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Biomedical subjects

L S Miller

Publications and source records attributed to L S Miller.

At least 127 records · Page 7Linked to original sources

The comparative evaluation of California's multipurpose senior services project.

The Multipurpose Senior Services Project implemented a case management model of service coordination for aged Medicaid recipients at eight sites throughout California. The answers to the evaluation questions--"What works?", "For whom?", and "At what cost?" provide policy direction for long-term care programs. The research and demonstration Project ended in June 1983 and an on-going Program began in July 1983. Dynamic modeling of the outcomes of MSSP and of a comparison group served by the existing service system showed that MSSP increased longevity, decreased nursing home days, and decreased hospital days (in 1982); these results were most efficient for the frailest clients. This group had the greatest savings on public service dollars, with the Federal government the beneficiary through lower than expected Medicare expenditures. In-home supportive services proved to be the most productive non-medical service in both systems, but was more productive through MSSP. The evaluation methodology provides a multivariate frailty measure based on expected nursing home entry that can be used to identify those individuals for whom case management is most likely to have efficient outcomes.

Aged↗

Augmentation of immunity to herpes simplex virus by in vivo administration of interleukin 2.

The immune mechanisms responsible for recovery from herpesvirus infections are multiple and include a principle role for aspects of T cell immunity. Our investigations add further support for this notion. We show that the ability of immune lymphocytes from animals infected i.p. 6 wk previously with herpes simplex virus type one (HSV-1) clear virus more effectively when interleukin 2 (IL 2) is injected into recipients of the adoptive transfers. Mice were treated on two consecutive days with cyclophosphamide and infected in the pinnae with 4 X 10(6) plaque-forming units of HSV-1. Three hours post-infection lymphocyte populations were injected i.v., and after a further 3 days the pinnae were removed, homogenized, and the content of infectious virus assayed. Purified IL 2 obtained from EL-4 cells either was given i.v. 2 hr before and 24 and 48 hr after cell injection or was given subcutaneously 2 hr before and 3, 24, and 48 hr after cell injection. The latter three injections were given i.p. and suspended in 15% gelatin. The immune lymphocyte cell populations were splenocytes and were either injected immediately after preparation of cell suspensions or after 5 days in vitro secondary stimulation with HSV-1. This latter cell population showed greater viral clearance activity, a function shown previously to be a property of Lyt-2+ cells. The clearance activity of cells was markedly enhanced in animals given IL 2 but only with a regimen that included injections in gelatin, a procedure that enhances in vivo circulation time of IL 2. The cell involved in clearance was a T cell and principally the Lyt-2+ subset. Treatment of recipient mice with anti-asialo GM-1 did not affect the clearance efficiency, indicating that NK cells were not responsible for the observed effect. Our experiments indicate that IL 2 may provide an important regulator of immune function in vivo and may warrant its investigation as a therapeutic agent to enhance antiviral immunity in certain circumstances.

Adjuvants, Immunologic↗

Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies.

Attempts at histochemical localization of estrogen receptor with anti-steroid antibody or some fluoresceinated estrogens have given unacceptable sensitivities and specificities when compared with biochemical methods or clinical response. In the present study a monoclonal antibody against estrogen receptor (H222 Sp gamma) was used on cryostat sections of freshly frozen breast tumors with a peroxidase-antiperoxidase immunoperoxidase technique. Biochemical receptor analyses were by dextran-coated charcoal analyses. Tumors from three separate cohorts of patients were studied as follows: population A, 62 primary breast cancers from 1983; population B, 72 primary lesions stored from 1976 to 1983; and population C, 23 patients with metastases, treated with hormonal therapy. Distinct staining was seen in the cell nucleus. A semiquantitative relationship was seen between histochemical score assessment of staining and biochemical assay in each cohort. The sensitivity and specificity using a threshold of 75 for the histochemical score and more than 20 femtomoles/mg of protein for dextran-coated charcoal analyses were as follows: population A, specificity, 89%, and sensitivity, 95%; population B, specificity, 94%, and sensitivity 88%; and for population C, the comparison was with objective clinical response yielding specificity, 89%, and sensitivity, 93%.

Antibodies, Monoclonal↗

Isolation and sequence analysis of cDNA clones coding for rat skeletal muscle creatine kinase.

A series of cDNA clones corresponding to 1494 bases of rat muscle creatine kinase mRNA has been isolated and characterized. The identity of these clones has been confirmed by DNA sequence analysis and by comparison of the predicted amino acid sequence with that determined for the purified protein. The cDNA sequence accounts for the entire coding sequence of the creatine kinase protein in addition to the complete 3' untranslated region and 68 bases of 5' noncoding region. Sequences corresponding to the active site region of the protein, the initiation codon, the termination codon, and poly(A) addition signal have been identified.

Amino Acid Sequence↗

Rehabilitation social workers: measuring their ability to predict discharge destination of rehabilitation patients.

Most rehabilitation centers only admit patients for rehabilitation who have a reasonable chance of being discharged to a noninstitutional setting. With certain classifications, such as stroke, 20 to 30% of patients are often discharged to a skilled nursing facility (SNF). Problems associated with rehabilitation admission procedures make careful psychosocial determinations difficult. We attempted to have experienced rehabilitation social workers predict discharge placement following a formal evaluation. Three experienced rehabilitation social workers met formally with patients and/or families for an initial interview following admission to the rehabilitation unit. They assessed the functional goals developed by the rehabilitation team and predicted which patients would go home and which would go to a SNF. Their predictions were compared to the actual discharge placement. A chi square test revealed that the social workers accurately predicted discharge home but were unable to accurately predict which patients would go to an SNF. Of those predicted to return home, 95% did so. Of those predicted to go to an SNF, only 57% did so. Of the total sample of 126 patients, 86% were discharged home and 14% were discharged to an SNF. This finding suggests that patients should not be denied a trial of rehabilitation solely on the basis of projected discharge placement.

Aftercare↗

Effect of chronic cold and submergence on blood oxygen transport in the turtle, Chrysemys picta.

Whole blood oxygen equilibrium curves (O2EC's) and related hematologic properties are reported for the turtle Chrysemys picta exposed to two experimental conditions. Summer turtles were maintained at 24 degrees C with free access to air; winter turtles were submerged for 4-12 wk in N2-bubbled water at 3 degrees C. Half-saturation Po2's at 3 degrees C for blood from summer and winter animals were 4.1 and 4.5 Torr, respectively. At 24 degrees C, summer and winter P50's were 20.2 and 22.7 Torr, respectively. The winter turtle P50 values were lower than predicted since prolonged submergence effected a severe metabolic acidosis; blood pH's for winter turtles were 0.65 pH unit lower than for summer animals at both temperatures. Cold submergence also had a profound influence on O2EC shape. Winter turtle curves exhibited high O2 affinity below P50 while they were distinctly right-shifted above 50% S. Winter animals also exhibited reduced CO2-Bohr coefficients (delta log Po2/delta pH) at 3 and 24 degrees C. Prolonged submergence did not affect the animal's isohemoglobin profile (demonstrated by isoelectric focusing) or [metHb]. The [ATP] and [DPG] in winter turtle red cells, however, decreased significantly; the ratio of organic phosphate ([ATP] + [DPG]) to Hb tetramer fell from 1.4 in summer animals to 0.5 in winter turtles. These findings suggest that the effect of chronic cold and prolonged submergence on turtle O2EC position and shape may result from reduction in RBC organic phosphates. Furthermore, these observed changes in blood oxygen transport may facilitate O2 loading during winter submergence via extrapulmonary gas exchange.

Acid-Base Equilibrium↗

Immunoperoxidase localization of estrogen receptors in human brest carcinoma.

Monoclonal antibodies to the estrogen receptor protein were used to evaluate the specificity of the peroxidase antiperoxidase (PAP) method for localization of estrogen receptors (ER) in human breast carcinoma. Twenty-five cases of breast carcinoma were selected, and they were roughly classified as ER-rich and ER-poor tumors based on ER levels as determined by dextran-coated charcoal (DCC) assay. ER-rich tumors showed strongly positive cytoplasmic and, to a lesser degree, nuclear staining. Both the cytoplasmic and nuclear staining were less intense in ER-poor tumors, and the staining intensity varied from one to another cell population in the same tumor. Completely negative cells were also observed. The results of the PAP and DCC methods correlated fairly well in ER-rich tumors but not in ER-poor tumors. The PAP method provided visual localization of ER combined with excellent tissue morphology. Application of both methods (DCC and PAP) may provide better assessment of the estrogen receptor levels in breast carcinomas.

Breast Neoplasms↗

Hyperthermia in cancer treatment: current and future prospects.

The renewed interest in the possible use of localized hyperthermia in cancer therapy is prompted by two major realizations. The first is the radiobiological evidence indicating that there may be a significant advantage in the use of heat alone or combined with radiation therapy or chemotherapy to enhance the inactivation of tumor cells The second is that early clinical investigation with refractory malignant tumors at temperatures between 41 degrees C and 45 degrees C have shown tumor regression response rate over 70% without increasing normal tissue complication. A phase I/II study using electromagnetic hyperthermia immediately following administration of ionizing radiation was begun at Duke in the fall of 1976 to evaluate the response of normal tissues, the regression of cutaneous and subcutaneous tumors, and the feasibility of such combined modalities in therapeutic radiology. Each hyperthermia session consisted of 45 minutes at 42-43.5 degrees C 2-3 times per week immediately following radiotherapy. The radiation therapy fraction size was usually 2-3 Gy 3-5 times per week with a maximum total of 48 Gy. The 60+ patients treated to date have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, liposarcoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 600 hyperthermia sessions, we have found: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a significantly higher level of preferential heat induction into tumor tissue is possible as compared to surrounding normal tissues; (3) repeated hyperthermia at 42-43.5 degrees C for 45 minutes per session immediately following radiation therapy yields favorable therapeutic results. Tumor regression response rate of over 70% was achieved without concomitant increase of normal tissue complication. Therefore, the potentially significant impact on clinical cancer therapy, whether of curative or palliative intent, by moderate thermotherapy is evident. Technical advances to optimize such treatment methods including R & D for delivering a known localized quantity of heat to tumors in any location in the body are expected to progress rapidly. The methods with most promising potential for inducing local thermotherapy are those involving the use of electromagnetic waves, e.g., radiofrequency energy, microwave energy, and ultrasound energy.

Aged↗

Microwave-induced local hyperthermia in combination with radiotherapy of human malignant tumors.

Since 1976, two groups of patients have been treated with local microwave hyperthermia immediately following ionizing radiation. Group A patients had measurable multiple lesions assigned radiotherapy only, microwave hyperthermia only, or combined treatment. Ionizing radiation in 200-600 rad fractions was used 2-5 times per week to a total of 1800-4200 rad in 5-14 fractions. Group B patients had combination treatment only, with radiation fractions of 200-600 rad 2-5 times per week to a total of 2000-4800 rad total in 6-20 fractions. Both groups received hyperthermia (42-44 C) 2-3 times per week, maximum ten sessions in four weeks. The 19 patients treated have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 150 hyperthermia sessions, we find: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a higher level of heat induction in tumor tissue as compared to surrounding normal tissues; (3) repeated hyperthermia at 42-43.5 C for 45 minutes per session immediately following photon irradiation yields a favorable therapeutic result, occasionally dramatic. Local microwave hyperthermia in combination with radiotherapy offers the possibility of substantial impact on clinical cancer therapy, whether of curative or palliative intent.

Adolescent↗

Rehabilitation outcome: comparative analysis of different patient types.

Postdischarge progress in 11 types of patients was analyzed with regard to eating, dressing, transfers, bladder management, ambulation, cognition, language comprehension and speech, placement (living arrangement), and mortality rates. Of 273 patients admitted, 263 were available for foillow-up, which disclosed that patients with lower bladder management and cognition scores are more likely to be directed into restrictive discharge placements (p < 0.05), and that CVA patients with right and left cerebral hemisphere involvement, cancer patients, and patients with brain stem infarctions make significant postdischarge gains in ADL (p < 0.05). The majority of patients showed continual improvement after discharge, some making significant gains in functional competency. Such program evaluation offers a systematic method for forecasting post-discharge outcome.

Activities of Daily Living↗

Pulmonary embolism in stroke: prevention by early heparinization of venous thrombosis detected by iodine-125 fibrinogen leg scans.

During an 8-month study of stroke patients, a 9% incidence of pulmonary embolism and a 1.5% incidence of thrombophlebitis was found among hemiparetic patients undergoing intensive rehabilitation after being medically stabilized. Patients were usually studied 10 days to 2 weeks after the onset of stroke. During the next 18 months, 141 subsequent patients were studied with 125I-fibrinogen uptake leg scans, disclosing a 29% incidence of deep venous thrombosis. Venograms were obtained in 28 patients; clots in 25 patients were confirmed in normal locations on the fibrinogen scan, and there was 1 false negative and 2 false positives. The subsequent 14 patients with clot were anticoagulated on the basis of the fibrinogen scan alone. Early anticoagulation of clinically silent leg thrombi prevented any pulmonary emboli.

Adult↗

Development of a statewide program for surveillance and reporting of hospital-acquired infections.

In 1974, a statewide program was begun to improve surveillance of nosocomial infection in Virginia hospitals. Infection control practitioners were trained at the University of Virginia Hospital, Charlottesville, and were encouraged to submit monthly surveillance reports for analysis. In the first three years of the project, 141 students from 65 hospitals within the state attended a two-week basic course, with eight to 10 students per class. Of the 98 Virginia hospitals that sent students, 75 (73%) submitted monthly reports. The consistency of reporting (number of monthly reports received divided by the number of possible reporting months) was 83%. The sensitivity of reported data was estimated in comparative daily prospective surveys to be 69% for participating hospitals, and the specificity was 99%. The crude infection rate for the first 1.1 million patients at risk was 3.3%.

Cross Infection↗

After-loading transperineal iridium-192 wire implantation of the prostate.

Aided by suprapubic surgical access, after-loading transperineal iridium-192 wire implantations have been done for prostatic cancer in 16 patients, with major complications in 3. Personnel exposure is reduced, and, more especially, precision and flexibility of dose control and source geometry are improved. The technique is thought to render permanent implantation with grains or seeds obsolete.

Humans↗