Postinfarction ventricular septal defect in a patient without coronary lesions

A 46-year-old man with polycystic kidney disease was referred to our institution for ventricular septal defect complicating myocardial infarction. Cardiac catheterization disclosed normal coronary arteries and absence of myocardial bridging. None of the more frequent causes of thrombosis were present, and histopathology proved negative for acute myocarditis. The surgical procedure was successful and the 11-month follow-up uneventful.     

Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice

Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G(4) (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF.     

Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis

OBJECTIVE: Our purpose was to examine the efficacy of a topical long-term treatment with boric acid versus an oral long-term treatment (itraconazole) in the cure and prevention of recurrent vulvovaginal candidiasis. STUDY DESIGN: A prospective, nonrandomized study of patients affected by recurrent vulvovaginal candidiasis was undertaken. In 3 years we recruited 22 consecutive patients who underwent therapy with itraconazole (group 1) or boric acid (group 2). Women were followed up for 1 year, with clinic and microbiologic controls after 1, 3, 6, and 12 months after the first visit. RESULTS: During the treatment, the positive culture results (15.1% vs 12.1%) and the signs and symptoms (33.3% vs. 24.2%) were similar within the 2 groups, with no significant statistical difference. With the withdrawal, after 6 months relapses were common in the 2 groups (54.5%). CONCLUSIONS: Boric acid seems to be a valid and promising therapy both in the cure of the vaginal infection and in the prevention of relapses of recurrent vulvovaginal candidiasis, but its efficacy ends with the suspension of the therapy.     

Insomnia is associated with systolic hypertension in uremic patients on hemodialysis

A newly developed questionnaire was administered to 140 hemodialyzed patients (82 M and 58 F) who have achieved adequate anemia correction according to the best guidelines with the aim: to evaluate the prevalence of clinical/subclinical dyssomnias in these patients; to study the influence of the dialytic shift (morning versus afternoon schedules) on sleep duration and disturbancies; and to evaluate the relationship between clinical sleep disorders and blood pressure values in uremic patients. Results indicated that 85% of uremic patients undergoing hemodialysis complain of clinical insomnia (frequent, persistent and associated with daytime consequences) or sub-clinical sleep disorders; patients dialyzing in the morning sleep significantly less during the night preceding the treatment, than those dialyzing in the afternoon; older patients complaining of clinical insomnia have a higher risk of failure to achieve target-optimal values in systolic blood pressure.     

Inhibition of fibroblast growth factor/fibroblast growth factor receptor activity in glioma cells impedes tumor growth by both angiogenesis-dependent and -independent mechanisms

We undertook a series of systematic studies to address the role of fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) activity in tumor growth and angiogenesis. We expressed dominant-negative FGFR2 (FGFR2-DN) or FGFR1 (FGFR1-DN) in glioma C6 cells by using constitutive or tetracycline-regulated expression systems. Anchorage-dependent or independent growth was inhibited in FGFR-DN-expressing cells. Tumor development after xenografting FGFR-DN-expressing cells in immunodeficient mice or after transplantation in rat brain was strongly inhibited. Quantification of microvessels demonstrated a significant decrease in vessel density in tumors derived from FGFR-DN-expressing cells. Furthermore, in a rabbit corneal assay, the angiogenic response after implantation of FGFR-DN-expressing cells was decreased. In tumors expressing FGFR-DN, vascular endothelial growth factor expression was strongly inhibited as compared with control tumor. These results indicate that inhibition of FGF activity may constitute a dominant therapeutic strategy in the treatment of FGF-producing cerebral malignancies and may disrupt both angiogenesis-dependent and -independent signals required for glioma growth and invasion.     

Human papillomavirus genital infection in modern gynecology: genetic and genomic aspects

HPV (human papillomavirus) is a virus responsible for many female and male genital tract diseases. It is a small nonenveloped virus with icosahedral symmetry that contains a double-stranded DNA genomes of approximately 7,900 bp. Approximately 200 different HPVs have been characterized, classified in mucosal and cutaneous viruses, responsible for a wide spectrum of clinical conditions, from simple feet and hands warts to genital cancer. Their genome is functionally distinct in three regions. The condition of the host immune system is one of the factors that can strongly influence the natural history of HPV infection. The primary response to viral infection is cell-mediated, so conditions that compromise the immune system increase the viral infection risk. The molecular mechanisms involved in the onset of the cervical carcinoma are well defined, and they are mainly associated to the ability of the proteins E6 and E7 to neutralize the activity of p53 and retinoblastoma protein, respectively. The infection of HPV is mainly diagnosed through molecular methods. Several assays have been developed for the simultaneous identification of HPV types, the majority of which are polymerase chain reaction-based assays. Side by side with these assays, the emerging technology of the DNA chip may offer a reliable diagnostic tool for discriminating easily between many HPV genotypes.     

Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study

Background: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule.Patients and methods: Thirty-six untreated patients with stage IIIB–IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on days 1, 8, and 15, followed by one week of rest.Results: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%–57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4–23) and the median survival time 11.8 months (range 1–24). World Health Organization (WHO) grade 3–4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity.Conclusions: This regimen appears to be active and to have a favourable toxicity profile.     

The epidural and intrathecal administration of ketamine

An overview of the spinal administration of ketamine is presented. Ketamine acts as a noncompetitive antagonist of the NMDA receptor Ca++ channel pore. This effect provides interesting possibilities in pain therapy. However, there are still contrasting results that seem to be due to a lack of comparative controlled studies. The presence of systemic and neurotoxic effects presently limits clinical use.