The carbamate insecticide ZZ-Aphox® induced structural changes of gills,liver, gall-bladder,heart, and notochord of Rana perezi tadpoles

Embryos of Rana perezi were kept under laboratory conditions and treated with carbamate ZZ-Aphox^® at chronic doses of 0.02 and 0.14 for 9 weeks. Both the histological study and the analysis of mortality show a direct relationship between the dosage and the effects of the pesticide. The histological study of the survivors over 56 days show damages in gills, liver, gall-bladder, heart, and notochord. Damages on the epithelia of gills (on their distal portion) and gall-bladder recover over a few days, whereas those provoked on the compacting of the hepatic parenchyma and the hepatocytes, the auricle and the perinotochordal collagenic fibers alter their structure in a lasting way. Potentials of such alterations are discussed, with special reference to the possible interference of the pesticide on the successful synthesis of the supporting connective sheaths.     

High-dose chemotherapy and autologous bone marrow rescue for patients with refractory germ cell tumors. Early intervention is better tolerated.

Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus autologous bone marrow rescue (AUBMR) was administered to 29 patients with advanced germ cell tumors (GCT) refractory to cisplatin-based chemotherapy. Two groups of patients with refractory disease were treated. Sixteen patients had been identified as "poor risk" at diagnosis and had an inappropriately slow decline of serum tumor markers after two cycles of induction cisplatin-based therapy (Group A). In addition, 13 patients were treated who had never had a complete response (CR) or had relapses after ifosfamide-based salvage chemotherapy (Group B). Patients in Group A were treated with high-dose carboplatin etoposide, and patients in Group B received high-dose carboplatin, etoposide, and cyclophosphamide. Fifteen of 29 (52%) patients had a CR (9, Group A; 6, Group B). The patients in Group A had fewer hematologic toxic effects, and the median number of days from day 0 to a granulocyte count greater than 0.5/microliters was 16 and to a platelet count of more than 50/microliters was 15, compared with 22 days and 23 days in Group B, respectively. There were fewer episodes of culture-positive sepsis in Group A (12%) compared with Group B (26%), and the only treatment-related death occurred in Group B. Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus AUBMR is effective for patients with GCT refractory to regimens of cisplatin with or without ifosfamide. Early use of high-dose chemotherapy reduces hematologic toxic effects and allows patients to start treatment in a more predictable fashion after cytoreduction, rather than when the disease is progressing rapidly.     

Mercury-induced necrosis of murine renal cell carcinoma

Administration of the nephrotoxic agent, bichloride of mercury (HgCl₂), to BALB/c mice bearing subcapsular renal tumor transplants induced early preferential necrosis of the tumor cells compared with mercury-treated normal kidney tubular cells and untreated control tumors. The principle is established that a selective proximal tubular poison is also toxic for a tumor of the same cellular origin.     

Disassociation of carbon disulfide-induced depression of flash-evoked potential peak N166 amplitude and norepinephrine levels.

Exposure to organic solvents frequently causes functional impairment of the central nervous system (CNS). One method to examine the effects of solvent exposure on visual function is flash-evoked potentials (FEPs). Greater knowledge of the role of various neurotransmitters in generating FEP peaks would be beneficial for understanding the basis of neurotoxicant-induced changes. FEP peak N166 is influenced by the psychological construct of arousal, which in turn is believed to be influenced by the function of neurons containing norepinephrine (NE). Because of its known effects on both NE and FEPs, we utilized carbon disulfide (CS2) as a means to examine the possible role of NE in modulating the amplitude of FEP peaks N36 and N166. Our hypothesis was that CS2-induced alterations in cortical NE levels would be correlated with changes in FEP peak N36 and N166 amplitudes. Adult male Long-Evans rats were implanted with electrodes over their visual cortex and allowed to recover. To develop peak N166, FEPs were recorded for two days prior to dosing. On the third day, FEPs were recorded prior to dosing, and one group of animals was sacrificed to serve as pretreatment controls. The remaining animals were dosed ip with 0 (corn oil vehicle; 2 ml/kg), 100, 200, or 400 mg/kg CS2. The treated animals were retested at 1, 4, 8, or 24 h after dosing, immediately sacrificed, and samples of the cortex, cerebellum, striatum, and brain stem were frozen for high performance liquid chromatography (HPLC) analysis of monoamine levels. Treatment with CS2 decreased peak N166 amplitude at 1 h, and peak N36 amplitude was depressed at 4 h, relative to the subject's pretreatment values. Peak latencies were increased, and colonic temperature was decreased by treatment with CS2. Exposure to CS2 depressed NE levels in the cortex, brain stem, and cerebellum 4 h after treatment. Conversely, at 4 h, levels of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid were increased in the brain stem and cerebellum, and levels of the DA metabolite homovanillic acid were increased in the brain stem. Levels of serotonin were unaffected by CS2 treatment. There was a slight increase in striatal levels of the serotonin metabolite 5-hydroxyindole acetic acid at all times after treatment with CS2. There was no apparent association between the decreases in NE levels and the reductions in amplitudes for peaks N36 and N166. The neurochemical mechanism for CS2-induced reductions in FEP peak amplitudes remains to be determined.     

Current use and questions concerning intravesical bladder cancer group for superficial bladder cancer

Bacille Calmette-Guerin (BCG) is the most effective therapy for CIS of the bladder. Although several series have shown a decrease in recurrence and progression of T1 tumor, this effect is temporary. More than one half of patients with T1 tumors treated with BCG will progress over the longterm. A second course of BCG is indicated after an initial complete response. There is no definitive answer regarding the efficacy of maintenance therapy or the optimum dose of BCG. Randomized trials are needed to address these issues in a more conclusive manner. Phase III trials have shown that mitomycin C can be as effective as BCG in the management of papillary tumors; however, BCG is more effective in patients with CIS and high-risk superficial tumors.     

Clinical measurement, statistical analysis, and risk-benefit: controversies from trials of spinal injury

BACKGROUND: The National Acute Spinal Cord Injury Studies have been a series of trials assessing the role of pharmacologic agents in the prevention of secondary neuronal damage after acute spinal cord injury. METHODS: The trials were multicenter randomized, controlled studies. RESULTS: Two trials have demonstrated the efficacy of high-dose methylprednisolone in improving neurologic and functional recovery and have shown a reassuring safety profile. CONCLUSION: This study responds to a recent commentary on these trials and examines in particular the roles of clinical measurement, statistical analysis, and risk benefit in assembling evidence for or against innovative therapies.     

Development of a diabetes care management curriculum in a family practice residency program.

Improving the quality of care for patients with chronic illness has become a high priority. Implementing training programs in disease management (DM) so the next generation of physicians can manage chronic illness more effectively is challenging. Residency training programs have no specific mandate to implement DM training. Additional barriers at the training facility include: 1) lack of a population-based perspective for service delivery; 2) weak support for self-management of illness; 3) incomplete implementation due to physician resistance or inertia; and 4) few incentives to change practices and behaviors. In order to overcome these barriers, training programs must take the initiative to implement DM training that addresses each of these issues. We report the implementation of a chronic illness management curriculum based on the Improving Chronic Illness Care (ICIC) Model. Features of this process included both patient care and learner objectives. These were: development of a multidisciplinary diabetes DM team; development of a patient registry; development of diabetes teaching clinics in the family practice center (nutrition, general management classes, and one-on-one teaching); development of a group visit model; and training the residents in the elements of the ICIC Model, ie, the community, the health system, self-management support, delivery system design, decision support, and clinical information systems. Barriers to implementing these curricular changes were: the development of a patient registry; buy-in from faculty, residents, clinic leadership, staff, and patients for the chronic care model; the ability to bill for services and maintain clinical productivity; and support from the health system key stakeholders for sustainability. Unique features of each training site will dictate differences in emphasis and structure; however, the core principles of the ICIC Model in enhancing self-management may be generalized to all sites.     

A practical radiosynthesis of a tritium‐labelled fluorocombretastatin

Zybrestat (combretastatin A‐4 disodium diphosphate) is currently in clinical trials as an antivascular anticancer agent. A similar fluorinated agent has shown promise as an antivascular agent, and a radiolabelled version would enable further understanding of its biological activities. Herein is described the synthesis of a tritiated fluorinated analogue of Zybrestat. Copyright © 2012 John Wiley & Sons, Ltd.