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Biomedical subjects

R Hamilton

Publications and source records attributed to R Hamilton.

At least 19 recordsLinked to original sources

Use of telemetry functions in the assessment of implanted antitachycardia device efficacy.

Twenty patients (aged 50 +/- 21 years and mean left ventricular ejection fraction 37 +/- 17%) with recurrent ventricular arrhythmias were treated with an investigational, implantable combined antitachycardia-pacing cardioverter defibrillator. The device's telemetry capabilities include both stored (1-second snapshots) and real-time display of endocardial and device-circuit signals. The device can store these before, during and after up to 50 tachycardia and antitachycardia pacing episodes. All stored events are indexed to a 24-hour internal clock. During 10.1 +/- 5.1 months of follow-up, the device was used in 11 of 20 patients. In the entire group, antitachycardia pacing was activated on 44 +/- 14 occasions per patient (total 874) and shock delivery occurred on 8 +/- 14 occasions per patient (total 156). Reconstruction by stored telemetry of all device-therapy episodes was possible. Twenty-six percent of all shocks delivered were not appropriate and were due to atrial arrhythmias in 2 patients and dysfunction of the sensing lead in 3. The absence of a relation between symptoms and appropriate shock delivery was documented in 1 patient. Antitachycardia pace acceleration occurred in 5.3% of cases; 7% of attempts at pacing were unsuccessful and needed shock therapy. It is concluded that the enhanced telemetry available in newer antitachycardia devices enables more accurate assessment of device use and enhances diagnosis of inappropriate therapy delivery.

Electric Countershock

Clinical impact of balloon angioplasty for branch pulmonary arterial stenosis.

The clinical impact of percutaneous balloon angioplasty on the management of patients with native or postoperative pulmonary arterial stenosis was reviewed. Seventy-four patients underwent 110 angioplasty procedures. Mean age at dilation was 6.7 +/- 5.3 years (range 0.2 to 18.1), 17 patients were aged less than 1 year, mean follow-up was 37.7 +/- 22.8 months (range 16 to 96), and 34 patients (44%) had follow-up angiography. Pulmonary artery dilation was acutely successful in 53% of patients, 17% had recurrent stenosis, and 5% had complications. The impact on subsequent care was favorably influenced in 26 of 74 patients (35%) with either complete resolution of stenosis (n = 7), optimizing future surgical conditions (n = 14), reduction in right ventricular pressure by greater than 20% (n = 3), or improvement of ipsilateral lung perfusion (n = 2). No patient previously considered inoperable was subsequently considered suitable for surgical repair owing to the intervention. No correlation was found between success and cardiac diagnosis (p = 0.48), site of stenosis (p = 0.78), balloon-vessel ratio (p = 0.42), or whether the stenotic area consisted of native or synthetic material (p = 0.22). No predictive factors for success could be defined, and often there was only a transient clinical impact. Due to the low complication risk and potential for a beneficial result, it still appears prudent to offer angioplasty as an initial therapeutic modality in this setting.

Adolescent

Pulmonary toxicity of inhaled polypropylene fibers in rats.

This study was initiated to assess the pulmonary toxicity of a polyolefin fiber composed of polypropylene in male Fischer 344 rats after 90 days of inhalation exposure. To increase fiber respirability in the rodent, polypropylene fibers were size-selected before aerosolization to have a geometric mean diameter of 1.6 microns (46% < 1 micron) and a geometric mean length of 30.3 microns. Three groups of animals were exposed in nose-only inhalation chambers, 6 hr/day, 5 days/week, for 90 days to 15, 30, or 60 mg/m3 of polypropylene, or filtered air (negative control). Microscopic examination of the polypropylene fiber-exposed lungs revealed that, at all time points examined in the study, there was a dose-dependent increase in pulmonary macrophages. These minimal or mild increases in cellularity appeared to be reversible, especially at the lower doses 30 days post exposure. No fibrosis was observed in any of the groups. A strong correlation was found between the external exposure concentration, the time of exposure, and the lung fiber burden. The number of partially degraded (segmented) fibers within the lung increased with the exposure concentration and period of exposure, as well as with the period of recovery after termination of exposure at 90 days. Fibers were recovered from exposed lungs using a hypochlorite digestion technique.

Administration, Inhalation

Frey's syndrome: prevention with conservative parotidectomy and superficial musculoaponeurotic system preservation.

Between 1980 and 1990, 35 patients underwent conservative parotidectomy combining a rhytidectomy incision and a superficial musculoaponeurotic system preservation technique to reduce the postoperative incidence of Frey's syndrome. All patients were evaluated by questionnaire for subjective symptoms of gustatory sweating and flushing as well as satisfaction with the aesthetic appearance of their cheek. Six percent of patients (2 of 35) complained of symptoms of Frey's syndrome. Ninety-four percent of patients (33 of 35) noticed minimal or no contour deformity of the surgical area. Twenty patients underwent Minor's starch iodine testing to identify objective evidence of aberrant nerve regeneration at the postoperative site. Fifteen percent of these patients (3 of 20) demonstrated a positive starch iodine test; however, one of these three patients was unaware of symptoms of Frey's syndrome. Symptoms of gustatory sweating are a reliable indicator of aberrant nerve regeneration. Conservative parotidectomy with superficial musculoaponeurotic system preservation for benign parotid disease produces a low incidence of Frey's syndrome and satisfactory cosmetic results.

Adenoma, Pleomorphic

Bleomycin stimulation of cytokine secretion by the human alveolar macrophage.

Bleomycin (BLM) is a very effective antineoplastic drug for many gynecologic and urinary tract carcinomas. However, its use, e.g., cumulative dosage, often is limited by the pulmonary fibrosis that it causes. The mechanism by which BLM causes fibrosis is not understood but is proposed to involve the pulmonary macrophage, a central cell in the cytokine network of the lung. To examine the direct effects of this drug on the human alveolar macrophage, we have treated human alveolar macrophages (isolated from normal subjects by bronchoalveolar lavage) with BLM in vitro and examined resultant macrophage secretory products that have importance for inflammatory and fibrotic processes. A 24-h treatment with BLM (0.5-100 mU/ml) was found to result in 1) a concentration-dependent decrease in the ability of the macrophage to produce superoxide anion in response to phorbol 12,13-dibutyrate, 2) an increase in secreted interleukin-1 beta (IL-1 beta), and 3) a decrease in intracellular levels of adenosine 3',5'-cyclic monophosphate. Kinetic studies revealed a time-dependent appearance of BLM-induced cytokines; tumor necrosis factor-alpha could be detected as early as 4 h after stimulation, followed by IL-1 beta at 8 h. The secretion of these cytokines was found to precede the release of prostaglandin E2, which became significant only at 24 h. Taken together, the present results imply that the human alveolar macrophage does not contribute to BLM-induced oxidant injury of the lung but that it may contribute to the development of BLM-induced pulmonary fibrosis.

Bleomycin

Effects of high-probability requests on the acquisition and generalization of responses to requests in young children with behavior disorders.

The failure to respond to requests in young children often is maintained by the reactions of the adults that encounter this behavior. This failure to respond to requests has been identified as a primary reason for the children's exclusion from community, social, and instructional opportunities. Numerous interventions that target the failure to respond have consisted of punishment and reinforcement procedures. More recently, antecedent interventions have focused on changing the context in which a request is delivered. In the current study, high-probability requests were provided as an antecedent to delivering a low-probability request. The requests were delivered by multiple trainers in an attempt to produce generalized appropriate responding to adults who did not use the high-probability sequence. Results showed an immediate increase in appropriate responding in 2 children when the intervention was delivered. In addition, when the intervention was implemented by more than one adult, spontaneous increases in responding also were observed toward adults who had never implemented the request sequence. Improvements in responding to requests were maintained after the intervention was discontinued.

Aggression

Immunochemical localization of extracellular materials in bone marrow of rats.

The distribution of type I collagen, fibronectin, laminin, and heparan sulfate was studied in marrow of rats by indirect immunofluorescence. Most of the type I collagen of marrow is associated with large blood vessels and connective tissue trabeculae, but type I collagen was also localized in a delicate meshwork throughout the marrow and in the basement membrane of the sinusoidal endothelium. Fibronectin is partially co-distributed with type I collagen, but is much more widely distributed. Sheets or septa of fibronectin-rich material divide the marrow into small compartments that contain and appear to separate clusters of developing blood cells. These septa may serve as a substrate for anchorage and migration of blood cells. Labeling of laminin was observed in the basement membranes of blood vessels, of fat cells, and of the sinusoidal wall, but only scattered labeling was seen in other extracellular materials. Heparan sulfate proteoglycan was poorly labeled in the extracellular matrix of marrow.

Animals

Mechanistic aspects of cromolyn sodium action on the alveolar macrophage: inhibition of stimulation by soluble agonists.

Despite wide use of the drug cromolyn sodium, its mechanism of action remains unknown. The alveolar macrophage plays a major role in the regulation of the inflammatory responses of the lung which may contribute to asthma. Since the biochemical mechanism by which agonists stimulate the alveolar macrophage to produce superoxide anion has been described, the effects of cromolyn sodium on this process were examined. Cromolyn sodium (0.5-4 mM) reversibly blocked macrophage stimulation by formyl peptide and leukotriene B4, but not by phorbol diester and concanavalin A. Cromolyn sodium inhibition was not calcium dependent and could be reversed by increasing the dose of agonist. Cromolyn sodium did not elevate intracellular cAMP, nor did the characteristics of inhibition resemble those observed using cAMP to inhibit agonist stimulation. However, cromolyn sodium did block agonist-mediated stimulation of the phosphatidylinositol (PI) pathway. Taken together, the present results suggest that one site of action of cromolyn sodium may be at the GTP-binding protein of the PI pathway.

Animals

HLA-DR expression in macaque neuroendothelial cells in vitro and during SIV encephalitis.

HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system.

Animals

Steroid-eluting epicardial leads in pediatrics: improved epicardial thresholds in the first year.

From 1986 to 1991, we evaluated the clinical use of three new epicardial lead designs incorporating a steroid-eluting electrode. Medtronic models SP2114 (bipolar high profile), 10320 (bipolar low profile), 10295A/4965 (unipolar low profile) steroid epicardial (SE) leads were used on either atrium or ventricle for a total of 21 lead placements in 17 patients. Energy thresholds (T) were calculated and compared with our most recent 16 nonsteroid epicardial (NE) Medtronic model 4951 lead implants for which T was available. SE leads demonstrated no acute T rise and continued T improvements at 1 year of follow-up. We conclude that epicardial application of SE lead technology offers a major improvement in pacing lead function and potential pacemaker longevity over NE leads in pediatric patients in whom endocardial pacing is precluded by size or anatomy.

Animals

Delayed reconstruction following Mohs' chemosurgery for skin cancers of the head and neck.

The case records of 52 patients with 55 cutaneous neoplasms treated by Mohs' chemosurgery and subsequently reconstructed by plastic surgeons were reviewed to determine if delay between resection and reconstruction adversely affected the outcome of reconstruction. Reconstruction was performed from 5 to 61 days after Mohs' chemosurgery for 45 basal cell carcinomas and 10 other cutaneous neoplasms. There were no complications during the interval between resection and reconstruction. Following reconstruction, minor wound complications occurred in 6% of patients; there were no major complications. Microscopic examination of the re-excised wound revealed residual disease in 2 of 45 cases of basal cell carcinoma and 0 of 10 other cutaneous malignancies. Both patients with residual basal cell carcinomas (i.e., false-negative margins after Mohs' surgery) had presented to the Mohs' surgeon with recurrent tumors. During a follow-up period of 3 months to 3 years after complete resection, recurrent tumor developed in 2 of 45 cases of basal cell carcinoma and 3 of 8 cases of squamous cell carcinoma. Delayed reconstruction, usually 5 to 20 days after Mohs' chemosurgery, can be performed without significant morbidity. Re-excision of the Mohs' chemosurgical wound for pathologic examination can detect residual disease and may be especially indicated for large recurrent wounds.

Adult

Pneumococcal polysaccharide vaccine in young adults and older bronchitics: determination of IgG responses by ELISA and the effect of adsorption of serum with non-type-specific cell wall polysaccharide.

Available pneumococcal vaccines provide only limited protection for certain at-risk populations. Fifteen healthy young adults and 11 older chronic bronchitics received 23-valent pneumococcal vaccine. ELISA showed that IgG reactive with capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 8, 14, and 19F increased after vaccination. Bronchitics exhibited lesser responses for four of these serotypes, although differences between the groups were significant only for serotype 3. Adsorption of postvaccination sera with pneumococcal cell wall polysaccharide significantly reduced mean antibody levels in both groups and lowered the proportion of sera that demonstrated type-specific antibody responses. Reactive IgG was largely restricted to the IgG2 subclass. Pneumococcal vaccine may provide suboptimal protection of older adults because antibody responses to some capsular polysaccharides are lower in elderly bronchitics than in healthy young adults. A substantial proportion of measured antibody reflects IgG reactive with cell wall polysaccharides rather than with type-specific, capsular constituents, suggesting that antibody responses in subjects of all ages deserve reappraisal.

Adsorption

Effects of storage time and temperature on measurement of small concentrations of albumin in urine.

Accurate measurement of albumin excretion rates is important in choosing treatment regimens that may reverse early diabetic renal damage. We report here determinations of slight albuminuria ("microalbuminuria") by radioimmunoassay of fresh specimens, frozen aliquots (stored at -20 degrees C for two, eight, and 24 weeks), and refrigerated specimens (stored at 4 degrees C for one, two, and eight weeks). Seven separate analyses were performed on 101 specimens of urine obtained from 37 subjects with insulin-dependent diabetes mellitus and from 10 nondiabetic healthy controls of a similar age. Storage of urine samples at -20 degrees C resulted in significantly lower measurements of microalbuminuria than in fresh urine (ANOVA, corrected for repeated measures: P = 0.01 to 0.0001). In contrast, storage of urine samples at 4 degrees C for as long as eight weeks did not significantly affect urinary albumin results. The pH values of the specimens were minimally altered and were not a likely cause of the decreased albumin values in the frozen specimens. We conclude that urine specimens for microalbuminuria measurements should either be analyzed as fresh specimens or stored at 4 degrees C and assayed as soon as possible.

Adult

Teacher perspectives after implementing a human sexuality education program.

To help teachers enhance the effectiveness of their classroom instruction in human sexuality education, it is necessary to understand their attitudes and concerns about their teaching experiences. Forty-seven sixth grade teachers were surveyed one year after curriculum implementation to examine perceptions of themselves, their students, colleagues, and community. Teachers answered 70% of the knowledge items correctly and indicated slightly liberal orientations. Overall levels of teachers' views generally were positive on scales designed to measure: importance of the items studied, responsibility for student outcomes, three measures of comfort, adequacy of preparation, required changes, ease of use, social supports, and student responses. However, patterns of teacher responses within scales indicated numerous concerns related to curriculum implementation. The concerns and teacher-identified benefits and barriers to teaching the course indicate a focus for continuing education.

Adult

Evaluation of training effects on teacher attitudes and concerns prior to implementing a human sexuality education program.

Teacher changes in knowledge, attitudes, and concerns about teaching a new human sexuality education curriculum due to inservice training were examined; 59 middle school teachers were surveyed before and after one week of training. Significant (p less than .05) increases in knowledge, perceptions of importance of teaching the curriculum, intent to teach, and level of comfort with course content suggest areas of positive learner changes. Effects were not noted for sexual orientation (liberal vs. conservative) or responsibility for student outcomes. Relationships (p less than .05) were noted between comfort, importance, responsibility, and intent to teach with expectations of how students, colleagues, administrators, parents, and community would respond, as well as perceptions of curriculum congruence with teaching style and the adequacy of preparation to teach the curriculum. Few responses were associated with teacher personal characteristics.

Attitude to Health

Zonal distribution of paracetamol glucuronidation in the isolated perfused rat liver.

1. The lobular distribution of paracetamol conjugation was studied using antegrade and retrograde perfusion of isolated rat liver. After addition of 25 mg of paracetamol, recovery of sulphate from antegrade perfusions was greater than from retrograde perfusions indicating periportal predominance of this metabolic pathway. 2. Recovery of sulphate was greater than recovery of glucuronide after addition of 25 mg of paracetamol during both antegrade and retrograde perfusions. Recovery of sulphate was similar after addition of 25 or 100 mg of paracetamol, whereas recovery of the glucuronide was increased at the higher dose, indicating a higher capacity for glucuronidation than for sulphation, but a higher affinity for sulphation. 3. Recovery of glucuronide from antegrade and retrograde perfusions was similar after addition of 25 mg of paracetamol, but was greater from antegrade perfusions after addition of 100 mg. This indicates that drug concentration may be an important determinant of the zonal distribution of drug metabolism. Factors other than localization of drug-metabolizing enzymes, such as competition with other metabolic pathways or availability of cofactors, may also influence the apparent zonal distribution of drug metabolism.

Acetaminophen

Metabolism and excretion of etoposide in isolated, perfused rat liver models.

The clearance of etoposide and formation of etoposide glucuronide have been measured in an isolated, perfused rat liver model to evaluate the effect of impaired hepatic function on etoposide kinetics. Hepatocellular injury was produced by pretreatment of rats with allyl alcohol or carbon tetrachloride; ligation of the bile duct simulated obstructive biliary disease. Etoposide clearance (3.59 +/- 1.06 ml/min) was reduced by both carbon tetrachloride (2.07 +/- 0.64 ml/min; P = 0.05) and allyl alcohol treatment (2.14 +/- 0.62 ml/min; P = 0.05). Biliary obstruction also impaired etoposide clearance but to a lesser extent than hepatocellular injury (2.47 +/- 0.69 ml/min; P = 0.20 versus control). In both hepatocellular and obstructive models, direct biliary etoposide excretion decreased. The metabolic clearance of etoposide to its glucuronide declined by 36% in the hepatotoxin models but was not decreased by biliary obstruction. Following hepatic injury, there is a reduction in the metabolism and excretion of etoposide by the liver. This effect is most marked on biliary drug excretion. Obstructive biliary disease does not significantly alter etoposide glucuronidation. Since most cancer patients have increased bilirubin on the basis of obstructive disease, little or no etoposide dose alteration will be needed. However, in the patient with significant hepatocellular injury, impaired etoposide clearance will be more pronounced, and etoposide dose alterations may be needed.

1-Propanol