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Biomedical subjects

S Stewart

Publications and source records attributed to S Stewart.

At least 253 records · Page 14Linked to original sources

Membrane and junctional properties of the isolated frog lens epithelium.

The isolated frog lens epithelium can be maintained intact in both appearance and electrical properties for more than 24 hours. The mean resting membrane potential was -80 mV and the cells were depolarized by both high potassium and low calcium Ringer's solution in a manner very similar to that of the whole lens. The epithelial cells were found to be well coupled using both electrical and dye-injection techniques. Electrical coupling was measured using separate current-injection and voltage-measuring electrodes and the relationship between the induced voltage and distance from the current-passing electrode could be well fitted by a Bessel Function solution to the cable equation. The values obtained from the fit for the membrane and internal resistances were 1.95 omega m2 and 25 omega m, respectively. Exposure to octanol (500 microM) or low external Ca2+ (less than 1 microM) failed to disrupt significantly the intercellular flow of current. There was evidence to suggest that raised intracellular calcium does, however, uncouple the cells. Dye coupling was investigated by microinjecting Lucifer Yellow CH into single epithelial cells. Diffusion into surrounding cells was rapid and, in control medium, occurred in a radially symmetrical manner. In contrast to the electrical coupling data, dye transfer appeared to be blocked by exposure to 500 microM octanol and was severely restricted on perfusing with low external calcium. Differences between the electrical and dye-coupling experiments indicate either that there are two types of junction within the cell and only the larger type, permeable to Lucifer Yellow, is capable of being uncoupled or that there is only one large type of junction which can be partially closed by uncoupling agents.

Animals↗

Heart-lung transplantation: better use of resources.

PURPOSE: Our goal was to review the experience at Papworth Hospital, Cambridgeshire, England, with combined heart-lung transplantation. PATIENTS AND METHODS: Since April 1984, 31 patients have undergone heart-lung transplantation. Donors and recipients are carefully matched with regards to serology, morphology, and cytomegalovirus compatibility. A pulmonary preservation fluid has been developed that allows distant organ procurement with a single pulmonary artery flush technique. RESULTS: Acute cardiac rejection has not occurred in these patients. Twenty-three patients are alive between two months and over three years following transplantation. The actuarial survival rate at one year is 78 percent, and 70 percent at two years. Three patients died as a result of cytomegalovirus pneumonitis; in two patients, obliterative bronchiolitis developed, and both died, one after an opportunistic infection developed. Three patients died from other causes. The use of transbronchial biopsy of the lung has provided accurate, early, and safe diagnosis of pulmonary rejection. CONCLUSION: Developments in organ preservation and patient management, as well as careful selection of recipients and donors, have led to the effective use of resources and thereby to these good results. In particular, the incidence of obliterative bronchiolitis has been low, which is attributed to the early treatment of pulmonary rejection following diagnosis by transbronchial biopsy.

Adolescent↗

Renal failure following cardiac surgery in a 2.8-kg infant managed with continuous arteriovenous hemofiltration.

Renal failure occurred after repair of transposition of the great vessels with ventricular septal defect in a 2.8-kg infant and was managed successfully with continuous arteriovenous hemofiltration. The infant lost the weight that had been gained as extravascular water, thereby simplifying her fluid, electrolyte, and nutritional management. She ultimately died of cardiac failure.

Acute Kidney Injury↗

Extended aortoplasty to relieve supravalvular aortic stenosis.

An extended aortoplasty was used to relieve severe supravalvular aortic stenosis in 5 patients whose preoperative left ventricular-aortic gradient ranged from 85 to 140 mm Hg (median, 120 mm Hg). The stenotic ring above the commissures was divided in two places by an inverted U incision extending into the right and noncoronary sinuses. A distal vertical incision in the ascending aorta converted this into an inverted Y. The ridge above the left coronary sinus was excised. The aortic incision was repaired with an inverted Y-shaped Dacron gusset. The postoperative gradient ranged from 0 to 30 mm Hg (median, 15 mm Hg). The extended aortoplasty provides excellent relief of supravalvular aortic stenosis and, in addition, restores the aortic root geometry to a much more anatomical configuration than is achieved with the simple patch technique.

Adolescent↗

Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients.

Long-term success of human lung transplantation has been hindered by the lack of an effective and repeatable method of obtained tissue from the transplanted lung for histology. Management of patients is complicated by the difficulty in distinguishing clinically between opportunistic infection of the lung and rejection. As a result, a large number of patients in recent reports develop chronic disabling obliterative bronchiolitis, believed to be the consequence of "chronic" rejection. Twenty-one patients have undergone heart-lung transplantation in our institute since 1984. During fiberoptic bronchoscopy, 43 transbronchial lung biopsies were performed in 15 patients. Twenty episodes of rejection occurred in 11 patients, from whom 16 sets of biopsies showed the typical changes of perivascular infiltrate and mucosal inflammation. Three biopsies were falsely negative; six routine biopsies performed when patients were well were all normal. Overall sensitivity was 84% and specificity 100%. By contrast, the sensitivity of the chest radiograph was only 40%. Opportunistic lung infection in 8 patients was diagnosed by transbronchial biopsy with a sensitivity of 38% and specificity of 100%. In no patient with opportunistic infection were the histologic features of rejection seen. Transbronchial lung biopsy offers a safe and repeatable method to obtain tissue from heart-lung transplants for histology. It has enabled the management of the lung transplant patient to be equivalent to that of the kidney, liver, and heart transplant patient.

Biopsy↗

Efflux of chloride from the rat lens: influence of membrane potential and intracellular acidification.

The efflux of 36C1 from perifused rat lenses consisted of two components: a fast (extracellular) component and a slow (cellular) component. The 36C1 efflux rate constant of the cellular component was 5.7 X 10(-3) min-1. The 36C1- efflux was sensitive to changes in lens potential induced by treatment with high-K+ solutions. The decrease in the 36C1- efflux rate constant caused by high-K+ solutions was consistent with the Goldman model, indicating that, under normal conditions, the majority of the 36C1 efflux is by diffusion. The 36C1- efflux rate constant corresponds to a C1 permeability of 1.3 X 10(8) ms 1. The C1- channel inhibitor anthracene-9-carboxylate (A-9-C), however, caused a relatively small reduction in the efflux rate constant. The anion-exchange inhibitor 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate (SITS) has little effect on the 36C1 efflux under control conditions. Intracellular acidification, induced by pre-treatment with NH1+, leads to a rapid stimulation of 36C1- efflux. This increased 36C1- efflux is blocked by SITS. Thus, it appears that at low intracellular pH (pH), a normally quiescent, SITS-sensitive, anion-exchange mechanism is activated. The possible role of this exchange mechanism in regulating pH, is discussed.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Clinical experience in the management of pulmonary opportunist infection and rejection in recipients of heart-lung transplants.

The main clinical problems that follow heart-lung transplantation are opportunist infections of the lungs and pulmonary rejection. Of 23 patients undergoing heart-lung transplantation, eight had opportunist infections and 12 had at least one episode of pulmonary rejection. Cardiac rejection occurred in only one patient, who did not need treatment. Of the 12 patients who had pulmonary rejection, nine recovered fully after augmented immunosuppression with high dose corticosteroids, although one patient required additional low dose corticosteroids for eight months before making a full recovery. Fatal opportunist lung infection followed treatment for rejection in two patients. One patient developed obliterative bronchiolitis. Of the eight patients with opportunist infections, five had primary cytomegalovirus pneumonitis, acquired from the donor. All three patients treated with acyclovir died, whereas the two treated with hyperimmune globulin and dihydroxy proxymethylguanine recovered fully. Two patients developed Pneumocystis carinii pneumonia, which was treated successfully in one patient with intravenous sulphadimidine and trimethoprim. The other patient died after a further episode of rejection and aspergillus bronchitis. One patient developed a tuberculous empyema. The calculated actuarial survival at one year was 78% and at two years 67.2%. Although it is still in its innovative stage heart-lung transplantation appears to have complications and results similar to those of transplantation of other organs.

Cytomegalovirus Infections↗

Long-term palliation with the classic Blalock-Taussig shunt.

Eighty-five patients received a classic Blalock-Taussig shunt between 1973 and 1986. Their age range was 1 day to 9.3 years and their median age was 4 months. Forty-one percent (35/85) were less than 1 month of age. The basic operative technique was unchanged throughout the time period. The subclavian artery opposite the side of the arch was used in 89% (79/88) of the patients. All anastomoses were done with monofilament suture and there was a tendency toward smaller suture material (7-0) in the latter years. All anastomoses except one were done with an interrupted suture technique. The operative mortality rate was 4.7% (4/85) and was not statistically related to age, diagnosis, or year of operation. Palliation was considered to be satisfactory until either a second shunt or a premature corrective operation were necessary. Seven patients required a second shunt and three, a premature corrective operation. The mean time between the initial shunt and the second procedure, either a second shunt or a corrective operation, was 2.9 years and 2.4 years, respectively. Twenty-five patients have had an elective corrective operation and the mean interval to that procedure was 3.9 years. Two years after the operation, 97% of patients older than 1 month of age at operation remain in well-palliated condition, as do 87% of those less than 1 month of age. At 4 years, 87% of those older than 1 month and 54% of those less than 1 month of age continue to be in well-palliated condition. The classic Blalock-Taussig shunt provides excellent palliation at a low operative mortality for virtually all patients for a minimum of 2 years. It will provide adequate pulmonary blood flow for most patients for an extended period of time beyond 2 years.

Anastomosis, Surgical↗

Membrane and communication properties of tissue cultured human lens epithelial cells.

Explant cultures were established from capsule/epithelium preparations from both normal and cataractous lenses to investigate properties of human lens epithelial cells. The cultured cells were found to have similar membrane potentials to whole human lenses and isolated epithelia, and similar free ionic concentrations of potassium, sodium, and calcium (131 mM, 17 mM and 0.8 microM respectively) to whole human lenses. The free ionic concentrations were measured in both cases using neutral resin-filled electrodes. Cellular communication was investigated using electrical (two internal microelectrodes) and dye injection techniques. The electrical resistance of a confluent cell monolayer was approximately 4 M omega when the voltage measuring and current passing microelectrodes were in neighbouring cells or several cell diameters apart. Additionally, Lucifer Yellow dye injected into one cell spread rapidly over a wide area of cells. The cells thus appear to be extremely well coupled. Electrical communication could be disrupted by internal acidification (following exposure to 100% CO2), exposure to 1 mM octanol and by membrane depolarization. In the latter case the blockade was only partial. All uncoupling methods proved to be reversible. The diffusion of Lucifer Yellow dye was also inhibited by internal acidification and exposure to octanol. The sensitivity of both dye and electrical coupling to internal acidification and exposure to octanol is similar to that observed in hepatocytes and other tissues, whereas the effect on cell communication induced by changing the resting potential appears to occur only in a few cell types such as those of embryonic origin.

Carbon Dioxide↗

Trimethoprim resistance in enterococci: microbiological and biochemical aspects.

Synergy was found between sulphonamide and trimethoprim in ratios 1:1 and 20:1 against both trimethoprim-sensitive enterococci (17 strains) and trimethoprim-resistant enterococci (23 strains). Many of these strains were resistant to kanamycin, tetracycline, streptomycin and/or erythromycin. Resistance to kanamycin, but not to trimethoprim, was clearly associated with the presence of a plasmid of molecular weight 35-45 Md. Elimination of this plasmid in three out of four highly trimethoprim resistant strains brought about loss of resistance to both kanamycin and trimethoprim. Furthermore, it was possible to transfer trimethoprim resistance from three of five highly resistant strains, but not from three strains with low-grade resistance. It is concluded that resistance to trimethoprim in enterococci can be encoded on a plasmid, and that the gene responsible may be on a transposon. No significant differences were found between the specific activities of dihydrofolate reductase from trimethoprim-sensitive and -resistant strains. The enzyme from resistant strains was several orders of magnitude less susceptible to inhibition by trimethoprim than was the enzyme from sensitive strains.

Conjugation, Genetic↗

The Lillehei-Kaster aortic valve prosthesis. Long-term results in 273 patients with 1253 patient-years of follow-up.

The Lillehei-Kaster aortic valve prosthesis was inserted in 313 patients between August 1975 and December 1984. Aortic valve replacement alone was done in 193 patients. Additional procedures included coronary artery bypass grafting in 62 patients, mitral valve replacement in 22, mitral valvuloplasty in 8, and miscellaneous procedures in 28. The 273 patients discharged from the hospital are the basis of this report. They have been followed up for 1253 patient-years. The range of follow-up is 1 to 11 years, and the mean is 4.6 years. The 5-year survival rate for all patients was 68%, whereas for aortic valve replacement alone it was 76%. The incidences of embolism, thrombosis, bleeding, periprosthetic leak, valve infection, and reoperation per 100 patient-years were 1.5, 0.2, 2.0, 0.8, 0.7, and 1.3, respectively. The 5-year rates of freedom from embolism, thrombosis, bleeding, periprosthetic leak, valve infection, reoperation, and any valve-related complication were 94%, 99%, 91%, 96%, 97%, 94%, and 76%, respectively. Four of 16 patients who required reoperation had a properly functioning valve whose effective orifice area was too small for the cardiac output. Each of these valves was of the smaller size. There were no instances of mechanical valve failure. The Lillehei-Kaster aortic valve prosthesis is an excellent aortic valve substitute in the larger sizes. It has an extraordinary record for mechanical durability and an excellent resistance to thromboembolism in patients receiving proper anticoagulation. The incidence of perivalvular leak and infection is similar to that of other prosthetic valves. However, it is not to be recommended in the smaller sizes because of an unfavorable ratio of effective orifice area to tissue diameter.

Adolescent↗

Protective monoclonal antibodies recognize epitopes located on the major outer membrane protein of Chlamydia trachomatis.

A panel of monoclonal antibodies (MAb) was generated against Chlamydia trachomatis serovar B, an etiologic agent of blinding trachoma. The specificities of MAb were determined by dot blot assay by using viable elementary bodies of 13 C. trachomatis serovars and two C. psittaci strains. The dot blot assay was used to identify those antigens that were unique and immunoaccessible on the chlamydial surface. MAb were identified that recognized bi-specific (serovars B and Ba) or subspecies-specific (various B complex serovars) surface-exposed antigenic determinants that were either resistant or sensitive to heat denaturation (56 degrees C, 30 min). All of the MAb recognized the major outer membrane protein as determined by either immunoblotting or radioimmunoprecipitation. MAb specific for immunoaccessible major outer membrane protein epitopes protected mice from toxic death after i.v. injection of B serovar elementary bodies and neutralized the infectivity of the organism for monkey eyes. In contrast, MAb reactive against non-immunoaccessible subspecies- or species-specific major outer membrane protein epitopes or against an immunoaccessible genus-specific epitope located on chlamydial lipopolysaccharide did not protect mice from toxic death or neutralize infectivity of the parasite for monkey eyes. These data suggest that those major outer membrane protein antigenic determinants that are serovar or serogroup specific and are accessible to antibody on the chlamydial cell surface may be useful as a recombinant subunit vaccine for trachoma.

Animals↗

Partial atrioventricular canal defect: the early and late results of operation.

Thirty-five patients underwent repair of a partial atrioventricular canal defect and have been followed for a mean of 8 years. Seventeen patients had either moderate or severe mitral incompetence prior to operation. The mitral valve was treated as a bileaflet structure. The cleft in its anterior leaflet was closed in each patient in whom the valve was incompetent. The septal defect was closed with pericardium, and the coronary sinus was left on the right atrium. Two patients required reoperation, 1 to close a recurrent septal defect and 1 to replace a mitral valve that had been competent for the first several years after the initial repair. All 33 survivors remain in New York Heart Association Functional Class I. Nineteen patients have no mitral incompetence, and the remaining 14 have only mild incompetence. These data demonstrate that excellent late results from repair of partial atrioventricular canal are possible when the mitral valve is managed as a bileaflet structure.

Adolescent↗

The mechanisms and management of noncardiogenic pulmonary edema following cardiopulmonary bypass.

Cardiac surgeons have become more cognizant of the syndrome of noncardiogenic pulmonary edema after cardiopulmonary bypass. Although this syndrome is rare, its occurrence can be catastrophic. This article reviews the current understanding of several factors that have been implicated in the cause of this syndrome and discusses the various options for management of the problem once it has arisen.

Bacterial Infections↗