Respiratory health status is impaired in UK HIV-positive adults with virologically suppressed HIV infection.

OBJECTIVES: We sought to evaluate whether people living with HIV (PLWH) using effective antiretroviral therapy (ART) have worse respiratory health status than similar HIV-negative individuals. METHODS: We recruited 197 HIV-positive and 93 HIV-negative adults from HIV and sexual health clinics. They completed a questionnaire regarding risk factors for respiratory illness. Respiratory health status was assessed using the St George's Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC) breathlessness scale. Subjects underwent spirometry without bronchodilation. RESULTS: PLWH had worse respiratory health status: the median SGRQ Total score was 12 [interquartile range (IQR) 6-25] in HIV-positive subjects vs. 6 (IQR 2-14) in HIV-negative subjects (P < 0.001); breathlessness was common in the HIV-positive group, where 47% compared with 24% had an MRC breathlessness score ≥ 2 (P = 0.001). Eighteen (11%) HIV-positive and seven (9%) HIV-negative participants had airflow obstruction. In multivariable analyses (adjusted for age, gender, smoking, body mass index and depression), HIV infection remained associated with higher SGRQ and MRC scores, with an adjusted fold-change in SGRQ Total score of 1.54 [95% confidence interval (CI) 1.14-2.09; P = 0.005] and adjusted odds ratio of having an MRC score of ≥ 2 of 2.45 (95% CI 1.15-5.20; P = 0.02). Similar findings were obtained when analyses were repeated including only HIV-positive participants with a viral load < 40 HIV-1 RNA copies/mL. CONCLUSIONS: Despite effective ART, impaired respiratory health appears more common in HIV-positive adults, and has a significant impact on health-related quality of life.

Age, time living with diagnosed HIV infection, and self-rated health.

OBJECTIVES: An increasing proportion of people living with HIV are older adults, who may require specialized care. Adverse physical and psychological effects of HIV infection may be greatest among older people or those who have lived longer with HIV. METHODS: The ASTRA study is a cross-sectional questionnaire study of 3258 HIV-diagnosed adults (2248 men who have sex with men, 373 heterosexual men and 637 women) recruited from UK clinics in 2011-2012. Associations of age group with physical symptom distress (significant distress for at least one of 26 symptoms), depression and anxiety symptoms (scores ≥ 10 on PHQ-9 and GAD-7, respectively), and health-related functional problems (problems on at least one of three domains of the Euroqol 5D-3L)) were assessed, adjusting for time with diagnosed HIV infection, gender/sexual orientation and ethnicity. RESULTS: The age distribution of participants was: < 30 years, 5%; 30-39 years, 23%; 40-49 years, 43%; 50-59 years, 22%; and ≥ 60 years, 7%. Overall prevalences were: physical symptom distress, 56%; depression symptoms, 27%; anxiety symptoms, 22%; functional problems, 38%. No trend was found in the prevalence of physical symptom distress with age [adjusted odds ratio (OR) for trend across age groups, 0.96; 95% confidence interval (CI) 0.89, 1.04; P = 0.36]. The prevalence of depression and anxiety symptoms decreased with age [adjusted OR 0.86 (95% CI 0.79, 0.94; P = 0.001) and adjusted OR 0.85 (95% CI 0.77, 0.94; P = 0.001), respectively], while that of functional problems increased (adjusted OR 1.28; 95% CI 1.17, 1.39; P < 0.001). In contrast, a longer time with diagnosed HIV infection was strongly and independently associated with a higher prevalence of symptom distress, depression symptoms, anxiety symptoms, and functional problems (P < 0.001 for trends, adjusted analysis). CONCLUSIONS: Among people living with HIV, although health-related functional problems were more common with older age, physical symptom distress was not, and mental health was more favourable. These results suggest that a longer time with diagnosed HIV infection, rather than age, is the dominating factor contributing to psychological morbidity and lower quality of life.

Particulate air pollution and hospital admissions in Christchurch, New Zealand.

AIMS: Winter air pollution in Christchurch is dominated by particulate matter from solid fuel domestic heating. The aim of the study was to explore the relationship between particulate air pollution and admissions to hospital with cardio-respiratory illnesses. METHODS: Particulate air pollution statistics (PM10) were obtained from the Canterbury Regional Council monitoring station in the city. The New Zealand Health Information Service provided data on admissions to the Princess Margaret and Christchurch Hospitals for the period June 1988 through December 1998 for both adults and children with cardiac and respiratory disorders. The relationship between PM10 and admissions was explored using a time series analysis approach controlling for weather variables. Missing values were interpolated from carbon monoxide data for the same time period, as carbon monoxide and PM10 were highly correlated. RESULTS: There was a significant association between PM10 levels and cardio-respiratory admissions. For all age groups combined there was a 3.37% increase in respiratory admissions for each interquartile rise in PM10 (interquartile value 14.8 mcg/m3). There was also a 1.26% rise in cardiac admissions for each interquartile rise in PM10. There was no relationship between PM10 and admissions for appendicitis, the control condition selected. CONCLUSIONS: In keeping with overseas studies, there is evidence in Christchurch of a relationship between ambient particulate levels and admissions with cardiac and respiratory illnesses. The size of the effect is consistent with overseas data, with the greatest impact for respiratory disorders. IMPLICATIONS: These results indicate that measures to control ambient particulate levels have the potential to reduce hospital admissions for cardio-respiratory illnesses.

Commentary on the Women's Health Initiative.

The Women's Health Initiative (WHI), established by the National Institutes of Health in 1991, is a long-term national health study that focuses on strategies for preventing heart disease, breast and colorectal cancer and osteoporosis in postmenopausal women. These chronic diseases are the major causes of death, disability and frailty in older women of all races and socioeconomic backgrounds. The WHI a 15-year multi-million dollar endeavor, and one of the largest U.S. prevention studies of its kind. The study involves over 161,000 women aged 50-79, and is one of the most definitive, far reaching clinical trials of women's health ever undertaken in the U.S. The WHI Clinical Trial and Observational Study will attempt to address many of the inequities in women's health research and provide practical information to women and their physicians about hormone replacement therapy, dietary patterns and calcium/vitamin D supplements, and their effects on the prevention of heart disease, cancer and osteoporosis. Emerging information from the NIH Women's Health Initiative and other studies of women's health begun in the 1990's should be changing the landscape of options for older women in the years to come.

The effect of photoperiod and food intake on daily changes in plasma calcitonin in broiler breeder hens.

The roles of photoperiod, energy balance, and concentrations of plasma total calcium (CaT) on daily changes in plasma calcitonin (CT) were investigated in broiler breeder hens (84-100 weeks old). In the first study, broiler breeder hens (n = 24), reared on 14L:10D, were divided into two groups. One group was transferred from a restricted diet (DR) of 150 g/day to ad libitum (AL) for 14 days, while the other group remained on DR. After 2 weeks of ad libitum feeding, birds from each group (AL and DR) were bled every 2 hr for 24 hr for measurement of plasma CaT and CT. In a second study, the hens (n = 20) were transferred to continuous light (LL) for 30 days. After the 30 days, food was removed from one group for 48 hr prior to blood sampling for 24 hr at 3-hr intervals. In a third study, birds were transferred to an ahemeral light cycle (11L:10D) for 28 days. Food was removed from the birds (n = 11) for 48 hr prior to blood sampling every 3 hr for 24 hr. Four weeks later the same birds were bled again for 24 hr, but this time the birds were maintained on a restricted feeding schedule. Plasma CT was measured by a specific heterologous electrochemiluminescent (ECL) assay while plasma CaT was measured by atomic absorption. The results showed that plasma CT concentrations did not correlate with plasma CaT concentrations. Comparisons made between initial and final CaT and CT concentrations indicated an effect of stress due to repeated handling of the birds. Concentrations of plasma CT were significantly reduced in the fasted animals (P < 0.05) compared to diet-restricted controls. There was a significant increase in plasma CT during the dark period of fed animals which was abolished in animals maintained on LL or fasted. In conclusion, a surge in plasma CT requires that the hens be provided food and that they be exposed to a dark cycle.

Bone: target and source of environmental pollutant exposure.

The skeleton can play a unique role in modulating and responding to environmental air pollutants. Bone and its metabolic activities may be immediate targets for particular agents, leading to skeletal disease. However, bone is also an important storage site in the body. Chemical pollutants may be actively absorbed into bone mineral and released later during the normal process of bone remodeling. Critical periods when bone remodeling is enhanced, such as pregnancy, lactation, menopause, immobilization, and exposure to microgravity, may be important to recognize because of the potential for enhanced release of previously stored chemical agents. Lead has been identified as a "criteria air pollutant" by the 1970 Clean Air Act because of its ubiquity in the environment and its effect on a multiplicity of health outcomes. It is used in this article as an example of a substance that can have both a direct effect on bone and a latent effect on other organ systems through release from bone long after the initial exposure.

The evolution of the Women's Health Initiative: perspectives from the NIH.

The Women's Health Initiative (WHI) addresses some of the major health concerns of postmenopausal women. It is designed to test whether long-term preventive measures will decrease the incidence of cardiovascular disease, certain cancers, and fractures, and it seeks to find better predictors of future health and disease in older women. This report traces the evolution of the clinical trial and observational study (CT/OS) components of WHI from early planning in the 1980s to the current status of the WHI CT/OS as an integrated, ongoing clinical study. Particular attention is directed to the antecedent planning meetings and feasibility studies that formed the underpinnings of the WHI. The issues of hormone replacement therapy and of the optimal diet for postmenopausal women were investigated for almost a decade prior to WHI. However, no studies of sufficient size and duration to confidently test the value and risks of these approaches were initiated because of the cost and insufficient political commitment. The initiation of WHI in 1991 represents the confluence of scientific need and capability with the social priorities to improve the health and welfare of women.

Hyperglycemia and non-enzymatic glycation of serum and tissue proteins in chickens.

The objectives of these studies were to determine whether elevated plasma glucose concentrations in broiler breeder chickens (200-250 mg/dl) can result in the non-enzymatic attachment of glucose to serum proteins (fructosamine) and eventual cross-linking of tissue proteins (basement membrane thickness), and to investigate the effects of a factor that may influence this cross-linking process. In response to feeding the satiety factor calcium propionate (CaP, 1.7%), plasma glucose and fructosamine concentrations were increased (P < 0.05) from 1 to 9 weeks of age, whereas concentrations of plasma glucose and fructosamine in feed-restricted chicks were reduced for the first 7 weeks after hatch. In a second study, the age-related increase in kidney capillary basement membrane thickness was prevented (P < 0.05) by feeding the cross-linking inhibitor aminoguanidine (AG, 800 ppm) to 30-week-old broiler breeder hens for 34 weeks. The results from these studies suggest that concentrations of plasma glucose in chickens may, in fact, be exerting long-term detrimental effects on tissue proteins, which can be ameliorated by factors that limit the cross-linking reaction.

Osteoporosis: assessment of bone loss and remodeling.

Osteoporosis, the most common metabolic bone disorder, is a major health problem in older individuals, and especially in postmenopausal women throughout the world. It is characterized by low bone mass, structural deterioration, and an increased risk of fracture. The expected growth in the percentage of the world population over 65 years of age suggests that control of the chronic diseases of the elderly must be a major international priority. In order to design and implement appropriate prevention and treatment strategies for osteoporosis, it is necessary to assess the extent of the disease or condition in populations, and in individuals in a clinical setting. This review focuses on available and emerging techniques to measure bone mass or density, and on the role of biochemical markers of bone remodeling in the prediction of future bone loss. In order to prevent a disease that progresses without any obvious symptoms, it is important to determine not only the current status of bone mass and remodeling but also to develop methods to predict future bone loss. Different information is derived from each of the assessment approaches, and a combination of measures may be necessary to develop accurate predictive models.

Acid-base disturbances in cardiogenic pulmonary edema.

Eighty-one consecutive cases of uncomplicated cardiogenic pulmonary edema (CPE) were retrospectively graded for severity of chest roentgenogram (CXR) changes and grouped according to primary acid-base abnormalities, either single or mixed. Mean age was 72, 50 male, 31 female. Twenty-three percent had no acid-base disturbances (ABD). Isolated respiratory alkalosis was most common (41%), followed by metabolic acidosis, 22%; metabolic alkalosis, 10%, and respiratory acidosis, 9%. Age, sex, race distribution, morbidity and mortality were not significantly different between the groups. Overall mortality was 17%. Significantly higher mortality was associated with age over 70, pH less than 7.4, and presence of acute myocardial infarction. CXR scores did not correlate with pH, pCO2 or pO2, mortality or morbidity. Some patients with the most severe ABDs recovered while others, who had no ABD on presentation, eventually died. Thus, in 81 consecutive episodes of uncomplicated CPE, isolated respiratory alkalosis was the commonest ABD, occurring in 41%. No correlation was found between ABD and severity of CPE, morbidity or mortality.

Climate and change in oceanic ecosystems: The value of time-series data.

The consequences of climatic change for the structure and function of oceanic ecosystems are of considerable current interest. A predictive, mechanistic model of these consequences based on our scanty knowledge of the dynamics of the systems' components seems unlikely: a complex set of simultaneous partial differential equations depicting population interactions and transfer rates of energy and materials would be necessary. A second approach is simply to measure the phenomenology of variations in both climate and ecosystem components, for the purpose of detecting shared patterns. Two studies of the latter type have been done. Both have been successful in revealing relationships between climatic variation and large-scale, large-amplitude, low-frequency biological variability. Both sets of results can provide models for the prediction of consequences, and both can serve as baselines for the definition of 'change'.

Reciprocal regulation of adult rat hepatocyte growth and functional activities in culture by dimethyl sulfoxide.

Hepatocyte DNA synthesis, initiated by epidermal growth factor (EGF), is reversibly inhibited by 2% dimethyl sulfoxide (DMSO). At that concentration, both the survival of the cells in culture and the expression of differentiated functions are prolonged. DMSO does not affect thymidine uptake or EGF receptor binding. Moreover, EGF receptor binding is maintained at 84% of initial 12 hr binding when cells are cultured for several days in the presence of DMSO, whereas specific receptor binding declines to 49% of initial binding under standard culture conditions without DMSO. Studies of hepatocyte functional activity indicate that, during early culture, total cellular export protein synthesis, specific albumin synthesis, and glycogen synthesis are enhanced in the presence of DMSO. Dexamethasone is required for the effect of DMSO on survival, and although dexamethasone alone enhances hepatocyte DNA synthesis in the presence of EGF, it does not reverse the inhibitory effect of 2% DMSO on DNA replication. The correlation of prolonged survival with growth inhibition supports the hypothesis that hepatic growth and differentiated functional activity may be reciprocally regulated.

Inhibitory effects of volume expansion performed in vivo on transport in the isolated rabbit proximal tubule perfused in vitro.

To examine the renal tubular sites and mechanisms involved in the effects of hypooncotic volume expansion (VE) on renal electrolyte excretion, we performed clearance and isolated tubular perfusion studies using intact and thyroparathyroidectomized (TPTX) rabbits. We also examined the effect of VE on luminal brush border transport. In the microperfusion studies, proximal convoluted (PCT) and straight (PST) tubules were taken from rabbits without prior VE or after 30 min of 6% (body wt) VE. Acute VE increased the percentage excretion of Na, Ca, and P in TPTX animals and the percentage and absolute excretions of these ions in intact rabbits. In PST from VE animals, fluid flux (Jv) was depressed compared with Jv in PST from nonVE rabbits: Jv = 0.18 +/- 0.03, (VE) vs. 0.31 +/- 0.03 nl/mm.min, (nonVE) P less than 0.02. Phosphate transport (Jp) in the PST from VE animals was also depressed: JP = 1.58 +/- 0.10 (VE) vs. 2.62 +/- 0.47 pmol/mm.min, (nonVE) P less than 0.05. Similar results were obtained with TPTX animals. In the PCT from VE animals, Jv was decreased (0.49 +/- 0.10 (VE) vs. 0.97 +/- 0.14 nl/mm.min, (nonVE) P less than 0.02), but JP was not affected significantly. Transport inhibition was stable over approximately 90 min of perfusion. In the brush border vesicle studies, sodium-dependent phosphate transport was inhibited compared with that in control animals, at the 9-, 30-, and 60-s time points. These findings indicate that the inhibition of renal ionic transport by VE occurs in both PCT and PST and is, in part, the result of a direct effect of VE on tubular transport mechanisms.

Climate and Chlorophyll a: Long-Term Trends in the Central North Pacific Ocean.

Since 1968 a significant increase in total chlorophyll a in the water column during the summer in the central North Pacific Ocean has been observed. A concomitant increase in winter winds and a decrease in sea surface temperature suggest that long-period fluctuations in atmospheric characteristics have changed the carrying capacity of the central Pacific epipelagic ecosystem.

The effects of atrial natriuretic peptide on whole-kidney and proximal straight tubular function in the rabbit.

The mechanisms by which atrial natriuretic peptide (ANP) produces a diuresis and natriuresis remain unclear. It has been suggested that the major if not sole mediator of ANP's renal effects is a hemodynamically induced increase in glomerular filtration rate (GFR). Data from clearance studies in anesthetized rabbits demonstrate that ANP administration can produce a significant increase in absolute and percentage sodium excretion (42.0 +/- 5.9----64.6 +/- 10.2 mu eq/min, P less than 0.01, and 1.97 +/- 0.28----3.12 +/- 0.35%, P less than 0.001, respectively) without increasing GFR (16.8 +/- 2.1----16.1 +/- 2.5 cc/min, P greater than 0.30). The natriuresis occurred despite a fall in renal plasma flow (RPF) (56.7 +/- 7.0----44.5 +/- 9.4 cc/min, P less than 0.01), a rise in filtration fraction (0.33 +/- 0.01----0.46 +/- 0.05, P less than 0.01), and an unchanged filtered load of sodium (2.28 +/- 0.27----2.16 +/- 0.32 mu eq/min, P greater than 0.10). Isolated tubular microperfusion studies demonstrated that ANP, present as a 10(-9) M concentration in the solution bathing perfused proximal straight tubules (PST), did not affect fluid flux (Jv) (0.38 +/- 0.07----0.41 +/- 0.07 nl/mm/min, P greater than 0.30) or phosphate reabsorption (Jp) (1.50 +/- 0.5----1.38 +/- 0.36 pmole/mm/min, P greater than 0.50). When ANP was infused into rabbits prior to harvesting the PSTs for isolated tubular microperfusion and the results were compared to tubules taken from control animals, there was again no effect on Jv (0.37 +/- 0.05 vs 0.42 +/- 0.05 nl/mm/min, P greater than 0.50) or Jp (2.41 +/- 0.27 vs 2.42 +/- 0.44 pmole/mm/min, P greater than 0.90). These findings suggest that ANP can inhibit sodium transport without increasing whole-kidney GFR or RPF, but does not directly inhibit transport in the proximal straight tubule.

Cholesterol atheroembolic renal disease. Report of 3 cases with emphasis on diagnosis by skin biopsy and extended survival.

Because antemortem diagnosis is difficult, renal failure due to cholesterol atheroembolism has, until recently, been regarded as a uniformly irreversible and generally fatal disease. Of late, recovery of renal function in several patients in whom the diagnosis was made by organ or other invasive biopsy has been reported. Three cases of cholesterol atheroembolic renal failure in which the diagnosis was made by simple, noninvasive biopsy of the skin in areas showing livedo reticularis are described. Two of the patients, including 1 who required dialysis for 2 months, had an extended survival with recovery of renal function.

Partial characterization of a hepatocyte growth factor from rat platelets.

Rat serum has been shown to stimulate DNA synthesis in primary cultures of adult rat hepatocytes 2-3 times more potently than serum from several other mammalian sources, including humans. Parallel to its stimulation of thymidine incorporation into DNA, rat serum increased the total DNA content of the hepatocyte cultures over time, and also increased the frequency of nuclear labeling and mitosis. Moreover, normal rat serum, derived from whole blood (NRS), stimulated DNA synthesis in hepatocytes twice as effectively as platelet-poor rat serum, derived from plasma (ppNRS). Addition of a rat platelet lysate (RPL) to ppNRS restored the activity to equal that of NRS. The avid binding of the active principle to CM Sephadex and its sensitivity to trypsin digestion suggest that it is a cationic polypeptide with an apparent molecular weight of about 65,000, as determined by gel filtration. It was inactivated by reduction of disulfide bonds, or by exposure to pH below 5.5, to NaCl concentration below 0.05 M, to 65 degrees C for 30 min, or to 100 degrees C for 10 min. Although it resembles the human platelet-derived mitogen platelet-derived growth factor (PDGF) in several of its properties, it differs in others. Hence the hepatocyte growth factor from rat platelets, which accounts for 50% of the DNA synthesis-stimulatory activity of rat serum, appears to be a distinct entity.

Biological properties of a hepatocyte growth factor from rat platelets.

In an accompanying communication we demonstrated that about half of the potency of rat serum to stimulate DNA synthesis in cultured adult rat hepatocytes resides in a polypeptidelike substance from the platelets. A lysate of rat platelets was able to restore the potency of platelet-poor rat serum, whereas a lysate of human platelets inhibited thymidine incorporation by the hepatocytes. Moreover, addition to these cultures of either highly purified human platelet-derived growth factor (PDGF) or human platelet factor 4 (PF-4) failed to influence DNA synthesis either alone or in the presence of rat or human platelet-poor serum, which is required for expression of PDGF activity. Unlike the human platelet factors, rat platelet lysate (RPL) was moderately active by itself and was augmented equally well by platelet-poor serum from either source. At concentrations below 5%, platelet-poor serum from hypophysectomized rats was as potent as that from normal rats in augmenting RPL activity. This suggests that, unlike PDGF, which is not activated by hypophysectomized rat serum, the hepatotrophic component of RPL does not require the presence of exogenous somatomedins for activity, but interacts instead with other plasma constituents or with somatomedins produced by the hepatocytes in vitro. Rat platelets do, however, appear to contain PDGF or its rat equivalent in addition to the hepatocyte growth factor, since if they are heated to 100 degrees C for 10 min, their ability to stimulate nuclear labeling in confluent BALB/c 3T3 cells is not impaired, while their ability to stimulate DNA synthesis in rat hepatocytes is destroyed. These studies indicate that the hepatocyte growth factor from rat platelets differs from PDGF in its biological as well as physical characteristics, but that rat platelets also contain PDGF or an equivalent substance.

Hepatocyte DNA replication: effect of nutrients and intermediary metabolites.

Isolated adult rat liver parenchymal cells maintained in serum-free medium are stimulated by insulin and epidermal growth factor (EGF) to undergo DNA synthesis. Pyruvate, lactate, and, to a lesser extent, several other intermediary metabolites strikingly enhance DNA synthesis both under serum-free culture conditions and in the presence of dialyzed rat serum. High concentrations (2-50 mM) of these low-molecular-weight metabolites are necessary to produce optimal stimulation. Both alanine (greater than 2 mM) and glutamine (greater than 4 mM) are inhibitory under similar conditions. Glucose, although not required for hepatocyte maintenance or stimulation in the presence of insulin and EGF, acts synergistically with pyruvate to enhance DNA synthesis in a complete mixture.