Detection by PCR of HHV-6 and EBV DNA in blood and oropharynx of healthy adults and HIV-seropositives.
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Biomedical subjects
Publications and source records attributed to J Fox.
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Computer systems are increasingly being introduced to assist in decision making, including hazardous decision making. To ensure effective assistance, decision procedures should be theoretically sound, flexible in operation (particularly in unpredictable environments) and effectively accountable to human supervisors and auditors. Strengths and weaknesses of classical statistical decision models are discussed from these perspectives. It is argued that more can be learned from human decision behaviour than has traditionally been assumed, and this motivates the concept of a symbolic decision procedure (SDP). The SDP is defined, described in terms of first-order (predicate) logic, and its use illustrated in a decision support system for medicine. We point out that the classical numerical decision procedure is a special case of a generalized symbolic procedure, and discuss the potential for rigorous formalization of the latter. We conclude that symbolic decision procedures may meet requirements for assisting human operators in hazardous situations more satisfactorily than classical decision procedures.
Thermal laser angioplasty uses constant laser power, producing widely variable tip temperatures in vivo. Results have been suboptimal. We studied the effect of 50-400 degrees C tip temperatures on depth of ablation at 192 sites on plaqued and normal human aorta in vitro, and the angiographic and histologic response in vivo of 300-400 degrees C at probe/vessel ratios of 0.5-1.0, in 40 normal canine femoral artery segments. In vitro, there was a direct relationship between tip temperature and depth of ablation, r = 0.71 (all segments), r = 0.74 for fibrous plaque, but a poor correlation in fatty plaque r = 0.35. In fibrous plaque, there was proportionately more ablation at tip temperatures greater than 300 degrees C, mean depth 0.62 mm, than at 150-300 degrees C, mean 0.37 mm, (P less than .001). Ablation was similar in plaqued and normal aorta. In vivo, 300 degrees C, 350 degrees C, and 400 degrees C produced similar effects. At probe/vessel ratios less than 0.8, only disruption of internal elastic lamina was observed. At ratios greater than or equal to 0.8, spasm occurred in 39% (7/18), transmural damage in 28% (5/18), and perforation in one of 18. Ablation is not selective for plaque and is highly variable in fatty plaque. Tip temperatures above 300 degrees C produce greater ablation than at lower temperatures. In clinical applications, probe/vessel rations less than or equal to 0.7 may be most appropriate, and it appears that thermal remodeling may contribute more to outcome than plaque ablation.
The functional role of exercise in the development of weight preoccupation and body dissatisfaction was examined. One hundred and twelve females, identified as regular participants in exercise programmes, completed an inventory that provided information on attitudes, behaviours and psychological characteristics related to dieting and weight-control, as well as a self-report of physical activity. A structural equation model was tested that provides support for the notion that Body Mass Index, emotional reactivity and physical activity have statistically significant direct effects on weight and diet concerns, but that weight and diet concerns do not predict the degree of participation in physical activity. Significant differences in eating disorder indicators were found between sub-groups identified as 'constantly dieting' and 'rarely dieting'. The tentative, but important, conclusion was drawn that regular participation in a fitness programme may be causally related to excessive concern with weight and dieting.
Forty-one patients with recurrent fatigue were studied for evidence of symptom clustering, abnormal laboratory findings and infection with novel viruses. Symptom enquiry and investigations were repeated 4 months later. Four patients were found to have diseases compatible with their symptoms. In those remaining, an initial acute onset of symptoms was associated with an intermittent course, tender glands and a raised number of T suppressor lymphocytes. Raised numbers of T suppressor lymphocytes at follow-up correlated with resolution of symptoms. Antibodies to human herpesvirus 6 (HHV-6) were found in 75% of the patients as compared to 53% of a control group and more patients than controls were strongly seropositive. Some patients with chronic fatigue have a pattern of illness which suggests glandular fever, although acute infection with Epstein-Barr virus (EBV) is not demonstrated. Primary or reactivation infection with HHV-6 may have a role in this syndrome.
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I have adapted the primed-infusion technique for the rapid estimation of the metabolic clearance rate (MCR) and production rate (PR) of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in chronically catheterized conscious rats. Following a bolus injection, [3H]-1,25(OH)2D3 was infused iv at a constant rate for 7 h. Steady-state [3H]-1,25(OH)2D3 levels in plasma were achieved within 3 h. HPLC-purification of plasma [3H]-1,25(OH)2D3 was necessary. This rapid, primed-infusion technique thus eliminates the need for protracted infusions to achieve steady-state plasma [3H]-1,25(OH)2D3 levels. The MCR averaged 0.201 +/- 0.003 ml.min-1.kg-1 in fed male rats weighing 200-300 g. This MCR is approximately 50% lower than that seen in other species. Overnight fasting was without effect on the MCR. The MCR increased in direct proportion to body weight in maturing rats (6-16 weeks old) weighing 150-450 g. Thus, the MCR can be normalized per kg across this age range. However, 1,25(OH)2D3 production and plasma levels both decreased by 65-67% as the rats matured. The failure of a 3-fold decrease in plasma 1,25(OH)2D3 levels to affect the MCR suggests that 1,25(OH)2D3 stimulates its own catabolism only at markedly elevated concentrations.
Photosensitization of atherosclerotic (Ath) plaque with exogenous chromophores may confine laser irradiation (LI) injury to Ath plaque and allow safer and more efficacious laser angioplasty. Dihematoporphyrin ether (DHE) accumulates preferentially in plaque, and previous in vitro LI studies have shown confinement of LI injury to plaque. To further evaluate DHE enhanced laser angioplasty, 5 Ath Yucatan miniswine with 8 iliofemoral stenoses (Sten) were treated with 2.5 mg/kg of DHE IV. Twenty-four hours later, 632 nm continuous wave LI was delivered to Sten using 200mu core optical fiber with a 582mu x 1cm diffusing tip. Angiograms were performed before, immediately after, and two weeks following LI. 6 of 8 vessels showed improvement. Control mean Sten was 71%, immediate post LI was 55% and 2 weeks post LI was 19% Sten. In 4 of 6 responding vessels, there was 0% Sten at 2 weeks post LI and the previously stenotic segments appeared normal. 2 of 6 responders showed only modest improvement, from control mean Sten of 83% to 55% Sten at 2 weeks. 2 of 8 vessels showed no improvement. There were no perforations or dissections. The excellent results in some vessels demonstrate the potential of photosensitizer enhanced LI as very effective primary therapy of Ath. The time course of improvement indicates that both immediate thermal and delayed photochemical (photodynamic therapy) effects are operative. Further studies are required to identify reasons for failure in some vessels.
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A prospective bacteriologic study of 18 infant pig-tailed macaques (Macaca nemestrina) housed in a nursery facility in which Campylobacter spp. are endemic was undertaken to determine the epidemiology of infection and reinfection. The isolates of Campylobacter jejuni and C. coli cultured from 8 of the 18 infants were characterized by serotyping, DNA hybridization, and polyacrylamide gel electrophoresis protein profiles. The chronology of infection was indicative of multiple reinfections with different strains of C. jejuni and C. coli during the 12-month study of each infant. The duration of infection with a particular strain was 3 to 4 weeks. Infants were also infected with nalidixic acid-resistant campylobacters. These observations indicated that long-term infections under endemic conditions are caused by continual reinfection. C. jejuni or C. coli infection correlated with diarrhea in 5 of the 18 infants at 1 to 4 months of age.
Establishment of infection with Helicobacter pylori and gastritis in nonhuman species is currently only successful in gnotobiotic piglets. This study was designed to determine whether H. pylori will colonize the gastrointestinal tract of gnotobiotic dogs. Gnotobiotic beagle pups were derived by standard methods. Group A (five dogs) was orally challenged with 3 x 10(8) H. pylori at 7 days of age. Group B (two dogs) received only peptone water but was contact-exposed beginning on day 23 postinfection (p.i.). Necropsy was performed on dogs on day 30 p.i. H. pylori colonized the stomach of all dogs (groups A and B). Urease map analysis correlated with the microbiologic findings and indicated that the density of colonization was less than that observed in human tissue. Organisms were also recovered from the pharynx, esophagus, duodenum, and rectum of 1, 2, 2, and 1 dog, respectively. All group A and one group B dog developed serum immunoglobulin G specific for H. pylori by day 30 p.i. Gross lesions were restricted to the stomach and consisted of small (less than 1 mm) lymphoid follicles. Microscopically, there were focal to diffuse lymphoplasmacytic infiltrates with follicle formation and mild to moderate infiltration of neutrophils and eosinophils in the gastric lamina propria. With the Warthin-Starry silver stain, organisms were seen on the surface of the gastric epithelial cells, beneath the mucus layer. We conclude that H. pylori colonizes the stomachs of gnotobiotic dogs for at least 1 month and the lesions resemble those seen in humans. H. pylori is transmissible by contact from infected to noninfected dogs.
Administration of large doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] to animals induces 1,25(OH)2D3 side-chain oxidative pathways. This study determined if the elevated plasma 1,25(OH)2D3 seen in rats fed low-Ca diets is associated not only with an increased production rate (PR) but also with an increased metabolic clearance rate (MCR) of the hormone. In vitamin D-replete rats fed a Ca-deficient diet for 3-4 wk, the PR increased 21-fold, plasma levels 15-fold, and the MCR by 37%. The increased MCR in Ca-deficient rats was associated with a 48% increase in hepatic microsomal UDP glucuronyl transferase enzyme activity, whereas 1,25(OH)2D3 catabolism by homogenates of liver and small intestinal mucosa was unchanged. In contrast to the effects of low-Ca diets, acute (7 h) pharmacological elevation of plasma 1,25(OH)2D3 to 1.5 ng/ml in normal rats did not influence the MCR. Thus chronically elevated 1,25(OH)2D3 levels are necessary to stimulate clearance. In conclusion, 1,25(OH)2D3 clearance in rats can be stimulated not only by chronic pharmacological doses of 1,25(OH)2D3 but also by the physiological stimulus of a low-Ca diet. Hence, plasma 1,25(OH)2D3 levels can be regulated by changes in both PR and MCR.
Previous studies have failed to show consistent differences in pulmonary function between wind instrument musicians and normal controls. In this study, respiratory sensation was assessed in 13 professional wind instrument players and 13 age-matched controls. Psychophysical techniques were used to assess magnitude estimation and reproduction of lung volumes and inspiratory pressures. The exponent for volume magnitude estimation was not different in musicians and controls (1.17 +/- 0.11 vs. 1.16 +/- 0.11), but volume reproduction was more accurate in musicians. The mean exponent for pressure magnitude estimation was 1.34 +/- 0.14 and 1.06 +/- 0.09 (P = 0.057) in musicians and controls, respectively. There was no difference between groups for absolute or constant error for pressure reproduction. Professional wind instrument players appear to have some inherent or acquired differences in respiratory perception and ventilatory neuromuscular control compared with other normal subjects.
We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.
This article deals with decision subsystems at the level of the organism. In recent years there has been debate as to whether linear models or clinical expert systems make clinical decisions more effectively. Previous articles in this journal have favored linear models. This article argues the opposite case. We show that expert systems are not necessarily more expensive or less accurate than linear models and that, in theory at least, they can perform many tasks that are beyond the scope of linear models. Indeed, while a linear model may serve as a subsystem of a human or computer expert system, an expert system cannot be seen as a subsystem of a linear model. We conclude that clinical expert systems and linear models are not interchangeable and users should not be forced to choose between them.
Duck cultured hepatocytes from Pekin ducks naturally infected by duck hepatitis B virus can remain functional twice longer if a coculture system with rat liver epithelial cells is used instead of ordinary primary culture. The use of a selective medium in which ornithine and lactate replaced arginine and glucose, respectively, allowed viral replication initiated in vivo to be maintained in the coculture for 2 months. Several antiviral compounds including the pyrophosphate analog (phosphonoformic acid) or nucleoside analogs (9 beta-arabinofuranosyl AMP, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine, 1,2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-ethyluracil and 1,2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl thymine) were studied in both culture systems for their ability to inhibit duck hepatitis B virus replication. Hepatocytes were treated for 7 days with 1,2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-ethyluracil (10 microM) and 1,2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl thymine (0.5 microM) or for 14 days with 9 beta-arabinofuranosyl AMP (90 microM), phosphonoformic acid (100 microM) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (6 microM). The effects of the drugs on viral replication were monitored by testing for duck hepatitis B virus DNA in the culture supernatant and in the cells by molecular hybridization.(ABSTRACT TRUNCATED AT 250 WORDS)
The study evaluated catheter-directed laser injury of the left ventricular myocardium in a canine model as a potential method for treatment of resistant ventricular tachycardia. The relationship between laser energy delivered, the laser delivery characteristics, and the lesion size was evaluated both in vitro and in vivo. The effect of laser injury on several hematologic and hemodynamic parameters was studied. Programmed electrical stimulation studies were performed to assess the proarrhythmia potential of laser injury of the myocardium. The results showed the depth and diameter of myocardial injury to be directly related to total laser energy applied. Both depth and diameter of injury were increased by multiple applications of laser energy to the same myocardial location. One-half to full thickness left ventricular injury was produced without perforation or embolization. Endocardial vaporization occurred only with laser powers higher than necessary to produce full-thickness injury. There was no sustained effect on the hemodynamic or hematologic variables studied, nor were proarrhythmia effects identified. The laser injury produced in these studies was of smaller magnitude than might be necessary for clinical arrhythmia ablation, and the lack of sustained hemodynamic effects and pro-arrhythmia potential needs to be verified in subsequent studies with larger laser lesions. The results support continued evaluation of catheter-directed laser injury of the myocardium as a potential method for elimination of life-threatening ventricular arrhythmias.
We evaluated two representative microcomputer-based programs for organizing a biomedical literature filing system. With a bibliography of 100 anesthetic references, a series of benchmark tests was developed to measure the speed and accuracy of typical searching, sorting, and formatting tasks. Each program performed the searching tasks accurately and at about the same speed. One program performed sorting without errors, provided the field order of the template used to enter references was unchanged. Both programs used "punctuation files," that is, templates for controlling author presentation; punctuation to suit style requirements of individual journals; and order of particular fields, such as publisher and year of publication. Each program was able to format journal, book, and chapter references correctly, but the resulting output required some refining in a word processor. Both require a major time commitment to learn and to create custom punctuation files for journals not included in the predesigned punctuation files. Once mastered, both programs are quite competent at organizing reprints and formatting journal references.