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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 1,009 records · Page 56Linked to original sources

Effect of treatment with cyclosporine versus azathioprine on incidence and severity of cytomegalovirus infection posttransplantation.

The incidence and severity of cytomegalovirus (CMV) infection were evaluated in 24 renal transplant patients treated with steroids and cyclosporine and compared with 40 patients treated with steroids and azathioprine: 58% of patients receiving azathioprine and 33% of patients receiving cyclosporine required additional therapy with antithymocyte globulin (ATG) to treat steroid-resistant rejections. CMV antibody titers and cultures of urine and saliva were determined monthly for 4-6 months following transplant in all patients. Both the frequency of CMV infection (occurring in 58% of patients on steroids and cyclosporine and in 48% of patients on steroids and azathioprine) and its severity (21% of cyclosporine-treated patients and 22% of azathioprine-treated patients with symptoms) were similar in both groups. Use of ATG was associated with an increased incidence of CMV disease, especially for patients in the azathioprine group. Both the incidence of CMV disease, and the number of patients with symptoms in the azathioprine group were significantly lower when patients who had received ATG were excluded from analysis. When results were analyzed in just the cadaveric recipients in each group, the incidence and severity of CMV infection tended to be higher in azathioprine-treated patients compared with those maintained on cyclosporine. This could have been explained by the more frequent use of ATG in 84% of azathioprine maintained patients compared with 35% of cyclosporine-treated patients (P less than 0.002) since other factors, such as risk for CMV infection and Solumedrol dose for rejection were similar in both groups. The data demonstrate that ATG has a deleterious influence on the incidence and severity of CMV infection in renal transplant patients, even when the dosage of other immunosuppressive drugs is decreased during ATG therapy. Since patients treated with steroids and azathioprine tend to require ATG to treat steroid-resistant rejection more frequently than do patients on cyclosporine, this effect of ATG must be taken into account when evaluating CMV infection in patients on these two drug regimens.

Azathioprine↗

Prevalence and features of asthma in a sample survey of urban Goroka, Papua New Guinea.

This study found a prevalence of asthma of 2.5% in adults and 0.2% in children in Goroka, the major town and administrative centre of the Eastern Highlands Province of Papua New Guinea. The disease features are similar to those found in previous studies in Papua New Guinea: late age of onset and virtual absence of childhood cases; strong association with allergy to house dust mite and high mite-specific IgE levels; and considerable impairment of resting lung function. However, the prevalence is much lower than that recently found in the nearby rural South Fore linguistic group of the Okapa District. Moreover, it was noted that a preponderance of the urban cases in the present study were originally from Okapa. The implication is that particular local aetiological factors may be responsible for the documented rise in prevalence in the South Fore (Okapa) people, rather than the process of 'Westernization' per se. This creates a valuable opportunity to learn more about the pathogenesis of asthma.

Adult↗

Respiratory impairment in coffee factory workers in the Asaro Valley of Papua New Guinea.

In a coffee growing area of Papua New Guinea, a developing country in the western Pacific region, coffee factory workers were found to have more chronic symptomatic respiratory impairment than a carefully matched group of neighbouring villagers. This impairment was not related to their duration of employment. Coffee factory workers were found also to have a greater prevalence of reversible but asymptomatic airways obstruction on entering their factories after two days off duty than a group of soft drink factory workers. These findings are thought to be related to exposure to the dust produced in large quantities during coffee processing.

Adult↗

Rat lung fibroblast collagen metabolism in bleomycin-induced pulmonary fibrosis.

Endotracheal bleomycin administration in rats and other animal species causes rapid development of pulmonary fibrosis, characterized by increased lung collagen synthesis and deposition. To clarify the mechanism, lung fibroblasts from bleomycin-treated rats (BRF) were isolated and maintained in tissue culture. They were then compared with those from normal untreated control animals, with respect to several key parameters of collagen metabolism. BRF synthesized collagen at a rate 35-82% above normal rat lung fibroblasts (NRF). This difference did not appear to be due to the selection of a clone by the subculture process. Furthermore, analysis of newly synthesized collagen type composition, revealed a significantly lower ratio of type III to type I collagen. Noncollagenous protein synthesis, however, was not significantly different from normal. Collagenase production and growth rate were also unaffected. BRF, however, was morphologically indistinguishable from NRF, even at the ultrastructural level. Upon further bleomycin (1 microgram/ml) exposure in vitro, BRF could be further stimulated to synthesize collagen at 82% above the rate for untreated BRF. This is comparable to the 90% increase in NRF treated in vitro (compared with untreated NRF). These results would favor the conclusion that bleomycin induces pulmonary fibrosis, by causing directly and/or indirectly lung fibroblasts (or a certain line of lung fibroblasts) to synthesize collagen at a higher rate without any associated increase in growth rate. The data, however, do not rule out the possibility that the fibroblast isolation procedure has selected for a certain population of fibroblasts that may not be typical of the in vivo situation.

Animals↗

Mechanism of liver glycogen repletion in vivo by nuclear magnetic resonance spectroscopy.

In order to quantitate the pathways by which liver glycogen is repleted, we administered [1-13C]glucose by gavage into awake 24-h fasted rats and examined the labeling pattern of 13C in hepatic glycogen. Two doses of [1-13C]glucose, 1 and 6 mg/g body wt, were given to examine whether differences in the plasma glucose concentration altered the metabolic pathways via which liver glycogen was replenished. After 1 and 3 h (high-dose group) and after 1 and 2 h (low-dose group), the animals were anesthetized and the liver was quickly freeze-clamped. Liver glycogen was extracted and the purified glycogen hydrolyzed to glucose with amyloglucosidase. The distribution of the 13C-label was subsequently determined by 13C-nuclear magnetic resonance spectroscopy. The percent 13C enrichment of the glucosyl units in glycogen was: 15.1 +/- 0.8%(C-1), 1.5 +/- 0.1%(C-2), 1.2 +/- 0.1%(C-3), 1.1 +/- 0.1%(C-4), 1.6 +/- 0.1%(C-5), and 2.2 +/- 0.1%(C-6) for the high-dose study (n = 4, at 3 h); 16.5 +/- 0.5%(C-1), 2.0 +/- 0.1%(C-2), 1.3 +/- 0.1%(C-3), 1.1 +/- 0.1%(C-4), 2.2 +/- 0.1%(C-5), and 2.4 +/- 0.1%(C-6) in the low-dose study (n = 4, at 2 h). The average 13C-enrichment of C-1 glucose in the portal vein was found to be 43 +/- 1 and 40 +/- 2% in the high- and low-dose groups, respectively. Therefore, the amount of glycogen that was synthesized from the direct pathway (i.e., glucose----glucose-6-phosphate----glucose-1-phosphate----UDP-glucose---- glycogen) was calculated to be 31 and 36% in the high- and low-dose groups, respectively. The 13C-enrichments of portal vein lactate and alanine were 14 and 14%, respectively, in the high-dose group and 11 and 8%, respectively, in the low-dose group. From these enrichments, the minimum contribution of these gluconeogenic precursors to glycogen repletion can be calculated to be 7 and 20% in the high- and low-dose groups, respectively. The maximum contribution of glucose recycling at the triose isomerase step to glycogen synthesis (i.e., glucose----triose-phosphates----glycogen) was estimated to be 3 and 1% in the high- and low-dose groups, respectively. In conclusion, our results demonstrate that (a) only one-third of liver glycogen repletion occurs via the direct conversion of glucose to glycogen, and that (b) only a very small amount of glycogen synthesis can be accounted for by the conversion of glucose to triose phosphates and back to glycogen; this suggests that futile cycling between fructose-6-phosphate and fructose-1,6-diphosphate under these conditions is minimal. Our results also show that (c) alanine and lactate account for a minimum of between 7 and 20% of the glycogen synthesized, and that (d) the three pathways through which the labeled flux is measured account for a total of only 50% of the total glycogen synthesized. These results suggest that either there is a sizeable amount of glycogen synthesis via pathway(s) that were not examined in the present experiment or that there is a much greater dilution of labeled alanine/lactate in the oxaloacetate pool than previously appreciated, or some combination of these two explanations.

Alanine↗

Dentista moderna.

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Dentist-Patient Relations↗

Screening for cognitive toxicity of anticholinergic drugs.

Impairment of memory by muscarinic anticholinergic drugs has been demonstrated with a variety of agents using both acute administration in normal volunteers and chronic treatment in patients. Cognitive toxicity must be considered in the evaluation of the risks versus the benefits of psychopharmacologic treatment. The relationship between serum levels of anticholinergic drugs measured by radioreceptor assay and performance on the Buschke Selective Reminding Test were investigated to develop strategies for identifying patients with drug-related cognitive impairment. The radioreceptor assay may be of value in screening for patients at high risk for cognitive toxicity. However, there appears to be no alternative to careful longitudinal evaluation of learning and memory in patients after appropriate trial modifications of their medication regimens to identify patients with drug-related impairment.

Adult↗

Upper abdominal lymphadenopathy as first presentation of relapse, identified by ultrasonography, in patients treated for small cell (oat cell) bronchogenic carcinoma.

Ten patients treated for 'limited' stage small cell lung cancer presented during follow-up with epigastric or back pain together with nausea and/or vomiting. Upper abdominal lymphadenopathy was shown to be the first symptomatic site of relapse. A single fraction of radiotherapy provided a convenient, effective form of palliation. Ultrasound scanning proved an accurate, readily available technique for the diagnosis of this form of intra-abdominal disease.

Abdomen↗

Detection of islet cell surface antibodies using cloned beta cells and comparison of their incidence with that of islet cell cytoplasmic antibodies.

We have investigated the occurrence of islet cell antibodies in sera from newly-diagnosed patients with insulin-dependent diabetes mellitus (IDDM). For detection of islet cell surface antibodies (ICSA), cloned hamster beta cells (HIT-T15) were used and reaction of antibody with the beta cells was assessed by indirect immunofluorescence or by [125I]-protein A binding; the 2 procedures were shown to give good agreement. The use of HIT-T15 beta cells was validated by demonstration of good correlation between results obtained using HIT-T15 beta cells with those using dispersed rat islet cells. The presence of islet cell cytoplasmic antibodies (ICA) and complement fixing islet cell antibodies (CF-ICA) was assessed by conventional indirect immunofluorescence on unfixed, frozen sections of human pancreas. Of 33 sera from newly-diagnosed diabetics, 21 (64%) were positive for ICSA. In comparison, of 40 control sera only 7 (17%) were ICSA-positive. When the diabetic sera were assessed for cytoplasmic antibodies, 20 (60%) were positive for ICA of which half were also positive for CF-ICA. There were 6 IDDM sera which were negative for ICSA but positive for ICA: 7 of the ICSA-positive IDDM sera were negative for both ICA and CF-ICA. In 9 IDDM sera, positive reaction was obtained for all 3 types of antibody. All 9 sera positive for CF-ICA were also positive for ICSA. These data confirm the high incidence (greater than 80%) in IDDM sera of antibodies reacting with islet cells. Of these, the ICSA, which appear from the data to be distinct from ICA and CF-ICA, are possibly most relevant to the pathogenesis of IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tissue plasminogen activator release in vivo in response to vasoactive agents.

Release of tissue plasminogen activator into the circulation of rats in response to intravascular injections of vasoactive agents is studied by using a sensitive and specific clot lysis assay. Intra-arterial bradykinin elicits a rapid and transient rise in circulating plasminogen activator, which is maximum within one minute and is cleared within four to eight minutes. The plasminogen activator is fibrin dependent and is neutralized by an antiserum to human tissue-type plasminogen activator. Bradykinin is 1,000-fold more potent than the other agonists tested, which include histamine, norepinephrine, epinephrine, eledoisin-related peptide, arginine-vasopressin, lysine-vasopressin, desmopressin acetate, carbachol, and acetylcholine. Potency of bradykinin is related to its amino acid sequence. Sequential infusions of bradykinin produce a tachyphylactoid response that could be overcome by increasing the dose of the sequential bradykinin challenge. It is concluded that the characteristics of the responses to bradykinin and other agents in vivo differ significantly from those observed in isolated tissue preparations.

Animals↗

A critical appraisal of impedance plethysmography in the diagnosis of acute deep venous thrombosis.

Compulsive performance of the test is paramount to obtaining good results. Sequential multiple tests with prolongation of the filling time to maximize venous filling and ultimately reaching a plateau is essential. Increase in venous filling by increasing the cuff pressure in the proximal lower thigh occluding cuff to 60 instead of 45 centimeters of water is helpful in obtaining optimum venous filling. Unrecognized patient apprehension or muscle contraction may be a reason for false-positive IPGs. Patient relaxation, local heat application or even electromyography attachment may be helpful. The IPG can be repeated after a few hours if a false-positive test result is suspected. If a test falls above the stop line, the NPV is so high that no repetition of the test is necessary and the limb is read out as showing no proximal venous thrombosis. If a test is normal or borderline, the test may be repeated with sequential testing until the test points seem to group together or a clear divergence of either normal or abnormal is achieved. If the contralateral limb is clearly normal and an abnormal test result is obtained in the suspected limb, the test is likely to be reliable. Bilateral abnormal IPGs, especially in the presence of congestive heart failure or severe edema, may indicate a false-positive test finding. Increased edema in the extremity decreases electrical resistivity and balancing the machine may become a technical problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Abnormal diastolic mechanical vibration transmission characteristics of the left ventricle.

In 18 open chest canine experiments, the ability of the left ventricle to transmit a mechanical vibratory tone from base to apex has been studied. An artificial tone source of constant amplitude and frequency was applied to the base of the exposed left ventricle. A miniature vibration sensor was applied to the anterior epicardium near the ventricular apex. This permitted us to obtain a heart surface phonocardiogram, in order to detect the portion of the source vibration which was transmitted to the apex. In three of the dogs, the heart surface phonocardiogram from the apex was compared with simultaneous intraventricular phonocardiograms which showed the amplitude of the vibration which reached the intraventricular blood mass. It was found that the normal ventricle transmits the tone from base to apex almost exclusively during systole, when the ventricle is contracted and stiff. In marked contrast, the normally relaxed and soft ventricle fails almost completely to transmit the tone to the apex. In conditions of poor relaxation ability of the left ventricle due to global hypoxemia, manifested by a long "Time Constant T", an abnormal diastolic transmission of the tone to the apex occurred during early diastole. We have defined this abnormal early diastolic "crescendo-decrescendo" type of transmissibility as "Type 1". The Type 1 transmission is related to impaired relaxation of the ventricle and is a manifestation of one or more abnormal ventricular muscle properties, such as myocardial stiffness, viscosity and density. In conditions of left ventricular hemodynamic failure caused by global hypoxemia, a separate abnormal mid-to-late diastolic "crescendo" type of transmissibility was found, and is defined as "Type 2".(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Psychiatric manpower in British Columbia.

The ideal psychiatrist population ratio of 1:11 000, as accepted by the Ministry of Health in British Columbia and the British Columbia Medical Association, is probably inadequate since it does not take into account increased utilization and demand, the ageing of the population, the reduction in the work week of psychiatrists and the expected absence of of increased productivity of psychiatrists. The increase in utilization and demand reflects treatment of disorders with high prevalence and chronic outcomes whose needs were previously met, rather than psychiatrists "chatting with the worried well", as is sometimes alleged. The concentration of psychiatrists in Vancouver reflects the needs of both tertiary care and migration of psychiatric patients. It is not a local aberration and does not reflect over supply. An adequate psychiatrist to population ratio for large geographic areas is less than 1:10 000. The ratio for urban areas has not yet been determined, but is probably less than half of the overall ratio. In any case, more study of this issue is required before draconian health policy measures are undertaken to solve a perceived problem which may not exist.

Aging↗