On the use of nonphysician "associate residents" in overcrowded specialty-training programs.
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Biomedical subjects
Publications and source records attributed to H K Silver.
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The Hospital Nurse Practitioner Program in Pediatrics at the University of Colorado Health Sciences Center, Denver, prepared staff nurses for a new and expanded role as health care providers in hospital settings. With the use of their increased skills and greater decision-making responsibilities, hospital nurse practitioners admitted patients to the hospital, assessed both the initial clinical status and subsequent changes in the patient's condition, wrote relevant orders, performed a variety of technical procedures (including many previously reserved to house staff and other physicians), ordered and interpreted laboratory studies, counseled patients and families, discharged patients, and provided other traditional nurse practitioner skills. Hospital nurse practitioners had an improved collaborative relationship with physicians. This program showed that hospital nurse practitioners can be as significant in affecting the health care that patients receive on the general units of hospitals, as are nurse practitioners who deliver care and services to ambulatory patients.
Interferon has been shown to have antineoplastic activity but an optimal dose schedule has not been defined. In this phase I study 12 patients with advanced cancer were treated with weekly high-dose human lymphoblastoid interferon given by 3-hour iv infusion to assess toxicity. The median maximum tolerated dose was 55 X 10(6) units/m2 and the dose-limiting toxicity was a complex of fever, fatigue, myalgias, anorexia, and weakness. Neither myelosuppression nor hepatotoxicity was encountered. One patient with metastatic melanoma achieved complete remission, which has been maintained for 2 years. Weekly high-dose iv infusion of interferon has antineoplastic activity, did not cause myelosuppression or hepatotoxicity, and was well-tolerated up to doses of 40-50 X 10(6) units/m2. Future trials should start at 30 X 10(6) units/m2 and should escalate by 10 X 10(6) units/m2/week to patient tolerance.
Initial adjuvant immunotherapy trials have demonstrated a greater disease-free interval in patients treated with bacille Calmette-Guérin (BCG) compared with historical controls. In this study 149 patients at high risk of recurrence after surgical treatment of local or regional malignant melanoma were given BCG for 2 years and were followed up for a median of 28 months from the start of immunotherapy. The 36 patients in the comparison group had a higher rate of recurrence than the patients treated with BCG, and the rate in the treatment group was close to that reported from a similar study at the University of California at Los Angeles. The relatively long disease-free interval for the high-risk comparison patients in this study suggests that the control groups at other centres may have included patients with unrecognized additional risk. The rates of survival in the Canadian treatment group were also comparable to those reported by other centres. However, reports of a favourable BCG-mediated pattern of recurrence could not be confirmed. Therefore, the routine use of adjuvant BCG immunotherapy is not recommended.
Since serum N-acetylneuraminic acid (NANA) can serve as a relatively sensitive monitor of tumor burden, we wished to examine the relationship of NANA to other suggested prognostic factors for malignant melanoma. Eligible patients included 151 patients with stage-I disease and 10 with stage-II regional lymphatic extension. A proportional hazards model was used to examine nine factors, of which five were not significant predictors of recurrence: age, sex, primary site, tumor diameter, and stage. Significant predictors included: measured depth p = 7 X 10(-7); anatomic depth (Clark level), p = 7 X 10(-6); NANA, p = 0.003; and growth pattern (superficial spreading vs nodular), p = 0.01. However, on multivariate analysis only two predictors were independent; measured depth and NANA. The latter could not be explained by non-specific factors. The data were examined to define optimal test values for assignment of risk. According to this model, patients with lesions greater than 1.75 mm and NANA less than 2 mumol/ml have a more than 12-fold greater risk of recurrence by 2 years than those with lesions less than or equal to 1.75 mm and NANA less than or equal to 2 mumol/ml.
The vast data pertaining to circulating immune complexes (CIC) detection and their possible clinical significance in human neoplasia have been reviewed. The clinical relevance of CIC occurrence in cancer patients' sera provide important non-diagnostic information on staging, evaluation of prognosis, detection of early recurrence, and quantitation of tumor response to treatment. A variable prevalence of CIC in cancer patients is now well established. The several reasons which made no available test entirely satisfactory for clinical use, have been discussed indicating the importance of molecular size and composition heterogeneity of CIC detected in cancer patients. Although the evaluation of CIC by current assays represents the antithesis of pre-diagnostic patients management, there are solid reports to suggest its possible clinical application. Those studies noting the relevance of CIC fluctuation to the evaluation of prognosis, monitoring of therapy and assessment of tumor burden were best attained when an effort to quantitate residual disease was undertaken. In addition, attempts to remove CIC from cancer patients circulation by plasma exchange alone or with extracorporeal immunoadsorption have resulted in a better understanding of a frequently observed immunomodulation. This modality provided a challenging and provocative new approach to cancer therapy which deserved prompt corroboration.
The effect of interferon dose on lymphocyte subsets is unclear for humans, especially with prolonged intermittent administration. Enumeration of T4 and T8 cells and natural killer (NK) cell activity against K562 cells were examined as part of our ongoing randomized clinical study comparing low- and high-dose treatment strategies. Fifty-four patients have been entered into study, of which 46 are now evaluable. High-dose patients showed no significant changes during actual interferon infusion. However, over the entire period on study, there was a significant increase in NK cell activity (p = 0.001), a concurrent decrease in T8 (p = 0.004), and an increase in T4/T8 (p = 0.02). By contrast, for low-dose patients there was a trend of increasing NK activity during interferon administration, but no change during the total time on study, with a concurrent trend of decreasing T4/T8 and a significant increase in T8 (p = 0.01). Although there is as yet no significant response difference between high- and low-dose treatments, a favourable response was associated with an overall increase in NK activity (p = 0.005), a decrease in T8 (p = 0.02), and an increase in T4/T8 (p = 0.03). In a preliminary study of immune complexes in selected patients, an inverse relationship between NK cell activity and immune complex concentration was suggested. This was supported by in vitro addition of autologous immune complex-containing sera during NK cell assay.
A radioimmunoassay (RIA) method for acid phosphatase detection was compared to a standard enzyme assay using sera from 210 normal volunteers and 285 patients with prostatic disease. Statistical and clinical comparisons were made between defined subgroups. All 55 normal females had RIA detectable serum acid phosphatase, implying that this assay cannot be entirely specific for enzyme of prostatic origin. Urinary catheterization did not affect acid phosphatase levels. In all stages of carcinoma there were more acid phosphatase elevations by the RIA method than enzyme method, but neither assay could differentiate intracapsular cancer from benign prostatic hyperplasia. A small number of patients with biopsy proven negative nodules had marginally elevated values, suggesting as obligation for closer follow-up. The RIA method may be superior for monitoring patients with more advanced malignancy. Additional practical advantages of the RIA include relative simplicity and elimination of the special serum handling required for the enzyme assay.
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Twenty-eight patients with advanced malignant melanoma were treated with high dose methotrexate (HDMTX) and folinic acid (FA) rescue. Nineteen patients were treated with 6-hour infusions and 10 patients with 24-hour infusions. One patient in the 6-hour infusion group showed a partial response. In the 24-hour infusion group there were no responses but there was a significant increase in renal toxicity. It is concluded that HDMTX and FA rescue are not useful agents in the treatment of advanced malignant melanoma.
More than 20 studies have been carried out of child health associates to assess their knowledge, training, and practice; their ability to interpret and integrate data; their cognitive knowledge and psychomotor and interpersonal skills; and their competence and effectiveness as a primary health care providers. The results of the assessment and evaluation studies of child health associates indicate that they can determine the health status and manage the health care of patients in ambulatory settings and in the newborn nursery with a degree of skill and competence approaching that of pediatricians. Child health associates can provide comprehensive primary health care for more than 90% of children seen in these settings. The high degree of acceptance of child health associates by families and their demonstrated proficiency and cost-effectiveness document that they can be an important source of primary health care for most children.
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Tumor-associated antigen(s) from a specimen of human malignant melanoma and from spent culture medium of a melanoma cell line were extracted and purified. The incidence of antibody activity to these antigens, in sera from cancer patients with neoplasms of various histologic types, was higher (65--83%) than normal donors' (19--25%) by the complement fixation assay. These purified antigens were then used to raise antisera in rabbits and sheep. After absorption with various human normal tissues, these antisera reacted against melanoma, sarcoma, and carcinoma extracts, but not against human normal liver, skin, or muscle extracts. However, the antisera showed reactivity against a human fetal homogenate. Results indicate that the xenogeneic antisera contained antibodies to fetal antigens and to tumor-associated antigen(s). Xenogeneic antisera could be used to purify tumor-associated antigens and oncofetal antigen(s) from crude extracts by affinity chromatography.
Reported elevations of total serum sialic acid may be a result of shed tumour-related membrane sialyglycoprotein and/or concurrent elevation of non-specific, acute-phase reactant sialoglycoprotein. To clarify further the specificity and sensitivity of serum sialic acid monitoring, analyses of sialic acid by the thiobarbituric acid method and acute-phase reactants by radial immunodiffusion were made using the same malignant melanoma patients' sera. Preliminary studies of IgG, IgA, IgM, ceruloplasmin and C-reactive protein suggested that these would not be valuable monitors of tumour burden. Single serum samples from 59 melanoma patients and age- and sex-matched controls were further examined for sialic acid, alpha 1-acid glycoprotein, alpha 1-antitrypsin, haptoglobin, and alpha 2-macroglobulin. Patients were grouped according to tumour burden. In pairwise statistical tests, differences between groups tended to be greater for sialic acid than for acute-phase reactants. On discriminant analysis , sialic acid was clearly the most significant single discriminator between groups, with an F statistic of P < 0.00005. Although alpha 1-acid glycoprotein was quite strongly correlated with sialic acid, it was not such a good discriminator and did not add significantly to the predictive power of sialic acid alone.
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