Validity of self-report of recent opiate use in treatment setting

Self-report validity of recent drug use among heroin abusers depends on many factors including the population being studied and the setting in which the study is carried out. This study was conducted by the treating physicians to assess the self-report validity of recent heroin use by heroin dependent patients in the outdoor setting using 'thin layer chromatography' (TLC) and two highly sensitive methods of urinalysis viz. 'gas liquid chromatography' (GLC) and 'high performance liquid chromatography' (HPLC). Out of seventy-six heroin dependent patients who entered the study, 64 provided urine sample on the same day. Patients' self-report about recent opiate use was found to have a moderate agreement with urinalysis report. However, it is important to validate it with urinalysis during the treatment process because a substantial proportion of patients fails to report recent opiate use. It is recommended that all drug dependence treatment centres should be equipped with a sensitive urinalysis facility. Otherwise, the outcome of the treatment process should be considered with caution.     

Immunoglobulin allotypes and virus antibodies in Finnish type 1 diabetic patients

We have found elevated IgA class mumps and Coxsackie B4 virus antibodies and IgA/IgG antibody ratios in type 1 diabetic patients. However, IgA class herpes simplex (HSV1) virus antibodies showed no difference between patients and controls. To study the possible contribution of genetically polymorphic immunoglobulin markers to the pronounced IgA class reactivity Ig allotypes (Gm, A2m and Km determinants) were compared to virus antibodies in diabetic patients and healthy controls. Ig allotypes were equally distributed in both groups suggesting that the genes coding for these structures are not in close linkage disequilibrium with susceptibility gene(s) for type 1 diabetes. Accordingly, pronounced IgA class immune response in diabetic patients is hardly due to Ig allotype related factors. Patients had elevated IgA class mumps and Coxsackie B4 antibodies and IgA/IgG antibody ratios independently of the Gm phenotype group. In healthy subjects but not in diabetic patients IgA class mumps antibody levels and IgA/IgG mumps antibody ratios significantly correlated with the Gm phenotypes. Such Gm association was not observed in Coxsackie B4 or HSV1 antibodies. These results suggest that though Gm phenotypes have a general effect on mumps specific antibody response, some other factors than Ig allotypes are responsible for the elevated IgA class mumps and Coxsackie B antibody levels and IgA/IgG antibody ratios in type 1 diabetes.     

Gm allotypes in blacks with systemic lupus erythematosus

Serum samples were collected from 328 healthy American Blacks and from 61 American Blacks with systemic lupus erythematosus (SLE). Sera were typed for the Gm1,2,3,5,6,13,17, and 21 allotypes as well as for the Km(1) allotype. The frequency of Gm phenotype 1,17;5,6,13 was significantly increased in the SLE patients (p = 0.0001, RR = 3.19, EF = 0.29). Our data suggest the existence of at least two immunoglobulin allotype associated genes that somehow interact to increase susceptibility to SLE in Blacks. To our knowledge, this is the first report of an association of Gm and SLE in Blacks.     

Effects of antidepressants on the uptake and release of norepinephrine from rat cerebral cortex

The effects of several antidepressants on the release of (³H)-norepinephrine (NE) from homogenates of rat cerebral cortex were studied. A continuous superfusion collection system was used in order to differentiate these effects from effects on reuptake. Amitriptyline, maprotiline, mianserin, and trazodone produced a statistically significant decrease in spontaneous tritium efflux when present in the superfusion medium at a concentration of 1.0 M. The other antidepressants studied had no effect. We used a buffer with the K⁺ concentration raised to 56 mM as a model of depolarization-induced release. Desipramine, fluoxetine, and iprindole (again at 1.0 M) caused a significant decrease in this measure. These results indicate that some of both the tricyclic and atypical antidepressants may alter spontaneous or depolarization-induced release of NE.This work was supported in part by a grant from the Pharmaceutical Manufactures Association Foundation-Medical Student Research Fellowship     

Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: −7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m²). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.     

Identifying children with high mortality risk

This issue reports selected results from a comprehensive study of infant and child mortality based on the National Family Health Survey data. The analysis distinguishes between neonatal, postneonatal, infant and child mortality since mortality and its causes vary considerably among children of different ages. Hazard regression analysis was used to estimate the effects of each individual variable as the factors that affect infant and child mortality tend to be correlated with each other. The study involves adjusted effects of selected socioeconomic and demographic characteristics on neonatal, postneonatal, infant, and child mortality for children born during the survey. Short birth intervals have a great effect on infant and child mortality. A previous birth interval of less than 24 months increases child mortality by about 67%. Neonatal mortality is highest among children of very young mothers. Child mortality is higher for girls in all states except Tamil Nadu, Kerala, and Goa. Seven groups of children who are especially vulnerable to infant and child mortality were identified. Thus, intervention programs, such as efforts to provide supplemental nutrition and basic immunization to pregnant mothers, infants and young children need to focus on these high-risk groups. Results for many states show elevated mortality rates for girls after the neonatal period. Family health programs aimed at overall improvement in mortality levels should pay attention to providing basic health care and supplemental nutrition to girls.     

Dengue haemorrhagic fever in children in the 1996 Delhi epidemic.

An epidemic of dengue haemorrhagic fever (DHF) occurred in Delhi in 1996. A total of 240 children between the age of 4 months to 13 years of either sex, admitted in one hospital, were evaluated. Two hundred and sixteen (90%) children were from Delhi. A clinical diagnosis of dengue fever (DF) was made in 25 (10%), dengue fever with unusual bleeding (DFB) in 22 (9%), DHF in 80 (33%) and dengue shock syndrome (DSS) in 113 (47%) of the children strictly according to the WHO classification. The age peaked at 8 years. There was no association between various grades of severity of illness and age-groups though girls suffered from more severe illness. No association between severity of malnutrition and severity of illness was observed. Tourniquet test was positive in 40% with DF, 18% with DFB, 62% with DHF and 64% with DSS. In DSS haematemesis was present in 55 (49%), epistaxis in 39 (35%), melaena in 27 (24%) and ecchymosis in 34 (30%) patients. Children diagnosed as DFB had haematemesis and epistaxis in 12 (55%) and 10 (45%) respectively. Intravenous fluid requirement was clearly less in DFB patients than in DHF/DSS patients. Unusual clinical features in the form of jaundice were present in 7 (6%), hepatic encephalopathy in 6 (5%) and dengue encephalopathy in 6 (5%) patients. Dengue 2 virus was isolated from 10 of the 50 patients for whom viral culture was done on C6/36 clone of Aedes albopictus cell line. Eighteen patients suffering from DSS died giving an overall case fatality of 7.5%. The mortality rate in DHF/DSS was 9.3%. It is further suggested that DFB is a distinct entity. Most patients could be classified by the WHO classification if a retrospective packed cell volume was used to assess haemoconcentration. We suggest that development of area-specific criteria for diagnosis and management is desirable.     

Human endothelin-1 clearance kinetics revealed by a radiotracer technique

Levels of endothelin-1 (ET-1) are elevated in many disease states, although its total body kinetics of elimination are poorly understood. Therefore, it remains uncertain whether the presence of elevated levels of ET-1 in the setting of disease are secondary to changes in production or clearance or some combination thereof. Using a 125I-labeled ET-1 infusion technique, the volume of distribution and kinetics of clearance of endothelin were described in five normal volunteers. Heart rate, blood pressure, right atrial pressure, and arterial blood samples for the counting of 125I and the measurement of ET-1 were obtained at multiple time points before and up to 45 h after the start of the infusion. The radiotracer infusion had no effect on heart rate, blood pressure, right atrial pressure, or endogenous ET-1 levels. ET-1 clearance was best described by a three-compartment model, which revealed that ET-1 has a much longer terminal half-life and volume of distribution than was previously reported. This suggests extensive uptake of ET-1 in various organ systems and slow clearance. These new findings have important implications for the understanding of the pathophysiology of ET-1 in disease states as well as for the understanding and development of ET-1 receptor blockers and endothelin-converting enzyme inhibitors.