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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 685 records · Page 38Linked to original sources

hobo enhancer trapping mutagenesis in Drosophila reveals an insertion specificity different from P elements.

P element enhancer trapping has become an indispensable tool in the analysis of the Drosophila melanogaster genome. However, there is great variation in the mutability of loci by these elements such that some loci are relatively refractory to insertion. We have developed the hobo transposable element for use in enhancer trapping and we describe the results of a hobo enhancer trap screen. In addition, we present evidence that a hobo enhancer trap element has a pattern of insertion into the genome that is different from the distribution of P elements in the available database. Hence, hobo insertion may facilitate access to genes resistant to P element insertion.

Animals↗

Reliability of observation variables in distinguishing infectious outcome of febrile young infants.

We prospectively evaluated 7 observation variables (level of activity, level of alertness, respiratory status/effort, peripheral perfusion, muscle tone, affect, feeding pattern) which qualify patient clinical appearance in order to determine reliability in distinguishing the infectious outcome of 233 febrile infants ages 0 to 8 weeks. Each variable was graded either 1, 3, or 5, with a higher score indicative of a greater degree of compromise. All infants received physical examination and sepsis evaluation (lumbar puncture, complete blood count/blood culture, urinalysis/urine culture). The 3 outcome groups compared were 29 cases of serious bacterial infections, (+SBI; 10 with bacterial meningitis, 12 with bacteremia, 7 with urinary tract infection), 45 cases of aseptic meningitis (AM) and 159 cases culture-negative with normal cerebrospinal fluid (CN-NCSF). The mean score for each of the 7 variables was significantly greater in the +SBI group compared with both the AM and CN-NCSF groups (P < 0.05), whereas there was no significant difference in mean score for each of the 7 variables between the AM and CN-NCSF groups. Stepwise discriminant analysis identified 3 variables that best distinguished outcome: affect; respiratory status/effort; and peripheral perfusion, which constituted the Young Infant Observation Scale. The mean total Young Infant Observation Scale score generated from assessing these 3 variables was significantly greater (P = 0.0001) in the +SBI, group (9) compared with both the AM (5) and CN-NCSF (5) groups. A total Young Infant Observation Scale score > or = 7 had a sensitivity of 76%, specificity of 75% and negative-predictive value of 96% for outcome of +SBI.

Bacterial Infections↗

Injuries sustained during flipping--a new fad activity.

This article describes a small series of injuries resulting from a new fad activity among children in Baltimore. "Flipping" involves jumping from an elevated surface and executing an aerial flip, with the intent to land upright. Because this activity takes place frequently on hard surfaces such as concrete, injuries often result. The spectrum of injuries is described and categorized, and injuries are compared with those received during similar activities, such as break dancing or skateboarding, and with playground injuries. Pediatricians and emergency physicians should be aware of the potential for injury in this activity.

Athletic Injuries↗

The impact of anger between adults on siblings' emotions and social behavior.

Peer and sibling dyads (older children = 5-7 years; younger children = 2-5 years) were presented with simulations of friendly, angry, and resolution interactions between a male adult and the mother in the context of play sessions. Expressions of positive effect increased among female siblings during the anger period and continued to be more common in the resolution period than in other groups. Prosocial behavior among male siblings greatly increased in the resolution period, with siblings generally more prosocial towards each other than peers in this period. The findings suggest that siblings may attempt to buffer each other from the stress of exposure to adults' discord.

Anger↗

Biparietal diameter and crown-rump length in fetuses with Down's syndrome: implications for antenatal serum screening for Down's syndrome.

OBJECTIVES: 1. To compare the ultrasound biparietal diameter and crown-rump length of fetuses with and without Down's syndrome in the first half of pregnancy; 2. To investigate the effect of estimation of gestational age using either measure on the detection rate of serum screening for Down's syndrome. DESIGN: Matched case-control study. Cases were singleton Down's syndrome pregnancies with a biparietal diameter or a crown-rump length recorded. Five controls were matched to each case on: medical centre; the date of the ultrasound scan examination (within two years); gestational age measured as the number of days since the first day of the last menstrual period; and the ultrasound measure used (ie the biparietal diameter (the measure of choice), or the crown-rump length otherwise). If a woman had a serum screening test for Down's syndrome, the biparietal diameter or crown-rump length measurement had to be taken prior to the screening test so that the result of the test could not influence whether a scan was performed. SETTING: Ten antenatal screening centres in seven countries in Europe and North America. SUBJECTS: Two hundred and one women with singleton Down's syndrome pregnancies and 1005 women with unaffected singleton pregnancies. RESULTS: The median biparietal diameter of fetuses with Down's syndrome was identical to that among the controls (median difference 0.0 mm, 95% confidence intervals (CI) -0.5 to 0.5 mm). The estimates of gestational age based on biparietal diameter yielded a median gestational age less than that based on the women's last menstrual period: three days less for cases and two days less for controls; small but statistically significant differences probably reflected a minor systematic difference in the conversion of a biparietal diameter to a gestational age estimate. The median crown-rump length of fetuses with Down's syndrome was also identical to that among controls (median difference 0.0 mm, 95% CI-1.5 to 2.0 mm). There was no significant difference between the median gestational age estimate based on crown-rump length and that based on the women's last menstrual period. CONCLUSION: In antenatal screening for Down's syndrome the routine use of an ultrasound biparietal diameter or crown-rump length measurement to estimate gestational age will not adversely affect the detection rate. To avoid differences in gestational age estimates using the last menstrual period and the biparietal diameter influencing screening performance, separate medians should be derived for each serum marker using the two methods of estimating gestational age. The appropriate set of medians can then be used to calculate the multiple of the median value for each woman screened depending on the method used to estimate her gestational age.

Case-Control Studies↗

Lack of effect of L-687,414 ((+)-cis-4-methyl-HA-966), an NMDA receptor antagonist acting at the glycine site, on cerebral glucose metabolism and cortical neuronal morphology.

1. N-methyl-D-aspartate (NMDA) receptor ion channel antagonists have been reported to cause pronounced increases in cerebral glucose metabolism (CMRglc) and transient reversible vacuolation within pyramidal cortical neurones. The present studies examined in rats the effects of the NMDA receptor antagonist, L-687,414 (R-(+)-cis-4-methyl-3-amino-l-hydroxypyrolid-2-one (+)-cis-4-methyl-HA-966) on regional CMRglc and cortical neuronal morphology. 2. L-687,414 was given as a steady state intravenous infusion for 4 h in a neuroprotective dose regime of 17.5 mg free base kg-1 bolus followed by 225 micrograms kg-1 min-1 (n = 8) or at the higher dose rate of 35 mg kg-1 bolus followed by 440 micrograms kg-1 min-1 (n = 10). Data were compared to a parallel series of experiments in rats given the NMDA receptor ion channel antagonist, dizocilpine for 4 h in the optimum intravenous neuroprotective dose-regime of 0.12 mg kg-1 bolus followed by 1.8 micrograms kg-1 min-1 (n = 8) or at the higher dose rate of 0.4 mg kg-1 bolus followed by 6 micrograms kg-1 min-1 (n = 4; morphology only studied). A saline-infused group of rats (n = 8) were used as controls. 3. CMRglc was studied by use of [14C]-2-deoxyglucose and autoradiography (n = 4 each group) whilst plasma drug levels were in a steady state during the final 45 min of the 4 h drug infusion. Effects on cortical neuronal morphology were assessed at the end of the 4 h infusion period using light microscopic techniques (n = 4-6 each group).4. The results showed a selective activation of limbic CMRglc by dizocilpine at optimal neuroprotective dose levels and showed that this dose was at the threshold for the neuronal vacuolation response as I of 4 rats showed morphological changes in the pyramidal neurones in the posterior cingulate and retrosplenial cortices. At the higher dose rate of dizocilpine, all 4 animals showed extensive morphological changes in these cortical neurones. In contrast, L-687,414 did not increase limbic CMRglc, nor evoke vacuolation when given in the neuroprotective dose-regime or at the higher dosage rate.5. The findings of the present study suggest that neuroprotection mediated through the NMDA receptor complex can be achieved without changes in CMRglc or cortical neuronal morphology by antagonism at the glycine modulatory site.

Animals↗

Seizure severity and the quality of life.

The efficacy of an antiepileptic drug (AED) is determined at present by the drug-elicited reduction in seizure frequency. Reduction of seizure frequency as the sole measure of efficacy does not account for treatment-induced reductions in seizure severity and positive psychological effects experienced by the patient. A clinical trial was undertaken in which seizure frequency was the primary and seizure severity and psychological well-being were the secondary measures of efficacy. Psychological assessment and seizure frequency were monitored in patients whose epilepsy was treated with lamotrigine (LTG) or placebo. The results indicate that LTG is an effective AED, causing reductions in seizure frequency and severity and improvements in mood and mastery. In addition, the study demonstrated that the use of seizure severity scales, especially the ictal subscale, may enhance the sensitivity of assessment of trials of AED treatments.

Anticonvulsants↗

Cytokines contribute to airway dysfunction in antigen-challenged guinea pigs: inhibition of airway hyperreactivity, pulmonary eosinophil accumulation, and tumor necrosis factor generation by pretreatment with an interleukin-1 receptor antagonist.

The role of pro-inflammatory cytokines in an animal model of allergic lung disease was examined by use of an interleukin-1 receptor antagonist (IL-1ra) and a specific bioassay for tumor necrosis factor (TNF). Ovalbumin-sensitized guinea pigs exhibit a marked bronchial hyperreactivity (assessed by airway responsiveness to intravenous histamine) and pulmonary eosinophil accumulation (assessed by bronchoalveolar lavage) 24 h after challenge with aerosolized antigen. Exposure of animals to an aerosol of IL-1ra (50 micrograms over 30 min) immediately before antigen challenge resulted in a marked protection against bronchial hyperreactivity and pulmonary eosinophil accumulation compared with IL-1ra vehicle-pretreated animals. Additionally, we report for the first time generation of TNF bioactivity in the bronchoalveolar lavage of antigen-challenged animals, which was significantly reduced in animals exposed to aerosolized IL-1ra before challenge. These studies point to a key role for the cytokines IL-1 and possibly TNF in the pulmonary changes observed during allergic airway disease.

Aerosols↗

Correlating changes in body temperature with infectious outcome in febrile children who receive acetaminophen.

We reviewed the body-temperature patterns of 140 children ages 2 to 24 months who had fever > or = 39.0 degrees C, received acetaminophen 10 to 15 mg/kg, and had their temperatures remeasured 60 to 90 min later. The children comprised three groups: 22 had bacterial meningitis; 59, isolated bacteremia; and 59, nonbacterial febrile illness. Percentages of patients who became afebrile (temperature < 38.0 degrees C) after receiving acetaminophen were not significantly different among the three groups. Differences in mean temperature decrease after antipyretic was given were significant within each group but not between groups. An inverse relation (P < .004) between patient age and magnitude of temperature was revealed by the following formula: degrees C of defervescence = 1.66 - (0.028 x patient age in months). Thus, highly febrile young children with and without invasive bacterial infections who receive a therapeutic dose of acetaminophen experience a significant temperature drop after 60 to 90 min but do not commonly defervesce to an afebrile state. The degree of defervescence is age-dependent and does not distinguish between infectious outcomes.

Acetaminophen↗

Efficacy of a protocol to distinguish risk of serious bacterial infection in the outpatient evaluation of febrile young infants.

A study of 534 febrile infants ages 4 to 8 weeks evaluated for sepsis assessed the efficacy of the Milwaukee Protocol (MP) for selecting patients at low risk for serious bacterial infection (SBI) who might benefit from outpatient management. Two groups were compared: 1) Infants with uncompromised presentation (UP) who met all MP criteria received ceftriaxone 50 mg/kg and were discharged, then reevaluated within 24 hours. 2) Infants with compromised presentation (CP) who did not meet MP criteria were hospitalized for antibiotic therapy pending culture results. Of 391 CP patients, 23 (5.9%) had SBI; of 143 UP patients, 1 (0.7%) had SBI (P < .02). The MP criteria had a sensitivity of 96% and a 99% negative predictive value for distinguishing SBI outcome. The only UP patient with SBI was afebrile and had a negative repeat blood culture after 24 hours, and recovered with no complications. Managing UP infants as outpatients avoided 48 to 72 hours of hospitalization, decreasing health-care costs by an estimated total of $465,170.

Bacterial Infections↗

Multiple cerebral hemorrhages in HTLV-I-associated myelopathy.

We describe a 66-year-old woman with long-standing HTLV-I-associated myelopathy who developed multiple parenchymal hemorrhages and whose angiogram suggested cerebral vasculitis. After cyclophosphamide and glucocorticoid therapy, both her acute deficits and chronic paraparesis improved. HTLV-I may be an etiologic agent in isolated angiitis of CNS.

Aged↗

Cataract incidence and analysis of lens crystallins in the water-, urea- and SDS-soluble fractions of Emory mice fed a diet restricted by 40% in calories.

Restriction of dietary calorie intake is associated with life extension and with the delay of age-related disorders. Preliminary studies demonstrated that by feeding the Emory mouse a diet restricted by 21% in calories cataract and insolubilization of protein could also be delayed. To observe the effects of calorie restriction over prolonged portions of adulthood, Emory mice were fed the control diet (C) or a diet restricted by 40% in calories (R). Feeding the R diet was associated with delayed formation or progress of cataract over virtually the entire second half of life. At 11 months of age, bilateral grade 5 cataracts were present in 17% and 2% of C and R lenses, respectively. At 22 months of age, bilateral grade 5 cataracts were present in 90% and 18% of C and R lenses, respectively. The distribution of alpha-, beta-, and gamma- crystallins in the water-soluble, urea-soluble, and SDS-soluble fractions indicates more similarities than differences between C and R lenses with a specific grade of cataract or of a given age. However, there were significant and abrupt (after grade 4 cataract) losses of particular gamma-crystallins; gamma-crystallins which were not prominent at earlier stages became the major gamma-crystallin moieties. Losses of alpha-crystallins were also noted upon cataract formation or aging in most of the fractions. Aggregates including gamma- and alpha-crystallins also accumulate faster in the C group.

Aging↗

Inhibition of endotoxin-mediated activation of endothelial cells by a perfluorocarbon emulsion.

Endothelial cell (EC) activation plays a key role in the inflammatory response by promoting the margination of leukocytes in inflamed loci. Augmented leukocyte margination to activated EC is mediated by the increased display of leukocyte adhesion molecules on EC surface membranes. The biocompatibility of synthetic oxygen-transport fluids is intimately linked to EC function, since one of the first tissues encountered by such fluids is the vascular endothelium. We investigated the effect of one such agent, a phospholipid-based perfluorocarbon emulsion containing 90% w/v perfluorooctyl bromide (perflubron, PFOB) on EC activation. Human umbilical vein EC (HUVEC) were activated by 5 U/ml interleukin-1 (IL-1), 20 U/ml tumor necrosis factor (TNF), or 50 ng/ml E coli endotoxin (LPS) in the presence or absence of up to 20%, w/v perflubron. HUVEC activation was monitored by the extent of up-regulation of expression of intercellular adhesion molecule-1 (ICAM) and endothelial-leukocyte adhesion molecule-1 (ELAM). Exposure of HUVEC to perflubron did not alter the upregulation of ICAM or ELAM in response to IL-1 or TNF (n = 20). However, at 10% perflubron ICAM upregulation in response to LPS was inhibited by 95 +/- 6% (n = 9; p < .05). ELAM expression was similarly affected. The concentration of perflubron required to diminish LPS-induced up-regulation by 50% was 6.0 +/- 0.6% (n = 3). The inhibitory effect of 10% perflubron was overcome by > 1 microgram/ml LPS (n = 3) and the inhibitory effect was attenuated by adding perflubron to the cultures after LPS. In agreement with the above, additional experiments showed that incubation of LPS with perflubron prevented LPS-induced stimulation of TNF synthesis by a murine macrophage (RAW) cell line (n = 3). We conclude: 1) perflubron neither activates HUVEC nor interferes with HUVEC activation by IL-1 or TNF, 2) perflubron prevented HUVEC activation by LPS in a dose and time-dependent manner, 3) perflubron prevented LPS-induced activation of more than one cell line. Taken together, the data suggest that perflubron may bind and sequester limited concentrations of LPS. Whether this property of perflubron also occurs upon in vivo infusion and whether it might be clinically useful in preventing some of the adverse effects of endotoxemia are unknown.

Cell Adhesion Molecules↗

Gait analysis of dysvascular below-knee and contralateral through-knee bilateral amputees: a preliminary report.

Four elderly peripheral vascular insufficiency below-knee amputees, average age 58, underwent contralateral through-knee amputation for gangrene. All four became household ambulators with end-weight bearing designed prosthetic sockets and four-bar linkage knees. Gait analysis was performed with two AMTI (Newton, Mass) Biomechanics Force Platforms and a Watsmart Motion Monitoring System (Waterloo, Ontario). All four were observed to apparently "lock" the four-bar linkage prosthetic knee into extension during midstance and double limb support phases of gait. All subjectively felt that their through-knee limb was their more stable limb. Weight-bearing occurred during 63% of the gait cycle on the below-knee limb, 54% on the through-knee limb, and 17% in double limb support. Walking propulsion, as measured by forefoot impulse, was similar in the two limbs. The first peak of vertical force, corresponding to the elevation of the center of body weight as it passes over the weight-bearing limb, averaged 98% of body weight on the through-knee limb and only 93% on the below-knee limb. The second peak, corresponding to the kinetic energy of the falling trunk and muscle function providing linear acceleration of the center of body weight during propulsion, averaged 96% of body weight on the through-knee limb, and only 73% on the below-knee limb. Progression of the center of pressure, a qualitative measure of limb stability, was more orderly in the through-knee limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Achieving empowerment through information.

Despite the problems we encountered, which are not uncommon with the development and implementation of any data system, we are confident that our success in achieving our goals is due to the following: establishing a reliable information database connecting several related departments; interfacing with registration and billing systems to avoid duplication of data and chance for error; appointing a qualified Systems Manager devoted to the project; developing superusers to include intensive training in the operating system (UNIX), parameters of the information system, and the report writer. We achieved what we set out to accomplish: the development of a reliable database and reports on which to base a variety of hospital decisions; improved hospital utilization; reliable clinical data for reimbursement, quality management, and credentialing; enhanced communication and collaboration among departments; and an increased profile of the departments and staff. Data quality specialists, Utilization Management and Quality Management coordinators, and the Medical Staff Credentialing Supervisor and their managers are relied upon by physicians and administrators to provide timely information. The staff are recognized for their knowledge and expertise in their department-specific information. The most significant reward is the potential for innovation. Users are no longer restricted to narrow information corridors. UNIX programming encourages creativity without demanding a degree in computer science. The capability to reach and use diverse hospital database information is no longer a dream.

Academic Medical Centers↗

Prostate cancer: perceptions of African-American males.

The purpose of this study was to determine black adult males' knowledge and perceptions of prostate cancer by using the Health Belief Model. The subjects were obtained by randomly approaching males in churches, housing projects, inner-city health clinics, and inner-city shopping centers in seven major Ohio cities. A total of 290 black males responded to the survey (58% usable response rate). The mean age of respondents was 60 years (standard deviation = 13.8). Subjects often did not identify trouble urinating, pain urinating, or blood in the urine as possible signs of prostate cancer. Less than half of the subjects knew at what age one should start to have prostate examinations. Forty percent did not believe they were more likely than most men to develop prostate cancer. Almost 60% did not know black men were more likely than white men to develop prostate cancer, whereas 45% thought that if they had prostate cancer it would kill them, and another 28% were not certain. The vast majority of respondents did not perceive any barriers to having their prostate checked, yet 19% identified cost of the examination as a potential barrier. Approximately 10% to 20% of the respondents were unsure of or did not agree with the benefits of a prostate examination. Analysis of the effects of age, education level, and income levels on the Health Belief Model variables found level of education had the most significant effect followed by level of income.

Adult↗