Alcoholic ketoacidosis with multiple complications: a case report.

Alcoholic ketoacidosis is a poorly diagnosed medical emergency usually identified in chronic alcohol misusers following an abrupt cessation or reduction of alcohol consumption. A high index of suspicion should be maintained by acute physicians as response to treatment is rapid with complete resolution of metabolic derangements. Complications are usually the result of not instituting the correct treatment or not addressing associated conditions. We describe a case of alcoholic ketoacidosis with multiple complications at presentation.

A clinical safety trial of stroma-free hemoglobin.

A stroma-free hemoglobin (SFH) solution was prepared which was sterile, pyrogen free, and contained only 1.2% of the stromal lipid present in unpurified hemolysate, 250 ml of which was administered slowly intravenously to 8 healthy men. Two control subjects received 250 ml of serum albumin. The SFH infusions were generally well tolerated by 7 of the 8 men. One subject developed abdominal pain and costovertebral angle tenderness after infusion, which disappeared within 48 hr. Bradycardia and a mild increase in blood pressure was present during ths SFH infusions and for 4 to 5 hr thereafter. A decrease in urine output and endogenous creatinine clearance appeared during the SFH infusions and for 2 to 4 hr after infusion. A mild prolongation of the activated partial thromboplastin time developed immediately after infusion. Gross hemoglobinuria appeared as expected during the SFH infusions and completely disappeared by 6 to 10 hr after infusion. All the cardiovascular, renal, and clotting changes were present for only a few hours after the SFH infusion, during the hemoglobinemia (free Hb in plasma). At 24 hr and 7 days after infusion all measurements were normal, and 6 mo follow-up showed no abnormalities or hepatitis.

Etodolac, aspirin, and gastrointestinal microbleeding.

The effects of etodolac, a new nonsteroidal anti-inflammatory drug, on gastrointestinal (GI) microbleeding were quantitatively assessed in two studies in healthy adult men. The first was a two-group, open-label, parallel comparison of etodolac, 600 mg/day, aspirin, 2600 mg/day, and placebo in 20 subjects; the second was a four-group, double-blind, parallel comparison of etodolac, 600, 800, and 1200 mg/day, aspirin, 2600 mg/day, and placebo in 41 subjects. Subjects in both studies received a single-blind placebo on days 1 through 7, either etodolac or aspirin on days 8 through 14, and a single-blind placebo on days 15 through 19. GI blood loss (milliliters per day) was estimated by the radiolabeled (51Cr) erythrocyte method and was based on daily radioactivity counts of stool specimens and regression-estimated daily blood radioactivity. Etodolac, 600 mg/day, induced no significant GI blood loss at any time during the experiments, nor was there significant blood loss after 800 and 1200 mg/day in experiment 2. Blood loss was noted after aspirin in both.

Single- and multiple-dose kinetics of estazolam, a triazolo benzodiazepine.

The pharmacokinetic properties of estazolam, a triazolo benzodiazepine hypnotic agent, were assessed in a series of healthy volunteers following single and multiple doses. After single oral doses of 2--16 mg, peak plasma concentrations were reached within 6 h. Values of elimination half-life ranged from 8.3--31.2 h (mean 17.0 h) and did not vary significantly with dose. During 3 weeks of therapy, steady-state plasma concentrations increased approximately in proportion to increasing doses. and accumulation was essentially complete within 3 days of each dose change. The mean observed accumulation ratio was 1.84, which was slightly larger than the predicted ratio of 1.53. Exposure to multiple-dose estazolam therapy had no significant influence on the kinetics of a single dose of antipyrine, suggesting that estazolam neither stimulates nor inhibits enzyme activity in humans. Thus the accumulation and elimination kinetics of estazolam can be classified as intermediate to those of the short-acting (such as oxazepam) and the long-acting (such as diazepam) benzodiazepine derivatives.

Effect of cetamolol on epinephrine-induced hypokalemia.

The effect of cetamolol (an investigational cardioselective beta blocker with intrinsic sympathomimetic activity) on the hypokalemic response to epinephrine infusions in normal subjects was evaluated and compared with placebo and two other beta-adrenergic blocking drugs. After two daily doses of cetamolol 15 mg, atenolol (a cardioselective beta blocker) 50 mg; a long-acting propranolol preparation (a nonselective beta blocker) 80 mg; or placebo, 12 men (mean age, 26.7 years) were infused with epinephrine. The resulting average plasma epinephrine level was 1123 pg/mL, whereas average baseline serum potassium levels for the four treatment groups ranged from 3.94 to 4.07 mEq/L. Epinephrine-induced hypokalemia occurred in the placebo group (maximum potassium decrease of 1.00 mEq/L) and in the atenolol group (maximum potassium decrease of 0.59 mEq/L); potassium levels did not decrease but rose slightly in subjects receiving cetamolol or propranolol. Subjects treated with placebo or atenolol also demonstrated statistically significant prolongation of the QTc interval (0.039 seconds with placebo; 0.023 seconds with atenolol) and frequently developed T-wave flattening and U-wave appearance. After pretreatment with cetamolol or propranolol, however, the QTc interval was unaffected, T-wave abnormalities did not occur, and U waves appeared only rarely. The results of this study indicate that cetamolol blocks epinephrine-induced hypokalemia and associated electrocardiographic changes.

The magnesium content of duodenal mucosa in man.

The magnesium content of duodenal mucosa was estimated in biopsy specimens from 50 patients, 43 of which had normal mucosal histopathology. There was no significant difference in the mean mucosal magnesium content of those speciments with normal and abnormal histopathology and overall the mean value was 30.9 mmol/kg dry weight of tissue, but there was a wide spread of values. The concentration of magnesium in plasma and duodenal fluid was also determined. There was no significant correlation between duodenal mucosal magnesium content and plasma magnesium concentration. However, there was a weak but statistically significant correlation between magnesium content in duodenal fluid and duodenal mucosa (r = 0.54, p less than 0.001).

The lens in hereditary hyperferritinaemia cataract syndrome contains crystalline deposits of L-ferritin.

BACKGROUND/AIM: Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disorder characterised by elevated serum L-ferritin and bilateral cataracts. The ocular manifestations of this disorder are poorly studied. This study therefore sought to determine the origin of cataracts in HHCS. METHODS: L-ferritin ELISA, immunohistochemical and ultrastructural analysis of a lens nucleus from an HHCS individual. RESULTS: The HHCS lens L-ferritin content was 147 microg/g dry weight of lens compared with <16 microg/g for a non-HHCS control cataract lens. The cataract comprised discrete crystalline inclusions with positive staining with anti-L-ferritin but not anti-H-ferritin. CONCLUSIONS: This unusual finding of crystalline opacities in the lens may be unique to HHCS and is likely to result from disturbed metabolism of L-ferritin within the lens or an abnormal interaction between L-ferritin and lens proteins.

Helicobacter pylori infection and upper gastrointestinal patholgy in a British immigrant Indian community.

OBJECTIVES: To assess the pattern of upper gastrointestinal pathology and the prevalence of Helicobacter pylori infection in the Southall Indian community. DESIGN: A prospective study of endoscopic findings in 124 Indian and 107 whites from the Southall area. In a separate study blood samples were taken from 100 Indian subjects presenting to a single general practitioner in Southall. METHODS: The presence of gastritis and H. pylori infection was assessed histologically in Indian and white patients undergoing endoscopy. Serum samples were analysed using a specific enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori immunoglobulin G. RESULTS: In the endoscopic study, Indian and white patients had the same rate of H. pylori infection (52% vs. 43%, respectively) (P= NS). The pattern of upper gastrointestinal pathology was similar in whites and Indians. In the general practice based study 41 subjects were H. pylori seropositive. Seropositivity increased with age (P<0.05). CONCLUSION: There is no excess of H. pylori-related pathology in Southall immigrant Indians. The similarity of upper gastrointestinal pathology in UK Indian and white patients presenting for endoscopy suggests that the high rates of duodenal ulceration, gastritis and H. pylori infection in India are environmentally rather than racially determined.

Comparative assessment of enprofylline and theophylline for chronic obstructive airways disease in the elderly.

Enprofylline, a recently developed xanthine derivative, is a more potent bronchodilator than theophylline. This study compares the efficacy and safety of enprofylline with theophylline for chronic obstructive airways disease (COAD) in elderly subjects. The study was of a randomized double-blind parallel design and commenced with a 1-week reference period when oral bronchodilators were withdrawn. Patients were then treated with either enprofylline or theophylline 150 mg bd for 2 weeks (period 1) followed by 300 mg bd for a further 3 weeks (period 2). Patients recorded peak expiratory flow rate (PEFR) and adverse experiences, if any, in a diary, daily. Of 111 patients recruited for the study, 85 entered active treatment (theophylline, n = 44; enprofylline, n = 41). Mean age was 72 years and mean bronchodilator reversibility was 22%. Enprofylline increased mean morning PEFR by 11% (period 1) and 19% (period 2) whereas theophylline increased PEFR by 13% and 19%, respectively. From the enprofylline group 29% were withdrawn from the study due mainly to headache and nausea/vomiting and from the theophylline group 7% were withdrawn due mainly to nausea/vomiting. Mean plasma concentrations of enprofylline were 2.0 mg l-1 and 3.4 mg l-1, and with theophylline 5.4 mg l-1 and 10.0 mg l-1 at the end of periods 1 and 2, respectively. Enprofylline and theophylline produced similar improvements in lung functions and symptoms of chronic obstructive airways disease, but enprofylline was less well tolerated than theophylline.

Longitudinal study of plasma ACTH and cortisol in very low birth weight infants in the first 8 weeks of life.

There are few published data on plasma ACTH and cortisol in very low birth weight (VLBW) infants beyond the first week of life. We therefore measured plasma ACTH and cortisol longitudinally in 25 infants (mean birth weight 1025 g, mean gestational age 28 weeks) at 1, 2, 4 and 8 postnatal weeks to document normative values for infants not receiving dexamethasone. We also examined the influence of clinical state and dexamethasone treatment on plasma ACTH and cortisol levels. Median plasma ACTH increased significantly with advancing postnatal age from 1 week to 8 weeks (21.0 vs. 40.0 ng/l; P = 0.01) but did not correlate with postconceptional age. Median plasma cortisol decreased significantly with advancing postnatal age from 1 week to 8 weeks (216 vs. 50 nmol/l; P = 0.001) and correlated inversely with postconceptional age (P = 0.004). At 8 weeks infants who were clinically well (n = 6) had lower plasma ACTH values compared with sick (n = 6) infants (median: 37.0 vs. 63.5 ng/l; P = 0.033). Plasma ACTH did not correlate with clinical state at 1, 2 and 4 weeks. At none of the postnatal ages studied was plasma cortisol influenced by the degree of sickness. Five infants received dexamethasone to assist weaning from mechanical ventilation. Their median plasma ACTH level, at 8 weeks, was significantly lower than that of the 12 infants who did not receive dexamethasone (11.0 vs. 40.0 ng/l; P = 0.0006). Plasma cortisol was not significantly influenced by dexamethasone treatment (P = 0.27). These data provide further information on the evolution of adrenocortical function in VLBW infants in the first months of life.

Etodolac, a new nonsteroidal anti-inflammatory drug: gastrointestinal microbleeding and endoscopic studies.

A review of the literature is presented on the gastrointestinal effects of etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), as evaluated in both microbleeding and endoscopic studies. In four microbleeding studies, gastrointestinal blood loss in healthy subjects was estimated by a 51Cr-erythrocyte labeling method before drug treatment, after 7 days of treatment with NSAIDs including etodolac, and 1 week after the last day of treatment. In these 7-day studies, the gastrointestinal blood loss seen with etodolac (600 to 1200 mg/day) was similar to that seen with placebo and significantly (p less than 0.05) less than that seen with aspirin (2600 mg/day), naproxen (750 mg/day), ibuprofen (2400 mg/day), or indomethacin (200 mg/day). Naproxen, ibuprofen, and indomethacin caused mean daily blood losses in excess of 1 ml/day over baseline values. The increase with aspirin was 4 to 5 ml/day. In contrast, the greatest mean daily increase in blood loss with etodolac therapy was 0.2 ml. In a 4-week study of etodolac (600 and 1000 mg/day) and piroxicam (20 mg/day) given to patients with osteoarthritis or rheumatoid arthritis, blood loss seen with etodolac was comparable to that seen with placebo and significantly less than that seen with piroxicam. Gastrointestinal irritation was also assessed by endoscopy after 1 week of NSAID or placebo treatment. Endoscopy scores after etodolac treatment (up to 1200 mg/day) were similar to scores at baseline and after placebo and were significantly lower than scores following treatment with aspirin (3900 mg/day), indomethacin (200 mg/day), ibuprofen (2400 mg/day), or naproxen (100 mg/day). The effects of etodolac (600 or 1000 mg/day) and diclofenac (150 mg/day) were not different from each other or from baseline. These data indicate that etodolac, in these studies, did not cause clinically significant gastrointestinal microbleeding or visible gastric injury. By the criteria used in these studies, etodolac is less irritating to the gastrointestinal tract than aspirin, indomethacin, ibuprofen, naproxen, or piroxicam, and compares favorably with diclofenac.

Adrenocorticotropin administration during early gestation on conceptus development in swine.

The purpose of this study was to examine the effect of exogenous adrenocorticotropin (ACTH), administered to gilts during early stages of gestation, upon fetal survival and various maternal and conceptus parameters. Forty-eight gilts of approximately 6-7 months of age were bred by means of artificial insemination after detection of the second estrus and randomly allotted to one of 12 treatment-period groups. Treatment consisted of a daily intramuscular injection of 0, 40 or 80 U.S.P. units of a long acting ACTH preparation for a period of five days. The injection periods were 1-5, 6-10, 11-15 or 16-20 days of gestation with day one corresponding to 48 hours post-estrus detection. All gilts were slaughtered at approximately 37 days of gestation. Forty-two of the 48 inseminated gilts conceived. Conception rate was not different (P>.10) among the 12 treatment-period combinations. Percent fetal survival was greater (P<.09) in gilts receiving 80 U.S.P. units of ACTH (82 +/- 4.3%; X +/- SEM ) than in gilts receiving 40 U.S.P. units of ACTH (68.8 +/- 4.5%). The percent fetal survival in the control group (71.7 +/- 3.9%) was not different (P>.10) from either of the two ACTH treatment groups. A significant (P<.05) treatment by period interaction for percent fetal survival was observed. The lowest percent fetal survival (48.0 +/- 9.0%) was observed in gilts receiving 40 U.S.P. units of ACTH on day 11-15 of gestation. No significant (P>.10) differences were detected among the 12 treatment-period combinations for any of the maternal or conceptus parameters measured.

The Neonatal Neurobiologic Risk Score: does it predict outcome in very premature infants?

OBJECTIVE: To examine the validity of the Neonatal Neurobiologic Risk Score (NBRS) for predicting neurodevelopmental outcome to 3 years in infants born at < 28 weeks gestation. METHOLDOLOGY: The NBRS was retrospectively determined for 56 consecutive infants cared for in our NICU and prospectively followed to 3 years. Neurodevelopmental assessments performed at 3 years were correlated with the NBRS, and the predictive powers of individual items in the NBRS determined. RESULTS: The mean (range) birth weight was 908 (514-1295) g and gestational age was 26 (24-27) weeks. Three-year outcome was abnormal in 12 (21%) infants. A high NBRS at discharge was associated with an increased risk of abnormal 3-year outcome (odds ratio 2.56; 95% C.I. 1.4-4.7, p = 0.002). A modified NBRS using only significantly predictive items (acidosis, hypoxemia, hypotension, intraventricular hemorrhage, infection and hypoglycemia) demonstrated high sensitivity (1.00), specificity (0.98), positive predictive value (0.92) and negative predictive value (1.00) for abnormal 3-year outcome. CONCLUSIONS: This study confirms the validity of the NBRS as a simple and objective means of identifying very premature infants at highest risk of abnormal neurodevelopmental outcome, and of identifying specific events which may contribute to such outcomes.