The association between birthweight and current blood pressure: a cross-sectional study in an Australian Aboriginal community

OBJECTIVES: To study the relationship of blood pressure to birthweight and current body mass index in a population with high rates of low birthweight (< 2.5 kg). DESIGN: A cross-sectional population screening program conducted between 1992 and 1998, with retrospective retrieval of birthweights. SETTING: A remote coastal Australian Aboriginal community with a high prevalence of diabetes, cardiovascular and renal disease. PARTICIPANTS: Eighty-two per cent of the community members (1473/1805) were screened. Birthweights were available for 767 (71%) of the screened participants aged 7-43 years. MAIN OUTCOME MEASURES: The association between birthweight and current blood pressure, accounting for current body mass index. RESULTS: Mean birthweights were low, and 18% of children and 35% of adults had been low-birthweight babies. In children (7-17 years), blood pressure was not correlated with birthweight, but in adults there was an inverse correlation - a 1 kg increase in birthweight was associated with a 2.9 mmHg (95% CI, 0.3-5.5 mmHg) decrease in systolic blood pressure, after adjusting for age, sex and current weight. Overweight adults with low birthweight had the highest blood pressures. CONCLUSIONS: Low birthweight is significantly associated with higher blood pressure in adult life, and the effect is amplified by higher current weight. Given the high rates of low birthweight in Aboriginal people in remote areas, and the detrimental effect of higher blood pressures on chronic diseases (currently present in epidemic proportions), interventions should focus on improving birthweights and on weight control in adolescents and adults. Special attention should be paid to children with low birthweight to avoid their becoming overweight in adult life.     

Social disadvantage and variation in the incidence of end-stage renal disease in Australian capital cities

OBJECTIVE: To evaluate variation in the incidence of end-stage renal disease (ESRD) within Australian capital cities. To explore the relation between the incidence of ESRD and socioeconomic disadvantage. METHODS: We obtained data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) regarding 5,013 patients from capital cities who started ESRD treatment between 1 April 1993 and 31 December 1998. We used the postcode at the start of treatment to calculate the average annual incidence of ESRD for each of 51 capital city regions using 1996 Census counts based on place of usual residence. We calculated standardised incidence ratios with 95% confidence intervals for each region. The standardised incidence ratios were examined in relation to the SEIFA Index of Relative Socio-economic Disadvantage (IRSD), derived from the 1996 Census. Low IRSD values indicate more disadvantaged areas. RESULTS: There is significant variation in the standardised incidence of ESRD within capital cities. There was a significant correlation (r=-0.41, p=0.003) between the standardised incidence ratio for ESRD and the SEIFA IRSD. CONCLUSIONS AND IMPLICATIONS: Capital city areas that are more disadvantaged have a higher incidence of ESRD. Socioeconomic factors may be important determinants of the risk of developing ESRD.     

Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay

Assessment of the chemosensitivity of dendritic cells (DC) may allow more rational development of combined chemotherapy and immunotherapy protocols. Human monocyte-derived DC generated reproducible results in the MTS (Owen's reagent) assay, which was then used to study DC survival after treatment with four different chemotherapy agents. DC preparations from three different donors were used per drug. DC were sensitive to doxorubicin (concentration range 0.1-50 microM) with variation in sensitivity between donors (IC50 244-1100 nM). The most extreme variation was seen for vinblastine (concentration range 250-0.025 microM with IC50 0.15-17.25 microM). In contrast, there was relative resistance to etoposide (concentration range 0.2-200 microM) and 5-fluorouracil (concentration range 0.7-7700 microM) with no toxicity seen until 50 microM and 770 microM respectively. The function of DC in allogeneic mixed leucocyte reactions closely paralleled results from the MTS assays. The differential sensitivity to chemotherapy agents did not appear to be due to expression of P-glycoprotein. These results suggest that etoposide or 5-fluorouracil is less likely to reduce the immunotherapeutic potential of DC and may be valuable in the design of prodrug activation therapy.     

Repeated coadministrations of pyridostigmine bromide, DEET, and permethrin alter locomotor behavior of rats

Interactions of pyridostigmine bromide (PB), permethrin (PERM), and the insect repellent DEET (DEET) have been suggested as possible causes of Gulf War Syndrome (GWS) in humans. Open field locomotor studies have long been used in behavioral toxicology. Using male and female Sprague-Dawley rats, video-computer analyses, and the isobolographic method we have determined the effects on locomotor speed and thigmotaxis following repeated administration of single-, double-, or triple-drug or vehicle controls in an open field. The effects were measured 24 hours after 7 daily drug administrations. Single-drug administrations caused no significant effects. Double-drug administrations resulted in significant effects in the following cases: males given PB + DEET had a significantly slower locomotion rate; males given DEET + PERM had a significantly faster locomotion rate; females given PB + DEET had a significantly slower locomotion rate; and females given PB + PERM spent significantly more time in the center zone (less thigmotaxis). Triple-drug administration caused no significant effect. These results in comparison with behavioral studies in chickens and insects show certain similarities. The implications of the lasting effects on animal models are relevant to GWS in humans.     

Disposition of haloperidol pyridinium and reduced haloperidol pyridinium in schizophrenic patients: no relationship with clinical variables during short-term treatment

In an open clinical trial, serum concentrations of haloperidol pyridinium (C(HP+)) and reduced haloperidol pyridinium (C(RHP+)), as well as haloperidol (CH) and reduced haloperidol (C(RH)), were measured in 57 schizophrenic and schizoaffective inpatients during 6 weeks of short-term treatment. Psychopathology was monitored with the Brief Psychiatric Rating Scale (BPRS), and extrapyramidal adverse effects were assessed with the Extrapyramidal Symptom Rating Scale (EPS). Significantly linear relationships were found between haloperidol dose (D) and pyridinium metabolite serum concentrations, as well as between C(H) and the pyridinium metabolite serum concentrations. C(HP+) (range, 0.2-4.9 ng/mL) and C(RHP+) (range, 0.03-6.23 ng/mL) were low compared with C(H) and C(RH), being as mean values approximately 7% and 14% of C(H) and C(RH), respectively. Additionally, the values of C(RHP+) and the slope of the correlation of C(H) with the C(RHP+)/C(HP+) ratio were considerably lower than in a previous report of long-term treatment with haloperidol. This is explained by the shorter time of treatment of the present study. Carbamazepine comedication was found to not influence relative pyridinium metabolite serum concentrations C(HP+)/D and C(RHP+)/D. However, the aromatization ratios of haloperidol (C(HP+)/C(H)) and reduced haloperidol (C(RHP+)/C(RH)) were increased by concomitant carbamazepine. As the main result, no relationships between the pyridinium metabolite serum concentrations and clinical variables (BPRS change, EPS, dose of biperiden) were detected. For instance, the aromatization ratios C(HP+)/C(H) and C(RHP+)/C(RH) did not predict clinical improvement or extrapyramidal adverse effects. Therefore, no confirmation of the "pyridinium hypothesis," which suggests haloperidol pyridinium metabolites to be the origin of adverse effects and decreased therapeutic effect, can be derived from this study. However, the authors emphasize that pyridinium metabolites cannot be excluded as the origin of decreased therapeutic effect in long-term treatment and of adverse effects not investigated in the present study, such as tardive dyskinesia. Finally, it is concluded that the serum concentration of the parent drug remains the main variable of interest in the therapeutic drug monitoring of haloperidol during short-term treatment.     

Femoral nerve block with ropivacaine or bupivacaine in day case anterior crucial ligament reconstruction

Background/Objective: Our aim was to evaluate analgesia, motor block and pharmacokinetics of ropivacaine 0.2% and 0.75% in a femoral nerve block (FNB) in day case patients for anterior crucial ligament (ACL)‐reconstruction compared with bupivacaine 0.25% and placebo. Methods: Following ethics committee approval and informed consent, 280 patients were randomly allocated to four groups for single‐shot FNB [30 ml ropivacaine 0.2% (group RO2.0), 0.75% (RO7.5), bupivacaine 0.25% (BU2.5) and NaCl 0.9% (NaCl)]. Analgesia (pain scores, primary outcome) and motor block were assessed at 4 h (dismissal) and up to 24 h. Plasma concentration was determined up to 240 min thereafter. Results: Pain scores at 4 h were significantly higher for NaCl 4 (0–8) (median, range) (vs.) BU2.5 2 (0–8), RO2.0 3 (0–9) and RO7.5 2 (0–8) (NS within the LA groups). Patients of the NaCl group needed analgesics significantly more often (93%) within 4 h after surgery vs. 16% of group RO2.0, 19% of group RO7.5 and 19% of group BU2.5. Motor block was significantly increased with all local anesthetics without a significant difference within the LA groups 3 (0–5) in RO2.0, 3 (0–5) in RO7.5 and 3 (0–4) in BU2.5 vs. 0 (0–3) in group NaCl (median (range); scale from 0=full strength to 5=complete paralysis). Peak plasma concentrations differed significantly: RO7.5: 1.4 ± 0.4 (0.73–2.6) [μg/ml, mean ± SD (range)] after 33 ± 14 (10–40) min, RO2.0: 0.6 ± 0.3 (0.13–1.0) after 22+17 (10–60) and BU2.5: 0.3 ± 0.16 (0.05–0.62) at 31 ± 17 (10–60), respectively. Conclusion: FNB for ACL reconstruction with ropivacaine or bupivacaine provided better post‐operative analgesia than placebo without reaching toxic plasma concentrations. Significant motor block was observed after 4 h in all groups including the lowest concentration of ropivacaine but occurred even with placebo.