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Biomedical subjects

M Perez

Publications and source records attributed to M Perez.

At least 145 records · Page 8Linked to original sources

Inhibition of autoimmune disease in a murine model of systemic lupus erythematosus induced by exposure to syngeneic photoinactivated lymphocytes.

MRL/l mice develop progressive, virulent autoimmune disease that has many of the features of systemic lupus erythematosus. Prophylactic treatment of MRL/l mice with syngeneic photoinactivated autoimmune splenocytes improves survival and inhibits the fulminant hyperproliferation of abnormal T cells and the production of high titer anti-DNA antibody invariably found in untreated mice. The proliferation of Thy 1+ splenic T cells was significantly decreased, and prolonged retention of the response to T-cell mitogen was found in treated mice. Treatment with unmodified cells induced a partial inhibition of disease features which did not prolong survival rates. These results suggest that phototherapy potentiates a normal immunoregulatory process which enables suppression of the development of abnormal cell populations in young MRL/l mice with relatively intact immune systems.

Animals↗

Serodiagnosis of leprosy in patients' contacts by enzyme-linked immunosorbent assay.

Serum samples from 3336 contacts of leprosy patients were tested for antiphenolic glycolipid I antibodies by enzyme-linked immunosorbent assay with the albumin coupled synthetic disaccharide antigen. The overall positivity rate was 9.3%. No significant differences were seen between a group of household contacts of lepromatous patients and those of the other types of the disease. The proportion of ELISA positives was slightly higher in the relatives as compared to workplace contacts and neighbours but significantly different only between the two former (p less than 0.05). Among those contacts with absorbance values higher than 0.100, 5 new leprosy patients were diagnosed, 2 of them with positive skin smears. A sixth contact was detected with a very high absorbance value in whom no single skin lesion was found but whose lepromin reaction was 0 mm and the skin smear showed a bacteriological index of 3+.

Antibodies, Bacterial↗

Probability of cardiac disease: Framingham revisited.

A study was undertaken to test the utility of a strict Bayesian formulation for the diagnosis of coronary disease. Using known probabilities of the disease for men and women in four different age groups and by estimating the probabilities of disease in patients with four important risk factors, we were able to estimate the probability of coronary disease in 512 different subsets of patients. We found that it was not possible to rigourously apply Bayes formula because neither the probability of the risk factor given the disease nor in patients without disease was obtainable in the medical literature. We conclude that to use Bayes formula without equivocation in coronary diagnosis does not appear possible in the present state of statistical knowledge. Rather, an expert system in the form of a knowledge-base would appear to be more achievable.

Adult↗

NK sensitivity and lung clearance of MHC-class-I-deficient cells within a heterogeneous fibrosarcoma.

The present study examines clonal variations in NK sensitivity in a methylcholanthrene-induced fibrosarcoma. Previous studies of clones from this tumor have shown considerable heterogeneity in H-2 expression, and an association between deleted or low levels of class-I products and increased tumorigenicity after subcutaneous implantation in immunocompetent syngeneic mice. Here, fibrosarcoma clones with no or low expression of MHC-class-I products were found to be sensitive to NK-mediated lysis, while clones with high levels of MHC-class-I expression were relatively resistant. One H-2+ (G2) and one H-2- (B9) clone were chosen for more detailed studies. Cold-target competition assays and conjugate cytotoxicity assays in agarose showed that splenic effector cells bound equally well to the H-2+ and H-2- tumor clone, although only the latter was sensitive to NK cell lysis. Treatment with 50 U/ml of rIFN-gamma for 48 hr increased the levels of H-2 expression and made both clones more resistant to NK-mediated lysis. In vivo studies with radiolabelled tumor cells showed that cells from the H-2+ clone survived better than cells from the H-2- clone in the pulmonary capillary bed after i.v. inoculation. This difference disappeared in mice treated with anti-asialo GM1 serum, known to deplete NK cell activity.

Animals↗

Effect of timing of hepatitis B vaccine doses on response to vaccine in Yucpa Indians.

In a large hepatitis B prevention programme, hepatitis B vaccine was given in standard doses to greater than 1000 susceptible Yucpa Indians between 1983 and 1985. Thirteen months after the programme began, 373 vaccine recipients were tested using commercial radioimmunoassay to titre antibody response to the vaccine. Because of logistic difficulties, only 32% had received vaccine by the recommended schedule (second and third doses at one and six months after the first, respectively). The second and third doses were received early by 4 and 31%, respectively, and 27 and 16% received these doses later than intended. Overall response to vaccine was excellent: 98% of vaccinees developed anti-HBs greater than 10 mIU (geometric mean titre 688 mIU). Multivariate analysis showed that the response to vaccination was inversely related to the age of the vaccinee and directly related to the timing of the third vaccine dose. In particular, those receiving the third vaccine dose late (greater than 7 months after the first dose) developed antibody titres two-fold higher than those receiving the third dose on schedule (p less than 0.01). The response to vaccination was not significantly related to the timing of the second dose. A satisfactory response was obtained with various schedules of dose timing, including early second and third doses, late second and third doses and late second but normal third doses. These findings suggest that the response to hepatitis B vaccine is not highly dependent on timing of vaccine doses and that modest alterations in timing of doses, such as those necessary to integrate hepatitis B vaccine with other childhood vaccines, do not affect the excellent response to this vaccine.

Adolescent↗

Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes.

Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histocompatibility antigens. This report describes a new approach that employs pretreatment of effector cells with 8-methoxy-psoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Reinfusion of photodamaged cells resulted in an immunosuppressive host response that permitted prolonged retention of histoincompatible skin grafts and specifically inhibited in vitro and in vivo responses that correlate with allograft rejection. Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes served as a source of alloreactive effector cells. The splenocytes were treated with 100 ng/ml 8-MOP and 1 J/cm2 UVA before reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft. Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T cell responses to CBA/j alloantigens in comparison with sensitized and naive controls. Splenocytes from these hyporesponsive mice suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. Moreover, BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 d posttransplantation without visual evidence of rejection. These results indicate that the in vivo and in vitro response to alloantigen can be attenuated by pretreating the host with photoinactivated splenocytes containing the effector cells of alloantigen rejection.

Animals↗

Population pharmacokinetic study of gentamicin and a Bayesian approach in patients with renal impairment.

A population pharmacokinetic study was conducted on a total of 70 patients receiving gentamicin therapy. The patients included those with normal renal function and those with varying degrees of renal impairment. The parameters studied were the apparent volume of distribution and the plasma clearance of gentamicin. The interindividual variability and the residual variability of those parameters in the different subpopulations were studied according to a statistical model that assumed log normal distribution. Use of the one-way ANOVA test revealed statistically significant differences (P = 0.004) in the population plasma clearance of gentamicin in patients below and above 50 years of age. A linear relationship was established between the plasma clearance of gentamicin and the creatinine clearance in those patients. At the same time, the coefficient of variation of the Clp increased progressively in patients with renal impairment, varying between 28.98% in patients with a ClCR greater than 100 ml/min and 76.53% in patients with a ClCR between 20 and 60 ml/min. The results obtained in the population study were later applied to drug monitoring in 23 patients with varying degrees of renal function and who received gentamicin therapy with different doses. The residual variability of the population allowed us to calculate a weighting factor (FF) between the experimental and the population data using Bayesian fitting. The weighting factor was 0.89 in patients with normal renal function and 0.80 in patients with renal impairment. Statistical comparison of the pharmacokinetic parameters obtained from the populational data, non-linear regression and the Bayesian method using revealed differences in the values for the apparent volume of distribution obtained with the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reactions to and antigenicity of two human-rhesus rotavirus reassortant vaccine candidates of serotypes 1 and 2 in Venezuelan infants.

The reactions to and antigenicity of two human-rhesus rotavirus (RRV) reassortants (human rotavirus strain D x RRV and human rotavirus strain DS1 x RRV) with the VP7 neutralization specificity of a serotype 1 or serotype 2 rotavirus were evaluated in a placebo-controlled double-blind trial in 116 1- to 5-month-old infants in Caracas, Venezuela. The children were randomly divided into five groups to receive orally the following inocula: (i) 10(4) PFU of D x RRV reassortant; (ii) 10(4) PFU of DS1 x RRV reassortant; (iii) 10(4) PFU of RRV; (iv) 5 x 10(3) PFU of D x RRV and 5 x 10(3) PFU of RRV; and (v) placebo. The children were examined daily for 7 days following vaccine administration; 8 to 26% of the vaccinated infants developed a mild febrile reaction which in most cases lasted only 1 day. Seroresponses to rotavirus were observed in 39 to 65% of the vaccinees by plaque neutralization assay and in 57 to 88% by an immunoglobulin A enzyme-linked immunosorbent assay. Vaccine shedding was detected in 53 to 86% of the vaccinees. Analysis of neutralization antibody responses indicates that the VP4 protein represents an important component of the response induced by the vaccines.

Age Factors↗

Family therapy with spinal cord injured substance abusers.

To incorporate family therapy into an inpatient treatment program for spinal cord injured substance abusers required overcoming both staff and patient resistance. Since it became an integral part of the program, family therapy has shown itself to be helpful in dealing with this population's tendency to adapt to their injury either by overdependency or overachievement. Its usefulness to patients with other chronic disabilities appears to warrant consideration.

Adult↗

[Axillary hyperhidrosis. Etiopathogenesis and surgical treatment].

Axillary hyperhidrosis consists of excessive sweating, producing severe embarrassment and a personal and social handicap. Anatomy and physiology of sweating are reviewed. A localized surgical attack on the excessively active sweat glands is preferred to topical anti-perspirants and systemic medications which are inadequate. Flaps are elevated and the resection includes the glands down to the dermal level. No skin excision seems to be necessary. Long term results are analysed, and the satisfaction of the patients demonstrates the efficacy of this treatment.

Axilla↗

Computer-assisted diagnosis of acute abdominal pain.

An acute abdominal pain program run on a microcomputer is described and the experiences tabulated for a series of 194 patients seen in a general hospital setting. The initial diagnostic accuracy of the program compared favorably with that of attending physicians and house staff, and suggests that improvements in the program can lead to a more effective and more accurate abdominal pain program. The possibilities for developing other programs, particularly chest pain, fever, and other global categories, are obvious. We are presently working on a chest pain program and a diagnostic strategy program. Based on the results reported here, we believe that several factors could improve program accuracy. For example, with additional clinical studies and refinement of the program structure, with more expert knowledge, and with further algorithmic development, the program could be made to outperform the average clinician and possibly approach the level of true clinical experts in abdominal pain diagnosis by mimicking their analysis. Indeed, since a program of this type is capable of incorporating the expertise of many different clinicians, it has the potential of outperforming any given expert in specific cases.

Abdomen↗

Vasoactive intestinal polypeptide and neuropeptide-Y, as possible mediators in laryngeal oedema. An immunofluorescence study.

Little attention has been paid to the autonomic innervation of the human vocal cord. Vasoactive intestinal polypeptide (VIP) and Neuropeptide-Y (NPY) are of interest because of their association with the autonomic nervous system. These neuropeptides have not been studied in the human vocal cord by immunofluorescence technique. Both neuropeptides were found in the connective tissue close to the basal layer of the mucosa, around glandular structures and arterial walls. Comments are made about the role these peptides might play in the physiopathology of vocal cord oedema.

Autonomic Nervous System↗