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Biomedical subjects

B J Harmon

Publications and source records attributed to B J Harmon.

14 recordsLinked to original sources

Prevention of disseminated Mycobacterium avium complex infection with reduced dose clarithromycin in patients with advanced HIV disease.

OBJECTIVE: To evaluate the ability of once daily reduced dose clarithromycin to prevent disseminated Mycobacterium avium complex (dMAC) infection in patients with advanced HIV disease. DESIGN: Non-randomized, retrospective study. SETTING: Outpatient clinic of an urban university-affiliated municipal hospital. PATIENTS: A group of 192 HIV-infected patients with a CD4 count < 100 x 10(6) cells/l who were followed for at least 90 days during a 6-year period (1991-1996) before the use of protease inhibitors. INTERVENTIONS: Clarithromycin 500 mg orally once daily (n = 84), rifabutin 300 mg orally once daily (n = 47) or no prophylaxis (n = 61). MAIN OUTCOME MEASURES: Positive blood culture for M. avium complex (MAC), time to development of dMAC, and time to death. RESULTS: When compared with no prophylaxis or rifabutin, the incidence of dMAC and time to development of dMAC were improved among those patients receiving clarithromycin (P < 0.001). Prolonged survival was associated with both clarithromycin and rifabutin use when compared with no prophylaxis (P < 0.002). In patients who failed prophylaxis, resistance to clarithromycin and rifabutin was observed. CONCLUSIONS: In the era prior to protease inhibitor use, once daily clarithromycin at a dose of 500 mg was associated with a reduction in the incidence of dMAC, appeared to be superior to rifabutin, and was associated with prolonged survival in patients with advanced HIV disease.

AIDS-Related Opportunistic Infections↗

Indomethacin-associated bowel perforations: a study of possible risk factors.

BACKGROUND: The association between indomethacin administration and bowel perforation in premature infants is well known. The goal of this study was to examine possible risk factors for this complication. METHODS: Fifteen cases of indomethacin-associated bowel perforation occurred from 1993 to 1996. All had a birth weight < or = 1,100 g. These patients were compared with a control group of 51 infants who were cared for contemporaneously, had birth weights < or = 1,100 g and received indomethacin. RESULTS: Survival rate in the control group was 96%. For the group with perforations, it was 53%. Two types of perforation were seen, one occurring in the setting of necrotizing enterocolitis, and the other, a simple perforation in an otherwise normal-appearing bowel. For the latter group, the survival rate was 86%, and, when possible, primary repair was the procedure of choice. Use of aminophylline was greater in the control group. Otherwise, there were no significant differences between the two groups in any of the variables observed. However, when the simple perforations were observed separately, these patients had, on average, received indomethacin at a younger age than the controls (P < .05). The clustering of perforation cases from May through August suggests an infectious agent might be involved. CONCLUSIONS: Earlier administration of indomethacin correlates with an increased risk of focal perforation. It is unclear, however, whether the risk factor is the drug itself or the earlier need for it. Aminophylline use was somewhat more in the control group, but this is not likely to reflect a protective role for that drug. The possible involvement of an infectious agent should be considered.

Anti-Inflammatory Agents, Non-Steroidal↗

Childhood sledding injuries.

Sledding is only rarely thought of as a potentially dangerous childhood activity. However, serious injuries and occasional deaths do occur. A review of patients 18 years old and younger admitted to a pediatric trauma center following a sledding accident from 1991 to 1997 was conducted. By design this study was expected to identify the most seriously injured patients. Twenty-five patients were identified, all but four younger than 13. Seventeen were boys. The mechanisms of injury were: collision with stationary object, 15; sled-sled collision, 1; struck by sled, 2; going off jump, 3; foot caught under sled or on ground, 3; fall off sled being towed by snowmobile, 1. The average pediatric trauma score was 10.5, and the average injury severity score 10.6. There were no deaths. The injuries were: head, 11; long bone/extremity, all lower, 10; abdomen, 5; chest, 1; facial, 2; spinal, 1. Five patients sustained multiple injuries. A surprisingly high number, 5, had pre-existing neurological conditions that could have played a contributory role in the accident. Sledding is predominantly an activity of children, and occasional serious injuries occur. Most are preventable. Obeying the simple caveat that sledding should only be done in clear areas away from stationary objects would eliminate the great majority of serious injuries.

Adolescent↗

Snowboarding injuries in children and adolescents.

To study snowboarding injuries in children and adolescents, a 6-year retrospective study was conducted of patients 18 years old and younger admitted to a pediatric trauma center after snowboarding accidents. The study was designed to identify the most severely injured patients. Comparison was made to data from a recent comparable study of skiing injuries. Twenty-seven patients were identified, all but one male and none under 10 years old. Nineteen were injured in a fall, 6 collided with a stationary object, one collided with a skier, and in one case the mechanism of injury was unclear. The average pediatric trauma score was 10.5, and the average injury severity score 10.2. Most of the 12 head injuries were minor. Most extremity fractures were to the upper extremity. There were two lumbar vertebral burst fractures, suggesting that the sport may predispose to this injury. There were no deaths. When compared with skiing, in snowboarding the overall severity of injury is lower, collision is a less common mechanism of injury and results in less serious injury, head injuries are less severe, the relative frequency of upper extremity fracture is higher, abdominal injuries are caused by falls rather than collisions, and facial injuries are less common. These differences are predictable on the basis of differences in the equipment. However, it is too early to say that snowboarding has less potential for life-threatening injury than skiing. Expected changes in the mix of participants, with an increase in the average skill level over time, may well result in different patterns, mechanisms, and severity of injury.

Adolescent↗

Rapid monitoring of site-specific glycosylation microheterogeneity of recombinant human interferon-gamma.

An analytical system is presented for rapid assessment of site-specific microheterogeneity of the two potential N-linked glycosylation sites of recombinant human interferon-gamma (IFN-gamma) derived from Chinese hamster ovary cell culture. The target protein is first purified from culture supernatant by immunoaffinity chromatography, and the acidic eluent is neutralized via an in-line mixing tee. On-line proteolysis is rapidly performed by an immobilized trypsin cartridge, and reversed-phase chromatography isolates the two pools of glycopeptides representing the potential glycosylation sites. Following off-line analysis by matrix-assisted laser-desorption ionization/time-of-flight (MALDI/TOF) mass spectrometry, observed mass shifts of glycopeptides relative to the known masses of their amino acid portions are correlated to site-specific oligosaccharide structures. Desialylation of glycopeptides by sialidase treatment on the MALDI sample plate allows for quantitative estimations of asialoglycan structures by MALDI/TOF. This methodology permits glycoprotein microheterogeneity to be evaluated in a time frame of approximately 2 h, utilizing as little as 0.5 microgram (25 pmol) of product. Results of monitoring a batch culture are presented as well as analysis of a culture containing deoxymannojirimycin, an inhibitor of glycoprotein processing.

1-Deoxynojirimycin↗

Dynamic modeling of electrophoretically mediated microanalysis.

A dynamic model is presented for simulation of reaction-based chemical analysis of enzymes and substrates in capillary electrophoretic systems by the methodology of electrophoretically mediated microanalysis (EMMA). The mathematical model utilizes mass balance expressions describing the time-dependent effects of electromigration, chemical reaction, and diffusional band broadening upon the concentration profiles of the various reagent and product species. The model is implemented in an iterative computer program in which the capillary is segmented into arrays of bins storing the concentration profiles of each of the chemical species. During each time increment, the effects of electrophoresis, reaction kinetics, and diffusion are calculated, and the concentrations stored in the arrays are updated. The flexibility of the model to accommodate various initial capillary conditions, sample introduction methods, and voltage programming allows diverse EMMA analyses to be simulated. The simulated results are shown to be in good qualitative agreement with experimental data for zonal injection and moving boundary EMMA determinations of leucine aminopeptidase as well as an EMMA analysis of ethanol.

Computer Simulation↗

Moving boundary electrophoretically mediated microanalysis.

Moving boundary sample introduction is described as an alternative to zonal injection methods for the electrophoretically mediated microanalysis (EMMA) of leucine aminopeptidase (LAP). The capillary was initially filled with the analyte solution while the faster-migrating substrate, L-leucine-p-nitroanilide, was maintained in the inlet reservoir. Upon application of an electric field, electrophoretic merging of the reagents proceeded, and the detectable reaction product, p-nitroaniline, was transported to the detector. The area, maximum height, inclining slope, and declining slope of the resulting triangular product profile were each directly proportional to the activity of LAP, and the observed migration times of the product profile features defined the volume and time of the incubation. The moving boundary technique offered more than an order of magnitude greater concentration sensitivity than the zonal injection EMMA method. This heightened sensitivity facilitated rapid analysis as the use of elevated electric field strenghts and short capillaries allowed for a 24-s kinetic determination of LAP.

Animals↗

Skiing injuries in children and adolescents.

OBJECTIVE: A study of major skiing injuries in children and adolescents. DESIGN AND MATERIALS AND METHODS: A 5-year retrospective study of patients 18 years old and under admitted to a pediatric trauma center after skiing accidents. A follow-up questionnaire was used to obtain additional information. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients, of which 34 were male. Age range was 5 to 18 years. Fifty-eight percent of the accidents were collisions with stationary objects. Alcohol and drugs were not implicated. Helmet use was negligible. Head injuries, especially skull fractures, were very common (27), followed by extremity fractures (13), facial fractures (8), and abdominal (6), thoracic (5), and spinal injuries (2). One third had multiple injuries. The average cost was $22,000. There were no deaths, but 26% had long-term sequelae. The skill breakdown was 26% beginner, 29% intermediate, 45% advanced. Willingness to accept responsibility for the accident correlated inversely with skill level. CONCLUSIONS: Prevention efforts must target excessive speed and loss of control. Beginners must be well supervised on appropriate terrain. The frequency of skull fractures suggests that helmet use should be encouraged for young recreational skiers.

Adolescent↗

Selectivity in electrophoretically mediated microanalysis by control of product detection time.

Differential electrophoretic mobility between an analyte and its product offers electrophoretically mediated microanalysis (EMMA) a unique capability to selectively control the detection time of the product of a reaction-based chemical analysis. If an analyte and its product differ in migration velocity under the influence of an applied electric field, the apparent velocity and, consequently, the detection time of the product are dependent upon the relative amounts of time the product effectively traverses the capillary with the respective mobilities of the analyte and the product. Consequently, by controlling when the analytical reaction is allowed to occur, the detection time of the reaction product can be selectively maneuvered within a time window defined by the mobilities of the analyte and the product. This paper describes the use of this technique to manipulate the detection time of product profiles independently of nonreacting matrix interferants for the determination of both enzymes and substrates by EMMA. Furthermore, the ability to manipulate product detection times allows for simultaneous EMMA determinations of multiple enzymes or substrates.

Alcohol Dehydrogenase↗

Electrophoretically mediated microanalysis of calcium.

Electrophoretically mediated microanalysis (EMMA) was used for the determination of calcium. The faster analyte zone containing the calcium was injected spatially behind a slower zone of o-cresolphthalein complexone in a capillary electrophoresis based system. Upon application of the electric field the calcium zone was electrophoretically mixed with the reagent and product was formed. The bulk electroosmotic flow carried the product to the detector where the absorbance of the resulting complex at 575 nm was measured. Quantitation using an internal standard yielded a linear response with an R.S.D. of 8.1%. An inter-method comparison was performed with the standard bulk method and yielded results that did not significantly differ. The advantages of EMMA with respect to traditional methods were addressed.

Calcium↗

Electrophoretically mediated microanalysis of ethanol.

Capillary electrophoresis was used to determine ethanol by the methodology of electrophoretically mediated microanalysis (EMMA). In EMMA, spatially distinct analyte and analytical reagent zones of differing electrophoretic mobility are merged under the influence of an electric field, and the resulting product is transported to the detector. The enzymatic oxidation of ethanol to acetaldehyde by alcohol dehydrogenase was utilized, and the concurrent reduction of NAD+ to NADH was monitored at 340 nm as a measure of the quantity of ethanol injected. Quantitation using an internal standard and normalization for peak migration time yielded a R.S.D. of 2.7%, and the linear range extended to that quantity of ethanol which could be reacted prior to passing by the detection window. Comparison of the EMMA technique to the Sigma spectrophotometric procedure revealed that the two methods do not yield significantly different values for the determination of ethanol. The EMMA method offered the advantages of electrophoretic mixing and miniaturization.

Acetaldehyde↗

Mathematical treatment of electrophoretically mediated microanalysis.

A new concept in reaction-based chemical analysis is introduced and theoretically described. By utilization of the variability in electrophoretic mobilities among charged species, spatially distinct zones of chemical reagents can be electrophoretically merged under the influence of an applied electric field. Electrophoretically mediated microanalysis (EMMA) exploits this phenomenon as a basis for chemical analysis utilizing capillary electrophoretic systems. EMMA is described in terms of the four stages required for reaction-based analysis: (1) analyte and analytical reagent metering; (2) initiation of reaction; (3) control of reaction conditions and product formation; (4) detection of species whose production or depletion is indicative of the concentration or quantity of the analyte of interest. The method is illustrated by the enzymatic oxidation of ethanol to acetaldehyde by alcohol dehydrogenase with the concurrent reduction of NAD+ to NADH monitored at 340 nm. Experimental results for both substrate and enzyme determinations are shown to agree with the presented theory.

Electrophoresis↗