Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle.

The mechanism underlying the regulation of basal metabolic rate by thyroid hormone remains unclear. Although it has been suggested that thyroid hormone might uncouple substrate oxidation from ATP synthesis, there are no data from studies on humans to support this hypothesis. To examine this possibility, we used a novel combined (13)C/(31)P nuclear magnetic resonance (NMR) approach to assess mitochondrial energy coupling in skeletal muscle of seven healthy adults before and after three days of triiodothyronine (T(3)) treatment. Rates of ATP synthesis and tricarboxylic acid (TCA) cycle fluxes were measured by (31)P and (13)C NMR spectroscopy, respectively, and mitochondrial energy coupling was assessed as the ratio. Muscle TCA cycle flux increased by approximately 70% following T(3) treatment. In contrast, the rate of ATP synthesis remained unchanged. Given the disproportionate increase in TCA cycle flux compared with ATP synthesis, these data suggest that T(3) promotes increased thermogenesis in part by promoting mitochondrial energy uncoupling in skeletal muscle.

Pancreatic resection: effects on glucose metabolism.

Pancreatic resection results in hormonal abnormalities that are dependent on the extent and location (proximal versus distal) of the resected portion of the gland. The form of glucose intolerance which results from pancreatic resection is termed pancreatogenic diabetes. It is associated with features distinct from both type I (insulin-dependent) and type II (insulin-independent, or adult-onset) diabetes. Hepatic insulin resistance with persistent endogenous glucose production and enhanced peripheral insulin sensitivity result in a brittle form of diabetes which can be difficult to manage. In addition to insulin deficiency, the endocrine abnormalities that accompany pancreatic resection can include glucagon deficiency or pancreatic polypeptide (PP) deficiency if the resection is distal or proximal, respectively. Glucagon deficiency can contribute to iatrogenic hypoglycemia, and PP deficiency can contribute to persistent hyperglycemia due to impaired hepatic insulin action. Pancreatic resections that spare the duodenum, such as distal pancreatectomy, duodenum-preserving pancreatic head resection (Beger procedure), or extended lateral pancreaticojejunostomy with excavation of the pancreatic head (Frey procedure), are associated with a lower incidence of new or worsened diabetes than the standard or pylorus-preserving pancreaticoduodenectomy (Whipple procedure) or total pancreatectomy. Operative considerations for the treatment of pancreatic disease should include strategies to minimize the hormonal impairment of pancreatic resection.

Prediction of bile duct stones and complications in gallstone pancreatitis using early laboratory trends.

OBJECTIVES: We aimed to determine whether early trends in the serum pancreatic enzymes and liver tests of patients with gallstone pancreatitis predict persistent common bile duct (CBD) stones and complications. METHODS: Medical records of patients with gallstone pancreatitis were reviewed retrospectively. Serial serum pancreatic enzymes and liver tests were recorded until the time of cholangiography. Laboratory trends were analyzed by comparing initial results obtained in the emergency department to subsequent results obtained 8-24 h, 24-48 h, and 48-72 h after presentation. RESULTS: Of 154 patients with gallstone pancreatitis, 28 (18%) had persistent CBD stones at cholangiography. Complications and death were more frequent in patients with persistent CBD stones than in those without CBD stones (29% and 11% vs 12% and 1%, respectively; p < 0.05). Laboratory trends predicted both persistent CBD stones and complications of pancreatitis. When any laboratory value rose between admission and 24-48 h of hospitalization, persistent CBD stones were present in 31% of cases, versus 8% of those in whom all laboratory values remained constant or fell (p = 0.001). Likewise, complications occurred in 21% of those with any rising laboratory value, versus 8% of those in whom all values remained constant or fell (p < 0.05). CONCLUSIONS: Patients with gallstone pancreatitis and rising serum chemistries had a 4-fold risk of persistent CBD stones and a nearly 3-fold risk of complications compared to patients in whom all chemistry values remained constant or fell. This simple prediction rule may identify patients with biliary pancreatitis who are most likely to benefit from early interventions to diagnose and remove persistent CBD stones.

Isolated hepatic cholinergic denervation impairs glucose and glycogen metabolism.

BACKGROUND: Hepatic innervation plays an essential role in insulin extraction and glucose production, but the specific role of hepatic cholinergic innervation remains unclear. We sought to establish a model of isolated hepatic cholinergic denervation (IHCD), and to assess whether glycogen storage or the control of net hepatic glucose production (HGP) was altered by IHCD. MATERIALS AND METHODS: Sprague-Dawley rats underwent either hepatic vagotomy or sham operation. Liver tissue was stained for vesicular acetylcholine transporter (VAChT) and (nonspecific neural) protein gene product 9. 5 (PGP) for verification of IHCD. Liver glycogen content was quantified in fed and fasted IHCD or sham-operated animals. HGP was determined after single-pass isolated liver perfusion, during which a 30-min 12 ng/ml glucagon infusion was begun after equilibration, and after 10 min, a 200 microU/ml insulin infusion was added. RESULTS: Uniform staining of PGP and absence of VAChT staining in hepatic vagotomized rats demonstrated the validity of our model. Glycogen content of sham-operated livers (n = 8) increased from 6.0 +/- 1.7 in the fasting state to 10.6 +/- 1.8 mg/g liver, after feeding (P < 0.05). IHCD livers (n = 8) showed no comparable increase (3.5 +/- 0.6 to 4.0 +/- 0.7 mg/g liver). Perfusion with glucagon alone resulted in less HGP in IHCD livers (n = 12) compared with sham-operated livers (n = 10) (integrated HGP 3.3 +/- 0.3 mg/g liver min(-1) vs 5.1 +/- 0.5 mg/g liver min(-1), P < 0.05). Insulin infusion revealed impaired responsiveness to insulin after IHCD; the ratio of HGP in the final 10 min of perfusion (glucagon and insulin) to HGP in the initial 10 min (glucagon alone) was 90.3 +/- 2.4% for IHCD livers versus 68.1 +/- 4.4% for sham-operated controls, respectively (P = 0.0002). CONCLUSIONS: Our study shows that IHCD results in significant impairment in liver glycogen storage and impaired hepatic sensitivity to glucagon and, possibly, to insulin. We conclude that hepatic cholinergic integrity is essential to normal hepatic glucose metabolism.

Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium.

AIMS: To determine if the stress of corticosteroid treatment increases chromium (Cr) losses and if corticosteroid-induced diabetes (steroid diabetes) can be reversed by supplemental chromium. METHODS: The effects of corticosteroid treatment on chromium losses of 13 patients 2 days prior to steroid administration and the first 3 days following treatment were determined. Since steroid-induced diabetes was associated with increased chromium losses and insufficient dietary chromium is associated with glucose intolerance and diabetes, we treated three patients with steroid-induced diabetes with 600 microg per day of chromium as chromium picolinate. RESULTS: Urinary chromium losses following corticosteroid treatment increased from 155+/-28 ng/d before corticosteroid treatment to 244+/-33 ng/d in the first 3 days following treatment. Chromium supplementation of patients with steroid-induced diabetes resulted in decreases in fasting blood glucose values from greater than 13.9 mmol/l (250 mg/dl) to less than 8.3 mmol/l (150 mg/dl). Hypoglycaemic drugs were also reduced 50% in all patients when given supplemental chromium. CONCLUSIONS: These data demonstrate that corticosteroid treatment increases chromium losses and that steroid-induced diabetes can be reversed by chromium supplementation. Follow-up, double-blind studies are needed to confirm these observations.

Binding forces of hepatic microsomal and plasma membrane proteins in normal and pancreatitic rats: an AFM force spectroscopic study.

The docking and fusion of membrane-bound vesicles at the cell plasma membrane are brought about by several participating vesicle membrane, plasma membrane, and soluble cytosolic proteins. An understanding of the interactions between these participating proteins will provide an estimate of the potency and efficacy of secretory vesicle docking and fusion at the plasma membrane in cells of a given tissue. Earlier studies suggest that in chronic pancreatitis, glucose intolerance may be associated with impaired exocytosis/endocytosis of hepatic insulin receptor and glucose transporter proteins. In this study, the binding force profiles between microsome membrane proteins and plasma membrane proteins in liver obtained from normal and pancreatitic rats have been examined using atomic force microscopy. The ability of a VAMP-specific antibody to alter binding between microsome- and plasma membrane-associated membrane proteins was examined. In pancreatitic livers, a significant loss in microsome-plasma membrane binding is observed. Furthermore, our study shows that, in contrast to control livers, the microsome-plasma membrane binding in pancreatitic livers is VAMP-independent, which suggests an absence of VAMP participation in membrane-microsome binding. In confirmation with our earlier findings, these studies suggest altered membrane recycling in liver of rats with chronic pancreatitis.

Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity.

To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects before and after a hyperinsulinemic-euglycemic clamp following a five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. Rates of insulin stimulated whole-body glucose uptake. Glucose oxidation and muscle glycogen synthesis were 50%-60% lower following the lipid infusion compared with the glycerol infusion and were associated with a approximately 90% decrease in the increment in intramuscular glucose-6-phosphate concentration, implying diminished glucose transport or phosphorylation activity. To distinguish between these two possibilities, intracellular glucose concentration was measured and found to be significantly lower in the lipid infusion studies, implying that glucose transport is the rate-controlling step. Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1-associated PI 3-kinase activity.

Efficacy and tolerability of slow release urapidil (ebrantil) in hypertensive patients with non-insulin dependent diabetes mellitus (NIDDM).

Urapidil, a new alpha-blocker that peripherally antagonizes postsynaptic alpha 1 receptors and centrally causes a reduction in sympathetic tone as agonist of the serotoninergic receptors, was assessed for its antihypertensive effect and its role on glucose and lipid metabolism and insulin sensitivity in diabetic hypertensive patients. Thirty-three non-insulin dependent diabetes mellitus (NIDDM) patients with diastolic blood pressure (BP) of 95-115 mm Hg were treated with either 30 or 60 mg urapidil twice a day, with a gradual increment up to a maximum of 90 mg b.i.d., in order to reduce diastolic pressure to < 90 mm Hg or by at least 10% in the sitting position. A significant reduction in systolic and diastolic arterial pressure, not accompanied by an increased heart rate, was achieved after 12 weeks of treatment. Lipid and carbohydrate homeostasis and glycemic control, as assessed by HbA1C levels, were not affected. The fasting insulin concentration before the glucose load remained similar, but there was a trend toward reduction in peak insulin concentration, and the ratio of insulin change to glucose change between fasting levels and peak levels was significantly lowered by treatment, suggesting improved insulin sensitivity. In conclusion, urapidil is an effective antihypertensive agent in NIDDM patients with essential hypertension, with a neutral effect on lipids and carbohydrates and a possible beneficial effect on insulin resistance.

Managing operating room budget variances.

Credibility, power, and the ability to obtain greater departmental resources are three benefits of managing the operating room (OR) department's operating budget effectively. Still, few resources exist to help novice as well as seasoned OR directors grapple with the practicalities of maintaining their budget after the annual budget process is completed. The authors examine how astutely controlling personnel, materials, and services budget variances will result in hospital administrators "hearing" and approving an OR director's requests for resources more readily, staff and physicians who enjoy the benefits of better-staffed services and new technology, and an OR director with a reputation as an effective department head among peers in the hospital.

[Misoprostol and de-nol in the treatment of patients with cimetidine-resistant stomach ulcer]. / Mizoprostol i de-nol w leczeniu chorych z wrzodem zoladka opornym na stosowanie cymetydyny.

Both misoprostol (synthetic PGE1 analog) and De-Nol (factor releasing endogenous prostaglandins in the gastric mucosa) can be useful in the treatment of patients with gastric ulcer resistant to cimetidine according to their gastroprotective properties. 64 patients whose gastric ulcer had not healed after 6 weeks of therapy with cimetidine in daily dose of 1000 mg were treated in a comparative short-term trial to assess the relative efficacy of misoprostol (Cytotec; Searle) in daily dose of 800 micrograms (I group; n = 32) and colloidal bismuth subcitrate (De-Nol; Gist-Brocades), four times a day in dose of 5 ml diluted with 15 ml of water (II group; n = 32). Both groups of patients were comparable according to age, sex, duration of ulcer disease, smoking habits, gastric acid secretion, ulcer size and localization in the stomach. The ulcer healing was controlled endoscopically after 2 and 4 weeks of the treatment. Healing rates after 2 weeks of therapy appeared to be 47% for misoprostol and 34% for De-Nol. After 4 weeks of therapy the healing rates were 72% with misoprostol and 63% with De-Nol. No statistically significant differences in the therapeutic efficacy were observed between two groups of the patients. No correlation was found between the ulcer healing rates and size of ulcer, its localization or smoking habits. The moderate side effects (transient diarrhea) were observed in 22% of patients treated with misoprostol. These findings suggest that misoprostol is as effective as De-Nol in the treatment of gastric ulcers resistant to cimetidine.

Footwear practices and operating room contamination.

The extent of bacterial transfer into the clean confines of the operating room (OR) was studied by comparing the use of protective footwear (i.e., polypropylene shoe covers and OR restricted shoes) with unprotected street shoes over a 5-week period. The study was divided into two experimental times: (a) early morning (disinfected floor) and (b) midmorning (dirty floor). Data obtained from the early morning experiment showed that OR restricted shoes and shoe covers transferred fewer bacteria onto the disinfected study area than unprotected street shoes; similar findings were obtained from the midmorning experiment for shoe covers, but not for OR restricted shoes. A comparison of changes in bacterial counts obtained from OR restricted shoes and shoe covers worn from the changing room through a common corridor to the disinfected study area did not differ significantly from OR restricted shoes and shoe covers that were put on immediately before walking through the study area at both experimental times. Overall results indicated that protective footwear may act to reduce bacterial contamination on OR floors.

Cover gowns. Researching their effectiveness.

1. Bacterial colony counts on the right shoulder of the subject's scrub suits were lower after lunch when a. cover gowns were worn over scrub suits outside the OR during lunch, and b. when fresh scrub suits were put on after lunch. 2. Bacterial colony counts were higher after lunch when a. scrub suits were worn without cover gowns outside the OR during lunch, and b. when they were removed before lunch, stored in a locker, and put on again after lunch. 3. The thigh region can be assumed to be dirtier than the shoulder area on scrub suits. From this study, the researchers concluded that wearing cover gowns outside the OR exerts a protective effect against bacterial contamination as determined by samples taken from the right shoulder. Furthermore, this protective effect is comparable to that seen when subjects changed into fresh scrub suits after lunch.

Covergowns and the control of operating room contamination.

This study assessed the effectiveness of cotton/polyester covergowns in protecting scrubsuits against bacterial contamination when operating room (OR) personnel are outside the clean environment of the operating suite. Rodac impression plates were used to measure bacterial contamination. The subjects were nurses working a normal daily OR routine. Bacterial colony counts on the right shoulder decreased when covergowns were worn over scrubsuits during the lunch period outside the OR and when fresh scrubsuits were put on following the lunch period. Colony counts rose over the lunch period when scrubsuits were worn unprotected outside the OR and when scrubsuits were removed before and put on again following lunch. Left thigh samples showed no significant effects of experimental treatments and yielded a mean colony count 2.8 times higher than right shoulder samples. Fifty-three percent of subjects were positive for Staphylococcus aureus and 16% yielded positive plates on 3 or more study days. The incidence of S. aureus contamination was affected by experimental treatments in a way similar to overall bacterial contamination. The results indicated that wearing covergowns protects against above-waist bacterial contamination of scrubsuits.