Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

BACKGROUND: Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. AIM: To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. METHODS: This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. RESULTS: Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. CONCLUSIONS: Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.

Differential responses to a simulated implantation signal at various stages of the luteal phase in women.

Human CG (hCG) was administered to three groups of four normally cycling women in the early luteal phase (LH +4 to +5, group I), the midluteal phase (LH +8 to +9, group II), and the late luteal phase (LH +11 to +12, group III). Two hundred and fifty IU hCG were given im followed in half of the subjects by 750 IU hCG 24 h later. Serial blood samples were then taken at 15- or 30-min intervals following either the first or second hCG injection and continued for 12 or 24 h. The samples were stored frozen at -20 C until assayed for LH, progesterone, estradiol, and hCG concentrations. Treatment with 250 IU hCG at each stage of the luteal phase did not result in any marked change in hormone concentrations. Further hCG administration (750 IU 24 h later) in both the early and the midluteal phases elicited a clear increase in progesterone concentrations. Further hCG treatment in the late luteal phase did not evoke any rise in progesterone levels. Further hCG administration in the midluteal phase resulted in a sharp decline in LH concentrations, brought about mainly by a decrease in LH pulse frequency, this response was not apparent at any other stage of the luteal phase. Despite the lack of any pulsatile steroidogenic stimulus at this time, progesterone was clearly secreted in a pulsatile manner. The decline in LH levels following hCG administration in the midluteal phase resembled that seen in spontaneous conception cycles following implantation. The restriction of this response to the time of normal implantation may suggest a role for the pituitary in the establishment of the "implantation window." The importance of this pituitary response and the mechanisms involved are currently unknown. Its absence in the early luteal phase would suggest that it cannot be directly attributed to either progesterone or hCG. It is possible that some other luteal factor may be responsible for the midluteal decline in LH concentrations.

Inhibin concentrations throughout the menstrual cycles of normal, infertile, and older women compared with those during spontaneous conception cycles.

Plasma immunoreactive inhibin levels have been measured in a series of normal conception cycles (group I; n = 7), and the data compared to inhibin concentrations in normal menstrual cycles (group II; n = 8), in women with luteal phase defects (group III; n = 7), and in women in the perimenopausal period (group IV; n = 6). Daily plasma levels of LH, FSH, progesterone, estradiol, and inhibin were determined in each subject, and daily mean profiles for each hormone in each subject group were calculated and expressed as geometric means with 68% confidence limits. During the follicular and early luteal phases, inhibin concentrations in the normal nonpregnant group (group II) were significantly higher than those in the conception cycles of group I, but after implantation in the conception cycles, inhibin concentrations increased to levels in excess of those seen at any time in nonconception cycles (716-1352 U/L; P less than 0.02). The postimplantation rise in inhibin did not initially appear to follow the same pattern as progesterone. While progesterone concentrations rose within 24 h of the first detectable increase in hCG, inhibin levels did not increase until 3 days later, although after this point concentrations increased serially and in parallel with progesterone. LH and FSH concentrations were markedly suppressed after implantation. Follicular and early luteal inhibin concentrations in cycles with luteal phase defects were also higher than those in conception cycles, although this difference was only significant in the midfollicular phase. Follicular phase inhibin concentrations in cycles from older women (group IV) were lower than those in groups II and III, but were not distinguishable from those in the conception cycles. Estradiol concentrations in the same subjects were significantly lower during the early follicular phase, while follicular and luteal FSH concentrations were significantly higher than those during conception cycles. Finally, examination of the relationship between inhibin, FSH, and estradiol around menstruation in the older women revealed a far closer temporal association between FSH and estradiol than between FSH and inhibin. In conclusion, inhibin concentrations rise and fall throughout the human menstrual cycle in a manner that is similar to but at specific times significantly different from that of either of the ovarian steroids estradiol and progesterone. It is considered to be a peptide of granulosa cell origin and may be an indicator of the size of the follicular pool during the early stage of the cycle. However, although there is some degree of inverse correlation between profiles of inhibin and profiles of FSH, this relationship is not particularly clear.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute respiratory illness in Adelaide children. II: The relationship of maternal stress, social supports and family functioning.

In a community-based study we investigated the relationships between maternal stress, maternal social supports, family functioning and proneness to acute respiratory illness (AR1) in childhood. 'Prone' and 'not prone' children were identified from the responses to a mail questionnaire sent to the addresses of a randomly selected group of Adelaide children who had been born in 1983. 'Prone' children (n = 255) were defined by a respiratory score (based on frequency and severity of reported symptoms in the preceding 12 months) in the top quintile of the distribution, while 'not prone' children (n = 227) were defined by a score in the bottom 20% of the range. Further information was obtained from a questionnaire administered at a home visit. Maternal stress levels were determined from a combination of major life events, minor life events and psychological distress. Maternal stress was significantly associated with respiratory proneness in a stepwise multiple logistic regression (adjusted odds ratio/high versus low = 3.8; 95% confidence interval 2.0-7.2; p = 0.000), while controlling for the effects of maternal smoking, group child care, early chest illness, number of siblings, breastfeeding, occupation, sex, age, home heating, birthweight and parental history of respiratory illness. Family dysfunction was associated with respiratory proneness in bivariate analyses but not after adjustment for the effects of other psychosocial factors in multivariate analyses. Lack of maternal social support was not associated with having a child who was prone to respiratory illness. These findings raise a number of questions about the nature and direction of the relationship between parental psychological status and child health.

Ecological effects in multi-level studies.

Multi-level research that attempts to describe ecological effects in themselves (for example, the effect on individual health from living in deprived communities), while also including individual level effects (for example, the effect of personal socioeconomic disadvantage), is now prominent in research on the socioeconomic determinants of health and disease. Such research often involves the application of advanced statistical multi-level methods. It is hypothesised that such research is at risk of reaching beyond an epidemiological understanding of what constitutes an ecological effect, and what sources of error may be influencing any observed ecological effect. This paper aims to present such an epidemiological understanding. Three basic types of ecological effect are described: a direct cross level effect (for example, living in a deprived community directly affects individual personal health), cross level effect modification (for example, living in a deprived community modifies the effect of individual socioeconomic status on individual health), and an indirect cross level effect (for example, living in a deprived community increases the risk of smoking, which in turn affects individual health). Sources of error and weaknesses in study design that may affect estimates of ecological effects include: a lack of variation in the ecological exposure (and health outcome) in the available data; not allowing for intraclass correlation; selection bias; confounding at both the ecological and individual level; misclassification of variables; misclassification of units of analysis and assignment of individuals to those units; model mis-specification; and multicollinearity. Identification of ecological effects requires the minimisation of these sources of error, and a study design that captures sufficient variation in the ecological exposure of interest.

Epidemiology of blindness and visual impairment in the kingdom of Tonga.

Data on the prevalence and causes of blindness and visual impairment in Polynesians are not readily available nor are they population based. This survey was designed to obtain an accurate estimate of blindness and its causes in Tonga. A sample of 4056 persons, aged 20 years and over, was selected by stratified cluster sampling. Participants received a screening, visual acuity examination, and, if visually impaired, were referred for detailed ophthalmic examination to determine the cause. The prevalence of bilateral blindness in the study population was 0.47% and all affected were aged over 50 years. It is estimated that the national prevalence of bilateral blindness, adjusted for the sample weight applied in the selection procedure, is 0.56% (95% confidence interval 0-1.13). Monocular blindness was three times more frequent. Cataract was responsible for 68.4% of bilateral and 30.3% of monocular blindness. Risk factors for life time experience of cataract included age and diabetes (self-reported). Neither smoking nor the presence of pterygium were independently associated with cataract. Increasing years of education were protective against cataract for women, but not men. Corneal opacity from infection or trauma, and diabetes were responsible for most of the remaining visual impairment. While these results do not represent a significant public health problem by world standards they do provide a basis for planning blindness prevention programmes in the region.

High-performance liquid chromatographic assay for N-acetylcysteine in plasma and urine.

A sensitive high-performance liquid chromatographic (HPLC) assay for N-acetylcysteine in human plasma and urine has been developed. The method employs a prechromatographic stage to produce the dinitrophenyl derivative of N-acetylcysteine, which is chromatographed on a 5-microns C18 bonded reverse-phase column using an external standard method. The derivatized N-acetylcysteine molecule has a retention time of congruent to 13 min at a flow rate of 1.0 mL/min for a mobile phase of methanol-aqueous 0.05 M citrate-0.001 M EDTA buffer pH 7.0 (30:70). In a multistep extraction procedure, which is slightly modified for the N-acetylcysteine assay in urine, the limits of sensitivity for the plasma and urine assays were found to be congruent to 60 ng/mL and congruent to 200 micrograms/mL, respectively. Preliminary data from pilot studies in human subjects are presented.

Determination of nitroglycerin and its dinitrate metabolites in human plasma by high-performance liquid chromatography with thermal energy analyzer detection.

A highly selective and sensitive high-performance liquid chromatographic assay employing a thermal energy analyzer as the detector for nitroglycerin and its dinitrate metabolites in human plasma has been developed. Prior to chromatography the method employs a simple one-stage extraction step. Nitroglycerin and its dinitrate metabolites are then chromatographed on a 10-micron nitrile bonded phase column using an internal-external standard method. The nitroglycerin and its 1,2,3-propanetriol-1,3- and -1,2-dinitrate metabolites (glyceryl-1,3- and -1,2-dinitrate) have a retention time of 8.5, 10.5, and 11.5 min, respectively at a flow rate of 2.0 mL/min for a mobile phase of 5% v/v acetone in n-hexane. The limits of sensitivity were 0.05 ng/mL for nitroglycerin and 0.25 ng/mL for the dinitrate metabolites. Linearity of response was observed over the 0.1-2.0-ng/mL range for nitroglycerin and 0.5-10.0-ng/mL range for the dinitrate metabolites. Blood level data from a pilot study with human volunteers in receipt of an oral form of nitroglycerin is presented.

Abatement of tropospheric ozone: effects of strategies to improve air quality on public health and other sectors.

The National Health and Medical Research Council's air quality goal for ozone in the troposphere (near the earth's surface) is 0.12 parts per million (ppm), averaged over one hour, similar to the United States standard, but less stringent than the guideline for Europe. We aimed to identify the environmental, economic and social changes that would be associated with changing the goal. Methods included literature review, economic assessments and group interviews. The group to benefit from lower exposures may include outdoor workers, school children and people not in regular day-time work indoors, because ozone is most prevalent during the daylight hours of the warmer months. A lower level could improve the yield of some crops. The causes and effects of tropospheric ozone are not appreciated except among groups with relevant commercial, industrial or scientific experience. However, the consultations identified frustration about the social problems caused by dependence on private motor vehicles. Short-term costs of compliance with a more stringent goal would fall principally on the users of transport. The value of the benefits was enough for many to support making the ozone goal more stringent, but those who required a demonstration of financial benefit (even including savings of health care costs) did not support any change to the goal. Based primarily on averted detriment to health, we recommend the more stringent level of 0.08 ppm (one-hour average) as the goal for the year 2005 in Australia and elsewhere. The addition of a goal with longer averaging time is also proposed.

Do bicycle safety helmets reduce severity of head injury in real crashes?

In the past, evaluation of helmet efficacy has been based on laboratory tests of limited relevance to real crashes. In the present study 894 South Australian bicycling enthusiasts returned mail questionnaires about their most recent bicycle crash and their helmet use at the time. 197 bicyclists reported a crash within the past five years in which they had struck their head or helmet. Helmet status at the time of the crash was reported as: no helmet used (n = 75), hairnet-style helmet (n = 69), hard-shell with soft or no liner (n = 37), or hard-shell helmet with stiff liner (n = 16). Analysis of the crude, unadjusted data showed a statistically significant association between helmet use and reduced severity of head injury. The association persisted after adjustment for age and sex of rider, and severity of crash forces. Using an unpublished method developed by Somers, it was estimated that the risk of death from head injury was considerably reduced for helmeted relative to unhelmeted bicyclists, depending on helmet type.

Something in the water? A health impact assessment of disinfection by-products in New Zealand.

Disinfection by-products (DBP) are a large group of halogenated chemicals formed by the reaction of disinfectant agents with naturally-occurring organic substances in water. Numerous studies have found associations between DBP and some cancers and adverse reproductive outcomes. For both cancer and birth defects the relative risk associated with exposure to DBP is about 1.5. About 66% of New Zealanders, or 2.4 million people, use chlorinated water supplies and are exposed to DBP. New Zealand's unique combination of flora, climate and geology will create unique mixtures of DBP but little detailed information is available on the level or composition of DBP in New Zealand. The population attributable risk per cent, for cancers and birth defects in New Zealand, is about 25%. In other words, a quarter of all bladder, colon and rectal cancers and birth defects may be preventable by reducing DBP exposure. This is equal to 329 preventable cancer deaths in 1995 and 94 preventable birth defects in 1996. DBP exposure can be reduced without compromising microbiological safety of water supplies. The health effects of DBPs must be weighed against the cost of DBP reduction and not against the potential water borne disease prevented by disinfection. Some aspects of New Zealand's water supplies and population provide a unique opportunity to undertake research. Further research is needed on the occurrence of DBPs and their health consequences in order to undertake a properly informed risk assessment.

Mammographic screening trials for women aged under 50. A quality assessment and meta-analysis.

OBJECTIVE: To carry out a systematic quality review and meta-analysis of all randomised trials of mammographic screening that included women aged under 50 years. DATA SOURCES: Reports of randomised trials of mammographic screening were identified via MEDLINE and checks of the bibliographies of retrieved articles and reviews. DATA SYNTHESIS: Identified trials were assessed for: (i) method of randomisation; (ii) documented comparability of baseline data; (iii) standardised criteria for breast cancer death; (iv) blinded review of cause of death; (v) completeness of follow-up; and (vi) use of an "intention-to-treat analysis". Seven randomised trials including almost 160,000 women aged under 50 were studied. The combined estimate of relative risk was 0.95 (95% confidence interval, 0.77-1.18), a statistically non-significant reduction of 5%. Adjustment for the cluster randomisation of two trials, and for degree of compliance, did not substantially change this result. CONCLUSIONS: These analyses suggest little, if any, benefit for women under 50 years of age. The results are not explained by the quality of the trials or the radiology. We recommend that women in this age group intending to be screened should be fully informed of these results.

Vehicle speed and risk of a severe crash.

We examined the relation between the speed of passenger cars and risk of involvement in a severe crash, in an urban setting, using a case-control study. "Cases" were 45 vehicles involved in severe crashes in the Adelaide metropolitan area; we determined their pre-crash speeds using accident reconstruction techniques. For each case, we measured the speeds of 10 controls using an amphometer; controls were cars not involved in crashes that passed through the crash location at the same time of day, day of week, and season. We found that the risk of involvement in a severe crash increased as vehicle speed increased. In particular, within 60 km per hour zones, compared with vehicles traveling at about the posted limit, vehicles traveling at 75-84 km per hour had an odds ratio of 7.8 [95% confidence interval (CI) = 1.4-38.8] for a severe crash, whereas vehicles with speeds in excess of 84 km per hour had an odds ratio of 39.0 (95% CI = 9.3-170.5).

Improved method for the determination of N-acetylcysteine in human plasma by high-performance liquid chromatography.

An improved method for the determination of N-acetylcysteine by paired-ion reversed-phase high-performance liquid chromatography has been developed. Following incubation with dithiothreitol to release bound N-acetylcysteine, free N-acetylcysteine and the internal standard N-acetylpenicillamine were derivatised with 2,4-dinitro-1-fluorobenzene. The samples were then deproteinised by ultrafiltration. The dinitrophenyl derivatives were extracted from acidified ultrafiltrate into diethyl ether and purified by using a back-extraction step. They were then separated from naturally occurring plasma components and reagent impurities by high-performance liquid chromatography, utilising an Ultrasphere ODS (5 microns) reversed-phase column and detection at 360 nm.