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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 397 records · Page 22Linked to original sources

Pneumocystis carinii pneumonia: diagnosis and management.

As management of HIV infection becomes more proactive, early identification of persons at risk for PCP and initiation of preventive therapy will become more routine, and the clinical impact of P. carinii may be ameliorated.

Acquired Immunodeficiency Syndrome↗

Spondylolisthesis treated by a single-stage operation combining decompression with in situ posterolateral and anterior fusion. An analysis of eleven patients who had long-term follow-up.

We treated eleven skeletally mature patients who had a high-grade lumbosacral spondylolisthesis by a single-stage operation that involved posterior spinal decompression, posterolateral arthrodesis with autogenous iliac-crest graft, and anterior arthrodesis with a fibular graft inserted from the posterior approach. We did not attempt to correct the deformity. Preoperatively, all but one patient had severe pain in the back and lower limb; the exceptional patient had severe pain only in the low back. All but one patient had sensory deficits and objective motor impairment before the operation, and five had cauda equina syndrome. Six patients had had a previous operation that had failed. The duration of follow-up ranged from two to twelve years. A solid fusion was obtained in all patients, and all had major or complete neurological recovery. The results did not deteriorate with time.

Adolescent↗

In vivo and in vitro cholinesterase inhibitor property of the antitumor agent caracemide.

The antitumor agent caracemide [N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea] has been observed to induce signs of cholinergic activation in both animal and human studies at high clinical and toxic levels. The present study was designed to further characterize the ability of caracemide to inhibit cholinesterase both in vivo and in vitro. Caracemide produced a time-dependent inhibition of purified acetylcholinesterase, pseudocholinesterase and rat brain homogenate cholinesterase with IC50 values of 0.60, 0.55 and 17.8 microM, respectively, at the maximal time point of inhibition. Analysis of Lineweaver-Burke plots derived from inhibition of brain homogenates revealed predominantly competitive type inhibition at both initial and maximal incubation times. Intravenous administration of caracemide to rats resulted in a dose-dependent inhibition of brain cholinesterase activity, with the greatest inhibition occurring in the cortex.

Animals↗

Usefulness of color Doppler flow imaging to distinguish ventricular septal defect from acute mitral regurgitation complicating acute myocardial infarction.

Several studies have found 2-dimensional echocardiography and conventional spectral Doppler ultrasound useful in the assessment of ventricular septal defect (VSD), but few data exist regarding the usefulness of color Doppler flow imaging in evaluating this problem. Thus, the results of color flow imaging performed in 14 patients who presented with a recent acute myocardial infarction (AMI), hemodynamic instability and a new systolic murmur were evaluated. All patients underwent cardiac catheterization for definitive diagnosis, which proved to be VSD in 7 and acute mitral regurgitation in 7. VSD, identified by turbulent flow traversing the ventricular septum during ventricular systole, was correctly identified in all 7 patients with septal rupture. In the remaining 7 patients with a new murmur after AMI, mitral regurgitation was demonstrated as turbulent systolic flow in the left atrium by both color flow imaging and cine ventriculography. In all 14 patients with new murmurs, color flow imaging was 100% accurate for the presence or absence of VSD. Color flow imaging localized the septal defect to the apical septum (3), inferior septum (3) or both inferior and apical septal regions (1), and was 100% concordant for location compared with cineangiography, surgery and conventional Doppler echocardiographic techniques. Color flow imaging was accurate in identifying the presence and location of VSD complicating AMI, and accurately differentiated VSD from mitral regurgitation. Color flow imaging provides safe, rapid diagnosis of VSD complicating AMI, and may alleviate the need for diagnostic right-sided heart catheterization and preoperative cine ventriculography in these seriously ill patients.

Aged↗

Quantitative assessment of mitral regurgitation by Doppler color flow imaging: angiographic and hemodynamic correlations.

This study was performed to test the hypothesis that measurements of jet area by Doppler color flow imaging can predict the angiographic severity and hemodynamic consequences of mitral regurgitation. Doppler color flow imaging was performed in 47 patients undergoing cardiac catheterization and left ventriculography. The jet area was measured as the largest clearly definable flow disturbance in the parasternal and apical views, and expressed as the maximal jet area, the mean of the largest jet area (average jet area) in two views or as the ratio of these measures to left atrial area. Correlation of all Doppler color flow measurements with angiographic grades of mitral regurgitation were comparable, maximal jet area being closest at r = 0.76. A maximal jet area greater than 8 cm2 predicted severe mitral regurgitation with a sensitivity of 82% and specificity of 94%, whereas a maximal jet area less than 4 cm2 predicted mild mitral regurgitation with a sensitivity and specificity of 85% and 75%, respectively. All patients with an average jet area greater than 8 cm2 manifested severe mitral regurgitation. However, jet area measurements showed limited correlation with regurgitant volume and fraction (r = 0.55 and 0.62, respectively) for maximal jet area, and were not predictive of hemodynamic abnormalities, including those of pulmonary wedge pressure, stroke volume or ventricular volumes. Thus, in patients with mitral regurgitation, maximal jet area from Doppler color flow imaging provides a simple measurement that predicts angiographic grade, but manifests a weak correlation with regurgitant volume and does not predict hemodynamic dysfunction.

Adult↗

Antinociceptive effect of spinal cholinergic stimulation: interaction with substance P.

Activation of central muscarinic receptors results in an antinociceptive response in experimental animals. Employing intrathecal (i.t.) injection and radiant heat applied to a rat's tail as the experimental paradigm, a spinally-mediated antinociceptive response was obtained following injection of cholinergic agonists. Since "cholinergic' analgesia is mediated independently of the opiate system, the possibility was considered that this response was mediated through inhibition of the local release of substance P. Rats were prepared with indwelling i.t. catheters which terminated in the L2-L3 region of the spinal cord. I.t. injection of carbachol (0.05-5 micrograms) or neostigmine (1-10 micrograms), but not nicotine (0.5-10 micrograms) produced dose-related increases in tail flick latencies. Pretreatment with i.t. injection of atropine or hemicholinium-3 significantly inhibited the antinociceptive response to neostigmine. Spinal substance P levels were measured 30 min following 0.5 micrograms carbachol. Levels in the dorsal horn were reduced by 30% compared with saline controls. Levels in the ventral horn were unchanged by carbachol. These results support the role of endogenous spinal acetylcholine in pain modification and suggest an interaction with substance P neurons of the dorsal spinal cord.

Acetylcholine↗

Shuttle plasmids constructed by the transformation of an Escherichia coli cloning vector into two Deinococcus radiodurans plasmids.

An Escherichia coli plasmid that confers kanamycin resistance (Kmr) was inserted into the large Deinococcus radiodurans cryptic plasmids pUE10 and pUE11, yielding pS28 and pS19. The method of insertion involved both in vitro splicing and the natural transformation of D. radiodurans and yielded full-length clones in E. coli of pUE10 and pUE11. Both pS28 and pS19 replicated and expressed Kmr in E. coli and D. radiodurans. In both pS28 and pS19, D. radiodurans plasmid sequences were immediately upstream from the Kmr determinant. Transformation experiments suggested that Kmr expression in D. radiodurans was initiated in upstream D. radiodurans sequences. Restriction maps of pS28 and pS19 showed that each plasmid contained three MraI sites. Both pS28 and pS19 transformed the MraI-producing D. radiodurans strain R1 at low frequencies. D. radiodurans strain Sark, which naturally contains pUE10 and pUE11, was transformed by pS28 and pS19 at much higher frequencies. A Sark derivative that was cured for pUE10 was isolated by screening Sark/pS28 subisolates for loss of kanamycin resistance.

Cloning, Molecular↗

Left heart opacification with peripheral venous injection of a new saccharide echo contrast agent in dogs.

Opacification of the left heart chambers after venous injection of echo contrast agents with transpulmonary capabilities has been difficult to achieve because of a lack of availability of a biodegradable nontoxic agent that produces uniformly small microbubbles. SHU-508 is a new saccharide echo contrast agent that produces bubble sizes from 2 to 8 microns in diameter, capable of traversing the pulmonary capillary bed and resulting in left heart contrast. The echo intensity produced by this agent was compared with that of agitated saline solution, indocyanine green and SHU-454 (another experimental saccharide agent for right-sided contrast) during 136 injections in eight dogs. Videotaped two-dimensional echographic images were digitized and analyzed with the use of videodensitometry for peak right and left ventricular intensity, pulmonary transit times and time of persistence of contrast. The highest right ventricular intensity value (3,594 +/- 1,393) was achieved with SHU-508 (p less than 0.05 compared with the other agents). The right ventricular contrast seen with SHU-508 also persisted for a longer period (22.8 +/- 12 s) than with the standard agents (p less than 0.001). Left ventricular contrast with SHU-508 was visually evident in all 42 injections, whereas the peak left ventricular intensity was 35% as bright as that produced in the right ventricle by the same agent. Peak left ventricular intensity values from SHU-508 were compared with those from agitated saline solution injected from the pulmonary capillary wedge position in four dogs. SHU-508 produced brighter left ventricular intensity (1,281 +/- 607) compared with that obtained with the saline-wedge technique (p les than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antimicrobial misuse in patients with positive blood cultures.

PURPOSE: Inappropriate antimicrobial use was examined among a randomly and prospectively selected cohort of patients with at least one positive result of blood cultures. This misuse was then analyzed with respect to hospital charges and length of stay (LOS). PATIENTS AND METHODS: The study consisted of 70 patients (average age, 58.5 years) who had not undergone bone marrow transplantation. Patient charts were reviewed daily for the following information: clinical signs and symptoms of infection, pertinent laboratory data, culture results, detailed data on each antimicrobial in every antimicrobial regimen and their appropriateness, hospital charges, LOS, diagnostic and procedure codes, and discharge status. Three severity of illness variables were generated. Inappropriate antimicrobial use was described according to one of 12 categories. RESULTS: The percent of antimicrobial misuse, defined as the proportion of days of administration of antimicrobials on which one or more antimicrobials were judged inappropriate, was found to be 22.3%. After adjustment for severity of illness and diagnosis, this average inappropriateness correlated with 4.2 additional hospitalization days and $5,368 additional hospital charges. CONCLUSION: Our results cannot distinguish among several possible reasons for these associations, including direct causality (e.g., toxicity and prolonged hospitalization for antimicrobial use) and indirect links such as inappropriate utilization of other resources and influences of severity of illness on antimicrobial use not accounted for in our equations. Nevertheless, the magnitude of the association gives import to the desirability of further studies.

Anti-Infective Agents↗

Demonstration of a functional variant of chloramphenicol acetyltransferase in Haemophilus influenzae.

Seven clinical isolates of chloramphenicol-resistant Haemophilus influenzae were studied. The products of chloramphenicol inactivation by chloramphenicol acetyltransferase (CAT) were identified by high performance liquid chromatography. The sole product in H. influenzae is a single monoacetyl compound, whereas variants of CAT isolated from other chloramphenicol-resistant bacteria usually produce both monoacetyl and diacetyl chloramphenicol metabolites. The chloramphenicol resistance gene was found to reside on a 65-kb plasmid which, in five of the six cases studied, appeared to be integrated into the host cell chromosome.

Anti-Bacterial Agents↗

Impaired delayed type cutaneous hypersensitivity in rheumatoid arthritis reversed by chrysotherapy.

A prospective 24 week study of 31 patients with active rheumatoid arthritis (18 women, 13 men) was undertaken to determine whether weekly intramuscular sodium aurothiomalate (gold) would influence delayed type cutaneous hypersensitivity (DTH) and other indices of cell mediated immunity. DTH to seven recall antigens was measured by Multitest on three occasions during the study. Twenty five patients completed the study. At entry 13 patients (12 female) were anergic, and no significant correlations were found between DTH and other clinical and immunological indices. Women showed a significantly greater depression of DTH than men. At week 24 only three of the patients were anergic with significant increase in mean DTH score being noted particularly to tuberculin, candida, and streptococcus. Improvement in DTH was observed in both gold responders and non-responders. In conclusion, patients with active rheumatoid arthritis show impairment of DTH, which is reversed by chrysotherapy. This effect is most apparent in women and appears to be relatively independent of the clinical response.

Adult↗