this assay is presented elsewhere in this issue. 125I-insulin and 131I-albumin were infused into male rats with increasing amounts of unlabeled insulin. Plasma samples were taken at 1-min intervals until the animals were killed at 5 min. Tissue samples were excised and weighed and the activity due to each isotope counted. By comparing the differential distribution of the labeled tracers and applying the results to a compartment model, the specific, displaceable binding of insulin to tissue receptors could be demonstrated. Binding was detected in the liver, muscle, fat, adrenal glands, pancreas, small intestines, and spleen.

Adrenal Glands↗

PubMed1985

Production of 12-hydroxyeicosatetraenoic acid and vitamin E status in platelets from type I human diabetic subjects.

Vitamin E content and biosynthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) have been measured in platelets from type I diabetic subjects and age- and sex-matched, nondiabetic control subjects. Platelets from diabetic subjects synthesized significantly greater quantities of 12-HETE than did platelets from control subjects when 12-HETE synthesis was induced by thrombin or collagen, either in the presence or absence of indomethacin. Platelet conversion of exogenously added arachidonic acid (AA) to 12-HETE was not significantly different between the diabetic and control groups in the absence of indomethacin, although a small but significant increase in the conversion of AA to 12-HETE was present in the diabetic group platelets when indomethacin was added to the reaction. Vitamin E content was significantly reduced in platelets from the diabetic subjects, when compared with platelets from the control subjects, although plasma vitamin E levels were not significantly different between the two groups. Thrombin- and collagen-induced platelet 12-HETE synthesis demonstrated a significant negative linear correlation with platelet vitamin E content when measurements from both diabetic and control groups were combined. The above data suggest a relationship between low vitamin E content and increased 12-HETE synthesis in platelets from type I diabetic subjects.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1985

Action of platelet-activating factor on type 1 diabetic human platelets.

Platelets from patients with type 1 diabetes have exhibited more sensitivity to aggregation when compared with platelets from controls without diabetes after challenge with platelet-activating factor (PAF). The production of thromboxane B2 (TxB2) and 12-hydroxyeicosatetraenoic acid (12-HETE) and the release of 5-hydroxytryptamine (5HT) were increased when the platelets were challenged by PAF (5.0 X 10(-6) mol/L and 1.0 X 10(-6) mol/L). The production of TxB2 and 12-HETE and the release of 5HT were related to the irreversible biphasic aggregation profiles observed in the patients with diabetes. Inhibition of thromboxane A2 (TxA2) production by acetylsalicylic acid abolished the secondary wave of aggregation of platelets from patients with diabetes, changing an irreversible aggregation to a reversible one. Inhibition of both TxA2 and 12-HETE production by eicosatetraynoic acid did not contribute further to the inhibition caused by acetylsalicylic acid alone, indicating that 12-HETE was not involved in the secondary wave of aggregation. These data show that the increased aggregation observed in the platelets from the group with diabetes in response to PAF results in part from their higher production of TxA2 and release of 5HT.

Adult↗

PubMed1984

Interrelation of platelet vitamin E and thromboxane synthesis in type I diabetes mellitus.

Platelet vitamin E content and thromboxane A2 (TxA2) synthesis have been investigated in type I diabetic subjects and age- and sex-matched controls. Platelets, but not plasma, from diabetic subjects contained significantly lower vitamin E levels and synthesized significantly greater amounts of TxA2 when challenged with collagen or thrombin than platelets from control subjects. Conversion of exogenously added arachidonic acid to TxA2 was unaltered between platelets from control and diabetic groups. Platelet vitamin E content from control and diabetic groups combined exhibited a significant negative linear correlation with collagen- and thrombin-induced TxA2 production. These data suggest that low platelet vitamin E levels could be a contributing factor to the increased thromboxane synthesis demonstrated by platelets from the above type I diabetic subjects.

Adult↗

PubMed1983

Diabetic nephropathy. Clinical course in patients treated with the subcutaneous insulin pump.

Twelve type I diabetic patients with established diabetic nephropathy were treated for 12 months with the insulin pump to determine whether glucoregulation would influence the clinical course of proteinuria. All of the subjects were known to have arterial hypertension and were receiving antihypertension medication. Despite good glucose control, as assessed by total glycosylated hemoglobin level, two clinical courses were observed: six patients demonstrated a progression in proteinuria and six appeared to experience a reduction in proteinuria. The group demonstrating a progression had significantly higher mean arterial pressure at six and 12 months of study compared with the group with a reduction in proteinuria. These results suggest that arterial hypertension is an important risk factor in the progression of diabetes nephropathy. Further studies should be designed to recognize early proteinuria and hypertension to determine whether mean normal glucose values and BP over a prolonged period will prevent renal failure.

Adult↗

PubMed1983

Postprandial release of gastric inhibitory polypeptide (GIP) and pancreatic polypeptide in dogs with pancreatic acinar atrophy. Correction of blunted GIP response by addition of pancreatic enzymes to a meal.

In order to evaluate the enteropancreatic hormone axis in dogs with pancreatic acinar atrophy, we measured the release of gastric inhibitory polypeptide and pancreatic polypeptide in response to a standard meal and a meal containing pancreatic enzymes in affected dogs and controls. Postprandial release of pancreatic polypeptide was normal in dogs with pancreatic atrophy and was not affected by addition of pancreatic enzymes to the food. Gastric inhibitory polypeptide was not released after a standard meal in affected dogs, but this blunted response was corrected by the addition of pancreatic enzymes to the food. Feeding the enzyme alone did not stimulate a gastric inhibitory polypeptide response. These results, in part, support similar observations previously reported in children with exocrine pancreatic insufficiency associated with cystic fibrosis. We conclude that dogs with idiopathic pancreatic acinar atrophy can be used as an animal model for future study of enteropancreatic hormonal abnormalities that occur in human beings with exocrine pancreatic insufficiency.

Animals↗

PubMed1983

Blood insulin, glucose, fructose and gastric inhibitory polypeptide levels in carbohydrate-sensitive and normal men given a sucrose or invert sugar tolerance test.

Twelve carbohydrate-sensitive and 12 normal men were selected for the study. Carbohydrate-sensitivity was based on an abnormal insulin response to a sucrose load. The subjects were fed a diet consisting of 45% of the calories as carbohydrate, 40% fat and 15% protein for 5 days prior to a sucrose or invert sugar tolerance test. In a crossover design, subjects were given 2 g/kg body weight of sucrose or invert sugar, and responses of insulin, glucose, fructose and gastric inhibitory polypeptide (GIP) were determined. Blood samples were taken at 0, 0.5, 1, 2 and 3 hours after being given the test loads. Insulin and glucose levels were significantly higher in carbohydrate-sensitive as compared to normal men. Glucose and GIP did not show any significant differences between the two carbohydrate loads. At 1 hour, the carbohydrate-sensitive men given sucrose had significantly higher insulin levels than carbohydrate-sensitive men given invert sugar (disaccharide effect). At 1, 2 and 3 hours, the disaccharide effect was shown in the fructose levels of the carbohydrate-sensitive men. In normal men, the disaccharide effect with levels of fructose was seen at 0.5 and 3 hours. This study indicates that the disaccharide effect on blood insulin cannot be explained by differences in gastric inhibitory polypeptide in unadapted human subjects.

Adult↗

PubMed1983

Pancreatic polypeptide responses to protein meal challenges in obese but otherwise normal children and obese children with Prader-Willi syndrome.

Children with hyperphagia and obesity of Prader-Willi syndrome (PWS) have previously been shown to have blunted pancreatic polypeptide (PP) response to low protein meal stimulation. To evaluate the effects of various protein challenges on PP release in children with PWS, we administered both a low protein (0.2 g/kg) and a high protein (2.0 g/kg) meal stimulation test to 12 children previously diagnosed as having PWS and to an age- and weight-matched group of 19 obese but otherwise normal children. Serum samples were collected just before and for 3 h after meal ingestion. The mean (+/- SD) age was 11.7 +/- 4.2 yr for the PWS group and 10.3 +/- 3.8 yr for the obese group (P = 0.323). The percent ideal body weight for height for the PWS group (mean +/- SD 186 +/- 48%) was not significantly different from the percent ideal body weight for height for the obese group (174 +/- 35%; P = 0.421). Peak PP responses were significantly less for the PWS group than for the obese group for both the low and high protein meal stimulations. The mean (+/- SE) peak PP response with the low protein meal was 76.1 +/- 13 pg/ml for the PWS group and 302 +/- 93 pg/ml for the obese group (P less than 0.05). The mean peak response with the high protein meal was 181 +/- 51 pg/ml for the PWS group and 581 +/- 127 pg/ml for the obese group (P less than 0.01). Glucose rises were similar for both tests, although the PWS group did have a slightly smaller rise in glucose after the low protein stimulation than was observed in the obese group. The insulin response was also significantly less for the low protein meal in the PWS group compared to the low protein insulin response of the obese group. There were no significant differences in the insulin responses observed in both groups with the high protein meal test. This study confirms our previous observation and suggests that many children with PWS have a functional deficiency of PP. Our current study demonstrates that this condition is not a result of their obese condition or an alteration in their response threshold to protein.

Adolescent↗

PubMed1983

Gastric inhibitory polypeptide (GIP) release by actively transported, structurally similar carbohydrates.

Six awake adult dogs prepared with a duodenocutaneous fistula were infused intraduodenally with one of the following solutions: 3% saline, 10% glucose, 20% glucose, 20% galactose, 20% fructose, 20% mannose, 20% sorbitol, 20% maltose, 20% lactose, or 20% sucrose. Both 10 and 20% glucose stimulated GIP release, and the response appeared to be dose related. Actively transported galactose (C-4 epimer) stimulated GIP release, but less than glucose. Fructose (C-2 keto sugar) which is absorbed by facilitated transport did not stimulate GIP release. Mannose (C-2 epimer) which is passively absorbed by diffusion did not release GIP. Sorbitol (reduced alcohol of glucose) which is not absorbed did not release GIP. Of the disaccharides tested, only maltose stimulated the release of GIP. The results suggest that structural integrity of the glucose molecule from the C-1 to C-4 carbon atoms, a free aldehyde group on the C-1 carbon atom, and a cyclic structure are all necessary for both the active transport of glucose and the release of endogenous GIP. It would appear that structurally similar receptors exist for both the active transport of glucose and for the release of GIP.

Animals↗