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Biomedical subjects

R A Miller

Publications and source records attributed to R A Miller.

At least 289 records · Page 16Linked to original sources
PubMed1990

The role of midazolam and flumazenil in urology.

The effects of midazolam (3-10 mg i.m.) and their reversal by flumazenil were studied in transurethral endoscopic procedures performed using topical analgesia. In one randomised study, patients (n = 84) received either no medication or flumazenil (0.5 mg i.v.) on completion of endoscopy. Recovery was assessed subjectively. Within 15 min, 83% of those receiving flumazenil were considered ready for discharge compared with only 24% of the control group (P less than 0.001). In a second randomised, double-blind, placebo-controlled trial of 44 patients, post-operative recovery was assessed using five objective psychomotor tests. Whereas the placebo group took up to 2 h to recover, those receiving flumazenil recovered fully or returned to near control values within 15 min. Sedoanalgesia--a technique combining adequate local anaesthesia with sedation (using midazolam)--has wide application in urology, and the introduction of flumazenil has major implications for the practice of day-case surgery.

Adult↗
PubMed1990

Sedoanalgesia in urology: a safe, cost-effective alternative to general anaesthesia. A review of 1020 cases.

Sedoanalgesia is a technique developed to provide safe and satisfactory operating conditions for a wide range of patients independent of age and overall level of fitness (although its use in children remains to be established). It is suitable for both endoscopic and open procedures, day-cases and in-patients. When used in day-case surgery it significantly improves overall efficiency. It is recognised that day-case surgery is an important and cost-effective element in surgical care. With increasing restraints being imposed upon hospital finances, patient beds and staffing levels, any strategies designed to improve efficiency in this sphere of surgical activity are to be welcomed. That 93% of patients prefer sedoanalgesia to conventional general anaesthesia attests to its high degree of acceptability. The technique of sedoanalgesia, its applications and potential impact for urology are detailed.

Ambulatory Surgical Procedures↗
PubMed1990

Day-case surgery: enhanced recovery with flumazenil.

In an open, randomized, parallel group study of 84 adult patients undergoing elective day-case urological surgery the specific benzodiazepine antagonist flumazenil was shown to reverse effectively subjective postoperative sedation due to midazolam and enabled 83% of patients to recover and be ready for potential discharge within 15 min of surgery (control group 24% p less than 0.001). The significantly shorter recovery time has benefits in terms of increased patient cooperation and reduced demands on postoperative nursing care. The implications of these findings for day-case surgery are discussed.

Adult↗
PubMed1990

Inhalation toxicology and carcinogenicity of 1,3-butadiene in B6C3F1 mice following 65 weeks of exposure.

1,3-Butadiene, a large-production volume chemical used mainly in the manufacture of synthetic rubber, was found to induce multiple-organ carcinogenicity in male and female B6C3F1 mice at exposure concentrations (625 and 1250 ppm) equivalent to and below the OSHA standard of 1000 ppm. Since this study was terminated after 60 weeks of exposure because of reduced survival due to fatal tumors, and because dose-response relationships for 1,3-butadiene-induced neoplastic and nonneoplastic lesions were not clearly established, a second long-term inhalation study of 1,3-butadiene in B6C3F1 mice was conducted at lower exposure concentrations, ranging from 6.25 to 625 ppm. Both the histopathological findings from animals dying through week 65 and the results of evaluations of animals exposed for 40 and 65 weeks are presented in this report. Exposure to 1,3-butadiene caused a regenerative anemia at concentrations of 62.5 ppm and higher. Testicular atrophy was induced at 625 ppm, and ovarian atrophy was observed at 20 ppm and higher. During the first 50 weeks of the study, lymphocytic lymphoma was the major cause of death of mice exposed to 625 ppm 1,3-butadiene. Neoplasms of the heart, forestomach, lung, Harderian gland, mammary gland, ovary, and liver were frequently observed in 1,3-butadiene-exposed mice that died between week 40 and week 65 of the study. Studies in which exposure to 1,3-butadiene was stopped after limited periods were also included to assess the relationship between exposure levels and duration of exposures on the outcome of 1,3-butadiene-induced carcinogenicity. In these studies, lymphocytic lymphomas were induced in male mice exposed to 625 ppm 1,3-butadiene for only 13 weeks. The incidence of lymphocytic lymphoma in male mice exposed to 625 ppm 1,3-butadiene for 26 weeks was two times that in mice exposed to 625 ppm for 13 weeks. However, when the exposure concentration was reduced by half to 312 ppm and the exposure duration extended to 52 weeks, the incidence of lymphocytic lymphoma was reduced by 90%. Thus, the multiple of the exposure concentration times the exposure duration did not predict the incidence of lymphocytic lymphoma in mice. The early mortalities resulting from lymphocytic lymphomas in male mice exposed to 625 ppm 1,3-butadiene limited the expression of tumors at other sites. A clearer dose-response for 1,3-butadiene-induced neoplasia should be apparent from experiments in mice exposed to lower concentrations of this chemical for 2 years.

Air Pollutants, Occupational↗
PubMed1990

Morphology of neoplastic lesions induced by 1,3-butadiene in B6C3F1 mice.

1,3-Butadiene (CAS No. 106-99-0) was studied for potential carcinogenicity and chronic toxicity by inhalation in B6C3F1 mice. Groups of 50 mice of each sex were exposed to 0, 625, or 1250 ppm 1,3-butadiene for 6 hr/day, 5 days/week for 60 weeks (male) or 61 weeks (female). The study was scheduled for 104 weeks of exposure but was terminated early because of reduced survival related to induction of a variety of tumors in 1,3-butadiene-exposed mice. A second chronic inhalation study was conducted in which male and female mice were exposed to 0, 6.25, 20, 62.5, 200, or 625 ppm for up to 2 years. Additional groups of 50 male mice were exposed to 625 ppm for 13 or 26 weeks, 312 ppm for 52 weeks, or 200 ppm for 40 weeks, then held without exposure until scheduled sacrifice 104 weeks after initial exposure. 1,3-Butadiene-exposed mice from both studies had increased incidences of malignant lymphomas that were observed as early as week 20 in the first study and week 23 in the second study. The lymphomas were primarily lymphocytic and originated in the thymus, although generalized lymphoma was often present. Exposed mice in both studies developed cardiac hemangiosarcomas that were observed as early as week 32 in the first study and week 41 in the second study. Also present were foci of endothelial hyperplasia in the myocardium that were regarded as early evidence of developing hemangiosarcoma. Alveolar epithelial hyperplasia, alveolar/bronchiolar adenomas and alveolar/bronchiolar carcinomas represented the spectrum of proliferative lung lesions induced by exposure to 1,3-butadiene in both studies. Exposure-related proliferative forestomach lesions observed in both studies included epithelial hyperplasia, squamous cell papillomas, and squamous cell carcinomas. 1,3-Butadiene-exposed female mice in both studies developed mammary gland neoplasms at increased incidences. Most of the mammary tumors were pleomorphic adenocarcinomas, but several adenoacanthomas were also seen. Granulosa cell tumors of the ovary were exposure-related neoplasms in both studies. Occasionally the granulosa cell tumors were malignant as evidenced by vascular invasion or pulmonary metastasis. Although there was an increased incidence of hepatocellular neoplasms in exposed females in the first study, by week 65 of the second study there was not evidence of a clear response of liver neoplasms. The preliminary results of the second study indicate there was induction of tumors similar to those seen in the first study but occurring in response to lower concentrations of 1,3-butadiene.

Animals↗
PubMed1990

Inhalation toxicology of isoprene in F344 rats and B6C3F1 mice following two-week exposures.

Isoprene (2-methyl-1,3-butadiene) was selected for toxicologic evaluations because of its structural similarity to 1,3-butadiene, a potent rodent carcinogen. Two-week inhalation toxicology studies of isoprene were conducted in F344 rats and B6C3F1 mice at exposure concentrations of 0, 438, 875, 1750, 3500, or 7000 ppm. For rats, there were no chemically related changes in survival, body weight gain, clinical signs, hematologic or clinical chemistry parameters, or gross or microscopic lesions. Exposure of mice to isoprene did not produce mortalities and only caused a decrease in body weight gain for male mice in the 7000 ppm exposure group; however, hematologic changes and microscopic lesions including testicular atrophy, olfactory epithelial degeneration, and forestomach epithelial hyperplasia were observed in isoprene-exposed mice. Similar toxicologic effects have been previously observed in B6C3F1 mice exposed to 1,3-butadiene. A species difference in susceptibility between rats and mice exposed to isoprene was evident in these short-term exposure studies.

Administration, Inhalation↗
PubMed1990

Therapy of lymphoma directed at idiotypes.

Anti-idiotype monoclonal antibodies are now available for up to one-third of all patients with B-cell cancer. This is because some antibodies made in the past for individual patients cross-react with the idiotype expressed by other patients' tumor cells. Clinical trials with anti-idiotype antibodies have demonstrated reproducible antitumor effects in patients who have failed conventional treatments. The anti-idiotype antibody treatments are not associated with any significant toxicity and rarely induce immune responses in patients with B-cell lymphoma. They can therefore be used repetitively. Future developments will include the combination of anti-idiotype antibodies with other biologic therapies and with chemotherapy. In addition, one may be able to induce the patient to make an active immune response against the idiotype expressed by his or her tumor cells.

Animals↗
PubMed1990

Clinical and parasitologic aspects of cryptosporidiosis in nonhuman primates.

Eighty-one cases of acute cryptosporidiosis were diagnosed among 157 (52%) infant primates, predominantly Macaca nemestrina, housed in the nursery unit of the Washington Regional Primate Research Center. The mean age at onset of oocyst passage was 38 +/- 25 days. The outbreak was confined to the nursery and no cases were detected among juvenile or adult primates housed in other rooms within the colony. All but one animal manifested symptoms of enteric infection, including severe diarrhea and dehydration. Infected animals excreted oocysts for a mean of 36 days (range 7-78 days). No reinfections occurred. Cryptosporidium was the second most common enteric pathogen detected in the population, after Campylobacter jejuni. The risk of infection was related to the length of time the animal was housed in the nursery and to social interaction with other monkeys. These findings are relevant to the understanding of the epidemiology of cryptosporidiosis among human infants and children in environments with close social interactions and minimal learned personal hygiene practices.

Animals↗
PubMed1989

Shared idiotypes expressed by human B-cell lymphomas.

Each B-cell lymphoma expresses a surface immunoglobulin that contains unique antigenic determinants (idiotypes). We have produced 199 murine monoclonal antibodies reactive with the idiotypes isolated from 67 patients with follicular small-cleaved-cell lymphoma. These antiidiotype antibodies were analyzed for their ability to react with lymphoma cells from patients other than the one against which each antibody was made. Twenty of the 199 antiidiotype antibodies were reactive with lymphoma cells from more than one patient. Depending on the antibody, the frequency of idiotype sharing ranged from 0.6 to 6.2 percent of B-cell lymphoma tumors evaluated. Tumors could be grouped into distinct families on the basis of their reactivity with these antibodies. In the aggregate, the 20 antibodies reacted with a total of 49 of 150 B-cell lymphomas (33 percent), including 30 of 110 follicular small-cleaved-cell lymphomas (27 percent). Many of these shared idiotypes were expressed by more than one histopathological subtype of lymphoma. We conclude that a panel of antibodies reactive with shared idiotypes can be produced for patients with B-cell lymphoma, obviating the need to produce an antiidiotype antibody for each patient.

Antibodies, Anti-Idiotypic↗
PubMed1989

A computer-assisted medical diagnostic consultation service. Implementation and prospective evaluation of a prototype.

STUDY OBJECTIVE: To evaluate the accuracy of a computer-aided consultation service using academic general internists and the Quick Medical Reference (QMR) diagnostic program: and to study the impact of the consultation on the diagnostic behavior of physicians caring for patients. DESIGN: Prospective study of the diagnostic accuracy of computer-aided consultation in 31 cases, as well as a prospective study of ward team diagnoses and opinions before and after consultation. SETTING: General medicine wards of two tertiary care centers. PARTICIPANTS: Thirty-one patients identified as posing a diagnostic challenge and meeting eligibility criteria, as well as the housestaff caring for these patients. MEASUREMENTS AND MAIN RESULTS: After 6 months follow-up, diagnoses were established in 20 of 31 cases. The diagnostic sensitivity of the computer-assisted diagnoses, 85% (95% CI, 56% to 97%), was similar to that of the consult service physicians, 80% (95% CI, 55% to 94%), but better than that of the ward teams, 60% (95% CI, 33% to 81%; P = 0.03 using the binomial test). The consultation influenced the postconsultation differential diagnoses of the ward teams in 26 of the 31 cases (95% CI, 92% to 95%). House officers rated the consultation service as being educationally helpful in 25 of the 31 cases (95% CI, 62% to 94%). CONCLUSIONS: Computer-aided diagnostic consultation, when provided by physicians familiar with the limitations of the system and capable of overriding inappropriate suggestions, was both accurate and educationally helpful in most cases. The system provided reasonable diagnostic suggestions not previously considered by the ward teams and these suggestions were valued sufficiently to cause alteration of the original differential diagnoses.

Diagnosis, Computer-Assisted↗
PubMed1989

Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon.

Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti-idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti-idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.

Antibodies, Anti-Idiotypic↗
PubMed1989

T lymphocyte heterogeneity in old and young mice: functional defects in T cells selected for poor calcium signal generation.

An increase in cytoplasmic free calcium ion concentration is thought to play a critical role in the entry of resting T lymphocytes into the mitotic cycle. Not all murine T cells, however, generate such a calcium signal when exposed to mitogenic doses of concanavalin A (Con A), and the proportion of nonresponsive cells increases with age in adult mice. Since the frequency of T cells able to generate cytotoxic or lymphokine-secreting cells in culture also declines in old age, we have speculated that the defect in changes in Ca2+ concentration might underlie this functional deficit. To examine the relationship between functional competence and the calcium signaling pathway, we performed limiting dilution analyses of T cells enriched (by a fluorescence-based cell-sorting method) for high or low calcium signal generation. We found that rapid Ca2+ signal generation after Con A exposure did indeed correlate well with functional competence in Con A-stimulated limiting dilution cultures. Furthermore, selection for Ca2+ signals induced by anti-CD3 antibody, or even by ionomycin, similarly enriched for the functionally competent set of T cells. The ionomycin result, in particular, suggests that the difference between the reactive and nonreactive sets of T cells is unlikely to result simply from alterations in receptor-linked signal transduction pathways. We discuss a model in which immune senescence involves an age-dependent increase in a subset of T cells in which changes in cytoplasmic Ca2+ concentration are relatively difficult to induce by either receptor-dependent mitogens or ionophores.

Aging↗