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Biomedical subjects

R Fisher

Publications and source records attributed to R Fisher.

At least 163 records · Page 9Linked to original sources

In vitro cytotoxicity of allyl alcohol and bromobenzene in a novel organ culture system.

Two well-known hepatotoxicants, allyl alcohol (AA) and bromobenzene (BB), were studied using an in vitro system of cultured liver slices from control and phenobarbital-treated rats, respectively. Dose- and time-dependent increases in media lactate dehydrogenase (LDH), and decreases in slice K+ content and in protein synthesis were observed in rat liver slices incubated with either compound at concentrations between 0.1 and 1 mM over a period of 6 hr. The histopathological changes which occurred in the intoxicated slices appeared to parallel these biochemical changes. Additionally, the toxicity of either BB or AA, evaluated at 4 hr, was inhibited when slices were preincubated for 30 min with beta-ethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) (0.1 mM) or pyrazole (1.0 mM), respectively. In this in vitro incubation system the cytotoxicity of xenobiotics can be studied under conditions where the multicellular hepatic lobular architecture is partially maintained, and alterations in biochemical and functional processes may be correlated to pathological changes.

1-Propanol↗

Critical evaluation of a pressure-sensitive capsule for measurement of esophageal varix pressure. Studies in vitro and in canine mesenteric vessels.

The accuracy and reliability of a noninvasive pressure-sensitive capsule for the endoscopic measurement of esophageal varix pressure was evaluated. Capsule pressure was correlated with direct intraluminal pressure measurements. The influence of vessel wall tension on capsule pressure was also assessed. In vitro studies demonstrated an excellent correlation (r greater than or equal to 0.94; p less than 0.001) between the pressure obtained with the capsule and intraluminal pressure over a range of vessel diameters and wall thicknesses. In vivo correlation of pressures obtained with the capsule with direct venous pressure measurements was excellent (r = 0.85). However, this correlation decreased with a decrease in vessel diameter (group 1 diameter greater than or equal to 10 mm, r = 0.95; group 2 diameter greater than or equal to 5 mm but less than 10 mm, r = 0.75; group 3 diameter greater than or equal to 3 mm but less than 5 mm, r = 0.81). This decrease in accuracy was significant (p less than 0.001) between group 1 and groups 2 and 3. In vitro and in vivo, capsule pressure variability was significantly greater (p less than 0.001) in vessels of smaller diameter. Wall tension significantly influenced capsule pressure (p less than 0.05), although this effect was only seen in large "vessels" with a diameter beyond a clinically relevant range. Therefore, despite obtaining technically acceptable capsule pressure measurements in ideal experimental conditions, the accuracy and variability of these measurements are limited by vessel size.

Animals↗

Proximal femoral fractures. A perspective from developing countries.

The approach to hip fractures in the developing world has been reviewed to give perspective to the problem on a larger scale. Hip fracture treatment in the developing world is a paradigm for treatment of other orthopedic problems as well as for medical care in general. The most successful approach has been to use the resources as sparingly as possible so as to provide care for the greatest number of people. Reliance on simpler, more basic techniques of nonoperative treatment reduces the complication rate and seems to provide a safer, more cost-effective approach, but the nonunion rate may be 30%-70%. The situation in which technical development exceeds resources is not unique to the developing world, although it is perhaps more apparent there because of a lower resource level. The "developed" world faces the same dilemma, the only real difference perhaps being a higher minimum. Probably no society today can provide the medical care it is technically capable of producing for all of its members. When viewed from a world-wide scale, the task of providing high-technology medical care seems daunting indeed. Development of more sophisticated, expensive technology may not be the appropriate direction; a more fundamental or preventive approach might in the long run be the most effective.

Developing Countries↗

Audit of the Medical Audit Committee.

We reviewed 39 medical audits started in one institution between 1981 and 1985 to determine whether they monitored the quality of health care in a scientific manner, whether recommendations were made that could improve the quality of health care and, if so, whether the recommendations were acted on. Thirty-three audits (85%) were completed; 21 (64%) failed to state their objectives, 30 (91%) failed to compare their results with those in the literature, 9 (27%) made no recommendations that could improve the quality of health care, and 9 were poorly researched and written. The number of patients in each audit was usually adequate. Feedback was rarely received by the Medical Audit Committee concerning the Medical Advisory Committee's response to the audit. Information concerning the implementation of recommendations was available for 17 of the 24 audits that made recommendations; 7 (41%) had failed to implement half or more of the recommendations. Despite these problems, 8 (24%) of the audits were considered to be of a quality that could improve health care. We present recommendations to improve the audit procedure and foster the growing confidence among doctors in the medical audit.

Canada↗

Excess prevalence of Pneumocystis carinii pneumonia in patients treated for lymphoma with combination chemotherapy.

A significantly greater prevalence of interstitial pulmonary infiltrates and Pneumocystis carinii pneumonitis occurred on one arm of a randomized study comparing ProMACE-CytaBOM (prednisone, methotrexate with leucovorin, doxorubicin, cyclophosphamide, etoposide; cytarabine, bleomycin, vincristine, methotrexate with leucovorin) to ProMACE-MOPP (ProMACE, mechlorethamine, vincristine, prednisone, procarbazine) chemotherapy in patients with lymphoma. Of the 37 patients receiving ProMACE-CytaBOM, 13 (35.1%) developed an interstitial pulmonary infiltrate compared with 3 of 32 (9.4%) patients receiving ProMACE-MOPP (p2 = 0.02). Of the 13 patients receiving ProMACE-CytaBOM who had infiltrates, open lung biopsy in 7 showed P. carinii; 5 others had clinically suspected P. carinii pneumonia, and 1 had blastomycosis. No patient receiving ProMACE-MOPP had documented or suspected P. carinii pneumonia. Of patients with infiltrates, 3 of 13 on ProMACE-CytaBOM but 0 of 3 on ProMACE-MOPP died. Two other patients on ProMACE-CytaBOM who had P. carinii pneumonia died. Groups did not differ in predisposing risk factors or patient history. The exact cause for the increased prevalence of P. carinii infection in patients receiving ProMACE-CytaBOM was not ascertained. These data emphasize that new drug regimens may lead to unanticipated complications.

Adult↗

Moderate essential hypertension control: a double-blind crossover study between a serotonin antagonist and a post-synaptic alpha-blocker.

The purpose of this study was to compare the effects of the serotonin antagonist ketanserin and the post-synaptic alpha-blocker prazosin on blood pressure in patients with essential hypertension. Both drugs lower blood pressure by a reduction in total peripheral vascular resistance and by reducing the pre- and afterload, apparently achieving these haemodynamic effects through different mechanisms. Ketanserin appears to have a greater effect on afterload. Six men and four women (mean age 47.2 years) with diastolic blood pressure greater than or equal to 100 mmHg were treated for 4 weeks with placebo and then randomized and treated for 8 weeks double-blind with either ketanserin or prazosin. A 4-week wash-out phase with placebo was then instituted followed by another 8 weeks of treatment in a crossover fashion with either ketanserin or prazosin. Blood pressure was measured on each occasion in the supine, sitting and standing positions. The results showed that both medications significantly lowered blood pressure (computed sitting values for all patients: ketanserin from 177/104 +/- 5/7 to 158/89 +/- 8/5 mmHg; prazosin from 176/103 +/- 11/8 to 156/88 +/- 6/4 mmHg). The data in this study show that ketanserin as an antihypertensive agent is as effective as prazosin, but in contrast requires no titration of dosage and better compliance can be expected with twice daily rather than three times daily dosing.

Adrenergic beta-Antagonists↗

Isolation and characterization of the human tissue-type plasminogen activator structural gene including its 5' flanking region.

mRNA specific for tissue type plasminogen activator (t-PA) is induced in HeLa cells by the tumor promoter phorbol myristate acetate (Waller, E.K., and Schleuning, W.D. (1985) J. Biol. Chem. 260, 6354-6360). To study the underlying mechanism, a cDNA library was constructed from phorbol myristate acetate stimulated HeLa cell mRNA and screened with two t-PA mRNA specific oligonucleotides (Edlund, T., Ny, T., Rånby, M., Heden, L.-O., Palm, G., Holmgren, E., and Josephson, S. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 349-352). Two nearly full length double-stranded cDNA clones were obtained. Suitable restriction fragments from the cDNA were employed as probes for the isolation of three recombinant bacteriophages, containing overlapping fragments of the t-PA gene. By restriction analysis, heteroduplex mapping, and DNA sequencing it was determined that the three overlapping fragments contain the complete t-PA structural gene and that the 2658 bases long t-PA mRNA is encoded by a gene of approximately 29 kilobases overall length, which is interrupted by 13 introns. To characterize the presumptive control region, a subcloned gene fragment, containing the 5' sequence of the cDNA, was sequenced, and the transcription initiation site was identified by nuclease S1 protection experiments. The putative transcription start site is located 24 base pairs (bp) downstream of a typical TATA consensus sequence. Two additional TATA motifs with hitherto unknown functions are found 93 and 226 bp upstream of the putative cap site. A recombinant plasmid was constructed, which accommodates the cap site including 475 bp of upstream sequences, fused to a double-stranded cDNA of t-PA mRNA which contains the complete translated and parts of the 5' and 3' untranslated regions. This plasmid directs t-PA biosynthesis in Xenopus laevis oocytes after microinjection into the germinal vesicle.

Amino Acid Sequence↗

Regional left ventricular wall motion assessment: comparison of two-dimensional echocardiography and radionuclide angiography with contrast angiography in healed myocardial infarction.

The diagnostic ability of radionuclide angiography (RNA) and 2-dimensional echocardiography (2-D echo) to assess regional left ventricular (LV) wall motion was compared with contrast angiography in 52 patients with healed myocardial infarction. After 5 patients were excluded for inadequate 2-D echocardiographic studies, the LV images of 47 patients obtained by all 3 techniques were divided into 7 segments for analysis. Both 2-D echo and RNA showed close agreement with contrast angiography in assessing normal vs abnormal wall motion in the anterobasal (91%, 91%), anterolateral (87%, 79%) and posterolateral segments (77%, 79%). The sensitivity in detecting wall motion abnormalities was highest for 2-D echo and RNA in the anterolateral (83%, 77%) and apical (95%, 84%) segments and lowest for the inferior segment (48%, 48%). Specificity of 2-D echo and RNA was high, ranging from 94% in the anterolateral segment to 71% in the septal segment for 2-D echo, and from 91% in the inferior segment to 81% in the posterobasal and septal segments for RNA. Major discrepancies with contrast angiography occurred more often in the posterobasal, posterolateral, inferior and septal LV segments. Thus, in comparison with contrast angiography, 2-D echo and RNA are reliable for detecting anterior and apical wall motion abnormalities, but relatively less sensitive for detecting wall motion abnormalities involving the inferior, posterobasal and posterolateral LV segments.

Aged↗

A multivariate analysis of clinical and pathological variables in prognosis after resection of large bowel cancer.

Data on 709 patients who had a resection for colorectal carcinoma at Concord Hospital between 1971 and 1980 were studied to determine the independent effects on survival of several patient characteristics and pathological variables using the Cox regression model. Clinicopathological stage had the strongest association. Other variables ranked according to their relative importance independent of stage were: histological grade, level of direct spread, the presence of venous invasion, age and sex of the patient and the presence of obstruction.

Adenocarcinoma↗

The relationship between different staging methods and survival in colorectal carcinoma.

A routine clinicopathologic (CP) staging system for patients who have had surgical resection for colorectal carcinoma was established at Concord Hospital in 1971. Research on this prospective series of resections has evaluated the CP staging system as a guide to prognosis. The aim of this study was to compare the CP system with the classic Dukes' staging system and its modified form introduced by Astler and Coller to determine which method provided the most accurate basis for prognosis. Life table survival analysis was used to examine the survival of 709 patients according to each staging system. Relative mortality rates for groups of patients cross-classified by each possible pair of staging systems were examined and the Cox regression model was used to determine the independent effects of staging by each system on survival. The CP system was found to have a stronger association with survival than either the classic Dukes' system or the Astler-Coller modification of the Dukes' system. The importance of supplementing data on the operative specimen with data about the spread of tumor beyond the limits of surgical resection is emphasized.

Aged↗

Mortality, morbidity, and cost-accounting related to coronary artery bypass graft surgery in the elderly.

The purpose of this study was to document early mortality, perioperative complication rate, duration of hospitalization, and costs related to coronary artery bypass graft (CABG) surgery in the elderly. Arbitrarily, elderly patients were defined by age greater than or equal to 65 years; younger patients were less than or equal to 60 years old. A detailed list of specific perioperative complications was analyzed. Early (30-day) mortality was similar between groups, while 120-day mortality was higher among elderly compared with younger patients (7.6% versus 1.3%; p = 0.05). The number of elderly patients with 1 or more complications was also higher than among the younger patients (62% versus 43%; p = 0.05). When the incidences of atrial arrhythmias and transient psychoses were considered minor complications and excluded from consideration, the incidence of major complications was higher in the elderly: 41 major events among 76 younger surviving patients compared with 89 major complications in 61 older surviving patients (p = 0.001). Time spent in the intensive care unit and the duration of postoperative hospitalization were also greater in the elderly (p = 0.01 and p = 0.001, respectively). Finally, the elderly group incurred greater costs than the younger patients (p = 0.03). The likelihood of increased perioperative morbidity in elderly patients is documented in this study. Also, it appears that the increased frequency of complications in elderly patients is associated with a longer hospital stay and greater financial expense. Consequently, the careful preoperative evaluation of these patients, including cautious patient selection, assumes greater importance. After CABG procedures, the highly symptomatic elderly patient may experience dramatic relief of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Use of complementary DNA oligomers to probe trp leader transcript secondary structures involved in transcription pausing and termination.

DNA oligomers were synthesized that are perfectly complementary to different segments of the tryptophan (trp) operon leader transcript. These 15 nucleotide long oligomers were used as probes of the involvement of transcript secondary structures in two processes: transcription pausing at the pause site located near base pair 90 in the leader region, and transcription termination at the attenuator. The 15-mers were complementary to the four segments of the trp leader transcript which have been shown to form the alternative secondary structures that are believed to be responsible for pausing, termination, and antitermination. Oligomers complementary to RNA segments 1 and 3 relieved termination while the 15-mer complementary to RNA segment 1 relieved pausing. 15-mers complementary to segment 2 had no effect on pausing and the oligomer complementary to segment 4 had virtually no effect on termination.

Base Sequence↗