Phase II study of 10-EdAM in patients with squamous cell carcinoma of the head and neck,previously untreated with chemotherapy

Fifteen patients with advanced head and neck cancer not curable with radiation or surgery were entered into a phase II study of 10-EdAM. None of the patients had received prior chemotherapy. 10-EdAM was administered intravenously at a dose of 80 mg/m2 each week. Four patients were not eligible for evaluation. Two died before completing four cycles of chemotherapy, one refused further treatment and one developed hepatic toxicity resulting in withdrawal. Of the remaining patients, three had a partial response. The major toxicities were leukopenia and mucositis.     

Indications for treatment of Helicobacter pylori infection: a systematic overview.

OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. DATA EXTRACTION: The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. DATA SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.     

Laparoscopic-assisted percutaneous endoscopic gastrostomy in children and adolescents.

OBJECTIVE: Pediatric gastric access for long-term enteral feeding may be performed via a laparotomy, laparoscopy, or a percutaneous approach. In children and adolescents, laparoscopic-assisted gastrostomy may be difficult due to a thick abdominal wall. Therefore, if the abdominal wall is estimated to be >2 cm on physical examination, or in children in whom a percutaneous endoscopic gastrostomy was unsuccessfully attempted by a gastroenterologist, we routinely perform a laparoscopic-assisted percutaneous endoscopic gastrostomy. METHODS: From January 1998 through February 2003, we retrospectively reviewed 15 cases of a laparoscopic-assisted percutaneous endoscopic gastrostomy. Instruments used to perform this technique are a percutaneous endoscopic gastrostomy kit, an Olympus flexible endoscope, and one 5-mm STEP port placed through an infraumbilical incision for a 5-mm, 30-degree scope. RESULTS: Age range was 2 years to 20 years (mean, 10). Operative time ranged from 20 minutes to 45 minutes. When a concurrent laparoscopic Nissen fundoplication was performed (n = 6), the percutaneous endoscopic gastrostomy was placed after completion of the Nissen fundoplication. No intraoperative complications occurred, and all tubes were successfully placed. Feeds were instituted the following day and advanced to goal. To date, no postoperative complications have occurred, and revision has not been necessary. CONCLUSIONS: Laparoscopic-assisted percutaneous endoscopic gastrostomy in children and adolescents is safe and effective. Utilizing laparoscopy permits evaluation of the peritoneum and lysis of adhesions, if necessary. Moreover, laparoscopy provides excellent exposure for accurate placement of the PEG, while avoiding injury to other organs.     

Differential etiology of posttraumatic stress disorder with conduct disorder and major depression in male veterans.

BACKGROUND: Epidemiologic studies reveal that posttraumatic stress disorder (PTSD) is highly comorbid with both conduct disorder and major depression in men. The genetic and environmental etiology of this comorbidity has not been examined. METHODS: Data were analyzed from 6744 middle-aged male-male monozygotic and dizygotic twins from the Vietnam Era Twin Registry. Conduct disorder, major depression, and PTSD were assessed via telephone interview using the Diagnostic Interview Schedule for the DSM-III-R in 1992. Structural equation modeling was used to estimate additive genetic, shared environmental, and individual-specific environmental effects common and specific to conduct disorder, major depression, and PTSD. RESULTS: The association between conduct disorder and PTSD was explained primarily by common shared environmental influences; these explained 10% (95% confidence interval: 6%-17%) of the variance in PTSD. The association between major depression and PTSD was largely explained by common genetic influences; these explained 19% (95% confidence interval: 11%-26%) of the variance in PTSD. CONCLUSIONS: Our findings suggest that different etiologic mechanisms explain the association of conduct disorder and major depression with PTSD in male veterans. If replicated in other populations, results suggest research aimed at identifying specific genetic and environmental factors that influence PTSD may benefit from starting with those that have been more consistently and strongly associated with major depression and conduct disorder.     

Human choriogonadotropin-induced coupling of receptor and Gs protein and the effect of hormone deglycosylation

The detergent-soluble extract of rat ovary plasma membranes contained a Gs protein of about 100 kDa as shown by its elution behavior on a Bio Gel A-1.5m column. However, the cell membranes exposed to hCG (37° C, 15 min) contained in addition a higher molecular weight Gs protein complex of 300 kDa comprised of human chorionic gonadotropin (hCG) receptor (hCGR) and Gs. The complex bound with an affinity column of GTP-Sepharose and could be released with Gpp(NH)p and GTP inhibited this binding. The presence of the hCGR in the complex was shown by its binding to ¹²⁵I-hCG. Furthermore, GTP inhibited the binding of hCG to the complex. These results indicate the presence of hCGR and Gs protein complex in the hCG-treated membranes. hCGR and Gs protein were individually purified and reconstituted into phospholipid vesicles. The protein-phospholipid vesicles showed saturation kinetics of binding of ¹²⁵I-hCG and ³H-Gpp(NH)p. Incubation of phospholipid vesicles with hCG resulted in a 2–3-fold increase in the binding of ³H-Gpp(NH)p and GTPase activity. Activation of Gs protein was dependent on the length of incubation and the hormone concentration. Deglycosylated hCG was about 10 times less potent than hCG suggesting a role of carbohydrates of hCG in inducing hCG-Gs protein interactions. The data with the in vitro reconstitution system rule out the involvement of a carbohydrate-binding lectin in the function of the hormone.     

Relationship between human papillomavirus infection and tumours of anogenital sites other than the cervix.

Although tissues in the case series of anal, penile, vaginal and vulvar neoplasms that have looked for evidence of HPV infection by probing for HPV DNA have been selected for convenience, they support the view that HPV, especially type 16, is associated with approximately 50% of these tumours. A higher percentage of the anal, vaginal and vulvar tumours are associated with HPV 16 than are penile tumours. This discrepancy may be due to the low number of penile tumours studied or to a true difference in the proportion of penile cancer cases related to HPV. HPV 6/11 and 18 are found less frequently at all anatomic sites. About 10% of tumours that are probed for these viruses are positive, although there are some notable exceptions such as a study that found 39% of penile tumours positive for type 18 and a study that found approximately two thirds of vulvar tumours positive for HPV 18 using Southern blot hybridization. For all of these tumours, there is likely to be a subset of the cases who develop their cancer through mechanisms that do not involve HPV. The case-control studies found a strong association with genital warts, number of sexual partners and, with the exception of vaginal cancer, smoking and/or heavy smoking at the time of diagnosis of the disease. A history of genital warts, smoking at diagnosis, and seropositivity to HSV2 are exposures that have also been found to be associated with cervical cancer. A population-based case-control study in western Washington and Vancouver, British Columbia that studied all anogenital cancers found that a history of genital warts was stronger among patients with vulvar, anal, vaginal and penile cancer than among those with cervical cancer. This was also true of smoking at diagnosis, with the exception of vaginal cancer, where there was little excess risk. This study and other supporting data indicate that these anogenital tumours share many of the same risk factors as cervical cancer.     

Alterations in xenobiotic metabolizing enzymes in brain and liver of rats coexposed to endosulfan and malathion

The effects of endosulfan (3 mg kg-1 body wt., i.p.) and malathion (30 mg kg-1 body wt.) and their coexposure on rat hepatic and brain xenobiotic metabolizing enzymes were investigated. Endosulfan was found to induce aminopyrine-n-demethylase (81%) and aniline hydroxylase (59%) activities significantly in liver and to a lesser extent in brain. Malathion treatment induced malathion carboxylesterase activity in both liver (50%) and brain (22%), significantly depleted liver glutathione (35%) content with stimulation of glutathione-S-transferase (50%) and inhibited the activity of mixed-function oxidases. In the coexposed animals, malathion's inhibitory influence on mixed-function oxidases and endosulfan's inhibitory effect on malathion carboxylesterase were found to dominate, while endosulfan potentiated the activity of glutathione-S-transferase significantly in liver (69%) and brain. A similar trend of alteration in coexposed brain was found, but to a lesser extent. A significant inhibition in brain acetylcholine esterase activity (42%) in the coexposed animals suggests that endosulfan may potentiate the toxicity of malathion by interfering with glutathione and carboxylesterase routes of malathion detoxification.     

Prevention of genital prolapse following Burch colposuspension: comparison between two surgical procedures

 Our objective was to evaluate the efficacy of cul-de-sac obliteration in preventing pelvic floor anatomical defects formation following Burch colposuspension. We evaluated 441 patients who had undergone Burch colposuspension. The patients were divided into two groups: group A (132 patients) who underwent Burch colposuspension only, and group B (309 patients) who had had a concomitant cul-de-sac obliteration. Cul-de-sac obliteration was performed using two different techniques, the Moschocowitz procedure in 131 patients, and approximation of the sacrouterine ligaments in 178 patients. The follow-up period was 8.6 years (range 3–16). In total we found 43/441 (9.7%) postoperative anatomical defects. Obliteration of the cul de sac significantly (P<0.0001) reduced the formation of anatomical defects compared to Burch colposuspension. In a comparison of the two surgical procedures for cul-de-sac obliteration, the approximation of the sacrouterine ligaments was significantly more effective than either the Moschcowitz procedure (P<0.001) or the Burch colposuspension alone (P<0.001). The Moschcowitz procedure reduced the formation of anatomical defects to 15/131 (11.4%) compared to Burch colposuspension only (25/132; 18.9%), but statistically the difference was insignificant. The time of anatomical defect detection was significantly reduced after cul-de-sac obliteration: 2 years 6/25 (24%) in group A compared to 1/8 (5.5%) in group B (P<0.01). After 5 years the detection rate was 64% (16/25) and 22.2% (4/18) respectively (P<0.01). It was concluded that cul-de-sac obliteration using approximation of the sacrouterine ligaments significantly reduced the incidence of anatomical defect formation following Burch colposuspension. A long follow-up period is needed to evaluate the truce incidence. Received: 2 October 2002 / Accepted: 2 July 2002