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Biomedical subjects

R Valenzuela

Publications and source records attributed to R Valenzuela.

At least 19 recordsLinked to original sources
PubMed2004

The impact of sildenafil citrate on sexual satisfaction profiles in men with a penile prosthesis in situ.

OBJECTIVE: To assess the efficacy of sildenafil in increasing penile glans tumescence and improving patient satisfaction in men with a penile prosthesis, as this remains a major treatment for erectile dysfunction but a common complaint is the lack of glans engorgement. PATIENTS AND METHODS: To determine whether sildenafil combined with a penile prosthesis improves satisfaction, patients used an implant alone for at least 1 month, after which they completed the International Index of Erectile Function (IIEF) questionnaire. The same patients were then given sildenafil citrate and completed the IIEF questionnaire after using the sildenafil/implant combination. RESULTS: Patients who responded to sildenafil with glans engorgement reported significantly greater satisfaction scores than with an implant alone. CONCLUSION: We currently offer sildenafil citrate after implantation to all men who have a penile prosthesis placed.

Adult↗
PubMed1999

Disease progression, adherence, and response to protease inhibitor therapy for HIV infection in an Urban Veterans Affairs Medical Center.

Indinavir therapy has demonstrated promise in the treatment of HIV-1 infection in clinical trials; however, its efficacy in a U.S. Veterans Affairs Medical Center, where access to therapy is generally unimpeded, is unknown. A review of the Miami cohort was conducted for the year beginning May 1996 to evaluate response to indinavir plus two nucleoside analogues. Of 483 HIV-1-positive patients (97% male; mean age, 46.7+/-9.7 years), 266 were offered indinavir based on their having CD4 counts <200 cells/microl or viral loads >10,000 copies/ml. Of these patients, 36% were adherent and experienced significant reductions in viral loads (-93,325+/-147,911 copies/ml) and elevations in CD4+ (111+/-103 cells/microl) and CD8+ (225+/-338 cells/microl) T cell counts. Adherent patients with baseline CD4 counts <100 cells/microl were 4.5 times more likely to have follow-up viral loads >10,000 copies/ml than those with CD4 >200 cells/microl. Adherent patients with CD4 counts <100 cells/microl did not show evidence of immune "exhaustion" because they were equal to those with CD4 counts >200 cells/microl in their capacity to replenish CD4 cells. Nonadherence to the regimen resulted in loss of therapeutic benefit and suggested that strategies to enhance adherence may become an essential component of treatment.

Adult↗
PubMed1999

High-affinity binding of fatty acyl-CoAs and peroxisome proliferator-CoA esters to glutathione S-transferases effect on enzymatic activity.

Acyl-CoAs are present at high concentrations within the cell, yet are strongly buffered by specific binding proteins in order to maintain a low intracellular unbound acyl-CoA concentration, compatible with their metabolic role, their importance in cell signaling, and as protection from their detergent properties. This intracellular regulation may be disrupted by nonmetabolizables acyl-CoA esters of xenobiotics, such as peroxisome proliferators, which are formed at relatively high concentration within the liver cell. The low molecular mass acyl-CoA binding protein (ACBP) and fatty acyl-CoA binding protein (FABP) have been proposed as the buffering system for fatty acyl-CoAs. Whether these proteins also bind xenobiotic-CoA is not known. Here we have identified new liver cytosolic fatty acyl-CoA and xenobiotic-CoA binding sites as glutathione S-transferase (GST), using fluorescent polarization and a acyl-etheno-CoA derivative of the peroxisome proliferator nafenopin as ligand. Rat liver GST and human liver recombinant GSTA1-1, GSTP1-1 and GSTM1-1 were used. Only class alpha rat liver GST and human GSTA1-1 bind xenobiotic-CoAs and fatty acyl-CoAs, with Kd values ranging from 200 nM to 5 microM. One mol of acyl-CoA is bound per mol of dimeric enzyme, and no metabolization or hydrolysis was observed. Binding results in strong inhibition of rat liver GST and human recombinant GSTA1-1 (IC50 at the nanomolar level for palmitoyl-CoA) but not GSTP1-1 and GSTM1-1. Acyl-CoAs do not interact with the GSTA1-1 substrate binding site, but probably with a different domain. Results suggest that under increased acyl-CoA concentration, as occurs after exposure to peroxisome proliferators, acyl-CoA binding to the abundant class alpha GSTs may result in strong inhibition of xenobiotic detoxification. Analysis of the binding properties of GSTs and other acyl-CoA binding proteins suggest that under increased acyl-CoA concentration GSTs would be responsible for xenobiotic-CoA binding whereas ACBP would preferentially bind fatty acyl-CoAs.

Acyl Coenzyme A↗
PubMed1998

Cohort size and maximum likelihood estimation of mortality parameters.

The purpose of this study was to investigate the effects of cohort size on maximum likelihood estimates of mortality parameters. Recent experimental investigations have stressed the importance of large cohorts for detecting leveling off of mortality rates at older ages. In the present study, emphasis was placed on evaluation of relatively small cohorts (about 150-300 individuals). Deaths were simulated under the assumption of the frailty mortality model. Two different parameter sets that resulted in differences in mean life span of more than twofold were used for simulations. Our smallest cohorts yielded parameter estimates that had generally good statistical properties, but relatively large standard errors. For tests of hypotheses concerning equality of parameters among populations or experimental treatments, empirical standard errors (obtained from several cohorts) were preferable to asymptotic standard errors (obtained for single cohorts). In particular, empirical standard errors yielded reliable type I error rates.

Cohort Studies↗
PubMed1997

Treatment of recurrent malignant glioma with BCNU-fluosol and oxygen inhalation. A phase I-II study.

OBJECTIVES: To evaluate the toxicity and response rate following BCNU with oxygen inhalation and escalating dosages of fluosol administered to patients with radiographic progression of malignant glioma after definitive surgery and radiotherapy. METHOD: This single arm, phase I-II multicenter trial, enrolled 99 patients with malignant gliomas recurrent after definitive surgery and radiotherapy. All patients received a fixed dose (200 mg/m2) of BCNU along with 100% oxygen and fluosol, a perfluorochemical. Fluosol doses were escalated between patients (150, 275, 400 and 600 ml/m2). Treatment was repeated every 6 weeks for a maximum of 6 cycles. Patients were assessed for toxicity at the time of infusion and sequentially thereafter. Response was evaluated clinically and radiologically at least every 6 weeks. RESULTS: Treatment was well tolerated. Dose reductions were required at least once in 18 patients, treatment delays were necessary at least once in 33 patients. Grade 3-4 leukopenia occurred in 6 patients (12 events), grade 3-4 thrombocytopenia in 10 patients (25 events) and grade 3-4 liver enzymes elevations in 18 patients (31 events). Higher fluosol dosages did not produce increases in toxicity or responses. Response or stabilization was seen in 57% (38% were stabilizations) of the patients who entered the trial with progressive disease. The median time to progression was 45 weeks, and median survival was 66 weeks for patients who had response or stabilization. For patients with glioblastoma response/stabilization was seen in 45% with a mean duration of 24 weeks, for patients with anaplastic astrocytoma response/stabilization was seen in 68% with a mean duration of 50 weeks. CONCLUSION: This treatment regimen is well tolerated. Our results suggest fluosol may enhance the effectiveness of BCNU for the treatment of recurrent malignant gliomas. Future studies will be performed using fluosol at the dose of 400 ml/m2.

Adolescent↗
PubMed1996

Successful renal transplantation in a patient with large granular lymphocytic leukemia with natural killer cell proliferation.

A patient with advancing renal failure attributed to focal segmental glomerulosclerosis was found to have marked NK (CD56+) cell expansion and large granular lymphocytic leukemia. Subsequent living-related renal transplantation was accomplished with two early bouts of acute cellular rejection requiring therapy with methylprednisolone and monoclonal antibody OKT3. Chronic triple drug immunosuppressive therapy has substantially reduced the marked NK (CD56+) proliferation. The renal transplantation remains successful after 15 months despite persistent but reduced numbers of circulating NK cells, the potential role of which in the pathogenesis of the underlying nephropathy or the cellular rejection process remains speculative.

Adult↗
PubMed1996

Late motor deficits of Chilean manganese miners: a blinded control study.

High-level chronic manganese (Mn) exposure produces dystonic rigidity and proximal tremor. The late effects of asymptomatic exposure are uncertain. To evaluate hand movements of asymptomatic Chilean miners, we utilized a manual tremormeter (EAP) and a digitizing tablet (MOVEMAP). In Andacollo, Chile, we examined 59 individuals aged > 50 years (mean age, 64.4 years). Twenty-seven exposed miners had heavy Mn dust exposure in Mn mines for more than 5 years (mean duration, 20.25 years), ending at least 5 years previously. Thirty-two control miners had never worked in Mn mines or had short-term Mn employment. Tests of resting tremor (EAP Tremormeter, MOVEMAP Steady paradigm), action tremor (MOVEMAP Square paradigm), and repetitive hand movements (EAP Tapping Test and Orthokinesimeter) differentiated performance of exposed miners from that of controls. Chronic asymptomatic Mn exposure results in detectable late-life abnormalities of movement.

Chile↗
PubMed1995

Comparative study of ELISA and indirect immunofluorescence for the detection of anti-neutrophil cytoplasmic antibodies. Evaluation of the SCIMEDX/EURO Diagnostica ELISA assay in a clinical setting.

This study evaluates the performance of a commercial ELISA assay for detection of anti-neutrophil cytoplasmic antibodies (ANCA). Anti-proteinase 3 (anti-PR3) and anti-myeloperoxidase (anti-MPO) ELISA by (SCIMEDX/EURO Diagnostica, Denville, NJ) were compared with the indirect immunofluorescence (IIF) method using ethanol-fixed neutrophils. Three hundred sixty serum samples were examined. There was complete correlation of results in 357 (99.2%) cases between cANCA pattern and anti-PR3 results, and in 356 (98.9%) cases between pANCA pattern and anti-MPO ELISA results. The specificity of ELISA for detection of vasculitis was 95.7% and sensitivity was 60%, whereas for IIF, they were 95.7% and 65%, respectively. The ELISA showed good reproducibility with interassay variation (CV), ranging from 7.1% to 13.2%. Our results show that SCIMEDX/EURO Diagnostica ELISA for ANCA is a reliable and reproducible method that is as good as IIF for detection of ANCA.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Lichen planus associated with neoplasia: a cell-mediated immune response to tumor antigens?

BACKGROUND: Individual case reports have suggested an occasional association of lichen planus with internal malignancy. OBJECTIVE: Our purpose was to describe five patients with a neoplastic disease in whom lichen planus developed. METHODS: Serologic and immunopathologic studies were conducted. RESULTS: No evidence of autoantibody production characteristic of paraneoplastic pemphigus was found, and antibodies reactive with basal cell keratinocytes were not detected. CONCLUSION: Lichen planus may be rarely induced by neoplasia. A cell-mediated immune reaction possibly causes this phenomenon.

Adenocarcinoma↗
PubMed1994

Diffuse intraepidermal deposition of immunoreactants on direct immunofluorescence: a clue to the early diagnosis of epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis is a distinctive disorder that is readily identified clinically and histologically in advanced cases. Early on, however, toxic epidermal necrolysis may be difficult to identify. Some consider fixed drug eruption a limited form of toxic epidermal necrolysis. METHODS: Direct immunofluorescence was performed on biopsy material of erythematous skin lesions. RESULTS: Diffuse deposition of immunoreactants in the midmalpighian layer was noted. This finding has not been encountered in other disorders studied in our immunopathology laboratory. CONCLUSIONS: Diffuse immunoreactant deposition in the mid-epidermis should suggest a diagnosis of epidermal necrolysis either from toxic epidermal necrolysis or fixed drug eruption. Additional cases will need to be assessed to document the usefulness of this pattern for prospective diagnosis.

Aged↗
PubMed1994

Induction, transcription, synthesis, and adsorption of interleukin-1 by dialyzer membranes.

This study was designed to dissect the direct effect of dialyzer membrane on interleukin-1 (IL-1) induction from those of complement activation, mechanical stimulation, acetate/bicarbonate and endotoxin diffusion, and cell type interactions. To this end, a suspension of P388D1 murine macrophages in a complement-free culture medium containing 10% heat-inactivated serum, a closed-loop system consisting of tubing alone or with a hollow-fiber cuprammonium cellulose (CU) or polyacrylonitrile (PAN) dialyzer, and a roller pump were used. The dialysate compartment was filled with the same medium and capped. Cell suspension was recirculated at 300 mL/min for 3 h. Cells and supernates were separated, and adhering proteins were eluted. All samples tested negative for endotoxin. IL-1 mRNA was greatest with CU, followed by PAN and tubing alone. IL-1 in the supernate was greater with CU than with either tubing alone or PAN (P < 0.005; analysis of variance), which showed comparable values. IL-1 eluted from loops was greatest with PAN dialyzers, followed by sets with CU dialyzers and tubing alone (P < 0.001; analysis of variance). Thus, both CU and PAN membranes directly induce IL-1. However, avid adsorption by PAN attenuates the rise in circulating IL-1.

Acrylic Resins↗
PubMed1994

Mouse antibody-coated lymphocytes during OKT3 therapy in liver transplantation.

Flow cytometry has been a technique in search of a use in transplantation. With each new monoclonal antibody, it has been hoped that the secrets of rejection would be unlocked. The usefulness of CD3+ T-lymphocyte counts to predict successful treatment of organ transplant rejection has been called into question. CD2+, CD3+, and mouse antibody-coated CD3 lymphocytes were followed by flow cytometry in 44 liver transplant patients during OKT3 therapy for induction or rejection. CD3+ lymphocyte counts did not predict successful management of rejection by OKT3. When expressed as percentages of the total lymphocyte count, an increasing trend in CD2+ and mouse antibody-coated CD3+ lymphocytes after day 7 of OKT3 therapy portended persistent or recurrent rejection within 2 months of treatment. It is uncertain if the increasing population of mouse antibody-coated CD3 cells is due to an immune phenomen or decreased clearance by an ailing liver. Care should be taken when using CD3 lymphocyte counts as indicators of adequate OKT3 therapy in liver transplantation.

Animals↗
PubMed1994

Anti-glomerular and anti-tubular basement membrane nephritis in a renal allograft recipient with Alport's syndrome.

A 28-year-old deaf, white man with a clinical diagnosis of Alport's syndrome since 4 years of age experienced renal failure, fever, and mental status changes suggestive of vasculitis following his first cadaveric renal transplant; these symptoms and changes resolved after removal of the allograft. Immunohistological stains demonstrated intense linear deposition of IgG and C3 in glomerular and tubular basement membranes in the absence of glomerular crescents. One year later, a second renal transplant led to similar symptoms. A biopsy was performed 14 days after engraftment, which demonstrated intense linear deposition of IgG in glomerular and tubular basement membranes, but cellular crescents were not present. A serologic profile was ordered to evaluate the patient further for vasculitis, and during the evaluation, circulating anti-glomerular basement membrane and anti-tubular basement membrane antibodies were identified by indirect immunofluorescence microscopy (titer, > 1:320). An open biopsy specimen obtained during repair of a renal laceration demonstrated a crescentic glomerulonephritis with immunohistologic findings identical to those of previous biopsies. Anti-glomerular basement membrane nephritis should be suspected in any patient with Alport's syndrome in whom progressive renal failure develops following renal transplantation. Detection of anti-glomerular basement membrane/anti-tubular basement membrane antibodies will assure the diagnosis, and early initiation of plasmapheresis may be helpful to prevent further renal damage.

Adult↗
PubMed1993

Paraneoplastic pemphigus. A distinct autoimmune vesiculobullous disorder associated with neoplasia.

A vesiculobullous disease termed paraneoplastic pemphigus with distinct autoantibodies was newly described in 1990. All reported cases have occurred in patients with a history of neoplasia, including lymphoma, chronic lymphocytic leukemia, poorly differentiated sarcoma, and benign thymoma. As in pemphigus vulgaris, intraepithelial clefts with acantholysis are noted histopathologically, and intercellular binding of immunoreactants is seen with direct immunofluorescence studies of mucous membrane and skin biopsies. However, immunoreactants may also be found along the basement membrane zone in paraneoplastic pemphigus. Indirect immunofluorescence using rat bladder epithelium as substrate shows an intercellular pattern that appears to be highly specific for paraneoplastic pemphigus. We report a patient with non-Hodgkins lymphoma of 8 years duration who developed severe erosive stomatitis and lichenoid dermatitis after receiving chemotherapy for a relapse of lymphoma. Her case illustrates the typical features of the disorder described as paraneoplastic pemphigus. Neoplasia-associated pemphigus may be a more precise term for this disorder because the course of the blistering eruption does not always parallel the course of the underlying cancer. The clinical features, histopathologic findings, and immunofluorescence findings of this unique syndrome are reviewed.

Aged↗
PubMed1993

Indirect immunofluorescence on rat bladder transitional epithelium: a test with high specificity for paraneoplastic pemphigus.

BACKGROUND: Paraneoplastic pemphigus is a blistering disease with specific serum immunoprecipitation findings. Although immunoprecipitation studies allow accurate diagnosis, they are time-consuming, expensive, and not readily available. In contrast, indirect immunofluorescence (IIF) testing of serum on transitional rat bladder epithelium is a simple and inexpensive method available to any immunopathology laboratory. OBJECTIVE: Our purpose was to determine the specificity of positive IIF on rat bladder epithelium for paraneoplastic pemphigus. METHODS: The IIF findings in four index cases of paraneoplastic pemphigus were compared with the findings in 47 patients with a variety of malignant neoplasms and no associated blistering disease as well as 49 patients with vesiculobullous or lichenoid disease but no neoplasia. RESULTS: IIF was negative in all patients with neoplasia and no blistering disease and negative in all but one of the patients with vesiculobullous or lichenoid disease without neoplasia (98.9% specificity). CONCLUSION: IIF on transitional rat bladder epithelium appears to be a highly specific test for paraneoplastic pemphigus. Because of its simplicity and inexpensiveness, we suggest that IIF be performed on transitional epithelium in any suspected case of paraneoplastic pemphigus.

Animals↗
PubMed1992

Phosphorous metabolite and cell cycle kinetic response of two human squamous cell carcinomas to radiation.

Phosphorous metabolism and cell cycle phase kinetics in response to radiation of two perfused human squamous cell carcinoma cell lines, SQ20B (radioresistant) and SQ38 (relatively radiosensitive), embedded in both basement membrane (Matrigel) and agarose gel threads were studied. The findings for these human cancer cells in response to 2- and 50-Gy irradiation are as follows. (a) Well perfused pure cancer cells (both SQ20B and SQ38) in both proliferative (cells embedded in Matrigel) and static (cells embedded in agarose threads) states did not show significant alteration in either phosphorous bioenergetics or membrane metabolites at 24 and 48 h after irradiation, although a large fraction of the population was clonogenically impaired. Previously reported, sensitively detected, metabolite alterations in response to radiation in rodent and human tumors in situ were not seen in these homogeneous cancer cell populations. (b) The radiosensitive squamous cell carcinoma cell lines SQ38 exhibited G1 block (from 54.38 +/- 1.40% in control to 73.93 +/- 1.01% after irradiation; mean +/ SD) in response to low-dose 2-Gy irradiation and G2 block (from 12.98 +/- 2.15% in control to 25.6 +/- 3.15% after irradiation) in response to high-dose 50-Gy irradiation, while the radioresistant cell line SQ20B showed only conventional G2 block in response to both doses. The differential cell cycle phase response may indicate the difference in radioresistance. (c) The membrane metabolites (including phosphomonoesters and phosphodiesters) and phosphocreatine gradually increased from the early passages to late passages, suggesting that cell proliferation rates were increasing as the cells adapted to tissue culture. The results suggest that the radiation-induced metabolite changes observed in solid tumors in situ may not be a direct response to interim changes within the cancer cells but, rather, a consequence of radiation damage either to the vasculature or to other host-mediated factors.

Animals↗