1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl- 1 piperazinyl)-3-quinoline carboxylic acids were prepared, Their structures were characterized by elemental analysis, IR, HNMR and MS spectra.Preliminary pharmacological tests indicated that some of compounds Ia～m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 μg/ml.     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Expression of ciliary neurotrophic factor (CNTF) in charcot‐marie‐tooth type 1A (CMT1A) disease

CMT1A patients bear the same genetic defect but often present with a wide range of clinical disability. Knowing the relationship between the phenotypic variability and other parameters, such as electrophysiological findings, age, gender, disease duration and environmental factors may be important for understanding the pathogenetic mechanisms underlying CMT1A. We studied 15 families and 7 sporadic cases affected by CMT1A (27 adults and 9 children) from the clinical, neurophysiological and genetic standpoint. A detailed patient history included: disease onset and progression, distribution of weakness, additional symptoms, life habits, genealogical tree, exposure to toxic substances, geographic provenance, instruction grade, job, use of drugs, and concurrent diseases. A questionnaire about diet was administered. The disability was evaluated by modified Rankin scale, deambulation index, functional independence measure and Barthel index. As previously reported, disease onset was in the first decade in 50% of cases and before the age of 20 years in 70% of cases. Severe disability was rarely observed, only 2 patients walking with a cane. No clear influence of gender over clinical severity was observed. Interestingly, genetic anticipation was observed in all the families. Data on the influence of environmental factors will also be presented.     

Contrast venography, the gold standard for the diagnosis of deep-vein thrombosis: improvement in observer agreement.

To determine whether the Rabinov-Paulin or the long-leg venography technique should be preferred in the diagnostic management of patients with clinically suspected deep-vein thrombosis, two independent experienced radiologists blindly assessed two different series of venograms of consecutive outpatients with clinically suspected deep-vein thrombosis. Venograms were obtained from two outpatient clinics of primary referral centres. In one centre the venograms were performed according to the technique of Rabinov and Paulin with the use of 100 ml of radiographic material and spot films of the calf, popliteal and more proximal veins. In the other centre, long-leg films were obtained after the administration of 150 ml of contrast material. The percentage venograms adjudicated as inadequate by at least one radiologist and inter-observer disagreement for both series were used as the main study outcome measures. Prior to the study, both radiologists agreed on the standardized criteria for a normal, abnormal and inadequate test result using a separate set of films. An inadequacy rate of 20% was found for the Rabinov-Paulin venography series (n = 123), whereas only 2% of the 126 long-leg films were inadequate for interpretation (p less than 0.001). The inter-observer diagreement for inadequacy, presence or absence of deep-vein thrombosis was 21% for the Rabinov and Paulin venograms and 4% for the long-leg films (kappa, 0.65 and 0.92; 95% confidence intervals: 0.53 to 0.77 and 0.84 to 0.99, respectively; p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Criteria for evaluating the clinical and practical utility of models used by nurses

Arguably, nursing, like all health care disciplines, is an applied science. Essentially, this refers to the application of theory in order to understand and respond to the health problems of clients. These theories may be drawn (borrowed) from any applied science, or generated inductively from clinical nursing practice. Alternatively, nurses may attempt to apply deductive theory (global theoretical frameworks) known as nursing models. In this paper, all theoretical approaches, irrespective of origin, are referred to as models used by nurses. Thirteen criteria by which clinicians, and others, can evaluate the clinical and practical utility of models used by nurses which are expressed in the form of questions are identified and discussed. The criteria are an extension, both in detail and in number, of those developed by Reynolds and Cormack and subsequently applied by those writers to the Johnson Behavioural System Model of Nursing. The value, or otherwise, of individual models, or of models in general, will not be discussed in this paper. However, the authors propose that if the evaluation criteria described here are applied to existing models, serious deficits will be identified in relation to their clinical and practical utility.     

Hydrogen peroxide: effects on DNA, chromosomes, cell cycle and apoptosis induction in Fanconi's anemia cell lines

Fanconi's anemia (FA) is an inherited autosomal recessive syndrome; cells from FA patients are very sensitive to crosslinking agents and to oxygen. Epstein-Barr virus (EBV)-transformed lymphoblasts belonging to different FA complementation groups and normal EBV-transformed lymphoblasts were studied for their response to treatment with the oxidizing agent hydrogen peroxide (H2O2). The analysis of 8-hydroxy-2'-deoxyguanosine (8-OHdG) content in the DNA of untreated cells showed an increased basal level of damage in cells from the complementation groups FA-C and FA-E. H2O2-induced 8-OHdG was higher in FA than in normal cell lines. The removal of 8-OHdG after H2O2 treatment was significantly reduced in the cells from complementation group E. However, all FA cell lines showed a normal ability in the resealing of DNA breaks, at least soon after treatment. All cell lines were also equally efficient in the removal of damaged pyrimidines. Compared with normal cells, FA cell lines showed an increase in the baseline level of micronuclei, but not in the number of micronuclei induced by H2O2. Micronuclei in FA cells originated prevalently from chromosomal fragmentation and, at a minor extent, from chromosome loss. After H2O2 treatment, FA cell lines accumulated in G(2) phase to a greater extent than normal lymphoblasts. However, reversion of mutation in FA-A and FA-C cells did not result in the correction of this phenotype. In cells evaluated for apoptosis no ladder formation was found in FA-C, FA-E and corrected FA-C cells. In conclusion, among the FA cell lines examined, only FA-E showed a defect in the repair of H2O2-induced damage. On the other hand, differences found in the cell cycle and apoptosis might be due to irreversible changes occurring in FA cell lines as a consequence of the primary defect.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.