Epidemiology of chronic suppurative otitis media and deafness in a rural area and developing an intervention strategy

Of 613 children evaluated in a village in Haryana 94 (15.3%) were observed to have chronic suppurative otitis media (CSOM). Fifty eight (61.7%) children had hearing impairment. CSOM contributed to 71.6% of the hearing impaired (58/81). On analysis of association of CSOM with literacy and socio-economic status of mothers, and age, sex, and upper respiratory tract infections (URI) in children positive correlation was observed only with URIs (P<0.001). Literacy and socio-economic status of the mothers did not correlate significantly with knowledge about treatment seeking, and ear cleaning practices, probably due to the narrow range of incomes and literacy levels. An intervention program consisting of play, demonstrations, health charts and slogans, and aural cleaning and antibiotic drops was introduced.     

Exposure to nicotine enhances acquisition of ethanol drinking by laboratory rats in a limited access paradigm

 Observations in humans suggest that the initial use of tobacco occurs in close temporal proximity to experimentation with alcohol. There have been relatively few research reports, however, examining possible interactions between these two agents. The present experiments examined the effect of nicotine exposure on the acquisition of ethanol drinking behavior in a limited access procedure. In experiment 1, rats were presented with 1-h access to ethanol solutions of increasing concentration for a period of 20 days. Subcutaneous injections of nicotine (0.6 or 1.2 mg/kg salt) or vehicle were administered 30 min prior to each ethanol presentation. Experiment 2 used a similar method, but rats were presented with water along with ethanol during the 1-h test session. Mecamylamine, a nicotinic receptor antagonist, was administered 30 min prior to the nicotine treatment. Nicotine was seen to produce a dose-dependent increase in ethanol drinking behavior which commenced at the 5% ethanol concentration and continued at 8% and again at 10%. In the second experiment, mecamylamine was observed to block completely the nicotine-induced increase in ethanol drinking behavior. The findings suggest that exposure to nicotine can facilitate the acquisition of ethanol drinking behavior in naive rats and that this effect is mediated by nicotine’s interaction at the nicotinic-cholinergic receptor. Received: 11 June 1998 / Final version: 1 October 1998     

Attenuation of voluntary ethanol consumption by dopamine-beta-hydroxylase inhibition (FLA-57): mediated by changes in aversion, reinforcement or both

The dopamine-beta-hydroxylase inhibitor, FLA-57, was reported by several investigators to reduce voluntary ethanol consumption in rats. The nature of the effect of FLA-57 on this behavior had been attributed to its involvement in both the mediation of positive reinforcing and aversive processes. In the present study, the capacity of FLA-57 to induce a conditioned taste aversion (CTA) in both a forward and a "nominally backward conditioning" paradigms was investigated. This was done in an attempt to assess the possible contribution of a FLA-57-induced CTA to the previously observed reduction in ethanol intake in several drinking studies. Furthermore, the ability of FLA-57 to induce a CTA in a nonnovel situation, where the taste of the presented solution (ethanol or saccharin) was familiar to the animals, was also assessed. The inclusion of these specific conditions was necessitated by the attempt to create conditions similar to those prevalent in drinking studies. We found that FLA-57, in both conditioning paradigms, induced a significant CTA. Animals, naive and experienced with the taste of ethanol or saccharin, exhibited a CTA following the administration of FLA-57. However, the magnitude and rate of extinction of the observed CTAs did not resemble those observed in studies on the effects of FLA-57 on ethanol intake. The results of this study suggest that while it is possible that FLA-57 exerts its effect on ethanol intake, at least in part, through an aversive mechanism, such a mechanism is unlikely to be the exclusive process through which ethanol ingestion is attenuated.     

Metastatic spinal cord compression: radiotherapy outcome and dose fractionation.

BACKGROUND AND PURPOSE: No standard dose fractionation has been defined for metastatic spinal cord compression. This retrospective analysis was undertaken to explore the impact of hypofractionated treatment compared to conventional multifraction treatment. MATERIALS AND METHODS: One hundred and two consecutive patients referred to Mount Vernon Cancer Centre with metastatic spinal canal compression confirmed on MR scan in 95% with median age 68 years (range 32-90) and main primary tumour types breast (28%), prostate (28%) and lung (20%); 51% of patients were fully ambulant at diagnosis, 41% ambulant but with paraparesis and 9% had complete paraplegia. Spinal radiotherapy was given delivering a single dose in 32% and 20 Gy in five fractions in 64%. RESULTS: The median survival was 3.5 months; survival was significantly related to primary site and motor function at presentation. Normal ambulation was achieved in 58% at 2 weeks and 71% up to 2 months after treatment. No patient who presented with paraplegia regained function. At presentation 59% of patients had severe pain, which fell to 8% at 2 weeks. Comparing those patients who received one or two dose treatments with those who received protracted fractionation, the two groups were matched for age, sex, primary site and site of compression. Relatively more patients treated with one or two doses had paraplegia; 19% vs. 3%. Despite this outcome in the two groups was equivalent for motor and sphincter function and pain control. CONCLUSIONS: Metastatic spinal canal compression carries a poor prognosis. Urgent treatment will maintain and improve motor function in patients presenting ambulant but those who have paraplegia at presentation do not improve and have a very short survival. In this series no difference in outcome was seen between patients treated with one or two radiation doses compared to multifraction treatment; a randomised trial comparing fractionation schedules would be justified.     

The statins as anticancer agents.

3-Hydroxy-3-methylgutaryl CoA reductase inhibitors, commonly referred to as the statins, have proven therapeutic and preventative effects in cardiovascular diseases. Recently, there are emerging interests in their use as anticancer agents based on preclinical evidence of their antiproliferative, proapoptotic, anti-invasive, and radiosensitizing properties. Inhibition of 3-hydroxy-3-methylgutaryl CoA reductase by the statins interferes with the rate-limiting step of the mevalonate pathway, leading to reduced levels of mevalonate and its downstream products, many of which play important roles in critical cellular functions such as membrane integrity, cell signaling, protein synthesis, and cell cycle progression. Perturbations of these processes in neoplastic cells by the statins may therefore result in control of tumor initiation, growth, and metastasis. The statins have demonstrated growth inhibitory activity in cancer cell lines and preclinical tumor models in animals. Phase I trials of statins in humans have demonstrated myotoxicity as their main dose-limiting toxicity, and Phase II trials in various tumor types are ongoing to evaluate their efficacy. Potential future directions in the development of the statins as anticancer agents include combinations with chemotherapeutic or other molecular-targeted agents, combinations with radiotherapy, maintenance therapy in minimal disease status, and as chemopreventive therapy.     

The ratio between carcinoma antigen-125 levels in the seminal plasma and serum may be a marker for fertilization in intracytoplasmic sperm injection

Objective: To assess the relationship between tumor marker carcinoma antigen-125 levels in seminal plasma and serum and fertilization rates in an IVF program, using intracytoplasmic sperm injection (ICSI).

Design: A prospective study.

Setting: IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Patient(s): Twenty-five infertile patients with severe oligo-terato-asthenospermia syndrome and 25 fertile male donors.

Intervention(s): None.

Main Outcome Measure(s): Serum and seminal plasma carcinoma antigen-125 concentrations and fertilization rate per cycle.

Result(s): In the infertile group, the seminal plasma carcinoma antigen-125 levels ranged from 22.0 to 1,284.0 U/mL (mean level ± SD, 229.9 ± 274.2 U/mL). In the normospermic fertile male donors, the seminal plasma carcinoma antigen-125 concentrations ranged from 12.2 to 336.7 U/mL (mean level ± SD, 110.1 ± 91.6 U/mL). This difference was statistically significant. The mean ± SD ratio between the seminal plasma/serum carcinoma antigen−125 levels differed significantly between the infertile group (47.9 ± 61.3) and the fertile male donors (5.7 ± 3.5). In the infertile group, the ratio between the seminal plasma/serum carcinoma antigen-125 levels was found to be negatively correlated with the oocyte fertilization rate.

Conclusion(s): The ratio between carcinoma antigen−125 levels in the seminal plasma and serum may be an indirect marker for male infertility and fertilization rate in IVF treatment using ICSI.     

Treatment variables in relation to oocyte maturation: Lessons from a clinical micromanipulation-assisted in vitro fertilization program

Objective: In an effort to understand the mechanism underlying the improved pregnancy rate observed in IVF cycles when gonadotropin-releasing hormone analogues (GnRH-a) are applied, we investigated a possible relationship between treatment variables and oocyte-nuclear maturity. Design: Nuclear maturity was retrospectively assessed in cumulus-free, denuded oocytes, obtained from women undergoing micromanipulation-assisted IVF treatment following controlled ovarian hyperstimulation with GnRH-a and menotropins. Setting: The setting was the infertility and IVF unit of a tertiary academic medical center. Participants: Two hundred twenty-one patients underwent 435 treatment cycles. Main Outcome Measure: This was the proportion of germinal vesicle-intact immature (GVII) oocytes. Results: One hundred fifty-four of the 3520 oocytes studied (4.4%) were in the GVII stage. These oocytes were found in 66 of the treatment cycles (15.2%) and in 54 of the patients (24.4%). Cycles in which GVII oocytes were detected did not differ from those in which all the aspirated oocytes were mature in the following respects: patient age, type and duration of infertility, controlled ovarian hyperstimulation protocol and time of ovum pickup. However, the GVII group was characterized by a significantly higher peak estradiol level, as well as a higher number of mature follicles visualized sonographically (diameter, >14 mm) and oocytes retrieved. Conclusions: Comparing the present findings with previously published data, it appears that the inclusion of GnRH-a in the stimulation regimen is associated with a lower proportion of immature oocytes. A higher occurrence of oocyte-nuclear immaturity is apparently associated with a significantly better ovarian response to stimulation. The high incidence of immature oocytes observed in patients with normospermic partners and low fertilization rates in previous cycles may suggest that the fertilization failure in some of these cases is due to oocyte, rather than sperm, dysfunction.     

Radiation therapy induced changes in apoptosis and its major regulatory proteins, Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of the cervix.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for cancer induces cell death by apoptosis. The major apoptotic regulatory molecules include Bcl-2, Bcl-XL (antiapoptotic), and Bax (proapoptotic) proteins. Invasive squamous cell carcinoma of the cervix is mainly treated by radiation, and hence our aim was to evaluate the changes induced by RT in the apoptotic index (AI) and to correlate this to the levels of the major pro- and antiapoptotic molecules. MATERIALS AND METHODS: Paired biopsies were obtained in 30 cases of invasive carcinoma cervix before and after 10 Gy RT. The TUNEL assay was performed to detect apoptotic nuclei and Bcl-2, Bcl-XL, and Bax proteins detected by immunohistochemistry (IHC). Statistical analysis was performed using the Spearman rank correlation coefficient test. RESULTS: Following RT, there was a significant increase in the mean AI [2.25 (+/-2.28) in post-RT vs 0.90 (+/-0.53) in the pre-RT group]. Bax, a major proapoptotic protein, was significantly increased following RT (P < 0.05), whereas the antiapoptotic Bcl-XL showed a significant decrease (P = 0.006). There was no significant change in Bcl-2 expression. The Bcl-2 and Bax IHC scores and the Bcl-2/Bax ratio did not correlate with AI in the 2 groups. There was an inverse correlation of Bcl-XL to AI in the pre-RT group (P = 0.003) but not in the post-RT group. CONCLUSIONS: RT for invasive squamous cell carcinoma of cervix results in increased apoptotic cell death with the up-regulation of Bax, a proapoptotic protein, and the down-regulation of Bcl-XL, an antiapoptotic protein, without any significant change in the levels of Bcl-2.