Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether

The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control.     

Long-limb gastric bypass in the superobese. A prospective randomized study.

This study was designed to determine whether greater diversion of bile and pancreatic secretions away from the functional gastrointestinal tract would produce greater weight loss in superobese patients (greater than or equal to 200 pounds overweight) in comparison with conventional Roux-en-Y gastric bypass (RYGB). During the past 7 years, two modifications of RYGB were prospectively compared in 45 superobese patients: RYGB-1, in which the length of defunctionalized jejunum measured 75 cm, and RYGB-2, in which the defunctionalized jejunum measured 150 cm. Respective mean preoperative weight/body mass indexes were 393 pounds/63.4 for 22 RYGB-1 patients and 404 pounds/61.6 for 23 RYGB-2 patients. Two patients (5%) had nonfatal early complications. There were six late incisional hernias. There were no cases of protein deficiency, hepatic dysfunction, or diarrhea after operation. Mean follow-up was 43 +/- 17 months. Postoperative weight loss in pounds and daily calorie intake were compared at 6-month intervals. Weight loss stabilized by 24 months at a mean 50% excess weight lost in RYGB-1 patients and 64% excess weight lost in RYGB-2 patients. Nineteen of 23 RYGB-2 patients achieved at least 50% excess weight lost versus 11 of 22 RYGB-1 patients (p less than or equal to 0.03). Weight loss was significantly greater at 24 through 36 months in RYGB-2 versus RYGB-1 patients (p less than 0.02). There was no significant difference in either calorie intake or incidence of iron and vitamin B-12 deficiency between the two groups. These data show that gastric restriction and biliopancreatic diversion without intestinal exclusion resulted in significantly greater weight loss than conventional RYGB but did not cause additional metabolic sequelae or diarrhea. This long-limb modification of Roux-en-Y gastric bypass is a safe and effective procedure in patients who are 200 pounds or more overweight.     

Benzoyl Peroxide Solubility and Stability in Hydric Solvents

Saturated solubility and reaction rate constants for the decomposition of benzoyl peroxide in solution and suspension were determined for use in formulation development. The solvents studied included ethanol, propylene glycol, and cosolvent mixtures of PEG 400 and water. The solubility of benzoyl peroxide was inversely related to the solvent polarity, with greater solubility occurring with semipolar solvents. The stability of benzoyl peroxide in solution was dependent on the solvent, concentration of benzoyl peroxide, and temperature. The compound was least stable in PEG 400. Stability was improved when water was added to PEG 400. Similar solvent effects were observed in suspension. In benzoyl peroxide suspensions of PEG 400 and PEG 400/water blends, benzoyl peroxide stability was dependent on solubility, with improved stability occurring in blends where the benzoyl peroxide was least soluble. Thus, solution formulations of benzoyl peroxide in pharmaceutically acceptable solvents are unlikely to show good stability; however, suspension formulations should be reasonably stable if the vehicle is selected to provide low benzoyl peroxide solubility.     

Patterns of spectrin expression in B-cell lymphomas: loss of spectrin isoforms is associated with nodule-forming and germinal center-related lymphomas.

Spectrins are a family of cytoskeletal proteins that organize and link membranes to subcellular motors and filaments. Although traditionally divided into erythroid and non-erythroid forms, the discovery of new spectrin isoforms in various tissues indicates that their distribution is not yet fully characterized. To our knowledge, there is no comprehensive analysis of spectrins in lymphoid malignancies. Using tumor microarrays of paraffin blocks, we immunohistochemically studied 10 lymph nodes with reactive lymphoid hyperplasia and 94 lymph nodes involved by B-cell malignant lymphoma. Expression of spectrins alphaI, alphaII, betaI, betaII, and betaIII was scored using a 20% cutoff for positive immunoperoxidase staining. All spectrin isoforms, except erythroid-specific alphaI spectrin, were detected in lymph nodes with reactive lymphoid hyperplasia. In contrast, various spectrins were lost in particular B-cell malignant lymphomas. Based on the absence of staining for one or more spectrin isoforms in at least 50% of cases, we identified three patterns: (1) loss of alphaII and betaII in follicular lymphoma, grades 2/3 and 3/3; nodular lymphocyte predominance Hodgkin's lymphoma; nodular sclerosis Hodgkin's lymphoma; (2) loss of betaI only in Burkitt lymphoma; and (3) loss of alphaII and betaI in mixed cellularity Hodgkin's lymphoma. In contrast, follicular lymphoma, grade 1/3 and diffuse large B-cell lymphoma retained spectrin in 67-100% of cases. The other lymphoma subtypes retained spectrin in greater than 50% of cases. We identified the loss of particular spectrin isoforms in B-cell malignant lymphomas that have a nodular growth pattern and/or are believed to arise from germinal center B-cells, that is follicular lymphoma, grades 2/3 and 3/3; Burkitt lymphoma; nodular sclerosis Hodgkin's lymphoma; mixed cellularity Hodgkin's lymphoma; and nodular lymphocyte predominance Hodgkin's lymphoma. The absence of particular spectrin isoforms may correlate with transformation or aggressive biologic behavior for some lymphoma subtypes.     

Air embolism of the brain in rabbits pretreated with mechlorethamine

Infusion of 400 microliters air into the left internal carotid artery of five anesthetized rabbits caused transient pial arteriole air embolism, an immediate 41.9 +/- 0.8% dilatation of the embolized vessels, suppression of the cortical somatosensory evoked response to 29.4 +/- 2.7% of baseline, and a progressive decline in ipsilateral cerebral blood flow (measured by hydrogen clearance) to 46 +/- 4.1% of baseline after 2 hours. These values were significantly different from those at baseline and from the responses of 10 control rabbits given equivalent intracarotid saline infusions. Twelve other rabbits were made leukopenic by treatment with 1.5 mg/kg i.v. mechlorethamine 72 hours prior to study. Mean +/- SEM leukocyte count decreased from 6,320 +/- 73/mm3 to 1,890 +/- 66/mm3 without any change in the leukocyte differential or erythrocyte and platelet counts. Intracarotid infusion of saline into seven of the leukopenic rabbits caused no changes. In the other five leukopenic rabbits, infusion of 400 microliters air caused air embolism but did not produce the anticipated declines in cerebral blood flow or the cortical somatosensory evoked response, both of which remained indistinguishable from baseline values and responses in the seven saline-treated leukopenic controls. Similarly, air-embolized arterioles showed nonsignificant dilatation in leukopenic rabbits. Our data suggest that the decreases in both cerebral blood flow and brain function seen after air embolism require the presence of leukocytes.     

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.