Reduction in oral corticosteroid use with mometasone furoate dry powder inhaler improves health-related quality of life in patients with severe persistent asthma.

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 microg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI-treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI-treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p<0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.     

Technetium-99-labelled methylene diphosphonate uptake scans in patients with dialysis arthropathy

Patients on long-term haemodialysis suffer from dialysis arthropathy due to the deposition of dialysis amyloid. We investigated the use of 99Tc-labelled methylene diphosphonate bone scans in 17 patients as a possible in vivo diagnostic technique. In most clinically affected joints, with the exception of shoulders and hands, there was increased radioisotope uptake consistent with uptake by periarticular bone. In addition, we describe intense soft-tissue uptake around some clinically affected large joints. In contrast, control groups of patients on haemodialysis without arthropathy and patients without renal failure did not have increased uptake. A semi-quantitative scale of uptake was devised, and the following correlations were significant: pain perception and isotope uptake score in the ankles and feet, and the number of radiological lesions and isotope uptake scores in the wrists and knees. The following sites where the radioisotope might bind in the affected joints are proposed: amyloid deposits, areas of soft-tissue calcification, or areas of increased bone turnover. It is concluded that whereas the scanning technique cannot make a definite diagnosis of amyloid and, therefore, cannot be expected to supersede histological diagnosis, it is a useful adjuvant investigation, of particular importance in those patients unable or unwilling to undergo biopsy.     

2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

Hippocampal nerve growth factor levels are related to spatial learning ability in aged rats.

Brain nerve growth factor (NGF) was determined in two groups of aged rats: 'good' and 'poor' performers. The animals were selected out of a population of 40 aged rats (26-28 months old) trained in a spatial learning task. Animals performing well in the test had significantly higher NGF in the hippocampus when compared to 'poor' performers. No differences in the levels of NGF were found in the cortex, septum and cerebellum. The results implicate hippocampal NGF in cognitive functioning of aged rats, and suggests that the forebrain cholinergic neuronal atrophy which has been observed in cognitively impaired aged rats may be due to reduced availability of target-derived NGF.     

Macroglossia and amyloidoma of the buttock: evidence of systemic involvement in dialysis amyloid

A 48-year-old male on cuprophane haemodialysis for 18 years, with a history of dialysis arthropathy and recurrent carpal tunnel syndrome developed macroglossia and bilateral buttock tumoral masses. The tongue and buttock masses were biopsied. Histology of both biopsies showed amyloid deposits of the beta 2-microglobulin (B2M) variety. Amyloidomas in the gluteal region and macroglossia have not been previously described in amyloid derived from B2M. These findings suggest that systemic B2M amyloidosis can have a similar tissue distribution to AL amyloidosis. This case also stresses the importance of inspection of the tongue, and palpation of the gluteal region for masses, in the assessment of patients with dialysis arthropathy.     

Spinal cord injury and the stress protein response

The heat shock or stress response is a highly conserved primary cellular response to injury. Synthesis of stress proteins (also called "heat shock proteins") is an integral component of this response. Protection from various forms of sublethal stress following increased production of stress proteins has been demonstrated in a number of systems, including the retina. This immunocytochemical study demonstrates the synthesis, accumulation, and redistribution of the 70-kD stress protein following spinal cord injury in rats. The observations confirm that stress protein production is a fundamental feature of the molecular response of the spinal cord to injury, and raise the possibility that augmentation of this response could enhance posttraumatic neuronal survival.     

Small vessel vasculitis caused by hepatitis B virus immune complexes: Small vessel vasculitis and HBsAg

In a comprehensive study of 80 patients with vasculitis, 4 had concurrent hepatitis B virus (HBV) infection. Polyarteritis nodosa was present in 2 and in the other 2, cutaneous vasculitis, presenting clinically as palpable or Henoch-Schönlein purpura. In one of these patients skin biopsies demonstrated granular deposits of IgM, C3, C4, and the hepatitis B surface antigen (HBsAg) and electron-dense deposits of aggregated 20-nm particles resembling HBsAg in postcapillary venules. Evidence for circulating HBsAg-immune complexes included increased serum C1q binding activity, decreased serum complement, and a cryoprecipitate containing both HBsAg and IgM anti-HBs. Aggregated 20-nm particles resembling intact HBsAg were also seen by negative staining electron microscopy of the serum cryoprecipitate. This patient fulfills all the criteria for a specific immune complex vasculitis caused by his immune response to a chronic HBV infection. These findings emphasize that HBV infection may be associated with small vessel vasculitis as well as polyarteritis nodosa, mixed cryoglobulinemia, and glomerulonephritis. A similar immune response to other viral infections may be expressed as palpable (Henoch-Schönlein) purpura also.     

Contraindications to lumbar puncture as defined by computed cranial tomography.

Papilloedema is not always an adequate predictor of potential complications from lumbar puncture, and many clinicians are using computed tomography (CT) before lumbar puncture in an effort to identify more accurately the "at risk" patient. This paper identifies the following anatomical criteria defined by CT scanning that correlate with unequal pressures between intracranial compartments and predispose a patient to herniation following decompression of the spinal compartment: lateral shift of midline structures, loss of the suprachiasmatic and basilar cisterns, obliteration of the fourth ventricle, or obliteration of the superior cerebellar and quadrigeminal plate cisterns with sparing of the ambient cisterns. These criteria should be considered to be contraindications to lumbar puncture.     

Dialysis arthropathy: complication of long term treatment with haemodialysis

Twenty eight patients who had received haemodialysis for more than 10 years were reviewed to establish the incidence of joint problems. Only six patients had no joint symptoms, one had avascular necrosis, one had had recent septic arthritis, and four had hyperparathyroidism. The remaining 16 patients had no evidence of hyperparathyroidism yet had an arthropathy causing pain and stiffness in many joints, particularly the shoulders. Ten of these 16 patients had a recurrent carpal tunnel syndrome requiring repeated surgical decompressions, which resulted in only partial improvement. Of the eight patients who had received dialysis for more than 15 years, seven had this "dialysis arthropathy" and six had recurrent carpal tunnel syndrome. Dialysis arthropathy is a common and often severe and disabling complication of long term treatment with haemodialysis. The cause is not known, but amyloid was found in a synovial biopsy specimen from one patient.     

Studies of 16-androstenes in an infant with virilizing adrenal carcinoma.

An 18-month-old girl with virilization was found to have an encapsulated right adrenal carcinoma (2 x3 cm) with great variation in nuclear size, frequent mitoses, and possible blood vessel invasion. Preoperative urinary excretions of 17-ketosteroids, androsterone, etiocholanolone, dehydroepiandrosterone, testosterone, pregnanetriol, 3alpha-androstenol, and 3 beta-androstadienol were elevated; all showed a noticeable decrease postoperatively. Cortisol acetate, given preoperatively, produced a definite decrease in the urinary excretion of 17-ketosteroids and dehydroepiandrosterone; administration of corticotropin resulted in an increase in levels of urinary 17-ketosteroids, 17-hydroxycorticosteroids, and pregnanetriol. Urinary testosterone and 3beta-androstadienol may have diagnostic value since neither was suppressed by cortisol therapy. The behavior of both 3alpha-androstenol and 3beta-androstadienol in this study suggests that they are of adrenal origin.