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Biomedical subjects

S A Baker

Publications and source records attributed to S A Baker.

At least 19 recordsLinked to original sources

Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria.

Pacemaker cells, known as interstitial cells of Cajal (ICC), generate electrical rhythmicity in the gastrointestinal tract. Pacemaker currents in ICC result from the activation of a voltage-independent, non-selective cation conductance, but the timing mechanism responsible for periodic activation of the pacemaker current is unknown. Previous studies suggest that pacemaking in ICC is dependent upon metabolic activity 1y1yand1 Ca2+ release from intracellular stores. We tested the hypothesis that mitochondrial Ca2+ handling may underlie the dependence of gastrointestinal pacemaking on oxidative metabolism. Pacemaker currents occurred spontaneously in cultured ICC and were associated with mitochondrial Ca2+ transients. Inhibition of the electrochemical gradient across the inner mitochondrial membrane blocked Ca2+ uptake and pacemaker currents in cultured ICC and blocked slow wave activity in intact gastrointestinal muscles from mouse, dog and guinea-pig. Pacemaker currents and rhythmic mitochondrial Ca2+ uptake in ICC were also blocked by inhibitors of IP3-dependent release of Ca2+ from the endoplasmic reticulum and by inhibitors of endoplasmic reticulum Ca2+ reuptake. Our data suggest that integrated Ca2+ handling by endoplasmic reticulum and mitochondria is a prerequisite of electrical pacemaking in the gastrointestinal tract.

Animals↗

Adherence to treatment in children with epilepsy: who follows "doctor's orders"?

PURPOSE: The goal of the present study was to examine sociocultural, medical, family environment, and individual cognitive factors that predict adherence to treatment in children with epilepsy. METHODS: The study subjects (4-13 years old) were enrolled in a longitudinal seizure study at the first visit to the seizure clinic, attended at least 6 months, and had at least two appointments. Baseline predictors, which were obtained by interview, chart review, and psychometric testing, included sociocultural and family environment, seizure and previous treatment history, child behavior, cognitive functioning (IQ), and family stress. Four latent factors tapping these indicators of risk (acculturative risk, seizure severity, behavior problems, family environment) and two measured variables (IQ and life events) were hypothesized. Outcomes were visit adherence (proportion of scheduled appointments kept, plus proportion without unscheduled contacts), medication report (proportion of visits at which parent report of medication agreed with records), and medication levels (proportion of serum anticonvulsant levels within expected range for dosage). Two-step analytic procedure included confirmatory factor analysis to validate the hypothetical structure of the baseline risk indicators, followed by structural equation modeling to examine longitudinal relations between baseline risk and subsequent adherence outcomes. RESULTS: Significant prospective relationships included acculturative risk associated positively with visit adherence and medication levels, behavior problems associated negatively with visit adherence and medication levels, family environment associated negatively with medication report, life events associated positively with medication levels and visit adherence, and cognitive functioning (IQ) associated positively with medication levels. Seizure severity was not associated significantly with any adherence outcome. There also were no significant within-time associations between adherence outcomes. CONCLUSIONS: Contrary to clinical expectations, families at higher acculturative risk and with higher life events reported greater adherence. Seizure severity did not influence adherence. The three adherence measures were statistically independent of each other.

Acculturation↗

An investigation of the effect of 2 sedation regimens on patient mood state following upper extremity surgery using local anesthesia.

Sedation techniques for patients undergoing minor outpatient surgery frequently include a variety of intravenous agents. The present study was designed to look for differential effects of 2 different sedation regimens on perioperative mood states. Twenty-two patients undergoing upper extremity surgery using local anesthesia were randomized to receive either propofol or midazolam intravenously for intraoperative sedation. Subjects were asked to complete a Profile of Mood States survey before and after surgery. The results of this survey were examined for differences in mood between the 2 groups that may be attributable to differences in drug effect. No significant differences were identified between propofol or midazolam regarding their effect on patient mood. Patients in both groups experienced a reduction in perioperative anxiety.

Adjuvants, Anesthesia↗

Self-inflicted and unintentional firearm injuries among children and adolescents: the source of the firearm.

CONTEXT: The source and ownership of guns used by children to shoot themselves or others is largely unknown. OBJECTIVE: To determine the ownership and usual storage location of firearms used in unintentional and self-inflicted intentional firearm deaths and injuries. DESIGN: Retrospective case series. SETTING: King County, Washington. PATIENTS: Youths aged from birth to 19 years who sought medical treatment at a level I trauma center for a self-inflicted or unintentional firearm injury between 1990 and 1995 or who presented to the county medical examiner with a fatal self-inflicted or unintentional firearm injury between 1990 and 1995. DATA SOURCES: County medical examiner records, regional police investigative reports, medical records from a level I trauma center, and surveys of victims' families. MAIN OUTCOME MEASURES: Source and ownership of the associated firearm. RESULTS: Fifty-six fatal injuries and 68 nonfatal firearm injuries that met the criteria were identified. Of these, 59 were intentionally self-inflicted deaths and injuries and 65 were unintentional deaths and injuries. A firearm owned by a household member living with the victim was used in 33 (65%) of 51 suicides and suicide attempts and 11 (23%) of 47 unintentional injuries and deaths. Additionally, a firearm owned by another relative, friend, or parent of a friend of the victim was used in 4 (8%) of the 51 suicides and suicide attempts and 23 (49%) of the 47 unintentional injuries and deaths. Parental ownership accounted for 29 (57%) of the 51 suicides and suicide attempts and 9 (19%) of the 47 unintentional injuries and deaths. More than 75% of the guns used in suicide attempts and unintentional injuries were stored in the residence of the victim, a relative, or a friend. CONCLUSION: Most guns involved in self-inflicted and unintentional firearm injuries originate either from the victim's home or the home of a friend or relative.

Accidents, Home↗

Development of techniques to genetically manipulate members of the genera Cytophaga, Flavobacterium, Flexibacter, and Sporocytophaga.

The Bacteroides-Cytophaga-Flavobacterium branch of the eubacterial phylogenetic tree contains a diverse group of bacterial species. Techniques for the genetic manipulation of Bacteroides spp. are well developed (A. A. Salyers, N. B. Shoemaker, and E. P. Guthrie, Crit. Rev. Microbiol. 14:49-71, 1987). Recently we developed techniques to genetically manipulate the gliding bacterium Cytophaga johnsonae (M. J. McBride and M. J. Kempf, J. Bacteriol. 178:583-590, 1996). We now demonstrate that some of these techniques allow genetic manipulation of a number of environmentally or medically significant bacteria in this group. The Bacteroides transposon Tn4351 was introduced into Cytophaga hutchinsonii, Cytophaga succinicans, Flavobacterium meningosepticum, Flexibacter canadensis, Flexibacter sp. strain FS1, and Sporocytophaga myxococcoides by conjugation. Tn4351 integrated itself into the host chromosomes and conferred erythromycin resistance. We isolated several auxotrophic mutants of Flavobacterium meningosepticum following Tn4351 mutagenesis. The C. johnsonae-Escherichia coli shuttle vector pCP11 functioned in C. succinicans but not in the other bacteria. pLYL03 did not replicate in any of these bacteria and should function as a convenient suicide vector. The identification of a system of gene transfer, a selectable marker, a suicide vector, and a transposon that functions in these diverse bacteria allows genetic manipulations to be performed.

Blotting, Southern↗

Using the theory of reasoned action (TRA) to understand the decision to use condoms in an STD clinic population.

The theory of reasoned action (TRA) provides useful information when designing health education interventions. In this study, 703 heterosexual STD clinic clients responded to a TRA-based survey. With steady partners, social norms and attitudes toward condom use were significant predictors of intention for both men and women. The interaction of attitude and norm increased prediction for men (R = .64, p < 0.001) and women (R = .70, p < 0.001). With casual partners, attitude was a predictor for men and social norm was a predictor for women. Prior use of condoms increased prediction for men (R = .38, p < 0.001) and women (R = .47, p < 0.001). Findings suggest that, in addition to traditional TRA model variables, the relationship between sexual partners and the individual's prior experience with condom use should be incorporated into attempts to understand this complex, dyadic behavior. Examining specific outcome and normative beliefs also provides important information for intervention design.

Adult↗

Beliefs about condoms and their association with intentions to use condoms among youths in detention.

PURPOSE: Youths in detention have been identified as a high-risk group for AIDS. To help inform AIDS-prevention efforts targeted for these youths, we surveyed youths in detention regarding their sexual behaviors, beliefs about condoms, intentions to use condoms, and actual condom use. We examined race and gender differences in these beliefs and behaviors, and we studied the relationship of these beliefs to condom-use intentions. METHODS: Questionnaires were administered to a sample of 201 youths in detention who were, on average, 16 years old. The sample was stratified on gender and race (African-American and white), with approximately equal numbers in each group. RESULTS: The results indicate that these youths had engaged in behaviors that put them at high risk of acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases. Although they used condoms somewhat more consistently with casual partners than with their steady partners, the majority did not use condoms consistently with either partner type. Very few race or gender differences were found with regard to condom use, intentions to use condoms, or beliefs about the consequences of using condoms. Beliefs associated with intentions to use condoms with steady partners included protection against sexually transmitted diseases (STDs), and the beliefs that condoms reduce pleasure, are artificial, unromantic, and interrupt sex. In contrast, only the belief that condoms prevent pregnancy was related to intentions to use condoms with casual partners. CONCLUSION: The results suggest that interventions targeted at African-American and white males and females in detention need not differ greatly in content as long as they include the most salient concerns of each group; that interventions include content on the two protective benefits of condom use (pregnancy and STD prevention), as well as on how to minimize the perceived negative aspects of condom use; that they stress the need for condom use with steady as well as casual partners; and that they stress that anal intercourse is especially risky with regard to AIDS transmission.

Acquired Immunodeficiency Syndrome↗

Psychosocial, behavioral, and medical outcomes in children with epilepsy: a developmental risk factor model using longitudinal data.

OBJECTIVE: We studied factors predicting the risk of adverse long-term psychosocial, behavioral, and medical outcomes in children with epilepsy. METHODS: Children (N = 157, 4.5 to 13 years) were enrolled in a prospective longitudinal study when first seen. Potential subjects were excluded if they were moderately or severely mentally retarded, had motor or sensory handicaps interfering with testing, or did not speak either English or Spanish. MEASURES: To develop risk predictors, we collected information regarding the child's medical and seizure history, cognitive functioning, and behavior problems, and family functioning. Children and their families were followed for a minimum of 18 months, then underwent reassessment of medical status, parent's attitudes toward epilepsy, and the child's behavioral and cognitive functioning. Data were analyzed by confirmatory factor analysis to develop baseline factors (Sociocultural Risk, Seizure Risk, and Behavior Problems) and outcome factors (Medical/Seizure Problems, Parent's Negative Attitudes Toward Epilepsy, and Behavior Problems), followed by structural equation modeling to determine across-time causal effects. Eighty-eight subjects completed all baseline and outcome measures. RESULTS: Among significant across-time effects, Medical Outcome was predicted by Seizure Risk. An increased number of stressful life events predicted better Medical Outcome. Low acculturation increased Parent's Negative Attitudes and was associated with increased Behavior Problems at baseline. Behavior Problems were stable across time. It is interesting that IQ did not affect any of the outcomes, although its effect may have been mediated through other baseline measures. CONCLUSIONS: Seizure history was the best predictor of ongoing medical difficulties, whereas the most important causes of ongoing parental anxiety and negative attitudes toward epilepsy were sociocultural. Variation in medical or attitudinal outcomes was not influenced by either the child's IQ or reported behavioral problems. These findings suggest that to alter attitudes toward epilepsy, programs should be tailored to the sociocultural background of the family. Studies of quality of life of children with epilepsy should include appropriate sociocultural measures.

Acculturation↗

Functional role for the M2 muscarinic receptor in smooth muscle of guinea pig ileum.

A functional role for the M2 muscarinic receptor in smooth muscle contraction was investigated in isolated guinea pig ileum. Contractile responses to the muscarinic agonist oxotremorine-M (oxo-M) were measured in isolated ilea that had been pretreated with histamine (0.32 microM) and isoproterenol (0.64 microM) to achieve conditions of elevated cAMP. The resulting concentration-effect curve was biphasic, consisting of high (0-50 nM) and low (> 50 nM) potency components. The reversible M2-selective antagonist AF-DX 116 ([[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11- dihydro-6H-pyrido[2,3b][1,4]benzodiazepine-6-one) (1 and 10 microM) shifted this curve in a manner that was inconsistent with competitive antagonism at a single receptor site; the high affinity component was significantly blocked, whereas there was little effect on the low affinity portion of the curve. To inactivate the M3 muscarinic receptors selectively, ilea were incubated with the irreversible M1/M3-selective muscarinic antagonist 4-DAMP mustard [N-(2-chloroethyl)-4-piperidinyldiphenylacetate] (40 nM) for 1 hr in the presence of AF-DX 116 (1 microM) and were then washed extensively. Under these conditions, the contractile responses to oxo-M, in the presence of histamine and isoproterenol or forskolin, were antagonized by AF-DX 116 (1 microM) in a manner consistent with that mediated by an M2 receptor. AF-DX 116 caused 6.6- and 11-fold increases in the EC50 value for oxo-M for ilea pretreated with isoproterenol and forskolin, respectively, and a significant increase in the Hill coefficient in both cases. Under basal conditions, AF-DX 116 caused only a 1.34-fold increase in the EC50 value and no change in the Hill coefficient. In addition, under basal conditions 4-DAMP mustard treatment shifted the oxo-M contractile response curve to the right approximately 20-fold. However, when histamine was present in combination with isoproterenol or forskolin 4-DAMP mustard treatment shifted the concentration-effect curves for oxo-M to the right only about 3.5-fold. Oxo-M produced an M3-mediated stimulation of phosphoinositide hydrolysis in the longitudinal muscle of rat ileum with an EC50 value of 30 microM. 4-DAMP mustard (10 nM; 1 hr) prevented this response, resulting in a 6.6-fold increase in the EC50 value with a 65% reduction of the maximal response. In contrast, this treatment blocked M2-mediated inhibition of isoproterenol-stimulated adenylate cyclase with only a 2-fold increase in EC50, without affecting maximum inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A comparison of tests of the difference in the proportion of patients who are cured.

We compared by simulation the likelihood ratio, Wald, and score tests based on a mixture model similar to that proposed by Farewell (1982, Biometrics 38, 1041-1046), and a simple nonparametric test based on the plateau value of the product-limit estimate, for testing the difference in cured proportions between two groups. The parametric tests obtained their asymptotic properties even in small samples provided that one could assume equal failure rates in the two groups. Otherwise, good agreement with predictions required that essentially all potential failures had been observed. The comparative properties of the parametric tests depended on whether the population survival functions crossed, with the power of the Wald test as good as or better than the others in the common situation when the survival functions do not cross. However, its size was sometimes less than nominal. The score test was often not defined and is therefore of limited value. The product-limit test often performed as well as the parametric tests, and despite being biased in some circumstances, may be a useful alternative to these, especially in small samples when some potential failures have not been observed.

Biometry↗

Reaction time, impulsivity, and attention in hyperactive children and controls: a video game technique.

Maturation of sustained attention was studied in a group of 52 hyperactive elementary school children and 152 controls using a microcomputer-based test formatted to resemble a video game. In nonhyperactive children, both simple and complex reaction time decreased with age, as did variability of response time. Omission errors were extremely infrequent on simple reaction time and decreased with age on the more complex tasks. Commission errors had an inconsistent relationship with age. Hyperactive children were slower, more variable, and made more errors on all segments of the game than did controls. Both motor speed and calculated mental speed were slower in hyperactive children, with greater discrepancy for responses directed to the nondominant hand, suggesting that a selective right hemisphere deficit may be present in hyperactives. A summary score (number of individual game scores above the 95th percentile) of 4 or more detected 60% of hyperactive subjects with a false positive rate of 5%. Agreement with the Matching Familiar Figures Test was 75% in the hyperactive group.

Attention↗

Methemoglobinemia: the hidden diagnosis.

Although methemoglobinemia is not commonly seen in the ER or the critical care setting, it can be life threatening if unrecognized and left untreated. A detailed case history illustrates the symptoms and some of the possible precipitating factors, and outlines treatment for a successful patient outcome.

Adolescent↗

Adaptive realtime compensatory feedback to open the light-pupil reflex loop.

Integrity of the visual pathway is often clinically determined from response of the pupil to light. The need for more quantitative measurement of pupillary response has led engineers to investigate the light-pupil reflex with systems analysis techniques. The results have made the light-pupil reflex a model of the application of the principles of control theory to physiologic mechanisms. This analysis required that the system be rendered open loop by focusing the stimulus at the center of the pupil. Patients may not be able to restrict their head and eye movement well enough to permit the feedback loop to be rendered open loop optically. Thus, clinical applications of the technique have been limited. A means of opening the feedback loop by using a realtime deterministic autoregressive moving average prediction algorithm integrated into a computer based television pupillometer has been developed. It employs a model reference adaptive scheme to identify the physiologic system, then predicts future values of pupil area to compensate for delays in the measuring apparatus. A computer driven liquid crystal display shutter controls retinal illuminance to render the light-pupil reflex open loop. This technique reduced the mean square error of retinal illuminance by about 75% compared to uncompensated pupil responses.

Algorithms↗

Parents' behavioral norms as predictors of adolescent sexual activity and contraceptive use.

The influence of parental factors on adolescent sexual behavior and contraceptive use has been examined previously, and findings have been contradictory. Previous studies, which found little relationship between parental norms and adolescent sexual activity, have been limited by their failure to recognize developmental differences in the relative weight of parent and peer influences between younger and older teens and by use of selected samples, resulting in a restriction of range. The current study differs in that it utilizes a clustered sample household survey of 329 males and females, aged 14 to 17, and 470 of their parents. Using multiple regression analysis, it was found that parents' reported behavioral norms account for 5% of the variance in whether adolescents have had intercourse, and for 33% of the variance in use of contraception at last intercourse. The study suggests that while parents' normative beliefs have limited effect in the decision to become sexually active, they have considerable impact on later contraceptive use.

Adolescent↗

Purification and structural characterization of herpes simplex virus glycoprotein C.

Purification of herpes simplex virus glycoprotein C (gC) in microgram amounts yielded sufficient material for an analysis of its secondary structure. Purification was facilitated by using the mutant virus gC-3, which bears a point mutation that interrupts the putative hydrophobic membrane anchor sequence, causing the secretion of gC-3 protein into the cell culture medium. gC-3 protein was purified by size fractionation of concentrated culture medium from infected cells on a gel filtration column of Sephacryl S-200, followed by immunoaffinity chromatography on a column constructed of gC-specific monoclonal antibodies cross-linked to a protein A-Sepharose CL-4B matrix. Purified gC-3 had a molecular weight of 130,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the size expected for gC, was reactive with gC-specific monoclonal antibodies in protein immunoblots, and contained amino acid sequences characteristic of gC as determined by radiochemical amino acid microsequence analyses. Polyclonal antisera obtained from a rabbit immunized with gC-3 reacted with wild-type gC in immunoprecipitation, enzyme immunoassay, and immunoelectroblot (western blot) assays. Deglycosylation by treatment with trifluoromethanesulfonic acid reduced the molecular weight of gC-3 by approximately 35%. Analyses of both native and deglycosylated gC-3 by Raman spectroscopy showed that the native molecule consists of about 17% alpha-helix, 24% beta-sheet, and 60% disordered secondary structures, whereas deglycosylated gC-3 consists of about 8% alpha-helix, 10% beta-sheet, and 81% disordered structures. These data were in good agreement with the 11% alpha-helix, 18% beta-sheet, 61% beta-turn, and 9% disordered structures calculated from Chou-Fasman analysis of the primary sequence of gC-3.

Amino Acid Sequence↗