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Biomedical subjects

S Stewart

Publications and source records attributed to S Stewart.

At least 271 records · Page 15Linked to original sources

Membrane conductance and potassium permeability of the rat lens.

The membrane potential, electrical impedance and 86Rb+ efflux rate constants were measured in the rat lens perifused at 35 degrees C. The membrane conductance was obtained from the difference between the magnitude of the impedance at low (less than 0.1 Hz) and high (greater than 100 Hz) frequencies. Values of the rubidium permeability coefficients (PRb) were obtained from the rate constant and potential data. The values for the membrane potential and conductance in control solution (5 mM potassium) were -69.6 mV and 5.5 X 10(-4) S respectively, while the computed permeability was 2.9 X 10(-8) m.s-1. On perifusing with 35 mM potassium, the membrane depolarized by 25 mV and the conductance and rubidium permeability increased considerably. These increases could be blocked by quinine (0.3 mM), tetraethylammonium (30 mM) and 4-aminopyridine (10 mM). The latter agent was more effective at alkaline pH (8.3). It is suggested that there are voltage-gated potassium channels that are inhibited by these three agents. After the initial depolarization in high potassium, there was little further change in membrane potential with any of the inhibitors. All three agents, however, produced a marked depolarization when applied in control solution. This was accompanied by a decrease in conductance and rubidium permeability, suggesting that, in the rat lens, some voltage-gated potassium channels are activated at the resting potential.

4-Aminopyridine↗

Tear and serum antibody response to Chlamydia trachomatis antigens during acute chlamydial conjunctivitis in monkeys as determined by immunoblotting.

In this study, we examined the temporal antibody response by immunoblotting analysis in tears and sera of three cynomolgus monkeys (Macaca fasicularis) with primary acute Chlamydia trachomatis serovar B conjunctivitis. The objective was to identify chlamydial antigens stimulating antibody during the host responses in the course of this self-limiting infection with the rationale that they may be protective antigens. The major outer membrane protein (MOMP), lipopolysaccharide (LPS), and polypeptides of 60 and 68 kilodaltons (kDa) were the predominant antigens recognized by immunoglobulin A (IgA) in monkey tears. Tear IgA antibody specific for the MOMP was first detected 14 days postinfection, whereas tear IgA reactive with LPS or the 68- and 60-kDa polypeptides was first detectable on day 21. Tear IgA antibodies specific for each of these antigens persisted in tears through day 56, 4 weeks after both peak clinical disease and recovery of the organism from the conjunctivae. In contrast, tear IgG antibodies peaked at approximately 28 days postinfection, the time of maximal inflammatory response. The IgG response in monkey sera was similar to that observed for tear antibodies, in that the MOMP, 60-, and 68-kDa polypeptides were the primary immunogens. The exception was that IgG antibody against these antigens was detected 1 week later than that observed for tear IgA antibodies. Of three monkeys that responded with tear IgA antibody against LPS, one did not have detectable serum IgG LPS antibody. The specificity of the tear IgA antibody response of monkeys was determined by immunoblotting nine other C. trachomatis serovars in addition to the homologous B serovar. The tear IgA response to the MOMP was predominantly B complex subspecies-specific (serovars B, Ba, D, and E), whereas the response to chlamydial LPS was found to be species-specific. The significance of these observations in relation to previous vaccine studies in nonhuman primates is discussed.

Animals↗

The low-molecular-mass, cysteine-rich outer membrane protein of Chlamydia trachomatis possesses both biovar- and species-specific epitopes.

We isolated, by hydroxylapatite high-performance liquid chromatography, 14- and 15-kilodalton (kDa), cysteine-rich outer membrane proteins from Chlamydia trachomatis TW-5/OT (serovar B) and LGV-434 (serovar L2), respectively. Monoclonal antibodies (MAbs) were generated against the purified proteins, and their specificities were determined by immunoblotting. MAb B-14k recognized an epitope located on the 14-kDa cysteine-rich protein of the TW-5/OT strain and was immunoreactive with a comigrating 14-kDa protein that was common to all trachoma biovar strains, but it did not react with the 15-kDa, cysteine-rich protein of LGV biovar strains. In contrast, MAb L2-15k, which recognized an epitope located on the 15-kDa protein of the LGV-434 strain, reacted with the 15- and 14-kDa, cysteine-rich proteins of both LGV and trachoma biovar strains, but did not react with related proteins of two Chlamydia psittaci strains. Thus, the low-molecular-mass, cysteine-rich outer membrane proteins of C. trachomatis possess antigenic determinants that are both biovar and species specific. Neither MAbB-14k nor MAb L2-15k was reactive by dot-blot assay when viable chlamydiae were used as test antigens, indicating that the cysteine-rich proteins are not accessible to antibody on the native chlamydial cell surface.

Antibodies, Bacterial↗

Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies.

Twenty-four patients with persistent epithelial ovarian cancer after chemotherapy with or without external beam irradiation, were treated with intraperitoneally administered 131I-labeled monoclonal antibodies HMFG1, HMFG2, AUA1, H17E2, directed against tumor-associated antigens. Acute side effects were mild abdominal pain, pyrexia, diarrhea, and moderate reversible pancytopenia. One patient developed a subphrenic abscess requiring surgical drainage. Eight patients with large volume disease, ie, greater than 2 cm tumor diameter, did not respond to antibody-guided irradiation and died of progressive disease within 9 months of treatment. Sixteen patients had small-volume (less than 2 cm) disease at the time of treatment with radiolabeled antibody. Seven patients failed to respond, and of nine initial responders, four patients remain alive and free from disease 6 months to 3 years from treatment. Analysis of the data on relapse indicated that doses greater than 140 mCi were more effective than lower doses. We conclude that the intraperitoneal administration of 140 mCi or more of 131I-labeled tumor-associated monoclonal antibodies represents a new and potentially effective form of therapy for patients with small-volume stage III ovarian cancer.

Antibodies, Monoclonal↗

The long-term risk of warfarin sodium therapy and the incidence of thromboembolism in children after prosthetic cardiac valve replacement.

Thirty children less than 18 years of age underwent cardiac valve replacement with a prosthetic valve between 1967 and 1984 and have been followed up for a mean of 6 years (range 1 to 17 years). Their mean age at the time of operation was 13 years (range 6 to 17 years). All patients were begun on a regimen of warfarin before hospital discharge. One major and four minor bleeding episodes occurred in 211 patient-years of warfarin therapy, an incidence of 2.3 per 100 patient-years. Three of those five episodes occurred in patients who were receiving excessively anticoagulation or who were participating in physical activities inappropriate for a patient on warfarin therapy. Thus, the majority of the bleeding episodes were preventable. There were five thromboembolic events in 211 patient-years, an incidence of 2.3 per 100 patient-years. Three of those five patients had intentionally stopped their warfarin therapy. The majority of thromboembolic episodes, like the bleeding episodes, were preventable. Eight teenage patients were noncompliant with the warfarin therapy. More than one third of that group experienced a thromboembolic event, an incidence of 5.5 per 100 patient-years (55 patient-years). Twenty-two patients adhered to the warfarin regimen and only two (9%) of them had a thromboembolic event, an incidence of 1.3 per 100 patient-years (156 patient-years). Warfarin therapy presented no greater risk of serious bleeding to this pediatric age group than it does to an adult age group. The incidence of thromboembolism among these patients was less than that which is generally reported for adult patients. Discontinuation of or noncompliance with warfarin therapy substantially increased the risk of thromboembolism. Continuous warfarin therapy is recommended for every child after prosthetic valve replacement.

Adolescent↗

Late results of the Mustard procedure in transposition of the great arteries.

Thirty-five patients were discharged from the hospital after a Mustard procedure and have been followed a mean of 4.5 years. Thirty remain in a stable atrial or sinus rhythm, 3 have required hospitalization and medication to control atrial dysrhythmias, 1 is in a junctional rhythm, and 1 requires a pacemaker. In no patient has there been clinical evidence of systemic or pulmonary venous baffle obstruction. Twenty-two patients have had an elective postoperative cardiac catheterization, which has confirmed the absence of baffle obstruction. We attribute the lack of baffle obstruction and the low incidence of atrial dysrhythmias to several technical points in the operation including: direct high cannulation of the superior vena cava, aggressive resection of the atrial septum except in the region of the atrioventricular node, an extremely large pericardial baffle trimmed in the manner of Brom, sharp divergence of the upper and lower limbs of the inferior suture line away from one another and toward the caval orifices once they enter the right atrium, and very superficial endocardial bites of the baffle suture line in the region of the sinoatrial and atrioventricular nodes.

Arrhythmias, Cardiac↗

The midterm and long-term results of the Mustard operation in patients with transposition of the great vessels and dynamic left ventricular outflow tract obstruction.

Eight of 43 patients with transposition of the great vessels (TGV) and either an intact ventricular septum or very small ventricular septal defect were found to have dynamic left ventricular outflow tract obstruction (LVOTO). The preoperative left ventricle-pulmonary artery (LV-PA) pressure gradient ranged between 14 and 60 mm Hg. In 3 patients the pulmonary artery could not be catheterized. They had a left ventricular pressure of 43, 45, and 62 mm Hg, respectively, no evidence of pulmonary vascular disease, and either echocardiographic or angiocardiographic demonstration of LVOTO. The outflow tract was explored in 3 patients at the time of the Mustard operation. Exposure of the LVOT was difficult, particularly in patients less than 6 months of age. A shallow septal myectomy was performed in 1 patient; a thin fibrous endocardial scar was resected in 2; and no procedure was performed in the third. All 8 patients survived and remain asymptomatic 1 to 11 years (mean, 5 years) after operation. The LV-PA pressure gradient has either remained the same or has increased in every patient except 1 in whom there was a slight reduction in the gradient. We conclude that dynamic LVOTO persists after the Mustard operation and is not amenable to direct surgical relief. However, an excellent clinical result can be obtained for up to 11 years after operation.

Child, Preschool↗

Early and late results of repair of partial anomalous pulmonary venous connection to the superior vena cava with a pericardial baffle.

The early and late results of repair of partial anomalous pulmonary venous connection to the superior vena cava with a simple pericardial baffle without enlargement of the superior vena cava were examined. Fifteen consecutive patients received operations between 1973 and 1983, and all survived. They have been followed for a mean of 6 years and a minimum of 2 years. Nodal rhythm and atrial dysrhythmias were present in 6 patients (40%) early after operation. However, every patient resumed normal sinus rhythm prior to hospital discharge except 1 adult who remained in the preoperative rhythm of atrial flutter-fibrillation. No patient has clinical evidence of a residual atrial level shunt or superior vena cava obstruction. All have received an excellent clinical result, and none, except the patient in chronic atrial fibrillation, require cardiac medication. These results are comparable or superior to those obtained with more intricate procedures that use either complex atrial flaps or translocation of the superior vena cava to the atrial appendage.

Adolescent↗

Morphologic and morphometric analysis of muscle in X-linked myotubular myopathy.

The X-linked form of myotubular myopathy is highly lethal in neonates. Several autopsy-derived muscles from two probands of a new kindred who survived for 100 days because of intensive supportive care were analyzed by light microscopy, morphometry, enzyme histochemistry, and electron microscopy. The results were compared with a similar analysis of muscle from control fetal and neonatal subjects. The findings, in addition to the characteristic centronucleated hypotrophic myofibers, included widespread myofiber degeneration and focal contraction band necrosis that differed from the types seen in other myopathic and dystrophic muscle diseases. A high frequency of degenerating nuclei that often contained large nucleoli was observed. Because of the paradoxic nuclear morphology, nuclear failure (in migration and myofibrillogenesis) is believed to be of central importance in the pathogenesis of this disease.

Histocytochemistry↗

Antibody-guided irradiation of malignant pleural and pericardial effusions.

Tumour-associated monoclonal antibodies (HMFG1, HMFG2 and AUA1) radiolabelled with iodine-131 were given intracavitary (intrapleurally and intrapericardially) to patients with malignant effusions. Ten out of 13 effusions (3 pericardial and 7 pleural) responded completely with no fluid reaccumulation between 3 and 18 months. No clinical or other toxicity was observed. This new method of treatment for recurrent malignant effusions is non-toxic and effective resulting in improved quality of life, and, in some cases, prolongation of survival.

Adult↗

Craniopharyngioma with hyperprolactinaemia due to a prolactinoma.

A case is presented in which a histologically proven prolactin secreting pituitary macroadenoma was associated with a large suprasellar craniopharyngioma. The pre-operative prolactin concentration was 8180 mU/l. Although hyperprolactinaemia up to 3000 mU/l in patients with a craniopharyngioma is usually due to stalk compression, greater values may indicate an associated prolactinoma.

Adenoma↗

Expectations and coping of women undergoing in vitro fertilization.

Approximately 15% of childbearing couples in America experience infertility. While dramatic progress has been achieved in relation to the diagnosis and treatment of the organic components of infertility, less attention has been paid to the emotional dimensions of this life crisis. Descriptive data were gathered from interviews with three women who completed an in vitro fertilization cycle at a large midwestern university hospital. Open-ended interview questions elicited information about each woman's in vitro experience with regard to the realization of her expectations, her coping mechanisms, and suggestions for what would have helped. Differences in the perception of the difficulty of the experience are suggested depending on pregnancy success. Health team strategies for supporting women undergoing in vitro fertilization are discussed.

Adaptation, Psychological↗

Bilateral phrenic nerve paralysis after the Mustard procedure. Experience with four cases and recommendations for management.

Unilateral phrenic nerve injury is a recognized complication of thoracic operations, but bilateral diaphragmatic paralysis after an intracardiac procedure in an infant has not previously been described. In the past 10 years, four infants have sustained a bilateral phrenic nerve injury during the performance of a Mustard procedure. They were managed with tracheostomy and prolonged mechanical ventilation. Their recovery period ranged between 30 and 103 days and each had a satisfactory outcome. This technique was preferred to bilateral diaphragmatic plication because the results of that procedure have been equivocal. Tracheostomy reduced the catastrophic risk of an obstructed endotracheal tube, allowed immediate oral intake, and simplified the weaning process from the ventilator.

Cardiac Surgical Procedures↗

Emergence of idiotype variants during treatment of B-cell lymphoma with anti-idiotype antibodies.

We studied two patients with malignant B-cell lymphoma that manifested resistance to the therapeutic effects of anti-idiotype antibody because of the emergence of subclones with changes in their immunoglobulin idiotypes. In both patients, tumor-cell populations arose that were unreactive with anti-idiotype antibody but that retained surface immunoglobulin. One of the patients had an additional subpopulation of tumor cells that had switched from mu to gamma heavy-chain expression. Study of the immunoglobulin genes in the tumors confirmed that the subpopulations were derived from the same original clone of neoplastic B cells in each patient. The available data suggest that the idiotypic variation observed was the result of somatic mutation in the variable region of the active immunoglobulin genes. The fact that such mutations became evident over a short time and in the context of a partial tumor response suggests that the antibody therapy exerted a strong selective force against tumor cells that expressed the idiotype determinant. Multiple anti-idiotype antibodies may therefore be needed to identify all cells of a malignant clone, and some patients may require treatment with more than one monoclonal antibody.

Adult↗

Interstitial haemosiderin in the lungs of sudden infant death syndrome: a histological hallmark of 'near-miss' episodes?

The occurrence of multiple intrathoracic petechial haemorrhages in sudden infant death syndrome is well-documented and undisputed. We describe a study of 24 consecutive sudden infant deaths in which Perls' method for staining of iron in lung sections has been employed in addition to standard post-mortem procedures. Haemosiderin-containing macrophages have been demonstrated in 13 infants in subpleural and interstitial lung tissue in the absence of local fresh interstitial haemorrhage; ten of these infants had no evidence of respiratory tract inflammation and died mainly between one and three months of age. Eleven babies without haemosiderin showed evidence of inflammatory lesions and were predominantly four months or older at death. The demonstration of previous haemorrhagic foci in babies showing no other pathological abnormality may represent a histological hallmark of previous 'near-miss' episodes of hypoxaemia from whatever cause.

Female↗