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Biomedical subjects

D B Smith

Publications and source records attributed to D B Smith.

At least 163 records · Page 9Linked to original sources
PubMed1989

The impact of learning on cost: the case of heart transplantation.

The effect of increased experience on outcomes is evaluated for a heart transplantation program. While previous research on surgical procedures has documented a strong and consistent relationship between experience and quality (mortality and complication rates), little correlation has been found between experience and cost. Most of this research has relied on comparisons between different-sized programs at the same point in time, making it difficult to interpret. The lack of clear financial incentives in the past may also have muted a relationship between cost and experience that has been consistently documented and used in planning the production of almost all other non-health-related goods and services. The traditional operations research or managerial accounting model for projecting the impact of learning on four measures of cumulative average resource consumption (death rates, length of stay, billing units, and charges), modified to include a lower limit, was applied to the experience of a heart transplant program. The data fit the model well. The slope of the learning curve is steepest for death rates and flattest for charges. Possible implications of such learning curves on the strategic thinking of institutions and the planning and management of health services are discussed.

Clinical Competence↗
PubMed1989

Sexual rehabilitation of the cancer patient.

Sexual rehabilitation has been identified by the Oncology Nurses Society, the American Nurses Association, and various other health care organizations as an expected aspect of care for patients. Addressed in this article are the following questions: who involved in the patient's care should be participating in sexual rehabilitation, what are barriers to this involvement, and how might they be overcome?

Humans↗
PubMed1989

Skin accelerometer displacement and relative bone movement of adjacent vertebrae in response to chiropractic percussion thrusts.

The authors studied relative bone movements in response to manipulative light taps to the spine. Piezoelectric accelerometers attached to bone of an anesthetized dog measured transverse, X-Z plane, movements of L2-L3 adjacent vertebrae while percussion thrusts of an instrument used for manipulation made inputs three vertebrae above and five vertebrae below the L2-L3 joint interface. Small, relative 1-mm translations and 0.5 degree rotations occurred during the first 19 msec. When one set of accelerometers were stabilized on the skin surface, half of the skin-bone translation maxima erred less than 2%. However, skin translations averaged 77% (SD = 2%) of bone translations and skin rotations averaged 95% (SD = 26%) of bone rotations. The results suggest the possibility that, with further development, piezoelectric accelerometers can be a noninvasive tool to study dynamic, relative, bone movement.

Animals↗
PubMed1988

Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.

Plasmid expression vectors have been constructed that direct the synthesis of foreign polypeptides in Escherichia coli as fusions with the C terminus of Sj26, a 26-kDa glutathione S-transferase (GST; EC 2.5.1.18) encoded by the parasitic helminth Schistosoma japonicum. In the majority of cases, fusion proteins are soluble in aqueous solutions and can be purified from crude bacterial lysates under non-denaturing conditions by affinity chromatography on immobilised glutathione. Using batch wash procedures several fusion proteins can be purified in parallel in under 2 h with yields of up to 15 micrograms protein/ml of culture. The vectors have been engineered so that the GST carrier can be cleaved from fusion proteins by digestion with site-specific proteases such as thrombin or blood coagulation factor Xa, following which, the carrier and any uncleaved fusion protein can be removed by absorption on glutathione-agarose. This system has been used successfully for the expression and purification of more than 30 different eukaryotic polypeptides.

Amino Acid Sequence↗
PubMed1988

Expression of an enzymatically active parasite molecule in Escherichia coli: Schistosoma japonicum glutathione S-transferase.

The NH2-terminal amino acid sequence of the Mr 26 000 glutathione S-transferase (EC 2.5.1.18) of Schistosoma japonicum (Sj26) has been deduced by RNA and protein sequence analysis. Using this information, a bacterial plasmid has been constructed that directs the synthesis of the entire Sj26 molecule in Escherichia coli. Recombinant Sj26 exhibits glutathione S-transferase activity and can be readily purified from bacteria in a one-step procedure under non-denaturing conditions. The availability of recombinant Sj26 in essentially unlimited quantities will aid its assessment as a candidate vaccine molecule in schistosomiasis and could eventually lead to the rational design of a drug targetted on schistosome glutathione S-transferases.

Amino Acid Sequence↗
PubMed1988

Double alkylating agent therapy with ifosfamide and cyclophosphamide for advanced non-small cell lung cancer. From the Manchester Lung Tumour Group.

Forty-five patients with advanced non-small cell lung cancer (NSCLC), with progressive inoperable tumors were treated. Twenty-three patients were of "limited" stage. Six patients had received previous thoracic radiotherapy. Patients with central nervous system (CNS) metastases, Karnofsky scores of less than 30 or more than 70, and patients over 70 years of age were excluded from the study. Cyclophosphamide (2.5 g/m2) was infused intravenously over 3 hours with the same Mesna dose. At the midpoint of the infusion, 3.5 g/m2 infosfamide was delivered as a bolus. Additional Mesna was administered over the next 8 hours. A maximum of four courses were given at three weekly intervals. One-hundred-thirty-eight courses were administered and 53% of patients completed all four treatments. The response rate was 38%, with three (7%) complete responses. Seven additional patients (15%) with stable disease symptomatically improved by two steps or more on the Karnofsky scale at the end of treatment. Median survival for all 45 patients was 7 months, range less than 1 to 25 months. Sixteen courses were complicated by Grade 3 thrombocytopaenia and/or leukopenia (Grade 4 on six occasions, Grade 3 on seven occasions) on the blood count taken immediately before chemotherapy. Intravenous antibiotics were required on 14% of the total number of courses; and three patients died of probable treatment related causes. Two episodes of severe ifosfamide encephalopathy occurred but recovery was complete, and four episodes of frank hematuria also occurred. The Karnofsky score was more than 70 in 33% of patients one month after the end of chemotherapy compared with 0% before treatment. Unlike many chemotherapeutic regimens for NSCLC, double alkylating agent treatment with ifosfamide and cyclophosphamide improved the performance status without major toxicity in a selected patient population. The overall survival, however, remains short and further alkylating agent combinations need to be considered in the future.

Aged↗
PubMed1988

Sensitization against the parasite antigen Sj26 is not sufficient for consistent expression of resistance to Schistosoma japonicum in mice.

Mice immunized with purified antigen preparations produced in Escherichia coli and containing the glutathione S-transferase (GST) isoenzyme of Schistosoma japonicum (Sj26) can be partially resistant to infection with this parasite. Maximum resistance was approximately 50% and no protection was obtained in BALB/c mice, known low responders to Sj26. Although only Freund's complete adjuvant has been used, the data obtained indicate that satisfactory levels of resistance to S. japonicum will not be attained by vaccination with Sj26 alone. Other antigens, including the additional GST isoenzyme of S. japonicum Sj28, will probably be required to establish whether Sj26 will be an important component of a defined multivalent vaccine against schistosomiasis japonica.

Animals↗
PubMed1988

Single agent activity of methotrexate in advanced non-seminomatous testicular germ cell tumours.

The single agent activity of methotrexate in non-seminomatous germ cell tumours (NSGCT), and thus the rationale for its inclusion in combination regimens, has never been documented clearly. We have therefore reviewed all patients with NSGCT treated in this hospital from 1967 to 1970. Seventeen patients were identified who had a rising HCG excretion and who were treated with methotrexate alone as first line chemotherapy. Nine patients (53%) obtained a partial remission and a further seven patients a reduction in HCG production that was less than one log. Methotrexate is an active agent in testicular germ cell tumours and should be of particular value in treating CNS disease where intrathecal treatment may be required.

Adolescent↗
PubMed1988

Phenytoin loading in chronic alcoholic patients.

Controversy exists concerning the appropriate loading dose of phenytoin in chronic alcoholic patients. Chronic alcoholics are frequently assumed to have low albumin levels secondary to malnutrition and liver disease. Phenytoin is bound to albumin, and therefore the usual loading dose of phenytoin might result in a higher percentage of unbound drug and increased toxicity in these patients. Thirty-six chronic alcoholic patients were given a 15-mg/kg loading dose of phenytoin by constant intravenous infusion. After the infusion, patients were evaluated for clinical signs of phenytoin toxicity. At 1 hour after infusion, blood was sent for determination of total phenytoin, free phenytoin, and albumin levels. Fifteen patients were hypoalbuminemic (mean, 3.4 g/dL); 21 patients had albumin levels within the normal range (mean, 4.3 g/dL). In the hypoalbuminemic group, the mean free phenytoin level was 1.1 micrograms/mL, and the mean total phenytoin level was 13.6 micrograms/mL. In patients with normal albumin levels, the mean free phenytoin level was 1.3 micrograms/mL, and the mean total phenytoin level was 15.7 micrograms/mL. There were no statistically significant differences in total phenytoin or free phenytoin levels between either groups. No patient had a postinfusion phenytoin level (either free or total) within the toxic range. Although our sample size was small, our results suggest that a 15-mg/kg loading dose of phenytoin does not produce toxic levels in chronic alcoholics.

Adult↗
PubMed1988

A negative phase II trial methylene dimethane sulphonate in advanced ovarian cancer (Cancer Research Campaign Phase I/II Trials Committee).

Methylene dimethane sulphonate (MDMS), the first member of the homologous series of dimethane sulphonic acid esters, was administered to 19 patients with advanced epithelial ovarian cancer. All patients had received prior chemotherapy and in addition 3 had received prior radiotherapy. MDMS was given as an i.v. bolus injection at a dose of 125mg m-2 and repeated in a q35 day schedule. Ten patients received only one course, six two courses, two three courses and one four courses. The major toxicity was thrombocytopenia which was cumulative. Serious neutropenia did not occur and no infective episodes requiring i.v. antibiotics were seen. Seven patients experience hair loss and four nausea and vomiting. Sixteen patients were evaluable for response but no objective remissions were seen although three patients had stable disease lasting at least 8 weeks. MDMS is therefore not recommended for further trial in epithelial ovarian carcinoma.

Adult↗
PubMed1988

A phase I and pharmacokinetic study of amphethinile.

Amphethinile is a new spindle poison with a novel structure that has shown activity in the L1210, ADJ/PC6 and Walker carcinoma rodent tumours. In addition the agent appeared to have an improved therapeutic ratio compared to existing spindle poisons and is well absorbed when administered orally. The starting dose for the phase I study was 40 mg m-2 (1/10th mouse LD10) and further patients were studied at 200, 400, 800 and 1200 mg m-2, dose escalation being based on pharmacological monitoring. Significant toxic effects were seen only at 800 and 1200 mg m-2. At these doses patients experienced nausea and vomiting, light headedness during the infusion and varying degrees of lethargy following therapy. Two of six patients at 800 mg m-2 developed severe pain in the tumour bearing area 1-2 h after treatment and one experienced colicky abdominal pain. At 1200 mg m-2 two patients died within 48 h of treatment from what appeared to be vascular causes. Following these episodes the trial was discontinued. Neutropenia and alopecia occurred in two patients, one at 800 and one at 1200 mg m-2. These patients achieved the highest drug exposure in terms of area under the concentration x time curve. It was not possible to achieve an AUC consistently high enough to produce cytotoxic effects due to the occurrence of dose limiting toxicities thus amphethinile cannot at present be recommended for phase II testing by the i.v. route. The dose escalation scheme based on pharmacological monitoring resulted in a considerable saving in the duration of the trial. Further evaluation of this methodology is recommended.

Adult↗
PubMed1988

Pre-clinical studies of a novel anti-mitotic agent, amphethinile.

A new antitumour agent is described, which has been shown to induce a G2/M block in murine leukaemia cells in vitro. In addition this agent has been shown to be equally toxic toward parental and daunorubicin-resistant P388 cells in vitro. These resistant cells are highly cross-resistant to the established anti-mitotic agents vincristine and vinblastine. Drug accumulation studies in cells have shown that whereas resistance in this cell line is associated with decreased drug accumulation in the case of daunorubicin, vincristine and vinblastine, this effect is much less pronounced for amphethinile. It is proposed that amphethinile is a poor substrate for the drug efflux process associated with the pleiotropic resistance mechanism operating in these cells. The data suggest that cell sensitivity towards amphethinile differs qualitatively from that of the vinca alkaloids and anthracycline. Pharmacokinetic studies in male mice were undertaken. Area under the curve values (AUC), show that levels of approximately 313 micrograms l-1 h-1 were attained at doses equivalent to the LD10. The alpha half life is approximately 8 min after a bolus intravenous injection. The beta half life was approximately 100 min and relatively independent of dose level.

Animals↗
PubMed1988

National field evaluation of a defined substrate method for the simultaneous enumeration of total coliforms and Escherichia coli from drinking water: comparison with the standard multiple tube fermentation method.

A defined substrate method was developed to simultaneously enumerate total coliforms and Escherichia coli from drinking waters without the need for confirmatory or completed tests. It is a new method based on technology that uses a hydrolyzable substrate as a specific indicator-nutrient for the target microbes. No equipment other than a 35 degrees C incubator and long-wavelength (366-nm) light is necessary. To perform the test, one only has to add water to the powdered ingredients in a tube or flask. If total coliforms are present in the water sample, the solution will change from its normal colorless state (no target microbes present) to yellow. The specific presence of E. coli will cause the same tube to fluoresce under a longwave (366-nm) UV lamp. The test, called Autoanalysis Colilert (AC), was compared with Standard Methods for the Examination of Water and Wastewater 10-tube multiple tube fermentation (MTF) in a national evaluation. Five utilities, representing six U.S. Environmental Protection Agency regions, participated. All water samples came from distribution systems. Split samples from a wide variety of water sources were analyzed for the MPN-versus-MPN comparison. A total of 1,086 tubes were positive by MTF, and 1,279 were positive by AC. There was no statistical difference between MTF and AC. Species identifications from positive tubes confirmed the sensitivity of the AC. A national evaluation of the AC test showed that it: (i) was as sensitive as Standard Methods MTF, (ii) specifically enumerated 1 total coliform per 100 ml, in a maximum of 24 h, (iii) simultaneously enumerated 1 E. coli per 100 ml in the same analysis, (iv) was not subject to false-positive or false-negative results by heterotrophic bacteria, (v) did not require confirmatory tests, (vi) grew injured coliforms, (vii) was easy to inoculate, and (viii) was very easy to interpret.

Bacteriological Techniques↗
PubMed1988

ATP-sensitive K+ channels are altered in hypertrophied ventricular myocytes.

Unitary K+ currents in single cells isolated from normal and hypertrophied feline left ventricles were studied with regard to ATP sensitivity using patch-clamp single-channel recording. Data were obtained from excised inside-out membrane patches with symmetrical transmembrane K+ concentration [K+] (140 mM) at 22 +/- 1 degree C and in the absence of divalent cations. In the absence of ATP at the intracellular membrane surface, K+ channel activity was observed during depolarizing and hyperpolarizing pulses ranging from 10 to 120 mV from the K+ equilibrium potential. The current voltage (I-V) curve displayed some inward rectification, with slope conductances becoming nonlinear at strong depolarizations. Rectification was particularly pronounced in cells from hypertrophied left ventricles relative to normal. Single-channel conductance determined from the linear portion of the I-V curve was 77 pS in both groups. The channels were blocked by intracellular Ca2+ (1 mM), extracellular tetraethylammonium (TEA; less than or equal to 2 mM) or 4-aminopyridine (0.5 mM); 2 mM ATP produced a total but reversible inhibition. The effect of ATP was to reduce channel openings; conductance was unaffected. The ATP concentration [( ATP]) that induced half-maximal inhibition of channel activity was 75 microM in normal myocytes but was 250 microM in cells from hypertrophied hearts. Rapid channel activation at diminished [ATP] may provide a protective function by maintaining resting potential or promoting vasodilation in hypertrophied myocardium.

4-Aminopyridine↗