Outcome of open antireflux surgery as assessed in a Nordic multicentre prospective clinical trial. Nordic GORD-Study Group

OBJECTIVE: To evaluate the outcome of antireflux surgery in various hospitals in Scandinavian countries. DESIGN: Partly randomised controlled study, and partly open study. SETTING: Hospitals throughout Norway, Sweden, Denmark and Finland. SUBJECTS: 310 patients with chronic reflux disease and oesophagitis who were initially entered into a randomised controlled study of omeprazole and antireflux surgery. INTERVENTIONS: Total fundic wrap, partial fundoplication, or omeprazole. MAIN OUTCOME MEASURES: Control of symptoms at one year. RESULTS: 154 patients who had their symptoms of reflux completely controlled with omeprazole were initially randomised to have an open operation but 10 refused, leaving 144 for analysis. 34 patients who had only a partial response were also offered operation; 120/178 (68%) had a total fundic wrap, and 53 (30%) partial fundoplication. 6 patients had postoperative complications that required reoperation and 123 made a completely uneventful recovery. Reflux was controlled in most patients, and only 10 (6%) required further treatment with omeprazole. The outcome in those patients who only responded partially to omeprazole was similar to that in patients who had a complete response. CONCLUSION: The outcome of antireflux surgery throughout Norway, Sweden, Denmark, and Finland is good.     

An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic hyperkeratosis, and ichthyosis

It has been observed that the occurrence of respiratory complications and diarrhoea among measles cases has changed over time but this change has not been quantified. A study was carried out in the city of Gweru, Zimbabwe, to quantify these changes. Rates of respiratory complications and diarrhoea among measles cases were determined in each year for the period 1968-89. It was found that mean rates of respiratory complications and diarrhoea during 1968-78 were 17.2 per cent (95 per cent CI = 11.6-22.8) and 5.2 per cent (95 per cent CI = 0-11) respectively while during 1979-89, mean rates of respiratory complications and diarrhoea were 6.5 per cent (95 per cent CI = 1-12.1) and 16.4 per cent (95 per cent CI = 10.1-22.0) respectively. Analysis of variance (ANOVA) to determine the main effects and the interaction showed that the main effects were not statistically significant (F = 0.01, d.f.1,2 = 1,40, p = 0.935; and F = 0.13, d.f.1,2 = 1,40, p = 0.725 respectively) Meanwhile the interaction term of complications and period was statistically significant (F = 15.7, d.f.1,2 = 1,40, p < 0.001). It was concluded that a change in rates of respiratory complications and diarrhoea had occurred among measles cases. It is suggested that the increase in vaccination coverage in 1979-89 and the shift in age at infection to older age groups in the same period may have brought about this change through selective suppression of respiratory complications among measles cases.     

Optimization of conducting structures by using the homogenization method

Approximation and numerical realization of a class of optimization problems with control variables represented by coefficients of linear elliptic state equations is considered. Convergence analysis of well-posed problems is performed by using one- and two-level approximation strategies. The latter is utilized in an optimization layout problem for two conductive constituents, for which the necessary steps to transfer the well-posed problem into a computational form are described and some numerical experiments are given.     

Purification, gene cloning, targeted knockout, overexpression, and biochemical characterization of the major pyrazinamidase from Mycobacterium smegmatis

The pyrazinamidase from Mycobacterium smegmatis was purified to homogeneity to yield a product of approximately 50 kDa. The deduced amino-terminal amino acid sequence of this polypeptide was used to design an oligonucleotide probe for screening a DNA library of M. smegmatis. An open reading frame, designated pzaA, which encodes a polypeptide of 49.3 kDa containing motifs conserved in several amidases was identified. Targeted knockout of the pzaA gene by homologous recombination yielded a mutant, pzaA::aph, with a more-than-threefold-reduced level of pyrazinamidase activity, suggesting that this gene encodes the major pyrazinamidase of M. smegmatis. Recombinant forms of the M. smegmatis PzaA and the Mycobacterium tuberculosis pyrazinamidase/nicotinamidase (PncA) were produced in Escherichia coli and were partially purified and compared in terms of their kinetics of nicotinamidase and pyrazinamidase activity. The comparable Km values obtained from this study suggested that the unique specificity of pyrazinamide (PZA) for M. tuberculosis was not based on an unusually high PZA-specific activity of the PncA protein. Overexpression of pzaA conferred PZA susceptibility on M. smegmatis by reducing the MIC of this drug to 150 micrograms/ml.     

Quantitation of vancomycin and its crystalline degradation product (CDP-1) in human serum by high performance liquid chromatography

Mantle cell lymphoma (MCL) patients represent a difficult problem, sometimes to establish the diagnosis but mostly because of their refractoriness to standard lymphoma treatments. Which treatments to apply and to whom is not yet defined. In this study, we attempted to analyze the clinical features, to identify the major prognostic factors, and to evaluate the outcome of 121 MCL patients treated in our institution between 1979 and 1997. Clinical data, treatment modalities, and International Prognostic Index (IPI) score were evaluated. Median age was 63 years. Patients usually presented with advanced stage disease (87%), disseminated lymph nodes (57%), bone marrow involvement (79%), but with a good performance status (PS) (81%). Lymphocytosis >4000/microl and/or peripheral blood involvement was present in 36% of cases, and gastrointestinal disease in 18%. The t(11;14)(q13;q32) and/or bcl-1 rearrangement was detected in 47/57 studied cases. Median overall survival (OS) was 3.12 years and a longer survival was significantly associated with younger age (<70 years), good PS (<2), localized disease (stage I-II), fewer than two extra-nodal sites, absence of spleen or peripheral blood involvement, normal serum LDH and beta2-microglobulin levels, and hemoglobin level greater than 12 g/dl. However, the IPI failed to identify patients with longer OS and in a multiparametric analysis, only older age, hemoglobin less than 12 g/dl, poor PS, and blood involvement were associated with a poorer outcome. Treatment modalities had no impact on survival with 75% of patients relapsing or progressing. Our data showed that the poor outcome of MCL patients is mainly related to adverse patient characteristics, a highly disseminated tumor, and some unknown parameters associated with the refractoriness to standard therapy.     

CD45 (leukocyte common antigen) immunoreactivity in metastatic undifferentiated and neuroendocrine carcinoma: a potential diagnostic pitfall

Leukocyte common antigen (CD45/LCA) and keratin expression are generally mutually exclusive in diagnostic surgical pathology. CD45 reactivity is a reliable indicator of the hematolymphoid nature of a tumor, whereas keratin reactivity is typical of epithelial differentiation (carcinomas and some sarcomas). Some lymphomas, however, might lack detectable CD45 expression, whereas occasional ones might express keratins. CD45 immunoreactivity has been considered exquisitely specific for hematopoietic cells. We report three undifferentiated or neuroendocrine carcinomas that showed membrane-associated immunoreactivity for CD45 in addition to showing distinctive keratin cocktail (AE1/AE3) and epithelial membrane antigen reactivity (all cases); also, keratin 7 was demonstrated in one case and keratin 19 in another. Two cases were lymph node metastases of undifferentiated carcinomas, one of them from the lungs and the other of an unknown origin; the former case showed neuroendocrine features. The third case represented a pulmonary large-cell undifferentiated carcinoma. These cases were negative for lineage-specific leukocyte antigens and did not show clonal immunoglobulin heavy-chain gene rearrangements. Electron microscopic studies demonstrated desmosomes and keratin-like tonofilaments in all three cases, thus confirming the epithelial nature of these tumors. The exceptional membrane staining for CD45 seen in these undifferentiated carcinomas might be comparable to experimentally detected incorporation of leukocyte antigens into the cell membranes of nonleukocytic cells in a leukocyte-rich environment. This rare diagnostic pitfall should be considered in the diagnostic surgical pathology of undifferentiated tumors. It is best avoided by employing a panel of leukocyte and epithelial antigens and by use of electron microscopy, if possible.     

Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.     

Spontaneous thrombosis of a basilar artery traumatic aneurysm in a child

Traumatic aneurysms are rare and occur most commonly in young adults; however, the relative frequency in the pediatric population is high, owing to the low prevalence of congenital saccular aneurysms in children. Traumatic aneurysms typically involve the anterior circulation, and spontaneous thrombosis is uncommon; hence, surgery is usually necessary. We present a case of a posttraumatic aneurysm in a child that occurred after a fall from a large height and that spontaneously thrombosed.     

Lateral nucleus of the rat amygdala is reciprocally connected with basal and accessory basal nuclei: a light and electron microscopic study

Information flow within the intra-amygdaloid circuitry has been generally believed to be unidirectional rather than reciprocal, in which case sensory inputs entering the amygdala via the lateral nucleus would not be modulated by inputs from other amygdaloid regions. In the present study we extend our earlier findings which indicated that the lateral nucleus of the rat amygdala is reciprocally connected with the basal and accessory basal nuclei. The type of synaptic contacts made by these connections is also characterized at the ultrastructural level. An anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into the basal (n=22) or accessory basal nuclei (n=12) of the rat amygdala. The results demonstrate that the ventrolateral division of the lateral nucleus receives projections from the basal nucleus, while the medial division receives projections from the accessory basal nucleus. Electron microscopic analyses revealed that axons projecting from the basal nucleus formed both asymmetric and symmetric contacts within the ventrolateral division of the lateral nucleus, whereas axons projecting from the accessory basal nucleus to the medial division of the lateral nucleus formed only asymmetric synapses with their targets. These findings suggest that the lateral nucleus receives both inhibitory and excitatory intra-amygdaloid projections and indicate that information flow within the amygdala is not unidirectional as previously thought. The results of this study provide evidence that the early phase of sensory processing within the amygdala is already modified by inputs from other amygdaloid nuclei.