Addressing Domestic Violence in Antenatal Care Environments in Nepal (ADVANCE) - study protocol for a randomized controlled trial evaluating a video intervention on domestic violence among pregnant women.

BACKGROUND: Domestic violence (DV) prior to, and during pregnancy is associated with increased risks for morbidity and mortality. As pregnant women routinely attend antenatal care this environment can be used to offer support to women experiencing DV. We have developed a video intervention that focuses on the use of behavioral coping strategies, particularly regarding disclosure of DV experiences. The effectiveness of this intervention will be evaluated through a randomized controlled trial (RCT) and a concurrent process evaluation. METHODS: All pregnant women between 12-22 weeks of gestation attending routine antenatal care at two tertiary level hospitals in Nepal are invited to participate. DV is measured using the Nepalese version of the Abuse Assessment Screen (N-AAS). Additionally, we measure participants' mental health, use of coping strategies, physical activity, and food security through a Color-coded Audio Computer Assisted Self Interview (C-ACASI). Irrespective of DV status, women are randomized into the intervention or control arm using a computer-generated randomization program. The intervention arm views a short video providing information on DV, safety improving actions women can take with an emphasis on disclosing the violence to a trusted person along with utilizing helplines available in Nepal. The control group watches a video on maintaining a healthy pregnancy and when to seek healthcare. The primary outcome is the proportion of women disclosing their DV status to someone. Secondary outcomes are symptoms of anxiety and depression, coping strategies, the use of safety measures and attitudes towards acceptance of abuse. Follow-up is conducted after 32 weeks of gestation, where both the intervention and control group participants view the intervention video after completing the follow-up questionnaire. Additionally, a mixed methods process evaluation of the intervention will be carried out to explore factors influencing the acceptability of the intervention and the disclosure of DV, including a review of project documents, individual interviews, and focus group discussions with members of the research team, healthcare providers, and participants. DISCUSSION: This study will provide evidence on whether pregnant women attending regular antenatal visits can enhance their safety by disclosing their experiences of violence to a trusted person after receiving a video intervention. TRIAL REGISTRATION: The study is registered in ClinicalTrial.gov with identifier NCT05199935.

Violence Exposed Nepalese Pregnant Women have an Accepting Attitude to Domestic Violence and Suffer from Emotional Distress.

Background Violence against women and girls is frequent, a third of all women is estimated to experience violence in their lifetime and mostly by an intimate partner. Women in Southeast Asia are most affected, and previous studies in Nepal found that one in five women had experiences of domestic violence, including being afraid of someone in the family. Objective To investigate women's attitudes to domestic violence and their emotional distress, in a specific group of pregnant women. Method Validated questions from the WHO multi-country study on women's health and experiences of domestic violence, and questions from the Hopkins Symptom Checklist (HSCL-5), measuring depression and anxiety, were used. Women could answer anonymously by hearing questions in a headset and touching a tablet screen, for 'yes' or 'no'. Result In total 1011 pregnant women participated in the research and 240 women admitted being exposed to domestic violence (23.7%). These women had a more accepting attitude to violence compared to non-violence exposed women. They agreed more that the husband had good reasons to hit his wife, if she does not complete the household work to his satisfaction, she disobeys or refuses to have sex with him. Violence exposed women also reported more emotional distress and subsequently reduced wellbeing. They admitted worrying too much, feelings of hopelessness, feeling blue, fearful, or nervous. Conclusion The present study found that the pregnant Nepali women having an accepting attitude to violence suffer from emotional distress.

Integrins as a drug target in liver fibrosis.

As the worldwide prevalence of chronic liver diseases is high and continuing to increase, there is an urgent need for treatment to prevent cirrhosis-related morbidity and mortality. Integrins are heterodimeric cell-surface proteins that are promising targets for therapeutic intervention. αv integrins are central in the development of fibrosis as they activate latent TGFß, a known profibrogenic cytokine. The αv subunit can form heterodimers with ß1, ß3, ß5, ß6 or ß8 subunits and one or more of these integrins are central to the development of liver fibrosis, however, their relative importance is not understood. This review summarises the current knowledge of αv integrins and their respective ß subunits in different organs, with a focus on liver fibrosis and the emerging preclinical and clinical data with regards to αv integrin inhibitors.

Prevalence and Associated Factors of Cesarean Section in Dhulikhel Hospital, Kathmandu University Hospital.

Background The Cesarean Section (CS) is a major obstetric life-saving procedure used to avoid pregnancy and childbirth complications. Cesarean sections are becoming more popular across the world, as well as in Nepal. Objective To assess the prevalence of cesarean section and its associated factors among women in Dhulikhel, Nepal. Method A cross-sectional study was conducted where 1246 pregnant women of age 15-45 years, admitted and delivered in hospital, were selected through purposive sampling technique and interviewed using structured questionnaires in Dhulikhel Hospital, Kathmandu University Hospital, Kavre, Nepal. Result The prevalence of cesarean section among women was 39.7% where the most common indication was previous cesarean section with scar tenderness, 27.9%. Half of the participants, i.e. 50.6%, were primigravida. Majority of women, 97.5% had done their antenatal checkup and among them 74.8% had their checkup in Dhulikhel Hospital, Kathmandu University Hospital. Most of them, i.e.76.2% had emergency cesarean section and 69.5% had primary cesarean section. Women of the age group 30-45 years (AOR=2.23) and women with higher secondary education level (AOR=2.03) were two times more likely to perform cesarean section. Women involved in service (AOR=1.37) and business (AOR=1.23) had greater odds of performing cesarean section than homemakers. Women giving birth to infants weighing 3.51- 5.00 kg were more likely to perform cesarean section (AOR=1.33). Conclusion The prevalence of cesarean section is noticeably high where the educated, employed and higher aged women are more inclined to cesarean section. More obstetric factors could be explored to determine the rise in cesarean section in Nepal which can help in decision making for clinicians.

Pharmacological characterisation of GSK3335103, an oral αvß6 integrin small molecule RGD-mimetic inhibitor for the treatment of fibrotic disease.

Fibrosis is the formation of scar tissue due to injury or long-term inflammation and is a leading cause of morbidity and mortality. Activation of the pro-fibrotic cytokine transforming growth factor-ß (TGFß) via the alpha-V beta-6 (αvß6) integrin has been identified as playing a key role in the development of fibrosis. Therefore, a drug discovery programme to identify an orally bioavailable small molecule αvß6 arginyl-glycinyl-aspartic acid (RGD)-mimetic was initiated. As part of a medicinal chemistry programme GSK3335103 was identified and profiled in a range of pre-clinical in vitro and in vivo systems. GSK3335103 was shown to bind to the αvß6 with high affinity and demonstrated fast binding kinetics. In primary human lung epithelial cells, GSK3335103-induced concentration- and time-dependent internalisation of αvß6 with a rapid return of integrin to the cell surface observed after washout. Following sustained engagement of the αvß6 integrin in vitro, lysosomal degradation was induced by GSK3335103. GSK3335103 was shown to engage with the αvß6 integrin and inhibit the activation of TGFß in both ex vivo IPF tissue and in a murine model of bleomycin-induced lung fibrosis, as measured by αvß6 engagement, TGFß signalling and collagen deposition, with a prolonged duration of action observed in vivo. In summary, GSK3335103 is a potent αvß6 inhibitor that attenuates TGFß signalling in vitro and in vivo with a well-defined pharmacokinetic/pharmacodynamic relationship. This translates to a significant reduction of collagen deposition in vivo and therefore GSK3335103 represents a potential novel oral therapy for fibrotic disorders.

Mail and Telephone Outreach from Electronic Health Records for Research Participation on Cognitive Health and Aging.

OBJECTIVES: This report describes the efficacy and utility of recruiting older individuals by mail to participate in research on cognitive health and aging using Electronic Health Records (EHR). METHODS: Individuals age 65 or older identified by EHR in the Mount Sinai Health System as likely to have Mild Cognitive Impairment (MCI) were sent a general recruitment letter (N=12,951). A comparison group of individuals with comparable age and matched for gender also received the letter (N=3,001). RESULTS: Of the 15,952 individuals who received the mailing, 953 (6.0%) responded. 215 (1.3%) declined further contact. Overall rate of expression of interest was 4.6%. Of the 738 individuals who responded positively to further contact, 321 indicated preference for further contact by telephone. Follow-up of these individuals yielded 30 enrollments (0.2% of 15,952). No differences in response rate were noted between MCI and comparison groups, but the comparison group yielded higher enrollment. 6 individuals who were not the intended recipients of mailing but nevertheless contacted our study were also enrolled. CONCLUSIONS: Mailings to individuals identified through a trusted source, such as a medical center from which they have received clinical care, may be a viable means of reaching individuals within this age group as this effort yielded a low rejection rate. However, EHR information did not enhance study enrollment. Implications for improving recruitment are discussed.

Translational pharmacology of an inhaled small molecule αvß6 integrin inhibitor for idiopathic pulmonary fibrosis.

The αvß6 integrin plays a key role in the activation of transforming growth factor-ß (TGFß), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvß6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvß6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFß signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvß6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvß6, induces prolonged inhibition of TGFß signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy.

Anxiety on Primigravid Women Attending Antenatal Care: A Hospital Based Cross-sectional Study.

Background High levels of anxiety during pregnancy have adverse effects on mother and baby. Objective To assess anxiety on primigravid women attending Antenatal Care. Method Analytical cross-sectional study was carried out on the primigravid women attending Antenatal Care out-patient department of Dhulikhel Hospital. Perinatal Anxiety Screening Scale (PASS) was used to assess anxiety on 502 women. Data were collected through face-to-face interview using Systematic Random Sampling Technique from May 2017 to December 2017. Chi-square test was applied to test the association between selected variables. All p- values less than 0.05 were considered statistically significant. Result The mean (± Standard deviation [SD]) age of the participants was 23.17±3.9 years. More than half (57.6%) of the women were from the age group 20-25 years. Just above two-fifth (41.4%) of the participants were in the third trimester of pregnancy. Out of 502 pregnant women, nearly half (46.4%) of them were at high risk of anxiety. High risk of anxiety was significantly associated with age and type of family. However significant associations were not seen between high risk of anxiety during pregnancy and residence, educational status, occupation, husband's occupation and gestational period of women. Conclusion The high risk of anxiety on primigravid women was quite up. Anxiety during pregnancy was more likely to fall on younger women (age < 20 years) and joint families in comparison to those women from age twenty and above and nuclear families respectively.

Intestinal Worm Infestation and Anaemia in Pregnant Women.

INTRODUCTION: Severe Anaemia during pregnancy is an important contributor to maternal mortality, as well as to the low birth weight which is in turn an important risk factor for infant mortality. We aim to determine the prevalence of anaemia in the region amongst pregnant women and identify their problems and to easily provide them with the clinical services. METHODS: A community based cross sectional study done in PHCRC Chapagaun, Lalitpur from July 17,2011 to September 17,2011. Date from pregnant women presenting at PHCRC, , were filled and analysed using standard guidelines from WHO and Indian council of Medical research. RESULTS: Out of 192 pregnant women, the average age of pregnancy was 21-25 years (46.55), mean haemoglobin (Hb) in pregnancy was 11g/dl. Majority pregnant women are Newar (35.4%) ethnicity,67.7% of them housewives and 31.5% have primary level education. Only 24% was found to have their haemoglobin level in anaemic range. Among the pregnant women (n) =192; 48 (25%) had worm infestation, 119 (62%) had negative stool report and 25 (13%) had other than worms were found. Only about one third of the sample has actually taken albendazole. CONCLUSIONS: Aanaemia is prevalent in pregnant women of PHCRC, chapagaun and there was a significant correlation between anaemia and worm infestation. However, the relation among the haemoglobin level, iron, folic acid and albendazole was not significant.

Outcome of adolescent pregnancy at Kathmandu University Hospital, Dhulikhel, Kavre.

BACKGROUND: Adolescence Pregnancy is a social problem worldwide with serious implication of maternal and child health. This study purposed to compare the maternal and neonatal outcome of the teenage mothers (15- 19 years) with that of the young mothers (20-24 years) to determine if adolescent pregnancies have increased risk of adverse outcomes. OBJECTIVES: This study aims to find out the outcomes of adolescent pregnancy at Kathmandu University Hospital, Dhulikhel Hospital, Kavre. METHODS: Descriptive cross sectional study was done. The study included all primiparous mothers of age 15-19 (n=168) and 20-24 (n=401) recorded in the delivery record book of Dhulikhel Hospital from June 2007 to May 2008. Chi-square test and relative risk (RR) for subgroups of study population was examined using the SPSS version 10.0. RESULTS: The low birth weight baby among teenage mothers and young mothers were 28% and 26.7% respectively (p=0.572). The Relative risk of low birth weight among adolescent is 1.1 (0.75-1.684) times to that of young mothers at 95% confidence interval. Preterm birth was not associated with adolescence pregnancy (7% Vs. 11.5%, p=0.141). Normal delivery was the common mode of delivery among both groups (77.4% Vs. 74.6%). Among the neonatal complication, newborns of adolescents had greater neonatal complications than newborns of the young mothers (17.2% Vs 16.7%). Maternal complication like antepartum hemorrhage (2.4% Vs. 1.7%) and postpartum hemorrhage (0.6% Vs. 0.2%) was higher among adolescents. CONCLUSIONS: Low birth weight, common neonatal complication, antepartum hemorrhage and postpartum hemorrhage are found more in adolescent group, however statistically insignificant.

Antenatal care practices in Tamang community of hilly area in central Nepal.

BACKGROUND: Antenatal care is provided during pregnancy to save lives of mother and foetus. World Health Organization recommends four focused visits as sufficient for normal pregnancy. OBJECTIVE: The objective of the study was to find out antenatal care practices in Tamang community of hilly areas of central Nepal. METHODS: Descriptive cross-sectional study was conducted in Tamang community of Lalitpur district. Systematic random sampling method was used to collect data from April to May 2011. Data of 194 women having ≥ 3 years of children was collected and analyzed in descriptive and inferential ways. RESULTS: Antenatal visits were made by 78.9% (153) of women but only 46.4% (71) completed four antenatal visits. Mean visit was of 3.5 +/- 1.13 times. Ninety four (61.4%) of first antenatal visits attainders completed the fourth visit. Age of women and antenatal visits, taking tetanus toxoid injection and knowledge on work of iron tablets exhibited significant association at 95% level of confidence (p less than 0.05). There was also significant association between numbers of childbirth and antenatal visits at 95% level of confidence (p less than 0.05). CONCLUSIONS: There was a high rate of early marriage and early pregnancy in the Tamang communities. Women did not place high importance on antenatal visits. A large percentage did not complete all four recommended antenatal visits. Use of necessary medicine like iron, albendazole tablets and tetanus toxoid injection was often incomplete.

Peripheral intravenous catheter related phlebitis and its contributing factors among adult population at KU Teaching Hospital.

BACKGROUND: Peripheral intravenous catheter-related phlebitis is a common and significant problem in clinical practice. This study was carried out to determine the occurrence of peripheral intravenous catheter related phlebitis and to define the possible factors associated to its development. MATERIALS AND METHODS: Prospective observational study was carried out on 230 clients who were under first time peripheral infusion therapy during two months period: September - October, 2007. Peripheral infusion site was examined for signs of phlebitis once a day. Jackson Standard visual phlebitis scale was used to measure the severity of the phlebitis. SPSS software was used to enter, edit and analyze the data and t-test, chi-square test, binary logistic regression and ROC curve were used to draw the statistical inferences. RESULTS: Phlebitis developed in 136/230 clients (59.1%). It was very mild in most cases. Increased incidence rates of infusion related phlebitis were associated with male sex, small catheter size (20 gauge), insertion at the sites of forearm, IV drug administration and blood product transfusions. The incidence rate of phlebitis rose sharply after 36 hours of catheter insertion. CONCLUSION: Peripheral Intravenous therapy related phlebitis at KUTH, Dhulikhel Hospital is a significant problem. Related risk factors as found in the present study were insertion site (forearm), size of catheter (20G) and dwell time (>or= 36 hours). There were higher incident of phlebitis among the client with Intra venous drug administration and especially between ages 21 - 40 years. Therefore more attention and care are needed in these areas by the care provider.

Ikappa-B kinase-2 inhibitor blocks inflammation in human airway smooth muscle and a rat model of asthma.

RATIONALE: Nuclear factor (NF)-kappaB is a transcription factor known to regulate the expression of many inflammatory genes, including cytokines, chemokines, and adhesion molecules. NF-kappaB is held inactive in the cytoplasm, bound to I-kappaB. The removal of I-kappaB, via the actions of inhibitor of kappaB (I-kappaB) kinase-2 (IKK-2), allows NF-kappaB to enter the nucleus. OBJECTIVES: To determine the impact of inhibiting IKK-2 on in vitro and in vivo models of airway inflammation. METHODS: The effect of inhibiting IKK-2 was assessed in stimulated, cultured, primary human airway smooth muscle cells and an antigen-driven rat model of lung inflammation. MEASUREMENTS: The release of cytokines from cultured cells and inflammatory cytokine expression and cellular burden in the lung were determined. MAIN RESULTS: Two structurally distinct molecules and dominant negative technology demonstrated that inhibition of IKK-2 activity completely blocked cytokine release from cultured cells, whereas the two glucocorticoid comparators had limited impact on granulocyte colony-stimulating factor, interleukin 8, and eotaxin release. In addition, in an in vivo antigen-driven model of airway inflammation, the IKK-2 inhibitor blocked NF-kappaB nuclear translocation, which was associated with a reduction in inflammatory cytokine gene and protein expression, airway eosinophilia, and late asthmatic reaction, similar in magnitude to that obtained with budesonide. CONCLUSION: This study demonstrates that inhibiting IKK-2 results in a general reduction of the inflammatory response in vitro and in vivo. Compounds of this class could have therapeutic utility in the treatment of asthma and may, in certain respects, possess a beneficial efficacy profile compared with that of a steroid.

First Report of the Association of a Nanovirus with Foorkey Disease of Large Cardamom in India.

Large cardamom (Amomum subulatum Roxb.) is affected by the serious disease 'foorkey', which is of unknown etiology (1). Excessive sprouting and formation of bushy dwarf clumps at the base of mother plants that gradually die, characterize the disease. In surveys in the Sikkim-Darjeeling Hill area during 2002 and 2003, as much as 27% of plants were found to be affected. Electron microscopy of negatively stained, partially purified preparations from field-infected large cardamom plants showed the presence of isometric particles measuring 17 to 20 nm. The causal agent was successfully transmitted by the aphid Micromyzus kalimpongensis Basu, in a persistent manner. Ten randomly selected field samples gave A405 0.1 to 0.23 compared with 0.57 with positive control with enzyme-linked immunosorbent assay using antiserum to an Indian isolate of Banana bunchy top virus (BBTV). A fragment of approximately 850 bp was amplified from the diseased plants using polymerase chain reaction (PCR) with primers 5'-ATGGCGCGATATGTGGTATGC-3' and 5'-TCAGCAAGAAAACCAACTTTATTC-3', designed to amplify the putative Rep gene based on the sequences of DNA1 of BBTV. The PCR product was cloned and sequenced (GenBank Accession No. AY 485960) and showed 80 to 82% identity with the corresponding region of DNA1 of BBTV and 47.6 to 48.5% with other recognized nanoviruses. These findings indicate that a nanovirus is associated with 'foorkey' disease of large cardamom, which is tentatively named as Cardamom bushy dwarf virus. Reference: (1) P. M. Varma and S. P. Capoor. Indian J. Agric. Sci. 34:56, 1964.

Age-related changes in plasma leptin binding activity in rats: A comparison of a simple acid-ethanol precipitation technique with column chromatography.

A novel assay for measuring the free leptin fraction was developed and validated against a chromatographic technique. The assay used acid-ethanol extraction (AEE) for separation of bound/free leptin moieties. The interassay coefficient of variation was 3.9%. The specificity for leptin binding was confirmed by incubation with 1 microg of unlabeled rat leptin that effectively competed with radiolabeled leptin whereas human growth hormone and interleukin-6 were ineffective in competing with radiolabeled leptin binding. Scatchard analysis of competitive binding experiments with rat plasma demonstrated a linear relationship with a binding affinity of 0.3-0.6 x 109 M-1. This novel assay was used to determine if age-related insensitivity to leptin action is secondary to altered serum leptin binding. Rats at various age groups were studied for changes in body adiposity and serum total and free leptin concentrations. Serum free leptin concentrations (ng/ml mean +/- SEM) were significantly increased in 24-month-old rats (5.56 +/- 0. 21) compared with 18-month-old rats (4.76 +/- 0.17) (P < 0.01) despite similar body weight and adiposity of the two age groups. The increase in plasma free leptin concentrations in 12-month-old rats (3.86 +/- 0.28) and 6-month-old rats (2.05 +/- 0.06) relative to 3-month-old rats (1.37 +/- 0.06) (P < 0.001) was out of proportion to the increase in body adiposity in aging rats. It is concluded that aging in rats is associated with relative insensitivity to leptin. This change cannot be attributed to increased plasma binding or to a reduction in the leptin free fraction.

Effects of ketoacidosis on rat apolipoprotein A1 gene expression: a link with acidosis but not with ketones.

To determine if ketoacidosis contributes to reduced apolipoprotein A1 (apoA1) expression in insulin-deficient diabetic rats, we examined the regulation of apoA1 gene expression in response to changes in ambient pH or ketone body concentrations. Hepatic apoAI mRNA levels were reduced 42% in diabetic rats relative to nondiabetic controls (means+/-s.d.; 321.8+/-43.7 vs 438.7+/-58.8 arbitrary units; P<0.03). Neither endogenous apoA1 mRNA nor transcriptional activity of the rat apoA1 gene promoter (from -474 to -7) were altered by sodium butyrate or isobutyramide (0.3 mM to 10 mM) in Hep G2 or Caco-2 cells. Rat hepatic and intestinal apoA1 mRNA levels, and plasma apoA1 concentration, were not altered 24 h after isobutyramide administration (500 mg/kg by gavage). When the effect of altering ambient pH within a wide range commonly encountered in vivo was studied, acidosis (pH 6.7), relative to alkalosis (pH 7.9), decreased apoAI mRNA levels relative to glyceraldehyde-3-phosphate dehydrogenase mRNA by 47% in Hep G2 cells (P<0.025) and by 24% in Caco-2 cells (P<0.017). Acidosis did not alter cytomegalo virus (CMV)-beta-galactosidase activity, or the activity of the simian virus (SV40) early-region promoter, in either cell line transfected with the respective constructs. The lowering of ambient pH was associated with a graded reduction in apoAI promoter activity. At pH 6.7, apoAI promoter activity was reduced by 75% compared with promoter activity at pH 7.9. These observations indicate that acidosis, but not ketosis, contributes to the reduction in apoA1 expression during diabetic ketoacidosis by down-regulating apoAI promoter activity.

Induction of the apolipoprotein AI gene by fasting: a relationship with ketosis but not with ketone bodies.

Apolipoprotein AI (apoAI) expression is inversely related to the incidence of atherosclerosis. ApoAI expression is also influenced by the nutritional state and diabetes. We used both cell culture and animal models to examine the effect of fasting and ketoacidosis on apoAI gene expression. Two days of food deprivation in rats increased hepatic and intestinal apoAI mRNA by 2.6- and 2.3-fold, respectively (P < .05). The absolute concentration of plasma apoAI did not change. However, the plasma apoAI concentration relative to the plasma concentration of serum proteins was increased 23% (P < .05). In fasting rats, there was a significant positive correlation between the serum beta-hydroxybutyrate concentration and hepatic or intestinal apoAI mRNA level. Despite this correlation, changes in apoAI mRNA are probably not mediated by ketone bodies, since neither hepatic nor intestinal apoAI mRNA levels were altered in rats maintained on a ketogenic diet for 10 days or treated with isobutyramide, an orally active ketone analog. In addition, the activity of the rat apoAI promoter was not altered in Hep G2 cells treated with isobutyramide or fatty acids or exposed to hypoglycemic conditions, while dexamethasone increased promoter activity 1.9-fold (P < .05). These data indicate that metabolic changes other than ketone bodies, such as an increase in plasma glucocorticoids, may account for starvation-induced expression of apoAI.

Expression of the death gene Bik/Nbk promotes sensitivity to drug-induced apoptosis in corticosteroid-resistant T-cell lymphoma and prevents tumor growth in severe combined immunodeficient mice.

Members of the Bcl-2 gene family have been implicated in the regulation of cell death induced by cytostatic drugs. In some malignancies such as B-cell lymphoma, there is evidence that high expression of Bcl-2 is an independent negative prognostic marker and the overexpression of Bcl-2 has been shown to confer resistance to cytotoxic drugs by preventing drug-induced apoptosis. This function of Bcl-2 can be antagonized by apoptosis-promoting members of the Bcl-2 family. We previously showed that overexpression of Bax restores the chemosensitivity of Bax-deficient breast cancer cell lines. Therefore, we investigated whether the death-promoting Bcl-2 homologue Bik/Nbk can enhance cytostatic drug-induced apoptosis. As a model, we used the T-cell leukemia H9 (CD3(+) and CD4(+)CD8(-)), which is resistant to corticosteroid-induced cell death and does not express endogenous Bik/Nbk. Sensitivity for drug-induced apoptosis was increased 10- to 39-fold in cells transfected with the full-length coding sequence of Bik/Nbk. In addition, apoptosis induced via CD95/Fas or heat shock was increased to a similar extent. These data show that Bik/Nbk, which, unlike Bax, carries only a BH3 but no BH1 or BH2 domain may be a target to enhance chemosensitivity. The complete suppression of tumor growth in a severe combined immunodeficient mouse xenotransplant model suggests that, in analogy to Bax, Bik/Nbk may function as a tumor suppressor gene.

Idiopathic intracranial hypertension: relation of age and obesity in children.

The relation between obesity and age in children with idiopathic intracranial hypertension (pseudotumor cerebri) has remained uncertain. The authors reviewed the records of 45 consecutive children with newly diagnosed idiopathic intracranial hypertension seen at two medical centers. Forty-three percent of patients aged 3 to 11 years were obese, whereas 81% of those in the 12- to 14-year age group and 91% of those in the 15- to 17-year age group met criteria for obesity (p = 0.01). Younger children with idiopathic intracranial hypertension are less likely to be obese than are older children or adults.