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Biomedical subjects

J Silva

Publications and source records attributed to J Silva.

At least 19 recordsLinked to original sources
PubMed1992

Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: preliminary results.

In an attempt to find a vaccine that gives greater and more consistent protection against leprosy than BCG vaccine, we compared BCG with and without killed Mycobacterium leprae in Venezuela. Close contacts of prevalent leprosy cases were selected as the trial population since they are at greatest risk of leprosy. Since 1983, 29,113 contacts have been randomly allocated vaccination with BCG alone or BCG plus 6 x 10(8) irradiated, autoclaved M leprae purified from the tissues of infected armadillos. We excluded contacts with signs of leprosy at screening and a proportion of those whose skin-test responses to M leprae soluble antigen (MLSA) were 10 mm or more (positive reactions). By July, 1991, 59 postvaccination cases of leprosy had been confirmed in 150,026 person-years of follow-up through annual clinical examinations of the trial population (31 BCG, 28 BCG/M leprae). In the subgroup for which we thought an effect of vaccination was most likely (onset more than a year after vaccination, negative MLSA skin-test response before vaccination), leprosy developed in 11 BCG recipients and 9 BCG/M leprae recipients; there were 18% fewer cases (upper 95% confidence limit [CL] 70%) in the BCG/M leprae than in the BCG alone group. For all cases with onset more than a year after vaccination irrespective of MLSA reaction the relative efficacy was 0% (upper 95% CL 54%; 15 cases in each vaccine group). Retrospective analysis of data on the number of BCG scars found on each contact screened suggested that BCG alone confers substantial protection against leprosy (vaccine efficacy 56%, 95% CL 27-74%) and there was a suggestion that several doses of BCG offered additional protection. There is no evidence in the first 5 years of follow-up of this trial that BCG plus M leprae offers substantially better protection against leprosy than does BCG alone, but the confidence interval on the relative efficacy estimate is wide.

BCG Vaccine↗
PubMed1992

Triage of patients out of the emergency department: three-year experience.

Because of severe emergency department (ED) overcrowding, the authors initiated a program of referring certain patients who were assessed as not needing emergency care away from the ED. A selected group of patients who presented to a busy university ED were refused treatment and triaged away following a medical screening examination performed by a nurse. In this 3-year study 136,794 patients presented to the triage area in the ED, of which 21,069 (15%) were refused care and referred elsewhere. Letters and calls to all referral clinics, eight local EDs, and the coroner's office identified no patients who had been grossly mistriaged, and only insignificant adverse outcomes could be identified. Additional follow-up on 3,740 individuals triaged away was performed by telephone. Responses from this survey indicated that 42% of persons received care elsewhere the same day, 37% within 2 days, and 22% decided not to seek medical care. A group of 1.6% sought care at other hospital EDs for minor complaints. The authors concluded that a group of patients can be selectively triaged out of the ED without significant adverse outcomes, which may offer one approach to the problem of ED overcrowding.

Adult↗
PubMed1991

A University of California State-supported AIDS research award program--a unique state and university partnership in AIDS research.

This article describes the State-supported University of California AIDS research award program and its major accomplishments. It shows how a partnership between a University and a State resulted in the formation of a successful, efficient, and cost-effective AIDS research award program. This program provides funds for rapid testing of investigator-initiated meritorious research ideas, new drugs, and treatment modalities. Funds were also utilized to establish three AIDS Clinical Research Centers, which evolved into regional consortia that coordinate trials of new drugs and other modalities. This program succeeded in involving investigators whose efforts have led to excellent medical care, advanced technologies, and new drugs for treating AIDS and AIDS-related diseases. The University remains committed to continuing support of all areas of AIDS research, emphasizing drug and vaccine development, pediatric AIDS, and AIDS prevention studies in groups at high risk for HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The mechanism of action of a synthetic immunomodulator, 3,6-bis(2-piperidinoethoxy)acridine trihydrochloride (CL 246,738), in natural killer cell activation in animals.

CL 246,738 is a low molecular weight, synthetic immunomodulator. The present study was done to determine the interaction among interferon (IFN), macrophages, and natural killer (NK) cells in mice following oral administration of CL 246,738. Splenic NK activity as evidenced by lysis of YAC-1 lymphoma cells in vitro was found to be augmented by the compound not only in normal mice, but also in immunodeficient beige and nude mice. Lytic activity remained elevated from one to seven days after a single treatment and the peak activation varied depending on the source of NK cells. NK cell activity associated with the peritoneal exudate cell population peaked at day 1 and returned to normal by day 2, whereas NK cell activity of peripheral blood lymphocytes peaked at day 3 and remained significantly elevated until day 7. Liver associated NK activity peaked at day 4 and remained significantly elevated at day 7 after treatment with CL 246,738. Lung associated NK activity was elevated by day 1 after treatment, peaked at day 4 and returned to normal by day 7 after drug administration. The drug was also effective in inducing IFN in all mouse strains tested. When these drug-treated mice were given antibody to IFN-(alpha + beta) but not to IFN-(beta), both IFN levels and NK cell activity decreased, suggesting the importance of IFN-(alpha) in this system. Furthermore, mice that had received carrageenan prior to, but not after CL 246,738 administration showed reduced serum IFN titers as well as decreased NK cell activity, indicating that macrophages played an intermediate role in immune enhancement by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗
PubMed1991

Depression of cell-mediated immunity in plasmacytoma-bearing mice.

Previous reports have documented that mice bearing plasmacytomas (PC) are suppressed in their ability to mount a primary antibody response, whereas cellular immunity appears to be normal. Studies presented here provide evidence that T cell responsiveness is also depressed in BALB/c mice bearing the Lieberman plasmacytoma (Lpc-1). For instance, splenocytes from mice bearing large tumours were impaired in their in vitro ability to respond to the T cell mitogen, mount an appropriate alloreactive cytolytic T lymphocyte response, and produce interleukin-2 (IL-2). A population of suppressor cells was detected in the spleens 7 days after tumour implantation as evidenced by their ability to prevent normal splenocytes not only from responding to antigens in mixed lymphocyte culture, but also from producing IL-2. A similar inhibitory effect was observed with culture supernatants of these cells, indicating the existence of a soluble suppressive factor. Therefore, the present study demonstrates that cellular immune responses are impaired in mice bearing Lpc-1 tumours and that this effect may be due to the generation of suppressor cells and/or a suppressive factor.

Animals↗
PubMed1991

Birth of the first 100 babies in Hawaii after conception in-vitro: experience at the Pacific In-Vitro Fertilization Institute.

This paper reports on the first 100 infants delivered consecutively the result of 63 pregnancies after conception in-vitro at the Pacific In-Vitro Fertilization (IVF) Institute. These pregnancies were established prior to the introduction of embryo-cryopreservation into the program. Ninety-seven percent (97%) of singleton pregnancies delivered after 36 weeks; only 5/31 (16%) required tocolytic therapy. The overall multiple gestation rate was 51%, higher than in many other IVF centers. Maternal complications and neonatal morbidity were associated primarily with these multiple gestations. Forty-one percent (41%) delivered in less than 36 weeks, and tocolytics were administered in 22/27 (81%) of twin and 5/5 (100%) of triplet gestations. Neonatal morbidity was noted in 39 infants (33 from multiple gestations); 28 neonates were admitted to the intensive care unit (27 from multiple gestations). Nine births had or developed minor abnormalities (hernias, pyloric stenosis). One case of Trisomy 21, and one infant death at 11 months occurred in the group. The caesarean section rate for all IVF deliveries was 65%. It is concluded that IVF is clearly established in Hawaii for infertility refractory to other methods of treatment. The risk associated with IVF stem from the possibility of multiple gestations, not whether the pregnancy was initiated in-vitro. In the future, embryo cryopreservation may help to reduce the risk of multiple pregnancy.

Adult↗
PubMed1991

Relapsing polychondritis and Reiter's syndrome.

We describe a case of relapsing polychondritis associated with Reiter's Syndrome in a 46-year-old white man. Relapsing polychondritis is a rare disorder of unknown etiology associated in about 30% of cases with other rheumatic disorders such as connective tissue diseases, vasculitis and exceptionally, seronegative spondyloarthritis. We found this association only once in our review of the literature.

Arthritis, Reactive↗
PubMed1990

Health status of Air Force veterans occupationally exposed to herbicides in Vietnam. I. Physical health.

The Air Force Health Study is a 20-year comprehensive assessment of the health of Air Force veterans of Operation Ranch Hand, the unit responsible for aerial spraying of herbicides in Vietnam. The study compares the health and noncombat mortality of Ranch Hand veterans with a comparison group of Air Force veterans primarily involved with cargo missions in Southeast Asia but who were not exposed to herbicides. This report summarizes the health of these veterans as determined at the third in a series of physical examinations. Nine hundred ninety-five Ranch Hands and 1299 comparison subjects attended the second follow-up examination in 1987. The two groups were similar in reported health problems, diagnosed skin conditions, and hepatic, cardiovascular, and immune profiles. Ranch Hands have experienced significantly more basal cell carcinomas than comparison subjects. The two groups were not different with respect to melanoma and systemic cancer.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1990

Toxicity of nitrobenzene compounds towards isolated hepatocytes: dependence on reduction potential.

1. The cytotoxicity of p-substituted nitrobenzenes towards isolated hepatocytes under aerobic or hypoxic conditions has been determined. The nitrobenzene concentration required to cause 50% cytoxicity in 2 h was a function of the one-electron reduction potential of the nitrobenzene, with the more cytotoxic compounds having the strongest electron-withdrawing substituents. 2. The effectiveness of the nitrobenzenes at causing cytotoxicity under aerobic but not hypoxic conditions was markedly increased if hepatocyte catalase was inhibited with azide. 3. Nitrobenzenes at cytotoxic concentrations induced cyanide-resistant respiration in isolated hepatocytes. Their effectiveness correlated with their cytotoxicity. 4. The rate of oxygen activation of these nitrobenzenes by ascorbate was also a function of the one-electron reduction potential. The nitro compounds with the strongest electron-withdrawing substituents were the most rapidly reduced. 5. Most nitrobenzenes were more cytotoxic under aerobic than hypoxic conditions. Ascorbate enhanced hypoxic, but not aerobic, cytotoxicity. 6. It was concluded that the cytotoxicity of different nitrobenzenes is related to their ease of reduction to nitro radical anions and nitrosobenzenes. Aerobic cytotoxicity is probably initiated by redox cycling and oxygen activation by the nitro radical anions whereas hypoxic cytotoxicity is probably initiated by the alkylation of macromolecules by nitrosobenzene metabolites.

Alkylation↗
PubMed1990

[Rhythm profile in patients with psoriatic arthritis].

OBJECTIVE: To analyze the rhythmic profile in patients with psoriatic arthritis (PA). DESIGN: In order to evaluate the rhythmic profile of patients with PA, we have carried out ambulatory 24 hour ECG recordings in 22 patients presented consecutively to the Holter ECG laboratory. SETTING: Patients followed in a specialised rheumatology consultation, in Santa Maria Hospital. PATIENTS: We have studied 22 patients (pts), 10 male and 12 female, aged 49.8 +/- 8.4 years, presenting PA diagnosed in average 12.9 years before. A group of 36 individuals, 25 male and 11 female, aged 37 +/- 8 years and without disease, were used as control. RESULTS: All patients were in sinus rhythm with a mean heart rate of 71 +/- 6 (min - 51.5 +/- 7.0 and max - 130.3 +/- 15.0). In 8 (36.6%) there were sinus bradycardia less than 50/min and sinus tachycardia (greater than 120/min) in 15 patients (68.1%). Two patients (9%) presented supraventricular tachycardia and one had AV block. There were premature atrial systoles in 14 pts (63.6%), and ventricular arrhythmias in 9 (40.9%). In control group, there were sinus bradycardia in 16.6%, sinus tachycardia in 33.3%, premature atrial systoles in 33.3% and ventricular arrhythmias in 25% of them; in 11% there were conduction disturbances. CONCLUSIONS: a) Premature atrial systoles were the rhythm disturbance more prevalent. b) Patients with PA presented a significant higher incidence of sinus bradycardia and sinus tachycardia. c) Cardiac conduction disturbances were not frequent. d) Our results may suggest the presence of a subtle autonomic dysfunction in patients with psoriatic arthritis.

Adult↗
PubMed1989

Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens.

PURPOSE: High-dose (500 mg orally four times daily) vancomycin is considered by many investigators to be the most effective treatment for antibiotic-associated Clostridium difficile colitis. However, a lower dosage of 125 or 150 mg given three or four times a day has become popular, has been shown to be effective, and is less expensive than the high-dose regimen. We therefore decided to compare two vancomycin dosage regimens in a randomized trial. PATIENTS AND METHODS: The study involved 46 hospitalized patients with serious underlying diseases complicated by C. difficile diarrhea or colitis. Patients were assigned (according to a table of random numbers) to treatment with either 125 or 500 mg of vancomycin orally four times daily for an average of 10 days. RESULTS: No significant differences in measurable responses to the two regimens were noted. There were no treatment failures. The mean duration of diarrhea after initiation of therapy was about four days, and almost all patients had no diarrhea after one week. The organism continued to be demonstrated in the stools of about 50 percent of patients for the first few weeks after completion of therapy, and nine (20 percent) patients developed a recurrence of their diarrheal illness. Vancomycin was well tolerated by all patients. CONCLUSION: Since the dose of 125 mg appeared to be as effective as the 500-mg dose, which is more expensive, the 125-mg dose is preferred when vancomycin is used in treatment of this disease, unless the patient is critically ill.

Administration, Oral↗
PubMed1989

Reconstitution of cytolytic alloreactivity with N-[4-[(4-fluorophenyl) sulfonyl]phenyl]acetamide (CL 259,763) in animals immunocompromised by cyclophosphamide.

A novel synthetic immunopotentiator, i.e. N-[4-[(4-fluorophenyl)sulfonyl]phenyl]acetamide (CL 259,763), was investigated for its potential in reconstituting the cell-mediated immune response of animals whose immunologic system had been severely depressed by cytoreductive agents. It was demonstrated that lymphocytes from mice which had received 300 mg/kg of cyclophosphamide (CY) immediately following antigen sensitization had a reduced capability of responding to alloantigens in mixed lymphocyte culture and failed to generate effective cytolytic T-lymphocytes (CTL) capable of destroying appropriate tumor target cells in a cytotoxicity assay. However, treatment of these immunocompromised animals with CL 259,763 produced a significant restoration of alloreactivity, as evidenced by an enhancement of the CTL response. Although effective doses of CL 259,763 ranged from 20 to 300 mg/kg, the optimal effect was observed at 75 mg/kg. Findings from a time course study indicated that the maximum restoration occurred when CL 259,763 was given to mice 2-5 days after, but not before or simultaneously with, CY treatment. Both the immunoimpairment by CY and its reversal by CL 259,763 appeared not to be antigen specific. The lessened immunoreactivity of CY-treated mice was explicable by the presence of suppressor cells in their spleens. These suppressors were able to adhere to plastic and resisted treatment with anti-Thy 1.2 antibody, indicating a macrophage characteristic. Flow cytometric analysis indicated a quantitative depletion of all T-lymphocytes, including Thy-1.2(+), Lyt-1(+), Lyt-2(+) and L3T4(+) subsets in the spleens of CY-treated mice; however, a population of Mac-1(+) cells was markedly expanded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1989

Clostridium difficile in the intensive care unit: management problems and prevention issues.

Several patients hospitalized in our 12-bed medical ICU were found to have Clostridium difficile associated colitis. Stool cultures of all patients identified eight cases (three culture positive, and five culture and cytotoxin positive), seven of which were geographically and temporarily clustered within a 2-wk period. At least one patient appeared to contract the disease after hospitalization and in the absence of antibiotic therapy or other known major risk factors. The outbreak highlights the problem of C. difficile in the ICU. We believe that a heightened awareness of the multiple risk factors and preventive measures, along with consideration of possible nosocomial transmission, will be necessary to prevent or arrest future clusters of cases in the ICU. The diagnosis of one patient with this infection in a unit should prompt a review of all other patients within the unit.

Aged↗
PubMed1989

Update on pseudomembranous colitis.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Homer A. Boushey, MD, Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

Enterocolitis, Pseudomembranous↗
PubMed1988

Restoration of cytolytic T-lymphocyte response with a new immunopotentiator, N-(4-[(4-fluorophenyl)sulfonyl]phenyl)acetamide (CL 259, 763), in mice.

The immunorestorative characteristics of a novel synthetic immunomodulator, N-(4-[(4-fluorophenyl)sulfonyl]phenyl)acetamide (CL 259, 763), has been investigated in several experimental models. In one situation, the compound was shown to enhance the induction of a cytolytic T-lymphocyte response to the murine MBL-2 leukemia implanted in its syngeneic host in which only a minimal reactivity to the tumor is normally displayed. In a Vaccinia virus model, the compound similarly augmented the lytic activity of cytolytic T-lymphocyte to virus-infected targets in not only viral antigen-primed but also cyclosporin A-impaired mice. Likewise, the alloreactive cytolytic T-lymphocyte activity was recovered in animals immunocompromised by inoculation with murine plasmacytomas or cytoreductive anticancer drugs, such as cyclophosphamide and 5-fluorouracil. Thus, the present findings suggest that CL 259,763 is effective in potentiating the immune response to weak antigens as well as in restoring alloreactivity by sparing the immunotoxicity associated with the administration of cytotoxic drugs and the growth of neoplasms.

Adjuvants, Immunologic↗
PubMed1988

Clostridium difficile as a nosocomial pathogen.

Patients admitted to a 19-bed floor with intermediate nursing care were studied for the onset of Clostridium difficile-associated diarrhoea during a six-month period (181 calendar days) in 1986-87. All admitted patients were reviewed weekly and followed after discharge from the study unit to other inpatient services. Multiple items in the environment of five patients' rooms were sampled bacteriologically for the presence of C. difficile weekly during the study period. Three of the rooms were selected for study because of a higher prevalence of C. difficile associated diarrhoea in the prior three years and two were selected because no cases had been discovered previously in these rooms ('control rooms'). Nine of 521 patients admitted to this unit developed C. difficile diarrhoea (1.73 cases/100 patients admitted) versus 0.30/100 patients admitted to all other sites in our hospital (24 of 7970 other patients). This represented respectively 3.91 cases per 1000 patient days on this floor versus 0.37 patients/1000 patient days throughout the hospital. Seven of the C. difficile diarrhoea cases were associated with stay in the C. difficile associated rooms, versus two cases in the two 'control rooms'. C. difficile was isolated from the toilet seats, bedpan hopper, night stands or food trays. Of some 1955 cultures taken, only 1.9% overall were positive for C. difficile.

Clostridium↗
PubMed1988

The metabolism of N-acetyl-3,5-dimethyl-p-benzoquinone imine in isolated hepatocytes involves N-deacetylation.

3,5-Dimethyl-N-acetyl-p-benzoquinone imine (3,5-dimethyl-NAPQI) was cytotoxic to isolated hepatocytes from Sprague Dawley rats at levels between 200 and 300 microM. It rapidly oxidized intracellular glutathione within 10 sec, with the formation of oxidized glutathione. The cytotoxicity of 3,5-dimethyl-NAPQI could be prevented over a 3.5-hr period with the carboxylesterase inhibitor bis(p-nitrophenyl) phosphate, indicating that cytotoxicity involved N-deacetylation. The N-deacetylated product could be trapped with glutathione as 3-(glutathion-S-yl)-4-amino-2,6-dimethylphenol in 3,5-dimethyl-NAPQI-treated hepatocytes but not in hepatocytes pretreated with bis(p-nitrophenyl) phosphate, indicating that N-deacetylation activity had been inhibited. 3,5-Dimethyl-NAPQI was readily N-deacetylated by rat liver microsomes, in contrast to 3,5-dimethylacetaminophen. The latter was also not cytotoxic to hepatocytes at up to 2 mM. The N-deacetylated product 4-amino-2,6-dimethylphenol rapidly underwent autoxidation to form 2,6-dimethylbenzoquinone imine and was highly cytotoxic to hepatocytes at 200-300 microM. The latter reacted with glutathione to give the above conjugate and no glutathione oxidation occurred. Dithioerythritol (2 mM) added at 10, 20, and 30 min after 3,5-dimethyl-NAPQI delayed but did not prevent cytotoxicity. Dithioerythritol also resulted in the partial restoration of GSH, presumably as a result of reduction of protein mixed disulphides. The mechanism of cytotoxicity of 3,5-dimethyl-NAPQI therefore appears to be a result of a combination of oxidative stress and deacetylation resulting in arylation.

Acetylation↗