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Biomedical subjects

J B Mitchell

Publications and source records attributed to J B Mitchell.

At least 271 records · Page 15Linked to original sources

Effects of carbohydrate ingestion on gastric emptying and exercise performance.

In an effort to determine the effects of 5 (CHO-5), 6 (CHO-6), and 7.5 (CHO-7.5) percent carbohydrate solutions on gastric emptying and performance, 8 trained male cyclists performed 4 trials of intermittent (7- x ;12-min bout) cycling at 70% VO2max. A final 12-min self-paced "performance" ride was performed on an isokinetic ergometer (Fitron) interfaced with a computer to provide total work output. A water placebo (WP) was used as a control. Each 12-min ride was followed by 3-min rest, during which a drink was consumed (8.5 ml.kg-1; mean total = 1,336 ml.2 h-1). Blood samples were taken at 0, 25, 55, 85, and 115 min for blood glucose analysis. Following the performance ride, gastric residue was obtained by intubation and aspiration. Of the original 1,336 ml ingested during each trial, the volumes emptied by the stomach for the four trials were 1,306 +/- 76, 1,262 +/- 82, 1,288 +/- 75, and 1,278 +/- 77 ml (+/- SE) for WP, CHO-5, CHO-6, and CHO-7.5, respectively. Only the volume in the CHO-5 trial was significantly different from WP. The performance data showed that in all of the CHO trials, significantly more work was produced compared to the WP trial (CHO-5 = 1.98 +/- 0.09 x 10(5) Nm vs WP = 1.83 +/- 0.11 x 10(5) Nm). There were no significant differences in performance between any of the CHO trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evaluation and treatment of chemonucleolysis failures.

Fifty patients underwent chemonucleolysis for the treatment of lumbar disk herniations unresponsive to conservative therapy. In patients treated with chymopapain, unrelieved sciatica was the most common cause of clinical treatment failure. Eight patients (16%) experienced no relief or only a transient reduction in their radicular symptoms following chymopapain injection. All eight patients were clinically reevaluated and underwent repeat neuroradiographic studies. Computed axial tomography and lumbar myelography demonstrated persistent nerve root compromise at the level of the injected disk space. Open diskectomy was performed in all eight cases. Postoperatively, seven patients noted complete resolution of their radicular symptoms; one patient had intermittent low back and leg pain following surgery.

Adult↗

To sign or not to sign: physician participation in Medicare, 1984.

Factors leading physicians to sign the 1984 Medicare participation agreement are assessed in this study. The decision was highly sensitive to Medicare reimbursement levels. A 10-percent increase in the Medicare reasonable charge increased average participation rates by 9.5 percent, or 3.2 percentage points (around the mean of 34 percent). Higher collection costs associated with obtaining that payment from Medicare discourage participation, and physicians with large Medicare caseloads were more likely to participate. Although board-certified physicians were no less likely to participate, graduates from non-English speaking non-Western European medical schools were more likely to sign. Physicians in more liberal States and in areas with greater health maintenance organization activity were significantly more likely to participate, as were those with lower malpractice costs and weaker private demand.

Data Collection↗

The changing nature of physicians' office visits.

Although there is a general feeling that, into the early 1980s, overall improvement was occurring in the content and quality of physicians' services, no time-series documentation to date has appeared to support this assumption. This article provides empirical evidence that physicians' office visits were in fact changing over time, though not in ways that one might expect. Rather than involving more diagnostic services, such as laboratory tests and x-rays, the typical office visit had come to include more therapeutic services, especially counseling. This is consistent with the observed increase in time spent with patients: between 1974 and 1981, the average office visit increased in length by nearly one full minute. Multivariate analysis indicates that the typical office visit was changing largely because physicians themselves were changing. Not only were physicians becoming increasingly specialized, but they were also more likely to be female, in group practice, and board-certified.

Certification↗

Influence of sodium bicarbonate on sprint performance: relationship to dosage.

The purpose of this investigation was to determine the minimum oral dosage of bicarbonate needed to significantly elevate blood bicarbonate and the influence of induced alkalosis on performance in high-intensity, short-duration exercise. Nine endurance-trained cyclists performed four 2-min sprints on separate occasions using an isokinetic cycle ergometer (Fitron, Cybex, Inc.). One hour before each test, the cyclists consumed either a placebo (A), a solution of 0.10 g NaHCO3.kg-1 body weight (B), a solution of 0.15 g NaHCO3.kg-1 body weight (C), or a solution of 0.20 g NaHCO3.kg-1 body weight (D) in random order. Arterialized venous blood was taken before (PRE) and after (POST) ingestion, and 1, 3, 5, 10, and 15 min following the 2-min bike sprint. The results showed a significant increase in POST blood bicarbonate, and the elevation was incrementally related to the dosage. There was, however, no significant improvement in performance. Total work (mean +/- SE) for each treatment (N.m per 2 min) were: A, 47,267 (+/- 2,472); B, 47,004 (+/- 3,094); C, 46,312 (+/- 2,964); and D, 47,190 (+/- 2,621). The results of this study show that incremental doses of NaHCO3 of 0.20 g.kg-1 and below produce incremental elevations in blood bicarbonate but do not produce improvements in performance for a sprint bout lasting 2 min.

Acid-Base Equilibrium↗

Potential applicability of nonclonogenic measurements to clinical oncology.

A number of assays are currently under evaluation for their potential usefulness in the selection of new chemotherapeutic agents or as predictive indicators for use in the design of optimal cancer treatment. Assays fall under the general categories of tumor cell survival, treatment-induced cellular damage, and determination of inherent tumor factors which includes tumor cell kinetics, tumor oxygenation, and measurement of specific biochemical systems. While technical advances to optimize these assays are continuing, possible inter- and intra-tumor cell variability to anticancer treatment modalities may complicate the interpretation and subsequent use of these assays. Regardless of their ultimate usefulness as clinical predictors, these assays will be extremely valuable in better characterizing and understanding the cell biology and biochemistry of human malignancies.

Drug Screening Assays, Antitumor↗

Chinese hamster pleiotropic multidrug-resistant cells are not radioresistant.

The inherent cellular radiosensitivity of a Chinese hamster ovary pleiotropic cell line that is multidrug resistant (CHRC5) was compared to that of its parental cell line (AuxB1). Radiation survival curve parameters n and D0 were 4.5 and 1.1 Gy, respectively, for the CHRC5 line and 5.0 and 1.2 Gy, respectively, for the parental line. Thus, the inherent radiosensitivity of the two lines was similar even though key intracellular free radical scavenging and detoxifying systems employing glutathione, glutathione transferase, and catalase produced enzyme levels that were 2.0-, 1.9-, and 1.9-fold higher, respectively, in the drug-resistant cell line. Glutathione depletion by buthionine sulfoximine resulted in the same extent of aerobic radiosensitization in both lines (approximately 10%). Incorporation of iododeoxyuridine into cellular DNA sensitized both cell lines to radiation. These studies indicate that pleiotropic drug resistance does not necessarily confer radiation resistance.

Animals↗

Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing.

Drug sensitivity assays were performed using a variation of a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] assay on V79, CHO-AuxB1, CHRC5, NCI-H460, and NCI-H249 cell lines following optimization of experimental conditions for each cell line. Results from this assay were compared with data assimilated simultaneously by clonogenic assay and by dye exclusion assay. Good correlation was observed using the CHO-AuxB1 cell line and the pleiotropic drug-resistant mutant CHRC5, with similar degrees of relative resistance observed with both the MTT and clonogenic assays. Good correlation was observed between the clonogenic and MTT assays for 1-h drug exposures, although the MTT assay was more sensitive to vinblastine. In general, the clonogenic assay was more sensitive when continuous drug exposures were utilized, although this was primarily related to the increased drug exposure time. While the use of the MTT assay in drug sensitivity testing of primary tumor samples is limited, since contaminating normal cells may also reduce the tetrazolium, the MTT assay can be semiautomated, and therefore it offers a valid, simple method of assessing chemosensitivity in established cell lines.

Animals↗

Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of radiosensitivity.

Radiation survival curves were generated for V79 Chinese hamster and two human lung cancer cell lines (NCI-H460 and NCI-H249) with doubling times of 10, 20, and 85 h, respectively, using a standard clonogenic assay, a dye exclusion assay, and a semiautomated colorimetric assay utilizing a tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan bromide. Comparable results for D0 and extrapolation number (n) were observed for all assays in the lines with doubling times of 10 and 20 h. In these instances the tumor cell lines had undergone seven or more doublings after radiation. For the tumor line (H249) with an 80-h doubling time the D0S were comparable between the assays while the extrapolation number was increased in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan bromide assay, a result probably related to the lower number of doublings (less than 4) after radiation. We then tested the ability of the assays to detect radiation protection and sensitization using known agents. We found that cysteamine treatment resulted in radioprotection (by a factor of 8 at 8 Gy) while 5-bromo-2-deoxyuridine incorporation caused enhancement of radiation sensitivity in all three assays. We conclude that, while optimal conditions for each cell line (cell number plated and doubling time) must be established, using characterized tumor cell lines, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan bromide assay could be automated and thus be of great value in screening large numbers of potential radiosensitizers or protectors.

Animals↗

Evaluation of incorporated iododeoxyuridine cellular radiosensitization by photon activation therapy.

Halogenated pyrimidines such as iododeoxyuridine (IdUrd), when incorporated into cellular DNA, sensitize cells to radiation. A technique known as photon activation therapy (PAT) has recently been proposed to further enhance IdUrd radiosensitization. This approach relies on the emission of high linear energy transfer Auger electrons as a result of photoelectric absorption of photons with energies slightly above the K shell binding energy for iodine. Thus, additional IdUrd radiosensitization has been predicted for this technique using photons either generated externally from orthovoltage units or with implants of radioisotopes with emissions of the appropriate energy range. We have tested this prediction by comparing the radiosensitization of Chinese V79 cells, which have incorporated IdUrd (16% replacement of thymidine with IdUrd), to megavoltage (15 MV) versus orthovoltage (100 KVp) radiation. Enhancement ratios at 1% survival levels for 15 MV vs. 100 KVp radiation were 1.8 and 1.95, respectively. This modest 10-15% additional enhancement was much less than that predicted by PAT. The discrepancy between experimental data and the theoretical predictions of PAT are discussed.

Animals↗

Enhancement of X ray induced DNA damage by pre-treatment with halogenated pyrimidine analogs.

The use of the halogenated pyrimidine analogs, including bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd), as potential clinical radiosensitizers is an area of renewed clinical research. Cellular radiation effects of these analogs using clinically achievable steady state plasma levels (10(-7)-10(-5) M) were measured in vitro using exponentially growing Chinese hamster V79 cells. Radiation response was determined by clonogenic survival and by the production of DNA single strand (SSB) and double strand breaks (DSB) using filter elution techniques. Replacement of thymidine in DNA by BrdUrd or IdUrd was also determined. Drug exposure of BrdUrd or IdUrd for two population doublings (17 hr) prior to irradiation resulted in a progressive reduction of n and D0 compared to untreated controls over the drug dose range of 10(-7)-10(-5) M. The percent thymidine replacement increased from 1% at 10(-7) M to 5% at 10(-6) M to 23% at 10(-5) M. Using a 17 hr exposure at 10(-5) of BrdUrd or IdUrd, the production of SSB and DSB was increased by greater than or equal to 2X and greater than or equal to 1.5X respectively. No differences in the kinetics of repair of SSB and DSB were found following 3 hr of post-irradiation repair. We conclude that in this in vitro model, there appears to be a direct relationship between percent thymidine replacement, reduction of radiation survival parameters (n, D0), and the production of DNA strand breaks in the clinically achievable dose range of these halogenated pyrimidine analogs. These filter elution assays may be adapted to in vivo studies and possibly may allow for monitoring of radiation-induced DNA damage and repair in clinical tumor specimens treated with these radiosensitizers.

Animals↗

Improvements in exercise performance: effects of carbohydrate feedings and diet.

In an effort to determine the effects of carbohydrate (CHO) feedings immediately before exercise in both the fasted and fed state, 10 well-trained male cyclists [maximum O2 consumption (VO2 max), 4.35 +/- 0.11 l/min)] performed 45 min of cycling at 77% VO2 max followed by a 15-min performance ride on an isokinetic cycle ergometer. After a 12-h fast, subjects ingested 45 g of liquid carbohydrate (LCHO), solid carbohydrate confectionery bar (SCHO), or placebo (P) 5 min before exercise. An additional trial was performed in which a high-CHO meal (200 g) taken 4 h before exercise was combined with a confectionery bar feeding (M + SCHO) immediately before the activity. At 10 min of exercise, serum glucose values were elevated by 18 and 24% during SCHO and LCHO, respectively, compared with P. At 0 and 45 min no significant differences were observed in muscle glycogen concentration or total use between the four trials. Total work produced during the final 15 min of exercise was significantly greater (P less than 0.05) during M + SCHO (194,735 +/- 9,448 N X m), compared with all other trials and significantly greater (P less than 0.05) during LCHO and SCHO (175,204 +/- 11,780 and 176,013 +/- 10,465 N X m, respectively) than trial P (159,143 +/- 11,407 N X m). These results suggest that, under conditions when CHO stores are less than optimal, exercise performance is enhanced with the ingestion of 45 g of CHO 5 min before 1 h of intense cycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Bicycling↗

An analysis of DRG-based reimbursement for psychiatric admissions to general hospitals.

The authors analyzed the potential financial impact of paying general hospitals on the basis of diagnosis-related groups (DRGs) for Medicare alcohol-drug abuse and psychiatric admissions. Average costs per admission were substantially higher for general hospitals with special psychiatric units that are currently exempt from the prospective payment system (PPS) than for hospitals without exempt units. Simulations of DRG-related payments indicated that these payments would be greater for admissions to hospitals with exempt psychiatric units than for admissions to hospitals without exempt units. However, the differences in costs between these two types of facilities were greater than the differences in payments that would occur under a PPS.

Alcoholism↗

Bringing psychiatric patients into the Medicare prospective payment system: alternatives to DRGs.

The basis of Medicare's prospective payment for alcohol, drug abuse, and mental illness hospital admissions has been the patient classification system known as diagnosis-related groups (DRGs). This paper describes two alternative patient classification systems, disease staging and clinically related groups, and reports how well each system predicts resource use compared to the DRG system. Medicare data from four states were used to test the comparative strength of these patient classification systems. Although disease staging and clinically related groups performed better than DRGs, they were still poor predictors of resource use.

Alcoholism↗