Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

Survival after transfusion in the Netherlands

Background Cost‐effectiveness analyses of blood safety interventions require estimates of the life expectancy after blood product transfusion. These are best derived from survival after blood transfusion, per age group and blood component type. Study design and methods In the PROTON (PROfiles of TransfusiON recipients) study transfusion recipient data was collected from a hospital sample covering 28% of the total blood use between 1996 and 2006 in the Netherlands. The dataset includes date of transfusion, blood component type transfused and recipient identification details. PROTON data were individually matched to mortality data of the Netherlands. Survival after first transfusion and after any transfusion was calculated, per blood component type and age group. PROTON mortality rates were compared to mortality rates in the general population. The results were used to estimate survival beyond the study period and to estimate life expectancy after transfusion. Results Of all 2 405 012 blood product transfusions in the PROTON dataset, 92% was matched to the national Dutch Municipal Population Register, which registers all deaths. After 1 year, survival after any transfusion was 65·4%, 70·4% and 53·9% for RBC, FFP and PLT respectively. After 5 years, this was 46·6%, 58·8% and 39·3% for RBC, FFP and PLT, respectively. Ten years after transfusion, mortality rates of recipients are still elevated in comparison with the general population. Conclusion Mortality rates of transfusion recipients are higher than those of the general population, but the increase diminishes over time. The mortality rates found for the Netherlands are lower than those found in comparable studies for other countries.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.