Spatial and Temporal Patterns of Neurogenesis in the Chick Retina

Chick embryo retinas were labelled in ovo by single injections of [3H]thymidine at selected times between days 2 and 12 of incubation. Embryos were later removed, at different stages of development, and the retinas processed for autoradiography of either serial sections or dissociated cell preparations. Analysis of unlabelled cells shows that neurogenesis starts, on day 2 of incubation, in a dorsotemporal area of the central retina, close to the posterior pole and to the optic nerve head. A gradient of neurogenesis spreads from this central area to the periphery, where neurogenesis ends, shortly after day 12, when the last few bipolar cells withdraw from the cell cycle. Additional dorsal-to-ventral and temporal-to-nasal gradients can be discerned in our autoradiographs. In all retinal sectors, ganglion cells start first to withdraw from the cell cycle, followed, with substantial overlapping, by amacrine, horizontal, photoreceptor plus Müller, and bipolar neuroblasts. Ganglion cells are also the first to reach the 50% level of unlabelled cells, followed this time by horizontal, photoreceptor, amacrine, Müller and bipolar cells. Finally, 100% levels of unlabelled cell populations are attained simultaneously by ganglion, horizontal and photoreceptor cells, followed by amacrine, then by Müller, and last by bipolar cells. Although all classes of neurons, in varying proportions, are being produced most of the time, our results also demonstrate that, in any given retinal area, the first cells leaving the cycle are determined to become ganglion cells, and the last ones bipolar cells, and not other types.     

Effects of Nd-YAG laser on platelet function in vitro: A comparative study using the spectraprobe, ‘hot tip’ and bare fibres

The effects of Nd-YAG laser irradiation on platelet function in vitro were studied using platelet rich plasma obtained from the blood of healthy volunteers. Laser delivery was effected via the bare optical fibre, thermal hot tip fibre and spectraprobe and the effects of these probes on platelet function were compared. Fall in platelet count and mean platelet volume (MPV) were proportional to increasing energy delivery with all three probes, the effect being maximal with the spectraprobe, moderate with the hot tip and least with the bare optical fibre. A significant decrease in percentage aggregation of platelets in response to added ADP, collagen and ristocetin with increasing energy delivery was also observed with all three probes. The formation of preformed aggregates, however, showed an increase proportional to energy delivery with all three probes.The differential effects of the various probes used in this study on platelet function may enhance our understanding of the complex role played by platelets in the pathogenesis of complications such as arterial thrombosis and re-occlusion after laser angioplasty.     

Staged TRAM Breast Reconstruction: Combining the Advantages of Tissue Expansion with Surgical Delay

The TRAM flap has become the gold standard in breast reconstruction but suffers from the disadvantages of poor color match, different texture, and impaired sensation compared to the normal breast. This study reports on a two-stage procedure to address these problems. The first stage consists of insertion of a tissue expander and surgical delay of the TRAM flap. The second stage consists of removal of the tissue expander and transposition of a deepithelized TRAM flap into the tissue expanded cavity. (The capsule is excised.) Four cases of breast reconstruction are reported. The advantage of this procedure is that it offers the benefits of tissue expansion, viz., normal color match, texture, and sensation, and in addition, reconstruction is achieved with autologous tissue by a pedicled TRAM flap. The vascularity of the TRAM is enhanced by a surgical delay procedure.     

Pharmacokinetics, in-situ absorption and protein binding studies of a new neuroleptic agent centbutindole in rats.

The present study reports the absorption kinetics, plasma protein binding and pharmacokinetic profile of the centbutindole (I) after i.v. and oral dosing in rats. In addition, an in-situ absorption study was carried out using a closed-loop technique at pH 2.6 and 7.4. The rate of absorption at pH 2.6 was 5-fold less compared to that observed at pH 7.4. In-vitro and in-vivo protein binding (ultra filtration technique) was independent of substrate concentration over a range of 1.25-10.0 microg/ml. Pharmacokinetic parameters of I were determined in male rats after administering a single 4 mg/kg oral dose and 2 mg/kg intravenous dose. The peak serum concentration of I was found to be 50.1 ng/ml at 30 min after oral administration followed by a secondary Cmax of 43.2 ng/ml at 180 min. For the hydroxy metabolite (II), a Cmax of 6.4 ng/ml was measured at 360 min after oral administration of I. After oral dosing an irregular concentration-time profile with secondary peaks was observed for both I and II. The terminal half-lives for I and II after oral dosing were 163 and 263 min, respectively. After intravenous dosing, the levels of I decreased biexponentially with a distribution (t(1/2) alpha) and elimination (t(1/2) beta) half-lives of 5.7 and 128 min, respectively. Comparison of the AUC after oral and intravenous dosing of I indicates that only about 24% of the oral dose reaches the systemic circulation. The limited bioavailability can either be due to the poor solubility of the compound and/or extensive first pass metabolism in the gastrointestinal (GI) tract. Co-administration of polyethylene glycol (PEG) at oral dosing improves solubilization and increases bioavailability.     

Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.     

Bladder schistosomiasis. Etiologic diagnosis of detrusor contraction insufficiency

This paper reports a case of bladder bilharziasis with histopathological exam and different patterns of urodynamic evaluation. The need for urodynamics is emphasized in order to avoid diagnostic and therapeutic mistakes.     

Radioactive iodine therapy in Graves' hyperthyroidism

Graves' disease is a common condition encountered in clinical practice. The available modes of therapy for Graves' disease are antithyroid drugs, radioiodine and surgery. Radioiodine therapy is indicated in patients with nearly all causes of hyperthyroidism and is considered the treatment of choice for most patients with Graves' hyperthyroidism who are beyond the adolescent years. Pregnancy and breast-feeding are absolute contraindications. Although there are many ways of calculating the dose of radioiodine, fixed dose regimens are gaining acceptance. Hypothyroidism follows sooner or later in nearly all patients treated with radioiodine. Available evidence suggest that patients are best treated by a single thyroablative dose, the aim being elimination of hyperthyroidism, with larger doses accomplishing it with more certainty, and the inevitable hypothyroidism develops under physician control. Radioiodine therapy can lead to exacerbation of infiltrative ophthalmopathy and this can be prevented by the concomitant administration of corticosteroids. Radioiodine therapy for Graves' hyperthyroidism has no adverse effects on the health of the offspring of treated patients. There are no definitive data that provide evidence for increased rates of thyroid cancer, leukaemia, infertility or neonatal abnormality in patients treated with radioiodine. Radioiodine therapy is safe, definitive and cost-effective.     

Zeniplatin in advanced malignant melanoma and renal cancer: phase II studies with unexpected nephrotoxicity

The antitumor activity of zeniplatin, a third-generation, water-soluble platinum compound that has shown broad preclinical antitumor activity and no significant nephrotoxicity in phase I trials, was tested in patients with advanced malignant melanoma and advanced renal cancer. Patients who had not previously been treated, except with local limb perfusion and immunotherapy, were given zeniplatin as bolus injections at 125 mg/m² every 3 weeks. The main hematological toxicity was leukopenia (7/30 patients, WHO grade ≥ 3) and the main nonhematological toxicity was nausea and vomiting (21/30 patients, WHO grade ≥ 2). Serious nephrotoxicity was observed early in the renal cancer study and, later, also in the melanoma study. Hyperhydration did not prevent the nephrotoxicity, and the studies were stopped after 6 renal cancer patients and 24 malignant melanoma patients had been included. Zeniplatin gave objective responses in 3 of the 21 evaluable malignant melanoma patients [2 complete responses (CRs) in patients with lymph-node metastases lasted 5 and 14 months, respectively; 1 partial response (PR) in a patient with lymph-node and liver metastases lasted 6 months]. In the renal cancer study, only four patients were evaluable for response and none responded. The results show that zeniplatin has some activity (14%) in patients with advanced malignant melanoma, but no conclusion can be drawn regarding the activity of zeniplatin in renal cancer as the number of patients was too low. The main toxicities were leukopenia and nausea and vomiting. Unexpected and serious nephrotoxicity was observed, and for this reason the studies were terminated before the planned number of patients had been included. A possible explanation for the nephrotoxicity may be drug interactions, but no firm conclusion can yet be drawn. Received: 16 March 1996 / Accepted: 25 March 1997     

Effects of physical training in asthma: a systematic review

OBJECTIVES: To assess the evidence for the effects of physical training on pulmonary function, symptoms, cardiopulmonary fitness, and quality of life in subjects with asthma. METHODS: A search was conducted for randomised controlled trials of subjects with asthma undertaking physical training using the Cochrane Airways Group register of controlled clinical trials, Medline, Embase, Sportdiscus, Science citation index, and Current contents index. Studies were included in the review if the subjects had asthma, were 8 years of age or older, and had undertaken physical training for at least 20 minutes per session, twice a week, for a minimum of four weeks. The eligibility of trials for inclusion in the review and the quality of the trials were independently assessed by two reviewers. RESULTS: Eight studies with a total of 226 subjects met the inclusion criteria for this review. Physical training had no effect on resting lung function but led to an improvement in cardiopulmonary fitness as measured by an increase in maximum oxygen uptake of 5.6 ml/kg/min (95% confidence interval 3.9 to 7.2). None of the studies measured quality of life. CONCLUSIONS: Physical training improves cardiopulmonary fitness without changing lung function. It is not clear if the improvement in fitness translates into a reduction in symptoms or an improvement in the quality of life. There is a need for further randomised controlled trials of the effects of physical training in the management of asthma.