A randomized prospective study comparing two flexible epidural catheters for labour analgesia.

BACKGROUND: Previous studies evaluating stiff epidural catheters found that the three-holed design provided superior labour analgesia compared with an end-holed design. This was believed due to improved medication distribution. Recently, flexible epidural catheters with both designs have been shown to be superior to the stiff epidural catheters. We investigated the success of labour analgesia comparing the flexible three-holed with the flexible end-holed epidural catheter. METHODS: This was a prospective, single-blinded randomized study. We enrolled 500 parturients in active labour. The primary outcome was complete relief of labour pain assessed at 30 min. We also assessed the occurrence of paresthesias, intravascular and intrathecal placement, catheter replacement, and treatment of breakthrough pain during labour. Comparisons were made using Pearson's chi(2), with significance determined at the 0.05 level. RESULTS: Four hundred and ninety-three subjects completed the study. Initial analgesia was similar (complete labour analgesia: end-holed=85% vs 80% 95% CI of difference: 13% to -3%; P=NS). The incidence of paresthesia was similar (end-holed=3.6% vs 5.3%; P=NS). There was one intrathecal and three intravascular catheters in the three-holed group and two intravascular catheters in the end-holed group. The number of supplemental boluses and catheter replacements required during labour was similar between the groups. CONCLUSIONS: There were no differences in the initial analgesia success rate, complications, or labour analgesia between end-hole vs multi-hole flexible epidural catheters.

Epidural anesthesia in a parturient with neurofibromatosis type 2 undergoing cesarean section.

Neurofibromatosis type 2 (NF2) is a rare condition only recently recognized. We present a case describing successful regional analgesia in a parturient with NF2 after thorough imaging revealed no tumors within the epidural space. The presence of tumors within the spinal cord and nerve roots and their potential enlargement during pregnancy make routine neuraxial anesthesia hazardous in patients with NF2. Lumbosacral imaging before performing regional anesthesia is recommended.

Rapid development of severe copper deficiency in a patient with Crohn's disease receiving parenteral nutrition.

A 32-year-old man with active Crohn's disease and recurrent small bowel strictures underwent abdominal surgery and was subsequently given total parenteral nutrition (TPN). Severe cholestasis developed and copper was removed from the TPN. Although serum ceruloplasmin levels were within normal limits, 8 weeks after copper removal, he developed pancytopenia. Serum copper levels were severely depressed. Bone marrow biopsy was consistent with copper deficiency; cytoplasmic vacuolization of both myeloid and erythroid precursors, megaloblastic erthropoiesis, and marked hypocellularity were observed. IV replacement with copper sulfate resulted in improvement in the patient's anemia, neutropenia, and thrombocytopenia, but the patient died suddenly from cardiac tamponade. Postmortem examination revealed fibrinous and hemorrhagic pericarditis. Despite the rare occurrence of overt copper deficiency, this case emphasizes the need to recognize copper deficiency as an important etiology of iron-resistant anemia in patients receiving TPN. Furthermore, the relative rapidity with which our patient developed pancytopenia suggests that, in view of the established recommendation that copper be removed from TPN in cholestatic conditions, serum copper levels must be measured periodically.

A double-blind, placebo-controlled study of the effectiveness and safety of nizatidine in the prevention of postprandial heartburn.

BACKGROUND: Heartburn is frequently associated with overindulgence in food and drink, meal-stimulated gastric acid secretion, and a gastroesophageal reflux with a pH of 4 or lower. Nizatidine is a selective histamine2 receptor antagonist that effectively suppresses gastric acid secretion at lower than prescription doses and has been approved for nonprescription use in the prevention of postprandial heartburn. OBJECTIVE: To examine the relative effectiveness of 3 dose levels of nizatidine (225 mg, 75 mg, and 25 mg) in preventing postprandial heartburn. METHODS: Four hundred thirteen subjects with documented moderate to severe heartburn following a standard meal that provoked heartburn were randomized to receive a single dose of nizatidine at 225 mg (n = 104), 75 mg (n = 101), or 25 mg (n = 105), or placebo (n = 103) 30 minutes before the meal, at 30 minutes (immediately after completing the meal), and at 60, 90, 120, 150, 180, and 210 minutes (from beginning the meal), subjects assessed the presence or absence of heartburn (yes or no) and the severity of heartburn (100-mm visual analog scale). RESULTS: The use of both 225 mg and 75 mg of nizatidine were significantly better than placebo in preventing heartburn in the proportion of subjects with complete prevention of heartburn (15 [14.4%] and 15 [14.9%], respectively, vs 3 [2.9%]; P < .001); the effects of nizatidine, 25 mg, in 7 subjects (7%) were not distinguishable from placebo. Similar results for nizatidine, 225 mg and 75 mg, were seen for longest duration of no heartburn, total duration of no heartburn, the average severity of heartburn, and the peak heartburn severity. All 3 doses of nizatidine were superior to placebo (P < .001) in reducing average and peak heartburn severity and were well tolerated. CONCLUSIONS: Single doses of 225 mg and 75 mg of nizatidine administered 30 minutes before a standard meal intended to provoke heartburn are significantly more effective than placebo for the prevention and/or reduction of postprandial heartburn.

Saccharomyces cerevisiae infections and antifungal susceptibility studies by colorimetric and broth macrodilution methods.

Saccharomyces cerevisiae was isolated in large numbers from operative specimens from two patients with perforated bowel and peritonitis and from the blood of another patient treated with extracorporeal membrane oxygenation. Susceptibility studies were performed on these three isolates and another 29 isolates that colonized or caused infection in a total of 19 patients seen over the last decade. All isolates had low minimum inhibitory concentration (MIC) values for amphotericin B (MIC90 of < or = 0.02 microgram/ml) and flucytosine (MIC90 of 0.2 microgram/ml), and a broader range of MIC values for itraconazole (MIC90 of 0.8 microgram/ml) and fluconazole (MIC90 of 4 micrograms/ml). A colorimetric method using Alamar blue reagent showed good concordance with the standard broth macrodilution method for amphotericin B, flucytosine, and fluconazole, but less good concordance for itraconazole. Serious infections with S. cerevisiae probably should be treated with amphotericin B, with or without the addition of flucytosine.

A 43 kD c-mos protein is only expressed before meiosis during rat spermatogenesis.

We have investigated the RNA and protein expression pattern of the rat c-mos proto-oncogene during spermatogenesis. In mouse testis a 43kD c-mos protein is expressed throughout spermatogenesis, which is in agreement with one report detecting a 1.7 kb c-mos RNA in pachytene spermatocytes and in early spermatids. However, several other reports show that the mouse 1.7 kb c-mos RNA is exclusively expressed in post-meiotic male germ cells. We report that in rat male germ cells three c-mos RNA species of 5, 3.6 and 1.7 kb are detectable by Northern blotting analysis both before and after meiosis, with highest levels in early spermatids. However, western immuno-blot analysis reveals the presence of a 43 kD c-mos protein in total testis and pachytene spermatocytes, but not in post-meiotic cells. These findings combined with those made in the mouse system strongly suggest that c-mos protein may be a regulator of meiosis during spermatogenesis.

Percutaneous transluminal renal angioplasty in management of atherosclerotic renovascular hypertension: results in 100 patients.

The long-term effect of percutaneous transluminal renal angioplasty (PTRA) on blood pressure and renal function was assessed in 100 consecutive patients with atherosclerotic renovascular hypertension. Technical success rates (complete plus partial) of a first PTRA averaged 76.2%, 74.1%, and 67.7% for the unilateral (n = 42), bilateral (n = 27), and solitary (n = 31) groups, respectively. Of the technical successes, 59% (43/73) experienced sustained blood pressure benefit (mostly amelioration) during a mean follow-up period of 29 months. Rates of blood pressure benefit were similar in the three groups. Ostial lesions comprised the majority of blood pressure benefit failures. Repeat angioplasty in 14 patients resulted in a 71% technical success rate and a 50% blood pressure benefit rate during a mean follow-up period of 22 months. Long-term stability of mean serum creatinine level was observed after technically successful angioplasty in all three groups. Acute renal insufficiency, which was reversible in all but one patient, complicated 26% of the procedures. Mechanical complications occurred in 14% (20/145) of the arteries acted on; surgical intervention was required in five patients. The mortality rate was 2%. These results suggest that angioplasty is effective in both the long-term management of renovascular hypertension and the preservation of renal function in a large fraction of patients with atherosclerotic renovascular hypertension.

Platelet membrane glycoprotein IIIa contains target antigens that bind anti-platelet antibodies in immune thrombocytopenias.

The precise pathogenic mechanism of platelet destruction in immune thrombocytopenias is not known, although many investigators have found that platelet-associated IgG is increased in these diseases. We report here the differentiation between specific binding of anti-platelet antibody, associated with platelet destruction, and the ubiquitous presence of nonspecific, platelet-associated IgG. Using an electrophoretic separation and antibody overlay technique, we have identified a specific membrane protein that bears target platelet antigens in immune thrombocytopenias. When posttransfusion purpura serum was studied, antibody binding to the PlA1 antigen on glycoprotein IIIa was readily distinguished from the nonspecific binding of immunoglobulin to a protein of 200,000 mol wt. After reduction of disulfide bonds, the PlA1 antigenicity was not observed, and IgG bound nonspecifically to a protein band with an apparent molecular weight of 45,000. We have also identified anti-platelet antibodies in patients with idiopathic thrombocytopenic purpura and determined their antigenic specificity. Antibodies which bind to a 100,000-mol wt protein were found in nine of thirteen patients with chronic disease. The antigens in three of these cases were studied in detail by using both reduced and nonreduced control and Glanzmann's thrombasthenic platelets. Target antigens were localized to glycoprotein IIIa, but are different from PlA1. The immune thrombocytopenic purpura antigenic system is clearly distinguished from nonspecific platelet-associated IgG. Sera from eight children with acute idiopathic thrombocytopenic purpura were also studied. In all cases, the nonspecific IgG binding to the 200,000-mol wt protein was observed. However, we were unable to demonstrate antibody binding to glycoprotein IIIa, which suggested that the acute childhood form of this disease may have a different pathogenic mechanism than that of the autoimmune chronic cases.

An analogue of the erythroid membrane skeletal protein 4.1 in nonerythroid cells.

Protein 4.1 is a crucial component of the erythrocyte membrane skeleton. Responsible for the amplification of the spectrin-actin interaction, its presence is required for the maintenance of erythrocyte integrity. We have demonstrated a 4.1-like protein in nonerythroid cells. An antibody was raised to erythrocyte protein 4.1 purified by KCl extraction (Tyler, J. M., W. R. Hargreaves, and D. Branton, 1979, Proc. Natl. Acad. Sci. USA, 76:5192-5196), and used to identify a serologically cross-reactive protein in polymorphonuclear leukocytes, platelets, and lymphoid cells. The cross-reactive protein(s) were localized to various regions of the cells by immunofluorescence microscopy. Quantitative adsorption studies indicated that at least 30-60% of the anti-4.1 antibodies reacted with this protein, demonstrating significant homology between the erythroid and nonerythroid species. A homologous peptide doublet was observed on immunopeptide maps, although there was not complete identity between the two proteins. When compared with erythrocyte protein 4.1, the nonerythroid protein(s) displayed a lower molecular weight--68,000 as compared with 78,000-and did not bind spectrin or the nonerythroid actin-binding protein filamin. There was no detectable cross-reactivity between human acumentin or human tropomyosin-binding protein, which are similarly sized actin-associated proteins, and erythrocyte protein 4.1. The possible origin and significance of 4.1-related protein(s) in nonerythroid cells are discussed.

High yield purification of protein 4.1 from human erythrocyte membranes.

Protein 4.1 has been purified from human erythrocyte membranes by a simple method employing the nonionic detergent Tween 20 and anion exchange chromatography. The procedure results in the production of large quantities of protein 4.1, which retains immunoreactivity and the functional properties of binding to spectrin and enhancing the interaction of spectrin and actin.

Metabolic regulation as a control for lipid disorders. II. Influence of (--)-hydroxycitrate on genetically and experimentally induced hypertriglyceridemia in the rat.

These studies were designed to determine whether genetically and experimentally induced hypertriglyceridemia were correlated with hyperlipogenesis, and whether inhibiting fatty acid synthesis would reduce serum triglyceride levels. Hypertrigylceridemia, resulting from genetic obesity in Zucker rats and fructose feeding or Triton administration to Charles River rats, was examined in relation to in vivo rates of heatic fatty acid synthesis, and the influence of (--)-hydroxycitrate (a potent competitive inhibitor of ATP citrate lyase) on serum triglyceride levels and lipogenesis was determined. Zucker obese rats demonstrated significantly increased rates of fatty acid synthesis and levels of serum triglycerides compared to their lean litter mates; lipogenic rates and circulating triglycerides were reduced markedly by the oral administration of (--)-hydroxycitrate. Fructose administered in the diet or drinking water induced a hypertriglyceridemia which was associated with a marked increase in hepatic lipogenesis, and (--)-hydroxycitrate reduced significantly both parameters. In contrast to the significant role that increased rates of lipogenesis apparently played in the development of hypertriglyceridemia in the Zucker rat and fructose-fed rat, Triton given intravenously produced a marked rise in serum triglycerides which could not be accounted for, to an appreciate extent, by increased rates of fatty acid synthesis. (--)-Hydroxycitrate reduced serum triglyceride levels and hepatic lipogenic rates equivalently in the Triton-treated and nontreated rats.