Tuberculosis notifications in Australia, 2005

The National Notifiable Disease Surveillance System received 1,072 tuberculosis (TB) notifications in 2005, of which 1,022 were new cases and 50 were relapses. The incidence of TB in Australia was 5.3 cases per 100,000 population in 2005 and has remained at a stable rate since 1985. The high-incidence groups remain people born overseas and Indigenous Australians at 20.6 and 5.9 cases per 100,000 population, respectively. By contrast, the incidence of TB in the non-Indigenous Australian-born population was 0.8 cases per 100,000 population. Rates in the Australian-born, both Indigenous and non-Indigenous have been declining since 1991, while rates in the overseas-born have been increasing. TB control in Australia relies on pre-migration screening and provision of free and effective treatment.     

The non-invasive acetylene rebreathing method for estimation of cardiac output: influence of breath-by-breath variation

The inert gas rebreathing method enables non-invasive estimation of pulmonary capillary blood flow, lung tissue volume, transfer factor and functional residual capacity. In the present study, we have examined the influence of breathing pattern during the rebreathing manoeuvre on the precision of the rebreathing method, both theoretically and experimentally. We examined whether the precision of the method could be improved by the guidance and training of the subjects doing the rebreathing manoeuvre. The results of the theoretical study showed that the precision and accuracy of the rebreathing method are practically insensitive to random variation in the breathing pattern. Simulated breath-by-breath variations up to ±50% of the average 3·0 l V_T resulted in coefficients of variation of about 3% for Q_C and about 5% for V_TC. Simulated breath-by-breath variations indicate that with mean tidal volume or rebreathing bag volume lower than 1·0 l the precision will worsen, and with tidal volume lower than 1·5 l the accuracy will worsen. The experimental results showed no significant improvement in the precision of the rebreathing method by visual guiding and training of the subjects to optimize the breathing pattern during the rebreathing manoeuvre.     

Haemodynamic and humoral effects of lower body negative pressure in normal, sodium-replete man during angiotensin-converting enzyme inhibition with captopril

The significance of the renin-angiotensin system (RAS) for circulatory homeostasis during gravitational stress (10 min of lower body negative pressure, LBNP, at -40 mmHg) was investigated in eight men on liberal sodium intake. The function of RAS was inhibited by a single oral dose of 100 mg captopril, an angiotensin-converting enzyme inhibitor. Plasma concentrations of renin and angiotensin I were normal before and increased after captopril and during LBNP. Plasma concentration of angiotensin II was normal before captopril, increased during LBNP, and fell to low values after captopril. Systolic blood pressure decreased more during LBNP after captopril than in the control situation. In three cases, the LBNP experiment after captopril had to be interrupted due to marked hypotension. Heart rate and plasma concentration of adrenaline increased above pre-captopril levels. In six subjects, plasma concentration of noradrenaline increased more during LBNP after captopril, less in two subjects, whereas the arginine vasopressin concentration increased more after captopril in all five subjects where measurements were available. The results demonstrate that RAS participates in blood pressure homeostasis also in sodium-replete, normal man. The enhanced increases in heart rate and plasma catecholamines after captopril do not suggest that sympathetic reflex activity during gravitational stress is blunted after captopril, in contrast to the evidence from animal experiments.     

Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine

The disposition of intravenous antipyrine and lorazepam, administered as model substrates for hepatic oxidative metabolism and conjugation, was evaluated in 50 children (mean age, 7.8 years; range, 2.3 to 17.8 years) with acute lymphocytic leukemia in complete remission and compared with a group of ten healthy adults. Antipyrine clearance normalized to body weight was significantly greater in children than in adults (0.91 versus 0.59 ml/min/kg; p = 0.012), but was not different when normalized to body surface area. In contrast, lorazepam total clearance (CL) and unbound clearance (CLu) normalized to body weight were not significantly different between children and adults but were smaller in children when normalized to body surface area (CL = 31.9 versus 40.6 ml/min/m2, p = 0.036; CLu = 352 versus 485 ml/min/m2, p = 0.010). The mean lorazepam fraction unbound in children was 0.087, which was not different from adult volunteers (0.084). This study has identified significant differences between children and adults in the disposition of these two compounds, with higher milliliter per minute per kilogram clearance for antipyrine but not lorazepam.     

Lipoprotein changes during continuous subcutaneous insulin infusion in insulin-dependent diabetic patients

We have studied the long-term effects (9 months) in plasma lipoprotein concentrations during continuous subcutaneous insulin infusion (CSII) (n = 11, six females, five males) and compared these changes to conventional insulin therapy (CIT) (n = 12, six females, six males). The two groups were allocated to CSII or CIT randomly, and were comparable as regards lipoprotein values at the start of the study. There were initially normal total plasma cholesterol values in both groups (CSII group: mean plasma cholesterol 3.77 +/- 0.57 mmol/l, CIT group: mean plasma cholesterol 4.37 +/- 0.55 mmol/l, means +/- SD). Further, there were normal total plasma triglyceride values at the start of the study (CSII group: mean plasma triglyceride 0.86 +/- 0.23 mmol/l, CIT group: mean plasma triglyceride 0.84 +/- 0.26 mmol/l, means +/- SD). There were no alterations seen in total plasma cholesterol and total plasma triglyceride in either groups during a 9 months observation period. In the same period no changes in LDL and HDL levels were registered. The very low density lipoprotein (VLDL) was separated into VLDL-1 and VLDL-2 by its binding to heparin-sepharose columns. It was found that CSII treatment for 9 months resulted in a decline in VLDL-2-triglyceride values (0.18 +/- 0.07 mmol/l before versus 0.10 +/- 0.07 mmol/l after, p less than 0.05, means +/- SD) which was not seen in the CIT group. Decline in VLDL-2-triglyceride might delay the development of late diabetic manifestations.     

Hemodynamics in diabetic orthostatic hypotension.

Hemodynamic variables (blood pressure, cardiac output, heart rate, plasma volume, splanchnic blood flow, and peripheral subcutaneous blood flow) and plasma concentrations of norepinephrine, epinephrine, and renin were measured in the supine position and after 30 min of quiet standing. This was done in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously in the standing position in the diabetics with orthostatic hypotension, whereas moderate decreases were found in the other three groups. Upon standing, heart rate rose and cardiac output and plasma volume decreased similarly in the four groups. The increases in total peripheral resistance, splanchnic vascular resistance and subcutaneous vascular resistance were all significantly lower (P less than 0.025) in the patients with orthostatic hypotension compared with the other three groups. The increase in plasma norepinephrine concentrations in the patients with orthostatic hypotension was significantly lower (P less than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy.