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Biomedical subjects

R Gore

Publications and source records attributed to R Gore.

29 records · Page 2Linked to original sources

Optimization of a recombinant von Willebrand factor fragment as an antagonist of the platelet glycoprotein Ib receptor.

The binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ib receptor is one of the initial events in thrombus formation. Previous studies have shown that RG12986, a reduced and alkylated recombinant fragment of vWF (Ser445-Val733), can inhibit binding of native vWF to GP Ib and offers potential as an anti-thrombotic agent. We have now evaluated a series of deletion mutants of RG12986 and found that reduced and alkylated rvWF508-704 is close to the minimal sequence with optimal RG12986-like activity (IC50 for inhibition of GP Ib-dependent platelet aggregation in the absence of modulators: 0.022 microM +/- 0.01, n = 3) and that it too binds directly to GP Ib. Under in vitro conditions, with no exogenous modulators present and in the absence of shear stress, oxidized rvWF508-704 (containing a disulfide bond between Cys508 and Cys659) is approximately 5-fold less active than reduced and alkylated rvWF508-704; the two fragments, however, display comparable activity in the presence of the modulator botrocetin. The smaller rvWF508-704 fragment offers distinct advantages over RG 12986. In particular, removal of non-active NH2 and COOH terminal sequences may reduce the risk of antigenicity and may contribute to rendering the molecule mostly monomeric in solution, as opposed to the monomer-dimer equilibrium previously described for RG12986.

Chromatography, High Pressure Liquid↗

A single-blind study of combined pulse oximetry and capnography in children.

This single-blind study examined four levels of monitoring in 402 pediatric cases. Patients were randomly assigned to one of four groups: 1) oximeter and capnograph; 2) only oximeter; 3) only capnograph; or 4) neither oximeter nor capnograph data available to the anesthesia team. An anesthesiologist, not involved in patient care, observed all cases and continuously recorded hemoglobin oxygen saturation (Spo2), ECG, expired CO2, and the oximeter plethysmographic output. Mean age, weight, ASA physical status, airway management (mask or endotracheal tube), and anesthetic technique were similar in each group. Two-hundred sixty problems were documented in 153 patients. Fifty-nine events in 43 patients resulted in "major" desaturation (Spo2 less than or equal to 85% for greater than or equal to 30 s). Fifteen "major" capnograph events (esophageal intubation, disconnection, accidental extubation, or obstructed endotracheal tube) were observed in 11 patients; 8 of these also developed varying degrees of desaturation. One-hundred thirty "minor" desaturation events (Spo2 less than or equal to 95% for greater than 60 s) and 79 "minor" desaturation events (hypercarbaria or hypocarbia) were observed. A number of problems fulfilled criteria in multiple categories. Infants less than or equal to 6 months of age had the highest incidence of major desaturation events (18 of 65 [27%]) compared to toddlers 7-24 months of age or children greater than 24 months of age (P less than 0.001). Blinding the oximeter data increased the number of patients (12 vs. 31) experiencing major desaturation events (P = 0.003); blinding the capnograph data altered neither the frequency of desaturation events nor the incidence of major capnograph events.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Comparative effects of nadolol-digoxin combination therapy and digoxin monotherapy for chronic atrial fibrillation.

In some patients with chronic atrial fibrillation, treatment with digitalis alone may fail to produce a satisfactory decrease in heart rate at rest or during exercise or emotional stress. Findings of a few clinical studies suggest that beta blockade in combination with digitalis therapy may be of benefit in these patients. In a randomized, double-blind, placebo-controlled, parallel-group, 8-week study of 32 patients with chronic atrial fibrillation, the effects of digoxin therapy alone were compared with a combination of digoxin and nadolol. Criteria for entry into the study included ventricular rate at rest greater than or equal to 80/min or greater than or equal to 120/min with exercise, and serum digoxin levels within the therapeutic range. After digoxin dose titration to produce therapeutic levels, digoxin dosage remained constant throughout the balance of the study. After a 2-week, single-blind placebo lead-in period, patients were randomized to receive either digoxin plus placebo or a combination of digoxin and nadolol. The dose of nadolol/placebo was titrated from 20 to 120 mg daily as tolerated. Twenty-four hour ambulatory electrocardiographic (Holter) recordings, symptom-limited exercise treadmill tests and serum digoxin and nadolol levels were obtained at the end of the single and double-blind treatment periods. Comparing endpoint with baseline, results from Holter recordings showed that patients treated with a combination of digoxin and nadolol had significant (p less than 0.001) decreases in 24 hour average (78 +/- 4 to 63 +/- 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of computed tomography and radionuclide scanning in the staging of cutaneous T-cell lymphoma.

Computed tomography (CT) of the abdomen and pelvis was performed on 30 patients with cutaneous T-cell lymphoma (CTCL) as part of their pretreatment staging evaluation. Twenty-two patients also had liver-spleen radionuclide scans. Physical examination revealed limited cutaneous plaque disease in five patients, extensive plaque disease in 11 patients, cutaneous tumors in six patients, and exfoliative erythroderma in eight patients. Generalized palpable adenopathy was detected in 11 patients, localized palpable adenopathy in ten patients, and no adenopathy in nine patients. Peripheral lymph node biopsy specimens showed CTCL in seven patients and dermatopathic lymphadenitis or sinus histiocytosis in 17 patients. Two patients were at disease stage Ia, five were at stage Ib, seven were at stage IIa, two were at stage IIb, seven were at stage III, and seven were at stage IVa. The CT did not reveal intra-abdominal, retroperitoneal, or pelvic adenopathy, or hepatic or splenic abnormalities in any patient. Radionuclide scans demonstrated nonspecific abnormalities in five patients, but did not appear to reflect disease involvement. Computed tomography of the abdomen and liver-spleen radionuclide scans should not be routine staging procedures for CTCL.

Humans↗

Losulazine, a new antihypertensive.

The efficacy of losulazine was determined in 32 patients with hypertension. Each subject was randomly assigned to receive either losulazine (n = 16) or placebo (n = 16) in a double-blind fashion. Losulazine in the dosage range of 10 to 30 mg b.i.d. effectively lowered the blood pressure. Diastolic blood pressure was lowered to less than or equal to 90 mm Hg in over 70% of the subjects receiving losulazine. There was no evidence of an increase in heart rate; to the contrary, there was a tendency for heart rate to decrease. Six subjects dropped out of the study before completion. Four of these were receiving placebo and dropped out because of lack of efficacy. One subject receiving losulazine dropped out for personal reasons during the first week of the study, and the other subject (also taking losulazine) dropped out when a drug-related pruritus (itchy eyes) developed. This event was readily reversed upon discontinuation of the drug. The drug was well tolerated and side effects were minimal, with no evidence of orthostatic effects or sexual dysfunction. There was a suggestion that nasal stuffiness and conjunctival congestion may be drug related. There were no changes in any laboratory values or body weight.

Adult↗

Aujeszky's disease in a pack of hounds.

Aujeszky's disease occurred in a pack of harrier hounds in the south west of England and caused the death of 11 of a pack of 51 animals. The onset appeared to have followed the feeding of pig carcase material from a very large fattening unit. No evidence of clinical disease was seen in pigs in this unit, but serological evidence of earlier infection was obtained. Interesting lesions in the intestinal wall of the hounds are described.

Animals↗

The treatment of adopted versus neglected delinquent children in the court: a problem of reciprocal attachment?

The authors investigated the discrepant treatment by a juvenile court of adopted versus neglected delinquents. Adopted delinquents received harsher dispositions in spite of the fact that neglected delinquents often faced more serious charges. The two groups are compared in terms of family structure and the criminal and psychiartic histories of their parents; none of these seems to account for the adoptees' harsher treatment. The authors hypothesize that an interplay of late adoption intrinsic vulnerabilities in the children, and weakness of parental bonds accounts for the differential outcomes.

Adolescent↗

The bacterial causation of postoperative osteitis pubis.

Five patients with a bacterial causation of postoperative osteitis pubis were treated during a three year period. In each patient, the bacterial cause was suggested by a known infectious process adjacent of the symphysis pubis. It is suggested that a bacterial causation be considered for the clinical and roentgenographic syndrome of osteitis pubis if a contigous infectious process is present.

Aged↗

Characterization of highly purified, inactivated HIV-1 particles isolated by anion exchange chromatography.

This report characterizes inactivated, gp120 depleted, HIV-1 particles purified by an anion exchange chromatography production process. This antigen formulated with incomplete Freund's adjuvant constitutes Remune, which is being evaluated in a phase III clinical endpoint trial to determine the effect of this immune-based therapy on clinical progression of HIV-1 seropositive patients. Multiple production lots of the inactivated HIV-1 antigen strain HZ321, isolated by anion exchange chromatography, exhibit purity of > 95% by gel filtration. These findings are corroborated by thin section electron microscopy showing a homogenous field of intact particles. Analyses of the purified virus particles for protein, lipid, carbohydrate and RNA show structural retention of the envelope proteins, lipid bilayer and core components after large scale processing. The qualitative identification of at least 85% of total HIV-1 protein is determined by ELISA, Western blot, HPLC and amino acid sequencing analyses. Quantitative values are assigned to 50% of these proteins. The data confirm the presence of virally encoded proteins p6, p7, pI15, p17, p24, p32, pI39Gag, gp41, pp55Gag, p66/51, Vpr, Vif and Nef. Excellent consistency between production lots and equivalency to HIV-1 preparations purified by sucrose density gradient sedimentation has been established for protein and lipid composition, and overall purity. These findings further establish that non-viral encoded proteins and lipids are integral structural components of the intact virion and are not contaminants unique to a particular isolation method. The data confirm the presence of multicomponent antigens in the viral particles for stimulating a broad HIV-1 specific immune response. Finally, the work demonstrates that the two inactivation procedures (beta-propiolactone and gamma irradiation), which achieve efficient viral inactivation meeting US FDA guidelines, do not damage the protein antigens of the viral particles.

Carbohydrates↗