Coronary artery disease in young patients: clinical review and risk factor analysis

Fifty consecutive younger patients (< or = 40 years) with coronary artery disease, who underwent coronary angiography in National Institute of Cardiovascular Diseases were evaluated clinically and coronary risk factors were analyzed and compared with those of fifty older patients with coronary artery disease. Mean age of younger and older patients were 37.31 and 54.58 years respectively and myocardial infarction was the most common presenting complain in both the groups. Smoking and family history of premature coronary artery disease were more common in younger patients but the older patients were more diabetic and hypertensive. Central obesity and dyslipidemia did not vary between the two groups. Fifty percent of younger patients had one or two modifiable risk factors where sixty four percent of older patients had three or more modifiable risk factors. Forty four percent younger patients had hypercholesterolemia but a majority of patients had either isolated hypertriglyciredemia or decrease high density lipoprotein cholesterol or both with normal total cholesterol level but the total cholesterol and high density lipoprotein cholesterol index were more than 4.5. Younger patients had more number of normal coronary or single vessel diseases but older group had more number of triple vessel diseases. So the higher incidence of non-insulin dependent diabetes mellitus with central obesity suggesting insulin resistance along with unique profile of dyslipidemia, higher incidence of smoking and familial predisposition of premature coronary artery disease may be responsible for higher incidence of coronary artery disease at a premature younger age in this population.     

In vivo genotoxic effects of mercuric chloride in rat peripheral blood leucocytes using comet assay

DNA damage induced by Mercuric chloride (HgCl2) in leucocytes of Wistar albino male rats has been studied in vivo. The comet assay or the alkaline single cell gel electrophoresis (SCGE) assay was used to measure the DNA damage. The rats were administered orally with doses ranging from 0.0054, 0.0108, 0.0216, 0.0432 to 0.0864 mg/kg body weight (b.wt.) of HgCl2. The assay was performed on whole blood at 24, 48, 72 h, 1st and 2nd week. The reason leucocytes were used was to reflect biomarker studies in humans. A significant increase in mean comet tail length indicating DNA damage was observed at all time intervals with HgCl2 except in 2nd week post treatment when compared to controls. The mean comet tail length revealed a clear dose dependent increase from 0.0054 to 0.0432 mg/kg b.wt. A maximum increase in mean comet tail length was observed at 0.0432 mg/kg b.wt. 24 h after treatment. From 48 h post treatment, the mean comet tail lengths of all the doses gradually decreased and by week 2 of post treatment, they had approached control levels, pointing to repair of the damaged DNA. These findings suggest that the comet assay is a highly sensitive technique to study DNA damage caused by metals.     

Health gain and outcome predictors during inpatient and related day treatment in child and adolescent psychiatry

OBJECTIVE: To investigate health gain and its predictors during inpatient and associated day patient treatment. METHOD: Consecutive admissions to two inpatient units for children and young adolescents in northwest England were studied (N = 55). Ascertainments were made from multiple perspectives, including family, teacher, clinician, and an independent researcher. Measures were taken at referral, admission, discharge, and 6-month follow-up; health gain was inferred from change scores on measures. Recruitment lasted from late 1995 to 1997; follow-up was completed during 1998. Independent variables tested as predictors included assessments of presenting symptoms, therapeutic alliance, and family functioning. RESULTS: Significant health gain during hospitalization was found on most measures and sustained to follow-up. There was no symptom change during the waiting-list control condition. Health gain was predicted independently by child and parental therapeutic alliance with the unit early in hospitalization and by preadmission family functioning. Externalizing problems did well if accompanied by good alliance. CONCLUSIONS: Assessment of health gain from multiple perspectives is possible and valuable. Inpatient treatment has significant therapeutic effect. Predictors for health gain lie in process variables of therapeutic alliance and family functioning rather than presenting symptoms. The results are discussed in relation to clinical practice and future research.     

Reducing maternal mortality from eclampsia, using magnesium sulphate

Since the introduction of low dose magnesium sulphate to treat eclamptic patients at Dhaka Medical College, mortality rates have fallen from 16% to 8%. Personal communications from other centres in Bangladesh show similar findings.     

Reduced expression of the CXCR4 receptor mRNA in hepatocellular carcinoma and lack of inducibility of its ligand alpha-chemokine hIRH/SDF1alpha/PBSF in vitro

Differential cDNA displays between hepatocellular carcinoma and adjacent non-malignant tissues have previously detected a PCR product, hIRH (human intercrine reduced in hepatomas), equivalent to SDF1alpha/PBSF whose mRNA was lost from human hepatocellular carcinoma and other malignant and pre-malignant samples and malignant cell lines. There are no reports to date of the mRNA status of the receptor for hIRH/SDF1alpha/PBSF, CXCR4 in malignant tissues. We report here that there is a reduction in the mRNA expression of CXCR4 in hepatocellular carcinoma as estimated by Northern blot and RT-PCR and compared to the adjacent non-malignant tissue. The average (mean SD) tumor/normal ratio for CXCR4 mRNA expression, determined by RT-PCR, was 0.65 0.36 in 10 pairs of hepatocellular carcinomas. There was no consistent loss of CXCR4 mRNA expression in a range of malignant cell lines. The 3'-non-coding region of hIRH, had typical early response gene element sequences. Despite the presence of these 3'-elements there was no induction of hIRH gene expression in human lung carcinoma A549 cells by tumor necrosis factor alpha, interleukin-2, lipopolysaccharide or phorbol myristic acetate, nor in human melanoma cell line SB-2 by uv irradiation, under conditions which induced the homologue CXC intercrine IL-8 expression. Furthermore, there was no induction of hIRH gene expression, but rather a suppression, upon serum or cytokine addition to serum-deprived fibroblast cell lines, to an in vitro mouse bone marrow preparation, and to monocytic cell line THP-1.     

Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Patients with head and neck squamous cell carcinoma (HNSCC) often clinically present with metastases to regional lymph nodes. Fine-needle aspiration of neck masses is routinely used to establish the presence of metastatic carcinoma and in turn to initiate a subsequent workup to determine the site of tumor origin. Human papillomavirus (HPV) 16 is an important etiologic agent for HNSCCs that arise from the oropharynx but less so for tumors from non-oropharyngeal sites. HPV16 detection thus provides a strategy for localizing an important subset of HNSCCs, but this approach has not been applied to fine-needle aspiration specimens. EXPERIMENTAL DESIGN: We did in situ hybridization for HPV16 on 77 consecutive aspirated neck masses diagnosed as metastatic squamous cell carcinoma. P16 immunohistochemistry was also done because p16 overexpression may serve as a surrogate marker of HPV-associated HNSCC. RESULTS: HPV16 was detected in 13 of the 77 (17%) aspirates. By site of origin, HPV16 was detected in 10 of 19 metastases from the oropharynx but in none of 46 metastases from other sites (53% versus 0%; P < 0.0001). HPV16 was not detected in 2 branchial cleft cysts misdiagnosed as metastatic squamous cell carcinoma, but it was detected in 3 of 10 metastases from occult primary tumors. P16 expression was associated with the presence of HPV16: 12 of 13 HPV16-positive metastases exhibited p16 expression, whereas only 4 of 62 HPV16-negative metastases were p16 positive (92% versus 6%; P < 0.0001). P16 expression also correlated with site of tumor origin: 13 of 19 oropharyngeal metastases were p16 positive, whereas only 1 of 46 non-oropharyngeal metastases was p16 positive (68% versus 2%; P < 0.0001). CONCLUSIONS: HPV16 status can be determined in tumor cells aspirated from the necks of patients with metastatic HNSCC. Its presence is a reliable indicator of origin from the oropharynx.     

Sialylation: an Avenue to Target Cancer Cells

Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration.     

Factors associated with low birthweight in rural Bangladesh

This study examines factors associated with low birthweight (LBW) in rural Bangladesh. Enrolled in early first trimester, 350 women were followed for duration of pregnancy and data gathered on maternal factors such as social, demographic, anthropometric, biochemical measures and newborn's birth weight within 48 hours of birth. Almost a quarter of babies (24%) were born with LBW and mean birth weight was 2961 g. Bivariate analysis found associations between LBW and mother's age, parity, weight and hemoglobin level at booking, weight gain and health problems during pregnancy, tobacco consumption, and gestational age. But no such association was seen for birth spacing, mother's height, economic status, educational level, body mass index, mid upper arm circumference and number of ANC visits. Multivariable analysis revealed gestational age, hemoglobin levels at first visit and weight gain during pregnancy as significant predictors of LBW in this rural setting. Although antenatal care provision is absolutely necessary, intervention approaches that go beyond clinical or primary care settings are also warranted for better nutrition of women. Concerted efforts in health and non-health sectors are necessary for improvement in health and social status of women in order to reduce low birthweight in Bangladesh.     

Differential effects of diabetes on adipocyte and liver phosphotyrosine and phosphoserine phosphatase activities.

We examined the activities of particulate and cytosolic phosphotyrosine phosphatase (PTPase) and phosphoserine phosphatase (PSPase) in adipocytes and livers of diabetic rats. PTPase activity was assessed with [32P]tyrosine-phosphorylated insulin receptor (IR), whereas PSPase activity was assayed with [32P]serine-phosphorylated glycogen synthase. Diabetes increased adipocyte particulate PTPase activity and enhanced IR dephosphorylation by 75% on the 2nd, 93% on the 14th, and 108% on the 30th day. In contrast, cytosolic PTPase activity decreased by 78% on the 14th and 45% on the 30th day (no change on the 2nd day). Similar changes were observed with PSPase (increased activity in particulate and decreased in cytosolic). Insulin therapy for 14 or 30 days restored PTPase and PSPase activities in both fractions. Vanadate, despite rapid normalization of glycemia, restored these activities only after 30 days of therapy. Diabetes-related changes in liver PTPase activity were observed on the 14th day only. At this time, it was increased in both particulate and cytosolic fractions. There was spontaneous normalization of the liver PTPase activity at 30 days of diabetes. In contrast, liver cytosolic PSPase activity was significantly inhibited and not normalized by the 30th day of disease without therapy. In summary, diabetes appears to induce tissue-specific changes in PTPase and PSPase activities resulting in significant alterations in dephosphorylation of IR and glycogen synthase. Moreover, there appears to be a differential regulation of PTPase and PSPase activities in diabetes, particularly in the liver.