[Familial forms of fronto-temporal dementia].
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Biomedical subjects
Publications and source records attributed to M Stevens.
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We have previously demonstrated that IL-9 induction in human T cells stimulated with PMA and anti-CD3 Ab is mediated by IL-2, as it was blocked by anti-IL-2R Ab. The experiments reported here indicate that anti-IL-2R Ab also inhibited the expression of IL-4, IL-6, and IL-10, thereby raising the possibility that the blockade of IL-9 production by anti-IL-2R mAb could be secondary to the blockade of these cytokines. We found that the inhibition caused by anti-IL-2R Ab on IL-9 production could be reversed by the addition of a combination of IL-4 and IL-10. Moreover, IL-9 production by T cells stimulated with PMA and anti-CD3 Ab was blocked by the addition of anti-IL-4 and anti-IL-10 Abs. Similar results were obtained with T cells cultured on B7-1/Fc gamma RII-transfected fibroblasts in the presence of anti-CD3 Ab. Analysis of cytokine production by different T cell subsets revealed that IL-4, IL-9, and IL-10 were produced only by CD45 Ro+ T cells. Importantly, CD45 Ra+ T cells were capable of producing IL-9 provided that both IL-4 and IL-10 were added to the cultures. The possible relationship between IL-4 production and IL-10 production was clarified by experiments indicating that IL-10 production was inhibited by anti-IL-4 Ab. However, IL-4 was not sufficient to trigger IL-10 production, which required both IL-2 and IL-4. Taken together, our results demonstrate the existence of a cascade of cytokines responsible for IL-9 expression, with IL-2 being required for IL-4 production, a combination of IL-2 and IL-4 for IL-10 production, and a combination of IL-4 and IL-10 for IL-9 production. Kinetics studies of cytokine gene expression in T cells further validated this model.
OBJECTIVE: To gather information on which to base decisions about a general notification program for pediatric patients a decade after their receiving transfusions. DESIGN: The physicians of a cohort of 1793 patients who underwent cardiac surgery were sent letters asking them to contact and counsel patients identified from cardiovascular surgery and blood bank databases about their risk for human immunodeficiency virus (HIV) infection. Questionnaires were used to collect data about physicians' HIV practices; telephone interviews were conducted to collect information about patients' and parents' knowledge and attitudes about HIV and transfusions. Because of unexpected media interest, questionnaires and interviews were modified to include questions about the source of information. The HIV-testing status of patients reported by physicians was anonymously cross-referenced with specimens received by the Laboratory Services Branch, Ontario Ministry of Health, Toronto. SETTING: A large Canadian pediatric tertiary care hospital in Toronto. PARTICIPANTS: Seven hundred ninety-three patients undergoing cardiopulmonary bypass between 1980 and 1985. RESULTS: The HIV Information Project successfully reached most (approximately 75%) of this cohort and, with the help of the media, many other at-risk transfusion recipients. The information was new for many; almost all informed wanted to undergo testing. The seroprevalence of this group that received multiple transfusions was, at minimum, 8.5 patients in 1000. Six previously unsuspected HIV-seropositive cases were diagnosed. CONCLUSIONS: Although we had assumed that most patients receiving transfusions would be aware of their risk for HIV infection, our results indicate that, even a decade after the transfusion, many recipients were not aware of the risk and wanted to undergo testing. Testing identified asymptomatic infected patients.
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A review of the literature suggests that psychosocial disability in traumatic brain-injured (TBI) individuals and distress in families continues long after the initial injury. In this study the relationship of family stress to a number of factors was studied longitudinally. Caregivers of 51 TBI inpatients were interviewed at rehabilitation admission and by phone at 6, 12, and 24 months postinjury. Caregivers' most common complaints about their relatives were a lack of involvement in leisure activities, fatigue, slowness, and forgetfulness. Increasingly severe temper outbursts, anxiety, and self-centeredness were reported over time. Aggressiveness was reported by caregivers as moderate or severe in 31% of cases by 2 years postinjury. Of all complaints, only reports of inappropriate social behavior decreased over time. Despite caregivers' increasing complaints about their relatives, there were no trends toward greater self-reported stress over time. At the 2-year assessment, stress was significantly higher for caregivers of those with an at risk psychosocial history, and for those without sufficient funds for services. Caregivers reporting financial strain increased 22% from rehabilitation admission. Forty-seven percent of caregivers had altered or given up their jobs at 1 year postinjury, and 33% at 2 years postinjury. Although self-perceived measurements of stress did not increase over time, caregivers reported notable increases in medication use and substance use, and decreases in employment and financial status over the 2-year time period. When spouse and parent caregiver responses were compared, spouses reported a consistently greater number of behavioral problems, which increased in severity over time. Those behaviors associated with mood disturbances predominated.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: One hundred twenty children, identified before birth as being at high risk for atopy, were prenatally assigned to prophylactic or control groups. METHODS: The infants in the prophylactic group either received breast milk from mothers on an exclusion diet or an extensively hydrolyzed formula. Their bedrooms and living rooms were treated repeatedly with an acaricide, and they used polyvinyl-covered mattresses with vented head areas. The infants in the control group were fed conventionally, and no environmental control was recommended. RESULTS: A significant advantage, first demonstrated at 1 year of age, persists for children in the prophylactic group. They have less of any allergy or eczema, but the reduced prevalence of asthma is no longer significant. Only three children in the prophylactic group had positive skin prick test results compared with 16 in the control group, suggesting a significant reduction in sensitization. CONCLUSION: A dual approach to allergen avoidance, focusing on foods and aeroallergens, appears to be beneficial in selected high-risk infants. Avoidance of potent allergens in early life increases the threshold for sensitization in these high-risk infants. Whether sensitization has been avoided or merely deferred has yet to be proved.
We have compared in 25 children the effect of preoperative with postoperative caudal block on pain after circumcision in a double-blind, randomized study. After induction of anaesthesia, patients were allocated randomly to receive a caudal block either before (n = 14) or immediately after (n = 11) surgery. Postoperative pain was rated on a paediatric pain scale. If pain occurred, children received paracetamol in a dose related to body weight. Using the Mann-Whitney U test (significance < or = 0.05) there was no significant difference in cumulative postoperative analgesic requirements within the first 48 h and in times to first analgesic administration between the groups. Cumulative pain score, assessed every 30 min for the first 8 h after operation, was significantly lower for those patients who received caudal anaesthesia after operation. Thus we could not demonstrate any advantage in performing caudal block before compared with after surgery.
The Biolog system (Biolog, Inc., Hayward, Calif.) was evaluated for the identification of 55 gram-negative taxa (789 strains) likely to be encountered commonly in clinical laboratories. The Biolog system performed best with oxidase-positive fermenters and biochemically active nonfermenters and had the most problems with unreactive nonfermenters. It gave significantly better results when the MicroPlates were read manually rather than when they were read by the automated reader. Plates read manually gave the following performances: oxidase-positive fermenters, five taxa, 64 strains, 92% correct, 3% not identified, and 5% incorrect; biochemically active nonfermenters, eight taxa, 122 strains, 88% correct, 6% not identified, and 6% incorrect; members of the family Enterobacteriaceae, 35 taxa, 511 strains, 77% correct, 8% not identified, and 15% incorrect; unreactive nonfermenters, seven taxa, 92 strains, 38% correct, 24% not identified, and 38% incorrect. We found the system easy to use, but while for 39 of 55 of the taxa an identification rate of > 70% was achieved, problems were encountered, particularly with identification of capsulated strains of some Enterobacter and Klebsiella taxa, as well as the least biochemically active Moraxella and Neisseria strains.
The BBL Crystal system (Becton Dickinson Microbiology Systems, Cockeysville, Md.) is a miniaturized bacterial identification method employing modified conventional and chromogenic substrates. Two products are currently available, the Rapid Stool/Enteric ID Kit and the Enteric/Nonfermenter ID Kit, each comprising thirty tests. We report an evaluation of both systems (using database version 1.1 for both) in the identification of 51 gram-negative taxa likely to be encountered commonly in the clinical laboratory. In all, 266 strains were tested in the Enteric/Nonfermenter ID Kit, and these represented 36 taxa of the family Enterobacteriaceae (188 strains), 5 oxidase-positive fermentative taxa (26 strains), and 10 nonfermentative taxa (52 strains). The majority of these same strains (203 of 266) were also tested in the Rapid Stool/Enteric ID Kit. The Enteric/Nonfermenter ID Kit performed as follows: Enterobacteriaceae, 93% correct, 6% not identified, and 1% incorrect; oxidase-positive fermenters, 88, 12, and 0%, respectively; and nonfermenters, 100% correct, although several only to the genus or group level. The Rapid Stool/Enteric ID Kit gave the following results: Enterobacteriaceae, 91% correct, 7% not identified, and 2% incorrect; oxidase-positive fermenters, 80, 13, and 7%, respectively (but results were based on only 15 strains); and nonfermenters, 100% correct (but results were based on only 11 strains). We found the systems extremely easy and rapid to use, and for the Enteric/Nonfermenter ID Kit an identification rate of 100% in 40 of 51 taxa was achieved, with corresponding figures of 29 of 39 taxa for the Rapid Stool/Enteric ID Kit.
Vision loss during a centrifuge run is an expected occurrence given the G-profile, physical fitness of the subject, expected visual endpoint [central light loss (CLL) or peripheral light loss (PLL)] of the experimental protocol, and the cyclic nature of the anti-G straining maneuver (AGSM). During a relatively low level G exposure, a subject experienced a unilateral loss of vision that did not resolve spontaneously upon removal of the G load. An extensive medical workup did not reveal any medical explanation for the vision loss.
The aeromedical research and operational flying communities have at least one common goal; ensuring the optimum combination of mission performance and safety for the aircrew. This is a continual challenge as aerospace technology leaps ahead while the human factor remains relatively constant. However, several issues interfere with the smooth interaction between these communities: 1) perceptions that the research and operational communities have towards human subjects and pilots respectively; 2) the legal and ethical considerations involved in exposing individuals to risk; and 3) the ever-present personality dynamics involved in any decision-making process (e.g., returning individuals to a centrifuge panel or flying duty after a medically disqualifying incident). All of these factors influence decisions made in both communities, and how they interact with each other. It is a dynamic process that varies between countries, individual services (e.g., Navy vs Air Force), and even between different geographical locations within the same service.
Gall bladder motor function is impaired in some patients with diabetes. It has been suggested that the abnormalities of gall bladder motility are confined to those patients with autonomic neuropathy. Erythromycin, a motilin receptor agonist, causes gall bladder contraction in both normal subjects and patients with gall stones with impaired gall bladder emptying. The effect of erythromycin on gall bladder motility in seven patients with diabetes with an autonomic neuropathy, six patients with diabetes without autonomic neuropathy, and 17 normal subjects was studied using ultrasound. There was no significant difference in gall bladder fasting volume between the three groups, but the patients with diabetes with autonomic neuropathy had impaired postprandial gall bladder emptying compared with normal subjects (percentage emptied (SEM) 40 (10.3)% v 64 (2.8)%, p < 0.01) and those with autonomic neuropathy (48 (7.7)%, NS). Erythromycin produced a dramatic reduction in gall bladder fasting volume in patients with diabetes with an autonomic neuropathy, compared with either normal subjects or patients with diabetes without autonomic neuropathy (percentage reduction 62 (4.6)% in patients with autonomic neuropathy, v 37 (17.6)% in those without autonomic neuropathy, and 26 (7.3)% in the normal subjects, (p < 0.02) and returned gall bladder emptying to normal in all patients with impaired emptying. The pronounced effect of erythromycin in diabetic autonomic neuropathy suggests denervation supersensitivity and that the action of erythromycin on the gall bladder is neurally modulated.
AIMS: To evaluate the Questor automated bacteriuria and pyuria screening system; to compare its performance with that of a reference method; and to assess its usefulness in a routine clinical laboratory. METHODS: The Questor urine screening system was compared with a comprehensive regimen to detect urinary tract infection, using pour-plate viable counts to determine the numbers of bacteria present in urine samples, a wide range of other cultural methods, microscopic findings and clinical information. RESULTS: The optimal performance in detecting significant growths was a sensitivity of 93%, a specificity of 74%, a positive predictive value of 43% and a negative predictive value of 98%. The list price per test is 0.17 pounds and the capital cost of the system is 39,950 pounds. Questor can test 50 samples an hour and can be operated by one member of the laboratory staff, who is not required to make interpretative judgments--for example, a medical laboratory assistant. CONCLUSIONS: The sensitivity and specificity of the Questor was better than that obtained from other screening systems using the same protocol. The system was easy to use and is a useful addition to the methods available for screening for bacteriuria.
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To study the risk factors for septic encephalopathy, we reviewed a consecutive series of 84 patients with septic syndrome and multiple-organ failure. Septic encephalopathy developed in 14 of these patients. Univariate analysis revealed that severe hypotension was significantly associated with the development of septic encephalopathy. In stepwise multiple logistic regression analysis, no other variable made a significant contribution in the presence of severe cardiovascular failure. Septic encephalopathy may be related to ischemic damage rather than to metabolic causes.
The cytochrome P-450 3A family is involved in the metabolism of several drugs, including nifedipine, cyclosporine, quinidine and erythromycin. The purpose of this study was to develop a reliable method to obtain a relative quantification of cytochrome P-450 3A apoproteins in rat liver specimens by immunocytochemistry and to correlate such quantification to erythromycin N-demethylase activity, a biochemical pathway sustained by that enzymatic system. Thirty-six male Wistar rats were treated with an injection of either saline or dexamethasone phosphate (10, 30 or 50 mg/kg), a potent inducer of cytochrome P-450 3A. Specimens taken from the same lobe were processed for immunocytochemistry and determination of erythromycin N-demethylase activity. Paraffin sections were treated with a polyclonal antiserum directed against cytochrome P-450 3A. The density of cytochrome P-450 3A immunostaining measured by an automatic image analyzer increased with the dose of dexamethasone pretreatment, and with the erythromycin N-demethylase activity, both parameters being closely correlated. Our data indicate that in rats, when cytochrome P-450 3A is concerned, there is a close correlation between the results of immunoquantitation and biochemical activity. This suggests that such a method of investigation might be used on small paraffin-embedded liver specimens obtained by needle biopsy.