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We report 12 cases of Fournier's Gangrene treated over an 19-month period; at Division Urology of the Hospital Gral. de Agudos Dr. José M. Ramos Mejia. We emphatized 58.3% of the patients had an urology origin. We considered diagnostic and therapeutic issues, and bibliografic review.
The African swine fever virus (ASFV) gene E165R, which is homologous to dUTPases, has been characterized. A multiple alignment of dUTPases showed the conservation in ASFV dUTPase of the motifs that define this protein family. A biochemical analysis of the purified recombinant enzyme showed that the virus dUTPase is a trimeric, highly specific enzyme that requires a divalent cation for activity. The enzyme is most probably complexed with Mg(2+), the preferred cation, and has an apparent K(m) for dUTP of 1 microM. Northern and Western blotting, as well as immunofluorescence analyses, indicated that the enzyme is expressed at early and late times of infection and is localized in the cytoplasm of the infected cells. On the other hand, an ASFV dUTPase-deletion mutant (vDeltaE165R) has been obtained. Growth kinetics showed that vDeltaE165R replicates as efficiently as parental virus in Vero cells but only to 10% or less of parental virus in swine macrophages. Our results suggest that the dUTPase activity is dispensable for virus replication in dividing cells but is required for productive infection in nondividing swine macrophages, the natural host cell for the virus. The viral dUTPase may play a role in lowering the dUTP concentration in natural infections to minimize misincorporation of deoxyuridine into the viral DNA and ensure the fidelity of genome replication.
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Apoptosis is a form of physiological cell death which can be initiated in response to various stimuli including virus infections. We show that vaccinia virus (VV) infection induces apoptosis in an immature B lymphocyte line, WEHI-231. In these cells, several VV-specific proteins were synthesized during the infection, but neither virus production nor viral DNA synthesis were detected. The intracellular levels of the proto-oncogene Bcl-2, which effectively protects cells from programmed cell death, were found to be down-regulated by the VV infection, suggesting that this down-regulation might be involved in the viral induction of apoptosis in WEHI-231 cells. Stable transfectants overexpressing human Bcl-2 were shown to be resistant to the apoptosis produced by the infection, a finding consistent with the proposed role for the down-regulation of endogenous Bcl-2 in VV-induced apoptotic death.
Acinetobacter sp. are gram-negative bacteria and usually resistant to multiple antibiotics. They are a customary cause of nosocomial infections, but are uncommon etiologic agents of endocarditis. We present a case of endocarditis caused by Acinetobacter iwoffi in a composite aortic graft with a St. Jude prosthetic valve, using the Bono and Bentall procedure, complicated with multiple graft dehiscenses causing first a peritube pseudoaneurysm and finally severe paraprosthetic valve regurgitation to the left ventricle which required emergency surgery.
The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% saturated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (< 10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrate, 38% fat (22% monounsaturated, < 10% saturated)]. At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT). Apo C-III genotype significantly affected basal glucose concentrations (P < 0.045) and insulin concentrations after the OGTT (P < 0.012). APOC3*S1/APOC3*S2 subjects (n = 13) had higher insulin concentrations after the OGTT than APOC3*S1/APOC3*S1 subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regression analysis showed that this polymorphism predicted the insulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest that the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sensitivity to insulin, especially when persons consume diets rich in saturated fat.
Lipid response to dietary fat is highly variable among individuals of a population. The aim of this study was to establish whether being overweight is one of the factors that determines this response. Forty-one non-obese healthy men were divided into two groups according to body mass index as follows: controls, <25 kg/m2; overweight, >25 kg/m2 but <30 kg/m2. After consuming a saturated fat-rich diet (SAT diet: 38% fat, 20% saturated) for 4 wk, subjects were switched to a low fat diet [National Cholesterol Education Program (NCEP)-I diet: 28% fat, 10% saturated] for 4 wk and then to a monounsaturated fat-rich diet (MUFA diet: 38% fat, 22% monounsaturated) for 4 wk. Data were analyzed by Student's t test and two-way ANOVA for repeated measures. After consuming the NCEP-I diet, the overweight subjects had a smaller decrease relative to the SAT diet period in plasma total cholesterol [-0.30 vs. -0.67 mmol/L (-7 vs. -16%), P < 0.02] and low density lipoprotein-cholesterol concentrations [-0.24 vs. -0.55 mmol/L (-9 vs. -21%), P < 0.04] than controls. However, in the overweight subjects, the MUFA diet produced a greater decrease in plasma triglycerides than in the controls relative to the SAT diet period [-0.36 vs. -0.03 mmol/L (-26 vs. -4%), P < 0.006] and to the NCEP-I diet period [-0.29 vs. 0. 01 mmol/L (-22 vs. 1%), P < 0.01). Plasma cholesterol concentrations changed to a lesser extent, and triglyceride concentration to a greater extent, in overweight but non-obese young men than in those of normal weight in response to changes in dietary fat composition. Our data suggest that in the diet treatment of obese hyperlipemic subjects, it is more important for them to lose weight than to change the fat composition of their diets.
An examination by electron microscopy of the viral assembly sites in Vero cells infected with African swine fever virus showed the presence of large clusters of mitochondria located in their proximity. These clusters surround viral factories that contain assembling particles but not factories where only precursor membranes are seen. Immunofluorescence microscopy revealed that these accumulations of mitochondria are originated by a massive migration of the organelle to the virus assembly sites. Virus infection also promoted the induction of the mitochondrial stress-responsive proteins p74 and cpn 60 together with a dramatic shift in the ultrastructural morphology of the mitochondria toward that characteristic of actively respiring organelles. The clustering of mitochondria around the viral factory was blocked in the presence of the microtubule-disassembling drug nocodazole, indicating that these filaments are implicated in the transport of the mitochondria to the virus assembly sites. The results presented are consistent with a role for the mitochondria in supplying the energy that the virus morphogenetic processes may require and make of the African swine fever virus-infected cell a paradigm to investigate the mechanisms involved in the sorting of mitochondria within the cell.
STUDY OBJECTIVE: We compared the long-term efficacy of the combination of colchicine and/or D-penicillamine with prednisone, in comparison to prednisone alone in patients with idiopathic pulmonary fibrosis (IPF). DESIGN: Nonrandomized prospective study in patients with IPF confirmed by biopsy specimen. SETTING: National Institute of Respiratory Diseases, Mexico. PATIENTS: Fifty-six IPF patients were included in this study. Patients received either colchicine/ prednisone (n=19), D-penicillamine/prednisone (n=11), D-penicillamine/colchicine/prednisone (n=11), or prednisone alone (n=15). Prednisone therapy was started at 1.0 mg/kg/d for 1 month followed by a biweekly taper to a maintenance dose of 15 mg/d. Colchicine was administered at a daily dose of 1.0 mg, and D-penicillamine was given at a daily dose of 600 mg. MEASUREMENTS AND RESULTS: Response to therapy was assessed by changes in lung function test results as measured by total and vital lung capacities, arterial blood gas analysis at rest breathing room air, and survival. No significant differences either in lung mechanics or in arterial gases were found in any group relative to the baseline measurement. Thirteen of the 56 patients died during the first 2 years, and 29 were dead at 5 years follow-up. Comparison of survival curves by Cox regression model showed no statistically significant difference among the four groups. Known side effects attributable to prednisone were more common and severe than those attributable to the other drugs. CONCLUSIONS: Our results suggest that neither colchicine nor D-penicillamine modified the progressive course of prednisone-treated IPF, and that the search for new drugs is imperative.
OBJECTIVE: The aim of this study was to observe whether the act of participation in a well-controlled clinical trial can, co-incidentally, modify the dyslipaemic patient's adherence to his/her diet. DESIGN AND SUBJECT: Food diaries of 55 men and 51 women (aged 46.4 +/- 10.6 and 55.8 +/- 12.1 years respectively) were analyzed at the beginning and the end of the double-blind stage of treatment (12 weeks). STATISTICS: Variance analysis and multi-variant analysis with repeated data by SPSS/PC statistical package. RESULTS: In neither sex were there any statistically significant differences between the start and end of the study with respect to the intake of energy, proteins, total lipids, carbohydrates, saturated fatty acids, polyunsaturated fatty acids, cholesterol, fibre and alcohol. CONCLUSIONS: Although in individual cases some changes in dietary awareness can occur, on a larger scale, the hypocholesterolaemic intervention trial induced no significant overall changes in the participants dietary/lifestyle patterns and, as such, augurs well for other such trials in which the effect of the therapy may sometimes be confounded by changes in the patients' life-style patterns coincidental to the act of participation in the trial.
An unusual postoperative complication of ulceration and hemorrhage during the postoperative period of a Nissen fundoplication in a patient with severe chronic periesophagitis is presented. In a review of the literature we could not find a similar report. The possible etiopathogenic mechanisms are discussed, and preventive measures are suggested.
African swine fever virus (ASFV) encodes a novel DNA polymerase, constituted of only 174 amino acids, belonging to the polymerase (pol) X family of DNA polymerases. Biochemical analyses of the purified enzyme indicate that ASFV pol X is a monomeric DNA-directed DNA polymerase, highly distributive, lacking a proofreading 3'-5'-exonuclease, and with a poor discrimination against dideoxynucleotides. A multiple alignment of family X DNA polymerases, together with the extrapolation to the crystal structure of mammalian DNA polymerase beta (pol beta), showed the conservation in ASFV pol X of the most critical residues involved in DNA binding, nucleotide binding, and catalysis of the polymerization reaction. Therefore, the 20-kDa ASFV pol X most likely represents the minimal functional version of an evolutionarily conserved pol beta-type DNA polymerase core, constituted by only the "palm" and "thumb" subdomains. It is worth noting that such an "unfingered" DNA polymerase is able to handle templated DNA polymerization with a considerable high fidelity at the base discrimination level. Base excision repair is considered to be a cellular defense mechanism repairing modified bases in DNA. Interestingly, the fact that ASFV pol X is able to conduct filling of a single nucleotide gap points to a putative role in base excision repair during the ASFV life cycle.
The aim of the study was to measure the changes in energy expenditure (EE) and respiratory quotient (RQ) induced by fever in children receiving total parenteral nutrition (TPN). Ten children aged 1-16 years (weight for height: 104.5 +/- 13%) were included. They underwent two EE recordings of 3 h duration using indirect calorimetry, during a febrile (38.9 +/- 0.5 degrees C) and afebrile conditions, after parameters (nutritional intake, ambient temperature) being equal. The EE, (febrile phase) was significantly higher than the EE(2) (afebrile) (2.13 +/- 0.48 vs 1.78 +/- 0.42 kcal/kg/h; P < 0.01). Increase in EE was significantly correlated with body temperature (r = 0.92, P < 0.001). The slope of the regression line indicates an increase of 16.2% in EE per degree of fever. By dividing the individual increase in EE by the individual increase in temperature, the energy expenditure during fever is 11.3% per unit rise ( degrees C). During the febrile phase urinary nitrogen excretion was significantly higher (280 +/- 90 vs 210 +/- 70 mg/kg fat free mass/day, P < 0.02). The RQ during the febrile phase (0.90 +/- 0.13) did not differ significantly from mean RQ during the afebrile phase (0.95 +/- 0.07). Fever due to infection or inflammatory process is partly responsible for an hypermetabolic state including increased EE.
BACKGROUND: Mithramycin, nogalamycin and aclacinomycins are aromatic polyketide antibiotics that exhibit antitumour activity. The precursors of these antibiotics are formed via a polyketide biosynthetic pathway in which acetate (for mithramycinone and nogalamycinone) or propionate (for aklavinone) is used as a starter unit and nine acetates are used as extender units. The assembly of building blocks is catalyzed by the minimal polyketide synthase (PKS). Further steps include regiospecific reductions (if any) and cyclization. In the biosynthesis of mithramycin, however, ketoreduction is omitted and the regiospecificity of the first cyclization differs from that of anthracycline antibiotics (e.g. nogalamycin and aclacinomycins). These significant differences provide a convenient means to analyze the determinants for the regiospecificity of the first cyclization step. RESULTS: In order to analyze a possible role of the minimal PKS in the regiospecificity of the first cyclization in polyketide biosynthesis, we expressed the mtm locus, which includes mithramycin minimal PKS genes, in Streptomyces galilaeus, which normally makes aclacinomycins, and the sno locus, which includes nogalamycin minimal PKS genes, in Streptomyces argillaceus, which normally makes mithramycin. The host strains are defective in the minimal PKS, but they express other antibiotic biosynthesis genes. Expression of the sno minimal PKS in the S. argillaceus polyketide-deficient strain generated mithramycin production. Auramycins, instead of aclacinomycins, accumulated in the recombinant S. galilaeus strains, suggesting that the mithramycin minimal PKS is responsible for the choice of starter unit. We also describe structural analysis of the compounds accumulated by a ketoreductase-deficient S. galilaeus mutant; spectroscopic studies on the major polyketide compound that accumulated revealed a first ring closure which is not typical of anthracyclines, suggesting an important role for the ketoreductase in the regiospecificity of the first cyclization. CONCLUSIONS: These experiments clearly support the involvement of ketoreductase and a cyclase in the regiospecific cyclization of the biosynthetic pathway for aromatic polyketides.
The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. The SstI polymorphism, arising from a cytosine to guanosine substitution in the 3' untranslated region of the APOC3 gene distinguishes between two alleles--S1 and S2. The S2 allele has been associated with elevated plasma triacylglycerol, cholesterol, and apolipoprotein (apo) C-III concentrations. In 90 young men we examined the effect of the same mutation on the response of low-density-lipoprotein (LDL) cholesterol to dietary monounsaturated fat. The frequency for the S2 allele was 0.14. Subjects were fed a low-fat diet for 25 d, followed by a diet rich in monounsaturated fatty acid (22% MUFA, 38% total fat) for 28 d; lipoproteins were measured at the end of each diet. There were no significant differences in initial total cholesterol between subjects with the APOC3*S1/APOC3*S1 (S1/S1) and APOC3*S1/APOC3*S2 (S1/S2) genotypes. After consumption of the diet high in MUFA, significant increases in LDL cholesterol (0.13 mmol/L, P < 0.027) were noted in the S1/S1 subjects whereas a significant decrease was observed in the S1/S2 subjects (-0.18 mmol/L, P < 0.046). Significant genotypic effects were seen for diet-induced changes in LDL cholesterol (P < 0.00034), total cholesterol (P < 0.009), and apo B (P < 0.0014). A study of the effect of the interaction between this mutation with that present in position -76 of the APOA1 gene promoter region (G/A) revealed that both mutations had an additive effect on changes in total cholesterol, LDL cholesterol, and apo B induced by diets. Plasma LDL-cholesterol responsiveness to the diet may be explained, at least in part, by variation at the APOC3 gene locus.
Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apoprotein (apo) A-IV has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. One mutation has been described in the apo A-IV gene that causes substitution of Ser for Thr at position 347. To study the influence of this mutation on the plasma LDL cholesterol (LDL-C) response in diets of various fat content and fatty acid saturation, 41 healthy male subjects were studied, 25 of whom were homozygous for the Thr allele (347Thr) and the rest who were either homozygous (n = 2) or heterozygous carriers of the Ser allele (347Ser). They consumed three consecutive diets, each of 4 weeks' duration: one rich in saturated fat (SFA diet: 38% fat, 20% saturated), a National Cholesterol Education Program (NCEP) type 1 diet (28% fat, 10% saturated), and a third rich in monounsaturated fat (MUFA diet; 38% fat, 22% monounsaturated). Carriers of the 347Ser allele presented a greater decrease in total cholesterol (-0.7 vs -0.44 mmol/L, P < .034), LDL-C (-0.62 vs -0.31 mmol/L, P < .012), and apo B (-14 vs -8 mg/dL, P < .01) levels when they were switched from the SFA to the NCEP type 1 diet than homozygous carriers of the 347Thr allele. The change from the NCEP type 1 to the MUFA diet resulted in a greater increase in total cholesterol (0.18 vs -0.05 mmol/L, P < .028) and apo B (5 vs -1 mg/dL, P < .006) levels in the 347Ser than in the 347Thr individuals. In a previous study, we demonstrated that the G-->A polymorphism at position -76 of the gene promoter of apo A-I affects the LDL-C response to dietary fat. We therefore decided to study the effect of the interaction between these mutations on this response. We found that both mutations have an additive effect on total cholesterol, LDL-C, and apo B dietary-induced changes. Our results suggest that total cholesterol and LDL-C response to dietary fat is influenced by the 347Ser mutation of apo A-IV.
Apolipoprotein B (apo B) plays a dominant role in cholesterol homeostasis. Several polymorphic sites within or adjacent to the gene locus for apo B have been detected. The X+ allele (XbaI restriction site present) of the XbaI restriction fragment polymorphism on the apo B gene has been found in some studies to be associated with higher serum cholesterol and/or triglyceride levels and with greater dietary response. The present study was designed to evaluate whether the apo B XbaI polymorphism was associated with the interindividual variability observed during postprandial lipemia. Fifty-one healthy young male volunteers [20 X-/X- (X-), and 31 X+/X- or X+/X+ (X+)], homozygotes for the apo E3 allele, were subjected to a vitamin A-fat load test. Subjects with the X- genotype had significantly greater retinyl palmitate (RP) and apo B-48 postprandial responses on both the large and the small TRL lipoprotein fractions compared with X+ subjects. In summary, subjects with the X-/X- genotype at the apo B locus have a greater postprandial response than X+ subjects. These differences observed in postprandial lipoprotein metabolism could explain some of the reported associations of this polymorphism to coronary heart disease risk.
We analyzed 36 open lung biopsy specimens from patients with chronic pigeon breeder's disease (PBD) to assess bronchiolar involvement and its relationship to the parenchymal pathologic abnormalities. Likewise, 21 biopsy specimens obtained from patients with usual interstitial pneumonia (UIP) were also examined. The bronchiolar abnormalities were scored by the method of Wright et al using a panel of photographs. In addition, the severity of lung fibrosis was evaluated in all samples and expressed as percentage in multiples of ten. A variable degree of epithelial cell metaplasia, bronchiolar inflammation and fibrosis, smooth muscle hypertrophy, extrinsic small airways narrowing, and intraluminal macrophages was observed in both diseases. Occasionally, hyperplasia of lymphoid follicles was also present. Bronchiolar changes were proportional in type and severity to the parenchymal damage. Spearman's nonparametric correlation between fibrosis in parenchyma and fibrosis in membranous bronchiole for the complete group (including patients with UIP and with PBD) showed a moderate but significant association (R = 0.51; p < 0.01). A significant association was also demonstrated when the score for bronchiolar fibrosis and inflammation was evaluated in relation to lung fibrosis divided in high degree (> 50%) and low degree (< 50%), respectively. In the case of patients with PBD, the correlation between bronchiolar and parenchymatous fibrosis was of 0.33 (p < 0.05). In general, bronchiolar fibrosis was less severe and inflammation more severe in PBD lungs compared with patients with UIP. Fibrosis in membranous bronchioles correlated with increased mortality in the complete group of patients, but the impact on mortality disappeared after correcting for overall fibrosis in the biopsy sample. Our findings demonstrate that a spectrum of bronchiolar lesions is usually observed in chronic PBD lungs, although the predominant pattern is similar to that found in the surrounding parenchyma, suggesting that the damage occurs in parallel.