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1.
Acta Paediatr ; 102(3): e120-5, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23205841

ABSTRACT

AIM: Little is known about bone and joint infections (BJIs) in children, despite the risk of growth disturbance. This study examined BJIs epidemiology using the French National Hospital Discharge Database (HD). METHODS: Any child <15 years hospitalized with an HD diagnosis of BJI, alone or in combination with sepsis or orthopaedic procedure, was included. The majority of BJIs (96%) were haematogenic infections. We conducted descriptive analyses to evaluate epidemiological and economic outcomes of paediatric haematogenic BJIs. RESULTS: There were 2592 paediatric patients with 2911 BJI hospitalizations and an overall incidence of 22 per 100 000. BJIs occurred more frequently in boys than girls (24 vs 19 per 100 000) and in toddlers. Septic arthritis (52%) and osteomyelitis (44%) were the most frequent infections, 16.6% of patients had a micro-organism coded (61% were Staphylococci) and 13% of had comorbidities. The mean hospital stay was 8.6 days, costing approximately €5200 per BJI stay. CONCLUSION: This national study of paediatric BJIs in France showed a higher prevalence in toddlers and boys and demonstrated that the HD database can be used to study BJIs. However, the number of BJI cases was maybe overestimated by coding reactive arthritis as septic arthritis in the absence of bacterial evidence.


Subject(s)
Bone Diseases, Infectious/epidemiology , Joint Diseases/epidemiology , Joint Diseases/microbiology , Adolescent , Bone Diseases, Infectious/microbiology , Bone Diseases, Infectious/therapy , Child , Child, Preschool , Cost of Illness , Databases, Factual , Female , France/epidemiology , Hospitalization/statistics & numerical data , Humans , Incidence , Infant , Joint Diseases/therapy , Male , Retrospective Studies , Risk Factors
2.
J Hosp Infect ; 82(1): 40-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22738613

ABSTRACT

BACKGROUND: Adult bone and joint infections (BJIs) often require repeated and prolonged hospitalizations and are considered as a serious public health issue. AIM: To describe the epidemiology and economical outcomes of BJI in France. METHODS: BJI hospitalizations with selected demographic, medical, and economic parameters from the French national hospital database for the year 2008 were identified. Overall patient characteristics and hospital stays for BJI underwent univariate analysis. Risk factors for device-associated infections were identified using multiple logistic regression modelling. FINDINGS: Of all hospitalizations in France, 0.2% were BJI-related, representing 54.6 cases per 100,000 population, with a higher prevalence in males (sex ratio: 1.54). BJIs were more often native (68%) than device-associated (32%). The mean age was 63.1 years. Only 39% of hospital discharges had microbiological information coded; Staphylococcus spp. were isolated in 66% of those cases. Obesity, Staphylococcus spp., male sex and age >64 years were important risk factors for device-associated infections, whereas diabetes and ulcer sores were significantly associated with native infections. The case fatality was 4.6%. Intensive care unit stays were needed in 6% of cases. Readmissions to hospital occurred in 19% of cases, with significantly longer stays for device-associated infections than for native BJIs (18.9 vs 16.8 days). The cost of BJIs was €259 million, or about €7,000 per hospitalization in 2008. CONCLUSIONS: This is the largest BJI study to date. The high economic burden of BJIs was mostly associated with more frequent and prolonged hospitalizations, high morbidity, and complexity of care.


Subject(s)
Hospitalization/statistics & numerical data , Osteoarthritis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , France/epidemiology , Health Care Costs/statistics & numerical data , Hospitalization/economics , Humans , Male , Middle Aged , Osteoarthritis/drug therapy , Osteoarthritis/economics , Osteoarthritis/mortality , Survival Analysis , Treatment Outcome , Young Adult
3.
Clin Infect Dis ; 39(10): 1454-9, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15546081

ABSTRACT

BACKGROUND: In 68% of foodborne disease outbreaks, no etiologic pathogen is identified. In two-thirds of outbreaks with no identified etiology, no stool specimens are submitted for testing. METHODS: From April 2001 to March 2003, we pilot-tested use of prepackaged, self-contained stool specimen collection kits in 3 states, delivered to and from patients by courier or mail, to improve rates of specimen collection in the outbreak setting. Specimens were tested for bacterial and viral pathogens at health department laboratories, and results were correlated with epidemiological investigation data. RESULTS: Specimens were returned by > or =1 person in 52 (96%) of 54 outbreaks in which kits were deployed; in total, 263 (76%) of 347 persons who received kits returned specimens. Resolution of symptoms was the most commonly cited reason for nonsubmission of kits. An etiology was confirmed in 37 (71%) of 52 outbreaks with specimens returned; 28 (76%) were attributable to norovirus, and 9 (24%) were attributed to bacterial pathogens. Stool kits were well received and cost an average of approximately 43 dollars per specimen returned. CONCLUSIONS: In two-thirds of foodborne disease outbreaks in which delivered stool collection kits were successfully deployed, an etiologic organism was identified. Delivery of kits to and from patients to improve rates of stool collection in outbreaks in which specimens might otherwise not be submitted could substantially reduce the number of outbreaks with an unknown etiology.


Subject(s)
Disease Outbreaks , Feces/microbiology , Food Microbiology , Infections/diagnosis , Infections/microbiology , Reagent Kits, Diagnostic , Humans , Pilot Projects , Specimen Handling
4.
J Card Fail ; 7(3): 221-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11561221

ABSTRACT

BACKGROUND: The importance of congestive heart failure (CHF) in patients with preserved left ventricular systolic function is increasingly recognized, but most studies have been conducted at a single, usually academic, medical center. The aim of this study was to determine the prognosis, readmission rate, and effect of ACE inhibitor therapy in a Medicare cohort with CHF and preserved systolic function. METHODS AND RESULTS: We examined a statewide, random sample of 1,720 California Medicare patients hospitalized with an ICD-9 diagnosis of CHF confirmed by a decreased left ventricular ejection fraction (EF) or chest radiograph from July 1993 to June 1994 and January 1996 to June 1996. Among the 782 patients with confirmed CHF and an in-hospital left ventricular EF measurement, 45% had reduced systolic function (ReSF) (EF < 40%) and 55% had preserved systolic function (PrSF) (EF > 40%). The PrSF group had a lower 1-year mortality rate but similar hospital readmission rates for both CHF and all causes. In patients with ReSF, ACE inhibitor treatment was associated with a lower mortality rate (P =.04) and a trend toward a lower CHF readmission rate (P =.13). In contrast, ACE inhibition therapy was associated with neither a lower rate of mortality nor CHF readmission in PrSF patients (P =.61 and.12, respectively). In multivariate analyses treatment with ACE inhibitors in PrSF patients was not associated with either a reduction in mortality (hazard ratio, 1.15; 95% CI, 0.79-1.67) or CHF readmission (hazard ratio, 1.21; 95% CI, 0.92-1.58). CONCLUSIONS: CHF with PrSF seems to be associated with high mortality and morbidity rates, but ACE inhibitors may not produce comparable benefit in this group as in patients with ReSF.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heart Failure/physiopathology , Ventricular Function, Left , Aged , California/epidemiology , Cohort Studies , Female , Heart Failure/drug therapy , Heart Failure/epidemiology , Hospitals, Community , Humans , Male , Medicare , Multivariate Analysis , Patient Readmission/statistics & numerical data , Proportional Hazards Models , Retrospective Studies , Sampling Studies , Systole/physiology
5.
N Engl J Med ; 343(24): 1758-64, 2000 Dec 14.
Article in English | MEDLINE | ID: mdl-11114314

ABSTRACT

BACKGROUND: Recent studies have shown that symptomatic venous thromboembolism after total hip arthroplasty most commonly develops after the patient is discharged from the hospital. Risk factors associated with these symptomatic thromboembolic events are not well defined. METHODS: Using administrative data from the California Medicare records for 1993 through 1996, we identified 297 patients 65 years of age or older who were rehospitalized for thromboembolism within three months after total hip arthroplasty. We compared demographic, surgical, and medical variables potentially associated with the development of thromboembolism in these patients and 592 unmatched controls. RESULTS: A total of 89.6 percent of patients with thromboembolism and 93.8 percent of control patients were treated with pneumatic compression, warfarin, enoxaparin, or unfractionated heparin, alone or in combination. In addition, 22.2 percent and 29.7 percent, respectively, received warfarin after discharge. A body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or greater was associated with rehospitalization for thromboembolism, with an odds ratio of 2.5 (95 percent confidence interval, 1.8 to 3.4). In a multivariate model, the only prophylactic regimens associated with a reduced risk of thromboembolism were pneumatic compression in patients with body-mass indexes of less than 25 (odds ratio, 0.3; 95 percent confidence interval, 0.2 to 0.6) and warfarin treatment after discharge (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 1.0). CONCLUSIONS: In patients who underwent total hip arthroplasty, a body-mass index of 25 or greater was associated with subsequent hospitalization for thromboembolism. Pneumatic compression in patients with a body-mass index of less than 25 and prophylaxis with warfarin after discharge were independently protective against thromboembolism.


Subject(s)
Arthroplasty, Replacement, Hip , Hospitalization/statistics & numerical data , Postoperative Complications/epidemiology , Thromboembolism/epidemiology , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Body Mass Index , Case-Control Studies , Female , Gravity Suits , Heparin/therapeutic use , Humans , Male , Multivariate Analysis , Postoperative Complications/prevention & control , Postoperative Complications/surgery , Risk Factors , Thromboembolism/etiology , Thromboembolism/prevention & control , Thromboembolism/surgery , Warfarin/therapeutic use
6.
Arch Dis Child ; 83(5): 439-42, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11040156

ABSTRACT

Progressive myelopathy is a rare complication of chronic hepatic disease which has never been reported in the paediatric age group. We describe the 11 year course of an adolescent male with hepatic myelopathy caused by cryptogenic micronodular cirrhosis. His condition has been associated with persistent polycythaemia and extraordinary increases of whole blood manganese, with magnetic resonance imaging evidence of manganese deposition within the basal ganglia and other regions of the brain. The patient has developed neither liver failure nor parkinsonism. The pathophysiological bases of this multiorgan system disorder are described.


Subject(s)
Liver Cirrhosis/complications , Manganese/blood , Paraparesis, Spastic/etiology , Polycythemia/etiology , Adolescent , Chronic Disease , Follow-Up Studies , Humans , Liver Cirrhosis/blood , Male
7.
J Neurophysiol ; 84(3): 1369-84, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10980010

ABSTRACT

The aim of this study was to determine whether neuronal activity in the macaque supplementary eye field (SEF) is influenced by the rule used for saccadic target selection. Two monkeys were trained to perform a variant of the memory-guided saccade task in which any of four visible dots (rightward, upward, leftward, and downward) could be the target. On each trial, the cue identifying the target was either a spot flashed in superimposition on the target (spatial condition) or a foveally presented digitized image associated with the target (pattern condition). Trials conforming to the two conditions were interleaved randomly. On recording from 439 SEF neurons, we found that two aspects of neuronal activity were influenced by the nature of the cue. 1) Activity reflecting the direction of the impending response developed more rapidly following spatial than following pattern cues. 2) Activity throughout the delay period tended to be higher following pattern than following spatial cues. We consider these findings in relation to the possible involvement of the SEF in processes underlying attention, arousal, response-selection, and motor preparation.


Subject(s)
Neurons/physiology , Pattern Recognition, Visual/physiology , Saccades/physiology , Space Perception/physiology , Visual Fields/physiology , Analysis of Variance , Animals , Behavior, Animal/physiology , Brain Mapping , Cues , Electrodes, Implanted , Frontal Lobe/cytology , Frontal Lobe/physiology , Macaca mulatta/physiology , Male , Photic Stimulation , Reaction Time/physiology , Regression Analysis
8.
Annu Rev Nutr ; 19: 197-216, 1999.
Article in English | MEDLINE | ID: mdl-10448522

ABSTRACT

Vegetable oils are a major component of human diets, comprising as much as 25% of average caloric intake. Until recently, it was not possible to exert significant control over the chemical composition of vegetable oils derived from different plants. However, the advent of genetic engineering has provided novel opportunities to tailor the composition of plant-derived lipids so that they are optimized with respect to food functionality and human dietary needs. In order to exploit this new capability, it is essential for food scientists and nutritionists to define the lipid compositions that would be most desirable for various purposes.


Subject(s)
Genes, Plant , Genetic Engineering , Lipids/genetics , Plants, Edible/chemistry , Plants, Edible/genetics , Dietary Fats, Unsaturated , Fatty Acids/analysis , Fatty Acids/genetics , Humans , Nutritive Value , Oxidation-Reduction
9.
Arch Intern Med ; 159(13): 1429-36, 1999 Jul 12.
Article in English | MEDLINE | ID: mdl-10399894

ABSTRACT

BACKGROUND: Studies to determine whether care by cardiologists improves the survival of patients with acute myocardial infarction (MI) have produced conflicting results, and it is not known what accounts for differences in patient outcome by physician specialty. OBJECTIVES: To evaluate whether cardiologists provide more recommended therapies to elderly patients with acute MI and, if so, to determine whether variations in processes of care account for differences in patient outcome. DESIGN: Retrospective cohort study using medical chart data and administrative data files. SETTING: All nonfederal acute care hospitals in California. PATIENTS: A cohort of 7663 Medicare beneficiaries 65 years and older directly admitted to the hospital with a confirmed acute MI from April 1994 to July 1995 with complete data regarding potential contraindications to recommended therapies. MAIN OUTCOME MEASURES: Percentage of "good" and "ideal" candidates for a given acute MI therapy who actually received that therapy, percentage who received exercise stress testing or coronary angiography, percentage who underwent revascularization, and 1-year mortality, stratified by specialty of the attending physician. RESULTS: During hospitalization, good candidates for aspirin were more likely to receive aspirin if they were treated by cardiologists (87%) than by medical subspecialists (73%; P<.001), general internists (84%; P = .003), or family practitioners (81%; P<.001). Cardiologists were also more likely to treat good candidates with thrombolytic therapy (51%) than were medical subspecialists (29%; P<.001), general internists (40%; P<.001), or family practitioners (27%; P<.001). Patients of cardiologists were 2- to 4-fold more likely to undergo a revascularization procedure. Despite these differences in utilization, we found similar 30-day mortality rates across physician specialties. However, 1-year mortality rates were greater for patients treated by medical subspecialists (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.3), general internists (OR, 1.4; 95% CI, 1.3-1.6), and family practitioners (OR, 1.7; 95% CI, 1.4-1.9) than for those treated by cardiologists. Adjusting for differences in patient and hospital characteristics markedly reduced the ORs for those treated by medical subspecialists (OR, 1.2; 95% CI, 0.9-1.4), general internists (OR, 1.1; 95% CI, 1.0-1.3), and family practitioners (OR, 1.3; 95% CI, 1.1-1.6), whereas further adjustment for medication use and revascularization procedures had little effect. CONCLUSIONS: Differences in the use of recommended therapies by physician specialty are generally small and do not explain differences in patient outcome. In comparison, differences among patients treated by physicians of various specialties (case mix) have a large impact on patient outcome and may account for the residual survival advantage of patients treated by cardiologists. With the exception of the in-hospital use of aspirin, recommended MI therapies are markedly underused, regardless of the specialty of the physician.


Subject(s)
Cardiology Service, Hospital/standards , Diagnosis-Related Groups , Medicine/standards , Myocardial Infarction/therapy , Quality of Health Care , Specialization , Aged , Aged, 80 and over , California/epidemiology , Drug Utilization Review , Female , Humans , Male , Medical Audit , Medical Records , Medicare Part A , Medicine/statistics & numerical data , Myocardial Infarction/mortality , Practice Patterns, Physicians' , Retrospective Studies , Treatment Outcome , United States
10.
J Neurophysiol ; 81(5): 2340-6, 1999 May.
Article in English | MEDLINE | ID: mdl-10322070

ABSTRACT

Macaque SEF neurons encode object-centered directions of eye movements regardless of the visual attributes of instructional cues. Neurons in the supplementary eye field (SEF) of the macaque monkey exhibit object-centered direction selectivity in the context of a task in which a spot flashed on the right or left end of a sample bar instructs a monkey to make an eye movement to the right or left end of a target bar. To determine whether SEF neurons are selective for the location of the cue, as defined relative to the sample bar, or, alternatively, for the location of the target, as defined relative to the target bar, we carried out recording while monkeys performed a new task. In this task, the color of a cue-spot instructed the monkey to which end of the target bar an eye movement should be made (blue for the left end and yellow for the right end). Object-centered direction selectivity persisted under this condition, indicating that neurons are selective for the location of the target relative to the target bar. However, object-centered signals developed at a longer latency (by approximately 200 ms) when the instruction was conveyed by color than when it was conveyed by the location of a spot on a sample bar.


Subject(s)
Eye Movements/physiology , Neurons/physiology , Orientation/physiology , Space Perception/physiology , Visual Fields/physiology , Animals , Cues , Macaca mulatta , Male , Vision, Ocular/physiology
11.
Am J Ind Med ; 33(2): 164-74, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9438049

ABSTRACT

The aerial application of malathion over large urban populations in Southern California during the early 1990s raised concerns about adverse health effects, including the potential to cause genetic damage. Workers in the Mediterranean fruit fly eradication program, which involved application of malathion as ground treatment, were studied to examine micronucleus formation and mutation frequencies assessed by the glycophorin A (GPA) assay. In the 1992 pilot project the mean micronuclei level appeared higher in lymphocytes of exposed workers (n = 13) compared to controls (n = 4) (20.1 +/- 7.1 vs 14.3 +/- 7.2 respectively, P = 0.09). During the 1993 season, neither of the cohorts examined showed a higher level of micronuclei in workers exposed to malathion compared to unexposed, nor did the pooled total (n = 53; means = 17.8 +/- 7.2 vs 18.5 +/- 6.3, respectively), even after adjustment by multiple regression. The GPA variant frequency was not associated with malathion exposure in any of the cohorts. These results suggest that any potential risk of genotoxic damage from exposure to malathion is relatively low, but other assays may be more sensitive, and the sample size was small.


Subject(s)
Agriculture , Malathion , Mutagenicity Tests , Occupational Exposure , Adult , Cohort Studies , Female , Glycophorins/analysis , Humans , Male , Micronuclei, Chromosome-Defective
12.
Brain Res Cogn Brain Res ; 5(1-2): 147-56, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9049081

ABSTRACT

Object-centered spatial awareness--awareness of locations of parts relative to a an object--plays an important role in perception and action. Indirect evidence from psychological and neuropsychological studies has indicated that this form of spatial awareness may be served by a cortical system in which neurons encode specific object-centered locations. We set out to obtain direct evidence for object-centered spatial selectivity by recording from single neurons in the frontal cortex of monkeys trained to make eye movements to particular locations on reference objects. We found that neurons in the supplementary eye field (SEF) fire differentially as a function of the location on an object to which an eye movement is directed.


Subject(s)
Attention/physiology , Frontal Lobe/physiology , Psychomotor Performance/physiology , Space Perception/physiology , Visual Fields/physiology , Animals , Functional Laterality/physiology , Macaca , Neurons/physiology
13.
Curr Opin Neurobiol ; 6(2): 165-70, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8725957

ABSTRACT

Object-centered spatial awareness underlies many important cognitive functions, including reading, which requires registering the locations of letters relative to a word, and pattern recognition, which requires registering the locations of features relative to a whole pattern. Recent studies have elucidated the nature of the brain mechanisms underlying this form of spatial awareness by showing the attention tends to focus on objects rather than on regions of space: by demonstrating that each hemisphere contributes selectively to awareness of the opposite half of object space, and by revealing that neurons in some cortical areas are selective for particular locations in object space. These results are concordant with the general idea that imagining or attending to an object is accompanied by projecting its image onto a neural map of object-centered space. An important aim for future studies will be to test and extend this 'object map' hypothesis.


Subject(s)
Brain/physiology , Space Perception/physiology , Attention/physiology , Brain/cytology , Humans , Neurons/physiology , Neuropsychology/methods
14.
Science ; 269(5226): 985-8, 1995 Aug 18.
Article in English | MEDLINE | ID: mdl-7638625

ABSTRACT

Object-centered spatial awareness--awareness of the location, relative to an object, of its parts--plays an important role in many aspects of perception, imagination, and action. One possible basis for this capability is the existence in the brain of neurons with sensory receptive fields or motor action fields that are defined relative to an object-centered frame. In experiments described here, neuronal activity was monitored in the supplementary eye field of macaque monkeys making eye movements to the right or left end of a horizontal bar. Neurons were found to fire differentially as a function of the end of the bar to which an eye movement was made. This is direct evidence for the existence of neurons sensitive to the object-centered direction of movements.


Subject(s)
Eye Movements/physiology , Frontal Lobe/physiology , Neurons/physiology , Visual Perception , Animals , Brain Mapping , Macaca , Male , Photic Stimulation
15.
J Cell Biol ; 129(4): 1127-41, 1995 May.
Article in English | MEDLINE | ID: mdl-7744961

ABSTRACT

Members of the integrin family of cell surface receptors have been shown to mediate a diverse range of cellular functions that require cell-cell or cell-extracellular matrix interactions. We have initiated the characterization of integrin receptors from the nematode Caenorhabditis elegans, an organism in which genetics can be used to study integrin function with single cell resolution. Here we report the cloning of an integrin beta subunit from C. elegans which is shown to rescue the embryonic lethal mutation pat-3(rh54) and is thus named beta pat-3. Analysis of the deduced amino acid sequence revealed that beta pat-3 is more similar to Drosophila integrin beta PS and to vertebrate integrin beta 1 than to other integrin beta subunits. Regions of highest homology are in the RGD-binding region and in the cytoplasmic domain. In addition, the 56 cysteines present in the majority of integrin beta subunits are conserved. A major transcript of approximately 3 kilo-base pairs was detected by RNA blot analysis. Immunoblot analysis using a polyclonal antiserum against the cytoplasmic domain showed that beta pat-3 migrates in SDS-PAGE with apparent M(r) of 109 k and 120 k under nonreducing and reducing conditions, respectively. At least nine protein bands with relative molecular weights in the range observed for known integrin alpha subunits coprecipitate with beta pat-3, and at least three of these bands migrate in SDS-PAGE with increased mobility when reduced. This behavior has been observed for a majority of integrin alpha subunits. Immunoprecipitations of beta pat-3 from developmentally staged populations of C. elegans showed that the expression of several of these bands changes during development. The monoclonal antibody MH25, which has been postulated to recognize the transmembrane component of the muscle dense body structure a (Francis, G. R., and R. H. Waterston. 1985. Muscle organization in Caenorhabditis elegans: localization of proteins implicated in thin filament attachment and I-band organization. J. Cell Biol. 101:1532-1549), was shown to recognize beta pat-3. Finally, immunocytochemical analysis revealed that beta pat-3 is expressed in the embryo and in many cell types postembryonically, including muscle, somatic gonad, and coelomocytes, suggesting multiple roles for integrin heterodimers containing this beta subunit in the developing animal.


Subject(s)
Caenorhabditis elegans/genetics , Genes, Helminth/genetics , Amino Acid Sequence , Animals , Antibodies, Helminth , Antibodies, Monoclonal , Antibody Specificity , Base Sequence , Caenorhabditis elegans/embryology , Caenorhabditis elegans/growth & development , Gene Library , Genome , Immunohistochemistry , Molecular Sequence Data , Precipitin Tests , Protein Binding , Protein Conformation , Sequence Analysis , Sequence Homology, Amino Acid , Tissue Distribution
16.
Eur J Clin Nutr ; 43(11): 749-61, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2627924

ABSTRACT

This study was designed to investigate the effects of aging and food intake on the serum beta-carotene (BC) response curve in humans. Ten elderly (71 +/- 4 years) and 17 young (28 +/- 7 years) healthy females were given 15 mg BC with a semi-solid test meal devoid of BC and vitamin A. All the elderly and 10 young subjects (control A) received a test meal of 500 kcal while the remaining 7 young subjects (control B) were given 700 kcal. Subsequently, blood was drawn hourly for 8 h and again at 24 and 48 h. Serum carotenoids and retinoids were measured by HPLC and triglycerides (TG) and cholesterol by enzymatic methods. Small intestinal transit time was determined in the elderly and in control group A by a breath hydrogen test following ingestion of lactulose (12 g) with the test meal. The area under the absorption curve (AUC) of serum BC over the first 8 h was higher in the elderly subjects than in either control group A or B (P less than 0.001). The slopes of the BC and TG curves were significantly higher as compared to control A, but similar to control B. There was a positive correlation between the ascending slopes of the BC and TG absorption curves of all groups (P less than 0.001). The AUC of the retinyl ester serum response of the elderly group was greater than that of control A (P less than 0.001). The slope of this curve was steeper (P less than 0.01) in the elderly group as compared to control A, but was similar to control B. Intestinal transit time was similar in all groups. In young subjects, the larger test meal of control group B appeared to increase the rate of absorption of BC. These data indicate that the rate of intact BC absorption and its conversion to retinyl esters may be enhanced in old age as compared to younger subjects receiving the same amount of food. Age-related alterations of enterocytes and the intestinal lumen could account for this phenomenon.


Subject(s)
Aging/blood , Carotenoids/blood , Administration, Oral , Adult , Aged , Breath Tests , Carotenoids/administration & dosage , Cholesterol/blood , Female , Gastrointestinal Transit/physiology , Humans , Hydrogen/analysis , Intestinal Absorption/physiology , Retinoids/blood , Triglycerides/blood , beta Carotene
17.
Food Chem Toxicol ; 27(1): 31-4, 1989 Jan.
Article in English | MEDLINE | ID: mdl-2703191

ABSTRACT

Trimethylamine and dimethylamine are important precursors of N-nitrosodimethylamine, which is a potent carcinogen in a wide variety of animal species. Choline, a component of the normal human diet, is metabolized by bacteria within the intestine to form trimethylamine and dimethylamine. However, animals on a choline-free diet continue to excrete some trimethylamine and dimethylamine, suggesting that other dietary precursors of these methylamines might exist. To determine whether C-N bond cleavage by the intestinal bacteria is specific to the choline molecule, we measured monomethylamine, dimethylamine, trimethylamine and trimethylamine oxide excretion in rat urine after the administration of compounds that shared structural features with choline. Water, choline, dimethylaminoethanol, diethylaminoethanol, phosphocholine, betaine, carnitine, beta-methylcholine or dimethylaminoethyl chloride were administered by orogastric intubation, and the urine was collected for 24 hr. Administration of choline (15 mmol/kg body weight) resulted in increased urinary excretion of dimethylamine, trimethylamine and trimethylamine oxide (increases of approximately twofold, 500-fold and 50-fold, respectively). Of the administered choline, 12% was converted to trimethylamine or trimethylamine oxide and excreted in the urine within 24 hr. Phosphocholine administration resulted in similar increases in dimethylamine, trimethylamine and trimethylamine oxide excretion by rats. Modification of the ethyl-backbone or quaternary amine end of the choline molecule resulted in marked suppression of methylamine formation. Though administration of some analogues of choline (methylcholine, betaine and carnitine) resulted in the formation of small amounts of trimethylamine or trimethylamine oxide, and the administration of others (dimethylaminoethanol and dimethylaminoethyl chloride) resulted in the formation of some dimethylamine, the amounts formed were minimal compared with the amounts of trimethylamine and trimethylamine oxide formed after choline administration. Thus, of the many components of foods, only choline and its esters are likely to be significant substrates for trimethylamine and dimethylamine formation. How then can we explain the persistence of trimethylamine and dimethylamine excretion observed in choline-deficient rats? We suggest that endogenous (non-bacterial) synthesis of trimethylamine and dimethylamine occurs within some tissue of the rat.


Subject(s)
Choline/metabolism , Dimethylnitrosamine/biosynthesis , Methylamines/biosynthesis , Administration, Oral , Animals , Choline/administration & dosage , Choline/analogs & derivatives , Dimethylamines/biosynthesis , Intestinal Mucosa/metabolism , Intestines/microbiology , Male , Methylamines/urine , Rats , Rats, Inbred Strains
18.
Ann Trop Med Parasitol ; 82(3): 243-9, 1988 Jun.
Article in English | MEDLINE | ID: mdl-3266914

ABSTRACT

The effects of levamisole on the course of Leishmania enriettii infection in guinea-pigs and L. major in mice were investigated. It was demonstrated that levamisole-treated guinea-pigs either did not develop an ulcerative lesion or developed a much smaller lesion than untreated animals. Moreover, metastases which are commonly produced in approximately 50% of animals receiving 2 x 10(6) L. enriettii did not occur in levamisole-treated guinea-pigs. Leishmania enriettii infection usually causes leukopenia and eosinophilia in guinea-pigs approximately two to three weeks after infection. These haematological changes did not occur in animals receiving levamisole. The percentage of rosette T-cells which diminished in the L. enriettii infection was normalized in the group of levamisole-treated and infected guinea-pigs. The severity of Leishmania infection in mice receiving levamisole was lower in comparison to a control group of the animals.


Subject(s)
Leishmaniasis/drug therapy , Levamisole/therapeutic use , Animals , Antibodies, Protozoan/biosynthesis , B-Lymphocytes/immunology , Eosinophils , Female , Guinea Pigs , Leishmania mexicana/immunology , Leishmaniasis/blood , Leishmaniasis/immunology , Leukocyte Count , Mice , Skin Tests , T-Lymphocytes/immunology
19.
Mol Cell Biol ; 8(5): 2224-8, 1988 May.
Article in English | MEDLINE | ID: mdl-3260331

ABSTRACT

The T-cell surface glycoprotein CD4 is thought to function as a receptor for class II major histocompatibility complex molecules. Human CD4 is also the lymphoid cell receptor for human immunodeficiency virus, the causative agent of acquired immune deficiency syndrome. The observed infection of the central nervous system in acquired immune deficiency syndrome patients raises the possibility that CD4 is also present in nerve tissue and that a cell surface receptor for class II major histocompatibility complex antigens could play a role in central nervous system function. This possibility is reinforced by the detection of unique CD4-related transcripts in mouse and human brain tissue. In this study, the structure of the mouse brain CD4 transcript was determined. It is identical to the last two-thirds of the CD4 message and is capable of encoding a 217-residue protein that would consist of a truncated, 154-residue, cell surface region, together with the complete CD4 transmembrane and cytoplasmic regions. It would not include an amino-terminal hydrophobic leader peptide.


Subject(s)
Antigens, Differentiation, T-Lymphocyte/genetics , Brain Chemistry , RNA, Messenger/genetics , Amino Acid Sequence , Animals , Base Sequence , Mice , Mice, Inbred C57BL , Molecular Sequence Data
20.
Nature ; 326(6108): 85-8, 1987.
Article in English | MEDLINE | ID: mdl-3102973

ABSTRACT

The majority of human T cells express an antigen receptor consisting of a disulphide-linked heterodimer (Ti) of relative molecular mass 80,000-90,000 (Mr 80-90K) which is noncovalently associated with a set of at least three proteins of Mr 20-28K termed CD3 (Leu4, T3). Whereas both chains of Ti, an acidic alpha-chain of Mr 48-54K and a more basic beta-chain of Mr 40-44K, contain variable and constant region domains, the component peptides of CD3 are invariant. Several laboratories have more recently reported the expression of CD3 in association with a novel protein. On the surface of long-term T-cell lines and one thymocyte clone this novel structure consists of a 40K protein noncovalently linked to a 55 or 62K protein identified as the protein product of the Ti gamma-chain gene, a T-cell specific gene which like the Ti alpha- and Ti beta-chain genes undergoes rearrangement of variable (V) and joining (J) region gene segments. On the human T-cell leukaemic line PEER we have detected only a single 55K glycoprotein associated with CD3. We here demonstrate that an anti-Ti gamma-peptide antiserum reacts with the 55K CD3-associated protein on PEER. Most previously described human Ti gamma-chain complementary DNA clones encode the products of non-functional rearrangements. One of the Ti gamma cDNAs isolated from PEER, however, represents a functional rearrangement reported for the first time in a cell which expresses a Ti gamma-chain protein product on the cell surface. Interestingly, a 48-base-pair (bp) sequence in the constant (C) region domain of this functional Ti gamma-chain cDNA is triplicated in PEER and duplicated in other cDNAs isolated from PEER and other cell lines.


Subject(s)
Antigens, Surface/analysis , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes/immunology , Antigens, Differentiation, T-Lymphocyte , Base Sequence , Cell Line , DNA , Humans , Molecular Weight , Polymorphism, Genetic , Repetitive Sequences, Nucleic Acid
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