Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.     

Congenital methemoglobinemia due to NADH-methemoglobin reductase deficiency in three Indian families

Congenital methemoglobinemia is a relatively rare clinical disorder characterized by life-long cyanosis, caused by either an inherited mutant hemoglobin (Hb-M) or deficiency of physiologically active NADH-dependent methemoglobin reductase (NADH-MR). NADH-MR deficiency leads to two different types of recessive congenital methemoglobinemia. In type I, cyanosis is the only major symptom and NADH-MR deficiency is restricted only to the red blood cells. In type II, cyanosis is associated with severe mental retardation and neurological impairment. The objective of this study is to establish the cause of cyanosis in our cases of congenital methaemoglobinemia. Erythrocyte NADH-MR activity was assayed spectrophotometrically. Spectral analysis of the hemolysate treated with potassium ferricyanide was recorded between 400-700 nm and Hb electrophoresis on starch gel at pH 7.0 was done to rule out the presence of Hb-M. NADH-MR deficiency was detected in 3 families. There was a history of consanguinity in one of these cases. The three propositi presented with breathlessness, fever and peripheral cyanosis. There was no history of cardiac illness or exposure to drugs and chemicals. There were no signs and symptoms of mental retardation. The presence of Hb-M was ruled out. Hb-A2, Hb-F, G6PD activity and reduced glutathione levels were normal. NADH-MR activity in all the cases ranged from 4.1 to 9.2 IU/g Hb (normal range 7.0-24.0 IU/g Hb). We describe NADH-MR deficiency in three unrelated cases (age 4 months to 6 years) where the activity of the enzyme was 30-40% of normal. These three cases of congenital methemoglobinemia are due to type-I NADH-MR deficiency without mental retardation.     

Allele sharing at six VNTR loci and genetic distances among three ethnically defined human populations

Because of their high degree of polymorphisms, the variable number of tandem repeat (VNTR) loci have become extremely useful in studies involving gene mapping, determination of identity and relatedness of individuals, and evolutionary relationships among populations. However, there are some concerns regarding whether or not the patterns of such genetic variation can be studied by the classical population models that are developed for studying genetic variation at blood groups and protein loci, since VNTR alleles detected by molecular size may not always be identical by descent. Although theoretical and empirical studies demonstrate that this concern is overstated, this study provides further support of the application of the traditional mutation-drift models to predict the pattern of intra- and inter-populational variation at VNTR loci. By comparing genetic variation at six VNTR loci with that at 16 blood groups and protein loci in three ethnically defined populations, we show that the patterns of variability at these two sets of loci are in general parallel to each other. Shared VNTR alleles among populations are generally more frequent than the ones which are not present in every population; the proportion of shared alleles among populations increases with increasing genetic similarity of populations; and the number of VNTR alleles is positively correlated with gene diversity at these loci. All of these observations are in agreement with the prediction of the mutation-drift models, particularly when the possibility of forward-backward mutations are taken into account. This parallelism of genetic variation at VNTR loci and blood groups/protein loci further asserts the potential of using such hypervariable loci for microevoltionary studies, where closely related populations may exhibit considerably less allele frequency differences at the classical blood group and protein loci. © 1992 Wiley-Liss, Inc.     

Respiratory syncytial virus infection: Clinical presentation and management

Summary RSV infection continues to be a major cause of morbidity and mortality throughout the world. Despite advances in the understanding of its pathogenesis, limited progress has been made in prevention and treatment of RSV infection. Based on the experiences thus far it seems that control of RSV infection will be a difficult and complex task.     

Studies on the mechanism of synthesis and release of the procoagulant activity from leukaemic cells

The synthesis and release of procoagulant activity (PCA) from leukaemic leucocytes was studied in anin vitro culture system stimulated by endotoxin. Puromycin, actinomycin-D, vinblastine, colchicine, dibutyryl cyclic AMP and ouabaln were added to the culture system to study some of the metabolic processes of these cells in relation to synthesis and release of PCA. It was found that production of PCA is an active process and depends on new protein synthesis. The release of PCA from cells can be inhibited by vinblastine, an inhibitor of microfilament and microtubules in the cell. The optimal release of PCA occurs at pH 7.2-@#@ 7.4 at 37°C and is not inhibited by the ATPase inhibitor ouabaln. Dibutyryl cyclic AMP inhibits the release/synthesis of PCA. Gram negative septicaemia and endotoxinaemia are capable of increased production and release of PCA from leukaemic cells and could contribute to the coagulation fallure seen in this disease.     

Progression or reactivation of Otosclerotic lesion despite Fluoride therapy

Progression or reactivation of Otosclerotic disease as shown by tomography, despitemoderate dosage Sodium Fluoride therapy, is due to poor intestinal absorption of the drug in its enteric coated form. It is also seen when the drug is often temporarily withdrawn. During Sodium Fluoride therapy for Otosclerosis an intestinal absorption test of the preparation is necessary.     

Levonorgestrel-releasing intrauterine system vs. transcervical endometrial resection for dysfunctional uterine bleeding.

OBJECTIVE: To compare the acceptability, efficacy, adverse effects, and user satisfaction of a levonorgestrel intrauterine system (LNG-IUS) and transcervical resection of the endometrium (TCRE) for the treatment of dysfunctional uterine bleeding. METHOD: Of 50 women with a pictoral blood loss assessment chart (PBAC) score of 100 or greater, 25 had a LNG-IUS inserted (Mirena; Schering, Berlin, Germany) and 25 underwent TCRE. Procedure-related complications, PBAC score, hemoglobin levels, adverse effects, and rates of acceptability and satisfaction were recorded at 3-month intervals for a period of 12 months. RESULTS: At the end of 1 year there were a 97% and a 94% reduction in menstrual blood loss in the LNG-IUS and TCRE groups, respectively, and hemoglobin concentration had increased by 5.5% in the LNG-IUS group and 5.2% in the TCRE group. Adverse effects were similar in both groups except for systemic effects, which were seen only in the LNG-IUS group. Satisfaction rates were about 80% in the 2 groups. CONCLUSION: Both treatments were found to be equally effective but LNG-IUS placement requires less operator skill and entails no operative hazards, and the device provides effective contraception.