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Biomedical subjects

J Costa

Publications and source records attributed to J Costa.

At least 19 recordsLinked to original sources
PubMed1992

Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.

A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process.

Base Sequence↗
PubMed1992

Pharmacokinetics of alfuzosin after single oral administration to healthy volunteers, of three different doses.

The aim of this study was to assess the linearity of pharmacokinetic of alfuzosin, administered by oral route, at the doses of 1, 2.5, and 5 mg to 12 young healthy volunteers. The pharmacokinetic parameters (tmax, Cmax, AUC, t1/2 beta) obtained from plasma alfuzosin concentrations after administration of the three doses show that pharmacokinetics of alfuzosin is linear in the range of doses 1-5 mg. Mean pharmacokinetic parameters of alfuzosin observed after 1, 2.5, and 5 mg were, respectively: tmax (h) 1.5 +/- 0.3, 1.1 +/- 0.2, 1.3 +/- 0.1; Cmax (ng ml-1) 2.6 +/- 0.3, 9.4 +/- 1.2, 13.5 +/- 1.0; AUC (ng ml-1 h) 17.7 +/- 2.9, 51.7 +/- 7.1, 99.0 +/- 14.1; t1/2 (h) 3.7 +/- 0.4, 3.9 +/- 0.2, 3.8 +/- 0.3. Cmax (corrected by the dose) obtained after 2.5 mg was significantly higher than those obtained after 1 and 5 mg. This difference seems to be due principally to the intraindividual variability. The absence of statistically significant difference on individual values of AUC corrected by the administered dose, supports the linearity of the pharmacokinetics of alfuzosin in the range of doses between 1 and 5 mg. Some postural hypotension, clinical criterion, was observed with a frequency increasing with the dose in these healthy subjects: 0 volunteers of 12 after 1 mg, 3 volunteers of 12 after 2.5 mg and 4 volunteers of 12 after 5 mg.

Administration, Oral↗
PubMed1992

Stability of K-ras mutations throughout the natural history of human colorectal cancer.

We have used a rapid, non-radioactive and sensitive method based on allele-specific amplification using the polymerase chain reaction for the identification of K-ras mutations in archival tissues of colorectal carcinomas. Our purpose was to determine whether or not K-ras mutation provides, when present, a tumour marker throughout the natural history of the disease. We have studied 35 patients who developed recurrent cancer. In 71% of these patients a ras mutation in codons 12 or 13 was observed in the primary tumour. For each of these cases an identical ras mutation was found in the DNA from the local or distant recurrence. In the 29% of cases where no ras mutation was observed in the primary tumour, no newly acquired ras mutation appeared in the recurrent tumour. The time interval between primary tumours and recurrences varied from 3 to 60 months. Our results indicate that K-ras mutation provides a stable tumour marker throughout the natural history of colorectal cancer.

Adenocarcinoma↗
PubMed1992

Impaired response to recombinant hepatitis B vaccine in HIV-infected persons.

We studied the immunogenicity of the standard schedule of recombinant hepatitis B vaccine (20 micrograms per dose at months 0, 1, and 6) in 21 anti-human immunodeficiency virus (HIV)-positive persons. Relatively low titers of anti-HBs developed in only five subjects (23.8%) 1 month after the third dose; all five had T4 cell counts greater than 700 cells/mm and none of the 11 subjects with a T4 cell count below this value responded. Five of the 16 nonresponders to the vaccine later had acquired immunodeficiency syndrome (AIDS)-related complex (two) and AIDS (three), while none of the responders did. Our results show that anti-HIV-positive persons are poor responders to the recombinant hepatitis B vaccine, and that the absence of a response is an indicator of a more severe immune deficiency and of a poor prognosis. An optimal regimen of hepatitis B vaccination in HIV-infected persons is still to be established.

Follow-Up Studies↗
PubMed1992

The dexamethasone suppression test as an adjunct in diagnosing depression.

Historically, affective disorders have been underdiagnosed among minorities, while schizophrenia is often overdiagnosed. Cultural differences in symptomatology, such as increased reports of auditory hallucinations, or language differences reportedly contribute to misdiagnoses in Hispanics. Consequently, we performed a thorough evaluation of Hispanic patients with a history of schizophrenia who remained diagnostic enigmas. Evaluation included the use of a Spanish-speaking interpreter, strict adherence to criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition (revised), and the dexamethasone suppression test. Five patients met criteria for major depression, and all but one were properly classified using the dexamethasone suppression test. Careful evaluation is needed with appropriate cultural and diagnostics support to avoid missing depression in Hispanics. The dexamethasone suppression test may be a useful adjunct in some difficult-to-diagnose patients.

Adult↗
PubMed1991

Incidence of non-A, non-B hepatitis after screening blood donors for antibodies to hepatitis C virus and surrogate markers.

OBJECTIVE: To compare the effect of screening blood donors for antibodies to hepatitis C virus (anti-HCV) on the incidence of non-A, non-B hepatitis in recipients with that of screening blood donors for antibodies to hepatitis B core antigen (anti-HBc) and elevated alanine aminotransferase levels. DESIGN: Cohort analysis of serum samples from donors and recipients. Recipients were followed for 12 months to determine the occurrence of non-A, non-B hepatitis. SETTING: The blood-transmitted viruses unit and the liver unit of a university teaching hospital. SUBJECTS: A total of 250 patients who had open heart surgery and their 3142 blood donors. MEASUREMENTS: Donor sera were tested for anti-HCV by enzyme-linked immunosorbent assay (ELISA) and, in the event of a positive result, by recombinant immunoblot assay (RIBA). Antibodies to anti-HBc and serum alanine aminotransferase (ALT) levels were also measured. Measurements of anti-HCV and ALT activity in recipients were done before transfusion and at regular intervals during follow-up. MAIN RESULTS: Of the 250 transfusion recipients, 40 developed non-A, non-B hepatitis. Of the 3142 donors, 70 were positive for anti-HCV by ELISA, 440 were positive for anti-HBc, and 177 had alanine aminotransferase levels between 0.67 and 1.33 mukat/L. The sensitivity (87%), specificity (89%), positive predictive value (59%), and negative predictive value (97%) of blood-donor screening were higher for anti-HCV than for anti-HBc (82%, 36%, 21%, and 91%, respectively) and 70%, 29%, and 91%, respectively). The expected number of donors excluded because of the presence of anti-HCV was considerably smaller than that of donors with positive results for surrogate markers of hepatitis. CONCLUSION: Screening blood donors for the presence of anti-HCV is more accurate than screening for surrogate markers (anti-HBc and ALT) and protects more effectively against post-transfusion non-A, non-B hepatitis.

Alanine Transaminase↗
PubMed1991

Alveolar soft-part sarcoma of the uterine corpus: histological, immunocytochemical and ultrastructural study of a case.

A case of alveolar soft-part sarcoma located in the uterine corpus is reported. It was an incidental finding in the hysterectomy specimen of a 40-year-old woman. Light and electron microscopic examination revealed periodic-acid-Schiff-positive, diastase-resistant, membrane-bound cytoplasmic granules and crystalloids. Tumour cells expressed immunoreactivity with vimentin, desmin, cytokeratins, NK1/C3 and HMB-45 antibodies. Four years postoperatively, the patient is still alive without evidence of disease. Differential diagnoses, immunocytochemistry and clinical management of uterine alveolar soft-part sarcoma are discussed and the literature reviewed.

Adult↗
PubMed1991

Squamous cell carcinoma of the lung in a nonsmoking, nonirradiated patient with juvenile laryngotracheal papillomatosis. Evidence of human papillomavirus-11 DNA in both carcinoma and papillomas.

Malignant transformation of laryngeal juvenile papillomatosis most often occurs in patients with previous radiation therapy or smoking histories. We report the case of a 35-year-old, nonsmoking, nonirradiated man who developed squamous cell carcinoma of the lung with a 33-year history of laryngotracheal juvenile papillomatosis. Postmortem examination showed pulmonary cavitating papillomatosis and chest wall, vertebrae, and peribronchial lymph node involvement by tumor. Molecular studies (Southern blot, polymerase chain reaction) showed extrachromosomal human papillomavirus-11 (HPV11) DNA in both carcinoma and two laryngotracheal squamous cell papillomas, including one excised 20 years previously. Our observation is analogous to the previously reported cases of spontaneous (not related to irradiation or smoking) malignant transformation of juvenile laryngotracheal papillomatosis. Although HPV11 viral infection likely played a role in the malignant transformation, other less likely factors, such as drugs given for treatment and radiography performed throughout the illness, should be considered. Repeated pulmonary infections and the host immune response are additional considerations.

Adult↗
PubMed1991

Hand and wrist strengthening exercises during rehabilitation of a patient with hereditary distal myopathy.

The effects of isometric and resistive strengthening exercises on myopathic distal muscles were examined by implementing a program of hand and wrist exercises during the rehabilitation of a patient with adult-onset hereditary distal myopathy. A 78-year-old man with this diagnosis for 18 years entered the hospital after a lumbar laminectomy and complete bedrest for seven weeks. After a three-week course of twice-daily Velcro board, therapeutic putty, and table-side isometric exercises, his hand and wrist manual muscle testing score, hand grasp and pinch strength, and nine-hole peg test times had all improved. In addition, the patient had moved from minimum-moderate assist in dressing and hygiene, and maximum assist in homemaking, to stand-by assist in both areas. The outcome demonstrates the feasibility and functional value of isometric and resistive strengthening exercises in muscles severely affected by a myopathic process.

Activities of Daily Living↗
PubMed1991

Occurrence of Ki-ras and p53 mutations in primary colorectal tumors.

Twenty-four colorectal tumors and their paired mucosa were examined for allele loss on chromosomes 5 and 17, using polymerase chain reaction-amplified DNA, and for mutations in the Ki-ras and p53 genes. In addition, 19 benign polyps were analysed for mutations in the p53 gene. RFLP analysis of the long arm of chromosome 5 indicated an allele loss frequency of 47% for malignant tumors, a value somewhat higher than previously observed. Examination of the short arm of chromosome 17 indicated an allele loss of 60%. Sequence analysis of the p53 gene in colorectal tumors indicated that 64% contained a mutation. All tumors showing allele loss on chromosome 17 were mutant for p53, suggesting that mutation of one p53 allele precedes the hemizygotic loss of the wild-type allele. Sequence analysis of the p53 gene in 19 benign polyps, devoid of severe dysplasia, did not reveal any mutants, suggesting that the mutation of one p53 allele is an event that takes place after polyp formation. Ki-ras mutations were observed in 48% of the tumors examined. All tumors which were mutant for Ki-ras, except for one, were also mutant for p53.

Blotting, Northern↗
PubMed1991

Negative symptoms: psychopathological models.

The psychopathological manifestations of schizophrenia have been broadly divided into positive and negative symptom groups. Even though there is no definitive consensus, psychomotor agitation, motor excitement, hallucinations, delusions and thought disorder constitute positive and psychomotor retardation, amotivation, apathy and decreased emotional expression are grouped into negative symptoms. The negative symptoms have been reported to appear late in the course of the illness and resistant to treatment with neuroleptics. While these claims have not been substantiated, the current interest on negative symptoms is related to the fact that many nonfunctioning institutionalized as well as ambulatory schizophrenics manifest negative symptoms. As chronic psychiatric beds have become scarce, many patients with negative symptoms who were harbored in the chronic mental hospitals have been released to the community care and some of these patients live on the streets. Thus their visibility has challenged psychiatry to focus its efforts on the etiology and treatment of negative symptoms.

Deinstitutionalization↗
PubMed1990

Risk factors for hepatocellular carcinoma in Catalonia, Spain.

The influence of hepatitis B virus infection, alcohol consumption, tobacco smoking and use of oral contraceptives on the risk of hepatocellular carcinoma (HCC) was evaluated in a hospital-based case-control study in Catalonia, in the Mediterranean coastal area of north-eastern Spain. A total of 96 HCC cases (86.5% of them with associated liver cirrhosis) and 190 age- and sex-matched controls were studied. The odds ratio of HCC and 95% confidence interval among hepatitis B surface antigen (HBsAg) carriers was 4.9 (1.3-21.9). The OR was not significantly elevated in smokers, and a marginally significant increased risk was found among users of oral contraceptives based on 6 female cases. There was a significant dose-response relationship between alcohol consumption and risk of HCC (chi 2 for trend: 24.3, p less than 0.001). Although hepatitis B infection was strongly associated with HCC, alcohol abuse leading to cirrhosis appears to be one of the main causes of HCC in this region.

Adult↗
PubMed1990

Hepatitis C virus infection in patients with nonalcoholic chronic liver disease.

STUDY OBJECTIVE: To determine the prevalence and meaning of antibodies to the hepatitis C virus (HCV) in patients with nonalcoholic chronic liver diseases. DESIGN: Cross-sectional study. SETTING: The liver unit of a referral-based university hospital. PATIENTS: Three hundred and forty-six consecutive patients, including 137 with cryptogenic chronic liver disease, 156 with chronic hepatitis B, 47 with primary biliary cirrhosis, and 8 with persistently abnormal aminotransferase serum levels and normal liver histology. Among patients with cryptogenic liver disease, 41 received blood transfusions before discovery of liver disease and 18 had circulating nonorgan-specific autoantibodies. For comparison, 1495 apparently healthy volunteer blood donors were included in the study. LABORATORY INVESTIGATIONS: The presence of anti-HCV antibodies (anti-HCV) was determined by a recently developed enzyme-linked immunoassay. MEASUREMENTS AND MAIN RESULTS: In patients with cryptogenic liver disease, the prevalence of anti-HCV was 82% (95% CI, 76% to 89%), being higher (P = 0.02) in patients with histories of blood transfusion than in those with unknown sources of exposure. Antibodies to HCV were not detected in patients with antinuclear antibodies at high titer. Among patients with chronic hepatitis B, anti-HCV were found in 11% (CI, 5% to 18%) of those with hepatitis B virus (HBV)-associated DNA in serum and in 29% (CI, 17% to 43%) of those with undetectable HBV replication (P less than 0.05). The prevalence of anti-HCV in blood donors was 1.2% (CI, 1.1% to 1.3%). CONCLUSIONS: Our results indicate that HCV infection probably plays an important etiologic role in cryptogenic liver disease and, in some patients, in chronic hepatitis B. Determining whether anti-HCV are present appears to be useful for differentiating viral from autoimmune chronic liver diseases.

Adolescent↗
PubMed1990

Dibucaine interaction with phospholipid vesicles. A resonance energy-transfer study.

Resonance energy transfer between a local anaesthetic, dibucaine (donor) and a set of functionalized probes [n-(9-anthroyloxy)stearic acids, n = 2, 3, 6, 7, 9 and 12 and 16-(9-anthroyloxy)palmitic acid] (acceptors) was found to be an efficient process with a critical radius of transfer Ro = 2.1 nm, this interaction being used to locate the drug in a model membrane system, small unilamellar vesicles of dipalmitoylglycerophosphocholine, both above and below the temperature of the gel-to-the-liquid-crystal transition of the phospholipid. From the sequence of relative quenching efficiencies of dibucaine fluorescence upon incorporation of the probes, it was concluded that the drug intercalates in the membrane near the glycerol backbone of the lipid. In addition, it was found that dibucaine location is not significantly affected upon crossing the phase-transition temperature of the phospholipid. Dibucaine photophysics was also studied and the short lifetime of the neutral form of the anaesthetic with respect to that of the monoprotonated species was attributed to an intramolecular charge-transfer interaction. From the study of its partition coefficient between the membrane and the aqueous phase, it was concluded that the only significant species present in the membrane is the charged one.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Hepatitis B virus and hepatitis D virus replication in HBsAg-positive fulminant hepatitis.

Hepatitis B virus DNA and hepatitis D virus RNA, the most sensitive markers of hepatitis B and hepatitis D virus replication, were sought by molecular hybridization with radioactive probes in serial serum samples from 29 consecutive patients with HBsAg-positive fulminant hepatitis. Nineteen patients had evidence of hepatitis D virus infection, as assessed by the presence in serum of delta antigen, anti-delta antibodies, or both. Hepatitis B virus DNA was found in only two patients: one was a chronic HBsAg carrier with hepatitis D virus superinfection and the other had fulminant hepatitis caused by hepatitis B and hepatitis D coinfection. Hepatitis D virus RNA was detected in three patients: two with hepatitis B and hepatitis D coinfection and also in the HBsAg carrier with positive hepatitis B virus DNA and hepatitis D virus superinfection. None of 10 patients with hepatitis B virus infection alone had detectable viral nucleic acids in serum. Overall, viral nucleic acids were detected in the sera of 4 of the 29 patients (14%). Hepatitis D virus antigenemia did not indicate hepatitis D virus replication because hepatitis D virus RNA was not detected in 9 of 12 patients with hepatitis D virus antigen in their sera. The low frequency of viral replication found in fulminant hepatitis B or D may explain the low recurrence rate of viral hepatitis in patients with fulminant hepatitis who have received liver transplantations.

Adolescent↗
PubMed1990

Subjective neuroleptic response and treatment outcome under open and double-blind conditions--a preliminary report.

1. A patient's early subjective response to a neuroleptic was recorded in 17 schizophrenic patients following a fixed dose of neuroleptic under both open and double-blind placebo-controlled conditions. 2. High correlations were found between a patient's subjective response at 2.5, 24 and 48 hours after the initial dose, suggesting that the timing of the initial subjective response rating is not critical. 3. The relationship between the psychiatric improvement and subjective response was not significant under double-blind conditions (r = 0.004), while the relationship under the open condition showed a trend towards significance comparable to earlier reports (r = 0.32). 4. The findings question the usefulness of applying early subjective response to a neuroleptic to predict clinical improvement.

Adult↗