His Bundle Extrasystoles Revisited: The Great Electrocardiographic Masquerader

A 74‐year‐old man with past history of near syncope presented with frequent periods of second‐degree atrioventricular block (2° AVB). An electrophysiological study revealed prolonged atrial‐His and His‐ventricular (HV) intervals and frequent His bundle (H) extrasystoles. The latter manifested in the surface electrocardiogram as premature atrial, junctional, or ventricular beats, as well as 2° AVB that mimicked Wenckebach or Mobitz II block. Procainamide markedly suppressed H extrasystole. However, because of the presence of prolonged HV interval and history of presyncope, a permanent pacemaker was inserted. The case illustrates the varied manifestation of H extrasystole and presents guidelines for management. (PACE 2011; e56–e59)     

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.     

Thymoquinone Crosstalks with DR5 to Sensitize TRAIL Resistance and Stimulate ROS-Mediated Cancer Apoptosis

Objective: Cancer treatment using a targeted inducer of apoptosis like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) faced the obstacle of resistance, thus providing a plus drug like Thymoquinone (TQ) could be of great interest to tackle breast cancer cells. The aim of the present work is to examine the genetic modulation impacts of the TRAIL receptors and apoptotic markers upon the combinatorial remedy of TRAIL plus TQ on human breast cancer cell lines. Methods: To achieve this rationale, the protein content-based cytotoxicity using SRB assay, as well as the genetic expressions of the TRAIL receptors (DR4 and DR5) and apoptotic markers (Bcl-2, Cas-8, and FADD) using real time qRT-PCR technique were preceded against breast cancer MCF-7 and MDA-MB-231 cancerous cell lines. Results: The current study showed that the combination therapy of TQ+TRAIL significantly inhibited the protein content-based proliferation of MDA-MB-231 cells more than MCF-7 cells. The synergistic effect of them significantly up-regulated the genetic expressions of DR4, DR5, Cas-8, and FADD genes and inhibited the genetic expression of the Bcl-2 gene in the proposed cell lines treated for 24 h. The induction of the apoptotic genes using the combined therapy was stimulated by the elevation of the reactive oxygen species (ROS); nitric oxide (NO) and malondialdehyde (MDA) levels. Conclusions: The synergistic influence between TQ which induced the DR5 and TRAIL, facilitating the connection between TRAIL and its receptors on the cancerous cell membrane. Hence, the proposed combination therapy induced the ROS-mediated apoptotic stimulus.     

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.     

Surface antigens on malignant Sezary and T-CLL cells correspond to those of mature T cells

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T- cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sezary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T- chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.