Maintenance of gastric pH above 6 with intravenous famotidine in patients with a bleeding duodenal ulcer

Background: The secondary prevention of bleeding from ulcers may be improved if antisecretory drugs are able to maintain a 24-h gastric pH close to neutral. Aim: To evaluate the effect of intravenous famotidine at a conventional dose of 40 mg/day on 24-h intragastric pH in patients with a bleeding duodenal ulcer, and to determine the dose required to maintain gastric pH > 6 by use of a Gastrojet (MIC, Switzerland) device (a pH meter-controlled programmable pump). Methods: Twelve patients (nine men, three women), aged 24–78 years, admitted for a bleeding duodenal ulcer, were studied after active bleeding had stopped for at least 6 h. Gastric pH was recorded for two consecutive 24-h periods, each starting at 16.00 hours. The patients were fasted during these periods and received an infusion of 2.5 L of isotonic glucose. They were given famotidine, as a continuous i.v. infusion of 40 mg during one period, and at a rate determined by the Gastrojet during the other period (in a random sequence), with the aim of maintaining the gastric pH above 6. Results: The 24-h median (interquartile range) pH and the mean (± S.E.M.) percentage of the 24-h period with a gastric pH > 6 were both significantly higher during the Gastrojet period than during the continuous infusion: 6.4 (6.3–6.5) vs. 5.7 (2.7–6.4) (P < 0.01) and 74±5% vs. 44 ± 7% (P < 0.002), respectively. The mean dose of famotidine delivered by the Gastrojet was 172 mg (range: 101–200 mg). The entire available amount of famotidine (200 mg) was delivered in four of the 12 patients. The percentage of time at pH > 6 (mean ± S.E.M.) was significantly higher at night (22.00 to 07.00 hours) than during the rest of the day (88 ± 2 vs. 70 ± 6%; P < 0.005) and the mean quantity of famotidine delivered per hour was significantly lower during the night (6.3 ± 0.8 mg/h vs. 8.4 ± 0.5 mg/h; P < 0.02). Conclusion: We conclude that 40 mg of famotidine delivered as a continuous i.v. infusion is not sufficient to maintain gastric pH > 6 for 24 h in duodenal ulcer patients. Our study with the Gastrojet device shows that it may be possible to achieve this goal by using a much larger dose, preferably delivered during the day.     

Mode of presentation and first line of management of non-recurrent urolithiasis in Kuwait

AIMS: To determine the incidence, mode of presentation, first line of management and composition of non-recurrent urolithiasis in Kuwait. METHODS: Consecutive patients admitted between January 1999 and December 2002 with non-recurrent urolithiasis were prospectively analyzed. RESULTS: The average annual incidence of hospital admission for non-recurrent urolithiasis in Kuwait was 43.44 per 100,000 population, representing men and women (ratio, 9:1) with a median age of 41.91 years. Of the hospital admissions for non-recurrent urolithiasis, 57.2% of cases were acute. Overall, the most predominant symptom was flank pain, while the least common symptom was acute urinary retention. Ureteroscopic stone manipulation was the most common initial treatment modality in the present series, as it was utilized in 43.3% and 37.09% for patients admitted on elective and emergency basis, respectively. Of the calculi available for chemical analysis, 91% contained calcium, 73% contained calcium oxalate, 17% contained mixed calcium and 1% contained calcium phosphate. The composition of the rest of the stones were urate in 7%, struvite in 1% and cystine in 1%. CONCLUSIONS: Urolithiasis is a common disease in the Kuwait region that mainly presents with flank pain. Ureteroscopic calculus removal is the most common modality of treatment. The majority of the calculi seen in Kuwait contained calcium.     

Short-Term Effects of an LHRH-Agonist alone or in Combination with Testosterone Propionate or Indomethacin on Rat Testes

The treatment of adult male Wistar rats with a LHRH-agonist (lutrelin Wyeth/WY 40972) resulted in severe damage of the seminiferous tubules as well as in remarkable changes of the blood vessels within 24 hours. First striking signs of alterations within the blood vessels were already found 6 hours after the injection of lutrelin: the blood vessels were almost totally filled with leucocytes. Neither the effects on the germinal epithelium nor the effects on the blood vessels were prevented by the simultaneous treatment with 3 mg testosterone propionate (TP). The treatment with indomethacin, however, clearly antagonized both events. The complete inefficiency of TP to overcome the inhibitory effects of lutrelin on the testes does argue against an androgen deficiency as the primary cause. The results obtained with indomethacin strengthen the hypothesis, that the early deleterious effects of LHRH-agonists on the germinal epithelium of the rat are primarily caused by circulatory disturbances in the testes and that prostaglandins may act as mediators.     

Vaginal reconstruction with a greater omentum–pedicled graft combined with a vicryl mesh after anterior pelvic exenteration. Surgical approach with long-term follow-up

Resection of anterior vaginal wall that occurs with some cases of anterior pelvic exenteration leaves the patient with a small and narrow vagina. This affects their sexual life leading to major psychologic problems, especially in young women. The aim of this study is to evaluate a new technique of vaginal reconstruction following anterior pelvic exenteration with clinical and cytohistologic follow-up. Between March 2002 and November 2004, ten sexually active female patients underwent vaginal reconstruction after radical cystectomy that required en bloc removal of the anterior vaginal wall, with a pedicle graft of greater omentum combined with a vicryl mesh. The mean age of the patients was 38 years. The mean operative time of the reconstructive procedure was 50 min. There were no complications regarding the reconstructive procedure. On follow-up, the neovagina accepted two fingers easily and showed a pink-colored smooth lining. Seven patients reported successful attempts of sexual intercourse. It was concluded that reconstruction of vagina after anterior pelvic exenteration in sexually active women can be done safely with the use of vicryl mesh combined with a pedicled omental graft. It is a simple, reliable, and not time-consuming technique. The long-term follow-up was very beneficial in detection of complete healing, postoperative infections, and hormonal activity of the graft and recurrence of malignancy.     

Biological and immunological characterization of ATG and ALG

Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are effective therapies in aplastic anemia; their mechanism of action is undefined. We assayed multiple properties of ATG and ALG to address the biological and immunological bases for differences between ATG and ALG and lot variation. In addition, we studied a lot reported to be inactive in an American clinical trial; however in retrospect, this lot appeared to be active in patients treated in Europe. Immunoprecipitation of thymocyte and lymphocyte membrane proteins with ATG and ALG showed between 14 and 18 major bands on SDS-PAGE, but the patterns for ATG and ALG were not identical. The ability of ATG and ALG to block binding of labeled monoclonal antibodies was assessed using flow cytometry and a radioimmunoassay. In general, there was more lot variation among ALGs than ATGs; however, all ALG lots were more potent blockers of binding of anti-HLA-DR and anti-Leu 1 antibodies than was ATG. Both ALG and ATG effectively blocked binding of anti-Leu 2a, anti- Leu 3a, anti-Leu 4, anti-Leu 5b, and anti-IL 2 receptor abs; neither blocked binding of anti-Leu 7. All preparations were capable of inducing T-cell blastogenesis, although there was considerable lot variation. All lots lysed 60% to 75% T cells in a rabbit complement- mediated cytotoxicity assay, with most having a plateau of activity at 5 to 10 ug/mL. Two lots of ALG, including the lot reported to be clinically inactive, showed less toxicity at suboptimal concentrations and did not plateau even at 80 ug/mL. In total, these results indicate important differences between ATG and ALG in general, more lot variation among ALGs than ATGs and only differences in cytotoxicity between an "inactive" lot of ALG and most, but not all, other active ATG and ALG preparations.     

An endogenous glycosylphosphatidylinositol-specific phospholipase D releases basic fibroblast growth factor-heparan sulfate proteoglycan complexes from human bone marrow cultures

Basic fibroblast growth factor (bFGF) is a hematopoietic cytokine that stimulates stromal and stem cell growth. It binds to a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan on human bone marrow (BM) stromal cells. The bFGF- proteoglycan complex is biologically active and is released by addition of exogenous phosphatidylinositol-specific phospholipase C. In this study, we show the presence of an endogenous GPI-specific phospholipase D (GPI-PLD) that releases the bFGF-binding heparan sulfate proteoglycan and the variant surface glycoprotein (a model GPI-anchored protein) from BM cultures. An involvement of proteases in this process is unlikely, because released proteoglycan contained the GPI anchor component, ethanol-amine, and protease inhibitors did not diminish the release. The mechanism of release is likely to involve a GPI-PLD and not a GPI-specific phospholipase C, because the release of variant surface glycoprotein did not reveal an epitope called the cross- reacting determinant that is exposed by phospholipase C-catalyzed GPI anchor cleavage. In addition, phosphatidic acid (which is specifically a product of GPI-PLD-catalyzed anchor cleavage) was generated during the spontaneous release of the GPI-anchored variant surface glycoprotein. We also detected GPI-PLD-specific enzyme activity and mRNA in BM cells. Therefore, we conclude that an endogenous GPI-PLD releases bFGF-heparan sulfate proteoglycan complexes from human BM cultures. This mechanism of GPI anchor cleavage could be relevant for mobilizing biologically active bFGF in BM. An endogenous GPI-PLD could also release other GPI-anchored proteins important for hematopoiesis and other physiologic processes.     

Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy

Fifty-two patients with stage III or IV nodular mixed lymphocytic- histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3-4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.     

Asymmetric polyarthritis as an initial presentation of Rosai‐Dorfman disease

Rosai‐Dorfman disease (RDD) is a rare benign reactive lymphoproliferative disorder characterised by a histopathological pattern with sinus histiocytosis and hemophagocytosis. It usually presents with fever, elevated erythrocyte sedimentation rate, cervical lymphadenopathy, other lymph node and extra‐nodal site involvement. We present the case of a 25‐year‐old female patient with polyarthritis mimicking rheumatoid arthritis (RA). When the para‐aortic lymph node was biopsied, it showed extensive histiocytic proliferation; some clusters of plasma cells, lymphocytes and rare multinucleated cells were seen, suggesting a diagnosis of RDD. There is nothing in the literature regarding the polyarthritic presentation of the disease. To the best of our knowledge, our patient is the first case of RDD presenting with a clinical picture mimicking atypical seronegative RA.