Chronic HCV hepatitis with normal level of alanine transaminase: interferon therapy of active observation?

AIM: This study of trimetasidine effects on plasmic hemostasis and blood biochemistry in patients with chronic heart failure (CCF) of NYHA functional class II-III. MATERIALS AND METHODS: This study enrolled 30 patients (24 males and 6 females) aged 40-72 years with class II-III CCF, postinfarction cardiosclerosis and ejection fraction under 40%. Previously the patients received perindopril (the inhibitor of angiotensin converting enzyme) in daily dose 2-4 mg, on-demand digoxin and diuretics. Trimetasidine was given in a daily dose 60 mg for 6 months. Before and after the treatment the patients' blood was examined for: levels of factors VII and X of antithrombin III coagulation, soluble fibrinomonomeric complexes (SFMC), fibrinogen, glucose, uric acid, creatinines, total cholesterol, high density lipoprotein, triglycerides, AST, ALT, LDH, acid phosphotase, gamma-GT, sodium, potassium, activated partial thrombin time. RESULTS: Initially, the patients had a 23.9% increase in the levels of factors VII and X, a 14.3% decrease of antithrombin III, 29.8 and 227.6% rise in concentrations of fibrinogen and SFMC, respectively, compared to controls. Aftertreatment values of fibrinogen, factors VII and X, SFMC fell by 21.1, 17 and 35.5%, respectively. The thrombin time arose by 17.9% (p > 0.05). Insignificant inhibition was registered in the activity of acid phosphotase and gamma-GT. Glucose, AST, ALT, LDH levels remained unchanged. Plasma creatinine tended to lowering. Total cholesterol insignificantly increased at high levels of HDL cholesterol (p > 0.05) and reduced levels of triglycerides (p > 0.05). CONCLUSIONS: Trimetasidine therapy, given after conventional treatment with diuretics, digoxin, inhibitor of angiotensin-converting enzyme, aspirin has a beneficial effect in patients with circulatory deficiency through improving hemostatic and biochemical parameters.     

Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients

PURPOSE: To determine the value of pretransplant studies in predicting day 100 nonrelapse toxic mortality following high-dose therapy. PATIENTS AND METHODS: A retrospective review of 383 consecutive hematopoietic stem-cell transplants was performed with attention to toxic mortality and pretransplant factors. Univariate log-rank analysis was used to yield the most significant cut-off values for individual factors. Multivariate analysis using Cox proportional hazards regression determined factors independently predictive of early toxic death. RESULTS: Nonrelapse toxic mortality before day 100 occurred in 23 of 383 (6.0%) transplant recipients. Factors associated with an increased risk of toxic death by univariate analysis included forced expiratory volume in 1 second (FEV1) less than 78% of predicted (P = .0002), allogeneic versus autologous transplant (P = .0003), diffusion capacity of carbon monoxide less than 52% of predicted (P = .002), serum creatinine concentration greater than 1.1 mg/dL (P = .003), Eastern Cooperative Oncology Group performance status greater than 0 (P = .006), preparative regimen containing total-body irradiation versus chemotherapy alone (P = .006), marrow versus blood stem cell (P = .01), serum ALT greater than 50 IU/L (P = .02), diagnosis of hematologic disorder versus solid tumor (P = .06), serum bilirubin level greater than 1.1 mg/dL (P = .08), left ventricular ejection fraction (P = .09), and growth factor use (P = .09). In the multivariate model, transplant type (relative risk, 4.2), FEV1 (relative risk, 4.5), performance status (relative risk, 3.7), serum creatinine (relative risk, 3.8), and serum bilirubin (relative risk, 3.7) were found to be independent predictors of early toxic mortality. CONCLUSION: The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.     

Reticulum cell neoplasms of lymph nodes: a clinicopathologic study of 11 cases with recognition of a new subtype derived from fibroblastic reticular cells

Lymph nodes contain nonlymphoid accessory cells including follicular dendritic cells (FDCs), interdigitating dendritic cells (IDCs) and fibroblastic reticular cells (FBRCs). Neoplasms derived from FDCs are uncommon, and those of IDC origin are even more rare. We report the clinicopathologic features of 11 reticulum cell neoplasms, including 2 of FBRC origin. There were seven male patients and four female patients ranging in age from 13 to 73 years. All cases involved lymph nodes (cervical or supraclavicular-6 cases), (abdominal--2 cases), epitrochlear (1 case); two had more than one site of involvement (cervical lymph node and mediastinum--1 case, cervical and abdominal lymph nodes--1 case). One case of FDC tumor had concomitant Castleman's disease, plasma cell variant. Each neoplasm showed similar histology with oval-to-spindle-shaped cells in a storiform or fascicular pattern. Based on immunophenotypic findings, the neoplasms were classified as FDC (five cases), IDC (two cases), FBRC (three cases), and reticulum cell neoplasm, not otherwise specified (one case). The FDC tumors showed immunoreactivity for CD21 or CD35, vimentin, and CD68. The IDC tumors showed strong positivity for S-100 protein and variable positivity for CD68 and CD1a. The cases derived from FBRCs were positive for vimentin, desmin, and smooth-muscle actin. The neoplasm classified as reticulum cell neoplasm, not otherwise specified had similar morphologic features but showed only equivocal positivity for CD68 and vimentin. Follow-up was available for 9 of 11 (82%) cases with a mean of 3.5 years. Four of five patients with FDC tumors were alive with disease when last seen; the fifth is alive and well with no evidence of disease at 4-year follow-up. One patient with IDC tumor had a recurrence in a different nodal site. Two patients with FBRC tumor were disease free at follow-up of 2 years and 8 years, respectively. The patient with reticulum cell neoplasm, not otherwise specified, was alive and disease free 8 years after diagnosis.     

Molecular mapping with functional antibodies localizes critical sites on the human IL receptor common gamma (gamma c) chain

The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands.     

Response of serum cytokines in patients undergoing laparoscopic cholecystectomy

The clinical observation that a laparoscopic cholecystectomy is a minimally invasive operation has not been demonstrated on a biochemical basis. Interleukin-6, a known endogenous pyrogen and hepatocyte-stimulating protein, correlates with the significance of surgical trauma. Utilizing the IL-6 immunoassay, we studied this biochemical parameter of trauma to compare its response in laparoscopic vs open cholecystectomy. Sixteen patients who underwent only laparoscopic cholecystectomy showed peak IL-6 concentrations of 51 pg/ml (22-86) vs a peak IL-6 concentration of 124 pg/ml (56-225) for open cholecystectomy. Six additional patients who underwent an ERCP followed by laparoscopic cholecystectomy showed a dramatic rise in peak IL-6 concentration to 315 pg/ml (15-634). These results biochemically confirm the true minimal invasiveness of laparoscopic cholecystectomy. The findings in the ERCP-followed-by-laparoscopic-cholecystectomy group support the theory that two invasive procedures in close proximity may prime the cytokine system in its response to surgical trauma.     

A probability matrix for the identification of campylobacters, helicobacters and allied taxa

A probabilistic identification matrix for campylobacteria, comprising 76 phenotypic characters and 37 taxa, is described. The accuracy and integrity of the matrix was evaluated using established computer-assisted methods. Certain taxa (for example, Campylobacter concisus and Camp. gracilis) demonstrated significant phenotypic diversity; previous data corroborated these findings. Differentiation between a few pairs of taxa proved difficult, although discriminatory characteristics were noted in each of these cases. The results indicate that most campylobacteria can be identified accurately and objectively with phenotypic tests when probabilistic methods of data assessment are employed.     

Diagnostic value of antibodies to filaggrin in rheumatoid arthritis

OBJECTIVE: To determine the prevalence of antibodies to filaggrin in a cross sectional sample of patients with rheumatoid arthritis (RA). METHODS: Filaggrin from human skin was either extracted with 0.05% Nonidet P-40 and then partially purified by precipitating in ethanol and resuspending in water (Nonidet preparation) or extracted with 9 M urea and then purified by sequential fractionation on a DEAE Sephadex column and on a strong cation exchange column (purified preparation). Antibodies to filaggrin were detected using immunoblotting techniques with sera diluted 1:50. Antikeratin antibodies (AKA) were detected using indirect immunofluorescence microscopy on sections of rat esophagus. RESULTS: Antibodies to filaggrin were detected in 5 of 30 sera of patients with RA using filaggrin from the Nonidet preparation and 6 of 49 sera using filaggrin from the purified preparation. AKA were detected in 13 of 40 sera. A positive correlation existed between the presence of AKA and the presence of antibodies to filaggrin using the purified preparation (p=0.017). CONCLUSION: These data indicate that the reactivity of RA sera with filaggrin is not identical to the presence of AKA and is variable depending upon the preparation of filaggrin used. The diagnostic value of antibodies to filaggrin remains to be proven.     

Primary pneumococcal peritonitis complicated by exudative pleural effusion in an adolescent girl

A healthy, young adolescent girl developed primary pneumococcal peritonitis, an infection rarely reported in this age group in North America. Her course was further complicated by exudative pleural effusion and pneumonia despite receiving 10 days of clindamycin therapy. Laparascopy proved useful in making the initial diagnosis, but may have contributed to the pathogenesis of the pulmonary process. Case presentation, management, and etiology are discussed.     

The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4

The Transforming Growth Factor-beta superfamily member decapentaplegic (dpp) acts as an extracellular morphogen to pattern the embryonic ectoderm of the Drosophila embryo. To identify components of the dpp signaling pathway, we screened for mutations that act as dominant maternal enhancers of a weak allele of the dpp target gene zerkn?llt. In this screen, we recovered new alleles of the Mothers against dpp (Mad) and Medea genes. Phenotypic analysis of the new Medea mutations indicates that Medea, like Mad, is required for both embryonic and imaginal disc patterning. Genetic analysis suggests that Medea may have two independently mutable functions in patterning the embryonic ectoderm. Complete elimination of maternal and zygotic Medea activity in the early embryo results in a ventralized phenotype identical to that of null dpp mutants, indicating that Medea is required for all dpp-dependent signaling in embryonic dorsal-ventral patterning. Injection of mRNAs encoding DPP or a constitutively activated form of the DPP receptor, Thick veins, into embryos lacking all Medea activity failed to induce formation of any dorsal cell fates, demonstrating that Medea acts downstream of the thick veins receptor. We cloned Medea and found that it encodes a protein with striking sequence similarity to human SMAD4. Moreover, injection of human SMAD4 mRNA into embryos lacking all Medea activity conferred phenotypic rescue of the dorsal-ventral pattern, demonstrating conservation of function between the two gene products.