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Biomedical subjects

J Roberts

Publications and source records attributed to J Roberts.

At least 307 records · Page 17Linked to original sources

Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY.

PURPOSE: To determine the prognosis of new patients with T1-4N0-1B0M0 mycosis fungoides treated with total skin electron beam radiation. METHODS AND MATERIALS: 25 consecutive patients received 30 Gy with 3 or 4 MeV electrons in 1977-1980; 121 received 35 Gy with 4 MeV in 1980-1992. Response rates, relapse-free survival, and overall and cause-specific survivals were assessed by explicit criteria. The relationships of T, N, gender, age, and radiation technique to prognosis were investigated by regression statistics. RESULTS: The average age was 55 years and the male:female ratio was 1:4. Forty-four percent were T1N0 and 34% were T2N0. The overall complete response rate was 82%, and lower T status, more radiation, and female gender were independently and positively associated with response. Median follow-up was 5.2 years. T1 patients who entered remission had a higher relapse-free survival compared to T2 through T4 patients. Thirty-four percent of T1 patients remained relapse-free at 6 years, compared to fewer than 20% of T2-4 patients. For all 146 patients the median overall survival was not reached at 15 years. Only 8 of 29 deaths were related to mycosis fungoides and these were significantly associated with higher T. The 54 T1N0 patients who had 35 Gy had a 10-year mycosis fungoides-specific survival of 100%. CONCLUSION: Total skin electron beam radiation gives good results with T1N0B0M0 disease. T3-4 disease is less likely to respond, it relapses more quickly, and it implies a poorer survival, but radiation offers palliation. T2 responds like T1, but relapses like T3-4. T2 also implies an intermediate survival. These results have implications for staging, informed consent, optimizing radiation treatment, and clinical trials.

Female↗

Interferon-alpha therapy for hepatitis C virus infection after liver transplantation.

The aims of this pilot study were to evaluate the safety and efficacy of interferon-alpha 2b for treatment of hepatitis C virus infection in liver transplant recipients, to monitor changes in hepatitis C virus RNA levels with treatment and to determine pretreatment parameters predictive of a complete response. Eighteen patients with documented hepatitis C virus viremia and histological evidence of hepatitis after liver transplantation received 3 million units of alpha interferon three times weekly for at least 4 mo. Pretreatment serum aminotransferase levels were at least 1.5 times the upper limit of normal and no patient had concomitant hepatitis B virus infection. Response to therapy was defined as normalization of both aspartate and alanine aminotransferase at the end of treatment. Five patients (28%) had a complete response, whereas 13 (72%) had persistent elevation of one or both aminotransferases (nonresponders). At the end of therapy, hepatitis C virus RNA levels were reduced in both responders and nonresponders (p = 0.043 and 0.039, respectively by Wilcoxon signed rank test). After cessation of treatment, aminotransferases remained normal in four of five responders but serum hepatitis C virus RNA levels returned to pretreatment levels in responders and nonresponders. There was no significant change in histological score with therapy. Responders were more likely than nonresponders to have low pretreatment hepatitis C virus RNA levels and low serum bilirubin (p = 0.0004 and 0.0077, respectively). Responders tended to have a prolonged interval between transplantation and initiation of therapy (p = 0.10 by rank logistic regression analysis). Side effects resulted in early cessation of therapy in two patients and dose reduction in six.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Somatic gene transfer to the adult primate central nervous system: in vitro and in vivo characterization of cells genetically modified to secrete nerve growth factor.

Somatic gene transfer offers a means of delivering substances to the central nervous system (CNS) in a regionally specific, high-dose, chronic and well-tolerated manner. Studies in rats have shown that genetically modified cell grafts can prevent neuronal degeneration and promote functional recovery after injury and can improve cognitive function in aged subjects. To assess the potential utility of somatic gene transfer techniques in primate models, retroviral vectors were used to modify genetically monkey and human primary skin fibroblasts to produce and secrete human nerve growth factor (NGF). In vitro, all cell types produced NGF and sustained this production through cell growth to confluency, as determined by both Northern blot analysis and ELISA. Adult human fibroblasts produced as much NGF as did young human fibroblasts. Monkey fibroblasts genetically modified to produce NGF were then grafted to intact adult rhesus and cynomolgous monkey brains. Among nine primates that received a total of 76 grafts, surviving cells were found in all subjects up to the maximal experimental timepoint of 6 months. Cholinergic fibres from the host brain penetrated NGF-secreting grafts up to 6 months after grafting, but showed little penetration in control grafts lacking the NGF gene. Autografts survived better than allografts. These findings indicate that both human and primate fibroblasts can be transduced to produce and secrete NGF, can maintain this production whether in a growing or quiescent state and can elicit robust sprouting responses when primate fibroblasts are grafted to the adult brain. Cells genetically modified to produce trophic factors are a useful model for studying in vitro and in vivo CNS plasticity and for testing potential therapies for neurodegenerative conditions.

Animals↗

Quantitation of hepatitis C virus RNA in liver transplant recipients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is common in liver transplant recipients, yet the effects of immunosuppression on HCV RNA levels and the relationship of HCV RNA levels to hepatic damage have not been studied. METHODS: To explore these issues, we measured HCV RNA in serum by polymerase chain reaction amplification and branched DNA assay from 100 HCV-infected patients undergoing liver transplantation. RESULTS: Mean posttransplant levels were 16-fold higher than pretransplant values (7,935,000 and 496,000 Eq/mL, respectively; n = 65; P < 0.0001). Patients with high pretransplant levels had higher mean posttransplant levels than those with low pretransplant levels (17,119,000 and 6,504,000 Eq/mL, respectively; P = 0.064). Posttransplant levels were similar in patients with recurrent and acquired infection and were independent of time of sampling. Fifty percent of patients with HCV infection had normal liver biopsy specimens, and there was no strong relationship between level of viremia and degree of hepatic damage. CONCLUSIONS: HCV RNA levels increase markedly following liver transplantation. The frequent finding of viremia in the absence of histological hepatitis suggests that a "carrier state" is common. Absence of allograft damage in some (despite high levels of viral RNA) suggests that in immunosuppressed patients, HCV infection may be tolerated without direct hepatic damage.

Base Sequence↗

Prenatal cocaine exposure affects the development of aortic adrenergic innervation and contractile responses.

This study examines the effects of prenatal cocaine administration on the development of vascular sympathetic innervation and contractile responsiveness. Rabbits received cocaine (4 mg/kg, iv, bid) or saline during gestational days 8 to 29. Aortas were obtained on postnatal days 10, 20, 30 and 50. Vascular smooth muscle responsiveness was assessed by measuring aortic contractile responses to norepinephrine (NE) and to other vasoconstrictors. Vascular adrenergic innervation was evaluated by measuring desipramine sensitive [3H]-NE uptake into aortic ring segments and aortic NE content. [3H]-NE uptake and NE content were reduced at postnatal days 10 and 20 in the rabbits exposed prenatally to cocaine. Differences were not observed at postnatal days 30 or 50. The contractile response to NE was reduced in rabbits exposed to cocaine prenatally. Maximal response and potency were decreased at postnatal day 10 and potency was still decreased at day 20, but not at the older ages. Contractile responses to serotonin (5-HT) and angiotensin II (AII) were not affected by prenatal cocaine exposure. These results suggest that prenatal cocaine exposure delays the development of aortic adrenergic innervation and alpha adrenoceptor responsiveness.

Angiotensin II↗

Assessing residents' performance in C-L psychiatry. Work in progress.

The scores from the Psychiatry Resident In Training Examination (PRITE) provide useful information concerning residents' acquired knowledge about consultation-liaison (C-L) psychiatry. However, a comparable method for assessment of C-L residents' clinical skills has not been developed. A task force was commissioned by the Consultation-Liaison Psychiatry Section of the Association for Academic Psychiatry to develop such an assessment system. This paper presents the work of that task force and includes a methodology for assessing clinical performance, a prototype evaluation form, and instructions for its use.

Clinical Competence↗

Liver transplantation for hepatitis C virus-related cirrhosis.

Since the introduction of techniques to reliably identify antibody to the hepatitis C virus and quantitation of hepatitis C virus, there has been an increasing interest in the behavior of chronic hepatitis C infection with liver transplantation. Ninety-seven patients with chronic active hepatitis C and fifty-nine patients with cryptogenic cirrhosis underwent 100 and 62 liver transplantation procedures, respectively, at a single institution. This represents 35% of the total liver transplantations performed during this time period. Twenty-three percent of transplants were performed in patients with evidence of chronic active hepatitis C. Patients and graft survival were excellent in both groups. One-, 2- and 3-yr patient survival rates for chronic active hepatitis C and cryptogenic cirrhosis were 94%, 89% and 87% and 84%, 84% and 73%, respectively. Hepatitis C can frequently be identified after transplantation. More than 95% of patients show persistence of antibody to the hepatitis C virus. Forty-one of 95 patients (surviving > 1 mo) showed recurrent hepatitis (initially seen 3 to 20 mo after transplantation), and 12 progressed to chronic active hepatitis. In 16 patients of the cryptogenic group in whom hepatitis developed, 11 were associated with de novo hepatitis C infection. Seven of these 11 cases went on to a chronic state. Of 11 deaths after transplant in the hepatitis C group, 2 were directly related to recurrent disease. There were 15 deaths in the cryptogenic group, 2 related to de novo hepatitis C. Patients were not serotyped. Interferon therapy was attempted in a small number of patients with disease, with inconclusive results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Audit of health services--the crucial role of information.

A healthcare delivery agency evaluates its effectiveness and efficiency by the use of audit techniques. The audit can either be an ad hoc occurrence or part of a scheduled programme of examination and can be initiated by a specific concern, review of good practice or a process of change. Information plays a crucial role in defining the actual situation and informing the discussion from the earliest pre-audit stage to the decision-making process which follows the assessment of the audit outcomes. Measurement of any changes that have actually occurred as a result of actions undertaken is very important. It is necessary to quantify the movement from a baseline since the last scrutiny, rather than rely on anecdotal evidence or perceptions. The information to underpin the consideration of the topic of the healthcare audit must be consistent, contemporary, complete and correct information. This paper makes observations based on a number of studies carried out in the UK for both public and private healthcare organizations, and stresses the need for the availability of good information to determine the benefits of actions taken and changes made.

Data Collection↗

Community-based epidemiological investigations of cysticercosis due to Taenia solium: comparison of serological screening tests and clinical findings in two populations in Mexico.

We compared a plate enzyme-linked immunosorbent assay (ELISA) with an immunoblot--or enzyme-linked immunoelectrotransfer blot--assay (EITB) for the identification of cases of human neurocysticercosis due to Taenia solium and of risk factors for this disease in two Mexican villages. Findings related to age- and sex-specific seroprevalence, risk factors for transmission, and associated morbidity differed significantly according to the assay used. Rates of EITB positivity were significantly higher among persons with a history of convulsions than among those without such a history (29% vs 8%; P < .05); in contrast, ELISA results were negative for all persons with a history of convulsions. The association of seizures with neurocysticercosis in this population was strengthened by the higher rate of abnormal findings compatible with neurocysticercosis on computed tomography of the brain among individuals with a history of convulsions than among those without such a history (70% vs 14%; P < .001). In summary, EITB was more sensitive and specific than ELISA for epidemiological studies of neurocysticercosis.

Adolescent↗

Nurses' attitudes towards termination of pregnancy.

This questionnaire study (n = 84) investigated several aspects of the attitudes of nurses of various grades and clinical settings towards termination of pregnancy (TOP). The majority of nurses had attitudes which lay within the undecided to positive range of the continuum, similar to findings from previous North American and British research. Very few were found to have extremely positive or negative attitudes. Several factors were significantly associated with negative attitudes towards TOP: frequency of involvement in TOP, length of time spent working on a gynaecology ward, religious affiliation, and ethnicity. Some discrepancy in nurses' attitudes was found with respect to both the length of a woman's gestation and the circumstances for which the procedure was being performed. In view of these findings, the implications for nursing practice are discussed.

Abortion, Induced↗

Evaluating physician impact analysis. Methods, results, and uses in Ontario Hospitals.

Physician impact analysis (PIA) is a planning tool intended to bring greater predictability to hospital medical staff resource planning by providing a means to predict the impact of a new or replacement physician's practice profile on a hospital's clinical program priorities, staffing resources, and costs. Two key methods advocated to undertake PIAs are the Department Survey Method and the Hospital Medical Records Institute Case-Mix Groups/Resource Intensity Weights Methods developed by the Hospital Medical Records Institute. This article discusses issues related to the methods, results, and uses of PIA information in Ontario hospitals. Further evaluation of the PIA process is recommended to increase our understanding of both the strengths and limitations of this planning tool.

Diagnosis-Related Groups↗

A new assay for intracellular measurement of inosine monophosphate dehydrogenase activity: a guide for better selection of patients for enzyme-targeted chemotherapy.

We developed a new cytochemical assay for identification of cells containing inosine monophosphate dehydrogenase (IMPDH) and measurement of tumor cell sensitivity to the escalating dose/schedule of the IMPDH pattern-targeting drugs. The assay is based on cytochemical principles for development of DH activity markers inside morphologically classified cells, image analysis for measuring the amount of this marker, and computer assistance for data management. The assay was optimized on a human leukemia cell line (K562-NS) and reference values for enzyme activity were established. Assay specificity was determined with different substrates and enzyme inhibitors. Sensitivity depends on the measuring instrument (image analyzing system), and the precision of the biological model used for assessment of reference values was high. IMPDH-positive malignant cells were found in all specimens obtained from acute leukemia and solid tumor patients (13/13 and 29/29) and in four human tumor cell lines (K562, K562-NS, HL60, and HL60-M). Cells of the K562-NS line were exposed to tiazofurin and ribavirin in conventional assays for assessment of drug-induced acute and subacute toxicity/sensitivity. A reduction of IMPDH activity was recorded at drug concentrations below the range at which cell damage appeared.

Acute Disease↗