Foot pressure measurements in diabetic and nondiabetic amputees.

OBJECTIVE--Foot problems are common in the remaining foot of diabetic amputees. Because high foot pressures are associated with foot ulceration, we studied foot pressures of the remaining foot of diabetic and nondiabetic unilateral amputees. RESEARCH DESIGN AND METHODS--Four age-matched groups of 11 subjects were studied. The groups were comprised of diabetic subjects with previous major amputation, nondiabetic nonneuropathic amputees, diabetic nonamputee patients with similar peripheral nerve involvement as the diabetic amputees, and nondiabetic control subjects. Vibration perception threshold (VPT) was assessed by biothesiometry and foot pressures with an optical pedobarograph. RESULTS--Mean +/- SE VPT in the diabetic amputees was significantly higher than the nondiabetic amputees (40.2 +/- 3.7 vs. 17.7 +/- 2.8 V, P less than 0.002) and similar to diabetic nonamputees (43.4 +/- 3.3 V, NS). VPT was abnormal in 9 (82%) diabetic amputees, 2 (18%) nondiabetic amputees, and 10 (91%) nonamputee diabetic patients. The mean peak foot pressure in the diabetic amputees was higher compared with nondiabetic amputees (18.3 +/- 2.2 vs. 11.3 +/- 1.4 kg/cm2, P less than 0.05) and control subjects (10.0 +/- 1.5 kg/m2, P less than 0.01), but no difference existed with diabetic nonamputees. Abnormally high foot pressures (greater than 12.3 kg/cm2) were present in 8 (73%) diabetic amputees, 3 (27%) nondiabetic amputees, 8 (73%) diabetic nonamputees, and 4 (36%) healthy subjects. CONCLUSIONS--We conclude that high pressures are present under the remaining foot in diabetic amputees, and that these pressures are associated with diabetic neuropathy. Prosthetic usage does not increase the pressures under the remaining foot in nondiabetic amputees.     

Color flow Doppler mapping studies of "physiologic" pulmonary and tricuspid regurgitation: evidence for true regurgitation as opposed to a valve closing volume.

Color flow Doppler mapping using either an Aloka 880 or a Toshiba SSH65A system was performed in 39 normal subjects (aged 13 to 45 years) and 43 patients (aged 13 to 82 years) with pathologic tricuspid or pulmonary regurgitation to evaluate the incidence of "physiologic" regurgitation of right heart valves and to determine the differentiating characteristics in the spatial distribution and velocity encoding of "normal" and "pathologic" regurgitant jets. In the normal subjects, tricuspid and pulmonary regurgitation were documented in 32 (83%) and 36 (93%), respectively, and were unrelated to the system being used. Flow acceleration and aliasing were imaged on the right ventricular side of the tricuspid regurgitant orifice and on the pulmonary artery side of the pulmonary valve (in both normal subjects and patients), and indicated flow convergence for true regurgitation through an orifice as opposed to blood being driven retrogradely by the closing valve. Such proximal acceleration was documented in all patients with pathologic tricuspid regurgitation, in 31/32 of the normal subjects with tricuspid regurgitation, and was also observed in 12/15 (80%) of the patients and 4/12 (33%) of normal subjects with pulmonary regurgitation who were examined with the Toshiba system. The dimensions (mean +/- SD) of tricuspid regurgitant jets (length [JL] and area [JA]) were consistently larger in the patients than in the normal subjects [JL: 3.4 +/- 0.9 vs 1.2 +/- 0.5 cm, p less than 0.001; and JA: 5.7 +/- 2.0 vs 1.4 +/- 0.7 cm2, p less than 0.001) as were the pulmonary regurgitation jet dimensions (JL: 1.8 +/- 0.4 vs 0.9 +/- 0.08 cm, p less than 0.001; JA: 1.8 +/- 0.7 vs 0.3 +/- 0.08 cm2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional blood volume changes during acute pericardial tamponade

Using radionuclide blood pool imaging, we evaluated sequential changes in heart, lung, liver, and spleen intravascular volumes were evaluated before and during acute pericardial tamponade in 9 anesthetized dogs. Tamponade resulted in an abrupt (less than 1 min) decline in mean right heart (-30 +/- 5%, p less than 0.001 vs control) and left heart volumes (-27 +/- 4%, p less than 0.001 vs control), with a concomitant reduction in pulmonary volume (-17 +/- 3%, p less than 0.01 vs control). Within this short time frame, both hepatic (+19 +/- 3%) and splenic (+16 +/- 4%, both p less than 0.01 vs control) volumes rose. Five min after the production of tamponade, right and left heart volumes were still significantly reduced (-28 +/- 4, p less than 0.005 vs control and -23 +/- 2%, p less than 0.005 vs control), though pulmonary (+2 +/- 5%, p = NS vs control), hepatic (+7 +/- 3%, p less than 0.05 vs control) and splenic (+9 +/- 3%, p less than 0.05 vs control) volumes had returned toward baseline values. These volume changes were similar at 20 min after tamponade. Thus, tamponade resulted in a sudden shunting of blood from the central to the peripheral circulation, initially from both the lungs and heart. After 5 min pulmonary volumes returned to baseline values, while splenic and hepatic volumes remained slightly, though significantly elevated.     

Effects of exercise on gallbladder volume and motility in obese women

PURPOSE: Comparatively few prospective studies have investigated the relationship between physical activity and gallbladder motility, and the results are controversial. Exercise may affect gallbladder motility via neural or hormonal mechanisms. The purpose of this study was to evaluate the possible effects of aerobic exercise on gallbladder motility in a group of obese women without gallstones. PATIENTS AND METHODS: Twenty-three obese women (age 41.2+/-10.3 years, body mass index 40.7+/-6.7 kg/m(2)) were included in the study. Following an overnight fast, fasting and postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) volumes and ejection fractions were evaluated with real-time ultrasonography before exercise. For all subjects, the exercise regimen consisted of daily 45-minute walking sessions at 60-80% of maximum heart rate for 4 weeks except weekends. Gallbladder volume and ejection fraction were again evaluated after exercise. RESULTS: Fasting and postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) volumes were 38.6+/- 10.9, 32.8+/- 8.8, 27.6/- 8.1, 22.7+/- 8.5, 21.4+/- 7.2, 20.8+/- 7.0, 22.8+/- 7.3, 29.6 +/- 7.0, and 36.8+/- 6.2 cm(3) before the exercise period, respectively, and 40.8+/- 18.9, 29.9+/-11.2, 25.3+/- 9.2, 22.4+/-8.5, 19.6+/-7.8, 17.7+/- 6.8, 17.8+/- 7.3, 23.1+/-10.8, and 29.0+/-14.4 cm(3) after the exercise period, respectively. Postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) ejection fractions were 13.5+/-15.9, 27.4+/-15.4, 39.5+/-20.0, 43.2+/-16.7, 44.3+/-17.3, 37.5 +/- 23.5, 23.5 +/-25.1, and 5.5+/- 21.6% before the exercise period, respectively, and 22.6+/- 20.1, 34.6+/-14.5, 42.0+/-13.6, 49.2+/-12.6, 53.1+/-14.1, 52.6+/-16.1, 43.6+/-17.0, and 29.2+/- 26.5% after exercise, respectively. After the exercise period, the 75, 90, 120, and 150 minute volumes were lower (p< 0.05, p< 0.05, p< 0.05, p< 0.01) and the 90, 120, and 150 minute ejection fractions were higher than before exercise (p< 0.05, p < 0.05, p< 0.01). CONCLUSIONS: Our study showed that exercise decreased late-phase postprandial gallbladder volume and increased late-phase postprandial gallbladder motility in these obese women.     

Influence of cefodizime on chemotaxis and the respiratory burst in neutrophils from diabetics

The effect of cefodizime on the function in vitro of neutrophils from poorly-controlled, non-insulin-dependent diabetics was demonstrated by the chemotactic index and by chemiluminescence. Without cefodizime treatment, the chemotactic index for diabetic neutrophils was significantly lower than that for healthy controls (1.0 +/- 0.1 vs 3.6 +/- 0.7; mean +/- S.E.M., P less than 0.01). When neutrophils were pretreated with cefodizime at 1 or 10 mg/l, cefodizime restored the chemotactic activity of diabetic neutrophils (1.0 +/- 0.1 vs 2.7 +/- 0.3, P less than 0.01), but did not affect the activity in healthy controls. Conversely, cefodizime at 100 mg/l had no enhancing effect on diabetic neutrophil chemotaxis, but decreased the chemotactic activity of healthy neutrophils (1.1 +/- 0.2 vs 3.6 +/- 0.7, P less than 0.01). A difference in neutrophil chemiluminescence was also found between diabetics and healthy subjects but no influence of cefodizime on chemiluminescence was noted in neutrophils from either diabetics or healthy subjects.     

Early recovery from heart failure: insights into the pathogenesis of experimental chronic pacing-induced heart failure

Chronic rapid ventricular pacing (250 beats/min) induces severe heart failure in a canine model. To assess the potential for recovery after cessation of pacing, simultaneous hemodynamic and two-dimensional echocardiographic studies were conducted in nine conscious dogs paced to severe heart failure (4.3 +/- 1.7 weeks). Heart failure was characterized by elevated left and right ventricular filling pressures from 9 +/- 3 and 7 +/- 2 mm Hg to 25 +/- 6 and 15 +/- 3 mm Hg (both p less than 0.01), respectively. Left ventricular cross-sectional area (an estimate of preload) and systolic wall stress (an estimate of afterload) increased from 12 +/- 2 cm2 and 119 +/- 23 10(3) dynes/cm2 to 17 +/- 3 cm2 and 210 +/- 46 10(3) dynes/cm2 (both p less than 0.01), respectively. Left ventricular ejection fraction decreased from 54% +/- 7% to 13% +/- 5% (p less than 0.01). When pacing was discontinued to allow resumption of sinus rhythm, left and right ventricular filling pressures declined rapidly at 48 hours after resumption of sinus rhythm, by 36% and 53%, respectively. Ejection fraction doubled, although left ventricular cross-sectional area and wall stress remained elevated at 48 hours. The recovery of systolic function in the absence of major changes in loading conditions suggests that pacing-induced heart failure is mediated by a decrease in left ventricular contractility. Moreover, the persistent dilation of the left ventricle after cessation of pacing suggests that structural remodeling of the left ventricle occurs during the development of pacing-induced heart failure.     

Association between increased atrial natriuretic peptide and reduced cisplatin nephrotoxicity in rats.

Plasma atrial natriuretic peptide (ANP) concentrations were monitored in two experimental models of protection from cisplatin nephrotoxicity. Sprague-Dawley rats made diabetic with streptozotocin (65 mg/kg) were protected from cisplatin-induced nephrotoxicity when compared to control rats as indicated by reduced plasma creatinine (0.49 +/- 0.02 vs. 0.9 +/- 0.06 mg/dl; P less than .001) and blood urea nitrogen concentrations (18.51 +/- 1.4 vs. 43.08 +/- 2.1 mg/dl; P less than .001). Plasma ANP was also increased with experimental diabetes (76.5 +/- 8.98 fmol/ml) vs. normoglycemic controls (43.8 +/- 8.9 fmol/ml; P less than .02). When diabetic rats were treated with insulin, the renal protection observed with the diabetic state was reversed (creatinine, 0.70 +/- .05 mg/dl); plasma ANP concentrations were also reduced (52.2 +/- 15.2 fmol/ml). Renal platinum concentrations were significantly lower in the diabetic group and the reversal of diabetic-induced renal protection with insulin was associated with increased renal platinum concentrations. In rats given a single i.p. dose of cisplatin (5 mg/kg), a reduction in cisplatin-induced nephrotoxicity was observed when 5% NaCl was the vehicle of choice compared to that seen in rats given the same dose of drug in 0.9% saline (creatinine, 0.43 +/- 0.07 with 5% NaCl vs. 0.63 +/- 0.03 with 0.09% NaCl). NaCl (5%) administration also resulted in increased plasma ANP concentrations when compared to rats receiving equivalent volumes of 0.9% NaCl (88.4 +/- 6.2 vs. 50.5 +/- 5.6 fmol/ml, respectively). These data suggest that increased endogenous ANP may be a mechanism of renal protection common to both experimental diabetes and hypertonic saline administration. Chronically increased ANP may prevent renal accumulation of platinum in the kidney.     

High protein diet complements resin therapy of familial hypercholesterolemia.

The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia.     

Effects of BAYm 1099, new alpha-glucosidase inhibitor, on acute metabolic responses and metabolic control in NIDDM over 1 mo

To examine the clinical role of BAYm 1099, 15 diet-treated non-insulin-dependent diabetic (NIDDM) subjects were randomized to start drug (50 mg 3 times/day) or placebo after a 4-wk run-in period in a double-blind crossover study. Treatment periods (4 wk) were separated by a 2-wk washout period. During the last week of each treatment period, three test meals (TMs) were administered: 60 g starch (TM1), 25 g sucrose (TM2), and combined 60 g starch and 25 g sucrose (TM3). Twelve subjects completed the study. The peak postprandial blood glucose, lactate, and pyruvate levels (means +/- SE) were significantly lower with active drug after all test meals, particularly TM2 (11.3 +/- 1.0 vs. 14.3 +/- 1.4 mM, P less than .001; 1.53 +/- 0.20 vs. 2.48 +/- 0.17 mM, P less than .001; and 105.1 +/- 17.6 vs. 147.6 +/- 11.1 microM, P less than) less than .001; and 105.1 +/- 17.6 vs. 147.6 +/- 11.1 microM, P less than .05, respectively. Peak blood glucose levels were significantly delayed. However, fasting blood glucose, HbA1, fructosamine, and cholesterol did not change during active treatment (10.0 +/- 1.0 vs. 9.9 +/- 1.0 mM, 10.0 +/- 0.7 vs. 9.4 +/- 0.7%, 2.44 +/- 0.10 vs. 2.37 +/- 0.07 mmol/100 g protein, and 6.7 +/- 0.3 vs. 6.5 +/- 0.3 mM, P NS). Flatulence and diarrhea were severe in 2 subjects, requiring termination of study. Thus, in NIDDM, BAYm 1099 was effective in diminishing and delaying postprandial excursions of blood glucose, lactate, and pyruvate after high- and low-sucrose meals, but overall metabolic control remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sensitivity of R-R variation and Valsalva ratio in assessment of cardiovascular diabetic autonomic neuropathy

R-R variation and the Valsalva ratio are commonly used to quantitatively assess diabetic autonomic neuropathy (DAN). To assess the sensitivity of these two measures to parasympathetic ablation, 12 nondiabetic subjects were tested before and after graded doses (0.3-4.0 mg i.v.) of atropine. R-R variation was significantly reduced at 0.7 mg, whereas Valsalva ratio was not significantly smaller until the 2.0-mg dose of atropine. R-R variation continued to become progressively smaller during the 0.85-, 1.0-, and 2.0-mg doses. Valsalva ratio, but not R-R variation, was further reduced by the 4.0-mg dose. To further compare these two measures, two groups of diabetic subjects were compared with a group of nondiabetic subjects (n = 22). One group of diabetic subjects had symptoms of DAN (n = 22), and the other diabetic group had no symptoms of DAN (n = 19). In DAN subjects, both R-R variation (nondiabetic 33.2 +/- 4.3 vs. DAN 9.8 +/- 1.2, P less than .001) and the Valsalva ratio (nondiabetic 1.98 +/- 0.07 vs. DAN 1.55 +/- 0.07, P less than .001) were reduced. However, in asymptomatic subjects, R-R variation (23.2 +/- 3.9, P less than .05), but not Valsalva ratio (1.94 +/- 0.13, NS), was less than nondiabetic subjects. Even after beta-blockade, R-R variation was still less in both groups of diabetic subjects (nondiabetic 34.4 +/- 4.2 vs. DAN 7.4 +/- 1.3, P less than .001; asymptomatic 21.8 +/- 3.3, P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Taste impairment and related factors in type I diabetes mellitus

To study taste in type I (insulin-dependent) diabetes mellitus, 57 consecutive diabetic outpatients (mean +/- SE duration of diabetes 11.4 +/- 0.4 yr) and 38 control subjects were screened for taste disorders with electrogustometry and chemical gustometry. Both groups were comparable for all subject characteristics except body mass index, which was higher in the diabetic group (P less than .05). A taste impairment was found in the diabetic group relative to the control group with electrogustometry (mean threshold 184.3 +/- 15.8 vs. 58.7 +/- 9.2 microA; P less than .001) and chemical gustometry (mean score 13.2 +/- 0.7 vs. 17.1 +/- 0.8; P less than .001). Hypogeusia was found among 73% of the diabetic patients versus 16% of the control subjects (P less than .001). The four primary tastes were involved in taste impairment. With multivariate analysis, taste disorders were related to diabetic status and tobacco and alcohol consumption. In the diabetic group, taste impairment was significantly associated with complications and duration of disease. With multivariate analysis, peripheral neuropathy had the strongest association with taste disorders. These results suggest that taste is impaired during the course of type I diabetes mellitus and that taste impairment could be a complication of the disease. A mechanism of the neuropathic type could be involved.     

Growth hormone suppression and nonproliferative diabetic retinopathy: a preliminary feasibility study

We used the long acting somatostatin analogue SMS 201-995 in order to examine the feasibility and effect of medical suppression of growth hormone in nonproliferative diabetic retinopathy. Six insulin-dependent diabetic subjects with nonproliferative retinopathy were studied. After eight weeks of SMS 201-995 administration, 24-hour integrated plasma growth hormone concentrations had declined by 47.0 +/- 9.3% of pretreatment values (p less than 0.01), and insulin requirements fell from 40.7 +/- 6.7 units per day to 32.2 +/- 6.9 units per day (p less than 0.01). Plasma levels of somatomedin-C were low before SMS 201-995 (0.5 +/- 0.1 U/ml) and remained unchanged at eight weeks (0.6 +/- 0.1 U/ml; p = ns). During SMS 201-995 administration, best corrected visual acuity improved in both right eyes (53.8 +/- 2.57 to 59.8 +/- 0.7 letters, p less than 0.05) and left eyes (54.8 +/- 2.8 to 61.7 +/- 1.23 letters, p less than 0.03). Fluorescein angiography and stereo fundus photography demonstrated concurrent improvement in retinopathy level in only two subjects. Following cessation of SMS 201-995 treatment, visual acuity returned to pretreatment levels in both right eyes (54.5 +/- 2.4 letters, p = ns compared to baseline) and left eyes (55.8 +/- 2.6 letters, p = ns compared to baseline). These results demonstrate that growth hormone was only partially suppressed by SMS 201-995 in insulin-dependent diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new method for hemodynamic and echocardiographic assessment of conscious dogs: comparison with thiopental-morphine anaesthesia

A method allowing assessment of cardiac structure and function in the conscious dog using readily available instrumentation is desirable and should provide physiologic advantages when compared to anaesthesia. Accordingly, we studied 19 dogs (22 +/- 2.5 kg), using two-dimensional echocardiographic and Swan-Ganz and femoral artery catheterization; ten were conditioned to permit conscious studies and nine received anaesthesia. Dogs receiving anaesthesia were induced with intravenous thiopental (16 +/- 4 mg/kg), followed by a maintenance dose (7 +/- 1 mg/kg/h) plus morphine sulphate (213 +/- 5 micrograms/kg/h). Cardiac index, mean blood pressure, and systemic vascular resistance were similar between groups. However, anaesthesia as compared to conscious studies resulted in a marked tachycardia (147 +/- 30 bpm, vs 98 +/- 19 bpm, p less than 0.0005), significantly lower right atrial pressure (5 +/- 2 mmHg vs 8 +/- 2 mmHg, p less than 0.05), and a trend towards a lower pulmonary capillary wedge pressure (6 +/- 5 mmHg vs 9 +/- 3 mmHg). Simultaneous echocardiography showed left ventricular diastolic cross sectional area to be smaller in the anaesthesia group (8.5 +/- 1.7 cm2 vs 10.4 +/- 1.5 cm2, p less than 0.05); however, ejection fraction in the two groups was similar. Velocity of circumferential fiber shortening (Vcf), normalized for heart rate and preload, was significantly lower in the anaesthetised dogs (0.63 +/- 0.22 circ/sec vs 0.89 +/- 0.26 circ/sec, p less than 0.05); this decline in Vcf, in association with a lower systolic wall stress (85 +/- 29 10(3) dynes/cm2 vs 119 +/- 23 10(3) dynes/cm2, p less than 0.05) indicates that thiopental-morphine anaesthesia depresses contractility.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sonographic evaluation of gallbladder volume and ejection fraction in obese women without gallstones

PURPOSE: Obese people have an increased incidence of gallstones. Although the exact pathogenic mechanisms of gallstone development are unknown, impaired gallbladder emptying has been suggested as a possible underlying mechanism. Our aim was to investigate this possibility by evaluating gallbladder motility and related factors in obese and nonobese women without gallstones. METHODS: This study included 79 obese women and 25 nonobese healthy women. Using real-time sonography, we evaluated fasting and postprandial (15th-, 30th-, 45th-, 60th-, 75th-, 90th-, 120th-, and 150th-minute) gallbladder volumes and ejection fractions. The smallest postprandial volume was considered the residual volume. RESULTS: Mean (+/- standard deviation) fasting and residual gallbladder volumes were 43.2 +/- 18.3 cm(3) and 21.4 +/- 11.2 cm(3), respectively, in the obese women and 28.1 +/- 12.3 cm(3) and 7.9 +/- 3.4 cm(3), respectively, in the nonobese women. Maximal ejection fraction was 49 +/- 19% in obese women and 63 +/- 29% in nonobese women (p = 0.001). The fasting and residual volumes and the postprandial volumes at all time points were higher in obese women than in nonobese women (p < 0.001). In addition, 15th-, 30th-, 45th-, 60th-, 75th-, and 90th-minute postprandial ejection fractions were lower in obese women than in nonobese women (p < 0.001). Positive correlations were found between fasting gallbladder volume and body mass index and body fat weight and between residual volume and body mass index, waist circumference, body fat percentage, and body fat weight (p < 0.05 for all comparisons). CONCLUSIONS: Our results show that fasting and postprandial gallbladder volumes are higher and that postprandial gallbladder motility is lower in obese than in nonobese women. There are positive correlations between fasting gallbladder volume and body weight, body mass index, and body fat weight.     

Skeletal muscle glucose uptake, glycogen synthase activity and GLUT 4 content during hypoglycaemia in type 1 diabetic subjects

In healthy subjects, hypoglycaemia induces a profound 80% reduction in skeletal muscle glucose uptake and a similar suppression of glycogen synthase activity. The aim of this study was to examine the efficacy of this counterregulatory mechanism in type 1 diabetic subjects, who are especially prone to hypoglycaemic incidents. Nine type 1 diabetic male subjects were examined twice; during 120 min of hyperinsulinaemic (1.5 mU x kg(-1) x min(-1)) euglycaemia followed by (i) 240 min of graded hypoglycaemia (glucose nadir 2.8 mM) or (ii) 240 min of euglycaemia. At 345-360 min a muscle biopsy was taken and indirect calorimetry was performed at 210-240 and 320-340 min. The sensitivity of glycogen synthase to glucose-6-P was reduced by hypoglycaemia, as shown by an increase in A0.5 for glucose-6-P (at 0.07 mmol/L) from 0.21+/-0.02 to 0.28+/-0.03 mM (p=0.06). Likewise, the fractional velocity for glycogen synthase was reduced by 25%; i.e. from 20.8+/-2.0 to 15.5+/-1.4% (p<0.05). Total glucose disposal was decreased during hypoglycaemia (5.3+/-0.6 vs. 8.3+/-0.7 mg x kg(-1) x min(-1) (euglycaemia), n = 9; p<0.05), primarily due to a reduction of non-oxidative glucose disposal (2.7+/-0.3 vs. 5.1+/-0.6 mg x kg(-1) x min(-1) (euglycaemia), n=7; p<0.05). Forearm arteriovenous glucose differences were decreased by 50% in the hypoglycaemic situation (0.7+/-0.1 vs. 1.4+/-0.3 mmol/L (320-340 min)), and counterregulatory hormonal responses seemed less conspicuous than described in healthy subjects. We conclude that hypoglycaemia induces decrements of forearm glucose uptake and glycogen synthase activity in type 1 diabetic subjects. The study indicates a decreased magnitude of these responses, but this remains to be confirmed.     

Three-dimensional sonographic evaluation of gallbladder contractility: comparison with cholescintigraphy

PURPOSE: To compare three-dimensional sonography (3D US) with quantitative cholescintigraphy for assessing gallbladder contractility. METHODS: Gallbladder radioactivity was assessed in 35 patients with suspected gallbladder disease using a gamma camera 5, 30, 60, and 90 minutes after technetium 99m (Tc-99m) DISIDA injection and 30 and 60 minutes after ingestion of a high-fat meal. Immediate gallbladder images were obtained via 3D US. Gallbladder radioactivity at 120 minutes after injection of Tc-99m DISIDA was defined as 100%, and gallbladder contractility was calculated. Gallbladder volume on 3D US was calculated using a dedicated software. Pearson correlation analysis and simple linear regression analysis were used. RESULTS: The mean gallbladder volume on 3D US was 25.3 ml after fasting and 6.6 ml after a high-fat meal. The mean gallbladder contractility index was 77.7% on cholescintigraphy (range, 18-99) and 73.4 on 3D US (range, 16.7-97.3). A linear correlation between cholescintigraphy and 3D US contractility indices was observed. The r value on Pearson analysis was 0.92 and R(2) of the coefficient of determination was 0.85. The difference in measured contractility between the 2 methods ranged from +21.5% to -15.0% (mean +/- SD, 4.4 +/- 8.7%). CONCLUSIONS: 3D US is a reliable and easy method for clinical measurement of the volume of the gallbladder and its contractility.     

Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism.

To assess the mechanisms responsible for increased gluconeogenesis in noninsulin-dependent diabetes mellitus (NIDDM), we infused [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose in 10 postabsorptive NIDDM subjects and in 9 age- and weight-matched nondiabetic volunteers and measured systemic appearance of alanine and lactate, their release from forearm tissues, and their conversion into plasma glucose (corrected for Krebs cycle carbon exchange). Systemic appearance of lactate and alanine were both significantly greater in diabetic subjects (18.2 +/- 0.9 and 5.8 +/- 0.4 mumol/kg/min, respectively) than in the nondiabetic volunteers (12.6 +/- 0.7 and 4.2 +/- 0.3 mumol/kg/min, respectively, P less than 0.001 and P less than 0.01). Conversions of lactate and alanine to glucose were also both significantly greater in NIDDM subjects (8.6 +/- 0.5 and 2.4 +/- 0.1 mumole/kg/min, respectively) than in nondiabetic volunteers (4.2 +/- 0.4 and 1.8 +/- 0.1 mumol/kg/min, respectively, P less than 0.001 and P less than 0.025). The proportion of systemic alanine appearance converted to glucose was not increased in NIDDM subjects (42.7 +/- 1.9 vs. 44.2 +/- 2.9% in nondiabetic volunteers), whereas the proportion of systemic lactate appearance converted to glucose was increased in NIDDM subjects (48.3 +/- 3.8 vs. 34.2 +/- 3.8% in nondiabetic volunteers, P less than 0.025); the latter increased hepatic efficiency accounted for approximately 40% of the increased lactate conversion to glucose. Neither forearm nor total body muscle lactate and alanine release was significantly different in NIDDM and nondiabetic volunteers. Therefore, we conclude that increased substrate delivery to the liver and increased efficiency of intrahepatic substrate conversion to glucose are both important factors for the increased gluconeogenesis of NIDDM and that tissues other than muscle are responsible for the increased delivery of gluconeogenic precursors to the liver.     

Increased plasma cholecystokinin levels and small gall bladders in adult patients with cystic fibrosis.

1. In patients with cystic fibrosis, abnormalities in plasma cholecystokinin level and gall-bladder emptying may contribute to the development of maldigestion and gall-stones. 2. Therefore, we have measured plasma cholecystokinin levels and gall-bladder volumes before and after ingestion of a standard breakfast in eight adult patients with cystic fibrosis and in eight normal control subjects. 3. In the patients with cystic fibrosis basal (2.8 +/- 0.4 pmol/l; P less than 0.05, t-test) and maximum post-prandial (5.7 +/- 0.5 pmol/l; P less than 0.05, t-test) plasma cholecystokinin levels were significantly higher than those in the control subjects (1.9 +/- 0.1 pmol/l, and 4.5 +/- 0.2 pmol/l, respectively). On the other hand, integrated plasma cholecystokinin secretion in response to the meal was similar (t-test, P = 0.4 versus control subjects). The increased plasma cholecystokinin levels in the patients with cystic fibrosis were accompanied by reduced gallbladder volumes in both the basal (7.8 +/- 2.1 cm3 versus 20.9 +/- 2.3 cm3 in control subjects; P less than 0.005, t-test) and the post-prandial state (2.2 +/- 1.0 cm3 versus 4.8 +/- 0.8 cm3 in control subjects; P = 0.06, t-test). Gall-bladder emptying in the patients with cystic fibrosis was well preserved (70 +/- 7% versus 78 +/- 9% in control subjects; P = 0.4, t-test). 4. In comparison with normal control subjects, patients with cystic fibrosis have an increased basal plasma cholecystokinin level and a reduced gall-bladder volume, whereas post-prandial gall-bladder emptying and plasma cholecystokinin secretion are not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)     

A prospective randomized study comparing the effects of large and small volumes of the sclerosant 5% ethanolamine oleate injected into esophageal varices

The safety efficacy and complications of injections of large and small volumes of 5% ethanolamine oleate (EO) were examined prospectively in the sclerotherapy of esophageal varices in 39 consecutive cirrhotic patients. Twenty patients were randomly allocated to the large-volume group (LVG) injected with up to 30 ml per session, and 19 to the small-volume group (SVG) injected with up to 15 ml per session. The two groups were comparable with regard to age, etiology and severity of liver disease. Post-injection bleeding occurred in 15.8% (3/19) after 1-3 sessions in the SVG and in 0% in the LVG. The LVG showed a significantly higher rate of decrease in variceal size (95.0% vs 53.2%, p less than 0.05) and disappearance of red color signs (RCS) on the variceal surface (95.0% vs 52.6%, p less than 0.01) one week after the initial session. The treatment period and number of sessions of endoscopic injection sclerotherapy (EIS) for eradication of varices were significantly (p less than 0.01) smaller in LVG than in SVG (LVG: 2.7 +/- 0.6 sessions over 4.2 +/- 0.7 weeks vs SVG: 5.4 +/- 0.9 sessions over 6.0 +/- 1.6 weeks). There were no life-threatening complications, and the incidence of minor complications did not differ between the two groups. The persistence of RCS and the occurrence of post-injection bleeding may imply that esophageal varices are not always completely obliterated despite 1-3 sessions in the SVG. We conclude that the large volume of EO is superior to the small volume for repeated EIS to eradicate esophageal varices.     

Platelet-derived growth factor and growth-promoting activity in the serum samples and platelets of patients with non-insulin-dependent diabetes mellitus.

Although platelet-derived growth factor (PDGF) is thought to be a major mediator of atherosclerotic disease, the pathophysiology of diabetic vasculopathy, including atherosclerosis, is unclear. By means of an enzyme immunoassay that used a monoclonal antibody against human PDGF-B chain, PDGF-like immunoreactivity was determined in serum, platelet-poor plasma, and platelet lysate of 28 patients with non-insulin-dependent diabetes mellitus and 11 control subjects. Growth-promoting activity was also measured by tritiated thymidine incorporation into DNA of cultured human fibroblasts. The PDGF-like immunoreactivity in serum was correlated (r = 0.42; p less than 0.01) with that in platelet lysate prepared from a fixed volume of blood. Furthermore, a correlation (r = 0.70; p less than 0.001) was found between the PDGF-like immunoreactivity and the growth-promoting activity in platelet lysate but not in serum. There was no significant difference between patients with diabetes and control subjects with respect to the PDGF-like immunoreactivity in serum or in platelet lysate (38.2 +/- 2.2 vs 42.8 +/- 3.1 ng/ml or 49.1 +/- 2.4 vs 56.2 +/- 3.4 ng/mg protein; mean +/- SEM). In contrast, the serum growth-promoting activity was lower (p less than 0.05) in patients with diabetes than in control subjects (88.1% +/- 7.1% vs 117.4% +/- 6.9%) and there was a negative correlation (r = -0.39; p less than 0.05) between the serum growth-promoting activity and the fasting plasma glucose level. The growth-promoting activity in platelet lysate of patients with diabetes did not differ from that of the control subjects (59.9% +/- 11.6% vs 65.9% +/- 11.2%).(ABSTRACT TRUNCATED AT 250 WORDS)