Paediatric bone and joint infections are more common in boys and toddlers: a national epidemiology study.

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.

Characterization of beta pat-3 heterodimers, a family of essential integrin receptors in C. elegans.

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.

Object-centered direction selectivity in the macaque supplementary eye field.

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.

Mouse brain CD4 transcripts encode only the COOH-terminal half of the protein.

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.

Brain representation of object-centered space.

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.

Outcome following acute myocardial infarction: are differences among physician specialties the result of quality of care or case mix?

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.

Use of stool collection kits delivered to patients can improve confirmation of etiology in foodborne disease outbreaks.

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.

Representation of object-centered space in the primate frontal lobe.

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.

Responses of human peripheral lymphocytes to soluble and insoluble antigens of Candida albicans.

Responses of peripheral lymphocytes from the blood of 20 healthy volunteers were determined in vitro by measurement of tritiated thymidine uptake in the presence of six different antigens prepared from Candida albicans. Crude antigens (disintegrated cells, culture filtrate) produced greater lymphoblast reactivity than purified preparations (cytoplasmic proteins, cell-wall mannan). Reactions to soluble mannan were uncommon but the number of subjects who responded to them increased from one to 14 when the material was rendered particulate by adsorption on to latex particles. Lymphocyte responses were also elicited by intact, heat-killed yeast cells.

Beta-carotene serum response in young and elderly females.

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.

Formation of aliphatic amine precursors of N-nitrosodimethylamine after oral administration of choline and choline analogues in the rat.

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.

Bone and joint infections in hospitalized patients in France, 2008: clinical and economic outcomes.

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.

Unusual intron in the immunoglobulin domain of the newly isolated murine CD4 (L3T4) gene.

The T-cell surface glycoprotein, CD4, is expressed predominantly on helper T cells and is thought to play a major role in cell-cell interactions. Monoclonal antibodies against CD4 have been shown to block numerous T-cell functions; moreover, recent results suggest that the CD4 molecule may be involved in transmembrane signal transduction. The human CD4 glycoprotein has also been shown to form at least part of the receptor for the AIDS virus, HIV-1. Elucidation of the functions of CD4 will be facilitated by the ability to manipulate the protein by genetic means. Because the mouse system is well suited for a variety of functional studies, we have isolated, sequenced and expressed cDNA clones encoding the murine CD4 (L3T4) glycoprotein. Comparison of the mouse and human CD4 sequences reveals striking evolutionary conservation of the cytoplasmic domain, suggesting that this region is essential for CD4 function. In addition, both the human and mouse CD4 gene contain a large intron in the coding region of the V-like domain. As no other members of the immunoglobulin gene superfamily have been shown to contain similarly placed introns, this finding may have important implications regarding the evolution of this gene family in particular and of introns in general.

Macaque SEF neurons encode object-centered directions of eye movements regardless of the visual attributes of instructional cues.

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.

Cross-agglutination reaction in Candida albicans and enteric bacilli.

Cross-reactivity between Candida albicans and representative Enterobacteriaceae was investigated by agglutination methods. It was observed that anti-Candida serum reacted to certain groups of salmonellae and shigellae. The only antiserum against the enteric bacilli that reacted with Candida was Salmonella C(1). When anti-Candida serum was adsorbed with C. albicans or S. montevideo, all the activity was removed. However, when the anti-Salmonella serum was adsorbed with the antigens, Salmonella adsorbed the whole antibody activity, whereas Candida removed only its corresponding antibody.

Genetic engineering of plant lipids.

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.

Enteric pathogens in infants and children in Shiraz, Iran: A study of their incidences and infectious drug resistance.

Gastroenteritis is a serious problem among young children in Shiraz Iran and often requires antibiotic therapy as it is commonly superimposed on other debilitating clinical conditions. Stool specimens from over four hundred cases of gastroenteritis among children up to six years of age were examined for the presence of bacterial pathogens and the pattern of drug sensitivity for each pathogenic genus was determined. The presence of infectious drug resistance factors among these isolates was also established.