Symptomatic and Clinical Improvement in Morbidly Obese Patients with Gastroesophageal Reflux Disease Following Roux-en-Y Gastric Bypass

Background: Patients who suffer with gastroesophageal reflux Disease (GERD) endure a worsening of symptoms as their weight increases. When medical treatment of this condition in the morbidly obese patients fails, surgical intervention may be indicated. Choosing a procedure which not only helps achieve weight control but which also relieves symptoms and complications of GERD is the goal. We present a review of patients who have undergone Roux-en-Y Gastric Bypass (RYGBP) and related procedures for this disease. Methods: One hundred eighty-eight patients undergoing surgery for morbid obesity and for GERD in 1992-1996 were contacted by mail or phone. All of these patients had undergone preoperative esophagogastroduodenoscopy to grade the severity of their disease. Their preoperative symptoms were compared to those experienced postoperatively. Results: One hundred thirty patients underwent a RYGBP with modified Hill fundopexy, 22 patients underwent a distal gastrectomy with modified Hill fundopexy, 8 patients underwent distal gastrectomy alone and 28 patients underwent RYGBP alone. There have been no deaths. There were nine surgical complications, eight early and one at 2.5 years postoperation. Follow-up is 4-48 months. The average BMI dropped from 43 to 30.2 kg/m². Whereas all patients were on some form of medical therapy before surgery, only 14 reported the need for medication postoperatively. Conclusions: Surgical intervention for weight control and treatment of GERD has been highly successful in our experience both with respect to weight control and to the reduction of reflux symptoms. Depending upon endoscopic and operative findings a RYGBP with or without an antireflux procedure can provide dramatic improvement. Gastrectomy with antireflux modifications is appropriate in selected cases.     

Neonatal necrotizing enterocolitis

PURPOSE: A retrospective, 12-year review of neonatal necrotizing enterocolitis was undertaken at a county hospital, with emphasis on presentation signs and symptoms. METHODS: Eighty-two patients with presence of intramural air were included in the study. The following signs and symptoms were studied: evidence of respiratory distress, use of umbilical catheters, white blood cell count and temperature at presentation, time interval from birth to diagnosis and time interval from diagnosis to operative intervention, presence of intramural air, air in biliary tree or free air, changes in abdominal girth, and presence of occult or gross blood in stools. Comparison was done among infants who had surgical or medical treatment, premature and full-term infants, and infants who had neonatal necrotizing enterocolitis less than or more than 20 days after birth. RESULTS: Eleven patients had a fatal outcome, with an overall survival of 87 percent. Sixty-four patients were treated medically and 18 had operative treatment. Mortality of the surgically treated group was 44 percent. Neonates who had surgical intervention had a left shift of the white blood cell count more commonly present, and all had documented abdominal distention. There were 62 premature and 20 full-term neonates in the group. Full-term neonates developed neonatal necrotizing enterocolitis earlier after birth (5.3 days compared with 15.3 days in the premature neonate group). Full-term neonates had a better prognosis in our series. Presentation of symptoms more than 20 days after birth did not change outcome. CONCLUSION: Our results reflect the experience of a community-based hospital. Clinical acumen remains the cornerstone of diagnosis and management.     

Rehabilitation of musicians with upper limb amputations

Three saxophone players with upper limb amputations have been successfully rehabilitated to play their musical instruments using skin-conductivity touch control. Each attained a standard of musicianship sufficient to perform the standard repertoire of the instrument in a concert setting. The mechanical and electrical modifications to the saxophone are described, as well as the principles of operation of the skin-conductivity touch control module. The touch control module is commercially available for prosthetists who wish to fit musicians or others with upper extremity amputations who require rapid accurate control of a number of channels of powered prosthetic function.     

Respiratory health status in swine producers using respiratory protective devices

A cross-sectional survey on respiratory health in swine producers showed that 30% of 301 examined men usually used a dust mask when working inside a barn. They did not differ significantly from dust mask nonusers in respect to respiratory symptoms and lung function. This analysis was undertaken to determine whether the respiratory health of dust mask users was associated with reasons why they had started individual respiratory protection. The subjects were recontacted in order to identify those who started using a mask to deliberately prevent symptoms (42 men) and those who started protection because of pre-existing respiratory symptoms (44 men). Not unexpectedly, betweengroup comparisons of respiratory symptoms and lung function suggest that swine producers who wear dust masks for preventive purposes have better respiratory health than those who wear dust masks because of symptoms or those who do not use individual respiratory protection. The individual reasons for starting dust mask usage should be examined among potential determinants of the outcomes of prospective studies which can then provide more valid assessment of the effect of individual respiratory protection. © 1993 Wiley-Liss, Inc.     

Effect produced by acute and chronic administration of the selective 5-HT3 receptor antagonist BRL 46470 on the number of spontaneously active midbrain dopamine cells in the rat

This study examined the effect of acute and chronic administration of the selective 5-HT₃ receptor antagonist BRL 46470A, an analog of granisetron, on the number of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (A9 or SNC) and the ventral tegmental area (A10 or VTA) in the rat. In the A10 area, the acute administration of BRL 46470A decreased the number of spontaneously active DA cells at a dose of 0.1 mg/kg (0.28 μmol/kg) ip, yet increased the number of spontaneously active DA cells at a dose of 0.3 mg/kg (0.84 μmol/kg). The chronic administration (21 days) of BRL 46470A appeared to produce a multiphasic dose-response curve. Thus, the chronic treatment with BRL 46470A increased the number of spontaneously active A10 DA cells at 0.03 (0.084 μmol) and 0.3 mg/kg, but decreased the number of spontaneously active A10 DA cells at a dose of 0.1 mg/kg. In contrast, BRL 46470A did not decrease the number of spontaneously active A9 DA cells after either acute or chronic administration (0.01-0.3 mg/kg). However, BRL 46470A did increase the number of spontaneously active A9 DA cells at acute and chronic doses similar to those that were effective in A10. The iv administration of (+)-apomorphine (APO) not only failed to reverse the decrease produced by chronic administration of BRL 46470A at 0.1 mg/kg, but further decreased the number of spontaneously active A10 DA cells. Similar to the results obtained with granisetron, the pretreatment of naive rats with either 0.01 or 0.1 mg/kg iv of BRL 46470A significantly potentiated (2-fold) the suppressant action of APO on the basal firing rate of A10, but not A9 DA cells. Overall, our results indicate that similar to granisetron, chronic BRL 46470A at 0.1 mg/kg selectively decreases the number of spontaneously active A10 DA cells, via a mechanism not related to depolarization inactivation. Presently, it is not clear what factors may contribute to the multiphasic dose-response curve of BRL 46470A. © 1994 Wiley-Liss, Inc.     

Chemistry,Pharmacology, Pharmacokinetics,and Clinical Applications of Mesalamine for the Treatment of Inflammatory Bowel Disease

Mesalamine is the therapeutically active moiety of sulfasalazine used to treat inflammatory bowel disease. A controlled-release mesalamine capsule (Pentasa) is designed to release the agent continuously, and largely unaffected by intestinal pH, throughout the small and large bowel due to a diffusion-dependent, semipermeable ethylcellulose coating. It is a safe and efficacious single agent for inducing remission and producing therapeutic benefit in patients with mild to moderately active ulcerative colitis (UC) (2 or 4 g/day) or Crohn's disease (4 g/day), as well as for significantly enhancing quality of life for patients with mild to moderately active UC (2 or 4 g/day). It is also effective for maintaining remission in patients with quiescent UC and Crohn's disease (4 g/day). Disease location (left-sided UC or pancolitis) did not affect the agent's effect in active disease or maintaining remission. Fewer treatment-related adverse events were reported with mesalamine than with placebo in treating UC. In the treatment of active Crohn's disease, data showed no statistically significant differences in response for patients with ileitis, ileocolitis, or Crohn's colitis. This formulation of mesalamine may also be a possible steroid-sparing agent for patients with either active or quiescent Crohn's disease.     

Differences in bioavailability between cocaine and cocaethylene and their implications for drug-reward studies

Cocaethylene, a psychoactive metabolite resulting from combined ethanol/cocaine consumption, is of interest because its psychostimulant properties may partially underlie combined cocaine/ethanol use, and because it has the potential for use as a probe of drug reward mechanisms due to its enhanced selectivity at monoamine uptake sites compared to cocaine. To determine the relative systemic bioavailabilities of cocaine and cocaethylene, sequential plasma samples were obtained from awake rats following drug administration. Following intravenous administration of 3 µmol/kg (molar equivalent of 1 mg/kg cocaine-HCl), both drugs achieved similar time courses and areas under the plasma concentration versus time curve. In contrast, intraperitoneal administration of 44 µmol/kg (molar equivalent of 15 mg/kg cocaine HCl) showed peak plasma levels, and the area under the plasma concentration vs time curve for cocaine to be approximately twice that for cocaethylene. Comparison of dose corrected areas under the curve of the two routes of administration for each drug indicated that relative systemic bioavailability of cocaethylene following intraperitoneal administration is only 58% that of cocaine. In addition, the elimination of both cocaine and cocaethylene was found to be slower following intraperitoneal administration compared to the intravenous route. The implications of these results are discussed with respect to the relative potency of these two compounds, as inferred from behavioral, drug reward, and lethality studies. Also, the differences noted will need to be taken into account when making mechanistic interpretations from comparative drug reward studies.     

Acute and chronic nicotine effects on measures of activity in rats: a multivariate analysis

Nicotine has been reported to increase or decrease measures of activity in rats, including locomotor activity and rearing. Nicotine dose and repeated exposure to nicotine are known to be important factors in determining the effects on locomotor behavior. Less information has been gathered on rearing and other measures of activity. Rats were tested repeatedly, once per day, in Digiscan automated activity analyzers that reported 19 measures of activity. Each rat was given the same drug and dose each day, either saline or 0.1, 0.2, or 0.4 mg/kg nicotine. The 19 measures were combined or modified to produce 14 measures that were examined using factor analysis to help select the most independent measures. Four measures were selected to describe the effects of dose and to compare day 1 results with day 5 results. Total distance moved was increased in a dose-related fashion and was greater on day 5 than on day 1. Rearing was increased at low doses and decreased at high doses on both days. Stereotypy was increased approximately the same amount by all three doses, and was greater on day 5 than on day 1. Center time was increased by the highest dose on both days. These results once again point out the influences of repeated testing and repeated nicotine exposure on behavior. They may also help to clarify why some studies have reported that both ambulation and rearing are increased after nicotine whereas others find opposite effects.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.