The antinociceptive effects of anterior pretectal stimulation in tests using thermal, mechanical and chemical noxious stimuli

Four behavioural tests have been used to study the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) in the rat. The antinociceptive effects of stimulating this nucleus, which lies dorsally in the posterior diencephalon, have recently been studied extensively but always using briefly applied heat stimuli. It is reported here that APtN stimulation effectively inhibited responses to briefly applied noxious pressure and longer-lasting noxious chemical (formalin) stimuli. Although the tail-flick reflex to noxious heat was very potently depressed by APtN stimulation, responses to noxious heat in the hot-plate test were not. Three doses of morphine were also studied with each test and it was concluded that 15 sec of 35 microA r.m.s. current into the APtN was as effective as 3-5 mg/kg morphine s.c. in the rat.     

Pharmacy customers’ views and experiences of using pharmacies which provide needle exchange services in Aberdeen and Glasgow, Scotland

Community pharmacists contribution to the management of drug problems is considerable. As the use of illicit drugs has increased, pharmacists have come under increasing pressure to offer services to problem drug users. However, there is concern among some pharmacists that offering such services may deter other customers. There is particular concern among some pharmacists about needle exchange services. Only 9.5% of Scottish pharmacies offer needle exchange services compared to 69% which are dispensing methadone (57% of which supervise methadone consumption). Qualitative interviews were used in a purposive sample of 10 pharmacies in Scotland. Eight customers were interviewed in each pharmacy to ascertain pharmacy customers’ views on these services. The majority of customers were supportive of these services. Customers were often unaware that the pharmacy they were interviewed in was offering services for people with drug problems. Pharmacy customers were more knowledgeable about, and more supportive, of needle exchange services than they were of methadone. This was because they believed needle exchange services helped to reduce the amount of discarded needles in public places. Pharmacy customers also recognised that needle exchange helped reduce the spread of disease. These findings should be used to encourage more pharmacists to offer needle exchange services.     

Twin study of genetic and environmental effects on lipid levels

A study of 106 pairs of monozygotic (MZ) and 94 pairs of dizygotic (DZ) twins tested the hypothesis that part of the previously described genetic influence on blood lipid levels can be ascribed to closer similarities among MZ than among DZ twin pairs in environmental factors that affect lipid levels. Participants were adult twin volunteers (age 17-66; 64 male and 136 female pairs) who were selected from the NH & MRC Twin Registry or were respondents to advertisements. They completed a 4-day weighed food diary from which mean nutrient intake was derived. Information on lifestyle and demographic variables was obtained by questionnaire and a nonfasting blood sample was taken for measures of total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol and the HDL2 and HDL3 subfractions. Height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Estimates of the heritability of sex-adjusted lipid levels were 0.72 for total cholesterol, 0.79 for HDL cholesterol, 0.69 for HDL2, 0.20 for HDL3, 1.06 for LDL cholesterol, and 0.44 for sex-adjusted BMI. In all cases except for HDL3, genetic variance was statistically significant. After adjusting for the effects of environmental variables in three different ways, the estimates of heritability were somewhat lower for total cholesterol, HDL2, and BMI, and those for HDL cholesterol (borderline) and LDL cholesterol (definitely) remained statistically significant but were decreased. A genetic influence on HDL3 was not found. Adjusted heritability estimates obtained from one method of analysis were 0.35 for total cholesterol, 0.49 for HDL, 0.04 for HDL2, -0.34 for HDL3, 0.66 for LDL, and 0.32 for BMI. These results suggest that the assumptions made in the classical twin study approach are not appropriate when examining genetic effects on lipid levels or BMI, or indeed on any biological variable that may be affected by environmental factors that tend to be more similar in MZ twins than in DZ twins. In these circumstances, more complex models may be needed to differentiate between genetic and environmental influences.     

The EPC Approach to Estimating Safety from Exposure to Environmental Chemicals

Reference doses (RfDs) and reference concentrations (RfCs) developed by the United States Environmental Protection Agency (USEPA) are typically used in the quantitation of risk of potential adverse human health effects from exposure to environmental chemicals. For a large number of chemicals, however, USEPA RfDs and RfCs have not yet been determined. Thus, for risk assessments that involve a large number of chemicals, there is insufficient toxicity information with which to evaluate potential adverse human health effects for all chemicals present at a particular site. Due to this insufficiency, the risk assessor must either (1) ignore potential exposures on the assumption that omitting these exposures does not significantly alter decisions concerning the remediation of the site or (2) undertake a lengthy and costly analysis to generate the necessary RfDs or RfCs. A potential solution to this problem is to develop estimated permissible concentrations (EPCs), values which represent permissible environmental concentrations or related acceptable daily dosages derived from occupational exposure limits. In the present analysis, acceptable daily dosages determined using the EPC method were compared to USEPA RfDs or RfCs which were converted to dosages based on standard exposure assumptions. Based on a comparative analysis of EPCs and USEPA reference values for 103 chemicals, it was found that EPC daily dosages represent a reasonably conservative surrogate value when USEPA or state reference values are unavailable. Given that there are hundreds of chemicals with occupational exposure limits but no state or USEPA reference values, acceptance of the EPC methodology would provide an interim solution for the problem of insufficient toxicity information for a substantial number of environmental chemical contaminants.     

Retinopathy of prematurity in infants less than 29 weeks' gestation at birth

From January 1986 to December 1991 we examined the eyes of 206 infants born at Westmead Hospital, Neonatal Intensive Care Unit who were less than 29 weeks' gestation at birth to determine the incidence of retinopathy of prematurity. Eighty-five infants (41.3%) had no retinopathy of prematurity (ROP) in either eye, 82 infants had stages 1 or 2 ROP (39.8%), 29 had stage 3 ROP (14.1%) and 11 had stage 4 ROP (5.3%). Of these, cryotherapy was performed in 18; six now have bilateral retinal detachment and are blind The more severe stages of ROP were significantly associated with an increase in the number of days of oxygen supplementation, an increase in the number of days of mechanical ventilation and the presence of patent ductus arteriosus. Infants receiving steroids for mechanical ventilator dependence had a significantly greater chance of requiring cryotherapy (11 or 22 receiving steroids versus seven of 43 without steroids; P < 0.01).     

Treatment of experimental pyelonephritis in the monkey

Previous studies show that chronic pyelonephritis and end stage renal disease may follow acute pyelonephritis in children and adolescents when improperly or inadequately treated. Our study shows that there is a significant decrease in renal function following untreated acute bacterial pyelonephritis due to nephron loss. The acute inflammatory response is responsible for much of the renal damage, although damage from renal ischemia is an additional significant factor. The present study used a combination of an antibiotic and a xanthine oxidase inhibitor (allopurinol) as compared to antibiotic therapy alone begun 72 hours after infection. Both were successful in eradicating the infection rapidly, but did not entirely prevent renal damage. Treatment prior to 72 hours thus is important. It appears that the combined treatment, designed to eradicate the bacteria as well as reduce the post-ischemic reperfusion damage and the phagocytic burst of phagocytosis is ideal, as this combined treatment was effective in preventing almost all renal damage and loss of renal function.     

Relationship between methaemoglobin production and methylene blue plasma concentrations under general anaesthesia

Recently, a family tree with a predisposition for the gene of multiple endocrine neoplasia Type 1 has been identified in Tasmania. As the surgical identification and localisation of parathyroid adenomas is facilitated by the administration of methylene blue, an opportunity has presented to measure the plasma concentration of methylene blue and methaemoglobin production. The study was undertaken to establish whether significant methaemoglobin concentrations were generated during the infusion and whether these concentrations could be related to the corresponding methylene blue concentrations. Mean peak methylene blue concentrations of 3.72 micrograms l-1, mean percentage methaemoglobin of 10.0 and a PaO2 within acceptable clinical ranges were found. No apparent relationship between methylene blue concentration and methaemoglobin production was found.