Hepatitis C--associated glomerular disease in liver transplant recipients

Hepatitis C virus (HCV) infection may be associated with extrahepatic illness including renal disease. We investigated the clinical and virological characteristics of three patients who developed a mesangial proliferative and sclerosing glomerulopathy alone or in association with membranoproliferative glomerulonephritis after liver transplantation for end-stage liver disease secondary to HCV infection. Using polymerase chain reaction technology and the IgM RIBA assay, viral load, genotype and IgM antibody response to HCV in the setting of glomerulonephritis was evaluated. Within 1 year of transplantation, the patients showed decreased renal function, proteinuria and recurrent hepatitis C liver disease. Likewise, HCV viral load increased following transplantation, whereas the viral genotypes remained unchanged. Although the first patient presented with classic type II cryoglobulinemia in association with glomerulonephritis, the second patient developed an IgM directed specifically against the hepatitis C core antigen. The third patient developed a low-titered IgM directed against the hepatitis C core antigen with rheumatoid factor activity but without cryoglobulinemia. All of the patients show IgM in glomerular capillary walls by biopsy. One patient has shown a clinical response to interferon (IFN) alfa-2b therapy without evidence of hepatic allograft rejection. The second and third patients have not responded to IFN or developed hepatic rejection. This study suggests that HCV-associated glomerulonephritis may complicate liver transplantation in conjunction with the production of increased amounts of IgM of variable specificity. The posttransplant setting may provide a unique situation in which to investigate the specific requirements for the onset of renal disease.     

Erythropoietin for mobilization of circulating progenitor cells in patients with previously treated relapsed malignancies

A trial to determine the usefulness of recombinant human erythropoietin (rhEpo) as a mobilizing cytokine for patients with previously treated relapsed malignancies was performed. An initial peripheral stem cell apheresis collection was conducted during steady-state hematopoiesis for each patient to provide baseline data. rhEpo, 200 U/kg/day, was administered subcutaneously until the last apheresis procedure was completed. Immediately after the fourth daily dose of Epo, apheresis procedures were resumed and continued beyond five collections, when necessary, to accrue a total of 6.5 x 10(8) mononuclear cells (MNCs)/kg. Eight female and four male patients (median age = 44 years) were evaluated. Five to 14 (median = 8) apheresis procedures were performed for each patient. Toxicity attributable to Epo administration was negligible. Mobilization effects, as determined by an increase in the number of colony-forming units granulocyte/macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E) in the apheresis products after Epo administration, were observed in all patients. Nine patients received high-dose chemotherapy and Epo-mobilized peripheral stem cell transplantation (PSCT). Beginning the day of the transplant, GM-CSF was administered until neutrophil recovery was satisfactory. The median time to recover 0.5 x 10(9)/L granulocytes was 16 days after PSCT. Epo appears to have mobilization properties. Further studies are needed to determine the clinical usefulness of Epo as a mobilizing cytokine. The addition of Epo to other mobilizing cytokines may provide increased effectiveness without adding toxicity.     

Visual improvement as a function of time after lamellar keratoplasty for keratoconus

PEFR is a simple and reliable way of following patients with bronchial asthma and other obstructive airway diseases. Normal data is available for Caucasian and North Indian children but not for ethnic South Indian children. We, therefore, measured Peak Expiratory Flow Rate (PEFR) in 345 healthy South Indian children aged 4-15 years, using the Wright mini peak flow meter. A nomogram was constructed relating PEFR to height. Prediction equations for PEFR using height alone or height, age and weight were determined for both sexes. The prediction equation for boys based on height alone was PEFR = 4.08 height (cm)--284.55 and for girls was PEFR = 3.92 height (cm)--277.01.     

Hox9 genes and vertebrate limb specification

Development of paired appendages at appropriate levels along the primary body axis is a hallmark of the body plan of jawed vertebrates. Hox genes are good candidates for encoding position in lateral plate mesoderm along the body axis and thus for determining where limbs are formed. Local application of fibroblast growth factors (FGFs) to the anterior prospective flank of a chick embryo induces development of an ectopic wing, and FGF applied to posterior flank induces an ectopic leg. If particular combinations of Hox gene expression determine where wings and legs develop, then formation of additional limbs from flank should involve changes in Hox gene expression that reflect the type of limb induced. Here we show that the same population of flank cells can be induced to form either a wing or a leg, and that induction of these ectopic limbs is accompanied by specific changes in expression of three Hox genes in lateral plate mesoderm. This then reproduces, in the flank, expression patterns found at normal limb levels. Hox gene expression is reprogrammed in lateral plate mesoderm, but is unaffected in paraxial mesoderm. Independent regulation of Hox gene expression in lateral plate mesoderm may have been a key step in the evolution of paired appendages.     

Activities of vancomycin and teicoplanin against penicillin-resistant pneumococci in vitro and in vivo and correlation to pharmacokinetic parameters in the mouse peritonitis model

The activities of glycopeptides against pneumococci were studied in vitro and in vivo. The MICs of two glycopeptides, vancomycin and teicoplanin, in different media against 10 strains of pneumococci with different susceptibilities to penicillin were determined. The MICs of teicoplanin were four times lower than those of vancomycin in Mueller-Hinton media supplemented with 5% blood, but the MICs were similar in mouse and human sera supplemented with 5% blood. The serum protein binding levels in mouse and human sera were 90% for teicoplanin in both and 25 and 35%, respectively, for vancomycin. The MICs for vancomycin and teicoplanin were only correlated in human serum (P < 0.001). The single doses giving protection to 50% of the animals in the mouse peritonitis model after a lethal challenge of pneumococci, the ED50s, were similar for vancomycin and teicoplanin, between 0.1 and 1 mg/kg of body weight for all 10 strains. The log ED50s were significantly correlated only to the log MICs of teicoplanin determined for mouse serum with 5% blood (P = 0.01) and to the log MICs of vancomycin determined by the E test (P = 0.03). Among the pharmacokinetic parameters analyzed at the ED50s, the most constant parameter was the time for which the drug concentration exceeded the MIC (T(>MIC)) when each drug was considered separately; however, when both drugs were considered together, the maximum concentration of drug in serum (Cmax) varied the least. This indicates that both these parameters are of importance for predicting the effect of the drugs. We conclude that the effect of glycopeptides was not influenced by the penicillin resistance of the pneumococci, either in vitro or in vivo, and that the superior activity of teicoplanin over that of vancomycin in vitro was abolished in vivo, an effect which probably was due to the high serum protein binding of teicoplanin. Both the pharmacokinetic parameters T(>MIC) and Cmax are important predicting the effect of glycopeptides, but the pharmacodynamics of glycopeptides are still not completely elucidated.     

On the need for standardization in panic disorder treatment research: survey of the literature, 1980-1992

A retrospective literature survey (1980-1992) was conducted to chronicle the development of panic disorder treatment research. Based on a National Institute of Mental Health conference on assessment standardization in this area (Shear and Maser, 1994), the results and implications of the survey are presented in terms of eight domains of measurement recommended as essential for high quality research.     

All prepro-VIP-derived peptides, except PHI/PHV, are expressed in the female rat anterior pituitary and increased by estrogen

The expression of VIP precursor products: prepro-VIP(22-79), peptide histidine isoleucine (PHI), peptide histidine valine (PHV), prepro-VIP(111-122), VIP, prepro-VIP(156-170), and prepro-VIP mRNA in the anterior pituitary of estrogen-treated, ovariectomized rats, of ovariectomized controls, and of sham-operated controls was examined. Using radioimmunoassays based on antisera against each of the prepro-VIP sequences, we found that all sequences were expressed and markedly induced by estrogen, except PHI and PHV, which both were undetectable. By immunohistochemistry, it appeared that the number of cells immunoreactive for each of these sequences was increased in the estrogen-treated animals. However, PHI/PHV-immunoreactive cells could not be detected, despite the use of four different PHI antisera with different specificities. Estrogen treatment increased the prepro-VIP mRNA as judged by Northern blotting. In situ hybridization signals for both VIP mRNA and PHI mRNA were observed in few pituitary cells from control animals whereas strong positive signals were observed in a larger number of cells after estrogen treatment. The findings show that estrogen causes activation of the VIP gene expression in anterior pituitary cells, and that the absence of PHI and PHV probably is due to translational or posttranslational events.