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Biomedical subjects

R Gonzalez

Publications and source records attributed to R Gonzalez.

At least 217 records · Page 12Linked to original sources

Reye's syndrome associated with acute myocarditis and fatal circulatory failure.

We describe an eight-month-old infant who had an unusually fulminant and fatal course of Reye's syndrome. The patient died 36 hours after admission because of irreversible circulatory failure not associated with clinical symptoms of increased intracranial pressure or cerebral herniation. Autopsy revealed the pathognomonic fatty degeneration of the liver and heart of Reye's syndrome, but the brain was normal. In addition, a marked inflammatory infiltration of the myocardium was also observed, which indicated that acute myocarditis had been the preceding underlying disease. This case report emphasizes the fact that the viral prodrome preceding Reye's syndrome may not be as benign as often observed with influenza and varicella. Acute myocarditis and Reye's syndrome are also a combination which may result in fatal cardiovascular collapse.

Acute Disease↗

Improved tumor imaging with radiolabeled monoclonal antibodies by plasma clearance of unbound antibody with anti-antibody column.

Imaging of tumors by using radiolabeled monoclonal antibodies (MoAs) is hindered by the presence of background activity. To reduce this problem, the authors investigated the process of removing labeled MoAs from plasma at selected times by means of extracorporeal immunoadsorption. In seven patients with either lung or breast carcinoma, an indium-111-labeled murine antibody was intravenously administered. Six to 24 hours later, immunoadsorption was performed by passing the patients' plasma through a goat anti-mouse antibody column connected to a plasma separator. Whole-body computer images were obtained before and after the treatment. Blood pool activity in the images was reduced by an average of 59%, while tumor activity dropped by only 10%. Tumor-to-blood activity ratios therefore more than doubled, improving by an average of 121% between the pre- and posttreatment image sets. Eight of 12 areas of known disease and three areas of unknown but later documented disease were detected after the immunoadsorption process, while the three areas of unknown disease and three of the areas of known disease were not detected in the preclearance images. Thus, the feasibility of using extracorporeal immunoadsorption to improve MoA imaging of tumors was demonstrated.

Adenocarcinoma↗

Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration.

A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway.

Administration, Oral↗

Testing the safety of non-disconnect disposable Y sets for peritoneal dialysis.

In order to test the efficacy of the Del Clamp as a contamination barrier, the following protocol was carried out. Sixty bags of dialysate (1.5 L, 1.5% Dextrose) were connected to matching disposable Y sets and 100 mL of dialysate allowed to flow into each drain bag, after which the clamps were closed. The bags were arranged in groups of 10 and each group was inoculated with 1 mL of a standard suspension of S. aureus, S. epidermidis, E. coli, E. faecalis, P. aeruginosa and C. albicans, respectively. 3 bags were inoculated and left with the clamp open as controls. After 6 hr, incubation at 37 degrees C, 20 mL duplicate samples from each drain bag were centrifugated and processed for anaerobic and aerobic culture. None of the specimens taken from the sets grew bacteria or fungi. All the drain bags of the control sets grew the inoculated organism. We conclude that the Del Clamp makes CAPD safer by working as an effective contamination barrier and eliminating a potential for combination during the dialysis exchange.

Bacteria↗

Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.

To determine the maximally tolerated dose of a ricin A chain-conjugated antimelanoma antibody (XomaZyme-Mel), 20 patients with metastatic melanoma were treated with escalating doses of the murine immunotoxin given as single intravenous infusion over 30 minutes. The starting dose was 0.6 mg/kg and was escalated in five groups to a maximum of 1.6 mg/kg. The maximally tolerated dose was 1.25 mg/kg as three of six patients treated at 1.6 mg/kg developed unacceptable toxicity. The dose-limiting toxicity consisted of profound fatigue, myalgias, and arthralgias. These occurred within 4 days and resolved in 7 to 10 days. Other non-dose-limiting toxicities encountered consisted of hypoalbuminemia, weight gain, peripheral edema, mild hypotension, and flu-like syndrome; the severity of these was also dose related. In addition, two allergic reactions occurred, one severe. There was one durable complete response of 12+ months' duration and one brief mixed response lasting 3 months. We conclude that the maximum tolerated single dose of XomaZyme-Mel is 1.25 mg/kg. Phase I studies evaluating 1.25 mg/kg given in multiple doses at 2- to 4-week intervals and phase II studies to determine the response rate of a single 1.25 mg/kg dose are warranted.

Adult↗

Syngeneic albumin can be used as a carrier in neonatal mice.

Free native horseradish peroxidase (PO) or PO coupled to either syngeneic mouse serum albumin (PO-MSA) or to xenogeneic bovine serum albumin (PO-BSA) in sterile phosphate buffered saline (PBS), were injected repeatedly into newborn BALB/c mice. Serum antibody titres were evaluated by enzyme immunoassay on 30 and 60 of age and on d 75 and 88 after 1 or 2 booster injections respectively. The response to PO was found in all sera from neonatal immunized mice with all forms of PO, but only in control adult mice immunized by PO-BSA. Immunization with either PO-MSA or PO-BSA induced mainly IgG anti-PO antibodies of high avidity while immunization with free PO resulted in the induction of both IgM and IgG anti-PO antibodies of low avidity. A large number of hybridomas with anti-PO specificity were obtained from the spleen of mice injected with PO-MSA. The results indicate that neonatal immunization of mice with PO is an effective procedure, which is probably applicable to other proteins.

Animals↗

Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine.

90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque-forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3 rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2, and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1 and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo. The frequencies of transient febrile responses in these four groups were 20%, 27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients showed a neutralising antibody response to M37; 27% showed such responses to human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients showed neutralising antibody responses to serotypes 1-4. 70-73% of the quadrivalent and balanced quadrivalent groups also showed neutralising antibody responses to RRV.

Antibodies, Viral↗

Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine.

The efficacy of a rhesus rotavirus vaccine (MMU 18006, serotype 3) against infantile diarrhea was evaluated by active home surveillance of a group of 320 children 1-10 months of age in Caracas, Venezuela. During a 1 year period following oral administration of vaccine or placebo under a double-masked code, over 600 diarrheal episodes were detected. Etiologic studies revealed that heat-stable toxin (ST) producing enterotoxigenic E. coli (ETEC) was the most common diarrheal agent detected (34%) followed by enteropathogenic E. coli (EPEC, 10.9%), heat-labile toxin (LT) producing ETEC (7.6%), rotavirus (6.9%), Cryptosporidium (4.8%) and Campylobacter (1.3%). ST-producing ETEC were also recovered from over 20% of control stool specimens obtained during diarrhea-free periods, whereas EPEC, rotavirus, Cryptosporidium, and Campylobacter were rarely detected in such control specimens. Rotavirus was responsible for about one-half of the more severe cases of diarrhea. Twenty-two of 151 infants who received placebo (14.6%) and eight of 151 receiving a 10(4) PFU dose of vaccine (5.3%) had rotavirus diarrhea during the follow-up period for an efficacy level of 64% against any rotavirus diarrhea. However, vaccine efficacy reached 90% against the more severe cases of rotavirus diarrhea and was noticeably high in the 1-4 month age group. Serotypic analysis of the rotaviruses detected suggests that the resistance induced by the vaccine was type specific since significant protection was only evident against serotype 3 rotaviruses. A 10(3) PFU dose tested initially in 18 children did not appear to protect against rotavirus diarrhea.

Complement Fixation Tests↗

Early bladder outlet obstruction in fetal lambs induces renal dysplasia and the prune-belly syndrome.

A model of posterior urethral valves in fetal lambs was developed in order to evaluate the effect of intrauterine urinary obstruction on the developing kidney. Complete urethral obstruction was induced in five fetal lambs at 43 to 45 days of gestation. Two control fetal lambs underwent sham operations. At full term (140 days), two of the five experimental lambs and both control lambs were available for postmortem examination. Results of gross and histological examination of the control lambs were normal. In contrast, the kidneys of the experimental lambs were markedly asymmetrical in size. Histological examination of the kidneys in experimental lambs showed cystic dilatation of the collecting ducts and occasional cystic dilatation of Bowman's spaces, features compatible with obstruction. Also noted were peripheral cortical cysts and primitive tubules lined with cuboidal epithelium and surrounded by fibromuscular collarettes, characteristic of renal dysplasia. One of the infant lambs had many characteristics of the prune-belly syndrome, including a wrinkled, markedly distended abdomen, deficient abdominal wall musculature, flared chest wall, limb deformities, and undescended testes. These results suggest that early in utero urethral obstruction (at the beginning of the second third of gestation) causes renal dysplasia. The results also support the hypothesis that the prune-belly syndrome results from abdominal distention that occurs early in gestation.

Abdominal Muscles↗

Percutaneous balloon dilation of ureteral strictures after failed surgical repair in children.

We attempted treatment of long-standing strictures of ureterovesical or ureterosigmoid anastomosis in 6 children by percutaneous balloon dilation. The 4 girls and 2 boys were between 2 and 19 years old (mean age 9 years) at the time of dilation. Obstruction occurred at the ureterosigmoid anastomosis in 3 patients and at the ureterovesical junction in 3. Obstruction was confirmed by diuresis renography, antegrade pyelography and pressure perfusion studies. An attempt at dilation was unsuccessful for 1 patient. For the remaining 5 patients the ureter has remained patent for a followup period of 7 to 18 months (mean 12 months). Percutaneous balloon dilation of established ureterointestinal and ureterovesical obstruction after failed surgical repair can be successful. The hospital stay is reduced and major surgery with its accompanying morbidity is avoided. If balloon dilation is unsuccessful, surgical repair remains an option. Balloon dilation should be seriously considered as an initial form of treatment in this group of patients.

Adolescent↗

Outcome of renal transplantation after urinary diversion and enterocystoplasty: a retrospective, controlled study.

A total of 17 patients with intestinal urinary diversion of enterocystoplasty underwent renal transplantation between 1970 and 1988. Patient age ranged from 4 to 35 years (mean age 20 years). The patients were divided into 2 groups. In group 1 (10 patients, 2 of whom required retransplantation) the ureter of the transplanted kidney was implanted into an ileal (7) or colonic (1) conduit or enterocystoplasty (2). In group 2 (7 patients, 1 of whom required a second transplant) the diversion was taken down and the transplanted ureter was implanted into the defunctionalized bladder. There were 14 living related and 6 cadaveric kidneys transplanted. Graft survival rates were 58 and 87% in groups 1 and 2, respectively, with an over-all rate of 70% (14 of 20 kidneys). There was no statistical difference in the graft survival rate between the 2 groups. The complications in group 1 included ureteroileal anastomotic leak (3 patients), ureteroileal stenosis (1), calculus formation (1), urosepsis (1), hyperchloremic metabolic acidosis (1), and wound infection and dehiscence (1). There were no complications in group 2. Renal transplantation into a pre-existing urinary intestinal conduit or augmented bladder does not statistically adversely affect patient or graft survival. However, the complication rate is much higher when the ureter is implanted into an intestinal segment. Therefore, it is preferable whenever possible to implant the ureter into the native bladder.

Adult↗

Single-stage feminization genitoplasty.

We present a modified technique for feminization genitoplasty, which combines the main features of the Hendren and Crawford pull-through operation and the Kogan reduction clitoroplasty. The unique features of the operation are the use of a flap of preputial skin to construct the vestibule and the anterior vaginal wall, and the universal use of the urogenital sinus to form the distal urethra, which avoids creation of female hypospadias. The new introitus is ample and, because there is no cut-back of the urogenital sinus, we avoid accidental incision of the urethral sphincter and the potential for urinary incontinence. There is no pull-through of the vagina because the introitus is created by mobilization of anterior and posterior skin flaps. The clitoris and the neourethra are exteriorized through the folded preputial skin, which simulates the normal female anatomy. The cosmetic and functional results in 9 children who have undergone this procedure have been excellent.

Adrenal Hyperplasia, Congenital↗

Success of the artificial urinary sphincter after failed surgery for incontinence.

We implanted the artificial urinary sphincter in 15 incontinent patients for whom multiple urethral and bladder neck operations, including sphincter placement, had been unsuccessful. The 5 male and 10 female patients ranged from 3 to 26 years old (mean age 11 years). The etiology of incontinence was neurogenic bladder in 10 patients, epispadias in 2, exstrophy in 1, ectopic ureters in 1 and traumatic urethral disruption in 1. Of the 15 patients 13 required augmentation enterocystoplasty and clean intermittent catheterization. The initial anti-incontinence procedures were Young-Dees-Leadbetter bladder neck reconstruction in 10 patients, artificial urinary sphincter placement in 4 and bladder neck suspension in 1. Causes of failure of the primary treatment were erosion (artificial urinary sphincter), and incontinence and/or difficult catheterization (Young-Dees-Leadbetter). Followup from the last salvage operation averaged 21 months (range 6 to 37 months). A total of 58 operations was performed. Among the 4 patients in whom the artificial urinary sphincter eroded the bladder neck repeated attempts to place the cuff at the same site were unsuccessful and erosion occurred in all 4 within 1 year. Sphincter placement was more successful among the 11 patients who initially underwent Young-Dees-Leadbetter bladder neck reconstruction or bladder neck suspension; acceptable continence was attained in 8 patients (73%). We conclude that placement of the sphincter cuff around a previously eroded bladder neck probably will result in erosion. Sphincter implantation should be attempted in patients in whom bladder neck reconstruction has failed. Persistence in the treatment of these patients is essential because multiple operations often are necessary to achieve continence.

Adolescent↗

Morphometric study of immunoreactive GH-cells of the adenohypophysis of rats treated with Met-enkephalin.

Morphological and morphometric changes were found in adenohypophyseal GH immunoreactive cells after intraventricular administration of Met-enkephalin to adult rats of both sexes. Morphologically, following Met-enkephalin treatment, the males showed cells stained intensely and homogeneously in their cytoplasm, while the females showed cells with a weaker degree of staining and a cytoplasm with a granular aspect; previous administration of naloxone prevented the changes observed in the males and intensified the reaction in the females. Morphometrically, in all the groups of animals studied, the males showed a greater cellular area than the females, accompanied by a decrease in the cytoplasmic area but without significant differences in the nuclear area. Met-enkephalin in both sexes produced an increase in cellular area, accompanied by a significant increase in the cytoplasmic area and, although less manifest, in the nuclear area. Neither kind of change appeared when naloxone was administered prior to Met-enkephalin treatment.

Animals↗

Pharmacokinetics and disposition of the lipid-lowering drug acifran in normal subjects and in patients with renal failure.

The pharmacokinetics and metabolic fate of the antihyperlipidemic drug acifran were assessed after a single oral dose of the 14C-labeled drug to healthy male volunteers. Peak serum acifran and radioactivity concentrations were attained 1 to 2 hours after dosing, and the drug was eliminated with a half-life of 1.6 hours. Virtually all of the recovered dose was excreted in the urine. All of the serum and urinary radioactivity was caused by unconjugated acifran. In patients with moderate chronic renal failure, the binding of acifran to plasma proteins was decreased, and the plasma concentrations of total and unbound drug were greater than those of healthy subjects. Renal failure substantially reduced the plasma and renal clearance of total and particularly of unbound acifran, moderately reduced its volume of distribution, and increased its elimination half-life from 1.4 to 1.7 hours to 5.7 hours. The results show that acifran is very well absorbed, is rapidly eliminated, is excreted in the urine, and does not undergo any detectable biotransformation in healthy human subjects.

Adult↗

Aggressive non-Hodgkin's lymphomas in AIDS: the University of Colorado experience.

The authors performed this retrospective study to further investigate the relationship between non-Hodgkin's lymphoma (NHL) and the Acquired Immunodeficiency Syndrome (AIDS). From January 1984 through December 1987 all cases of AIDS and NHL diagnosed at the University of Colorado affiliated hospitals were identified and submitted to chart review. Twenty-five patients fulfilled criteria for the diagnosis of AIDS and 24 had biopsy-proven NHL, an additional patient met criteria for the diagnosis of primary central nervous system lymphoma and was included in the analysis. All patients had known risk factors for the development of AIDS. Of the biopsy proven tumors, 23 were categorized as high grade. Most patients (68%) presented with stage IV disease and 92% with extra nodal involvement. Median survival was 5 months and the cause of death was most often progressive lymphoma and/or opportunistic infections. These data are similar to previously published series. Clinical trials to evaluate effective treatment are warranted.

Acquired Immunodeficiency Syndrome↗

Uterus-like mass of the small intestine. Heterotopia or monodermal teratoma?

A 12-year-old girl with multiple lower-intestinal and urogenital tract anomalies and a past history of sacrococcygeal teratoma had an intramural mass of the ileum discovered as an incidental finding at surgery. The predominant mass had the features of the uterine fundus and two smaller contiguous nodules resembled the fallopian tube. A normal uterus and ovaries were observed at surgery. Somewhat similar lesions have been reported in the past in the ovary, ileum, scrotum, and possibly the bladder. Neither the metaplastic nor malformational theories are entirely satisfactory, yet they can be stated for most examples of heterotopias or choristomas.

Abnormalities, Multiple↗