Which way for housing and human settlements?

In order to clarify the housing and settlements component of the European health-for-all programme and to identify perceived priorities with a view to the preparation of training materials, members of WHO's Rural and Urban Development and Housing Network were invited to complete a questionnaire. The results are reported below. The questionnaire can be used in identifying local development priorities, comparing attitudes, and studying perceived needs. Intended as a tool for policy-makers, course organizers and public health professionals, it is available from the authors of the present article.     

Exhaled nitric oxide in healthy children: Variability and a lack of correlation with atopy

Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme nitric oxide synthetase (NOS) and can be easily measured in exhaled air by chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines and endotoxin, NO is elevated in several chronic inflammatory airway diseases. Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway inflammation in daily routine, the role of possibly influencing factors such as age, time of the day, smoking exposure and intra-individual variability have to be clarified. NO concentrations were measured in 107 healthy children aged 4–18 years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were performed and a questionnaire on family history of atopy, personal symptoms of atopic disease and smoke exposure was completed. For intra-individual variability nitric oxide was measured in six children three times daily on 6 consecutive days. Median eNO concentration was 5.7 p.p.b., and increased significantly with age but did not vary with gender. No correlation was found between eNO and smoke exposure, positive skin-prick test, FEV ₁, MEF₂₅ and time of the day. There was no circadian rhythm found in the six children measured on 6 consecutive days, but the eNO showed an intra-individual coefficient of variation of 25.9%. With the help of a two-compartment model of the lung the alveolar NO concentration was estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the airway part of NO steadily increased with age. When comparing eNO values with standardized measurement techniques, the age of the children and the large intra-subject coefficient of variation have to be taken into account, whereas in healthy children subject-specific factors such as atopic history, gender and skin test reactivity did not affect eNO measurement.     

Intense vasoconstriction in response to aspirate from stented saphenous vein aortocoronary bypass grafts.

OBJECTIVES: We sought to identify soluble vasoconstrictor substances that are released during stent implantation into saphenous vein aortocoronary bypass grafts. BACKGROUND: Atherosclerotic saphenous vein aortocoronary bypass grafts are particularly vulnerable to plaque rupture. Protection devices prevent particulate debris from being embolized. Additional soluble vasoconstrictor substances possibly also contribute to impaired microvascular perfusion. METHODS: Peripheral venous blood (VB) and aspirate (AS) were obtained from 14 patients with a significant stenosis in a saphenous vein graft during stent implantation under protection with a distal balloon occlusion device. In five additional patients, arterial blood (AB) was also taken distal to the stented lesion before intervention. Vasomotor substances in VB, AB, and AS plasma were identified in a bioassay of rat mesenteric arteries with intact (+E) and denuded endothelium (-E). Vasoconstriction was normalized to that induced by potassium chloride depolarization (100%). RESULTS: Venous blood, AB, and AS plasma induced maximum vasoconstriction within six minutes. The AS plasma induced a vasoconstriction of 138 +/- 13% (-E) and 87 +/- 14% (+E); VB, of 70 +/- 14% (-E) and 23 +/- 4% (+E); and AB plasma obtained before intervention, of 49 +/- 9% (-E) and 36 +/- 8% (+E). The vasoconstrictor potency of AS plasma in endothelium-denuded vessels was related to the severity of anginal symptoms, angiographic stenosis severity, plaque volume, and plaque burden as determined by intravascular ultrasound. The AS plasma-induced vasoconstriction was largely attenuated by combined serotonin/5-hydroxytryptamine (5-HT)(2A/2C)- and 5-HT(1A/1B)-receptor blockade and eliminated by additional thromboxane A2 thromboxane-prostanoid (TP)-receptor blockade. CONCLUSIONS: Stent implantation releases, apart from and in addition to particulate debris, soluble vasoconstrictor substances that possibly contribute to impaired microvascular perfusion.     

Primary porcine proximal tubular cells as a model for transepithelial drug transport in human kidney.

BACKGROUND: Kidney proximal tubular cells play a major role in the transport of endogenous and exogenous compounds. A multitude of different transporters are expressed starting with multidrug ABC transporters (e.g. abcb1, abcc1-6), slc22a6-8 (organic anion transporters) and slc22a1-3 (organic cation transporters). For transport studies of renal drug transport, cell lines like MDCK and LLC-PK1 are often used to overexpress and study one or two transporters, such as abcb1 or abcc1-6. However, the use is limited since under physiological conditions xenobiotics are transported through different transporters at the same time. Therefore, a primary in vitro model expressing functionally different transporters simultaneously, as it is the case in vivo, would be of great benefit. METHODS: Primary proximal tubular cells were isolated from porcine kidney. Cells were cultured under selective culturing conditions leading to specific growth of primary proximal tubular cells. Expression of important proximal transporters was checked at mRNA level with RT-PCR, at protein level with immunocytochemistry and functionally by transport and uptake assays. RESULTS: A model of primary proximal tubular cells was established expressing the most important transporters: abcb1, abcc1, abcc2, slc22a8, slco1a2, slc15a1, slc5a2 and slc4a4. In freshly isolated cells, slc22a1 and slc22a6 were expressed, but were down-regulated in culture. Abcb1, abcc1, abcc2 and slc4a4 were detected at protein level with immunostaining. Functional activity was confirmed for abcb1, abcc1/2, slc22a8, slc15a1/2 and slc5a1/2. The tightness of the monolayers of this model was better than in previously established in vitro models. CONCLUSION: This primary cell culture model might be an interesting tool to investigate proximal tubular transport and to predict toxicity and drug interactions since it expresses functionally several transporters simultaneously.     

Hibernation, stunning, ischemic preconditioning--new paradigms in coronary disease?]

Myocardial ischemia has traditionally been characterized as an imbalance between energy supply and demand. In the initial seconds after a sudden reduction of coronary blood flow, myocardial energy demand most certainly exceeds the reduced energy supply. This temporary mismatch, however, is an inherently unstable condition because regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function of the acutely ischemic myocardium are still poorly understood. If some residual blood flow exists, a state of "perfusion-contraction matching" can be maintained without the development of irreversible damage. The metabolic status of such hypoperfused myocardium improves as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. The hypoperfused myocardium can respond to inotropic stimulation by dobutamine with increased function. The recruitment of an inotropic reserve implies increased energy utilization. In fact, the partially normalized lactate production is again increased, and creatine phosphate is decreased again. Apparently, the inotropic challenge once again precipitates a supply-demand imbalance which had been at least partially corrected by the ischemia-induced decrease of regional contractile function. A situation of chronic contractile failure in viable myocardium which normalizes upon reperfusion has been termed myocardial "Hibernation". Myocardial "Stunning" is characterized by a reversible post-ischemic contractile dysfunction despite full restoration of blood flow. The underlying mechanisms are not clear in detail. An inadequate energy supply and an impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (1) damage of membranes and enzymes by free radicals, (2) an increase in free cytosolic calcium during ischemia and reperfusion, and (3) a decrease of the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and "stunned" myocardium during intracoronary calcium infusion, postextrasystolic potentiation and the infusion of the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium. Interventions to reduce free radical formation or to increase their elimination attenuate myocardial stunning. Likewise, pretreatment with calcium antagonists before ischemia attenuates myocardial stunning. This effect is probably related to an attenuated myocardial calcium overload during early ischemia. The potential benefit from calcium antagonists when given after established reperfusion remains controversial.(ABSTRACT TRUNCATED AT 400 WORDS)     

Computed tomography in depression: association between ventricular size and psychopathology

The relationship between psychopathology and brain alterations, measured by computed tomography (CT), was investigated in 44 depressed patients. Comparisons of ventricle-brain ratio (VBR) between "endogenous" vs. "nonendogenous" subgroups, classified by six distinct diagnostic systems, revealed no significant differences. The VBR and the width of the third ventricle correlated significantly with scores on the Brief Psychiatric Rating Scale, the Global Assessment Scale, the Bech-Rafaelsen Melancholia Scale, the Rating for Emotional Blunting, and the Scale for the Assessment of Negative Symptoms, but not with scores on the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Item analyses of the Bech-Rafaelsen Melancholia Scale revealed that retardation-related items were most significantly correlated with ventricular size. The wider diameter of the third ventricle in psychotic patients was associated with higher scores on retardation in the psychotic subgroup, whereas the greater distances of both Sylvian fissures showed no relationship to psychomotor retardation. No significant correlations were found between CT values and anxiety, suicidal impulses, somatic complaints, and sleep disturbances.     

Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia

The brain serotonin-2A receptor (5-HT_2AR) has been implicated in both the pathology of schizophrenia and the therapeutic action of atypical antipsychotics. However, little is known about the 5-HT_2AR status before the onset of schizophrenia and before the exposure to antipsychotics. We used [¹⁸F] altanserin and positron emission tomography (PET) in a pilot study of 6 individuals suspected to be at elevated risk for schizophrenia and seven age-matched controls to test the hypothesis that regional 5-HT_2AR binding is altered in the prodromal stages of schizophrenia. Distribution volume ratios (DVRs) as a proxy for 5-HT_2AR availability were significantly reduced in prefrontal cortex regions of at-risk subjects, implicating early abnormalities of serotonergic neurotransmission that antecede the onset of schizophrenia.     

A Decline in C6 Antibody Titer Occurs in Successfully Treated Patients with Culture-Confirmed Early Localized or Early Disseminated Lyme Borreliosis

C₆, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C₆-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C₆ antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C₆ negative or had a ≥4-fold decrease in C₆ antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C₆ negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C₆ antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis.     

Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study

BACKGROUND: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent. OBJECTIVE: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study. METHODS: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background. RESULTS: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined. CONCLUSION: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.