FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis

Fatty acid synthase (FAS), a key enzyme of the fatty acid biosynthetic pathway, has been shown to be overexpressed in various types of human cancer and is, therefore, considered to be an attractive target for anticancer therapy. However, the exact mechanism of overexpression of the FAS gene in tumor cells is not well understood. In this report, we demonstrate that the expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression in the case of prostate cancer in the clinical setting, and inhibition of the PTEN gene leads to the overexpression of FAS in vitro. We also found that the combination of the expression status of these two genes is a better prognostic marker than either gene alone. Furthermore, our results indicate that the specific inhibition of FAS gene by siRNA leads to apoptosis of prostate tumor cells, and inhibition of PI 3-kinase pathway synergizes with FAS siRNA to enhance tumor cell death. These results provide a strong rationale for exploring the therapeutic use of an inhibitor of the PTEN signaling pathway in conjunction with the FAS siRNA to inhibit prostate tumor growth.     

Biology versus environment in low birth weight children

OBJECTIVE: To explore the contribution of biologic risk factors versus socio-demographic and environmental risk factors in cognitive development of children with birth weight less than 2000 g, at the age of 12 years. DESIGN: Prospective cohort study. SETTING: Infants discharged from a NICU of a referral hospital, with birth weight less than 2000 g between 1987-89 and followed up in the High Risk Clinic. METHODS: The children were assessed at the age of 12 years, with the Weschlers Intelligence Scale for IQ and by Wide Range Achievement Test for mathematics skills. Mothers education, fathers education, socio-economic status, family structure, spaciousness of the house, the locality in which the child lived and the type of school the child attended, were all recorded. A stimulation score was determined at 6 and 12 months and 3 years. Family environment score was used at 12 years. RESULTS: The cohort consisted of 180 children, with 90 controls. The mean IQ of the study group was 89.5 +- 16.9, which was significantly lower than that of controls (97.2 +- 14.1) (P lessthan 0.05). The mathematical skills of the study group were significantly poorer (P lessthan 0.05) than that of controls. A multiple linear regression analysis was done using IQ as the dependent variable and all risk factors at birth, stimulation scores and socio-environmental factors as independent variables. Mothers education was the most important factor contributing to the total IQ, a variance of 25.2percent of the total variance 44.2 PERCENT. Fathers education emerged as an important factor for mathematics skills. School was the next important factor for IQ as well as academics. Controlling for all other background factors, birth weight was the only biologic factor of significance, and this had a very small contribution. CONCLUSION: Parental education and the type of school attended by the child were the most important factors influencing cognitive development. The only biologic factor of importance was birth weight, but this too had a very small contribution.     

Cataract surgery in sympathetic ophthalmia

PURPOSE: To analyze the results of cataract surgery in patients with sympathetic ophthalmia. SETTING: Sankara Nethralaya, Medical Research Foundation, Chennai, India. METHODS: This study comprised 66 patients (132 eyes) with sympathetic ophthalmia seen at the uveitis referral clinic between January 1990 and July 2001; 42 eyes (31.8%) had cataract. Cataract surgery was performed in 17 sympathizing eyes and 1 exciting eye (17 patients). The records of these 18 eyes were retrospectively analyzed. Three eyes had extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation, 6 eyes had ECCE without IOL implantation, and 9 eyes had phacoemulsification with IOL implantation. The mean follow-up was 28.7 months (range 3 to 60 months). RESULTS: The causes of sympathetic ophthalmia were penetrating trauma (n = 8 eyes), ocular surgery (n = 6), perforated corneal ulcer (n = 2), and cyclocryotherapy (n = 1). The most common cataract type, present in 7 eyes (38.8%), was mixed (posterior subcapsular and posterior polar). Visual acuity improved after surgery in 13 eyes (72.2%). The main factors impairing visual recovery were submacular scar and optic atrophy, which were sequelae of the sympathetic ophthalmia. Posterior capsule opacification was noted in 14 eyes (77.7%); it was visually significant in 6 eyes. There was no significant difference in postoperative inflammation or disease reactivation between the 3 types of surgery. CONCLUSIONS: Cataract extraction in cases of sympathetic ophthalmia can be safely and successfully performed with vigilant preoperative and postoperative control of inflammation, careful surgical planning, and meticulous surgical technique. The final visual outcome, however, depends on the posterior segment complications of the disease.     

Small group health insurance: ranking the states on the depth of reform, 1999

States are ranked based on the potential of their small group health insurance reforms to enhance health insurance uptake. Reforms were quantified based on their market impact potential. Five dimensions of reforms were identified, Access Improvement, Premium Reduction, Premium Differential Reduction, Continuity of Coverage, and Enhancing Valued Plan Features. The reform indices representing these dimensions were developed based on document review of state statutes, combined with actuarial judgment to identify and assign scores to market-relevant regulations in line with their impact potential. The distribution of the states' reform scores and rankings show wide variation in the depth and focus of their reforms. Only seven of the top ten states on the Total Reform index had consistently higher scores on two or more reform dimensions. The conceptual linkages between specific regulations and the documented small group market problems lead to normative expectations of an association between the depth of state reforms and the prevalence of uninsurance.     

Massive cystic degeneration of a uterine leiomyoma presenting as an ovarian cyst: a case report

An unusual case of massive cystic degeneration in an uterine leiomyoma measuring 21 cm in diameter, in a 40 year old female is being presented. It was diagnosed as a cystic adnexal tumor on ultrasonogram. Interlacing bundles of smooth muscle were identified in the cyst wall, which was confirmed on special stains. The differential diagnoses considered in this case are discussed. To the best of our knowledge, this is the largest cystic degeneration in an uterine leiomyoma reported in the literature.     

Ulcerative post-kala azar mucosal leishmaniasis masquerading as a carcinoma--a case report

Post kala-azar mucosal leishmaniasis (PKML) is relatively rare in the Indian subcontinent. We describe an ulcerative variant of PKML with nasal involvement in a Nepalese adult male. He had ulcerated plaque over the upper lip with extensive involvement of nasal columella and septum. He came from endemic area for kala-azar and had a previous history of kala-azar. There were plenty of LD bodies in microsections and FNA of submandibular lymph node.     

Quality of diet,body position,and time after feeding influence behavioral states in low birth weight infants

The effects of variations in carbohydrate and fat intake and body position on behavioral activity states were evaluated in 64 healthy, growing low birth weight infants (birth weight, 750-1600 g). The infants, enrolled in a prospective, randomized, double-blind, controlled study of effects of quality of dietary energy, were fed one of the five formulas. These formulas contained fixed intakes of protein (4 g/kg per day) but different intakes of carbohydrate (9.1 to 20.4 g/kg per day) and fat (4.3 to 9.5 g/kg per day). Six-hour daytime sleep studies were performed at 2-wk intervals from time of full enteral intake until discharge (mean postconceptional age at first study, 33.2 +/- 1.8 wk). Infants were randomly assigned to the prone or supine position for the first 3-h postprandial period; the position was reversed during the second 3 h. Behavioral activity state, i.e. quiet sleep (QS), active sleep, indeterminate sleep, awake, or crying was coded each minute throughout the postprandial period. The overall incidence of QS was almost double in the prone position versus the supine (p < 0.0001). In contrast, the probability of being in either of the two wakeful states (awake and crying) was increased when infants were placed in supine position (p < 0.0001). Increased likelihood of being in QS while prone was found only during the 30 min after and before feeding in a 150-min prandial cycle. In contrast, increased amounts of awake and crying in supine position were observed throughout the feeding interval. As carbohydrate intake increased, time spent in QS in supine position increased (from 8.6% to 12.5%, p < 0.02), and a trend in the same direction was noted for the prone position (p = 0.06). However, during postprandial minutes 10-100, when QS is likely to be entrained by the nutrient intake, enhancement of QS was found in the prone position only (p < 0.02). Carbohydrate intake influences the total time spent and the distribution of behavioral activity states within the postprandial period in low birth weight infants. The effect of nutrient intake on sleep profile is dependent on body position and time after feed. Mechanistic hypotheses relating sudden infant death syndrome to sleeping position may need to take these observations into account.