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Biomedical subjects

R Gonzalez

Publications and source records attributed to R Gonzalez.

At least 19 recordsLinked to original sources

Selective decrease of CD26 expression in T cells from HIV-1-infected individuals.

The decrease of CD4+ cells in AIDS patients is widely documented, although the selective loss within different subsets of CD4+ cells and the mechanisms involved in this phenomenon are controversial. In the present report we have analyzed the proliferative response to Ag and mitogen of peripheral blood T lymphocytes from HIV-infected individuals, the phenotype profile of CD26+ and CD26- subset of cells and their infectivity by the HIV. The expression of CD26 Ag, either in CD4+ or CD8+ cells, was clearly diminished in all the patients tested. On the other hand, the expression of CD29 seems not to be affected, nevertheless T cells from these patients were unable to generate a proliferative response against soluble Ag. In 11 out of 13 patients, polymerase chain reaction studies demonstrated that the CD26- subset of CD4+ cells was the main reservoir for HIV-1 in infected individuals and HIV-1 virus preferentially infected in vitro CD4+/CD26- subpopulation. This capacity for preferential infectivity, together with the selective loss of cells expressing CD26 Ag, helps to explain the progressive impairment in the immune system of these patients and sheds new light on our understanding of the AIDS pathophysiology.

Acquired Immunodeficiency Syndrome

Outcome of renal transplantation or dialysis in patients with a history of renal cancer.

BACKGROUND: Therapeutic options for patients with bilateral renal cancer or cancer in a solitary kidney are limited to partial nephrectomy or bilateral radical nephrectomy with subsequent renal transplantation or dialysis. The outcome after partial nephrectomy is well documented, but few reports discuss the long-term survival of patients receiving chronic dialysis or after renal transplantation. Information regarding the long-term prognosis for these patients is important when deciding on the appropriate treatment. METHODS: The authors retrospectively evaluated the long-term prognosis of 23 patients who lost renal function because of surgery for renal cell carcinoma or Wilms' tumor between 1970 and 1990. RESULTS: Twelve patients had renal transplantation (Tx group), and 11 had chronic dialysis (DS group). In the Tx group, four patients had Wilms' tumor and eight had renal cell carcinoma (Stage I, 5 patients; Stage II, 2 patients; Stage III, 1 patient). In the DS group, three patients had Wilms' tumor, and eight had renal cell carcinoma (Stage I, 5 patients; Stage III, 2 patients; Stage IV, 1 patient). Unexpectedly, 9 of 11 (82%) patients from the DS group died of cancer, compared with 1 of 12 (8%) patients who had transplantation (P = 0.0133) despite comparable stages of renal cell carcinoma and Wilms' tumor in the two groups. CONCLUSIONS: For patients who have had bilateral nephrectomy or removal of a solitary kidney, the authors recommend waiting at least 12 months, during which time the patient receives dialysis, before proceeding with transplantation if there is no evidence of recurrent tumor.

Adolescent

Low-dose alpha-interferon treatment of chronic myeloid leukemia.

We treated 29 patients with chronic-phase and accelerated chronic myeloid leukemia (CML) with alpha-interferon in a dose of 2 mU/m2 given subcutaneously daily for 30 days and then three times per week. Most had received prior treatment. Three patients have had sustained hematologic and karyotypic remissions after a median of 22 months of treatment. Three further patients have had complete hematologic and partial karyotypic remissions. At a median follow-up of 48 months, the median survival has not been reached. This dose of alpha-interferon may induce sustained remissions even in pretreated patients and may prolong survival in CML.

Adult

Immunoglobulin M antibody to hepatitis C virus during interferon therapy for chronic hepatitis C.

Testing for immunoglobulin (Ig) M antibody to hepatitis C virus (anti-HCV) as a predictive factor of therapeutic response to recombinant interferon alfa (rIFN-alpha) in chronic hepatitis C was evaluated in 122 patients with IgG anti-HCV. IgM anti-HCV was present in the pretreatment sample of 88% of patients who responded to treatment, including 20 of 21 (95%) long-term responders and 24 of 29 (83%) responders who had relapses after cessation of therapy. In contrast, IgM anti-HCV was present in only 23 of 39 (59%) nonresponders and 22 of 33 (66%) untreated controls (P less than 0.05). The number of cases with detectable IgM anti-HCV tended to decrease in responder patients, which was more evident for complete responders (42%) than for responders who relapsed (72%). During follow-up, the antibody became undetectable in the majority of long-term responders (28% were still IgM anti-HCV positive) but remained detectable in 69% of responders who relapsed (P less than 0.05). No special changes were noted in nonresponder or control patients. Thus, testing for IgM anti-HCV may help to identify a subset of patients who will benefit from rIFN-alpha therapy in chronic hepatitis C.

Adult

Preferential chromosome 11q and/or 17q aberrations in short-term cultures of metastatic melanoma in resections from human brain.

Thirteen specimens of metastatic malignant melanoma resected from eight patients undergoing craniotomy were analyzed cytogenetically from short-term cultures. All patients had chromosome 1 aberrations, as did three of four patients with metastases only to extracranial sites. Both groups had variable involvement of chromosomes 3, 6, 7, and 8. Only those with brain metastases had 11q and/or 17q involvement in six of eight patients. In reported cases of nonbrain metastases, when chromosome 11 was involved, the short arm was usually deleted or replaced through translocation; on the contrary, in reports on patients with brain metastases, the long arm of chromosome 11 was deleted at q23 or was the recipient of a translocation at q23, and/or 17q was present as an isochromosome. These aberrations were similar to those found in the patients with brain metastases in this report. Two patients undergoing brain resections did not show 11q or 17q aberrations, one near diploid with t(10;19) and the other near hexaploid with few structural rearrangements. The neural cell adhesion molecule gene is located near 11q23, and the neural growth factor receptor is located near 17q21-q22. The relevance of these genes to brain metastases in melanoma is under investigation.

Brain Neoplasms

Immune response to hepatitis B vaccine in parenteral drug abusers.

Responsiveness was assessed to a programme of vaccination of hepatitis B vaccine in a cohort of 197 intravenous drug addicts (mean age, 23.7 years) and their antibody response was compared with that of 271 healthy controls (mean age, 24.2 years). All participants were seronegative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). The vaccination schedule consisted of three intramuscular injections (deltoid area) at months 0, 1 and 2. Although 70% of parenteral drug abusers received the three doses of vaccination, only 43.6% were evaluable for immune response. Fifty-eight per cent of heroin addicts and 80% of controls had evidence of anti-HBs seroconversion at 1 month after vaccination (chi 2 = 15.52, p less than 0.001). Geometric mean antibody titres were also significantly higher in controls (69.1 IU l-1; confidence interval 95%, 56.83 and 84.04) than in parenteral drug abusers (18.2 IU l-1; confidence interval 95%, 12.85 and 25.73) (F = 20.951, p less than 0.0001). The anti-HBs response was not influenced by coexistent anti-HBc, HCV antibody or HIV antibody seropositivity.

Adult

Isolation of proteoglycans synthesized by rat heart: evidence for the presence of several distinct forms.

1. The proteoglycans (Ps) synthesized by auricle and ventricle from adult rat heart were studied. 2. Auricle tissue incorporated over two times radioactive sulfate compared to ventricle tissue and the Ps were mainly found in the detergent insoluble fraction. 3. The Ps from both tissues were isolated by ion-exchange chromatography on DEAE-Sephacel, followed by gel filtration on Sepharose CL-6B and SDS-PAGE electrophoresis. 4. Enzymatic and chemical degradation of these Ps suggest that at least three and probably four different species of Ps can be observed in heart tissue. 4. A high molecular weight chondroitin sulfate-P, a high molecular weight heparan sulfate-P, a chondroitin/dermatan sulfate-P of 240-200 kDa and a dermatan sulfate of 115 kDa. 5. This latter P was specifically immunoprecipitated using rat decorin antiserum.

Animals

Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance.

OBJECTIVE: The purpose of this study was to determine the prevalence and clinical significance of microbial invasion of the amniotic cavity in patients presenting with cervical dilatation in the midtrimester of pregnancy. STUDY DESIGN: Amniocentesis for microbial studies was performed in women admitted with cervical dilatation > or = 2 cm, intact membranes, and without active labor between 14 and 24 weeks of gestation. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Gram stain was performed on all samples. RESULTS: The prevalence of microbial invasion of the amniotic cavity was 51.5% (17/33). The most common microbial isolates were Ureaplasma urealyticum, Gardnerella vaginalis, Candida albicans, and Fusobacterium sp. All patients with microbial invasion of the amniotic cavity had complications. Patients who underwent cervical cerclage in the presence of a positive amniotic fluid culture had rupture of membranes, clinical chorioamnionitis, or pregnancy loss. On the other hand, the prognosis of patients with a negative amniotic fluid culture was better than that of patients with a positive culture. Of 16 patients with a negative amniotic culture, nine were delivered at > 34 weeks. CONCLUSIONS: (1) Microbial invasion of the amniotic cavity occurs frequently in women presenting with cervical dilatation in the midtrimester; (2) the microbiologic state of the amniotic cavity is an important prognostic factor for pregnancy outcome; (3) amniocentesis to determine the microbiologic characteristics of the amniotic cavity should be considered before a cerclage is placed in women presenting with cervical dilatation in the midtrimester.

Abortion, Spontaneous

Prognosis for patients with prenatally diagnosed posterior urethral valves.

Children in whom posterior urethral valves are diagnosed shortly after birth are at higher risk for renal failure than children in whom posterior urethral valves are diagnosed later in life. The influence of prenatal diagnosis of posterior urethral valves on clinical outcome has not been established. We collected data on children with posterior urethral valves treated since birth at our hospital between 1975 and 1990. The clinical outcomes for 8 patients diagnosed prenatally and 15 diagnosed neonatally were compared. Of the 8 patients in the prenatal group 5 (64%) had renal failure compared to 5 of 15 (33%) in the neonatal group (p greater than 0.05). Nadir creatinine of more than 1.2 mg./dl. correlated with the development of renal failure in all patients in the neonatal and prenatal groups. There was 1 death in the prenatal group. In our experience prenatal diagnosis of posterior urethral valves has grave implications, including a 64% incidence of progressive renal failure and a 64% incidence of transient pulmonary failure. Oligohydramnios and postnatal pulmonary insufficiency are predictive of progressive renal failure. Earlier diagnosis and treatment of children with posterior urethral valves did not improve the clinical prognosis.

Congenital Abnormalities

Perforation of the gastric segment of an augmented bladder secondary to peptic ulcer disease.

Gastrocystoplasty consists of bladder augmentation using part of the gastric body. We describe a child in whom peptic ulcer disease developed in the gastric portion of the bladder, with subsequent perforation of the ulcer. Chronic renal failure, hypercalcemia and oliguria are potential ulcerogenic conditions commonly present in patients with gastrocystoplasty. Perforation of the ulcer is a potentially fatal complication. Periodic cystoscopy and prophylactic treatment with hydrogen blockers and alkalization of the urine should be considered in patients with those risk factors.

Child, Preschool

Influence of initial therapy on progression of renal failure and body growth in children with posterior urethral valves.

Children with posterior urethral valves are at high risk for renal failure and growth retardation. It has been proposed that the type of initial surgical treatment (that is primary ablation versus high diversion) can affect the outcome of children with posterior urethral valves. We evaluated 43 children with posterior urethral valves treated and followed at our hospital from 1975 to 1990 (17 since birth and 26 referred patients). A total of 19 patients was treated by a high urinary diversion, (high urinary diversion group), 19 were treated by primary fulguration and 2 by vesicostomy (fulguration and vesicostomy group), and 3 underwent fulguration and unilateral diversion (mixed treatment group, excluded from study). The clinical outcome and body growth were compared for the high urinary diversion, and fulguration and vesicostomy groups. A normal stature (above the 25th percentile) was reached by 4 patients (21%) from the high urinary diversion group and 11 (52%) in the fulguration and vesicostomy group. This difference was not statistically significant. In contrast, renal function was predictive of body growth: 73% of the children with normal serum creatinine and 20% of the children with renal failure achieved a normal stature (p less than 0.05). One patient from the mixed treatment group died of pulmonary hypoplasia. We conclude that the type of primary surgical treatment (fulguration and vesicostomy or high urinary diversion) did not influence progression of renal failure or body growth in children with posterior urethral valves. Regardless of the surgical or medical treatment, which can greatly influence mortality, renal failure developed in almost 50% of the children with posterior urethral valves.

Child

The influence of urinary diversion on experimental gastrocystoplasty.

Gastrocystoplasty is used to augment the bladder of patients with decreased renal function to prevent development or worsening of metabolic acidosis. We recently observed a perforated peptic ulcer in the gastric portion of a defunctionalized gastrocystoplasty. We postulated that the lack of buffering action of urine precipitated peptic ulcer disease in the gastrocystoplasty. To explore this possibility further, we conducted an experiment. In 12 adult female mongrel dogs (weight 15 to 26 kg.) the bladder was divided into right and left segments. One kidney was removed and both hemibladders were capped with a vascularized segment of gastric body. Thus, 1 side (wet) remained exposed to urine, while the other side (dry) was drained to the abdominal wall with a cystostomy tube. The animals were divided into 2 groups: 9 in group 1 received no drugs to modify gastric secretion and 3 in group 2 received a hydrogen (H2) blocker. Three animals in group 1 had perforation of the vesical part of the dry gastrocystoplasty 2 to 3 weeks postoperatively and were sacrificed. The others were sacrificed 3 to 6 weeks postoperatively. Serum gastrin levels remained normal in all animals. Gross and histological examinations of the augmented bladders in group 1 revealed ulcerations of the bladder segment of the wet and dry gastrocystoplasties but the lesions were more numerous and prominent on the dry side in all animals, particularly those in which the perforations occurred. A peptic ulcer was noted in the gastric portion of the dry gastrocystoplasty in 1 animal. The bladder epithelium of the dry gastrocystoplasty showed glandular metaplasia in several animals in this group. In group 2 the wet gastrocystoplasty showed normal histology except in 1 dog that had mild inflammation and focal superficial ulceration in the vesical portion. On the other hand, the dry gastrocystoplasty showed severe inflammation and ulcerations in 2 animals, and mild inflammation of the vesical portion in 1. There were no perforations in this group. This experiment demonstrates that gastrocystoplasty produces cystitis but that these changes are more prominent in the absence of urine, as indicated by the severity of the lesions, perforations and metaplasia. Peptic ulcer disease occurred in the gastric portion of the dry gastrocystoplasty in 1 animal. The use of H2 blockers decreases the incidence of ulceration in wet gastrocystoplasty but it seems to have less influence on the ulceration of dry gastrocystoplasty. Clinicians must be alerted to the risk of perforation of dry gastrocystoplasty.

Animals

Influence of preoperative bladder capacity and compliance on the outcome of artificial sphincter implantation in patients with neurogenic sphincter incompetence.

We performed a retrospective study of 23 patients with neurogenic sphincteric incompetence who had undergone implantation of an artificial urinary sphincter to determine if bladder capacity and compliance as determined by cystometrography could predict the need for enterocystoplasty. Study criteria were neurogenic sphincteric incompetence, no previous operations on the lower urinary tract, and performance of preoperative and postoperative cystometrography. Patients were 5 to 17 years old at implantation. Incontinence was caused by myelomeningocele (18 patients), sacral agenesis (3) and spinal cord tumor (2). The 8 patients for whom preoperative cystometric bladder capacity was greater than 60% of the expected capacity for age have been followed for a mean of 60 months. All 8 patients are continent and none required enterocystoplasty. Preoperative bladder compliance exceeded 2 ml./cm. water in all patients (group 1). Of the 15 patients for whom preoperative cystometric bladder capacity was less than 60% of the expected value (group 2, small bladders) 8 followed an average of 72 months had a compliance greater than 2 ml./cm. water and have done well without bladder augmentation. In contrast, 7 patients in this group (46%) required enterocystoplasty: 6 for persistent or recurrent incontinence and 1 for upper tract changes. The average interval between artificial sphincter placement and enterocystoplasty was 14 months. Patients with a small bladder that required augmentation had a preoperative bladder compliance of less than 2 ml./cm. water. We conclude that small bladder capacity, as determined by cystometrography in patients with neurogenic sphincteric incompetence but a bladder compliance of less than 2 ml./cm. water predicts the future need for bladder augmentation. In all other patients, with good medical treatment and followup, the possible adverse effects of a small capacity bladder can be prevented or corrected. With this strategy we have been able to avoid enterocystoplasty with its attending potential complications in 70% of our patients with neurogenic incontinence and favorable urodynamics regardless of preoperative cystometric bladder capacity.

Adolescent

The two major xylanases from Trichoderma reesei: characterization of both enzymes and genes.

As a first step to exploit the potential of Trichoderma reesei to produce hemicellulases, we have purified two endo-beta-1,4-xylanases (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) and cloned their genes. The enzymes were isolated from culture filtrates of T. reesei C30 grown on xylan as a carbon source, using two steps of cation exchange chromatography. They exhibited molecular weights of 19 (XYN I) and 21 (XYN II) kD, and isoelectric points of 5.2 and 9.0, respectively. These enzymes differed in their pH optimum for activity and affinity for xylan, and accounted for more than 90% of the total xylanolytic activity of the fungus. The purified enzymes were subjected to N-terminal sequence analysis, and after cleavage with trypsin and endoproteinase Glu-C the resulting peptides were sequenced. Oligonucleotides based on these sequences were used to clone gene fragments via PCR, and these were used as probes to isolate full-length copies of xyn1 and xyn2 from a lambda gene bank of T. reesei. The products of xyn1 and xyn2 share considerable homology, but the enzyme encoded by xyn2 appears to more closely resemble several other bacterial and fungal xylanases than does that of xyn1.

Amino Acid Sequence

A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer.

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.

Adult

Early diagnosis of toxoplasmic encephalitis in AIDS patients by dot blot hybridization analysis.

Central nervous system toxoplasmosis is a life-threatening infection with a mortality rate of higher than 60%. An early and rapid diagnosis is important for effective treatment of the disease. A new approach for detection of cerebral toxoplasmosis is described here. DNAs extracted from cells in cerebrospinal fluid samples (0.3 to 0.8 ml) of patients suspected of having cerebral toxoplasmosis were analyzed by a dot blot hybridization technique. A highly repetitive DNA sequence of Toxoplasma gondii (ABGTg4) was nonisotopically labelled with digoxigenin-dUTP and used as a specific DNA probe. Four of six patients analyzed gave positive signals in our hybridization assay. Two of them recovered with pyrimethamine-sulfadiazine, a drug recommended for treatment of toxoplasmosis. The other two patients with positive signals died soon after diagnosis. Patients with negative signals were found to suffer from mycobacterial infection (patient 1) or varicella-zoster virus infection (patient 6).

AIDS-Related Opportunistic Infections

Distribution of a breast-directed I-131-radiolabeled monoclonal antibody in blood and bone marrow: implications for radiation immunotherapy.

Bone marrow is most often the dose-limiting organ in radiation immunotherapy. Controversy exists over optimal methods of estimating radiation dose to bone marrow. The authors compared findings in serial blood samples to findings in bone marrow biopsy samples as measures of bone marrow activity from which to calculate bone marrow dose. Peripheral blood samples and bone marrow biopsy samples were obtained from 11 female patients at 48 and 168 hours after infusion of iodine-131-labeled Mc5 antibody. Bone marrow biopsy data demonstrated markedly decreased specific activity compared with that measured in the peripheral blood. Activities at 48 hours after infusion ranged from 3% to 22% of the peripheral blood activity. These results indicate that activity concentration in the bone marrow is not equivalent to activity concentration in the blood for the Mc5 antibody. These results imply that a dose three to four times that indicated from serial blood samples could be tolerated by patients, provided the antibody-radioisotope does not bind to the marrow.

Bone Marrow