Cycling and physical exercise. Cycling has "street cred" among young people.
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Biomedical subjects
Publications and source records attributed to D Sloan.
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Prior literature suggests that length of stay (LOS) on medical inpatient units is increased by the coexistence of depression and physical illness. The present study examined 532 psychiatric inpatient admissions to determine if physical illness increased LOS for patients grouped by diagnostic categories of psychosis, depression, personality disorder, anxiety disorder, adjustment disorder, bipolar disorder (not depressed), and other psychiatric disorders. LOS for depressed patients was significantly longer for those with any physical final diagnosis (mean = 20.08 days) than for depressed patients with no physical diagnosis (mean = 11.48 days). LOS was also longer for all patients with physical diagnoses (mean = 19.31 days) than all patients with no physical diagnosis (mean = 13.13 days). No other specific diagnostic group (psychosis, personality disorder, and so forth) showed significant differences in LOS for any associated physical illness vs no physical illness. The study results tend to indicate that physical illness is associated with increased LOS for depressed psychiatric patients but not for other specific diagnostic groups. Depressed patients may 1) mask physical illness by depression-generated physical complaints; 2) prioritize mood symptoms over physical symptoms; and/or 3) may suffer from feelings of hopelessness or be pessimistic that their physical symptoms will be effectively treated and, therefore, not report their physical symptoms.
We describe the case of a patient with breast cancer who developed bilateral malignant knee effusions, and review the English language literature. Patients with solid tumors who develop malignant joint effusions are rare; 27 cases have been reported (including our patient). The knee is the predominant site of joint involvement (p < 0.001). Synovial fluid (SF) analysis often demonstrates noninflammatory bloody effusion. Synovial biopsy was positive in 11 of 16 cases in which it was performed. SF cytology was positive in one half of cases in which it was obtained. Arthritis secondary to metastasis is a poor prognostic finding. A strong clinical suspicion is necessary to make the diagnosis; SF cytology or synovial biopsy can confirm it.
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Ornithine decarboxylase may be a useful biomarker for risk of neoplasia in colorectal tissues. Investigators have reported enzyme activities varying by as much as 10- to 20-fold using variations of the usual 14CO2 release assay. We have examined the effect of different methodologic factors on calculated ornithine decarboxylase activity. Major effects on the assay result (greater than 20% change) were produced by: (1) use of Tris vs. phosphate buffer, the former yielding 1.5- to 4-fold greater activity; (2) protein content of the reaction mixture with significant error if less than 50 micrograms; (3) use of alpha-difluoro-methylornithine-inhibited blank versus buffer-only blank. Other changes in assay conditions, including addition of sucrose, detergent, protease inhibitors, specific activity of 14C-ornithine, the nature of the trapping agent used, and incorporation of a sonication step, did not have a significant effect on ODC quantification (less than or equal to 20%). Thus, seemingly minor variations in assay conditions can greatly affect the results, which may provide a partial explanation for the variability of ODC activities reported in the literature. Strict quality control measures are mandatory in the interpretation of clinical observations utilizing this marker as an endpoint.
We have measured the frequency of the carbon-hydrogen stretching mode of the pro-R and pro-S C4-H bonds of NADH in solution and when bound to pig heart lactate (LDH) or mitochondrial malate (mMDH) dehydrogenases. This is achieved by specifically deuterating the C4 pro-R or pro-S hydrogens of NADH and determining the frequencies of the resulting C4-D stretches by Raman difference spectroscopy. We find that the frequencies of the two C4-D stretching modes for the two bonds are essentially the same for the unliganded coenzyme. On the other hand, the position of the pro-S-[4-2H]NADH stretch shifts upward by about 23-30 cm-1 in its binary complex with either lactate or malate dehydrogenase relative to that observed in solution, while that for the bound pro-R-[4-2H]NADH is relatively unchanged. The fact that the frequency of the pro-R hydrogen is not significantly affected during complex formation suggests that the rate enhancements for reaction of substrate with NADH brought about by both pig heart LDH and mMDH apparently do not involve either stabilization or destabilization of the pro-R hydrogen of NADH in enzyme-coenzyme binary complexes, in agreement with previous chemical studies. That these proteins are able to regulate the frequencies of the two C4-D bonds differentially, and hence the electronic distributions in these bonds, has important implications for the stereochemical reactions catalyzed by the NAD dehydrogenases, and this is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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A procedure is described for the tissue culture of epithelial cells from Barrett's specialized columnar epithelium. The method employs use of nonenzymatic disaggregation techniques and use of a specialized growth medium, M-19. Successful growth can be achieved in 60-70% of cases. Characteristics of four cultures are presented including PAS, Alcian blue, and cytokeratin staining properties. Ultrastructural studies showed the presence of distended rough endoplasmic reticulum, abundant Golgi apparatus, glycogen granules, and cell-cell junctional complexes. Colony formation in anchorage-independent growth in soft agar was not observed in any culture. The cultured cells were not capable of indefinite growth. Thus, they do not behave as fully transformed cells. Availability of this culture system should be of use to the study of the biology of this metaplastic premalignant lesion.
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Squamous cell cancers occurring at the various sites within the head and neck are remarkable for their differences with respect to clinical presentation, staging, risk of neck disease, anatomic considerations, histology, and response to conventional therapy. In general, either surgery alone or radiation alone can be used effectively for early (T1, T2, favorable T3) tumors. If surgery can be done safely and without significant disruption of normal function or cosmesis, as in early oral cavity tumors, surgery is preferable because it avoids a prolonged and uncomfortable acute treatment and long-term radiation complications. Otherwise, as in early oropharyngeal and laryngeal tumors, radiotherapy is favored. Although single modality therapy can be given for advanced disease, combined surgery and radiotherapy appear to offer improved locoregional control and enhanced survival. The status of neck nodes is a critical prognostic factor, and the neck remains the most common site of treatment failure. Consequently, treatment of the neck can never be divorced from treatment of the primary. For early neck disease, single modality therapy suffices, but for more extensive disease, combined treatment is indicated. In view of the complexity of head and neck cancer both in terms of diagnosis and treatment, management of the patient should begin in a multidisciplinary setting in which all tumor and patient factors can be evaluated and a treatment plan agreed upon by both surgeon and radiotherapist.
We studied left ventricular endomyocardial adenosine triphosphate levels in 13 large mongrel dogs before and during ventricular fibrillation induced cardiac arrest to assess whether myocardial adenosine triphosphate content could predict successful cardiopulmonary resuscitation. Endomyocardial biopsies were performed during sinus rhythm (control), after 15 min of ventricular fibrillation or 10 min of ventricular fibrillation and 5 min of open chest cardiopulmonary resuscitation, after 20 min of ventricular fibrillation and 10 min of open chest cardiopulmonary resuscitation and after 40 min ventricular fibrillation and 15-20 min open chest cardiopulmonary resuscitation. Myocardial adenosine triphosphate was measured utilizing a bioluminescence method adapted for use with endomyocardial biopsies and normalized to protein content. Left ventricular endomyocardial adenosine triphosphate content fell significantly over time from a control level of 8.88 +/- 0.9 micrograms/mg protein to 5.73 +/- 0.5 micrograms/mg protein at 15 min of cardiac arrest, to 3.4 +/- 0.4 micrograms/mg protein after 30 min of cardiac arrest and to 1.98 +/- 0.3 micrograms/mg protein after 60 min of cardiac arrest (P less than 0.001). Adenosine triphosphate levels were significantly different between animals that received 10 min of ventricular fibrillation and successful open chest cardiopulmonary resuscitation and those that received 40 min of ventricular fibrillation and unsuccessful open chest cardiopulmonary resuscitation (4.35 +/- 0.48 vs. 2.11 +/- 0.43 micrograms/mg protein; P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
A new reversed-phase high-pressure liquid chromatography assay procedure for dihydropteroate synthetase (DHPS) that involves the elution of the enzyme incubation solution with a series of three solvents of decreasing polarity (ammonium phosphate buffer, 10% methanol, and 50% methanol) was designed. By this procedure DHPS was detected in Escherichia coli and Pneumocystis carinii with specific activities of 450 and 14 U/mg, respectively. A comparison of the effects of five sulfa drugs on P. carinii DHPS activity revealed that dapsone is the most potent of these drugs.
Current obstetric risk-scoring systems depend upon simple addition of weighted or unweighted risk factors. In this study a population of 994 pregnant women (470 primiparae; 524 multiparae) has been examined in order to compare the use of weighted and unweighted risk scores, together with Bayes theorem, in estimating an overall risk score from the presence of individual risk factors. The findings have been related to fetal outcome in these pregnancies and expressed as receiver-operating characteristic (ROC) curves for different cutoff levels between normal and abnormal. In primiparae, the use of weighted risk factors, with or without Bayes theorem, was clearly superior to the use of unweighted factors. In multiparae there was only a marginal difference between the three approaches. The increasing use of computerised information system in antenatal care should make calculation of risk scores for every pregnant woman a practical option.
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The binding of the coenzymes NAD+ and NADH to lactate dehydrogenase causes significant changes in the Raman spectra of both of these molecules relative to spectra obtained in the absence of enzyme. The molecular motions of the bound adenine moiety of both NAD+ and NADH as well as adenine containing analogues of these coenzymes produce Raman bands that are essentially identical, suggesting that the binding of adenine to the enzyme is the same regardless of the nicotinamide head-group nature. We also have observed that the molecular motions of the bound adenine moiety are different from both those obtained when it is in either water, various hydrophobic solvents, or various other solvent compositions. Protonation of the bound adenine ring at the 3-position is offered as a possible explanation. Significant shifts are observed in both the stretching frequency of the carboxamide carbonyl of NAD+ and the rocking motion of the carboxamide NH2 group of NADH. These shifts are probably caused by hydrogen bonding with the enzyme. The interaction energies of these hydrogen-bonding patterns are discussed. The aromatic nature of the nicotinamide moiety of NAD+ appears to be unchanged upon binding. Pronounced changes in the Raman spectrum of the nicotinamide moiety of NADH are observed upon binding; some of these changes are understood and discussed. Finally, these results are compared to analogous results that were recently reported for liver alcohol dehydrogenase [Chen et al. (1987) Biochemistry 26, 4776-4784]. In general, the coenzyme binding properties are found to be quite similar, but not identical, for the two enzymes.
We have studied the binding nature of an aromatic aldehyde to the catalytic site of liver alcohol dehydrogenase from horse (LADH) using preresonance Raman spectroscopy. The compound p-(dimethylamino)benzaldehyde (DABA) is converted to the corresponding alcohol in the presence of nicotinamide adenine dinucleotide (NADH) and a catalytic amount of enzyme at neutral pH. A stable ternary complex of LADH/NADH/DABA can be formed if enzyme and coenzyme are in excess at high pH [Jagodzinski, P. W., Funk, G. F., & Peticolas, W. L. (1982) Biochemistry 21, 2193-2202]. We have obtained the preresonance Raman spectrum of bound DABA by subtracting the contribution of the binary complex of LADH/NADH from the spectrum of this stable ternary complex. In order to understand the normal mode patterns of DABA, four isotopically labeled DABA derivatives were synthesized and their Raman spectra, in solution and in the ternary complex, were measured. Three of these compounds contain substitutions in the functionally important aldehyde moiety: (i) In one such substitution, the aldehydic hydrogen atom was replaced by a deuterium; (ii) in another, this hydrogen atom was replaced by deuterium, and the aldehydic carbon atom was replaced by 13C; and (iii) in the third derivative, only the carbon atom was replaced by 13C. The fourth derivative has had the two hydrogen atoms at the 3- and 5-positions of the DABA ring replaced by deuterium atoms. We find that many of the spectral modes are fairly extended, involving both stretching and bending motions of the entire molecule, although a few modes are quite localized. We find that the normal mode structure of DABA changes considerably when it binds to LADH/NADH. As a model for the bound DABA, we have examined the zinc complexes of DABA (and all four isotopically labeled samples) in anhydrous diethyl ether and methylene chloride. A striking correspondence between the Raman spectra of the enzyme-bound DABA and DABA-Zn complexes in solution is found, which extends to all the isotopically labeled derivatives. This suggests that one of the major roles of LADH in the binding of DABA is to provide a divalent zinc ion to form a first-sphere Lewis acid complex. The data also suggest other interactions between enzyme-bound DABA with its protein surroundings and with the coenzyme NADH are quite minor. An estimate of the carbonyl bond character of bound DABA had been made on the basis of the response of Raman bands to isotopic labeling and on trends observed in spectra of DABA in solvents of various polarities.(ABSTRACT TRUNCATED AT 400 WORDS)