Montreal MD's AIDS-related collapse raises disclosure issue at McGill teaching hospitals.
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Biomedical subjects
Publications and source records attributed to K Dunn.
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A case-control study was conducted to determine whether household exposure to environmental tobacco smoke is associated with an increased risk for lung cancer in pet dogs. Lung cancer cases and controls with other forms of cancer were obtained from two veterinary teaching hospitals during 1985-1987. Exposures assessed included the number of smokers in the household, the amount smoked, and the proportion of time spent indoors by the pet. A weak relation was found for exposure to a smoker in the home (odds ratio = 1.6, 95% confidence interval 0.7-3.7), after controlling for confounding in stratified analyses. Strong evidence for a further increase in risk associated with more than one smoker in the home was not found, nor was a significant trend observed for increasing number of packs of cigarettes smoked per day or an exposure index based on number of smokers in each household, packs smoked per day, and the proportion of time the dog spent within the home. However, skull shape appeared to exert effect modification; the risk was restricted to breeds with short and medium length noses (odds ratio = 2.4, 95% confidence interval 0.7-7.8). Despite the inconclusive findings of the current study, epidemiologic studies in pet animals may add to our understanding of environmental tobacco smoke effects in human populations.
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Hypocalcemia is a major stimulus for parathyroid hormone secretion and presumably the major cause of parathyroid hyperplasia in chronic hypocalcemic syndromes. We could find no data to indicate what degree, duration, or frequency of hypocalcemia is needed to produce parathyroid hyperplasia in humans. We have monitored the effects of thrice weekly hypocalcemic parathyroid stimulation for 10 weeks. Measurements were made during a study designed to test the feasibility of carrying out a randomized, blinded trial of "chelation therapy," a widely used but unproven method to treat atherosclerotic symptoms. Eight patients received infusions of disodium ethylenediaminetetraacetic acid (EDTA) and six received placebo infusions thrice weekly for ten weeks. The EDTA infusions (50 mg/kg over three hours) lowered serum ionized calcium at two hours by an average of 0.20 mmol/L and trebled the immunoreactive parathyroid hormone (iPTH) value. Basal serum iPTH, ionized calcium and 1,25-dihydroxyvitamin D values, measured just before the infusion, did not change significantly after 10 weeks of treatment with either EDTA or placebo. The increment in serum iPTH produced by the EDTA-induced hypocalcemia was also unchanged. Lowering ionized serum calcium to values below the normal range three times a week for 10 weeks is not a sufficient stimulus to cause a detectable increase in basal or stimulated parathyroid function.
Intramuscular midazolam frequently results in excessive sedation in elderly patients. The effects of preanesthetic medication with intramuscular midazolam were examined in 100 elderly patients, aged 60-86 yr, given 1, 2, or 3 mg midazolam or placebo using a randomized, double-blind study design. Level of sedation and anxiety were assessed every 15 min for 1 h. Picture cards were presented at the same times in order to assess recall of these cards 24 h later. All three doses of midazolam produced rapid onset of sedation, anxiolysis, and anterograde amnesia. These effects decreased in intensity by 60 min after drug injection. The intensity and extent of these effects were comparable with those reported with higher doses in younger patients, although with the 1-mg midazolam dose the effects were shorter-lived, and a difference from placebo was not consistently seen. Three patients (3%), all older than 70 yr, became unresponsive to vocal and tactile stimuli. This level of drowsiness was unrelated to body weight, age, or ASA physical status. We conclude that in adults between 60-69 yr old, midazolam 2 or 3 mg intramuscularly can be effective as preanesthetic medication without causing excessive drowsiness. However, intramuscular midazolam should be used cautiously, under continuous observation, in patients aged 70 yr and older because excessive drowsiness may occur.
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Seizures are a frequent sequela of impaired brain development and can be expected to affect more children with radiation-related brain damage than children without such damage. This report deals with the incidence and type of seizures among survivors prenatally exposed to the atomic bombing of Hiroshima and Nagasaki, and their association with specific stages of prenatal development at the time of irradiation. Fetal radiation dose was assumed to be equal to the dose to the maternal uterus. Seizures here include all references in the clinical record to "seizure," "epilepsy," or "convulsion." Histories of seizures were obtained at biennial routine clinical examinations starting at about the age of 2 years. These clinical records were used to classify seizures as febrile or unprovoked (without precipitating cause). No seizures were ascertained among subjects exposed 0-7 weeks after fertilization at doses higher than 0.10 Gy. The incidence of seizures was highest with irradiation at the eighth through the 15th week after fertilization among subjects with doses exceeding 0.10 Gy and was linearly related to the level of fetal exposure. This obtains for all seizures without regard to the presence of fever or precipitating causes, and for unprovoked seizures. When the 22 cases of severe mental retardation were excluded, the increase in seizures was only suggestively significant and only for unprovoked seizures. After exposure at later stages of development, there was no increase in recorded seizures.
In a two-part study, the dose-response relationships of doxacurium chloride (BW A938U) were evaluated during general anesthesia maintained with commonly used anesthetic techniques. In part 1, cumulative dose-response methodology was used to establish the ED95 of doxacurium in 36 patients receiving 70% nitrous oxide and fentanyl, or 50% nitrous oxide and either 1.26% enflurane, 0.84% isoflurane, or 0.57% halothane anesthesia. Mechanomyographic response to train-of-four stimulation was used to monitor neuromuscular blockade. The peak effect of doxacurium following each 5 micrograms/kg incremental dose was noted and a log-probit dose-response curve was constructed for each individual patient. The median ED50s were 11 micrograms/kg, 6 micrograms/kg, 8 micrograms/kg, and 8 micrograms/kg for patients receiving fentanyl, enflurane, isoflurane, or halothane anesthesia, respectively. The median ED95s were 24 micrograms/kg, 14 micrograms/kg, 16 micrograms/kg, and 19 micrograms/kg for patients receiving fentanyl, enflurane, isoflurane, and halothane anesthesia, respectively. In part 2, 72 additional patients received a rapid single injection of the ED95 (n = 36) or 2 X ED95 (n = 36) of doxacurium appropriate for the administered anesthetic as estimated from part one of the study. Peak effects of the ED95 given as single injections correlated well with the results in part 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Non-ulcer dyspepsia (NUD) is a common complaint in which no systematic illness or organic proximal alimentary tract disease can be identified. The pathophysiology of NUD is probably heterogeneous. Eighty-two subjects with NUD were studied in a prospective randomized placebo-controlled study to assess the efficacy of colloidal bismuth subcitrate (CBS) chewable tablets at a dose of four tablets daily for 1 month. The role of Campylobacter pylori and associated histological gastritis was evaluated. Sixty-one percent of NUD patients had C. pylori in the gastric antrum compared with 25% of age-matched controls. C. pylori was associated with acute and chronic inflammation (P less than 0.001) in the antrum. C. pylori was cleared in 59% of CBS-treated subjects compared with only 4% placebo (P less than 0.05). Both acute and chronic inflammation improved in subjects cleared of bacteria. Clearance of C. pylori and histological improvement was associated with a significant decrease in symptoms. In C. pylori negative subjects improvement in symptoms occurred in both the placebo and active treatment groups. This study would suggest that C. pylori and associated histological gastritis may play a role in non-ulcer dyspepsia.
To assess the effect of specific immunotherapy (IT) on the immediate and late asthmatic responses induced by cat or dog extract bronchial provocation testing, we studied seven cat-sensitive and six dog-sensitive subjects with asthma. Among the cat-sensitive subjects, two of three subjects displaying only an immediate asthmatic response before IT lost the response after 3 months of IT with cat extract, whereas only one of four subjects with the dual (immediate and late) asthmatic responses had ablation of such responses (no significance for the one-tailed test). Three subjects had worsening of the immediate response after IT. Among dog-sensitive subjects with asthma, three of five subjects with only an immediate response demonstrated an ablation of the immediate response, whereas the one subject who was the only subject with a dual response before IT lost the dual response after dog-extract IT (p value of 0.005 on one-tailed test). Immediate systemic side effects, including one episode of anaphylaxis, occurred on seven occasions of 326 injections with cat extract compared to only one episode of rhinitis of 289 injections with dog extract.
We have cloned alfalfa nodule-specific cDNAs that code for leghemoglobin (Lb), glutamine synthetase (GS), and three unidentified nodulins. Hybrid-select translation of nodule RNA followed by 2-D gel electrophoresis showed that the Lb-specific cDNA corresponded to at least four Lb species of 12 kDa. One of the unidentified cDNA clones (N-32/34) corresponded to at least five polypeptides of 32-34 kDa; a second unidentified cDNA clone (N-14) corresponded to an individual polypeptide of 14 kDa. The in vitro translation product(s) of the RNA hybrid selected by the third unidentified cDNA clone (N-22) formed a single band at 22 kDa on a one-dimensional gel. Northern and dot blot analyses of RNA isolated from wild-type nodules and from defective nodules elicited by a variety of Rhizobium meliloti mutants showed that 1) RNAs corresponding to the Lb, nodule-specific GS, and three unidentified nodulins were coordinately expressed during the course of nodule development, and 2) all five nodulins were expressed in Fix- nodules that contained infection threads and bacteroids but were not expressed in nodules that lacked infection threads and intracellular rhizobia.
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We studied the effects of different procedures of blood collection and processing on quantification of apolipoprotein A-I (apoA-I) by radioimmunoassay. ApoA-II and apolipoproteins of low- and very-low-density lipoproteins did not cross react in the assay. Analytical recovery of apoA-I at different doses was complete. ApoA-I concentration in pooled human plasma was stable for as long as a year stored at -70 degrees C. Inter- and intra-assay CVs averaged 7% and 5%, respectively. We collected blood from 20 subjects into tubes containing EDTA alone or EDTA with antiproteolytic agents, then separated the plasma either immediately or after 3 h at 4 degrees C. We tested various formulations of antibacterial, antiproteolytic, and anti-oxidant agents added to plasma, measuring apoA-I concentrations either within 24 h of blood collection or after storage of plasma for 6 weeks at -70 degrees C. No significant difference in the concentrations of apoA-I was found in these specimens, regardless of the conditions studied. We conclude that addition of protective agents other than EDTA is not necessary during blood collection or specimen processing for reliable quantification of apoA-I in fresh or frozen human plasma.
There is good evidence that the idiotypic network of the immune system can be implicated in the synthesis of pathogenic subsets of autoantibodies. The individual with systemic lupus erythematosus must have the immunoglobulin gene information which permits synthesis of those idiotypes, helper T populations which drive or select for the B cells producing them, and inadequate mechanisms to suppress those activated effector cells.
A prospective study of diaphragm users at the Family Planning Association of Victoria was undertaken. Despite the women being well motivated and instructed the pregnancy rate was high (24 per 100 woman years) and the continuation rate was only 35% at 12 months. Three-quarters of the women who became pregnant admitted that they did not use a diaphragm on every occasion. Therefore emphasis must be placed on the committed use of the diaphragm every time coitus occurs. Even so, the diaphragm does not appear to be a very safe method of contraception, and may be better suited to family spacing rather than as a method when high efficacy is required.
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The bone vitamin K-dependent protein osteocalcin has been suggested to play a role in bone resorption. By administering sodium warfarin to rats, it is possible to inhibit the vitamin K-dependent addition of the their gamma-carboxyglutamic acid residues to osteocalcin. This results in reduced amounts of osteocalcin bone, probably because devoid of the calcium-binding Gla residues, the protein no longer accumulates in bone. Preparations of bone obtained from rats treated with sodium warfarin for 6 weeks contained only 0.2% of normal levels of osteocalcin and were 90% reduced in the concentration of Gla. This bone could not be degraded by human monocytes in vitro as well as control bone (only 54% of control; P less than 0.003). Defects in the movement of cells to the bone were documented by phase contrast microscopy. Only 60% as many monocytes attached to the osteocalcin-depleted bone as to control bone in an in vitro attachment assay. These effects do not appear to be related to direct cellular toxicity. The degradation of bone in this in vitro system appears to be dependent on the osteocalcin content in matrix. This may result from defective movement of cells to bone and/or attachment to the bone.
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