Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators

BACKGROUND: Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can accurately diagnose this condition. AIM: To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine. METHOD: Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed. RESULTS: Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3-12.6). Their median daily faecal weight was 285 g (range 85-676) and median faecal fat output was 17 mmol/24 h (range 8.3-38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea. CONCLUSIONS: Idiopathic bile acid malabsorption, once suspected, especially by documenting true 'large volume' watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.     

Correction of unilateral cleft lip nasal deformity with modified Bardach''s technique

Measurements were made of the intake of a WHO/UNICEF glucose-based and a rice cereal-based oral rehydration solution (ORS) by children with diarrhoea. Twenty children who presented to the Children's Outpatient Department at Port Moresby General Hospital with acute diarrhoea and mild dehydration were randomly assigned to an ORS and measurements were taken over the following 3 hours. For data analysis, the patients were paired by weight. Testing the means of the paired samples by t test showed that there was no significant difference between the amount of rice ORS and the amount of glucose ORS taken over 3 hours.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean+/-SD of total stool output (g kg(-1)) was 532+/-476 vs 479+/-354 and the duration (h) of diarrhoea was 108+/-68 vs 103+/-53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Mechanisms of diarrhoea in myotonic dystrophy

BACKGROUND: Gastrointestinal (GI) symptoms are common in myotonic dystrophy (MD). Diarrhoea is one of the more disabling of these GI complaints. The mechanisms behind diarrhoea in MD have not previously been investigated systematically. OBJECTIVE: To elucidate the mechanisms behind diarrhoea in MD. METHODS: Twenty patients with MD and suffering from diarrhoea were investigated in order to detect malabsorption (blood tests and faecal fat excretion) and bile acid malabsorption ([75Se]selenahomocholic acid-taurine (SeHCAT) retention) and to study intestinal morphology (duodenal and rectal biopsies). RESULTS: Two patients had deficiency of folic acid and four showed reduced levels of pancreatic isoamylase, but none of them had steatorrhoea. Two out of eight patients had abnormal bile acid breath tests with normal SeHCAT, indicating small bowel bacterial overgrowth and 12 displayed reduced SeHCAT retention. Duodenal biopsies were normal in eight patients and five out of nine rectal biopsies displayed slight inflammation. CONCLUSIONS: A possible mechanism of diarrhoea in MD could be identified in most of the patients. Bile acid malabsorption seems to be a frequent cause and can be treated successfully.     

The combination of paclitaxel and carboplatin as first-line chemotherapy in patients with stage III and stage IV ovarian cancer: a phase I-II study

BACKGROUND: Stool softening is a physician's first step in the management of chronic constipation. AIM: To compare stool softening (stool water content) and laxative efficacy of psyllium hydrophilic mucilloid vs. docusate sodium. METHODS: The multi-site, randomized, double-blind, parallel-design study of 170 subjects with chronic idiopathic constipation involved a 2-week baseline (placebo) phase followed by 2 weeks of treatment. The treatment phase compared psyllium (5.1 g b.d.) plus docusate placebo to docusate sodium (100 mg b.d.) plus psyllium placebo. Stools were collected and assessed. RESULTS: Compared to baseline, psyllium increased stool water content vs. docusate (psyllium 2.33% vs. docusate 0.01%, P = 0.007). Psyllium also increased stool water weight (psyllium 84.0 g/BM; docusate 71.4 g/BM; P = 0.04), total stool output (psyllium 359.9 g/week: docusate 271.9 g/week; P = 0.005), and O'Brien rank-type score combining objective measures of constipation (psyllium 475.1; docusate 403.9; P = 0.002). Bowel movement (BM) frequency was significantly greater for psyllium (3.5 BM/week) vs. docusate (2.9 BM/week) in treatment week 2 (P = 0.02), with no significant difference (P > 0.05) between treatment groups in treatment week 1 (3.3 vs. 3.1 BM/week). CONCLUSION: Psyllium is superior to docusate sodium for softening stools by increasing stool water content, and has greater overall laxative efficacy in subjects with chronic idiopathic constipation.     

Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea

Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5-193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1-174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS.     

Determination of 14CO2 in breath and 14C in stool after oral administration of cholyl-1-[14C]glycine: clinical application

Twenty patients with intestinal bacterial overgrowth and 20 control subjects were investigated for bile acid deconjugation, by measuring 14CO2 in the breath after cholyl-1-[14C]glycine administration. 14CO2 output/24h was 11.0 +/- 5.2% (mean +/- SD) in controls and 54.2 +/- 14.0% (mean +/- SD) in bacterial-overgrowth patients (P less than .001). 14CO2 excretion rate in 12h, when normalized to 100% of the dose at the 12th hour, gave an even finer discrimination between the two groups (no false responses). 14C in stool, analyzed in 20 malabsorption patients and 20 controls by two different techniques, was 6.6 +/- 4% and 31.38 +/- 21.7% (mean +/- SD), respectively. Results by the two different techniques described here correlated well (r = .99). Bile acid malabsorption was in reasonable agreement (r = .67) with percentage of "chenoid" (chenodeoxycholic acid plus ursodeoxycholic acid) in the stool by gas-liquid chromatography; a poorer correlation was observed when "chenoid" plus "choloid" (cholic acid plus its epimers) were plotted vs. -4C in stool (r = .57, n = 15).     

Laparoscopic resection of a benign true cyst of the spleen with the harmonic scalpel producing high levels of CA 19-9 and carcinoembryonic antigen

BACKGROUND: Oral ingestion of immunoglobulins in humans has been shown to be effective as prophylaxis against enteric infections. However, its therapeutic effect in children with infectious diarrhea has hitherto not been proven. We treated children with rotavirus diarrhea with immunoglobulins extracted from immunized bovine colostrum (IIBC) containing high titers of antibodies against four rotavirus serotypes. METHODS: In this double blind placebo-controlled trial, 80 children with rotavirus diarrhea were randomly assigned to receive orally either 10 g of IIBC (containing 3.6 g of antirotavirus antibodies) daily for 4 days or the same amount of a placebo preparation. The daily stool output (grams/kg/day), intake of oral rehydration solution (ml/kg/day), stool frequency (number of stools/day) and presence of rotavirus in stool were monitored for the 4 days during treatment. RESULTS: Children who received IIBC had significantly less daily and total stool output and stool frequency and required a smaller amount of oral rehydration solution than did children who received placebo (P < 0.05). Clearance of rotavirus from the stool was also earlier in the IIBC group compared with the placebo group (mean day, 1.5 vs. 2.9, P < 0.001). No adverse reactions from the colostrum treatment were observed. CONCLUSIONS: Treatment with antirotavirus immunoglobulin of bovine colostral origin is effective in the management of children with acute rotavirus diarrhea.     

Chronic enteropathy of unknown etiology in patients with AIDS. An analysis of 40 cases

BACKGROUND: Data about the etiology of chronic enteropathy in AIDS patients are scarce and are very dependent upon the geographical area. The aim of this study was to detect microorganisms potentially associated with chronic enteropathy in AIDS patients with diarrhoea for more than one month, and initial negative routine stool bacterial cultures and examinations for ova and parasites. The degrees of associated intestinal malabsorption and immunodeficiency were also analysed. PATIENTS AND METHODS: Forty consecutive patients were recruited from January 1993 to December 1994. The following studies were performed: Intestinal absorption tests (d-xylose and 14C-triolein), CD4/CD8 cell counts, microbiological studies (standard stool cultures for detection of bacteria and examinations for ova and parasites including the detection of Enterocitozoon bieneusi spores by the Weber's stain), upper gastrointestinal endoscopy or colonoscopy with intestinal biopsies and blood cultures for CMV and mycobacteria. RESULTS: The median duration of diarrhoea was 4 months and the mean weight loss was 8.4 kg. Ninety percent of patients had less than 0.1 x 10(9) CD4+ cells/l, with a mean CD4+ cell count of 0.035 x 10(9)/l. Malabsorption was found in 84% of patients. An etiological diagnosis of chronic enteropathy was reached in 60% of the patients. The yield of pathological examination was 37% and the microbiological test using samples of faeces and blood were positive in 45% and 20% of cases respectively. The most frequently identified microorganisms were CMV (10 cases), E. bieneusi (9), enterobacteria (8), Cryptosporidium parvum (5), Leishmania donovani (2). Patients with enteropathy caused by E. bieneusi had lower count of CD4 cells (p = 0.005) and with higher serum levels of alkaline phosphatase (p = 0.02) than patients with CMV enteropathy. CONCLUSIONS: Stool Weber's stain and CMV and mycobacterial blood cultures should be added to the standard work-up diagnosis in patients with chronic diarrhoea and a CD4+cells count below 0.1 x 10(9) l. Upper and/or lower gastrointestinal endoscopies with intestinal biopsies should be performed only in patients with persistent diarrhea without microbiological diagnosis or a lack of response to treatment.     

Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins

The primary objectives of these studies were to determine the clinical efficacy and safety of the potential antisecretory and antimicrobial drugs in the treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC). The drugs evaluated were chlorpromazine (CPZ), nicotinic acid, berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin. Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera diarrhoea has been studied. The drug studies were carried out as placebo-controlled, randomized clinical trials in patients with active diarrhoea due to vibrio cholerae and ETEC. All patients received intravenous (i.v.) or oral rehydration solutions (ORS), but no other medications except the study drugs. Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal patients without significant side effects. It appeared that berberine was more effective in ETEC diarrhoea than in cholera. However, chloroquine, indomethacin, clonidine, and bioflorin had no clinically useful effects. Among the antimicrobial agents, a single dose of tetracycline was found to be effective in cholera, because the drug significantly (p < 0.05) reduced the total stool volume from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to furazolidone. Drugs other than antimicrobial and antisecretory agents were also evaluated in the treatment of cholera. It has been shown that treatment with bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium, did not significantly (p > 0.05) reduce fluid-loss in cholera. Additional studies in animals indicated that treatment with short chain glucose polymers, alone or in combination with a chloride blocking agent, anthracene-9-carboxylic acid (A9C), significantly reduced intestinal secretion in a rat model of secretory diarrhoea. For the first time it was demonstrated that jejunal prostaglandin (PG) E2 concentrations were significantly increased during acute cholera and correlated with the volumes of stool and duration of diarrhoea. Furthermore, it was shown that treatment with indomethacin, a potent inhibitor of PG synthesis, significantly reduced jejunal PGE2 output in adults with acute cholera, in addition to net secretion of water and electrolytes. In summarizing the results, it is concluded that: (1) CPZ, berberine, and nicotinic acid are potential antidiarrhoeal agents, (2) PGs are involved in the pathogenesis of cholera, (3) tetracycline and furazolidone are effective antimicrobial agents in cholera, (4) and glucose short-chain polymers (used with the chloride blocking agent, anthracene-9-carboxylic acid) are better sources of carbohydrates in oral rehydration solutions.     

Preservation of physiological responses to hypoglycemia 2 days after antecedent hypoglycemia in patients with IDDM

OBJECTIVE: To assess the effects of short-term antecedent hypoglycemia on responses to further hypoglycemia 2 days later in patients with IDDM. RESEARCH DESIGN AND METHODS: We studied eight type I diabetic patients without hypoglycemia unawareness or autonomic neuropathy during two periods at least 4 weeks apart. On day 1, 2 h of either clamped hyperinsulinemic (60 mU.m-2.min-1) hypoglycemia at 2.8 mmol/l or euglycemia at 5.0 mmol/l were induced. Hyperinsulinemic hypoglycemia was induced 2 days later with 40 min glucose steps of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/l. Catecholamine levels and symptomatic and physiological responses were measured every 10-20 min. RESULTS: When compared with the responses measured following euglycemia, the responses of norepinephrine 2 days after hypoglycemia were reduced (peak, 1.4 +/- 0.4 [mean +/- SE] vs.1.0 +/- 0.3 nmol/l [P < 0.05]; threshold, 3.4 +/- 0.1 vs. 2.9 +/- 0.1 mmol/l glucose [P < 0.01]). The responses of epinephrine (peak, 4.0 +/- 1.4 vs. 3.5 +/- 0.8 nmol/l [P = 0.84]; threshold, 3.8 +/- 0.1 vs. 3.6 +/- 0.1 mmol/l glucose [P = 0.38]), water loss (peak, 194 +/- 34 vs. 179 +/- 47 g-1.m-2.h-1 [P = 0.73]; threshold, 2.9 +/- 0.2 vs. 2.9 +/- 0.2 mmol/l glucose [P = 0.90]), tremor (peak, 0.28 +/- 0.05 vs. 0.37 +/- 0.06 root mean square volts (RMS V) [P = 0.19]; threshold, 3.2 +/- 0.2 vs. 3.1 +/- 0.2 mmol/l glucose [P = 0.70]), total symptom scores (peak, 10.6 +/- 2.1 vs. 10.8 +/- 1.9 [P = 0.95]; threshold, 3.3 +/- 0.2 vs. 3.6 +/0 0.1 mmol/l glucose [P = 0.15]), and cognitive function (four-choice reaction time: threshold, 2.9 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l glucose [P = 0.69]) were unaffected. CONCLUSIONS: The effect on hypoglycemic physiological responses of 2 h of experimental hypoglycemia lasts for 1-2 days in these patients with IDDM . The pathophysiological effect of antecedent hypoglycemia may be of shorter duration in IDDM patients, compared with nondiabetic subjects.     

Optimization of evening insulin dose in patients using the short-acting insulin analog lispro

OBJECTIVE: A three-way, crossover, open-label, randomized study was designed to compare the evening and night (1800-0800) glycemic control when the evening premeal lispro dose was reduced by 20% and the bedtime basal NPH dose increased by 25%, or when the basal NPH dose was moved to before dinner at 1800, compared with the control arm on standard premeal human regular insulin and pre-bedtime NPH insulin. RESEARCH DESIGN AND METHODS: A total of 13 type 1 diabetic patients who use a premeal plus basal insulin regimen were studied on three separate days, with identical meals and snacks at the same times on each study day. On the control study day, patients received human regular insulin before dinner and NPH at bedtime in their usual doses. On another day, lispro was given before dinner with a dose reduction of 20%, and NPH at bedtime at 125% of usual dose. In the third regimen, the lispro and NPH were administered together in their usual dose before the evening meal by separate injections. The three regimens were tested in random order. RESULTS: Postprandial (1800-2200) blood glucose concentrations were lower after reduced-dose lispro compared with human regular insulin (6.0 +/- 0.3 [SEM] vs. 7.4 +/- 0.3 mmol/l, P < 0.05). Nighttime (2400-0400) blood glucose concentrations were not different (8.6 +/- 0.3 vs. 9.2 +/- 0.3 mmol/l, NS), and prebreakfast concentrations were also unchanged (7.7 +/- 0.9 vs. 8.7 +/- 0.8 mmol/l) after lispro with increased-dose NPH compared with standard insulin. By contrast, both nighttime (10.0 +/- 0.3 mmol/l, P < 0.05) and fasting glucose concentrations (10.8 +/- 0.6 mmol/l, P < 0.05) were significantly higher with dinnertime usual-dose lispro plus dinnertime usual-dose NPH compared with standard human insulin. Hypoglycemia at night (blood glucose < 3.0 mmol/l) did not differ between study days, but it was more frequent postprandially after dinner usual-dose lispro plus early NPH (2 vs. 7 patients, P = 0.062). CONCLUSIONS: With lower mealtime and higher basal bedtime insulin doses, patients using insulin lispro may be able to gain an overall improvement in evening blood glucose control without deteriorated nighttime glucose levels. Earlier basal NPH dosage alone does not ameliorate the nighttime hyperglycemia of short-acting insulin analog regimens.     

Effects of hypertonic sodium lactate dextran resuscitation in severely burned dogs

12 dogs with 35% TBSA third degree burns received HLD resuscitation (HLD group, n = 6) or LR resuscitation (LR group, n = 6). Fluid resuscitation started one hour postburn. The amount of fluid infused with HLD resuscitation was calculated by that after giving HLD 19.6 ml/kg in 3 hours and 6 ml/kg/% TBSA lactate Ringer's solution followed. The amount of fluid infused with LR resuscitation was calculated by 8 ml/kg/% TBSA lactate Ringer's solution. Infusion of lactated Ringer's solution in both groups was adjusted by maintaining urinary output 0.5-1 ml/kg/h. The volume of fluid infused in HLD group (5.05 +/- 1.11 ml/kg/% TBSA) was much less than that of LR group (10.03 +/- 1.30 ml/kg/%TBSA) (P < 0.01). There was no significant difference in urinary output, serum Na+ and albumin, and plasmacrystalloid osmolarity between two groups. Plasma level of MDA decreased after resuscitation with HLD, which (0.81 +/- 0.20 mmol/g Hb) was much lower than that (1.39 +/- 0.44 mmol/g Hb) of LR group 4 hours postburn (P < 0.05). Plasma SOD activity (7.22 +/- 0.68 u/g Hb) of HLD group were much higher than that of LR group (4.86 +/- 0.53 u/g Hb) 4 hours postburn (P < 0.05). HLD resuscitation could significant reduce the amount of fluid infused comparing with lactate Ringer's solution. HLD resuscitation could attenuate postburn damage to tissue induced by lipid peroxide by elevating plasma SOD activity.     

Oral rehydration therapy

Oral rehydration solution (ORS), the best treatment of dehydration due to acute diarrhea, is the most important medical advance of this century since it is key to reducing infant and child morbidity and mortality. Pathogens responsible for acute diarrhea include those which produce enterotoxin at the intestinal mucosal surface, inducing secretion but are not invasive (e.g., Vibrio cholerae); those which invade and disrupt the mucosal lining (e.g., shigella species); and rotavirus. The World Health Organization (WHO)/UNICEF ORS is considered a universal ORS. Much research has been done on the ideal composition of an ORS. An ORS must have sufficient sodium to replace losses on a volume to volume basis, a glucose concentration that matches that of sodium to ensure its delivery to the ileum, sufficient amounts of potassium and base (e.g., sodium bicarbonate or trisodium citrate dihydrate) to correct acidosis and to enhance sodium absorption, and sufficient amounts of liquid. The risk of hypernatremia with use of the WHO/UNICEF ORS is a concern since infants and young children have an immature renal concentrating capacity, increased insensible water losses, and an impaired natriuretic response. Neonates and young infants may be prone to relatively slow correction of acidosis. It appears that the potassium content (20 mmol/l) of WHO-ORS should be higher to promote a net positive potassium retention. Too much glucose in the ORS will induce reverse osmosis of water into the gut, effectively making the ORS a dehydrating solution rather than a hydrating solution. Some carbohydrates other than glucose have proven effective glucose substitutes (e.g., sucrose, rice starch and powder, other cereals). Cereals have higher acceptability levels in developing countries. Research is investigating the nutritional benefits of supplementing ORS with micronutrients (e.g., vitamin A, folic acid, and zinc). ORS use with early refeeding has a beneficial effect on nutritional status after an acute diarrhea episode.     

Rice water with and without electrolytes in diarrhea with a high stool output

The objective of the study was to determine the efficacy and safety of two rice-based oral rehydration solutions, with and without added electrolyte in children presenting acute diarrheal dehydration with high stool output (> 10 mL/kg/h) during a two-hour rehydration period. Twenty-two patients of one to 18 months old were recruited and randomly distributed into two groups: group A received the rice-based solution without electrolytes, and group B received the rice-based solution with electrolytes. A stool output diminishing was observed in both groups and rehydration was achieved in 4.0 +/- 0.9 hours in 21 patients from group A and in 4.6 +/- 0.9 hours in 13 patients group group B. There was not a statistically significant difference between the groups regarding the laboratory results. The rice-based oral rehydration solution without added electrolytes was useful for rehydration of children presenting high stool output, after administering the WHO/ORS recommended formula during a two-hour period.     

Reduced beta-adrenergic sensitivity in patients with type 1 diabetes and hypoglycemia unawareness

OBJECTIVE: We tested the hypothesis that impaired tissue sensitivity to catecholamines contributes to hypoglycemia unawareness in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 21 subjects with type 1 diabetes underwent a standardized insulin infusion protocol to produce a stepwise decrease in plasma glucose to 45-min plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l. Glycemic thresholds, maximum responses for adrenergic and neuroglycopenic symptoms, and counterregulatory hormones were determined. Patients were classified as hypoglycemia unaware if the initiation of adrenergic symptoms occurred at a plasma glucose level 2 SD below that of nondiabetic volunteers. beta-Adrenergic sensitivity was measured as the dose of isoproterenol required to produce an increment in heart rate of 25 beats per minute above baseline (I25) in resting subjects. RESULTS: Subjects with type 1 diabetes and hypoglycemia unawareness experienced the onset of adrenergic symptoms at a lower plasma glucose level than did those with awareness (2.5+/-0.1 vs. 3.7+/-0.1 mmol/l, P < 0.001), whereas neuroglycopenic symptoms occurred at similar glucose levels (2.7+/-0.2 vs. 2.8+/- 0.1 mmol/l). The plasma glucose levels for counterregulatory hormone secretion (epinephrine 2.9+/-0.2 vs. 4.1+/-0.2 mmol/l; norepinephrine 2.7+/-0.1 vs. 3.2+/-0.2 mmol/l; cortisol 2.5+/-0.2 vs. 3.3+/-0.2 mmol/l, P < 0.01) were also lower in subjects with unawareness. The maximal epinephrine (1,954+/-486 vs. 5,332+/- 1,059 pmol/l, P < 0.01), norepinephrine (0.73 +/- 0.14 vs. 1.47+/-0.21 nmol/l, P = 0.04), and cortisol (276+/-110 vs. 579+/-83 nmol/l, P < 0.01) responses were reduced in the unaware group. I25 was greater in unaware subjects than in subjects without unawareness (1.5+/-0.3 vs. 0.8+/-0.2 microg), where I25 was not different from that of controls (0.8 +/-0.2 microg). CONCLUSIONS: We conclude that subjects with type 1 diabetes and hypoglycemia unawareness have reduced beta-adrenergic sensitivity, which may contribute to their impaired adrenergic warning symptoms during hypoglycemia.     

Effects of the angiotensin converting enzyme (ACE) inhibitor, captopril, on the cardiovascular, endocrine, and renal responses to furosemide in conscious lambs

Data were prospectively collected on 306 Kenyan children, including blood gases in 258 (75%). Severe malaria caused a predominantly high-anion-gap metabolic acidosis in at least 43% of children. Children with coma and respiratory distress (CM + RD) had greater evidence of renal dysfunction, lower mean pH and higher mean plasma osmolality than those with respiratory distress (RD) or coma (CM) as isolated findings (mean urea 10.7 vs. 6.0 vs. 4.3 mmol/l; mean creatinine 97 vs. 74 vs. 58 mumol/l; mean osmolality 301 vs. 288 vs. 283 mosmol/l; and mean pH 7.16 vs. 7.29 vs. 7.39, respectively, p < 0.001 for each comparison of CM + RD vs. RD or CM). In addition, children with CM + RD had a higher mean blood lactate (6.7 vs. 3.3 mmol/l, p < 0.001), a lower mean haemoglobin (5.5 vs. 7.0 g/dl, p = 0.002) and a lower mean age (26.4 vs. 41.9 months, p < 0.001) than children with CM and accounted for 15/24 (63%) of all deaths. These and previous data implicate hypovolaemia and renal impairment in the pathogenesis of metabolic acidosis in severe childhood malaria. In children who are acidotic, anaemia is strongly associated with lactic acidaemia and may therefore contribute to its pathogenesis. These data also imply that coma in acidotic children (CM + RD) and those with an isolated encephalopathy (CM) may result from quite different pathophysiological mechanisms.     

Differential regulation of genes encoding 1-aminocyclopropane-1-carboxylate (ACC) synthase in etiolated pea seedlings: effects of indole-3-acetic acid, wounding, and ethylene

OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years; sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6 years) who were treated by external pump for 5.1 +/- 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS: The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13 vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs. 8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/- 0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.     

Effects of medium-chain triglyceride ingestion on fuel metabolism and cycling performance

On three occasions separated by 10 days, six endurance-trained cyclists rode for 2 h at 60% of peak O2 uptake and then performed a simulated 40-km time trial (T-trial). During the rides, the subjects ingested a total of 2 liters of a [U-14C]glucose-labeled beverage containing a random order of either 10% glucose [carbohydrate (CHO)], 4.3% medium-chain triglycerides (MCTs); or 10% glucose + 4.3% MCTs (CHO+MCT). Although replacing CHO with MCTs slowed the T-trials from 66.8 +/- 0.4 (SE) to 72.1 +/- 0.6 min (P < 0.001), adding MCTs to CHO improved the T-trials from 66.8 +/- 0.4 to 65.1 +/- 0.5 min (P < 0.05). Faster T-trials in the CHO+MCT trial than in the CHO trial were associated with increased final circulating concentrations of free fatty acids (0.58 +/- 0.09 vs. 0.36 +/- 0.06 mmol/l; P < 0.05) and ketones (1.51 +/- 0.25 vs. 0.51 +/- 0.07 mmol/l; P < 0.01) and decreased final circulating concentrations of glucose (5.2 +/- 0.2 vs. 6.3 +/- 0.3 mmol/l; P < 0.01) and lactate (1.9 +/- 0.4 vs. 3.7 +/- 0.5 mmol/l; P < 0.05). Adding MCTs to ingested CHO reduced total CHO oxidation rates from 14 +/- 1 to 10 +/- 1 mmol/min at 2 h and from 17 +/- 1 to 14 +/- 1 mmol/min in the T-trial (P < 0.01), without affecting the corresponding approximately 5 and approximately 7 mmol/min rates of [14C]glucose oxidation. These data suggest that MCT oxidation decreased the direct and/or indirect (via lactate) oxidation of muscle glycogen. A reduced reliance on CHO oxidation at a given O2 uptake is similar to an endurance-training effect, and that may explain the improved T-trial performances.     

Colonic dysfunction in acute diarrhoea: the role of luminal short chain fatty acids

Faecal concentrations and output of short chain fatty acids (SCFA) were assessed on successive days by gas-liquid chromatography in 24 patients with acute watery diarrhoea. Absorption of water and sodium from the rectum was also measured by a dialysis technique in 17 of these patients and in nine normal subjects in the presence and absence of luminal SCFA. Faecal SCFA concentrations were low on the first day of diarrhoea (mean (SEM) 9.9 (5.8) mmol/kg) and increased to 94.8 (16.4) mmol/kg by the fifth day. Faecal output of SCFA corresponded to these figures. Net water absorption, in the absence of luminal SCFA, was stopped in patients with acute diarrhoea (-59 (81) nl/cm2/min) compared with healthy controls (+322 (63) nl/cm2/min) (p < 0.01). Luminal SCFA restored net water absorption to +184 (67) nl/cm2/min in patients with acute diarrhoea (p < 0.01). Net absorption of sodium decreased in patients with acute diarrhoea in the absence of luminal SCFA, but returned to normal with luminal SCFA. Net secretion of potassium increased in acute diarrhoea, and did not change in the presence of SCFA. Defective absorption from the rectum in acute diarrhoea is reversed by luminal SCFA. The reduction of luminal SCFA in acute diarrhoea treated conventionally may be a factor contributing to colonic dysfunction.