Changes in asthmatic patients' symptoms and lifestyles on institution of inhaled budesonide therapy

An open, multi-centre, general practice study was carried out in 1661 asthmatic patients to assess the efficacy, in terms of symptom relief and changes in lifestyle, of budesonide and to record objective lung function changes and any adverse events. After a 1-week run-in period on any pre-trial anti-asthma medication, patients received either 200 micrograms or 400 micrograms budesonide twice daily by metered dose inhaler for 4 weeks. Peak expiratory flow rate (PEFR) was measured by the doctor on entry, after the run-in, and at the end of the study and patients were asked to complete diary cards on a daily basis to record compliance, bronchodilator usage and the severity of cough, wheeze and sleep disturbance, and weekly to record 5 lifestyle assessments, e.g. physical activity. Analysis of data from the clinic visits and 1375 completed diary cards showed that PEFR increased significantly from 321 +/- 3 l/min at the end of the run-in to 368 +/- 3 l/min at the end of the trial; 77% of patients had an improved PEFR. Bronchodilator use decreased significantly from 4.2 +/- 0.1 times/day during the run-in period to 3.0 +/- 0.1 times/day at the end of the study; 65% of patients used less bronchodilator. Significant improvements were recorded in all the symptoms and lifestyle indices monitored; 76% of patients improved in at least 5 of the 11 assessments. Treatment-emergent adverse events occurred in 103 (6%) of patients: none was classified as serious or unexpected. No sub-group of patients was identified in which the results were at variance from the full sample. It is concluded that budesonide improves patients' lifestyle and ability to carry out normal activities, as well as improving PEFR and reducing bronchodilator use, in mild to moderately severe asthmatics treated in general practice.     

Hypoplasia of the cerebellar vermis in neurogenetic syndromes

There are conflicting reports on the relationship between cerebellar vermal lobule hypoplasia and autism. Using quantitative magnetic resonance image analysis, we measured the cerebellar vermis in 125 normal individuals with a broad age range and 102 patients with a variety of neurogenetic abnormalities. We conclude that hypoplasia of cerebellar vermal lobules VI and VII is a nonspecific finding that even occurs in several conditions without autistic behavior. This suggests that it is not a specific neuroanatomical marker for autism, nor is cerebellar dys- genesis likely to be solely responsible for clinical autistic behaviors.     

A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm-Horsfall protein and thrombomodulin

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesotheliomas. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulopapillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thromobomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours.     

Wegener granulomatosis: CT and MR findings.

PURPOSETo demonstrate the spectrum of CT and MR imaging findings in patients with Wegener granulomatosis and to determine how often these findings could be attributed to either direct extension from paranasal or orbital disease sites, remote granulomas, or central nervous system (CNS) vasculitis.METHODSWe retrospectively reviewed the CT or MR studies of 15 patients with Wegener granulomatosis.RESULTSAbnormal findings were seen in 7 patients (5 examined with MR imaging, 2 with CT). Findings included dural thickening and contrast enhancement (3 patients), infarcts (2 patients), regions of hyperintense signal on T2-weighted MR images (2 patients), and abnormal MR signal in the brain stem (2 patients). Three patients with imaging findings of dural enhancement and thickening were thought to have remote granulomatous lesions involving the dura. No patients had extension from sites external to the CNS or clinical findings suggestive of CNS vasculitis.CONCLUSIONThe spectrum of CT and MR findings in Wegener granulomatosis includes dural thickening and enhancements cerebral infarction, and MR signal abnormalities in the brain stem and white matter. Presumed remote granulomatous lesions were the most common causes of CNS findings in this study. Complications related to non-CNS disease (eg, hypertension, endocarditis) also appear to have played a role in some patients.     

Lens complementation system for the genetic analysis of growth, differentiation, and apoptosis in vivo.

A genetic approach has been established that combines the advantages of blastocyst complementation with the experimental attributes of the developing lens for the functional analysis of genes governing cellular proliferation, terminal differentiation, and apoptosis. This lens complementation system (LCS) makes use of a mutant mouse strain, aphakia (ak), homozygotes of which fail to develop an ocular lens. We demonstrate that microinjection of wild-type embryonic stem (ES) cells into ak/ak blastocysts produces chimeras with normal ES-cell-derived lenses and that microinjection of Rb-/- ES cells generates an aberrant lens phenotype identical to that obtained through conventional gene targeting methodology. Our determination that a cell autonomous defect underlies the aphakia condition assures that lenses generated through LCS are necessarily ES-cell-derived. LCS provides for the rapid phenotypic analysis of loss-of-function mutations, circumvents the need for germ-line transmission of null alleles, and, most significantly, facilitates the study of essential genes whose inactivation is associated with early lethal phenotypes.     

Novel antibiotic regimens against Enterococcus faecium resistant to ampicillin, vancomycin, and gentamicin.

Enterococci have emerged as significant nosocomial pathogens. Enterococci with resistance to commonly used antibiotics are appearing more frequently. We encountered at our institution several infections caused by Enterococcus faecium with high-level resistance to ampicillin, vancomycin, and gentamicin. The optimal antibiotic therapy for serious infections with unusually resistant enterococci has not been established. Using time-kill studies, we tested the effectiveness of various antibiotic combinations against 15 isolates of multidrug-resistant enterococci. No antibiotic was consistently effective when used alone. The combination of ampicillin plus ciprofloxacin was bactericidal for the 12 isolates for which the ciprofloxacin MIC was < or = 8 micrograms/ml. The combination of ciprofloxacin plus novobiocin also demonstrated activity against these isolates. No combination was found to be bactericidal for the remaining three isolates, which were highly ciprofloxacin resistant. These antibiotic combinations may be important for the future treatment of serious infections caused by these resistant pathogens.     

Bilateral Ulnar Agenesis: Case Report and Review of the Literature

Bilateral ulnar agenesis is a rare abnormality. A total of 36 cases are analyzed: 35 of these are documented in the literature and 1 stillborn male is presented in this study. Most patients had one of the three conditions: Al-Awadi/Raas-Rothschild syndrome, syndrome of ulnar aplasia with split hand/split foot deformity, or the Brachmann—de Lange syndrome. Fifty percent of all cases with bilateral ulnar agenesis were associated with lower limb defects and these cases, for the most part, also belonged to the aforementioned syndromes. Nonskeletal, internal organ malformations were identified in 34% of all patients. Nine patients presented with isolated bilateral ulnar agenesis. The Al-Awadi/Raas-Rothschild syndrome and the split hand/split foot deformity are heritable disorders. There was no evidence for genetic etiology in most of the other cases. Bilateral ulnar agenesis in our fetus was part of the Brachmann—de Lange syndrome with associated cardiac defect, diaphragmatic hernia, and umbilical artery agenesis.     

Proliferative activity of mast cells in allergic nasal mucosa

The proliferative activity of mast cells in the nasal mucosae of allergic (n= 14) and non-allergic (n= 18) rhinopathic patients was studied by a sequential double immuno-histochemistry using anti-proliferating cell nuclear antigen (PCNA) and anti-tryptase antibodies. Two hundred to 300 tryptase-positive cells (mast cells) were studied in each allergic nasal epithelium. In case of non-allergic nasal mucosa, only a few mast cells existed in the epithelial layer. The total number of mast cells which we could detect in all patients was 168 cells. One of these cells contained PCNA. Three hundred to 500 mast cells were studied in each subepithelial layer and deep layer of lamina propria of both diseases. PCNA-positive mast cells were observed in the nasal epithelia of 10 allergic patients. In the subepithelial layer, PCNA-positive mast cells were observed eight allergic patients and four non-allergic patients, respectively, In the deep lamina propria, PCNA-positive mast cells were observed in a few patients with both diseases. The percentage of PCNA-positive mast cells of all mast cells each area ranged from 0 to 1.7%. The incidence of PCNA-positive mast cells was statistically higher in the allergic epithelium and subepithelial layer than in the deep layer of lamina propria. Moreover, that of PCNA-positive mast cells in the subepithelial layer was higher in allergic than in non-allergic nasal mucosa. Our results suggest that mast cell proliferation may contribute to the number of mast cells in the nasal epithelium and subepithelial layer of allergic patients.