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Biomedical subjects

J Burke

Publications and source records attributed to J Burke.

At least 127 records · Page 7Linked to original sources

Bronchial artery ligation modifies pulmonary edema after exposure to smoke with acrolein.

Pulmonary edema can follow smoke inhalation and is believed to be due to the multiple chemical toxins in smoke, not the heat. We have developed a synthetic smoke composed of aerosolized charcoal particles to which one toxin at a time can be added to determine whether it produces pulmonary edema. Acrolein, a common component of smoke, when added to the synthetic smoke, produced a delayed-onset pulmonary edema in dogs in which the extravascular lung water (EVLW) as detected by a double-indicator technique began to rise after 42 +/- 2 (SE) min from 148 +/- 16 to 376 +/- 60 ml at 165 min after smoke exposure. The resulting pulmonary edema was widespread macroscopically but appeared focal microscopically with fibrin deposits in alveoli adjacent to small bronchi and bronchioles. Bronchial vessels were markedly dilated and congested. Monastral blue B when injected intravenously leaked into the walls of the bronchial vessels down to the region of the small bronchioles (less than or equal to 0.5 mm ID) of acrolein-smoke-exposed dogs but not into the pulmonary vessels. Furthermore, ligation of the bronchial arteries delayed the onset of pulmonary edema (87 +/- 3 min, P less than 0.05) and lessened the magnitude (232 +/- 30 ml, P less than 0.05) at 166 +/- 3 min after acrolein-smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrolein↗

Can UK-14, 304-18 lower IOP in rabbits by a peripheral mechanism?

Unilateral topical administration of alpha 2 adrenoceptor agonists lowers intraocular pressure (IOP) bilaterally in laboratory animals and man. Investigators have suggested that this decrease in IOP is mediated, in part, by alpha 2 adrenoceptors in the central nervous system (CNS). In the present study, the hypotensive activity of the alpha 2 agonist, UK-14,304-18 (UK), was evaluated following topical and intracameral administration. The unilateral administration of a relatively selective alpha 2 adrenoceptor agonist, UK (50 micrograms), lowered IOP bilaterally when applied topically to the eyes of rabbits. Intracamerally administered UK (0.05-50 ug) lowered IOP unilaterally in a dose-related manner with minimal pupillary and cardiovascular changes. The ocular hypotensive action of UK administered intracamerally was absent in rabbits that had been surgically sympathectomized. While these data demonstrate that UK can lower IOP in the rabbit independent of alpha 2 adrenoceptor stimulation in the CNS and other systemic sites, the expression of this response is dependent upon the presence of intact sympathetic innervation.

Administration, Topical↗

Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40.

The anticoagulant action of heparin is mediated through antithrombin III, and the postoperative decrease in the plasma concentration of antithrombin III may contribute to the relative ineffectiveness of prophylaxis with low-dose heparin in preventing venous thrombosis after total hip arthroplasty. We conducted a prospective, randomized trial to compare the effectiveness of a regimen of antithrombin III, given intravenously once daily, and low-dose heparin with a regimen of dextran 40, given intravenously, in preventing venographically documented venous thrombosis after total hip arthroplasty. The results demonstrated an incidence of venous thrombosis of 4.9 per cent in patients who received antithrombin III and heparin; this was significantly lower than the incidence (28.6 per cent) in patients who received dextran 40 (p less than 0.005). Venous thrombosis occurred only in patients who had total hip arthroplasty with a cemented prosthesis (fourteen of fifty-seven patients, or 24.6 per cent); none of the twenty-six patients in whom a non-cemented prosthesis was used had venous thrombosis (p less than 0.01). Of the patients in whom a cemented prosthesis had been inserted, the incidence of venous thrombosis was lower in those who were treated with antithrombin III and heparin (7.4 per cent) than in those who were treated with dextran 40 (40 per cent) (p less than 0.005). Postoperative levels of antithrombin III were maintained at more than 90 per cent of the baseline level in patients who received it; this was significantly higher than in patients who received dextran 40.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

Interference of eicosapentaenoic and docosahexaenoic acids with arachidonate-and U46619-induced platelet activation and desensitization.

In previous studies we showed that arachidonate (AA) and the cyclic endoperoxide/thromboxane (Tx) A2 mimic U46619-induced auto- and cross-desensitization of human platelets to either agonist. The desensitizing effect of U46619 is direct, whereas that of AA is mediated by a cyclooxygenase-dependent metabolite. Desensitization by AA and U46619 is suppressed by antagonists of the endoperoxide/Tx receptor sites. In the present investigation we demonstrated that eicosapentaenoic (EPA) and docosahexaenoic acid (DCHA) the major polyunsaturated fatty acids of fish oil suppressed TxB2 formation and prevented platelet activation by AA and U46619. This inhibition required the presence of EPA or DCHA, since platelets pre-treated with these fatty acids and washed before testing responded as controls to the stimulating agents. At 0.1 and 0.3 mM respectively, DCHA and EPA behaved as reversible inhibitors of cyclooxygenase or Tx synthetase (inhibition of the effects of AA) and as endoperoxides/TxA2 receptor antagonist (inhibition of the effects of U46619). Co-exposure of DCHA (0.1 mM) with AA or U46619 prevents auto- and cross-desensitization to AA and U46619. Platelets exposed to 0.3 mM DCHA and washed became refractory to stimulation by AA, but responded as controls to U46619. EPA (0.3 mM) was fully removed from platelets, which responded to AA and to U46619. EPA and DCHA antagonize endoperoxide/TxA2 directly, and thus prevent the stimulation-dependent desensitization, and additionally, inhibit the cyclooxygenase activity required for desensitization.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

The Composite International Diagnostic Interview. An epidemiologic Instrument suitable for use in conjunction with different diagnostic systems and in different cultures.

The Composite International Diagnostic Interview (CIDI), written at the request of the World Health Organization/US Alcohol, Drug Abuse, and Mental Health Administration Task Force on Psychiatric Assessment Instruments, combines questions from the Diagnostic Interview Schedule with questions designed to elicit Present State Examination items. It is fully structured to allow administration by lay interviewers and scoring of diagnoses by computer. A special Substance Abuse Module covers tobacco, alcohol, and other drug abuse in considerable detail, allowing the assessment of the quality and severity of dependence and its course. This article describes the design and development of the CIDI and the current field testing of a slightly reduced "core" version. The field test is being conducted in 19 centers around the world to assess the interviews' reliability and its acceptability to clinicians and the general populace in different cultures and to provide data on which to base revisions that may be found necessary. In addition, questions to assess International Classification of Diseases, ninth revision, and the revised DSM-III diagnoses are being written. If all goes well, the CIDI will allow investigators reliably to assess mental disorders according to the most widely accepted nomenclatures in many different populations and cultures.

Cross-Cultural Comparison↗

Four mating-type genes control sexual differentiation in the fission yeast.

The mating-type region of fission yeast consists of three components, mat1, mat2-P and mat3-M, each separated by 15 kb. Cell-type is determined by the alternate allele present at mat1, either P in an h+ or M in an h- cell. mat2-P and mat3-M serve as donors of information that is transposed to mat1 during a switch of mating type. We have determined the nucleotide sequence of each component of mat. The P and M specific regions are 1104 and 1128 bp, respectively, and bounded by sequences common to each mating-type cassette (H1; 59 bp and H2; 135 bp). A third sequence is present at mat2-P and mat3-M but absent at mat1 (H3; 57 bp), and may be involved in transcriptional repression of these cassettes. mat1-P and mat1-M each encode two genes (Pc; 118 amino acids, Pi; 159 amino acids, Mc; 181 amino acids and Mi; 42 amino acids). Introduction of opal or frame-shift mutations into the open-reading-frame of each gene revealed that Pc and Mc are necessary and sufficient for mating and confer an h+ or h- mating type respectively. All four genes are required for meiotic competence in an h+/h- diploid. The transcription of each mat gene is strongly influenced by nutritional conditions and full induction was observed only in nitrogen-free medium. The predicted product of the Pi gene contains a region of homology with the homeobox sequence, suggesting that this gene encodes a DNA binding protein that directly regulates the expression of other genes.

Amino Acid Sequence↗

Comparison of high performance liquid chromatographic and microbiological methods for determination of itraconazole.

A reversed-phase high-performance liquid chromatographic (HPLC) method, with internal standard quantification, is described for the analysis of itraconazole in human serum. No interference was encountered from over 60 drugs tested. The standard curve was linear from 10 to 10,000 micrograms/l. The detection limit of the method was 10 micrograms/l, with coefficients of variation from 2.2 to 7.8% over a range of itraconazole concentrations from 20 to 1600 micrograms/l. An agar diffusion method is also described with a lowest reproducible limit of 100 micrograms/l. This method had coefficients of variation from 11.0 to 17.1% over a range of itraconazole concentrations from 100 to 1600 micrograms/l. Comparison of the methods showed that HPLC gave much lower values of itraconazole concentrations in patient serum samples than did the microbiological method.

Antifungal Agents↗

Artificial dermis for major burns. A multi-center randomized clinical trial.

This communication presents an 11-center prospective randomized trial using the artificial dermis invented by Burke and Yannas. Patients with life-threatening burns who underwent primary excision and grafting within 7 days of injury had comparable sites randomized to receive either the artificial dermis (study site) or the investigator's usual skin grafting material (control site). Control materials were autograft, allograft, xenograft, or a synthetic dressing. Epidermal grafts were applied to the study site during a second operation, and surviving patients were followed for 1 year after grafting. One hundred thirty-nine sites on 106 patients were studied. Mean burn size was 46.5 +/- 15% mean total body surface (TBSA). Overall mortality was 13%, and mean hospital stay was 68 +/- 45 days. Median artificial dermis take was 80% compared with 95% for all comparative sites, but the take was equivalent to that of all nonautograft control materials. Results with the artificial dermis improved slightly as the investigators became more familiar with the material. Donor site thickness for the study site averaged .006'' +/- .002'' compared to .013'' +/- .018'' for control (p less than .0001) and the epidermal donor site healed an average of 4 days sooner (10 +/- 6 vs. 14 +/- 8 days) (p less than .0001). As the wounds matured during the first year, both patients and surgeons felt that both sites became more comparable in appearance and function. At the completion of the study, there was less hypertrophic scarring of the artificial dermis, and more patients preferred the artificial dermis to the control graft. Artificial dermis with an epidermal graft provides a permanent cover that is at least as satisfactory as currently available skin grafting techniques, and uses donor grafts that are thinner and donor sites that heal faster.

Adolescent↗

Effect of helicopter transport of trauma victims on survival in an urban trauma center.

This paper reports a retrospective analysis of patients with serious yet substantially survivable injuries represented by ISS scores from 20 to 39 and whether or not survival was influenced by the use of helicopters. A review of 606 of these patients with blunt trauma was performed for the period from 1983 through 1986. When the group was evaluated there were 451 patients in the ISS cohort of 20-29 and 155 in the 30-39 group. The mean age was 30.5 years and 76% were males. A total of 259 patients were transported by ambulance and 347 by helicopter. Characteristics of the two groups were similar. The mean TS was 12.7 for ambulance and 12.1 for helicopter patients. Mean GCS was 10.4 in the ambulance group and 9.6 for helicopter patients. Overall the mortality for ambulance transported patients was 13% compared to 18% for the helicopter group. We conclude that there is no survival advantage in the helicopter transported group in an urban area with a sophisticated prehospital care system. Patients of rural origin deserve further study.

Adult↗

A Mup promoter-thymidine kinase reporter gene shows relaxed tissue-specific expression and confers male sterility upon transgenic mice.

A hybrid gene was made by fusing the 2.2-kilobase 5' promoter region of a mouse group 1 major urinary protein (Mup) gene to the coding region of the herpes simplex virus type 1 thymidine kinase gene (HSV tk) and introduced into the genomes of mice by microinjection. Transgenic G0 males were sterile, or when fertile did not transmit the foreign gene, and the transgenic male descendants of G0 females were also sterile. Seven "lines" were established by breeding from G0 females and their transgenic female descendants. Six lines expressed HSV thymidine kinase activity in the liver, and activity correlated perfectly with the presence of HSV tk RNA. In three of four lines examined, expression was lower in female than in male liver, and in these lines the same sex difference was observed in the rate of run-on transcription of the foreign genes in liver nuclei. When females of one of the sexually dimorphic lines were treated with testosterone, the levels of HSV tk RNA and thymidine kinase activity were increased, although not to male levels. In these aspects of liver expression, and also in a lack of expression in seven other tissues, the hybrid gene exhibits many of the characteristics of an endogenous group 1 Mup gene. However, the gene was also expressed (at high levels) in the preputial gland and testis, two tissues in which Mup genes are not expressed. The gene, when introduced into five of the seven lines, carried a copy of the Escherichia coli supF gene attached beyond the 3' end of the HSV tk gene, but this did not affect the overall expression pattern. All of the lines were male sterile and expressed HSV thymidine kinase in the testis, but one line showed no activity in the liver, and another showed none in the preputial gland. Testicular expression is therefore the likely cause of sterility. Data are described which suggest that the causes of misexpression in the preputial gland and testis are different. Since expression in each tissue occurred in several lines, the structure of the hybrid gene must be responsible in each case. Five intensively studied lines showed at least four consistently different patterns of relative expression in preputial gland, testis, male liver, and female liver. These differences do not correlate in any way with the copy number of the foreign gene in the different lines and must be due to some other aspect of line specific integration.

Animals↗

Synthetic smoke with acrolein but not HCl produces pulmonary edema.

The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time. We delivered synthetic smoke to dogs for 10 min and monitored extravascular lung water (EVLW) accumulation thereafter with a double-indicator thermodilution technique. Final EVLW correlated highly with gravimetric values (r = 0.93, P less than 0.01). HCl in concentrations of 0.1-6 N when added to heated carbon (120 degrees C) and cooled to 39 degrees C produced airway damage but no pulmonary edema. Acrolein, in contrast, produced airway damage but also pulmonary edema, whereas capillary wedge pressures remained stable. Low-dose acrolein smoke (less than 200 ppm) produced edema in two of five animals with a 2- to 4-h delay. Intermediate-dose acrolein smoke (200-300 ppm) always produced edema at an average of 147 +/- 57 min after smoke, whereas high-dose acrolein (greater than 300 ppm) produced edema at 65 +/- 16 min after smoke. Thus acrolein but not HCl, when presented as a synthetic smoke, produced a delayed-onset, noncardiogenic, and peribronchiolar edema in a roughly dose-dependent fashion.

Acrolein↗

Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase.

The intron/exon organization of the human gene for glycogen phosphorylase has been determined. The segments of the polypeptide chain that corresponds to the 19 exons of the gene are examined for relationships between the three-dimensional structure to the protein and gene structure. Only weak correlations are observed between domains of phosphorylase and exons. The nucleotide binding domains that are found in phosphorylase and other glycolytic enzymes are examined for relationships between exons of the genes and structures of the domains. When mapped to the three-dimensional structures, the intron/exon boundaries are shown to be widely distributed in this family of protein domains.

Amino Acid Sequence↗

Granulomatous pseudotumors in total joint replacement.

Fourteen patients (15 joints) developed a foreign body reaction to methylmethacrylate, polyethylene, or metal adjacent to a total joint implant, a condition we would like to term granulomatous pseudotumors. There were eight male and six female patients. Their average age was 61 years. The hip was involved in 14 joints (femoral component 11 times, acetabulum 7, and greater trochanter once). One patient presented with granulomatous pseudotumors of the knee. The principal findings included increasing pain and radiographic evidence of loosening occurring on average 2.7 years following the implant. This was followed by a characteristic and gradually developing radiographic pattern of discrete rounded lucencies. These developed into large ovoid lytic areas, destroying both methylmethacrylate and bone. Histologically, the appearances were characterized by histiocytic infiltration and the presence of multiple foreign body giant cells. Foreign material was identified in 9 of 11 cases. The pathogenesis is unknown but appears related to micromovement or loosening of the implant.

Female↗

Phosphorylcholine-bearing antigens in filarial nematode parasites: analysis of somatic extracts, in-vitro secretions and infection sera from Brugia malayi and B. pahangi.

A set of cross-reactive antigens is described which are present in somatic extracts and in-vitro secretions of the filarial nematodes Brugia pahangi and B. malayi. A monoclonal antibody reactive with a repeating epitope on these molecules readily detects circulating antigen in the serum of animals infected with lymphatic filariae, using either an immunoradiometric assay or enzyme-linked immunosorbent assay (ELISA). This epitope has the immunological reactivity and chemical characteristics of the phosphorylcholine (PC) hapten. The anti-PC monoclonal has been used to define the antigens bearing this epitope, and in chromatographic studies on material from extracts of Brugia adult worms, a heterogeneous profile of PC-positive molecules are found. In sera from Brugia-infected jirds, an antigen with a native molecular weight of approximately 500,000 is observed, which displays limited sensitivity to protease degradation. However, denatured samples on Western blots show a major parasite circulating antigen of Mr 90,000. The detection of this antigen in the presence of excess host antibody is also demonstrated, taking advantage of the stability of the target epitope to a range of treatments designed to dissociate and eliminate immune complexes.

Animals↗