What are the standards for standards? Round table discussion.
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Biomedical subjects
Publications and source records attributed to J Blair.
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It has been considered unusual for periarticular calcifications to consist of calcium pyrophosphate dihydrate (CPPD). We describe a patient presenting with pain and inflammation adjacent to the site of tumoral calcifications and extending to the first metatarsophalangeal joint. Aspiration of the material revealed weakly positive birefringent rhomboid shaped crystals that proved to be CPPD by atomic force microscopy. The patient had no metabolic abnormalities or radiographic chondrocalcinosis. We believe other cases similar to ours represent another clinical form of CPPD deposition disease-periarticular pseudogout.
Exposures of as little as 2.5 per cent of the body surface to concentrated hydrofluoric acid (HF) may be fatal. Survival after major HF exposures is facilitated by aggressive emergency management which, we feel, includes wound irrigation, subeschar injection of calcium gluconate, monitored supplementation of serum calcium, and prompt wound excision carried out as an emergency procedure. The following case reports and literature review illustrate the important differences between exposures to concentrated HF of as little as 2 per cent of the body surface and smaller exposures to concentrated HF or exposure to dilute HF.
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Neurotrophins are known to have important functions in the survival of embryonic and adult subpopulations of neurons. The identification of Trk family RTKs as receptors for NGF-related neurotrophins indicates phosphotyrosine-mediated signal transduction as a principal mechanism for neurotrophin signaling. Previous trk and trkB expression studies (Klein et al. 1989, 1990b; Martin-Zanca et al. 1990) and more recent studies with trkC (L. Tessarollo et al., in prep.) provide important clues about function. Thus, trkB and trkC expression in motor neurons and in many nonneuronal cells suggests that these cells are targets for neurotrophin action in vivo, even though this has not been demonstrated in the classic in vitro survival assays. Expression of trkB and trkC in nonneuronal cells implies that these receptors may act in additional aspects of organogenesis and development. Current approaches to assay Trk receptor and neurotrophin function will be complemented by further studies in the living organism. Transgenic approaches aimed at ectopic expression and at interfering with normal receptor function should provide additional insights. Finally, reverse genetic approaches using targeted mutation of Trk receptors in embryonic stem cells (Stanton et al. 1992) will allow assessment of critical receptor requirements and provide powerful reagents for studying nervous system development and function.
Neurotrophic factors are essential for neuronal survival and function. Recent data have demonstrated that the product of the tyrosine kinase trk proto-oncogene binds NGF and is a component of the high affinity NGF receptor. Analysis of the trkB gene product, gp145trkB, in NIH 3T3 cells indicates that this tyrosine kinase receptor is rapidly phosphorylated on tyrosine residues upon exposure to the NGF-related neurotrophic factors BDNF and NT-3. Furthermore, gp145trkB specifically binds BDNF and NT-3 in NIH 3T3 cells and in hippocampal cells, but does not bind NGF. Thus, the trk family of receptors are likely to be important signal transducers of NGF-related trophic signals in the formation and maintenance of neuronal circuits.
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The psychomotor function of 27 long-term haemodialysis patients with apparently normal cerebral function, who had only mildly raised serum aluminium (mean 59 [SEM 9] micrograms/l), was measured by means of a computerised version of the symbol digit coding test. Compared with those of control subjects matched for age and the patients' estimated premorbid IQ, the patients' response times were significantly longer (2.51 [0.10] vs 1.88 [0.05] s). Abnormalities were also detected in five other computerised tests of psychomotor function. The mean activity of erythrocyte dihydropteridine reductase (DHPR), which is inhibited by aluminium, rose during 3 months' desferrioxamine treatment in most of the 15 patients so treated. Although there was no relation between baseline psychomotor function and either indices of cumulative aluminium exposure or erythrocyte DHPR activity, changes in DHPR induced by desferrioxamine correlated with changes in psychomotor performance (r = 0.62). The flash-stimulated visual evoked potential (measured in 10 patients) was delayed (133.4 [2.4] ms), although the pattern-stimulated visual evoked potential remained normal (101.8 [3.2] ms). The difference between the visual evoked potentials stimulated by flash and pattern was significantly greater in the patients than in the controls (31.6 [4.3] vs 19.4 [2.4] ms) and was significantly related to the symbol digit coding response times and to the oral aluminium intake. The results suggest that much more rigorous exclusion of aluminium from the dialysate and diet of dialysis patients is necessary.
To determine whether naloxone infusion is efficacious in severe hyperdynamic septic shock, we conducted a prospective study of 22 patients randomly assigned to a naloxone or placebo group. Patients were treated 12 +/- 2 h (SEM) after the onset of shock, with a mean arterial pressure (MAP) of 63 +/- 3 mm Hg. All patients had clinical evidence of an infectious process and required dopamine 20 +/- 2 micrograms/kg.min. Five (46%) of 11 patients in the naloxone group and one (9%) of the other 11 patients in the placebo group responded clinically. The MAP among the five responders increased from 62 +/- 5 to 89 +/- 4 mm Hg within 20 min of naloxone treatment (p less than .01). This favorable hemodynamic response was sustained throughout the patients' clinical course. In contrast, the MAP did not change significantly in the nonresponders who received naloxone, nor did it change in the placebo group. More patients in the naloxone group than in the placebo group received steroids concurrently. Survival rate was 100% in those who responded to naloxone clinically. However, overall survival rate in each group was essentially the same. No adverse effects were observed, except for mild agitation in some of the patients receiving naloxone. We conclude that naloxone infusion is clinically efficacious in improving the hemodynamic profile of a subgroup of patients with severe early hyperdynamic septic shock, but does not appear to improve the overall survival rate.
Previous studies from our laboratory on the feminization of the male mouse reproductive tract after prenatal exposure to diethylstilbestrol (DES) showed that the mRNA for the major estrogen-inducible uterine secretory protein, lactoferrin (LF), was constitutively expressed in the seminal vesicle of male mice exposed prenatally to DES, but not in the seminal vesicle of control mice. After castration, treatment with 17 beta-estradiol (20 micrograms/kg.day) for 3 days induced the LF mRNA in the seminal vesicle of both control and prenatally DES-exposed mice; however, the levels in DES-treated tissues were approximately 6-fold higher than those in control tissue. This report describes the presence of LF in seminal vesicle tissues and secretions of prenatally DES-exposed mice, as determined by immunohistochemistry and Western blot analysis. Further, these data are correlated with immunolocalization of the estrogen receptor in the seminal vesicle tissue. We conclude that the seminal vesicle of prenatally DES-exposed male mice has acquired two key characteristics of female tissues, namely LF production/regulation and estrogen receptor localization/distribution similar to that in uterine tissues.
The validity and reliability of nine senior sawmill workers' estimates of frequency, duration, and routes of exposure were compared with individual workers' ratings of their own job titles and industrial hygienists' ratings of all job titles in the plant. The reliability of the senior workers' mean exposure estimates [group intraclass correlation coefficient (ICC) = 0.71] compared favorably with those of three pairs of hygienists (group ICC = 0.57, 0.67, and 0.81). The validity of their ratings was assessed in a comparison with urinary chlorophenate measurements representing 92% of the job titles in the sawmill. The senior workers' ratings [coefficient of determination (R2) = 0.22] resembled those of two pairs of industrial hygienists (R2 = 0.24, 0.22) and was significantly greater than that of the third pair (R2 = 0.08). The validity of the self-reports was also low (R2 = 0.15), but the difference was not statistically significant. Senior workers' exposure ratings appear to be as effective as the other methods tested.
A retrospective review was undertaken to determine factors important in predicting functional results following the ileal reservoir and ileoanal anastomosis procedure. One hundred seventy-nine patients underwent ileal reservoir and ileoanal anastomosis at the University of Toronto between December 1981 and January 1987. One hundred sixty-three patients had ulcerative colitis, 11 had familial adenomatous polyposis, and five had Crohn's disease. A J-reservoir was constructed in 72 patients and an S-reservoir in 107 patients. Functional results were assessed in 102 patients who had their loop ileostomies closed for more than one year. The most significant technical complications were anal anastomotic leaks (10 percent), reservoir anastomotic leaks (3.9 percent), anal anastomotic stricture (7.8 percent), late fistula-inano (2.8 percent), small-bowel obstruction (19 percent), and loop ileostomy complications (23 percent). Overweight males and patients with operative blood loss greater than 1000 cc developed anal stricture more frequently (P less than .005). Patients who had a stapled J-reservoir had a higher rate of reservoir leak. The average number of bowel movements reported by patients for 24 hours was 6.2 +/- 3.1. Only ten (9.8 percent) patients had to intubate their reservoir to empty it. Urgency was experienced by 24 patients and soilage at night by 23 (22.5 percent) and during the day by 18 (17.6 percent). Seven patients (6.8 percent) were incontinent during the night and only one during the day. Pouchitis was reported in 16 patients (15.7 percent). Patients with anal anastomotic stricture had more urgency and pouchitis, and had to intubate their reservoir more frequently (P less than .05). No other factors analyzed affected technical or functional results.
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Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.
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