Hyperphosphataemia and related mortality.

Sir, With great interest we read the editorial review of Jean etal. [1] on the relationship between hyperphosphataemia and mortalityin end-stage renal disease patients. The authors summarize resultsfrom the large USRDS and DOPPS studies in which associationsof hyperphosphataemia and increased mortality risks were     

Sudden infant death, Williams-Beuren-Syndrom oder beides?

SummaryThe Williams-Beuren syndrome is a genetic disorder caused by a deletion of the elastin gene mapped on chromosome 7 (7q11.23). This results in multi-organ malformation, mental retardation and generalised elastin arteriopathy, which can lead to cardiac and vascular complications and to sudden death. We present two cases in which a postmortem examination was initially carried out with the presumptive diagnosis of sudden infant death, but cardiac malformations and facial dysmorphisms were recognised that could confirm the diagnosis of Williams-Beuren syndrome. In both cases nearly the same pathological findings were seen in the heart and lungs by histological examination. We will discuss if these findings could have caused death and if they can confirm our presumptive diagnosis of a William-Beuren syndrome which could not be verified by a genetic investigation.     

Postoperative naproxen after coronary artery bypass surgery: a double-blind randomized controlled trial.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used after coronary artery bypass surgery (CABG), yet their effects have seldom been evaluated in randomized controlled settings. The aim of this study was to examine the efficacy and safety of a commonly used NSAID, naproxen. We hypothesized that naproxen would reduce postoperative pain following CABG without increasing complications. METHODS: Patients (N=98) undergoing primary CABG were randomized to receive naproxen (500 mg q12hX5 doses via suppository started 1h after operation, followed by oral 250 mg q8hX6 doses) or placebo. Standard analgesic and anti-emetic regimens were available to both patient groups. Interventions were double-blinded. Primary end-points were postoperative pain measured before and after chest physiotherapy by visual analog scale and pulmonary slow vital capacity (SVC). RESULTS: Baseline characteristics were equivalent between the two groups. Over the first 4 postoperative days, naproxen decreased pain by 47+/-17% on average before chest physiotherapy (P=0.034), and 44+/-13% after chest physiotherapy (P=0.0092). Patients who received naproxen also had better preservation of SVC over the first 4 postoperative days (mean loss of SVC from baseline: 2.1+/-0.1 vs. 2.5+/-0.1l, naproxen vs. placebo, P=0.0032). This was concomitant with a lower white blood cell count observed in naproxen patients (9.2+/-0.3 vs. 12.7+/-1.5x10(9)/l, naproxen vs. placebo, P=0.03). Patients who received naproxen had more chest tube drainage after 4h postoperatively, but there was no difference in the incidence or amount of transfusions. There was no difference in medication use, length of stay, or in the incidence of atrial fibrillation, azotemia, and other complications. CONCLUSIONS: Naproxen is an effective and low-cost adjunct for optimization of pain control and lung recovery after CABG. Its use may result in increased chest tube drainage, but no apparent increase in other complications.     

Radioanatomy of upper airways in flexion and retroflexion of the neck

Summary Ten flexion-retroflexion radiographs of the cervical spine (in lateral projection) were utilized to study anatomical configuration and topography of the upper air passages in these two positions. Measurement of AP diameters revealed narrowing in flexion and widening in retroflexion, being maximat at the region of the epiglottis, and minimal at the regions of larynx and trachea. The distance from the pharyngeal attachment of the skull-base, to the upper chest aperture proved to be markedly greater in retroflexion than in flexion. As the pharynx virtually does not change its length during these movements, it is drawn up (with respect to the upper chest aperture) in retroflexion, and pushed down in flexion, over a mean distance of 42 mm. The up and down movement of the upper part of the trachea is slightly less: 38 mm. No correction for radiological magnification of 15–20%.     

Preventing percutaneous absorption of industrial chemicals: the "skin" denotation

Percutaneous absorption has received comparatively little attention in occupational health, although this route of entry has repeatedly caused occupation-related intoxications. In practice, the evaluation of skin penetration rates is far from simple. Much evidence has been obtained from studies of chemicals used for cosmetics and topical therapeutics, but the information available on compounds encountered in occupational health is limited. The data obtained from experimental studies have confirmed that the concentration, type of vehicle, skin area, skin condition, and extent of occlusion are important factors in determining the degree of percutaneous absorption, but no general model has been developed. Also, too little is known about the basic chemical properties governing the rate of penetration. Thus, prediction is difficult and bound to be rather inaccurate. Current preventive practice follows the procedure used by ACGIH and is mainly based on a "skin" denotation in official listings of chemicals to which exposure limits have been allocated. The number of substances and groups of chemicals which have received skin denotation in 17 selected countries varies between 24 and 179 and a total of 275 are listed as a skin hazard in one or more countries; ACGIH lists 143. Thus, the denotation practice varies. As an unfortunate result of these discrepancies and the dichotomy of skin denotation, the absence of skin denotation may erroneously indicate that efforts to protect the skin are unnecessary. Thus, an evaluation of skin penetration potentials should be incorporated in occupational health practice as a supplement to the official denotations.     

Does the beneficial effect of HRT on endothelial function depend on lipid changes

OBJECTIVES: To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. METHODS: Hundred-and-five healthy postmenopausal women, aged 50-65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. RESULTS: Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: -0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: -18%; -7%), LDL-cholesterol with 23% (95% CI: -30%; -15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: -26%; -2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. CONCLUSIONS: The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.     

Antiinflammatory effects of second-generation leukotriene B4 receptor antagonist,SC-53228: Impact upon Leukotriene B4- and 12(R)-HETE- mediated events

Leukotriene B₄ (LTB₄) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] are proinflammatory products of arachidonic acid metabolism that have been implicated as mediators in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB₄ and 12(R)-HETE elicit a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 {7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxyl]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid}, a first-generation LTB₄ receptor antagonist, inhibited the chemotactic actions of LTB₄ when given orally with an ED₅₀ value of 1.7 mg/kg. The second-generation LTB₄ receptor antagonist, SC-53228 [(+)-(S)-7-(3-{2-(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl]phenoxy} propoxy)-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid], inhibited LTB₄-induced chemotaxis when given intragastrically with an ED₅₀ value of 0.07 mg/kg. Furthermore, SC-53228 inhibited 12(R)-HETE-induced granulocyte chemotaxis with an oral ED₅₀ value of 5.8 mg/kg. When dosed orally over a range of 0.03–100 mg/kg, SC-53228 gaveC _max plasma concentrations of 0.015–41.1g/ml. SC-53228 inhibited LTB₄-primed membrane depolarization of human neutrophils with an IC₅₀ value of 34 nM. As a potent LTB₄ receptor antagonist, SC-53228 may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, in which LTB₄ and/or 12(R)-HETE are implicated as inflammatory mediators.     

Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2

Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. USH is clinically and genetically heterogeneous with at least 11 chromosomal loci assigned to the three USH types (USH1A-G, USH2A-C, USH3A). Although the different USH types exhibit almost the same phenotype in human, the identified USH genes encode for proteins which belong to very different protein classes and families. We and others recently reported that the scaffold protein harmonin (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein network. Here, we investigated the relationship between the USH2 molecules and this USH1-protein network. We show a molecular interaction between the scaffold protein harmonin (USH1C) and the USH2A protein, VLGR1 (USH2C) and the candidate for USH2B, NBC3. We pinpoint these interactions to interactions between the PDZ1 domain of harmonin and the PDZ-binding motifs at the C-termini of the USH2 proteins and NBC3. We demonstrate that USH2A, VLGR1 and NBC3 are co-expressed with the USH1-protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells. In hair cells, these USH proteins are also localized in the signal uptaking stereocilia. Our data indicate that the USH2 proteins and NBC3 are further partners in the supramolecular USH-protein network in the retina and inner ear which shed new light on the function of USH2 proteins and the entire USH-protein network. These findings provide first evidence for a molecular linkage between the pathophysiology in USH1 and USH2. The organization of USH molecules in a mutual 'interactome' related to the disease can explain the common phenotype in USH.     

Comparison of immunofluorescence, enzyme immunoassay, and Western blot (immunoblot) methods for detection of antibody to human T-cell leukemia virus type I.

A total of 3,349 serum samples were screened by the immunofluorescence (IF) method for antibody to human T-cell leukemia virus type I (HTLV-I). Only 9 of 2,409 specimens from selected individuals, blood bank donors, patients with encephalitis-meningitis, and human immunodeficiency virus antibody-positive homosexual or bisexual men were reactive by IF. In addition, 940 serum samples from intravenous drug abusers were tested by IF and also by an HTLV-I enzyme immunoassay (EIA) method. Of these, 222 (24%) were positive for both HTLV-I and HTLV-II antigens by IF, and 191 of these 222 were also reactive in the HTLV-I EIA. Of the 31 IF-positive, EIA-negative serum samples, 20 exhibited optical density readings greater than or equal to 70% of the positive cutoff in the EIA, and 29 samples reacted with 1 or more bands in the Western blot (immunoblot) test. An additional 10 specimens that were EIA negative reacted only with HTLV-I by IF. Differences in staining morphology and in reactions on HTLV-I and HTLV-II antigens before and after absorption of the serum specimens with HTLV-I and HTLV-II-infected cell pellets revealed six distinct serological patterns by IF. These results indicate that infections by HTLV-I or by another closely related retrovirus(es) occur in California. Further studies utilizing statistically valid sampling methods are needed to estimate true prevalence rates among various groups. IF and Western blot tests should supplement the EIA method to maximize sensitivity and specificity of test procedures.