Biomedical subjects
Publications and source records attributed to M Cassidy.
This is the second paper in the two-part series which considers the developments and clinical techniques of resin-bonded bridges with the emphasis on methods for increasing success from a functional and aesthetic view point. Part 1 focused on the development and types of resin-bonded bridge and tooth preparation. This article describes the clinical application of this type of bridge and discusses failures.
The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 56,000,000 nucleotides in 45,000 entries. The input stream of data coming into the database has largely been shifted to direct submissions from the scientific community on electronic media. The data have been installed in a relational database management system and are made available in this form through on-line access, and through various network and off-line computer-readable media. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.
Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.
Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.
Twenty-two patients with adenocarcinoma metastatic to the liver were treated with rapid fractionation whole-liver irradiation (1350-2100 rads in 300-rad fractions) with simultaneous intrahepatic 5-fluorouracil (10-15 mg/kg/day) and intrahepatic Adriamycin 2.5-10 mg/m2/day) as part of a Phase I-II study. Of the 21 patients who completed therapy, 19 had colorectal carcinoma and 2 had metastatic adenocarcinoma of unknown origin. Objective response was judged by measurement of liver size, evaluation of liver function tests, and by liver scan or CAT scan of the liver. Ten of the 21 evaluable patients responded, yielding an overall response rate of 47.6%. The response rate in patients with colorectal carcinoma was 55% (10/19). At this time, median duration of response is 14+ weeks and median survival from onset of therapy is 15+ weeks. Hematologic and gastrointestinal toxicity were tolerable. No hepatic toxicity was documented. This combined modality therapy was found to be a safe effective method for the palliation of liver metastasis.
The indirect effects of short-term (3-day) feeding of several types of dietary fiber and nonnutritive materials on the subsequent absorption of cholesterol has been investigated in thoracic duct cannulated rats. Absorption was studied at timed intervals over 24 hr after duodenal introduction of a tracer dose of cholesterol at least 20 hr after the last feeding. In animals fed for 3 days with diets containing cholestryamine, bran, or cellulose, cholesterol absorption was significantly less than in control animals maintained on rat chow. Rats fed for 3 days with an alfalfa-containing diet showed large variations in cholesterol absorption that were not significantly different from controls. However, after 5 weeks, rats on the alfalfa diet showed a marked reduction in lymphatic absorption of the tracer sterol. These indirect effects of cholestryamine and fibers on cholesterol absorption were not attributable to a common mechanism; i.e., differences in transit times that were not significant, or dirrect binding of bile acids and cholesterol by the test materials.
Maytansine is a new drug undergoing clinical investigation. It has functional similarities to vincristine. Maytansine and vincristine were given to CDF1 mice with P388 leukemic ascites, and the cytokinetic response of the tumor cells was analyzed with a flow microfluorometer; mithramycin was used as the DNA fluorochrome. The results indicated a similar series of cytokinetic effects after administration of both drugs, though these effects were greater and more persistent after maytansine was given. Although both drugs produced some degree of multinucleation and endoreduplication, vincristine produced a discrete population of cells with a DNA content (fluorescence) equivalent to octoploidy (8C). Microscopy of the sorted 8C cells at 24 hours indicated 54% multinucleation and 33% mitotic figures. Most cells remained blocked in the G1-phase for at least 96 hours after administration of both drugs, which indicated that rapid DNA content distributions can be used to determine not only the effects of drugs on cell cycle distribution but also the duration of drug action.
Use of a biological standard (chicken erythrocytes) mixed with experimental cell populations allows control of all variables in flow microfluorometric determination of DNA content. These variables include both staining and instrument procedures. In addition, the use of a biological standard allows determination of cellular DNA mass in unperturbed cell populations. DNA mass measured by FMF technique correlates closely with values reported in the literature that used biochemical techniques.
Seventy cervical cytology specimens have been screened by a xero resolution flow analyzer-sorter using propidium iodide and fluorescein isothiocyanate as fluorochromes for nucleus and cytoplasm, respectively. This system shows a 1% sensitivity for detection of abnormal cells using only crude visual data analysis. Screening of clinical specimens was performed on the instrument with a 5.8% false negative rate and a 11.8% false positive rate by comparison with routine visual cytologic evaluation of the same samples.
Human peripheral blood lymphocytes were stimulated with phytohemagglutinin and tuberculin-purified protein derivative to determine if flow microfluorometric techniques had the sensitivity to detect high and low levels of blastogenic response. The deoxyribonucleic acid content of the lymphocytes was analyzed after culture. Blastogenic response was found to be measurable both sensitively and reproducibly. Tritiated thymidine incorporation measurements were also made. Preliminary experiments using inactivated Herpesvirion (type I) as a stimulant showed blastogenic response detectable by flow microfluorometric deoxyribonucleic acid measurements. Refinements of this technique may prove to be useful in the study of lymphocyte response to viral antigens in patient populations.
The data presented show that the blastogenic response of human peripheral lymphocytes to mitogens and specific antigens can be easily evaluated with rapid flow analysis of mithramycin stained cells. The precision, reproducibility and rapidity of the method make it highly suitable to study lymphocyte response to antigens in patient populations.
Peripheral blood and buccal cells were used as "model" cell populations to indicate where in the electronic cell volume (ECV) spectrum the individual cell populations of vaginal and cervical irrigations would appear. Four clinical samples each representing a different stage of abnormality were evaluated and compared with the "model" cell populations. The pattern was the same for all of the clinical samples and correlated with the blood and buccal cell populations. Only two distinct ECV populations were observed, the inflammatory cells and the epithelial cells. There was no difference in pattern of any of the volume distributions to indicate abnormality to any degree.
This series of two articles will consider the developments and clinical techniques of resin-bonded bridges with the emphasis on methods for increasing success from a functional and aesthetic view point.
Chylopericardium is an infrequent cause of pericardial effusions after heart surgery and to our knowledge has not been reported after orthotopic transplantation. We report the occurrence of chylopericardium in a heart transplant recipient who was successfully treated with a pericardial window, pericardiocentesis, and a diet rich in medium-chain triglycerides.