Biomedical subjects
Publications and source records attributed to R Thomas.
A patient with an occult primary adenocarcinoid tumor of the appendix metastatic to the ovary is presented. Only one similar case has been reported previously. A review of the literature of Krukenberg tumors and appendiceal epithelial tumors emphasizes terminology, sources of primary malignancy, treatment, and prognosis.
After 5 months of intense training, eight male swimmers were studied during 4 wk of inactivity. Biopsy specimens from the deltoid muscle revealed that its respiratory capacity (QO2) decreased by 50% (5174 to 2559 microliter X h-1 X g-1) after 1 wk of inactivity. Subsequent weeks of detraining did not change the QO2. Although the trained swimmers' muscle phosphofructokinase and phosphorylase activities were significantly higher (P less than 0.05) than those from a group (N = 8) of untrained men, 4 wk of detraining had no effect on these enzyme activities. Mean (+/-SE) resting muscle glycogen concentrations were significantly higher (P less than 0.05) for the trained swimmers (153 +/- 3 mmol X kg-1) than for the untrained men (85 +/- 7.5 mmol X kg-1). Over the 4 wk of inactivity, the swimmers' muscle glycogen progressively decreased from 153 (+/- 3) to 93 (+/-7) mmol X kg-1. After a standard 183-m swim at 90% of the swimmer's best time for that distance, blood lactate rose from a mean of 4.2 (+/-0.8) at week 0 to 9.7 (+/-0.8) mmol X 1(-1) at week 4. These observations demonstrate dramatic changes in the metabolic characteristics of the swimmer's muscle with a 1-4-wk interruption in training.
A case history of a 34-year-old white woman with recurrent inflammatory lesions involving the inguinal areas bilaterally is presented. Salient points of diagnosis, pathophysiology, and differential diagnosis are discussed. In this patient, steroid injections, incision and drainage, and topical and systemic antibiotics were unsuccessful, and a modified vulvectomy with inguinal skin resection was performed. An historic review of hidradenitis suppurativa is presented, and current options of management are discussed.
Since the advent of modern antibiotic therapy and active surgical treatment of bacterial endocarditis, septic embolization of the systemic circulation is rarely seen. An unusual presentation of a mycotic aneurysm with gastrointestinal haemorrhage in a patient with non-Hodgkin's lymphoma and aortic valvular endocarditis which had been managed by aortic valve replacement six weeks before the haemorrhage occurred is reported.
Four classes of monoclonal antibody-producing cell lines have been obtained that detect human cytomegalovirus virion structural proteins. These antibodies react with (1) a major outer membrane virion glycoprotein(s) gp58-gp130, whose molecular weight varies between strains of cytomegalovirus, (2) a phosphoprotein, pp71, localized inside the virion membrane, (3) a phosphorylated nucleocapsid protein, pp155, and (4) a virion-associated phosphoprotein, pp29. Polyclonal immune human sera react with a large number of virion proteins including those detected by these monoclonal antibodies. These monoclonal antibodies were employed in a radioimmune assay to detect low levels (6 X 10(3) PFU/ml) of human cytomegalovirus in solution and human urine. These antibodies were also employed in a fluorescent antibody format to identify cytomegalovirus-infected cells obtained from human urine and nasopharyngeal aspirates. These reagents provide useful tools for studying the molecular biology of virus replication, for diagnosing cytomegalovirus infections, and for studying virus latency and activation.
We used 14 easily measured biologic and clinical variables to develop a simple scoring system reflecting the risk of death in ICU patients. The simplified acute physiology score (SAPS) was evaluated in 679 consecutive patients admitted to eight multidisciplinary referral ICUs in France. Surgery accounted for 40% of admissions. Data were collected during the first 24 h after ICU admission. SAPS correctly classified patients in groups of increasing probability of death, irrespective of diagnosis, and compared favorably with the acute physiology score (APS), a more complex scoring system which has also been applied to ICU patients. SAPS was a simpler and less time-consuming method for comparative studies and management evaluation between different ICUs.
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The inotropic activity of eleven 5 alpha-cardenolides and six 5 beta-cardenolides was determined using guinea pig left atria and the results were compared with published data obtained from cat toxicity studies. The guinea pig atrial studies showed that the configuration of the A/B ring junction did not influence significantly the cardiotonic potency of digitoxigenin and its 5 alpha-epimer, uzarigenin, but was of significance with respect to the influence of substituent groups. Glucosidation decreased the potency of uzarigenin but increased that of digitoxigenin. By contrast, conjugation with rhamnose increased the activity of both uzarigenin and digitoxigenin. Cat toxicity data did not correlate well with that obtained using guinea pig atria, possibly because of the variable influence of pharmacokinetic factors applicable to the cat toxicity studies.
We have performed direct and indirect binding studies with [3H]ouabain or [3H]digitoxin on beef or guinea pig cardiac (Na+ + K+)-ATPase to measure the potencies of a broad range of cardiotonic steroids for structure-activity relationship (SAR) studies for comparison with previously determined positive inotropic potencies. The positive inotropic potencies of twelve compounds on contracting guinea pig left atria correlated well with the equilibrium dissociation constants (KD values) from the inhibition of [3H]ouabain binding to guinea pig cardiac (Na+ + K+)-ATPase (r = 0.98 for seven 5 beta-compounds, r = 0.95 for five 5 alpha-compounds). Further we calculated KD values from the inhibition of [3H]ouabain binding data for a total of 33 digitalis derivatives on the digitalis-sensitive beef cardiac (Na+ + K+)-ATPase. For the 27 compounds tested on both beef cardiac (Na+ + K+)-ATPase and guinea pig left atria, the potencies showed a significant correlation (r = 0.92 for 22 5 beta-compounds, r = 0.96 for five 5 alpha-compounds. For seven compounds, KD values were measured on beef cardiac (Na+ + K+)-ATPase using inhibition of binding of [3H]digitoxin. These values correlated well (r = 0.99) with the KD values from the [3H]ouabain studies. These results show that: (1) The significant correlation observed between KD values on guinea pig cardiac (Na+ + K+)-ATPase and positive inotropic potency in guinea pig left atria is further evidence that the pharmacological receptor for inotropy is part of the enzyme, (2) Inhibition of the binding of [3H]ouabain or [3H]digitoxin can be used to determine the relative potencies of unlabelled digitalis derivatives. The similar relative potencies on beef and guinea pig cardiac (Na+ + K+)-ATPase of a broad range of digitalis derivatives indicate that the binding site is similar for both species; and (3) SAR studies indicate that functional groups on these steroids have the same influence on potency on either the positive inotropy or cardiac (Na+ + K+)-ATPase studies.
A universal severity index for acutely ill patients was applied to 794 acute patients treated in eight medical and surgical French intensive care units located in teaching or community hospitals either in Paris or in provincial towns. Measured on the first day in hospital from objective numerical data, the index proved reliable and correlated well with hospital mortality and the sustained therapeutic efforts of the first 24 hours. It could be used in multicentre studies to compare outcomes and evaluate new treatments.
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p53 is a cellular protein whose levels are some 1500-2000 times higher in adenovirus and SV40-transformed human cell lines than in homologous nontransformed cells. Monoclonal antibodies have been produced that detect p53 of primate origin but not of rodent origin. These monoclonal antibodies have been employed to study the properties of p53 antigens from human cell lines. Human p53 proteins of at least five different apparent molecular-weight classes in SDS-polyacrylamide gels have been detected. In some cell lines, at least two distinct molecular-weight species are expressed and these two forms have similar or identical partial peptide maps. Both molecular-weight forms can be resolved into seven or eight species upon isoelectric focusing in a two-dimensional gel system. There is also some indication of differences in the partial peptide maps of human p53 antigens derived from different human transformed cell lines. A radioimmunometric assay was employed to study the steady-state levels of oligomeric p53 in normal and transformed cell lines. Antibody affinity chromatography has been employed to purify p53 protein which was then used to quantitate the steady-state levels of p53 in different human cell lines. Normal cells had little or no detectable p53 antigen. Transformed cells or tumor-derived cell lines varied between no detectable p53 protein and 450 micrograms of p53 protein/g of cellular protein (in SV80 cells). There was a great diversity in the levels of p53 antigen in human cells. SV40- and adenovirus-transformed cells had by far the highest levels of p53 antigen. These are the viruses whose tumor antigens have been shown to be associated in an oligomeric complex with p53 in transformed cells. Eleven out of fifteen human tumor derived or transformed cell lines contained greater than five-fold higher levels of p53 antigen than normal human cells.
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The inotropic activity of 19 cardioactive steroids was determined using the electrically driven left atrium of the guinea pig. The compounds tested included five alpha-L-rhamnosides and four alpha-L-thevetosides. These were compared with their related genins and with representative examples of beta-D-glycosides. The study showed that rhamnosides and thevetosides were amongst the most active of all cardiac glycosides. The high activity of these compounds was probably related to the alpha-L-glycoside linkage and the configuration of the 4'-hydroxyl group and the 5'-methyl group. There was a stepwise loss of activity when the hydroxyl groups of the sugars were acetylated. The extent to which rhamnose enhanced the potency of different genins varied with the nature of the genin and ranged from 6- to 35-fold. The great variation in the published values for some of the glycosides tested demonstrates the need to standardize methods for testing cardiac glycosides.
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