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Biomedical subjects

A M Baker

Publications and source records attributed to A M Baker.

At least 37 records · Page 2Linked to original sources

Influenza immunization in a managed care organization.

OBJECTIVE: To compare the effects of different types of computer-generated, mailed reminders on the rate of influenza immunization and to analyze the relative cost-effectiveness of the reminders. DESIGN: Randomized controlled trial. SETTING: Multispecialty group practice. PATIENTS: We studied 24,743 high-risk adult patients aligned with a primary care physician. INTERVENTION: Patients were randomized to one of four interventions: (1) no reminder, which served as control; (2) a generic postcard; (3) a personalized postcard from their physician; and (4) a personalized letter from their physician, tailored to their health risk. MEASUREMENTS: The immunization rate was measured using billing data. A telephone survey was conducted in a subgroup of patients to measure reactions to the mailed reminders. To evaluate the cost-effectiveness, a model was constructed that integrated the observed effect of the interventions with published data on the effect of immunization on future inpatient health care costs. MAIN RESULTS: All three of the reminders studied increased the influenza vaccination rate when compared with the control group. The vaccination rate was 40.6% in the control group, 43.5% in the generic postcard group, 44.7% in the personalized postcard group, and 45.2% in the tailored letter group. The rates of immunization increased as the intensity of the intervention increased (p < .0001). Seventy-eight percent of patients in the letter group deemed the intervention useful, and 86% reported that they would like to get reminders in the future. The cost-effectiveness analysis estimated that in a nonepidemic year, the net savings per 100 reminders sent would be $659 for the personalized postcard intervention and $735 for the tailored letter intervention. When these net cost-savings rates were each applied to the entire high-risk cohort of 24,743 patients, the estimated total net savings was $162,940 for the postcard and $181,858 for the tailored letter. CONCLUSIONS: Although the absolute increase in immunization rates with the use of reminders appeared small, the increases translated into substantial cost savings when applied to a large high-risk population. Personalized reminders were somewhat more effective in increasing immunization, and personalized letters tailored to the patients' condition were deemed useful and important by the individuals who received them and had a beneficial indirect effect on patient satisfaction.

Adult↗

Expression of antioxidant enzymes in human prostatic adenocarcinoma.

BACKGROUND: Antioxidant enzymes (AEs), which catalyze the conversion of reactive oxygen species (ROS) to water, include catalase (CAT), manganese-containing superoxide dismutase (MnSOD), and copper and zinc-containing superoxide dismutase (CuZnSOD). Previous work has indicated that MnSOD, CAT, and CuZnSOD levels are nearly always low in cancer cells. METHODS: Formalin-fixed, paraffin-embedded tissue from 31 radical prostatectomy specimens was immunohistochemically stained with polyclonal antibodies to CAT, MnSOD, and CuZnSOD. RESULTS: Malignant glands are typically stained with less intensity than benign/ hyperplastic glands. Marked heterogeneity of staining intensity was seen in the malignant glands for each of the three enzymes. A similar, though less marked, spectrum of heterogeneity of staining intensity was observed in the benign/hyperplastic epithelium contained in the specimens. No statistically significant correlation was found between intensity of staining for any of the three antioxidant enzymes and Gleason score, tumor stage, or preoperative prostate-specific antigen (PSA). CONCLUSIONS: Cellular levels of CAT, MnSOD, and CuZnSOD in prostatic adenocarcinoma reveal that many tumors appear to have decreased levels of expression. The finding that malignant prostate epithelium may have lowered expression of AEs suggests that further study of the role of AEs in malignant transformation in the prostate is warranted.

Adenocarcinoma↗

The impact of political violence on moral reasoning in children.

OBJECTIVE: The moral development of three groups of children, who had been subjected to varying degrees of political violence and economic advantage, was examined in an attempt to determine if group membership or gender influenced the level of moral reasoning or orientation. METHOD: Ninety-three 8- to 13-year-old Israeli Jewish and Bedouin school children, and Palestinian West Bank school children were asked various moral reasoning questions based on an animal fable involving a moral dilemma under three (hypothetical, role-taking, political) conditions. RESULTS: Results indicate that mutuality solutions to moral dilemmas were given more frequently by Israeli Jewish children than Israeli Bedouin or Palestinian children as the questions shifted from abstract to real-life situations. No significant gender differences were found between Jewish children and Bedouin children in hypothetical issues; however, violence and limited resources were found to affect moral judgment in real-life situations for boys, but not for girls. CONCLUSIONS: These findings supported the hypothesis that moral reasoning in children is significantly linked to real-life situations and resources. The results were discussed in terms of their relevance to future researchers and the manner in which children interpret moral questions.

Adolescent↗

Bronchoscopic evaluation of pulmonary infiltrates following bone marrow transplantation.

STUDY OBJECTIVE: To determine the impact of fiberoptic bronchoscopy (FOB), including quantitative bacterial cultures obtained by BAL and protected specimen brushing on therapeutic decisions and outcome in bone marrow transplant (BMT) patients. DESIGN: Retrospective review of all BMT patients undergoing FOB during a 4-year period. SETTING: A tertiary care university hospital. RESULTS: Three hundred five patients underwent BMT; 71 (23%) had FOB to assess pulmonary infiltrates. Allogeneic BMT recipients underwent FOB 3.37 times more often than autologous recipients (p < 0.001). Pathogens were identified in 31 (46%) patients undergoing FOB; bacteria were most commonly isolated although 86% of patients had received broad-spectrum empiric antibiotics. Therapy was changed in 20 (65%) patients when a microorganism was identified and in 9 (22%) with nondiagnostic results (p = 0.0026), but isolation of a presumed pathogen had no apparent effect on survival. There were 19 (27%) FOB complications, including bleeding in 8 (11%) patients and death in 2 (3%). Major complications were associated with prolonged prothrombin time (p = 0.006) and were more common (36% vs 14%; p < 0.05) in patients who had protected specimen brushing vs BAL alone. Mortality at 40 months in BMT patients not requiring FOB was 33% compared with 61% mortality in those undergoing FOB (p < 0.001); mortality was 96% in patients with respiratory failure requiring mechanical ventilation. CONCLUSION: FOB is diagnostically useful in the evaluation of some BMT patients with pulmonary complications and often influences therapy, although no impact on survival was clearly demonstrated. FOB should be performed only after benefits of the procedure are weighed carefully against its increased risk in this select population.

Adult↗

Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously.

BACKGROUND: Prompt recognition of the reversal of respiratory failure may permit earlier discontinuation of mechanical ventilation, without harm to the patient. METHODS: We conducted a randomized, controlled trial in 300 adult patients receiving mechanical ventilation in medical and coronary intensive care units. In the intervention group, patients underwent daily screening of respiratory function by physicians, respiratory therapists, and nurses to identify those possibly capable of breathing spontaneously; successful tests were followed by two-hour trials of spontaneous breathing in those who met the criteria. Physicians were notified when their patients successfully completed the trials of spontaneous breathing. The control subjects had daily screening but no other interventions. In both groups, all clinical decisions, including the decision to discontinue mechanical ventilation, were made by the attending physicians. RESULTS: Although the 149 patients randomly assigned to the intervention group had more severe disease, they received mechanical ventilation for a median of 4.5 days, as compared with 6 days in the 151 patients in the control group (P=0.003). The median interval between the time a patient met the screening criteria and the discontinuation of mechanical ventilation was one day in the intervention group and three days in the control group (P<0.001). Complications -- removal of the breathing tube by the patient, reintubation, tracheostomy, and mechanical ventilation for more than 21 days -- occurred in 20 percent of the intervention group and 41 percent of the control group (P=0.001). The number of days of intensive care and hospital care was similar in the two groups. Total costs for the intensive care unit were lower in the intervention group (median, $15,740, vs. $20,890 in the controls, P=0.03); hospital costs were lower, though not significantly so (median, $26,229 and $29,048, respectively; P=0.3). CONCLUSIONS: Daily screening of the respiratory function of adults receiving mechanical ventilation, followed by trials of spontaneous breathing in appropriate patients and notification of their physicians when the trials were successful, can reduce the duration of mechanical ventilation and the cost of intensive care and is associated with fewer complications than usual care.

Adult↗

Adaptation of TCR expression vectors for the construction of mouse-human chimeric MBP-specific TCR transgenes.

T cell receptor (TCR) transgenic mice have been used extensively to study T cell development in vivo. Such studies have demonstrated high levels of expression of the TCR transgenes. Although a number of human T cell receptors appear to play a role in the development of autoimmune diseases, in vitro studies have proven inadequate for investigation of their putative pathogenicity. Several groups have reported the isolation of myelin basic protein (MBP)-reactive T cell clones from patients with multiple sclerosis and many of the T cell receptors from such clones have been well characterized. Since a number of inbred mouse strains have demonstrated susceptibility to a similar T cell-mediated inflammatory demyelinating disease known as EAE, a useful animal model is likely to be generated by expressing human MBP-specific TCR in susceptible mice. As a first step toward this goal we have cloned a number of TCR genes into an expression vector previously used for murine TCR genes. Here we report the development of a rapid cloning system for the generation of mouse-human chimeric TCR transgene constructs and the use of this system for the production of MBP-specific TCR transgenes. Human MBP-specific TCR transgenic mice will provide a unique system for the investigation of T cell-mediated demyelinating disease in the central nervous system (CNS).

Amino Acid Sequence↗

Pneumonia in intubated trauma patients. Microbiology and outcomes.

To describe the epidemiology of nosocomial pneumonia in trauma patients and its impact on outcome, we performed a retrospective case-control analysis. Quantitative bronchoscopic cultures were collected from 62 intubated patients with suspected pneumonia. Patients with proven pneumonia had higher abdominal injury scores. Those with bronchoscopy-negative pneumonitis were older. Age and injury severity were used to match two controls to each case. The incidence of pneumonia was 5.8% Streptococci and Hemophilus were common pathogens, but gram-negative rods were isolated more frequently after lengthier intubation. Polymicrobial infections were common. There were no serious complications of bronchoscopy, and culture results often led to antibiotic therapy. No excess mortality could be attributed to pneumonia. Patients with pneumonia and those with bronchoscopy-negative pneumonitis required prolonged care compared with others (p < 0.05). Patients with pneumonia did not receive excess ventilation or hospitalization but incurred hospital charges 1.5 times higher than controls (p = 0.04). Pneumonia was confirmed in less than half of those suspected of having it on the basis of clinical findings. When severity of injury was considered, pneumonia was associated with neither increased mortality nor increased hospital care, but the clinical features suggesting respiratory infection identified trauma patients requiring prolonged hospitalization and incurring higher costs.

Adult↗

Messenger RNA recognition by fragments of ribosomal protein S4.

Ribosomal protein S4 from Escherichia coli binds a large domain of 16 S ribosomal RNA and also a pseudoknot structure in the alpha operon mRNA, where it represses its own synthesis. No similarity between the two RNA binding sites has been detected. To find out whether separate protein regions are responsible for rRNA and mRNA recognition, proteins with N-terminal or C-terminal deletions have been overexpressed and purified. Protein-mRNA interactions were detected by (i) a nitrocellulose filter binding assay, (ii) inhibition of primer extension by reverse transcriptase, and (iii) a gel shift assay. Circular dichroism spectra were taken to determine whether the proteins adopted stable secondary structures. From these studies it is concluded that amino acids 48-104 make specific contacts with the mRNA, although residues 105-177 (out of 205) are required to observe the same toeprint pattern as full-length protein and may stabilize a specific portion of the mRNA structure. These results parallel ribosomal RNA binding properties of similar fragments (Conrad, R. C., and Craven, G. R. (1987) Nucleic Acids Res. 15, 10331-10343, and references therein). It appears that the same protein domain is responsible for both mRNA and rRNA binding activities.

Amino Acid Sequence↗

Differential effects of trauma on spouses of traumatized households.

The responses of 60 households subjected to varying degrees of traumatic events were examined. Specific attention was given to the differential effect that traumatic events have on spouses, especially in terms of general anxiety, state anxiety, trait anxiety, depression, and other symptoms related to trauma. The findings showed that degree of traumatization was proportional to number and intensity of stress related symptoms. Mothers, however, manifested depression and anxiety levels twice as high as fathers. The validity of these results was discussed in terms of cultural beliefs and practices.

Adaptation, Psychological↗

Decision making in nosocomial pneumonia. An analytic approach to the interpretation of quantitative bronchoscopic cultures.

Quantitative cultures of specimens obtained at fiberoptic bronchoscopy have been used to diagnose nosocomial pneumonia in research settings, but their clinical role remains controversial. We reviewed the literature comparing these culture techniques with other accepted methods to diagnose pneumonia in mechanically ventilated patients and extracted data to describe the receiver operator characteristics (ROC) of quantitative cultures of protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples. Analysis of ROCs reveals that these tests have a discriminating power comparable or superior to that of many widely accepted routinely used tests. Current data do not suggest that either culture technique offers an advantage over the other. Since benefits of antibiotic therapy of pneumonia and risks of treatment of noninfected critically ill patients are not well quantified, universally applicable recommendations for appropriate values to define an abnormal test result cannot logically be made. Multiple decision analytic tools show that values lower than those previously recommended are more appropriate in patients suspected of having pneumonia unless the risk of antibiotic therapy is judged to be extreme. On the basis of these findings, we suggest guidelines for clinicians' interpretation of PSB and BAL quantitative culture results.

Bacteria↗

Genomic organization and sequence of the human NRAMP gene: identification and mapping of a promoter region polymorphism.

BACKGROUND: Murine Nramp is a candidate for the macrophage resistance gene Ity/Lsh/Bcg. Sequence analysis of human NRAMP was undertaken to determine its role in man. MATERIALS AND METHODS: A yeast artificial chromosome carrying NRAMP was subcloned and positive clones sequenced. The transcriptional start site was mapped using 5' RACE PCR. Polymorphic variants were amplified by PCR. Linkage analysis was used to map NRAMP. RESULTS: NRAMP spans 12kb and has 15 exons encoding a 550 amino acid protein showing 85% identity (92% similarity) with Nramp. Two conserved PKC sites occur in exon 2 encoding the Pro/Ser rich SH3 binding domain, and in exon 3. Striking sequence similarities (57 and 53%) were observed with yeast mitochondrial proteins, SMF1 and SMF2, especially within putative functional domains: exon 6 encoding the second transmembrane spanning domain, site of the murine susceptibility mutation; and exon 11 encoding a conserved transport motif. No mutations comparable to the murine susceptibility mutation were found. The transcriptional initiation site mapped 148 bp 5' of the translational initiation codon. 440bp of 5' flanking sequence contained putative promoter region elements: 6 interferon-gamma response elements, 3 W-elements, 3 NF kappa B binding sites and 1 AP-1 site. Nine purine-rich GGAA core motifs for the myeloid-specific PU.1 transcription factor were identified, two combining with imperfect AP1-like sites to create PEA3 motifs. TATA, GC and CCAAT boxes were absent. A possible enhancer element containing the Z-DNA forming dinucleotide repeat t(gt),ac(gt),ac(gt),g was polymorphic (4 alleles; n = 4,9,10,11), and was used to map NRAMP to 2q35. CONCLUSIONS: This analysis provides important resources to study the role of NRAMP in human disease.

Alleles↗

Genetic regulation of leishmanial and mycobacterial infections: the Lsh/Ity/Bcg gene story continues.

A common basis to genetic regulation of leishmanial and mycobacterial infections is provided by the action of the murine Lsh/Ity/Bcg gene in controlling the priming/activation of macrophages for antimicrobial activity. This relies on the TNF-alpha-dependent sustained expression of the inducible nitric oxide synthase (iNOS) gene responsible for the generation of large amounts of toxic nitric oxide (NO). The Lsh/Ity/Bcg gene has many pleiotropic effects, including differential expression of the early response gene KC following stimulation of macrophages with bacterial lipopolysaccharide (LPS) and mycobacterial lipoarabinomannan (LAM). The major signal transduction pathway involved in KC induction requires the generation of low levels of NO via constitutive nitric oxide synthase (cNOS) activity, leading to activation of guanylate cyclase and the cGMP-dependent kinase pathway. NO therefore appears to provide a common link between the early influence of Lsh in regulating the expression of genes which mediate many pleiotropic effects, and the later production of NO as the final effector mechanism for kill. The recently cloned candidate for Lsh/Ity/Bcg, designated Nramp for Natural resistance associated macrophage protein, encodes a polytopic integral membrane protein that has structural features common to prokaryotic and eukaryotic transporters and includes a conserved binding-protein-dependent transport motif which may be involved in interaction with peripheral ATP-binding subunits. The N-terminal sequence also carries a proline/serine rich putative SH3 binding domain, consistent with a role for tyrosine kinases in regulating Nramp function. (ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Nabumetone in elderly patients with osteoarthritis: economic benefits versus ibuprofen alone or ibuprofen plus misoprostol.

Nonsteroidal anti-inflammatory drugs (NSAIDs) vary in their potential to produce gastropathy. We compared the 3-month direct medical costs, including those associated with treating NSAID-induced adverse events, of nabumetone, ibuprofen, or ibuprofen plus misoprostol in 171 elderly patients with osteoarthritis. Total direct medical costs per patient treated were $US183 for nabumetone, $US252 for ibuprofen, and $US270 for ibuprofen plus misoprostol. Differences resulted from higher costs associated with treatment of drug-related adverse events with ibuprofen, and higher drug acquisition prices with the combination regimen. Sensitivity analyses demonstrated that direct costs with nabumetone approached those for the other 2 regimens if the price of nabumetone increased by 60%, the probability of lesion formation with nabumetone increased 4-fold, the probability of a lesion greater than 0.5cm being symptomatic and needing treatment was 31%, or the price of misoprostol decreased by 50%. Although this study found more lesions because of mandated endoscopies than might be recognised or treated in clinical practice, the results suggest an economic benefit of nabumetone.

Aged↗

Comparative evaluation of detection assays for Chlamydia trachomatis.

The performances of a commercial nucleic acid hybridization test (Gen-Probe Pace 2 Chlamydia trachomatis) and two commercial enzyme immunoassays (EIAs) (Abbott Chlamydiazyme and Pharmacia Chlamydia EIA) were evaluated against cell culture for the detection of C. trachomatis infection, with cervical swabs obtained from 1,037 women visiting a public sexual health center. The positivity rate by cell culture was 4.7%. Sensitivity and specificity for each test were as follows: Gen-Probe, 95.8 and 98.3%; Chlamydiazyme, 80.4 and 99.3%; Pharmacia EIA, 80.8 and 99.1%. Analysis of discrepant results with probe confirmation assay (Gen-Probe) and direct immunofluorescence (Syva Microtrak) revealed 12 cases of C. trachomatis infection for which culture was negative, resulting in the definition of a true-positive case as opposed to a culture positive. The positivity rate by true-positive definition was 5.9%, and sensitivity and specificity for each test were as follows: Gen-Probe, 96.7 and 99.6%; Chlamydiazyme, 77.5 and 100%; Pharmacia EIA, 77.0 and 100%; cell culture, 80.0 and 100%. We conclude that the Gen-Probe Pace 2 C. trachomatis test is a sensitive and specific alternative to cell culture for the detection of C. trachomatis.

Bacteriological Techniques↗

Cl- channels of the gastric parietal cell that are active at low pH.

HCl secretion across mammalian gastric parietal cell apical membrane may involve Cl- channels. H(+)-K(+)-ATPase-containing membranes isolated from gastric mucosa of histamine-stimulated rabbits were fused to planar lipid bilayers. Channels were recorded with symmetric 800 mM CsCl solutions, pH 7.4. A linear current-voltage (I-V) relationship was obtained, and conductance was 28 +/- 1 pS at 800 mM CsCl. Conductance was 6.9 +/- 2 pS at 150 mM CsCl. Reversal potential was +22 mV with a fivefold cis-trans CsCl concentration gradient, indicating that the channel was anion selective with a discrimination ratio of 6:1 for Cl- over Cs+. Anion selectivity of the channel was I- > Cl- > or = Br- > NO3-, and gluconate was impermeant. Channels obtained at pH 7.4 persisted when pH of medium bathing the trans side of the bilayer (pHtrans) was reduced to pH 3, without a change in conductance, linearity of I-V relationship, or ion selectivity. In contrast, asymmetric reduction of pH of medium bathing the cis side of the bilayer from 7.4 to 3 always resulted in loss of channel activity. At pH 7.4, open probability (Po) of the channel was voltage dependent, i.e., predominantly open at +80 mV but mainly closed at -80 mV. In contrast, with low pHtrans, channel Po at -80 mV was increased 3.5-fold. The Cl- channel was Ca2+ indifferent. In absence of ionophores, ion selectivity for support of H(+)-K(+)-ATPase activity and H+ transport was consistent with that exhibited by the channel and could be limited by substitution with NO3-, whereas maximal H(+)-K(+)-ATPase activity was indifferent to anion present, demonstrating that anion transport can be rate limiting. Cl- channels with similar characteristics (conductance, linear I-V relationship, and ion selectivity) were also present in H(+)-K(+)-ATPase-containing vesicles isolated from resting (cimetidine-treated) gastric mucosa, exhibiting at -80 mV a pH-independent approximately 3.5-fold lower Po than stimulated vesicle channels. At -80 mV, reduction of pHtrans increased Po of both resting and stimulated Cl- channels by five- to sixfold. Changing membrane potential from 0 to -80 mV across stimulated vesicles increased Cl- channel activity an additional 10-fold.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

The psychological impact of the Intifada on Palestinian children in the occupied West Bank and Gaza: an exploratory study.

The mental health of 796 Palestinian children living in the occupied West Bank and Gaza Strip was assessed in terms of reported psychological status and behavioral symptoms. Results, interpreted within the context of the 1987 uprising (Intifada), indicate that exposure to political and military violence may be associated with the onset of conduct problems and fears, although active participation in the conflict may enhance self-esteem and shield children from development of psychological symptoms.

Adolescent↗

Toward comprehensive nursing care of the total artificial heart patient.

At this time, heart transplantation is the only form of intervention for some end-stage cardiac diseases. The use of the artificial heart has been adopted at the Ottawa Institute as a bridge to transplant when a heart is needed, and there are no suitable donors available. The patient is maintained with this technology until a donor heart can be found and transplanted. This article chronicles the steps that were taken by the nursing staff in preparation for these unique patients. The nursing process was the main framework around which we developed our plan of action, assessed and evaluated our interventions and modified nursing care accordingly. The basic functioning of the system that operates the heart is described, as well as nursing care specific to the Total Artificial Heart patient.

Adult↗