Mammary gland morphology in Sprague-Dawley rats following treatment with an organochlorine mixture in utero and neonatal genistein.

In a related reproductive toxicology study designed to investigate the effects of in utero exposure to environmental toxicants and potential interaction with postnatal genistein, gross enlargement of thoracic mammary glands was observed in female offspring at 200 days of age. Therefore, the objective of this study was to analyze the effect of in utero exposure to a mixture of toxicants on mammary gland morphology. Time-mated Sprague-Dawley rats were treated on days 9-16 of gestation with vehicle or a mixture of environmental toxicants at 1x the acceptable daily intake. Furthermore, it is unclear whether postnatal exposure to phytoestrogens in soy formulas poses breast cancer benefit or risk, and potential interactions with environmental toxicants are unknown. Therefore, half the female pups from each treatment group received either subcutaneous vehicle or genistein (10 microg/g body weight [bw]/day) on postnatal days 2-8. Following necropsy at 200 days of age, a pathologist, blinded to treatment groups, examined mammary gland histopathology. Only mild histological changes were found in mammary glands of rats exposed to the mixture in utero while pronounced ductal hyperplasia, lactational changes, and fibrosis were observed in mammary glands from the genistein group and were more prominent in the mixture + genistein group. Mammary glands of the control group were histologically normal. Collectively, our results reveal that postnatal exposure to pharmacological levels of genistein induces profound morphological changes in the mammary glands of adult female rats, and that high levels of phytoestrogens possess the potential to modulate the toxicological effects of toxicant mixtures.     

Prevalence and risk factors for refractive errors in adult Chinese in Singapore

PURPOSE: To determine the epidemiology of refractive errors in an adult Chinese population in Singapore. METHODS: A disproportionate, stratified, clustered, random-sampling procedure was used to select names of 2000 Chinese people aged 40 to 79 years from the 1996 Singapore electoral register in the Tanjong Pagar district in Singapore. These people were invited to a centralized clinic for a comprehensive eye examination, including refraction. Refraction was also performed on nonrespondents in their homes. Myopia, high myopia, and hyperopia were defined as a spherical equivalent (SE) in the right eye of less than -0.5 D, less than -5.0 D, and more than +0.5 D, respectively. Astigmatism was defined as less than -0.5 D of cylinder. Anisometropia was defined as a difference in SE of more than 1.0 D between the two eyes. Only phakic eyes were analyzed. RESULTS: From 1717 eligible people, 1232 (71.8%) were examined. Adjusted to the 1997 Singapore population, the overall prevalence of myopia, hyperopia, astigmatism, and anisometropia was 38.7% (95% confidence interval [CI]: 35.5, 42.1), 28.4% (95% CI: 25.3, 31.3), 37.8% (95% CI: 34.6, 41.1), and 15.9% (95% CI: 13.5, 18.4), respectively. The prevalence of high myopia was 9.1% (95% CI: 7.2, 11.2), with women having significantly higher rates than men. The age pattern of myopia was bimodal, with higher prevalence in the 40 to 49 and 70 to 81 age groups and lower prevalence between those age ranges. Prevalence was reversed in hyperopia, with a higher prevalence in subjects aged 50 to 69. There was a monotonic increase in prevalence with age for both astigmatism and anisometropia. Increasing educational levels, higher individual income, professional or office-related occupations, better housing, and greater severity of nuclear opacity were all significantly associated with higher rates of myopia, after adjustment for age and sex. CONCLUSIONS: The results indicate that whereas myopia is 1.5 to 2.5 times more prevalent in adult Chinese residing in Singapore than in similarly aged European-derived populations in the United States and Australia, the sociodemographic associations are similar.     

N064A (Alliance): Phase II Study of Panitumumab,Chemotherapy, and External Beam Radiation in Patients with Locally Advanced Pancreatic Adenocarcinoma

BackgroundThis North Central Cancer Treatment Group (NCCTG) N064A (Alliance) phase II trial evaluated upfront chemoradiotherapy incorporating the EGFR inhibitor panitumumab, followed by gemcitabine and panitumumab for unresectable, non-metastatic pancreatic cancer.MethodsThe treatment consisted of fluoropyrimidine and panitumumab given concurrently with radiotherapy followed by gemcitabine and panitumumab for 3 cycles followed by maintenance panitumumab. The primary endpoint was the 12-month overall survival (OS) rate and secondary endpoints included confirmed response rate (RR), OS, progression-free survival (PFS), and adverse events. Enrollment of 50 patients was planned and the study fully accrued.ResultsFifty-two patients were enrolled, but only 51 were treated and included in the analysis. The median age of patients was 65 years and 54.9% were women. Twenty-two patients received at least 1 cycle of systemic therapy following radiotherapy, but 29 patients received chemoradiotherapy only without receiving subsequent chemotherapy after completion of chemoradiotherapy. The overall RR was 5.9% (95% CI: 1.2%-16.2%). The 12-month OS rate was 50% (95% CI: 38%-67%) which fell short of the per-protocol goal for success (51.1%). The median PFS was 7.4 months (95% CI: 4.5-8.6) and the median OS was 12.1 months (95% CI 7.9-15.9). Grade 3 or higher adverse events were reported by 88%.ConclusionThe combination of panitumumab, chemotherapy, and external beam radiation therapy was associated with very high rates of grades 3-4 toxicities and survival results did not meet the trial’s goal for success. This regimen is not recommended for further study (ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT00601627","term_id":"NCT00601627"}}NCT00601627).     

Cataract surgery in ocular cicatricial pemphigoid

The authors report the results of their experience with cataract surgery in 20 patients (26 eyes) with biopsy-proven cicatricial pemphigoid. All patients were on systemic immunosuppression at the time of surgery (dapsone, azathioprine, cyclophosphamide, or combinations) and were treated with perioperative oral corticosteroids. Patients were evaluated pre- and postoperatively for conjunctival inflammation, conjunctival cicatrization, degree of keratopathy, and disease stage. No patient progressed in disease stage. Vision improved an average of 3.5 Snellen lines (-3 to +8). Worse outcome was associated with chemotherapy intolerance or the presence of any preoperative conjunctival inflammation. Thirteen patients remained on immunosuppressives for the entire study. Corneal ulcers developed postoperatively in three patients in whom continued immunosuppression was not tolerated. Possible mechanisms for inflammatory exacerbation after surgery are discussed. Results indicate that after successful abolition of all conjunctival inflammation through chemotherapy, cataract surgery may be safely performed in patients with cicatricial pemphigoid.     

Interstitial retinol-binding protein and cellular retinal-binding protein in the mammalian pineal

Antibodies against bovine interstitial retinol-binding protein (IRBP) and cellular retinal-binding protein (CRA1BP) were used in immunochemical and immunocytochemical studies of the pineal glands of cattle, hamsters and rats (RCS and RCS-rdy+). On immunoblots, IRBP (Mr 144,000) was identified in cattle, hamster and rat pineal extracts. The abundance of IRBP in bovine pineals was 33 +/- 6 ng.mg-1 (mean +/- SD, n = 12) soluble protein. RCS (Royal College of Surgeons) rat pineals gave a strong IRBP reaction on immunoblots, even when virtually no IRBP could be found in the eye due to photoreceptor degeneration. In the hamster retina IRBP immunostaining was distributed throughout the entire interphotoreceptor matrix and the outer segment layer. The pineal also showed strong IRBP-like immunostaining scattered uniformly throughout the gland. Other hamster brain regions showed no specific immunostaining; however, an immunoreactive protein with the same Mr as IRBP was detected on Western blots of bovine cerebral cortex, spinal cord and brainstem soluble proteins. Immunoreactive proteins at lower Mr were also detected in these tissues. CRA1BP immunoreactivity (Mr about 32,000) was observed in immunoblots of bovine, hamster and rat pineal proteins. These findings suggest that some mammalian pinealocytes are related to the retinal cells that contain CRA1BP (i.e. pigment epithelium, Muller cells) while others are related to the photoreceptors, which synthesize IRBP.     

Uncomplicated urinary tract infections in women

Uncomplicated urinary tract infections (UTIs) present a significant problem for women and a challenge for the doctors who care for them. The diagnosis of uncomplicated UTI, which usually is not challenging, can be achieved best by a thorough assessment of patient symptoms with or without the addition of a urine dipstick test. Treatment should be based on the most recent Infectious Disease Society of America guidelines, taking into account resistance patterns in the local community. The patient who suffers from recurrent UTIs can be treated safely and effectively with continuous antibiotic prophylaxis, postcoital therapy, or self-initiated treatment.     

CHEMICAL STUDIES ON BACTERIAL AGGLUTINATION : VII. A QUANTITATIVE STUDY OF THE TYPE SPECIFIC AND GROUP SPECIFIC ANTIBODIES IN ANTIMENINGOCOCCAL SERA OF VARIOUS SPECIES AND THEIR RELATION TO MOUSE PROTECTION

1. The quantitative method for the estimation of agglutinins has been applied to antimeningococcal horse, rabbit, and chicken sera and to the sera of humans convalescing from meningococcus meningitis. The type-specific and group-specific agglutinin N can be measured, using homologous and heterologous suspensions of meningococci. 2. Type I horse, rabbit, and chicken antimeningococcal sera contain considerable amounts of antibody which cannot be removed either by Type II meningococcus suspension or by preparations of the Type I specific polysaccharide. This residual type-specific antibody has marked potency in protecting mice against subsequent infection with meningococci. 3. Most human convalescent sera contain group-specific antibody. Small amounts of protective antibody and of antipolysaccharide are also formed. 4. Type I antisera absorbed with Type I polysaccharide and with Type II meningococci could be used as a guide in the purification of this new antigen.