The development of novel and selective p56lck tyrosine kinase inhibitors

Early T-cell receptor mediated signal transduction involves the activation of several tyrosine protein kinases. One of these tyrosine kinases, p56lck, is expressed primarily in T-cells and Natural Killer (NK) cells and has been shown to be critical for their proliferative and effector functions. Indandiones have been identified as a potent and selective chemical class that inhibits p56lck.     

Silent myocardial ischaemia and left ventricle hypertrophy in diabetic patients

The purpose of this study was to evaluate the ability of three noninvasive techniques to detect silent myocardial ischaemia and analyse the factors associated with this condition, particularly left ventricular hypertrophy, in diabetic patients. An ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole intravenous infusion, ambulatory 48 h ECG monitoring and an echocardiographic study were performed in 92 diabetic patients without cardiac symptoms but with > or = 2 additional cardiovascular risk factors. At least one of these tests was positive in 28 patients (30.4%), suggesting silent myocardial ischaemia. Twenty-four of these patients had a coronary angiography which showed significant coronary stenosis in only 9 cases. An accurate echocardiographic tracing was obtained in 79 patients, particularly in 7 of the 9 with coronary stenosis. Left ventricular hypertrophy was detected in 34 patients, 6 of whom had coronary stenosis. In patients with left ventricular hypertrophy, the positive predictive values of myocardial scintigraphy and the ECG stress test were respectively 50% and 100%, as compared to only 33% and 11% in those without hypertrophy. In summary, coronary stenoses were found in < 10% of asymptomatic diabetic patients with > or = 2 cardiovascular risk factors, but more frequently in individuals with left ventricular hypertrophy. Thus, silent myocardial ischaemia should be searched for first in diabetic patients with hypertrophy, for which the stress test was the most accurate detection method in this study.     

Disseminated intrathoracic desmoplastic small round-cell tumor: a case report

OBJECTIVE: To identify risk factors associated with complicated eclampsia. METHODS: Twenty-four patients with eclampsia complicated by intracerebral hemorrhage, pulmonary edema, renal, hepatic, or respiratory failure, disseminated intravascular coagulation, abruptio placentae, pulmonary aspiration, or hemolysis, elevated liver enzymes, low platelets syndrome were compared retrospectively with 101 uncomplicated eclamptic controls. Information on maternal demographic factors, medical and obstetric histories, and maternal and perinatal outcomes was retrieved and analyzed by univariate and multivariate analysis. RESULTS: By multiple logistic regression, the only risk factors associated with the development of complicated eclampsia were maternal age over 26 years (adjusted odds ratio [OR] 6.3, 95% confidence interval [CI] 2.17, 18.48), multiparity (adjusted OR 4.5, 95% CI 1.55, 13.60) and no prenatal care (adjusted OR 3.3, 95% CI 1.25, 9.60). CONCLUSION: Maternal age above 26 years, multiparity, and no prenatal care are the maternal risk factors identified for the development of complicated eclampsia.     

Sexual behavior of HIV-seropositive young men with congenital coagulopathies. Hemophilia Behavioral Intervention Projects (HBIEP) Study Group

The purpose of this study was to investigate the attitudes towards attempted suicide patients among registered nurses involved in the somatic care of such patients, and to compare them with those of psychiatric nurses. The attitudes were measured on a newly constructed scale, the Understanding of Suicide Attempt Patients Scale (USP-Scale), and three brief clinical vignettes with the answer format of a visual analogue scale (VAS). The nurses working within the psychiatric services were more understanding and more willing to nurse suicide attempt patients than nurses in somatic disciplines. Among all the nurses, older personnel were more favourably disposed than the younger, and more frequent contact with suicide-prone patients was related to more positive attitudes. The perceived need for further training in suicidology was significantly stronger among the nurses in the general hospitals. This suggests that their 'negative attitudes' may to some extent be a result of lack of knowledge and uncertainty rather than a hostile attitude. The nurse has a responsibility to create a positive climate in the patient's encounter with the health services. Knowledge and understanding are needed to enable the nurse to provide professional care for a difficult and challenging patient group.     

Early effects of iodine deficiency on radial glial cells of the hippocampus of the rat fetus. A model of neurological cretinism

The most severe brain damage associated with thyroid dysfunction during development is observed in neurological cretins from areas with marked iodine deficiency. The damage is irreversible by birth and related to maternal hypothyroxinemia before mid gestation. However, direct evidence of this etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine content (LID), or LID supplemented with KI. Other rats were fed the breeding diet with a normal iodine content plus a goitrogen, methimazole (MMI). The concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were determined in the brain of 21-d-old fetuses. The proportion of radial glial cell fibers expressing nestin and glial fibrillary acidic protein was determined in the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the LID and MMI fetuses, as compared to their respective controls. The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams. These results show impaired maturation of cells involved in neuronal migration in the hippocampus, a region known to be affected in cretinism, at a stage of development equivalent to mid gestation in humans. The impairment is related to fetal cerebral thyroid hormone deficiency during a period of development when maternal thyroxinemia is believed to play an important role.     

Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal fluid and viral resistance to zidovudine in children with HIV encephalopathy

The amount of human immunodeficiency virus (HIV) type 1 RNA and the presence of a codon 215 mutation indicative of zidovudine resistance were evaluated in cerebrospinal fluid (CSF) and plasma obtained from HIV-1-infected children. The level of HIV-1 RNA in CSF was highest in children with severe encephalopathy (n = 25; median, 430 copies/mL; range, 0-2.2 x 10(5) copies/mL) followed by the moderately encephalopathic (n = 7; median, 330; range, 0-1130) and nonencephalopathic groups (n = 9; median, 0; range, 0-566) (P = .007). There was no correlation between CSF and plasma HIV-1 RNA levels. Five of 7 children with the codon 215 mutation in CSF had a progression of encephalopathy, while all 8 children with wild type codon 215 had improved or stable disease during zidovudine treatment (P = .007). These findings suggest that increased viral replication and emergence of drug-resistant HIV-1 variants within the central nervous system may play a role in progression of HIV encephalopathy.     

Impaired processing of proopiomelanocortin in corticotroph macroadenomas

The p53 mutations in the reported 243 lung cancers and our 59 cases were analyzed. The common base substitutions found in the lung cancer were G to T transversion (35%), C:G to T:A (26%) and A:T to G:C transitions (11%). Four types of the hot spot, 1) G to T transversion, 2) A to G transition in ApT site, 3) C to T transition in CpG site and 4) mix of the transversion and transition were identified. It is suggested that A to G transition at ApT site in the non-transcribed strand may be a new hot spot in the p53 gene in lung carcinoma. We also show that microscopic selection of cancer cells will facilitate the detection of p53 mutations in adenocarcinomas.