Age-related changes in brain: II. Positron emission tomography of frontal and temporal lobe glucose metabolism in normal subjects

While many neuropsychological studies have demonstrated age-related performance alterations in tests thought to reflect frontal and temporal lobe function, there is little direct observation and comparison of these hypothesized brain changesin vivo. The cerebral glucose metabolism of frontal, temporal, and cerebellar regions was examined in 40 young ( =27.5±4.9) and 31 elderly ( =67.6 ± 8.8) normal males using PET-FDG. Univariate analysis showed age-related metabolic reductions in all frontal and temporal lobe regions. The reductions ranged from 13%–24% with the greatest changes in the frontal lobes. Multiple regression analyses showed a stronger age relationship with frontal lobe than with temporal lobe metabolism. The dorsal lateral frontal lobe was the region that appears to change most within the frontal lobes. Examination of the temporal lobe showed that age contributed equally to the metabolic variance of both the lateral temporal lobe and hippocampus. These results suggest that age-related metabolic changes exist in both frontal and temporal lobes and that the frontal lobe change is greater.     

Selecting a pharmacy computer system for the future

Major advances are occurring in the field of computer science that have placed us at the threshold of a significant revolution in the management and application of clinical data. These advances will have a profound effect on the practice of pharmacy and are occurring at a time when many hospital pharmacies are deciding whether to enhance or replace their current systems. To best position your department for the future, it is essential that you are knowledgeable of the advances being made, have a vision for how they will affect your practice, and undergo a well-organized and thorough selection process.     

Short-term associations between emergency hospital admissions for respiratory and cardiovascular disease and outdoor air pollution in London

There are concerns about the possible short-term effects of outdoor air pollution on health in the United Kingdom. In a study conducted during the time period between 1987 and 1992, investigators determined that ozone had small, but significant effects on emergency respiratory admissions. In the current study, the authors investigated associations between emergency admissions and outdoor air pollution for the time period from 1992 to 1994, inclusive, and compared the results with those obtained in the earlier study. The authors also examined particulate matter less than 10 microm in diameter (PM10) and carbon monoxide in the current study. Appropriate confounding factors, such as seasonal patterns, temperature, and humidity, were controlled for, and the authors used Poisson regression to estimate the association between daily emergency admissions for respiratory and cardiovascular diseases and ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, particles measured as Black Smoke, and PM10. Significant positive associations were found between emergency hospital admissions for respiratory disease and PM10 and sulfur dioxide, but such an association did not exist for ozone. The results were not significantly different from earlier results from London and were comparable with those determined in North America and Europe. Cardiovascular disease was associated with carbon monoxide and Black Smoke, but weaker associations existed with the other pollutants studied.     

Maternal zinc supplementation does not affect size at birth or pregnancy duration in Peru.

To estimate the effect of maternal zinc deficiency on pregnancy outcomes, we conducted a zinc supplementation trial in an urban shantytown in Lima, Peru, a population with habitual low zinc intakes. Beginning at 10-24 wk gestation, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg iron and 250 (g folate, with or without 15 mg zinc. Women were followed up monthly during pregnancy. At birth, newborn weight was recorded, and crownheel length, head circumference and other circumferences and skinfold thicknesses were assessed on d 1. At delivery, 1016 remained in the study; duration of pregnancy was known for all women, and birth weight information was available for 957 newborns. No differences were noted in duration of pregnancy (39.4 +/- 2.2 vs. 39. 5 +/- 2.0 wk) or birth weight (3267 +/- 461 vs. 3300 +/- 498 g) by prenatal supplement type (iron + folate + zinc vs. iron + folate; P > 0.05), and there were no differences in the rates of preterm (<37 wk) or post-term (>42 wk) delivery, low birth weight (<2500 g) or high birth weight (>4000 g). Finally, there were no differences by prenatal supplement type in newborn head circumference, crownheel length, chest circumference, mid-upper arm circumference, calf circumference or skinfold thickness at any of three sites. Adjustment for covariates and confounding factors did not alter these results. Adding zinc to prenatal iron and folate tablets did not affect duration of pregnancy or size at birth in this population.     

Pregnancy outcomes and outdoor air pollution: an ecological study in districts of the Czech Republic 1986-8

OBJECTIVES: Outdoor air pollution has consistently been shown to predict mortality. The finding that this association is stronger in infants than in children or adults raises the question whether air pollution could also be related to pregnancy outcomes--such as birthweight and stillbirth. The association between outdoor air pollution and stillbirths and low birthweight in the Czech Republic, where air pollution was high, was examined. METHODS: An ecological study was conducted, with routinely collected data on stillbirths and low birthweight (< 2500 g), air pollution (total suspended particulates, sulphur dioxide (SO2), and nitrogen oxides (NOx)), and socioeconomic factors (mean income, car ownership, divorce rate, etc). The analyses were restricted to 45 districts on which data on air pollution were available for the period 1986-8. The effects of exposure variables on frequency of pregnancy outcomes were estimated by logistic regression with district-years as the units of analysis. RESULTS: Stillbirth rate (4.2/1000 births in monitored districts) was not significantly associated with any indicator of air pollution, and was weakly related to mean income and proportion of births outside marriage. Crude prevalence of low birthweight (prevalence 5.5%) showed highly significant associations with several socioeconomic factors; after controlling for these, odds ratios (ORs)/50 micrograms/m3 increase in pollutant were: 1.04 (95% confidence interval (95% CI) 0.96 to 1.12) for total suspended particles, 1.10 (1.02 to 1.17) for SO2, and 1.07 (0.98 to 1.16) for NOx. When all pollutants were included in one model, SO2 remained related to low birthweight (OR 1.10 (1.01 to 1.20), p = 0.033). CONCLUSION: These results are consistent with a recent study in China where birthweight was also associated with total suspended particles and SO2 but ecological studies must be interpreted cautiously. Residual confounding by socioeconomic factors cannot be ruled out. The association between air pollution and birthweight requires further investigation.

 

     

Genetic analysis of three patients with an 18p- syndrome and dystonia

Some patients with an 18p- syndrome show dystonia, and a focal dystonia gene has been mapped to chromosome 18p. The authors evaluated the extent of the deletion in three patients with an 18p- syndrome and dystonia using 14 DNA markers on 18p. A common deleted area, covering the DYT7 locus, places the putative dystonia gene between the telomere of 18p and D18S1104 (49.6 cM). Dystonia in these patients may be caused by haploinsufficiency of the DYT7 gene, a new dystonia gene on 18p, or may result from developmental brain anomalies.     

Modified therapeutic community for mentally ill chemical abusers: outcomes and costs.

Several studies have established that the personal and social consequences of substance abuse are extensive and costly. These consequences are frequently compounded by mental illness. Although interventions that target mentally ill chemical abusers (MICAs) present several challenges, the potential benefits of successful interventions are significant. This article presents outcomes and costs of a modified therapeutic community (TC) intervention for homeless MICAs. Outcomes at follow-up are compared with those for a control group of homeless MICAs receiving standard services in a "treatment-as-usual" (TAU) condition. Annual economic costs for the modified TC and the average weekly cost of treating a single client are estimated. Treatment and other health service costs at 12 months postbaseline are compared for modified TC and TAU clients. The results of this study indicate that, suitably modified, the TC approach is an effective treatment alternative for homeless MICAs, with the potential to be highly cost-effective relative to standard services.     

Cancer mortality in Russia and Ukraine: validity, competing risks and cohort effects

BACKGROUND: The dramatic increase in mortality in Russia and Ukraine in the late 1980s and 1990s has been due to increases in certain causes of death, particularly cardiovascular disease and accidents and violence. In contrast, there has been a slight fall in mortality from cancer. METHODS: This paper presents an analysis of trends and patterns in cancer mortality and examines four possible explanations for its recent fall: changes in data collection; cohort effects; competing mortality from other causes of death; and improvements in health care. RESULTS: All contribute to some extent to the observed changes, with each affecting predominantly different age groups. There is evidence of a significant underrecording of cancer deaths among the elderly especially in rural areas and of significant changes in coding practices in the early 1990s. Competing mortality from cardiovascular diseases and accidents can explain some reduction in male deaths from cancer in middle age. Birth cohort effects can explain some reduction among males after early middle age and among females at all ages. The impact of changes in health care are more difficult to identify with certainty but there is evidence of reduced deaths from childhood leukaemia. IMPLICATIONS: Recent changes in mortality in Russia are complex and their understanding will require a multidisciplinary approach embracing demography, epidemiology and health services research.     

Comparative effects of a glucocorticosteroid, theophylline and the peptido-leukotriene-antagonist CGP 45715A on antigen-induced early and late phase airway response and inflammatory cell influx in sensitised guinea pigs

A novel model of allergic early and late-phase reaction in the airways of conscious guinea pigs was developed and the effect of established and novel antiasthmatic drugs on peak of immediate response, late phase response and associated inflammatory cell influx investigated. Guinea pigs were sensitised twice in adjuvant (50 mg/kg silica + 0.1 ml/kg Bordetella pertussis). Under cover of 10 mg/kg i.p. mepyramine guinea pigs exhibited still a pronounced immediate reaction. During a screening phase about 75% of guinea pigs demonstrated a late phase reaction of decrease of tidal volume between 4-10 h after ovalbumin inhalation. In a cross over study theophylline at 50 mg/kg p.o. (-1 h before ovalbumin) tended to attenuate not only the peak of the immediate reaction by about 69% (P>0.05, n = 12), but inhibited the airway late phase response significantly (P<0.05, 5-10 h, n = 12). Methylprednisolone (40 mg/kg p.o. 1 h before ovalbumin) did not inhibit the immediate response, but the late phase response. In contrast the cysteinyl-leukotriene antagonist CGP 45715A (Iralukast; 30 mg/kg p.o. 2 h before ovalbumin) neither interfered with the peak of the immediate, nor with the late phase response. When bronchoalveolar lavage by orotracheal route was performed 24 h after ovalbumin inhalation, total cell count, eosinophils, neutrophils, macrophages and lymphocytes were significantly increased in ovalbumin-controls compared to sham (n = 5; P<0.05). Methylprednisolone reduced significantly the antigen-induced increase of total cell count and eosinophil number. Neither theophylline nor the cysteinyl-leukotriene receptor antagonist attenuated the antigen-associated cell influx. The results do not provide evidence for a major role of cysteinyl-leukotrienes in the late phase response and inflammatory cell influx in this model.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.