The newcomers. A visitor's views.
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Biomedical subjects
Publications and source records attributed to B Smith.
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In epidemiological/disease control studies, one might be interested in estimating the parameters community probability infection (CPI) and the household secondary attack rate (SAR), as introduced by Longini and Koopman. The quasi-binomial distribution I (QBD I) with parameters n, p and theta, introduced by Consul, is proposed as a model for the final-size distribution of household infections, where p (CPI) is the probability of an individual being infected from the community and theta (SAR) is the rate of secondary transmission of infection within household. An individual can be infected either from within the household or from the community. Let X be the total number of infected members in a household of size n. Then the distribution of X is given by the QBD I with the probability mass function: (formula: see text) with 0 < p < 1, theta > or = 0 such that p + n theta < 1. The epidemic model is derived from a directed random graph. Data from influenza epidemics in Asian and American households are used to test the model and a comparison is made with the Longini-Koopman model. It is shown empirically that the QBD I is as good as the L-K model in describing the household infectious disease data, and both models provide almost identical estimates for community and household transmission parameters although they are derived from different perspectives and conditions.
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The messenger ribonucleic acid (mRNA) of gap junction protein connexin 43 was quantified in the tetanus toxin rat model of focal epilepsy following injection of toxin into the left amygdala. Animals were monitored electrographically at weekly intervals with bilateral amygdala electrodes. Cohorts of 3 rats were sacrificed at weeks 1, 2, 3, 4, 6, 8, and 10, and bilateral regions containing the amygdala and posterior cerebral cortex were sampled, frozen, and later pooled for northern blot analysis. Spike generation was manifest in all animals during the first 4 wk followed by variable attenuation and cessation by 10 wk. Electrode implantation alone was shown by regression analysis to cause significant (p < 0.05) elevation of connexin mRNA in weeks 1-4. Injection of toxin diminished connexin mRNA expression in the amygdala when compared to electrode implantation alone. No trend in connexin mRNA expression was established over time in either amygdala or cerebral cortex in the acute epileptic or chronic postepileptic phase. No association between connexin 43 mRNA expression and the development of epileptogenicity was found in the context of a self-limiting animal model of focal epilepsy.
The expression of mRNA for connexin 43, a gap junction protein putatively found in astrocytes, is studied in two experimental models of epilepsy: the electrically kindled rat and the tetanus-toxin-injected rat. Rats were kindled by electrical stimulation of the amygdala to Racine class 5 seizures and divided into cohorts of three to undergo 3, 6, or 10 such events, respectively. Another two cohorts of rats received injections of tetanus toxin at strengths of 3 and 9 MLD50, respectively, into the amygdala. Features of epileptogenicity were identified electrographically in both cohorts during the first 4 wk following toxin injection with spontaneous ictal events recorded in the latter cohort. All rats were sacrificed 4 wk after electrode or cannula implantation, except for two toxin-injected cohorts that were sacrificed at wk 8 or 10. The epileptogeonic area in the region of the amygdala was harvested and pooled by cohort for Northern blot analysis. These were compared with control nonimplanted tissues. In the tetanus-toxin-injected animals, at time-points of 4, 8, and 10 wk, connexin 43 mRNA expression in epileptogenic tissues is found to be decreased or unchanged relative to control cases. Kindled rats demonstrated reductions of connexin mRNA with a trend toward normalizing levels with increasing numbers of stimulations when compared to control animals. Connexin 43 immunostained sections of the basolateral amygdala showed a similar trend in protein expression. Both experimental models of epilepsy show no connexin 43 mRNA upregulation despite varying degrees of epileptogenicity. This study therefore does not support the hypothesis that an increase in transcription is the basis for any proposed increase in gap junction communication involving connexin 43 in the context of epileptogenicity or as a reaction to increased neuronal excitability.
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Four Rh-positive patients with severe aplastic anemia received equine anti-lymphocyte globulin. Each developed a positive direct antiglobulin test. Anti-D was identified in eluates prepared from the patients' sensitized red cells. The administered lot of anti-lymphocyte globulin was found to contain anti-D. Red cell sensitization due to passively acquired Rh antibodies can result from the administration of anti-lymphocyte globulin.
An enzyme-linked antiglobulin test (ELAT) method was developed to estimate survival of transfused red cells. This procedure is based on a principle analogous to that of the Ashby technique were antigenically distinct red cells are transfused and their survival studied. We compared the ELAT survival to the 51Chromium method (51Cr) in four patients. Three patients with hypoproliferative anemias showed T 1/2 by ELAT of 17.5, 18, and 17 days versus 18.5, 20, and 19 days by the 51Cr method. A fourth patient with traumatic cardiac hemolysis had two studies performed. In this case, the ELAT showed a T 1/2 of 10 and 8.1 days while 51Cr T 1/2 values were 11 and 10.5 days. The ELAT method for measuring red cell survival yielded data which agreed closely with the results of the 51Cr method. Although 51Cr is the accepted method for red cell survival, the ELAT method can be used to estimate transfused red cell survival.
In order to evaluate the efficacy of performing red cell elutions in pretransfusion testing, the serologic records of 638 patients with positive direct antiglobulin tests (DAT) were reviewed. These patients were identified by routine antibody screening procedures that included an autologous control. DAT results on the red cells of these patients showed 279 with IgG and C3d sensitization, 319 with IgG alone, and 40 with C3d sensitization alone. Of 638 patients' red cell eluates, 401 demonstrated no reactivity, 154 demonstrated panagglutination, and 60 demonstrated passively acquired anti-A,B. Only 23 of 638 patients had alloantibody sensitization of their red cells. Of the 23, 19 had serum antibody corresponding to the specificity of antibody detected in the eluate. Thus, only four of 638 (0.6%) eluates gave results unavailable by serum testing alone. This study indicates that routine eluate investigation provides little useful information in assuring compatibility. Serum antibody testing and careful review of the clinical and transfusion history constitute appropriate pretransfusion testing in patients with positive direct antiglobulin tests. Eluate testing should be restricted to cases in which immune hemolysis is suspected clinically.
The authors identified persistent Th activation in five of seven children (71.4%) diagnosed as having Fanconi's anemia or Diamond-Blackfan syndrome. Th reactivity was no longer present in one patient after bone marrow transplantation. Tests on family members and other patients with bone marrow dysfunctions of childhood showed no Th activation. Less than 1 percent of healthy children or blood donors had Th activation. Patients with a variety of hemolytic and hypoplastic conditions also had a low incidence of Th activation. However, 13.5 percent of cord blood specimens demonstrated Th reactivity. This study indicates that Th activation may be a red cell developmental marker present in congenital hypoplastic anemias and also expressed on newborn red cells.
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Platelets and neutrophils accumulate rapidly in infarcted myocardium. Although antineutrophil agents reduce the size of the infarcted area, this is not observed with antiplatelet drugs. The possibility that myocardial ischemia-induced platelet deposition was secondary to a neutrophil-mediated event was assessed by injecting prostacyclin-washed autologous 111In-labeled platelets and measuring the amount of radioactivity in different regions of the heart following 90-min occlusion of the left anterior descending coronary artery followed by reperfusion for periods up to 5 h. Platelet deposition during the reperfusion phase was linear with time and similar to the time course of neutrophil accumulation. There was a transmural distribution of radioactivity across the myocardium where the "zone" between infarcted and risk regions, called the "interface," greater than infarct greater than risk greater than normal. Neutropenia (21 +/- 2% control levels), induced with specific sheep anti-dog neutrophil antiserum, had minimal effects on platelet aggregation ex vivo, but significantly reduced platelet accumulation in the ischemic myocardium following 5-h reperfusion and abolished the transmural platelet distribution. These results suggest that myocardial platelet deposition is secondary to a neutrophil-mediated event in this occlusion-reperfusion model of myocardial injury. Interactions between platelets and neutrophils at the site of tissue damage may influence the process of myocardial ischemic injury.
Specimens of urethral exudate from 200 men with uncomplicated urethritis were tested for Neisseria gonorrhoeae by the limulus amebocyte lysate assay, culture on modified Thayer-Martin medium, and gram-stained smear. As compared with cultures, the sensitivity and specificity of the limulus assay were 94.8% and 89.3%, respectively, while the sensitivity and specificity of the gram stain were 98.8% and 100.0%, respectively. The accuracy of prediction of the presence of N. gonorrhoeae was significantly better by gram-stained smear than by the limulus assay. Unless the limulus assay is modified, as it was in this study, it does not appear to have a role in the presumptive diagnosis of the gonorrhea in men at a clinic for sexually transmitted diseases.
Use of intramuscular botulinum-A toxin (Botox) to produce neuromuscular blockade has been effective in treating certain ocular and facial muscular imbalances as well as spasmodic torticollis. In this preliminary open study, the effectiveness of intramuscularly injected Botox on the muscular imbalances of cerebral palsy was assessed in 27 pediatric patients. Each patient had "dynamic deformities" unresponsive to other treatment, and operation was the only other realistic alternative. The dose of Botox was calculated on a unit/body weight basis. In ambulatory patients, clinical changes in gait were assessed by a physician's rating scale. Reduction in spasticity became apparent in 12-72 h after injection; the effect of Botox after target threshold was reached lasted 3-6 months. No major side effects occurred. Botox may prove a useful adjuvant in conservative management of the spasticity of cerebral palsy. Successful management with these injections may allow delay of surgical intervention until the child is older and at less risk of possible complications, including the need for repeated surgical procedures.