Showing papers by "Baylor College of Medicine published in 1973"

A clinicopathologic analysis of adriamycin cardiotoxicity

Abstract: The cardiotoxic effects of adriamycin were studied in 399 patients treated for far-advanced carcimma. Forty-five patients (11%) exhibited transient electrocardiographs changes. Eleven others developed severe congestive heart failure. Eight of these latter patients died within 3 weeks of the onset of the cardiac decompensation. The diffuse nature of this myocardiopathy was suggested by: 1. a conspicuous decrease in the QRS voltage on the electrocardiograms; 2. rapidly occurring cardiac dilatation and ventricular failure, and 3. refractoriness to inoiropic drugs and mechanical ventricular assistance. Postmortem examination of the hearts in two cases showed a striking decrease in the number of cardiac: muscle cells present, degeneration of the remaining myocardial cells, loss o contractile substance, mitochondrial swelling, and intramitochondrial dense inclusion bodies. Congestive heart failure occurred only once in the 366 patients who were treated with less than 550 mg/m2 of adriamycin (0.27%), but there were 10 cases of cardiac failure in the 33 patients who received more than 550 mg/m2 of this drug (30%). Therefore, until more direct means are established to prevent adriamycin-induced congestive heart failure, it is suggested that the total dose of adriamycin should be limited to less than 550 mg/m2 to permit safer use of this efficacious cancer chemotherapeutic agent.

Membrane Fatty Acids Associated with the Electrical Response in Visual Excitation

Abstract: The fatty acid composition of rat photoreceptor membranes was altered by dietary manipulation. A functional alteration was also observed in the component of the electroretinogram which is generated by the photoreceptors. A membrane fatty acid, docosahexaenoic acid, appears to be involved in the transduction process of visual excitation.

Biochemical and morphologic correlates of cardiac ischemia

Abstract: Functions of membrane-linked myocardial systems and morphology of the myocardial cell were examined in normal and acutely and chronically ischemic myocardium. Hemodynamic measurements of ischemic tissue showed depressed force development as well as decreased (and variable) ventricular peak pressures. Mitochondrial respiratory function was reduced, with state 3 (phosphorylating) respiration showing the most marked impairment. Losses in cytochromes c and a 3 were observed. Diminished mitochondrial calcium uptake with subsequent release of the calcium taken up during continued respiratory activity was characteristic of severely ischemic tissue, that is, 7 days after ligation. Defects in the carnitine-mediated oxidation of palmitic acid in isolated mitochondria were severe between 1 and 8 days after ligation. Losses in tissue carnitine also occurred simultaneously with decreased mitochondrial carnitine palmityltransferase activity. During this period the oxidation of hexanoic acid was unaffected. The binding and release cycle of calcium was studied in sarcoplasmic reticulum (cardiac relaxing system) isolated from control tissues and from acutely and chronically ischemic heart. An early impairment in the release phase of calcium from an acutely ischemic preparation occurred at times (12 to 60 minutes after ligation) when the other membrane-associated functions maintained normal integrity. In the chronically ischemic dog, there was marked impairment of calcium-binding variables in the first 2 weeks after ligation. This impairment occurred at times when both mitochondrial and sodium, potassium adenosine triphosphatase (Na + ,K + -ATPase) activity levels were severely impaired. The Na + ,K + -ATPase activity level was consistently lower than the control level by 7 days after ligation. However, there was no change in kinetic indexes or in the ouabainbinding characteristics in the functional enzyme remaining. Morphologic studies of tissue taken from left posterior papillary muscle 3 to 8 days after ligation revealed significant and specific changes in ultrastructure (disrupted Z and I bands, appearance of pseudo-N band and appearance of dense bodies in mitochondria); the greatest occurrence of damaged cells occurred 7 to 8 days after ligation.

Profile of volatile metabolites in urine by gas chromatography-mass spectrometry.

Abstract: Profiles of volatile metabolites of 150 urine samples from normal individuals and 40 samples from subjects with diabetes mellitus have been studied by gas chromatography and mass spectrometry. The technique involves adsorption of the urinary headspace volatiles on Tenax GC, heat desorption with helium, trapping on a cooled precolumn, and chromatography on 100-m X 0.50-mm i.d. nickel columns. Individual profiles were observed over a period of 2 months. Characteristic constituents in normal urines are 2-butanone, 2-pentanone, 4-heptanone, dimethyl disulfide, several alkyl furans, pyrrole, and carvone. In subjects with diabetes mellitus under insulin treatment, high concentrations of pyrazines, cyclohexanone, lower aliphatic alcohols, and octanols were found.

Impaired Neurogenic Cerebrovascular Control and Dysautoregulation After Stroke

Abstract: Cerebral autoregulation was tested in 32 patients with various anatomical locations and stages of ischemic cerebrovascular disease. Cerebral perfusion pressure (CPP) was raised or lowered in a standard manner by the use of head-up tilting (induced hypotension) and head-down tilting (induced hypertension). Any impairment of cerebral autoregulation was analyzed quantitatively by the ratio of the change in cerebral blood flow (CBF) over the change in CPP. There was significant correlation between the degree of dysautoregulation whether CPP was increased or decreased. An inverse correlation was shown between the degree of dysautoregulation and the duration after the ischemic episode during both induced hypotension and hypertension. Patients with brainstem lesions including those with transient ischemic attacks (TIAs) showed a greater impairment of autoregulation which persisted longer than those with hemispheric lesions. Patients with severe cerebral hemispheric infarction showed greater impairment of autoreg...

The specific resistance of blood at body temperature

Abstract: The specific resistance of human, canine, bovine, and equine blood with a haematocrit range extending from 0 to 70% and at 37°C was measured at 25 kHz. The data obtained were subjected to various curve-fitting procedures; in all cases, the resistivity was found to increase with increasing haematocrit.

Selective broth medium for isolation of group B streptococci.

Abstract: A selective medium containing Todd-Hewitt broth, sheep blood, nalidixic acid, and gentamicin sulfate was found to enhance significantly the isolation of group B streptococci from vaginal cultures. Preparation of the medium, which is stable for up to 4 weeks at 4 C, is simple and inexpensive. Use of such a medium should facilitate identification of vaginal colonization with group B streptococci.

Biosynthesis of prodigiosin, a secondary metabolite of Serratia marcescens.

Abstract: Prodigiosenes (prodigiosin and prodigiosin-like pigments) are known to be synthesized by only one genus of Eubacteriales and by two genera of Actinomycetales. Biosynthesis by Serratia marcescens occurs over a relatively narrow range of temperatures, although the bacteria grow over a broad range. When cultures of S. marcescens were incubated at 27 C in 1.0% casein hydrolysate, viable count and protein attained maximal values within 24 to 48 h, whereas prodigiosin did not reach a maximum until 96 h. The greatest amount of pigment was synthesized when cultures were in the senescent phase of growth. Suspensions of nonproliferating bacteria incubated at 27 C in only L-alanine also synthesized prodigiosin, although at a slower rate than growing cultures. Kinetics of growth for the wild-type, red S. marcescens and a white mutant were identical when incubated at 27 C, but the wild type produced abundant pigment. These results plus other data obtained from the literature suggest that prodigiosin is a secondary metabolite. The importance of this proposal to understanding the function of prodigiosin in S. marcescens is discussed.

Carcinoma and diffuse interstitial fibrosis of lung

Abstract: A review of 16 cases of diffuse interstitial fibrosis of the lung revealed three cases of coexistent carcinoma of the lung. All three tumors occurred in regions of severe fibrosis. There was one instance each of squamous cell carcinoma, small cell undifferentiated carcinoma, and adenocarcinoma. The three patients were men with a mean age of 66 years. Review of the tissue sections of the diffuse interstitial fibrosis suggests an apparent transition from atypical or dysplastic bronchiolar-alveolar epithelium to carcinoma. The greater rarity of pulmonary carcinomas in diffuse interstitial fibrosis, as contrasted with localized or focal interstitial fibrosis, may be related to the shortening of life by the diffuse lesion.

Concentration of enteroviruses from large volumes of water.

Abstract: An improved method for concentrating viruses from large volumes of clean waters is described. It was found that, by acidification, viruses in large volumes of water could be efficiently adsorbed to epoxy-fiber-glass and nitrocellulose filters in the absence of exogenously added salts. Based upon this finding, a modified version of our previously described virus concentration system was developed for virus monitoring of clean waters. In this procedure the water being tested is acidified by injection of N HCl prior to passage through a virus adsorber consisting of a fiber-glass cartridge depth filter and an epoxy-fiber-glass membrane filter in series. The adsorbed viruses are then eluted with a 1-liter volume of pH 11.5 eluent and reconcentrated by adsorption to and elution from a small epoxy-fiber-glass filter series. With this method small quantities of poliovirus in 100-gallon (378.5-liter) volumes of tapwater were concentrated nearly 40,000-fold with an average virus recovery efficiency of 77%. Images

Abnormal biochemistry in myocardial failure.

Abstract: The important subcellular systems involved in the regulation of intracellular calcium were studied in normal and in diseased heart muscle. These include mitochondria, fragments of sarcoplasmic reticulum, sodium, potassium adenosine triphosphatase and the tropomyosin-troponin system. Normal and pathologic tissues were obtained from human and animal models. In all specimens taken from areas in which a significant diminution of contractility was measured, one of the earliest defects was found in isolated fragments of sarcoplasmic reticulum. The rate of calcium released from the sarcoplasmic reticulum was decreased, compared to that in control preparations. When the severity of failing process increased, the rate of calcium binding by isolated fragments of sarcoplasmic reticulum was also attenuated. Alterations of intracellular pH may play a role in these early aberrations. Mitochondria isolated from severely failing hearts were defective with respect to respiration control and calcium accumulation. During “nonfailing” compensatory cardiac hypertrophy, mitochondria exhibited increased rates of respiration and no defect in oxidative phosphorylation. Another significant, albeit preliminary observation of an early defect in “pump failure” involved the tropomyosin-troponin system. Isolated, purified actomyosin from cardiac muscle exhibited a significant diminution in calcium sensitivity due to a defect in the tropomyosin-troponin system.

Concentration of enteroviruses from large volumes of water

Abstract: An improved method for concentrating viruses from large volumes of clean waters is described. It was found that, by acidification, viruses in large volumes of water could be efficiently adsorbed to epoxy-fiber-glass and nitrocellulose filters in the absence of exogenously added salts. Based upon this finding, a modified version of our previously described virus concentration system was developed for virus monitoring of clean waters. In this procedure the water being tested is acidified by injection of N HCl prior to passage through a virus adsorber consisting of a fiber-glass cartridge depth filter and an epoxy-fiber-glass membrane filter in series. The adsorbed viruses are then eluted with a 1-liter volume of pH 11.5 eluent and reconcentrated by adsorption to and elution from a small epoxy-fiber-glass filter series. With this method small quantities of poliovirus in 100-gallon (378.5-liter) volumes of tapwater were concentrated nearly 40,000-fold with an average virus recovery efficiency of 77%. Images

A stable ultraminiature catheter-tip pressure transducer.

Abstract: THE DYNAMIc-response problems associated with liquidfilled catheters connected to external pressure transducers for cardiovascular studies are well known. Relief from these problems has been sought through various forms of catheter-tip transducers, the most promising of which have been those utilising semiconductor strain gauges. The primary drawbacks of the semiconductor units have been their fragility, limited life and their lack of resistance stability, which precluded long-term in vivo calibration. Recently, in response to needs in this laboratory for the continuous recording of the aortic-pressure pulse wave for the assessment of cardiac output, a semiconductorstrain-gauge catheter-tip pressure transducer has been developed which overcomes these problems. The transducer has such high sensitivity that, connected into a simple d.c. bridge circuit, it can provide stable high-level output without the use of a carrier amplifier. In addition, the transducer is temperature-stable and insensitive to flow.

Influence of adeno-associated satellite virus on adenovirus-induced tumours in hamsters.

Abstract: ADENO-ASSOCIATED satellite viruses (ASV)1,2, like other members of the parvovirus group, contain single-stranded DNA3. However, satellite viruses are unique in that each capsid contains either a plus or a minus strand of nucleic acid4,5. Although adeno-associated satellite viruses are extreme in their defectiveness and they do not appear to replicate unless viable adenoviruses6,7 or herpes viruses8–10 are present in the system, they do apparently code for their own protein coats which are antigenically distinct from those of the helper adenoviruses11,12. Adeno satellite viruses interfere with the growth of helper adenoviruses13 and also with each other14.