A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat

A Dose-Response Analysis of Methoxychlor-Induced Alterationsof Reproductive Development and Function in the Rat. GRAY, L.E., JR., OSTBY, J., FERRELL, J., REHNBERG, G., LINDER, R., COOPER,R., GOLDMAN, J., SLOTT, V., AND LASKEY, J. (1989). Fundam. Appl.Toxicol12, 92–108. In the present study rats were dosed fromweaning, through puberty and gestation, to Day 15 of lactationwith methoxychlor at 25, 50, 100, or 200 mg/kg/day. Morphologicallandmarks of puberty were measured, including the ages at vaginalopening, first estrus, and first estrous cycle in females andat preputial separation in males. In the female, estrous cyclicity,fertility, litter size, number of implantation sites, organweights, and ovarian and uterine histology were also measured.The viability of the offspring (F1) and their fertility wereevaluated using a continuous breeding protocol. Males were necropsiedafter breeding, the reproductive organs were weighed, and thecauda epididymal sperm counts were determined. One testis wasused for histopathology, while the other was used to quantifyinterstitial fluid (IF) content, IF testosterone concentration,and testicular sperm production. Testosterone and an drogen-bindingprotein were measured in the caput epididymis, and sperm motilityand morphology were evaluated from a caudal sample. The serumand pituitary were saved for hormonal determinations. Methoxychloraccelerated the age at vaginal opening and first estrus, andthe vaginal smears were cornified. Growth was retarded at 100and 200 mg/kg/day and fertility was reduced when the femaleswere bred with untreated or similarly treated males. In thehighest- dose group, the mated females went from constant estrusinto pseudopregnancy following mating, but they had no implants.In males, methoxychlor treatment markedly reduced growth, seminalvesicle weight, cauda epididymal weight, caudal sperm content,and pituitary weight. Puberty was delayed in the two highest-dosagegroups. Testicular sperm measures were much less affected thancaudal measures. Testis weight and histology were slightly affected,and testicular sperm production, sperm morphology, and motilitywere unaffected. Endocrine function of the testes and pituitarywas altered by methoxychlor administration. Leydig cell testosteroneproduction, in response to human chorionic gonadotropin challenge,was reduced and pituitary levels of prolactin, thyroid-stimulatinghormone (TSH), and follicle-stimulating hormone (FSH) were altered.In contrast, serum levels of prolactin, FSH, and luteinizinghormone were unaffected. Serum TSH was reduced by 50% of controlat 100 and 200 mg/kg/day, while pituitary levels were increased.Gonadotropin-releasing hormone concentration in the mediobasalhypothalamus was also elevated. In spite of the many reproductivealterations, the fertility of treated males was not reducedwhen they were mated with untreated females. Growth and viabilityof the offspring (F1) from the 50 mg/kg/day treatment groupwere normal, but in the females, vaginal opening was accelerated,estrous cyclicity was abnormal in the rats during middle age,and fecundity was reduced.     

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus

Background : Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux.
Aim : To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus.
Methods : An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2–4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8.
Results : The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups.
Conclusion : In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.     

Vesicocutaneous fistula: An unusual complication of inguinoscrotal hernia

Involvement of the urinary bladder in an inguinal hernia is common, but massive bladder hernia is rare. Most urinary bladder herniations are discovered and repaired during surgery. We report a case of large incarcerated inguino-scrotal hernia, which was reduced only to present as a scrotal abscess and vesicocutaneous fistula; an unusual complication. The patient was managed conservatively due to underlying comorbidities.     

Automatic Implantable Cardioverter Defibrillator/Permanent Pacemaker Interaction: Loss of Pacemaker Capture Following AICD Discharge

A 78-year-old man treated with amiodarone for recurrent ventricular tachycardia, had sequential placement of a bipolar VVI pacemaker and an automatic implantable cardioverter defibrillator (AICD). During defibrillation threshold testing, there was failure to capture of the pacer in the post-shock period. The time of failure to capture appeared energy-related: the greater the energy delivered, the longer the failure to capture. Careful attention will be necessary in constructing combined AICD/pacemaker units.     

The Effect of Quisqualic Acid-Induced Lesions of the Nucleus Basalis Magnocellularis on Latent Inhibition

Latent inhibition (LI) is a reduction in the rate of acquisition of a Pavlovian conditioned response that results from prior nonreinforced preexposure to a conditioned stimulus (CS). LI has been suggested to reflect the operation of mechanisms involved in stimulus selection for subsequent cognitive processing. The present experiment was conducted to assess the effect of bilateral lesions of the nucleus basalis magnocellularis (NBM) on LI employing a conditioned emotional response paradigm. Bilateral lesions of the NBM were produced by administration of 0.12 M quisqualic acid and resulted in decreased cortical acetylcholinesterase staining, as well as a 40% reduction in cortical choline acetyltransferase activity. Following lever press training, preexposed animals received 40 presentations of a 60-s tone CS. Nonpreexposed animals received no tone presentations. Acquisition of conditioned suppression was then assessed over the course of 4 tone-shock (0.6 mA, 0.5 s) pairings. Control, preexposed animals displayed a retarded rate of acquisition in comparison to nonpreexposed controls, thereby demonstrating that the parameters used in the present experiment produced LI. In contrast, lesioned animals preexposed to the CS acquired conditioned suppression as readily as non-preexposed lesioned animals. However, the acquisition of conditioned suppression in both lesioned groups was found to be similar to that displayed in the preexposed control group. This pattern of results was interpreted as being attributable to a lesion-induced impairment in the ability to maintain stimulus processing, rather than a deficit in the ability to filter a stimulus. Copyright © 1996 Elsevier Science Inc.