Effects of exercise-induced sympathoadrenergic activation on portal blood flow

We examined the relationship between portal venous blood flow and sympathoadrenergic activation after muscle exercise. For this purpose, we used echo Doppler and measured plasma noradrenaline concentration before and after mild (7 metabolic units,N=8) and maximal exercise (14 metabolic units,N=8) in 16 patients without significant disease. Portal venous flow did not change after mild exercise. In contrast, a significant reduction in portal venous flow was observed after maximal exercise (P<0.01). This was due to reductions in both cross-sectional area of the portal vein (P<0.01) and portal venous velocity (P<0.01). Overall, there were significant inverse relationships between the change in plasma noradrenaline concentration and that in cross-sectional area of the portal vein [r=–0.44,P<0.01 (absolute change);r=–0.47,P<0.01 (relative change)], that in portal venous velocity (r=–0.63,P<0.01;r=–0.61,P<0.01), and that in portal venous flow (r=–0.54,P<0.01;r=– 0.59,P<0.01). These results suggest that the reduction in portal venous flow after exercise is related to the degree of sympathoadrenergic activation. This reduction may be due mainly to splanchnic vasoconstriction.     

Decreased vasoactive intestinal peptide levels and glutathione depletion in acquired megacolon

We reported decreased vasoactive intestinal peptide levels in acquired megacolon. The origin of altered neuropeptide levels is unknown, but recent work suggested that tissue antioxidants may function as neuroprotectants. Our hypothesis was that altered levels of inhibitory neurotransmitters in human colon are associated with depletion of the tripeptide thiol, glutathione. Normal colon samples (N=10; from patients 41–80 years old) and acquired megacolon samples (N=10; from patients 31–98 years old) were obtained at surgery. Vasoactive intestinal peptide levels were decreased in muscularis externa from acquired megacolon (P=0.01), while there was a modest increase in NADPH diaphorase activity in muscularis externa from megacolon (P=0.10). Glutathione in acquired megacolon was detectable in muscularis externa from only five specimens (P<0.05), but was not significantly different (P>0.05) in the mucosal-submucosal layer. The results supported the presence of vasoactive intestinal peptide and NADPH diaphorase in distinct subpopulations of nerves in human colon. The results also supported the hypothesis that glutathione functions as a neuroprotectant in a subset of patients with acquired megacolon.Supported by VA Medical Research Funds.     

Vasoactive intestinal peptide

Dose—response characteristics of feline corpus circular muscle were studiedin vitro for three neuropeptides individually and with vasoactive intestinal peptide. Bombesin, substance P, and cholecystokinin-octapeptide each elicited concentration-dependent isometric contractions that were reduced by 10^–8 M or 10^–7 M vasoactive intestinal peptide (P<0.01). The concentration of each neuropeptide producing a half-maximal response was increased more than one logfold to 10^–6 M by vasoactive intestinal peptide. Tetrodotoxin blocked responses to bombesin (P<0.001) and reduced responses to substance P (P<0.05), but had no effect on responses to cholecystokinin-octapeptide (P>0.1). These results demonstrate inhibition of neuropeptide responses of gastric smooth muscle and support vasoactive intestinal peptide as an inhibitory regulator of gastric motor function.     

Serological parameters in assessment of degree of gastritis in healthy volunteers

This study was undertaken in healthy volunteers to determine the relation between serum levels of pepsinogen A, pepsinogen C, pepsinogen A:C ratio, and gastrin on the one hand and histology of the gastric mucosa on the other. The grade of gastritis was scored separately for antral and fundic mucosa by three different classifications: Whitehead, activity, and the Sydney score. Among 48 healthy volunteers studied, 17 were found to have gastritis according to the criteria of Whitehead. Fourteen of these 17 subjects with gastritis hadH. pylori in gastric biopsies. In all 48 subjects serum pepsinogen A (r=0.298–0.506;P<0.01–P<0.05), pepsinogen A:C ratio (r between –0.377 and –0.495;P<0.001–P<0.05) and gastrin (r=0.38–0.695;P=0.007–P<0.01) were significantly correlated to the severity of both antral and body gastritis as assessed by all three classifications. In contrast, there was no significant correlation between serum pepsinogen C and any of the gastritis scores. When the 17 subjects with gastritis were analyzed separately, there were no correlations between the parameters studied and gastritis of the antrum. Regarding the corpus mucosa, serum PgA correlated significantly with the activity score (r=0.520;P=0.03), weakly with the Sydney score (r=0.465;P=0.06), but not with the Whitehead score. Serum PgC correlated with the Whitehead (r=0.555;P=0.02) and Sydney score (r=0.523;P=0.03), but only weakly with the activity score (r=0.441;P=0.08). The pepsinogen A:C ratio showed only a weak inverse correlation with the Whitehead gastritis score (r=–0.471;P=0.06), but not with the two other scores. Serum gastrin was significantly correlated with the Whitehead (r=0.634;P=0.006) and the Sydney score (r=0.501;P=0.04), but not with the activity score of the fundic mucosa. It is concluded that among healthy volunteers with gastritis, serological parameters are only correlated to the severity of corpus but not of antral gastritis. Serum PgC and gastrin correlated to the severity of corpus gastritis only if atrophy is comprised in the classification. In contrast, serum PgA correlates only with the activity of corpus gastritis. Thus, serological parameters reflect specific histologic features of gastritis of the gastric body, but not of the antrum.     

NMR spectrometry

In the present investigation, suitability of nuclear magnetic resonance (NMR) spectrometry for total stool fat quantification in patients with normal or impaired exocrine pancreatic function (chronic pancreatitis) has been analyzed in comparison with a conventional chloroform-methanol extraction technique. Basic temperature-dependence studies of NMR spectrometry (90°/180° radiofrequency pulse sequence) on 21 chloroform-methanol extracted pure total stool lipid standards (weight range: 0.05–1.6 g) revealed significantly (P<0.05) improving correlations between NMR signal amplitudes and corresponding weights at increasing temperatures (r=0.952/40° C,r=0.965/60° C,r=0.988/80° C), thus indicating 80° C as optimal temperature for NMR spectrometric total stool fat quantification. In subsequent comparative measureemnts of lyophilized stool samples, NMR spectrometry (at 80° C) and conventional chloroform-methanol extraction provided significantly (P<0.001) correlated results with respect to total fecal fat contents/day of quantitatively collected and homogenized stools in 93 patients with known exocrine pancreatic function (secretin-pancreozymin test), irrespective of whether correlations were determined for all 93 patients (r=0.983) or separately for patients with normal (N=45;r=0.867), moderately reduced (N=31;r=0.946), or highly reduced (N=17;r=0.992) exocrine pancreatic function and correspondingly increased total fecal fat excretions.     

Lipoprotein profile in limited systemic sclerosis

The objective of this study was to determine the lipoprotein profile of limited cutaneous systemic sclerosis (LcSSc). Fasting lipids were determined in 24 female patients and 24 healthy age-matched and sex-matched controls. Exclusion criteria were conditions that induce an altered lipid profile. Lipoprotein levels of risk were determined in accordance with the National Cholesterol Education Program (NCEP). Significantly lower levels of high-density lipoprotein (HDL) cholesterol (47.6±12.4 mg dL^–1 vs. 58.2±12.3 mg dL^–1; P=0.003) and total cholesterol (197.0±40.7 mg dL^–1 vs. 222.0±34.0 mg dL^–1; P=0.02) were observed in LcSSc patients than in controls. The presence of anti-centromere antibodies (ACA) was also associated with lower HDL levels (45.0±12.1 mg dL^–1) compared to ACA-negative patients and controls (50.2±12.6 and 58.2±12.3 mg dL^–1, respectively, P=0.01). The only clinical variable associated with low HDL levels was pulmonary hypertension (PH) (33.6±2.3 mg dL^–1 vs. 49.6±11.9 mg dL^–1, P=0.01). No significant correlation was observed among HDL levels and ESR (r=–0.313; P=0.14), CRP (r=–0.296; P=0.16), or BMI (r=–0.263; P=0.21). Remarkably, a higher percentage of risk HDL levels was identified in LcSSc patients (41.6%) than in healthy controls (8.3%) (P=0.02). Our data suggest that LcSSc patients, particularly those who are ACA positive, have an adverse lipid profile characterized by low HDL levels, a known independent risk for CAD in women. The relevance of this finding for the development of atherosclerosis in this disease must be confirmed by epidemiological studies.     

Evaluation of the turkish version of the bath ankylosing Spondylitis Patient Global Score (BAS-G)

The objective of this study was to investigate the reliability and validity of the Turkish version of the Bath Ankylosing Spondylitis (AS) Patient Global Score (BAS-G). Seventy-one consecutive patients with AS were enrolled into the study. Patients were requested to fill in the questionnaire on the day of admission (first visit), on a second occasion within 24 h after admission (second visit) for test–retest reliability analysis, and on a third occasion for assessing sensitivity to change. Construct validity was assessed by correlation analysis with the Bath AS Functional Index (BASFI), Dougados Functional Index (DFI), Dougados Articular Index (DAI), physical examination findings, and several other parameters. Test–retest reliability analysis of individual BAS-G scores at initial and second visits showed good intraclass correlations [n=46, intraclass correlation=0.928 (0.870–0.960) and intraclass correlation=0.853 (0.725–0.920), for 1-week and 6-month scores, respectively]. Both 1-week and 6-month scores showed moderate correlations with the BASFI (r=0.586 and r=0.503, respectively, P=0.000 for both). The 1-week score also showed moderate correlation with the DFI (r=0.530, P=0.000). The 1-week score showed weak correlations with finger-to-floor distance (r=0.263, P=0.027), chest expansion (r=–0.245, P=0.039), and DAI (r=0.271, P=0.036). Change in the 1-week score at the third visit showed good correlation with the BASFI score (r=0.670, P=0.000, n=36) and moderate correlation with the DFI (r=0.440, P=0.017, n=29). The Turkish version of the BAS-G has good reliability and validity. It is a good tool for assessing patients with AS or other rheumatic diseases in clinical practice and research.     

Osteoprotegerin and the receptor activator of NF-kappa B ligand in the serum and synovial fluid. A comparison of patients with longstanding rheumatoid arthritis and osteoarthritis

We examined OPG and soluble RANKL in the serum (sOPG, sRANKL) and synovial fluid (synOPG, synRANKL) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). OPG and RANKL were measured in 85 patients (44 with RA, 41 patients with OA) in serum and synovial fluid as well. For measuring of OPG and RANKL ELISA tests were used. The results of OPG and RANKL were compared with clinical and radiological scores. We found a negative correlation for OPG and RANKL in synovial fluids: not only for the whole group of patients (P< 0.003, r=–0.32), but also for the subgroups (RA: P<0.04, r=–0.28, OA: P<0.002, r=–0.54). SRANKL and synRANKL were positively correlated in the whole group (P<0.01, r=0.25) and in the OA group (P<0.02, r=0.35); the RA group was showing a trend (P<0.063, r=0.24), however. Serum OPG was lower in RA, synOPG higher in OA. The difference between the two patient groups was only significant for synOPG (P<0.03, r=0.056), but not for sOPG (P<0.09, r=0.19), sRANKL (P<0.43, r=0.85) or synRANKL (P<0.11, r=0.22). The synOPG:synRANKL ratio was significantly correlated with the Larsen score (P<0.004, r=0.38). Synovial OPG is significantly decreased in rheumatoid joints, whereby synovial RANKL is increased. Lower synOPG could reflect a lower protective effect on bone, thus leading to an earlier and more pronounced bone destruction in RA. However, the effect of different mediators for joint destruction in RA and OA seems not to be important to the pathophysiological changes in the joints. The upregulation of serum OPG might be the result of the inflammation; in contrast, an upregulation of RANKL could not be found in the serum of patients with RA and OA.     

Delayed pudendal nerve conduction and endosonographic appearance of the anal sphincter complex

PURPOSE: The aim of this study was to test the hypothesis that a delay in pudendal nerve conduction as measured by pudendal nerve terminal motor latency should be associated with atrophy of the external anal sphincter as measured using endoanal ultrasound. METHODS: Sixty-two adult females (median age, 58.9 (range, 22–88) years) presenting for evaluation of fecal incontinence with no evidence of an external anal sphincter tear on ultrasound were recruited. Ultrasound was performed with a 7.5-MHz radial rotating axial endoprobe in the left lateral position. Four measurements were made in the transverse plane—the external anal sphincter thickness in the midanal canal at the 6 o'clock and 9 o'clock positions, the internal sphincter at the 9 o'clock position, and the external anal sphincter in the low canal at the 9 o'clock position. Pudendal nerve terminal motor latency was measured using a transrectal nerve stimulation technique with measurement of the evoked muscle response. RESULTS: Although there was a trend toward thinner external sphincter muscles in those with bilateral prolonged pudendal nerve terminal motor latency, independent sample t-tests and Pearson correlation coefficients showed no statistically significant relationship (right pudendal nerve terminal motor latency:P=0.083, 0.184, 0.128, 0.910;r=0.228, 0.175, –0.201, –0.015; left pudendal nerve terminal motor latency:P=0.946, 0.276, 0.510, 0.123;r=–0.009, –0.143, –0.087, –0.201). CONCLUSIONS: No statistically significant relationship between ultrasound-measured anal sphincter muscle thickness and pudendal nerve terminal motor latency was identified. Although a trend was suggested that could be further evaluated by a study with a larger sample size and a control group with asymptomatic patients, the small differences in muscle thickness involved and the difficulties in measurement suggest that the establishment of clinically useful ultrasound criteria for the detection of the neuropathic anal sphincter complex is unlikely.     

The importance of anal endosonography in the evaluation of idiopathic fecal incontinence

PURPOSE: The aim of the study was to evaluate the use of anal endosonography in idiopathic incontinence. METHODS: In 29 patients and 26 normal controls, the relationship between sonography images and physiologic parameters was studied. RESULTS: External anal sphincter function, measured as fiber density by single-fiber electromyography (P=0.0001) and pudendal nerve terminal motor latency (P=0.04), was significantly impaired in patients with idiopathic incontinence compared with controls. Both the external and internal anal sphincter could be identified by anal endosonography, and the thickness directly measured. The thickness of the external anal sphincter was significantly negatively correlated to muscle fiber density (r=–0.65,P=0.0002) and to pudendal nerve distal conduction velocity (r=–0.74,P=0.008). The thickness of the internal anal sphincter was significantly correlated to resting pressure (r=–0.67,P=0.0001). CONCLUSION: The ratio between the thickness of the external and internal sphincter muscles measured on the sonography screen was significantly reduced in patients with neurogenic incontinence compared with controls (P <0.01).     

Nitrate nitrogen levels in drinking water of urban areas with high- and low-risk populations for stomach cancer: an environmental epidemiology study

Summary A correlation study between mean nitrate nitrogen levels (ppm) in drinking water samples (N=1389) of Chilean urban areas and age-adjusted death rates per 100000 population from stomach cancer, by province or region and sex, was made.Drinking water samples from all provinces (N=25) had a weighed mean of 1.446 ppm (S.E.M. 0.068) with a range of 0.00–30.00 ppm.Nitrate nitrogen levels showed a positive but not significant association with male death rates. The correlation coefficient was +0.0335. Similarly, such levels did exhibit a positive but not significant correlation with female death rates (r=+0.0486). When NO₃-N levels and male (r=+0.1367) or female (r=+0.1143) death rates were studied, by region, positive but insignificant correlations were detected. Using Cochran's approximation, mean nitrate nitrogen levels in drinking water samples from six provinces with 50% of the Chilean population (period 1953–55 versus 1973–75), showed a decrease from 1.835 to 1.291 ppm, but there was no significant difference (t=1.32) between the two values, except in samples from Santiago Province (t=2.11, P<0.05). Provinces (south central area) showing the highest gastric cancer mortality rates in the world for females (up to 40.8/100,000), and ranking second for males (up to 84.1/100,000), exhibited a very low mean level (0.825 ppm).     

Insulin sensitivity is related to the fatty acid composition of serum lipids and skeletal muscle phospholipids in 70-year-old men

Summary Recent data indicate that peripheral insulin sensitivity may be influenced by dietary fat quality and skeletal muscle phospholipid fatty acid composition. During a health survey of 70-year-old men insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp technique and the fatty acid composition of the serum cholesterol esters was determined (n=215) by gas liquid chromatography. In a subsample the fatty acids of the skeletal muscle phospholipids and triglycerides were determined after fine needle biopsy from m. vastus lateralis (n=39). The peripheral insulin sensitivity was significantly and negatively correlated to the proportion of palmitic (r=–0.31, p<0.001), palmitoleic (r=–0.25, p<0.001) and di-homo--linolenic (r=–0.33, p<0.001) acids and positively to the content of linoleic (r=0.28, p<0.001) acid in the serum cholesterol esters. There was an even stronger negative relationship to the proportion of palmitic acid in the skeletal muscle phospholipds (r=–0.45, p<0.004). The fatty acid composition was also significantly related to insulin sensitivity in a stepwise multiple regression analysis in the presence of other clinical variables, which were associated with insulin action in univariate analysis. Thus, more than 51% of the variation of the insulin sensitivity was explained by an equation containing body mass index, serum triglyceride concentration and the content of palmitic acid in the skeletal muscle phospholipids. It is concluded that the fatty acid composition in serum and of the phospholipids of skeletal muscle may influence insulin action in elderly men.     

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects

Summary The relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq ^99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at — 2, 2, 5, 10, 15, 30, 45, 60, 75, 90, 105, 120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3±0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r=–0.55, p<0.05) and directly related to the retention in the distal stomach at 120 min (r=0.72, p<0.01). Peak plasma glucose was related to the amount emptied at 5 min (r=0.58, p<0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r=0.58, p<0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r=–0.56, p<0.05) and plasma insulin at 30 min (r=–0.53, p<0.05). Plasma insulin at 120 min was inversely related (r=–0.65, p<0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r=0.53, p<0.05). These results indicate in normal subjects that (i) gastric emptying accounts for about 34 % of the variance in peak plasma glucose after a 75-g oral glucose load (ii) plasma glucose levels at 120 min are inversely, rather than directly, related to gastric emptying (iii) the distal stomach influences gastric emptying of glucose.     

Characterization of distal colonic motility in early postoperative period and effect of colonic anastomosis

Under standardized conditions, the manometric motility of the distal colon following rectosigmoid anastomosis (N=11, median age 70 years, range 47–80), was compared to that following laparotomies not involving colonic anastomosis (N=9, 56 years, 32–65). Microtransducer probes were inserted peroperatively and colonic activity recorded continuously (median 96 hr, range 48–109 anastomotic and 75 hr, range 46–107 control group) employing an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program. Total postoperative analgesic doses and duration of surgery were similar in both groups. The first return in the anastomotic group of isolated waveforms [median 1.8 hr, interquartile range (IQR) 1–3] and propagated waves (92 hr, 79–100), was comparable to the control group (4 hr, 1.8–7, and 73 hr, 72–101, respectively). Motor complexes, characterized by bursts of regular contractile activity at 3–5 cpm, returned faster in the control group (3 hr, 2–24 vs 24 hr, 19–30,P<0.05). Motility index was significantly depressed during the first 72 hr following surgery in the anastomotic group compared to controls (P<0.001). Flatus was passed at a median of 72 hr (IQR 45–79) in the control and 94 hr (81–105) in the anastomotic group (P=0.05). The presence of a left-sided colonic anastomosis has a major inhibitory effect on distal colonic motility, compared to nonanastomotic surgery of similar severity, in the early postoperative period.Funded by M.R.C. grant.     

Calcium Signaling Is Involved in EthanolInduced Volume Decrease and Gap Junction Closure in Cultured Rat Gastric Mucosal Cells

Ethanol is a well-established barrier breaker in gastric mucosa, but its detailed effects at the cellular level remain unclear. We have previously shown that the intracellular free calcium concentration is increased, gap junctions are closed, and cell volume is decreased after exposure to 5% (v/v) ethanol in primarily cultured rabbit gastric epithelial cells. Rat gastric mucosal (RGM) cells were grown to confluence on a coverslip or on a filter membrane. Gap junctional diffusion was measured in 5-carboxyfluorescein-loaded cells by bleaching a small area with a laser and measuring the recovery with confocal microscope. Intracellular calcium was measured spectrofluorometrically in fura-2-loaded cells. For cell volume measurements the cell monolayer was loaded with calcein and imaged along the Z-axis with a confocal microscope. The changes in fluorescence intensity were intercepted as a measure of cell volume change. TMB-8 was used to inhibit intracellular calcium release and lanthanum to block plasma membrane calcium selective ion channels, while BABTA served as an intracellular calcium chelating agent. Results showed that ethanol (7.5%, v/v) exposure increased intracellular calcium from 69± 7 to 142± 11 nM (N = 5; P < 0.05), decreased cell volume by –23± 5% (N = 8; P < 0.05), and induced gap junction closure (fluorescence recovery from 37± 9 to 15± 3%; N = 6; P < 0.05). A serosal potassium channel blocker, quinine, almost completely prevented the ethanol-induced cell volume decrease (from –23± 5 to –3± 3%), suggesting that opening of basolateral potassium channels underlies cell shrinkage. BABTA inhibited completely (from 35± 3 to 39± 4 nM; N = 6; P < 0.05), and TMB-8 + lanthanum partially (from 60± 6 to 92± 12 nM; N = 6; P < 0.05), the ethanol-induced intracellular calcium increase. BABTA also abolished the ethanol-induced volume decrease (from –23± 5 to 1± 4%; N = 6; P < 0.05), while TMB-8 + lanthanum had a lesser effect on it (from –23± 5 to –11± 3%; N = 9; P < 0.05). They also abolished the closure of gap junctions induced by ethanol (fluorescence recovery, 38± 5% for BABTA and 30± 4% for TMB-8 + lanthanum). We conclude that luminal ethanol opens basolateral calcium-dependent potassium selective channels with resultant shrinkage of the cells and blocks the intercellular gap junctions. These actions are mediated by intracellular calcium signaling.     

Risk factors for the progression of diabetic nephropathy: role of hyperlipidaemia and its correction

Hypertension, proteinuria and hyperlipidaemia are major factors implicated in the progression of chronic renal failure towards uraemia. All of these factors are frequently more pronounced in diabetic nephropathy. We evaluated the rate of progression of renal insufficiency in 12 patients with diabetic nephropathy (DN group) and 18 patients with non-diabetic chronic nephropathy (CN group) during a 2-year period. All patients had high blood pressure on angiotensin-converting enzyme (ACE) inhibitor therapy, hypercholesterolaemia and proteinuria in the non-nephrotic range. Basal glomerular filtration rate (GFR) had an overlapping range in the two groups. The rate of GFR decline during the 2-year period was similar for the DN and CN groups (0.23 vs 0.21 ml/min per month) and correlated with the mean values of low-density lipoprotein (LDL)-cholesterol for both groups (DNr=0.569, CNr=0.511,P<0.05). After 1 year of ACE inhibitor therapy we randomly allocated a subset of patients in each group (6 DN and 9 CN) to receive HMG-CoA-reductase inhibitor (simvastatin or pravastatin 10 mg/day). We observed a decrease in total (–21%) and LDL-cholesterol (–32%) and triglycerides (–11%) and an increase in high-density lipoprotein (HDL)-cholesterol (+8%). The rate of GFR decline was lower in the statin-treated group compared with the previous period (DN–0.21 vs –0.25 ml/min per month; CN –0.18 vs –0.22 ml/min per month). Our data support the hypothesis that associated risk factors rather than diabetes per se are responsible for the rate of progression of renal failure in DN and that the correction of lipid abnormalities may play a key role in slowing the rate of renal function decline.     

Body mass index and blood glucose: correlations with serum insulin, growth hormone, and insulin-like growth factor-1 levels in patients with diffuse idiopathic skeletal hyperostosis (DISH)

Obesity is a frequent co-morbid condition associated with diffuse idiopathic skeletal hyperostosis (DISH). Serum growth hormone (GH), insulin-like growth factor (IGF-1) and insulin are significantly elevated in patients with DISH. In this study, we examined the relationship between body mass index (BMI) and basal serum GH, IGF-1, and insulin concentration in a group of 36 DISH patients. Basal serum insulin levels were significantly elevated (P<0.001) in DISH patients with a BMI>28 kg m^–2, classified as obese, compared with DISH patients with BMI ranging from 23 to 28 kg m^–2. In addition, BMI strongly positively correlated with serum insulin concentration in DISH patients (adjusted r²=0.348, P<0.001). However, BMI did not correlate with either basal serum GH (adjusted r²=–0.013) or IGF-1 levels (adjusted r²=–0.010) in DISH. We conclude that BMI does not seem to contribute to elevated serum GH and IGF-1 levels in symptomatic DISH.     

Clinical analysis of the serum muscle enzyme spectrum of patients with newly diagnosed Sheehan’s syndrome

We investigated the factors associated with serum muscle enzyme elevation in patients with Sheehan’s syndrome. A total of 48 patients who were newly diagnosed with Sheehan’s syndrome were included and divided into 3 groups: Group 1, creatine kinase (CK) ≥ 1000 U/L; Group 2, 140 < CK < 1000 U/L; and Group 3, CK ≤ 140 U/L. Differences in serum muscle enzymes, serum electrolytes, blood glucose and hormones were compared among the 3 groups. A Spearman correlation analysis and multiple linear regression analysis were performed on serum muscle enzymes and the other variables. Four patients in Group 1 underwent electromyography. Fourteen, 26 and 8 patients were divided into Group 1, Group 2, and Group 3, respectively. The levels of plasma osmolality, serum sodium, free triiodothyronine (FT3) and free thyroxine (FT4) in Group 1 were lower than those in Group 3 at admission (P < .05). There were significant differences in CK, CK-MB, aspartate aminotransferase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase among the three groups (P < .05). CK was correlated with serum sodium (r = −0.642, P < .001), serum potassium (r = −0.29, P = .046), plasma osmolality (r = −0.65, P < .001), FT3 (r = −0.363, P = .012), and FT4 (r = −0.450, P = .002). Moreover, creatine kinase isoenzyme-MB (CK-MB) was correlated with serum sodium (r = −0.464, P = .001) and plasma osmolality (r = −0.483, P < .001). The multiple linear regression showed that serum sodium was independently and negatively correlated with CK (r = −0.352, P = .021). The electromyogram results supported the existence of myogenic injury. Sheehan’s syndrome is prone to be complicated by nontraumatic rhabdomyolysis, with both a chronic course and acute exacerbation. Serum muscle enzymes should be routinely measured. For patients with CK levels > 1000 U/L, a CK-MB/CK ratio < 6% can be a simple indicator to differentiate rhabdomyolysis from acute myocardial infarction. Abnormal serum muscle enzymes observed in Sheehan’s syndrome may be associated with hypothyroidism and with hyponatremia in particular.     

Muscle enzyme activity and insulin sensitivity in Type 1 (insulin-dependent) diabetes mellitus

Summary The mechanisms of insulin insensitivity in diabetes are poorly understood. We have therefore assessed the relationship between glucose disposal during a euglycaemic clamp, muscle glycogen formation, and the activities of insulin regulated enzymes within skeletal muscle in five Type 1(insulin-dependent) diabetic patients, both on conventional injection therapy (HbA₁ 11.0±1.0 (SD) %) and after 6 weeks continuous subcutaneous insulin infusion (HbA₁ 7.6±1.4%,p < 0.01). On both regimens, overnight euglycaemia before the clamp was maintained with an intravenous insulin infusion. The increase in clamp glucose requirements (insulin 0.1 U kg^–1·h^–1) between injection therapy and continuous subcutaneous insulin infusion was significant (6.2±0.9 (SE) to 7.0 ± 0.9 mg·kg^–1·min^–1,p<0.05), but small compared to differences between subjects. Glucose requirement remained lower than in control subjects (10.4 ± 0.7 mg·kg^–1·min^–1,p < 0.05). The increase in muscle glycogen with the clamp was slightly higher on continuous subcutaneous insulin infusion (9.5 ± 2.5 mg/g protein) than on injection therapy (8.5 ± 2.4 mg/g,p < 0.05), but less than in control subjects (17.9 ± 2.1 mg/g,p < 0.05). The expressed activity of glycogen synthase and pyruvate dehydrogenase increased significantly between fasting and the end of the clamps in the patients (p < 0.001 and < 0.005), but was not significantly different between the two treatment regimens. Expressed glycogen synthase activity at the end of the clamp was lower on both treatments than in control subjects (p < 0.05). Both enzyme activities were, however, highly correlated with glucose requirement between patients, (r=0.89–0.94,p<0.05-0.02), and glycogen synthase was similarly correlated in the control subjects (r = 0.84,p < 0.05). Patients had significantly different enzyme activities, glucose requirement, and glycogen stored by analysis of variance (p < 0.05-0.01). Correlation of each enzyme activity between subjects on the two treatment regimens was also high (r=0.94–0.98,p < 0.02–0.01). At the end of the clamp the enzyme activities were themselves closely related (injectionsr = 0.99,p < 0.001; infusionr = 0.88,p < 0.05), and glycogen synthase activity predicted muscle glycogen deposition (r=0.94–0.97,p < 0.02–0.01). We suggest that: (1) preceding metabolic control has a relatively small influence on whole body insulin sensitivity measured immediately after careful overnight control; (2) insulin sensitivity derived from glucose clamp data is strongly related to skeletal muscle glycogen deposition and skeletal muscle enzyme activities.     

In vitro studies of gastric juice in patients with food-cobalamin malabsorption

Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and anin vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best within vivo egg yolk-cobalamin absorption test results in the 14 patients (r=0.731,P<0.005). Transfer also correlated inversely with gastric juice pH (r=–0.619,P<0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0–1.3. Pepsin levels did not correlate within vitro transfer or with absorptionin vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poorin vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity. The finding that the ability of a gastric juice to promote the transfer of cobalaminin vitro was the best overall indicator of a patient's ability to absorb food cobalaminin vivo suggests that gastric juice defects are responsible for most cases of food-cobalamin malabsorption. The phenomenon may also provide a practicalin vitro estimate of a patient's ability to absorb food cobalamin.This study was supported by grant DK 32640 from the National Institutes of Health.