Synthese neuer Indolmethanamine durch Leimgruber-Batcho Reaktion

Synthesis of New Indolemethanamines Using the Leimgruber-Batcho Reaction A short and efficient synthesis of the title compounds is reported starting with commercially available carboxylic acids 1 and 5 , respectively. By appropriate modifications in the course of the Leimgruber-Batcho reaction used in the key step quite stable 1-hydroxy-indole derivatives became available.     

Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m²) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apprarent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor.     

Sympathetic reinnervation after heart transplantation, assessed by iodine-123 metaiodobenzylguanidine imaging, and heart rate variability.

OBJECTIVE: Complete allograft denervation occurs during heart transplantation. Partial ventricular sympathetic reinnervation may develop one year or later after transplantation and can be measured with iodine-123-meta-iodobenziylguanidine (MIBG) uptake. Aim of this study was to assess sinus node sympathetic reinnervation measured with heart rate variability and ventricular sympathetic reinnervation evaluated with MIBG. METHODS: Twelve patients and 14 healthy controls were included. In patients, MIBG scintigraphy with early and late imaging was performed. Heart to mediastinum ratio (HMR) was calculated and patients were divided in groups with (HMR>1.3) and without left ventricular reinnervation (HMR<1.3). Bipolar ECG with high sampling rate and resolution was recorded over 8.5 min in supine position and in upright position after 10 min interval. R-R intervals in time domain and heart rate variability in frequency domain through spectral power analysis of R-R intervals were analysed to evaluate sinus node reinnervation. Spectral power in low frequency range (0.04-0.15 Hz) above 4.5 ms(2) was considered as sinus node sympathetic reinnervation. RESULTS: Six (50%) patients had evidence of left ventricular sympathetic reinnervation on scintigraphy. Sinus node sympathetic reinnervation based on heart rate variability was detected in 6 (50%) patients in supine, and in 4 (33%) patients in upright body position. Four patients groups were discerned: (1) with ventricular and sinus node sympathetic reinnervation, (2) with sinus node sympathetic reinnervation, (3) with ventricular sympathetic reinnervation and (4) without atrial or ventricular sympathetic reinnervation. Ventricular reinnervation process was time dependent and sinus node reinnervation was not. CONCLUSIONS: Simultaneous ventricular sympathetic reinnervation assessed by MIBG and sinus node sympathetic reinnervation assessed by heart rate variability in supine as in upright position were detected only in two patients (17%). The results of our study show that eventual sinus node sympathetic reinnervation and left ventricular sympathetic reinnervation do not occur simultaneously.     

Management of status dystonicus: our experience and review of the literature.

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.     

Hand hygiene and glove use behavior in an Italian hospital.

In an Italian hospital, we observed that hand hygiene was performed in 638 (19.6%) of 3,253 opportunities, whereas gloves were worn in 538 (44.2%) 1,218 of opportunities. We observed an inverse correlation between the intensity of care and the rate of hand hygiene compliance (R2=0.057; P<.001), but no such association was observed for the rate of glove use compliance (R2=0.014; P=.078). Rates of compliance with hand hygiene and glove use recommendations follow different behavioral patterns.     

Nasal lavage leukotrienes in infants with RSV bronchiolitis

Respiratory syncytial virus (RSV) bronchiolitis is a very common infection in infants and, after the acute phase, a number of patients develop a reactive airway disease that lasts for years. Although the pathogenesis of the lung damage after RSV bronchiolitis is still largely unknown, previous studies suggest that leukotrienes may play an active part in it. The aim of this study was to measure leukotriene levels in the nasal lavage fluid (NLF) collected in infants during RSV bronchiolitis and 1 month later. Cysteinyl leukotrienes (Cys-LTs) and leukotriene B(4) (LTB(4)) were measured in the NLF of 22 infants with their first episode of RSV bronchiolitis and 16 healthy infants. A second NLF sample was collected to measure leukotriene levels 1 month after the acute disease. NLF Cys-LT levels were significantly higher in infants with RSV bronchiolitis than in healthy controls [950 pg/ml (285.5-2155.9) vs. 110.5 pg/ml (66.5-451.3), p = 0.01], and they remained so a month after the acute infection (p = 0.02). A subanalysis showed no difference in Cys-LTs concentrations, either between bronchiolitis infants with and without a family history of atopy, or between those with and without passive exposure to cigarette smoke. No significant difference was found between the LTB(4) levels measured in the bronchiolitis cases and the control children. Cys-LTs are significantly increased in the NLF of infants with acute RSV bronchiolitis, and remain so at 1-month follow-up, suggesting a possible role of these eicosanoids in the pathogenesis of the disease.     

Cervical bruits: clinical correlates of stenosis

To analyze the relationship among characteristics of buits, degree of underlying stenosis, and neurologic symptom complexes, the authors studied 157 patients with bruits undergoing digital subtraction angiography. Symptom status assignment (definite lateralizing, possible lateralizing, vertebrobasilar, diffuse, and asymptomatic) and cervical auscultation for location, duration, and other bruit characteristics were performed independently. Bruit occurrence was associated with stenosis of greater than or equal to 50% of the underlying vessel with the association being no stronger at higher levels of stenosis (greater than or equal to 80%). No relationship existed between the side of bruit and side of symptoms in those with lateralized symptoms. The authors found more severe degrees of carotid stenosis in two symptomatic groups (vertebrobasilar insufficiency [VBI] and definite lateralized) compared with asymptomatic patients. Those with VBI had more high-grade stenosis, whereas those with lateralized symptoms had more occlusions, which tended to be ipsilateral to the symptoms.     

Mortality study of asbestos cement workers

The present study describes cause-specific mortality of asbestos cement workers in the Emilia Romagna region of Italy. The cohort included workers in ten factories, most of which started operating between 1955 and 1965. Asbestos, mainly chrysotile, constituted 10%–20% of the dry component of the mixture. Crocidolite range between 5% and 50% of total asbestos. Asbestos concentrations up to 44 ff/cc were reported prior to 1975, while in recent years they have usually been below 0–1 ff/cc. The cohort included 3341 workers who had at some time been employed in the ten factories under study. Their mortality experience was compared with that of the population resident in Emilia Romagna. Vital status was ascertained at 1989. Seventy-three subjects were lost to followup (2.2%). Mortality from all causes and from all types of cancer was increased in the cohort. Malignant neoplasms of the respiratory tract showed a significant increase (SMR: 134; 90% confidence interval: 101–175; 40 observed) due to lung cancer (SMR: 124; 90% confidence interval: 91–166; 33 observed) and neoplasms of the pleura, mediastinum, and other parts of the respiratory tract (SMR: 602; 90% confidence interval 237–1267; 5 observed). The discrepancy between observed and expected mortality mainly concerned subjects with at least 20 years of employment in the factories. Five more cases of histologically confirmed mesothelioma occurred after the end of follow-up.     

Comparing different methods for homocysteine determination.

Slightly elevated values of homocysteine are commonly associated with thromboembolic diseases, while high values can be found in patients with congenital metabolic defects or nutritional problems. The clinical use of homocysteine as an independent marker of cardiovascular disease was limited in the past by technical problems with its measurement, the instrumentation (HPLC, radioenzymatic assays, gas chromatography-mass spectrometry, etc.) and the necessary skills required. Commercially available immunoassays now permit a simpler and more rapid measurement of homocysteine, that is more suitable for routine clinical laboratories; in this paper we analyze the results obtained by using three fully automated methods for homocysteine determination (Abbott IMx immunoassay, Abbott AxSYM immunoassay and Immulite 2000 homocysteine immunoassay) and their correlation with the widely used HPLC method. The results clearly indicate that all three automated immunochemical methods correlate well with the HPLC method (slope 0.97-1.03; intercept 0.95-1.91 with a recovery above 95% for all three methods).     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.