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Biomedical subjects

J Foote

Publications and source records attributed to J Foote.

At least 37 records · Page 2Linked to original sources

Lipids, lipoprotein (a) and coronary artery disease in patients following cardiac transplantation.

Cardiac allograft vascular disease (CAVD) is the most important cause of late mortality in cardiac transplant recipients. While the pathogenesis of the disease is believed to be immunological, other factors like hyperlipidaemia may contribute. Total cholesterol, LDL cholesterol. HDL cholesterol, triglycerides, apolipoprotein A1 and B and Lp(a) levels were measured in 174 cardiac transplant recipients attending our clinic for routine follow-up. Univariate and multivariate logistic regression analysis was carried out to assess the relationship of the variables studied to the presence of CAVD diagnosed with coronary angiography. CAVD was present in 42 of the 174 patients. The group with CAVD had a higher total cholesterol (6.8 vs 6.3 mmol/l), lower HDL cholesterol (0.8 vs 0.9 mmol/l), higher triglyceride (2.8 vs 2.0 mmol/l) and higher Lp(a) level (317.5 vs 95 mg/l) than the group without CAVD. In multivariate analysis, after adjusting for gender, hypertension, time from transplantation, preoperative diagnosis and lipid-lowering therapy, Lp(a), total cholesterol, HDL cholesterol and triglycerides remained significantly correlated with CAVD. The results indicate a significant association between hyperlipidaemia, Lp(a) levels and allograft vascular disease. Further studies are needed to show whether treatment of hyperlidaemia in this population delays the onset or slows the progression of CAVD.

Adult↗

Video techniques with chemically-dependent patients.

This paper describes the use of videotaping as an adjunctive intervention in the treatment of substance-dependent patients. In the context of a cognitive-behavioral treatment extensively modified to work with inner-city, methadone-maintained cocaine users, videotaping in both individual and group formats is described. Video sessions create an opportunity for patients to reflect on their experience, enhance their self-esteem, aid in teaching social skills, and help hard-to-engage patients begin to participate in treatment. In order to compete with both the powerfully reinforcing qualities of cocaine and the extreme degree of avoidance exhibited by this population, therapy has to provide intense capturing experiences at the outset of treatment. Patient's reactions indicate that the experience they have is captivating and stimulating more than most other early therapy experiences. It is additionally concluded that the use of video can be instrumental in addressing the severe psychological deficits of this population that otherwise impede treatment efforts. While the role of video was not independently evaluated for its contribution to patient retention, 62% of patients were retained through completion of an intensive 6-month protocol.

Adult↗

Comparison of the hemodynamic and metabolic effects of low-dose hydrochlorothiazide and lisinopril treatment in obese patients with high blood pressure.

Patients with high blood pressure tend to be insulin resistant, glucose intolerant, hyperinsulinemic, and dyslipidemic. Since these metabolic defects are accentuated by obesity, we thought it important to compare the effects of 3 months' treatment with either lisinopril (20 mg/day) or low dose hydrochlorothiazide (12.5 mg/day) on blood pressure and glucose, insulin, and lipoprotein metabolism in obese patients with hypertension. There were 14 patients in each group, and they were similar (mean +/- SE) in age (54 +/- 3 v 50 +/- 4 years), gender (nine men/five women), and body mass index (33.4 +/- 0.8 v 33.9 +/- 0.9 kg/m2). Patients treated with lisinopril had a somewhat greater fall in both systolic (18 +/- 3 v 10 +/- 3 mm Hg) and diastolic (12 +/- 2 v 8 +/- 1 mm Hg) blood pressure, but only the change in systolic pressure was statistically significant (P < .05). Plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at 12 PM), and there was a modest increase in all three variables following hydrochlorothiazide treatment (P < .05 to P < .09). However, daylong plasma glucose, insulin, and triglyceride concentration did not change with lisinopril treatment. Finally, neither the ability of insulin to mediate glucose disposal nor fasting lipid and lipoprotein concentrations, changed with either treatment. In conclusion blood pressure decreased significantly following treatment with either lisinopril (20 mg/day) or hydrochlorothiazide (12.5 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Initial reliability and validity of the childhood trauma interview: a new multidimensional measure of childhood interpersonal trauma.

OBJECTIVE: The Childhood Trauma Interview, a new instrument for brief and comprehensive retrospective assessment of childhood interpersonal trauma, is presented with initial evidence of its reliability and validity. METHOD: Drug- or alcohol-dependent patients (N = 220) were given the Childhood Trauma Interview and a questionnaire measure of child abuse, the Childhood Trauma Questionnaire. Convergent and discriminant validity for the Childhood Trauma Interview were tested by comparing correlations between analogous and nonanalogous trauma scales to those of the Childhood Trauma Questionnaire. RESULTS: Interrater reliability for the majority of trauma dimensions measured by the Childhood Trauma Interview was very high (63% had intraclass correlations above 0.90). Principal-components analysis yielded six rotated factors that accounted for 74% of the variance among scores: separations and losses, physical neglect, emotional abuse or assault, physical abuse or assault, witnessing violence, and sexual abuse or assault. Since these six factors exactly represented the areas that the interview was designed to assess, the construct validity of the Childhood Trauma Interview was supported. Without exception, convergent correlations were significantly higher than discriminant correlations, and convergence was improved when multidimensional variables from the Childhood Trauma Interview and their interactions were regressed onto Childhood Trauma Questionnaire scores. CONCLUSIONS: These initial findings suggest that the Childhood Trauma Interview is a reliable and valid method for brief assessment of multiple dimensions of six types of childhood interpersonal trauma.

Adult↗

Conformational isomerism and the diversity of antibodies.

The fact that one cell encodes a single antibody sequence does not necessarily mean that the resulting antibody folds into a single structure, although this is a common assumption. Here we challenge this view and suggest that many antibodies do not have a single conformation at the combining site. The basis for this proposal comes from the kinetic analysis of a set of murine hybridomas derived from defined stages of the immune response to 2-phenyl-5-oxazolone (Ox). Among them we have identified three antibodies that exhibit complex hapten-binding kinetics. We observed biphasic or triphasic reactions in stopped-flow fluorescence experiments, indicating that ligand binding involved isomerization, as well as associative steps. The existence of an equilibrium between at least two antibody conformations, with ligands binding preferentially to one form, was deduced from the variation with hapten concentration of the apparent rate of each phase.

Animals↗

Hyperinsulinemia, coronary artery disease and syndrome X.

OBJECTIVES: This study was conducted to compare the insulin responses to an oral glucose load in healthy volunteers and patients with syndrome X and patients with coronary artery disease. BACKGROUND: An abnormal coronary flow reserve has been reported in syndrome X by several investigators. However, its cause is not known. Recently, it has been suggested that elevated insulin levels in syndrome X may contribute to microvascular dysfunction. METHODS: Insulin responses to an oral glucose load (75 g) were compared in 17 patients with coronary artery disease, 17 patients with chest pain, positive exercise test findings, normal coronary arteries and impaired coronary flow reserve (syndrome X) and 17 healthy volunteers (control subjects). All were matched for age, gender and body weight. Patients with overt diabetes mellitus or hypertension were excluded. Venous blood samples were taken during fasting and at 30, 60, 90 and 120 min after the glucose load. Samples were analyzed for glucose, immunoreactive insulin and C peptides. RESULTS: There was no significant difference in the glucose levels at all sampling points among the three groups. The C peptide and immunoreactive insulin levels were significantly higher than values in the control group at 60, 90 and 120 min in the groups with syndrome X and coronary artery disease. The peak responses and the areas under the curve were also significantly greater in the latter two groups. There was no significant difference at all sampling points between the group with syndrome X and the group with coronary artery disease. CONCLUSION: Patients with syndrome X have stimulated hyperinsulinemia, which may contribute to the pathophysiology of syndrome X.

Blood Flow Velocity↗

Initial reliability and validity of a new retrospective measure of child abuse and neglect.

OBJECTIVE: This report presents initial findings on the reliability and validity of a new retrospective measure of child abuse and neglect, the Childhood Trauma Questionnaire. METHOD: Two hundred eighty-six drug- or alcohol-dependent patients were given the Childhood Trauma Questionnaire as part of a larger test battery, and 40 of these patients were given the questionnaire again after an interval of 2 to 6 months. Sixty-eight of the patients were also given a structured interview for child abuse and neglect, the Childhood Trauma Interview, that was developed by the authors. RESULTS: Principal-components analysis of responses on the Childhood Trauma Questionnaire yielded four rotated orthogonal factors: physical and emotional abuse, emotional neglect, sexual abuse, and physical neglect. Cronbach's alpha for the factors ranged from 0.79 to 0.94, indicating high internal consistency. The Childhood Trauma Questionnaire also demonstrated good test-retest reliability over a 2- to 6-month interval (intraclass correlation = 0.88), as well as convergence with the Childhood Trauma Interview, indicating that patients' reports of child abuse and neglect based on the Childhood Trauma Questionnaire were highly stable, both over time and across type of instruments. CONCLUSIONS: These findings provide strong initial support for the reliability and validity of the Childhood Trauma Questionnaire.

Adult↗

Neurobehavioral treatment for cocaine-using methadone patients: a preliminary report.

Preliminary outcome evaluation results are reported for an innovative cocaine abuse treatment model adapted for cocaine-using methadone patients. Sixty-two patients were randomly assigned to six months of high intensity ("neurobehavioral") or lower intensity ("control") therapy for cocaine dependence. Therapy was completed by 49% of neurobehavioral and 53% of control patients. In paired comparisons between intake and six-month follow-up, neurobehavioral patients but not controls showed significant declines in cocaine and other drug use (measured by urinalysis and self-reports), as well as significant improvement in psychological status. The findings suggest that specialized cocaine abuse treatment can benefit methadone patients; intake to the study is continuing.

Adult↗

Antibody framework residues affecting the conformation of the hypervariable loops.

Rodent monoclonal antibodies have been "humanized" or "reshaped" for therapy by transplanting the antigen-binding loops from their variable domains onto the beta-sheet framework regions of human antibodies. However, additional substitutions in the human framework regions are sometimes required for high affinity antigen binding. Here we describe antigen binding by a reshaped antibody derived from the mouse anti-lysozyme antibody D1.3, and several variants in which point mutations had been introduced into framework positions to improve its affinity. The affinities were determined from the relaxation kinetics of reactant mixtures using quenching of fluorescence that occurs upon formation of the antibody-antigen complex. The dissociation constant of lysozyme ranged from 3.7 nM (for D1.3) to 260 nM. Measurement of antibody-antigen association kinetics using stopped-flow showed that D1.3 and most of the reshaped antibodies had bimolecular rate constants of 1.4 x 10(6) s-1 M-1, indicating that differences in equilibrium constant were predominantly due to different rates of dissociation of lysozyme from immune complexes. Mutations in a triad of heavy chain residues, 27, 29 and 71, contributed 0.9 kcal/mol in antigen binding free energy, and a Phe to Tyr substitution of light chain residue 71 contributed an additional 0.8 kcal/mol. The combined effect of all these mutations brought the affinity of the reshaped antibody to within a factor of 4 of D1.3. All of these substitutions were in the beta-sheet framework closely underlying the complementarity-determining regions, and do not participate in a direct interaction with antigen. The informed selection of residues in such positions may prove essential for the success of loop transplants in antibodies. Variation of these sites may also have a role in shaping the diversity of structures found in the primary repertoire, and in affinity maturation.

Amino Acid Sequence↗

Peptidergic nerve involvement in the control of endothelium-dependent vascular relaxation.

The ability of Acetylcholine (ACh) and A23187 to induce endothelium-dependent relaxation was compared in the isolated perfused mesenteric arterial bed of untreated adult rats, adult rats treated neonatally with capsaicin, and adult rats treated as adults with capsaicin. Following neonatal capsaicin treatment, the response to both agents was reduced. Following adult treatment, the response to both agents was reduced seven days following capsaicin treatment. The same results were obtained in the presence of L-arginine or indomethacin. Tissues from all rats responded equally to sodium nitroprusside. Following capsaicin treatment no change in the structural relationship of the arterial intima was detected but no perivascular nerve fibres immunoreactive to substance P (SP) or calcitonin gene-related peptide (CGRP) could be demonstrated. It is suggested that the reduced response to ACh and A23187 does not involve a change in endothelial muscarinic receptors or a structural change in the arterial intima, but is directly related to the absence of immunohistochemically demonstrable CGRP/SP-containing perivascular innervation.

Acetylcholine↗

Kinetic maturation of an immune response.

Is the affinity maturation of antibodies under thermodynamic or kinetic control, or both? We compared the physical constants of hapten binding by antibodies from 2-phenyl-5-oxazolone-specific hybridomas from primary, secondary and tertiary responses. In addition to an increase in equilibrium constant, there was a shift in the antibody repertoire after the primary response towards an immunoglobulin family with an extremely high on-rate constant. This shift occurred in spite of the average or below-average affinity of this group of antibodies. This is consistent with B-lymphocyte proliferation being subject to a kinetic selection, with a premium on binding target antigens rapidly, in parallel with a thermodynamic selection based on binding tightly.

Animals↗

Postprostatectomy incontinence. Pathophysiology, evaluation, and management.

Given the prevalence of bladder dysfunction (i.e., poor compliance or detrusor instability) as a cause of postprostatectomy incontinence, urodynamic studies are essential in the evaluation of such patients. Appropriate management strategies based on the findings of a pertinent history and physical examination, appropriate radiologic studies, and urodynamics optimize the opportunity for successful treatment. Because bladder dysfunction frequently accompanies sphincter insufficiency, bladder dysfunction must be diagnosed and treated effectively before implantation of an artificial urinary sphincter.

Humans↗

The peptidergic innervation of the developing mesenteric vascular bed in the rat.

We have followed the development of perivascular nerve fibres using antisera to substance P, calcitonin gene related peptide, neuropeptide Y and vasoactive intestinal polypeptide in the mesenteric vascular bed of developing Sprague-Dawley rats. The pattern and density of innervation appeared to be determined by one week of age. The pattern of innervation by SP- and CGRP-positive fibres was similar. The pattern of innervation by neuropeptide Y-containing fibres was distinct from that of SP and CGRP. The VIP-positive fibre plexus was sparse and irregular compared with the others examined. The density of innervation by all fibre types was highest in the jejunal arteries.

Animals↗

Expression of an antibody Fv fragment in myeloma cells.

The antigen binding site on antibodies is fashioned by loops at the tips of the beta-sheet framework of both heavy and light chain variable domains. A heterodimer of both variable domains (Fv fragment), incorporating loops from an anti-lysozyme antibody, was expressed and secreted from myeloma cells in good yield (8 mg/l in supernatant from roller bottles), and shown to bind lysozyme. The two subunits were found to be in dynamic equilibrium but are overwhelmingly associated at neutral pH. The small size of Fv fragments (25 x 10(3) Mr) make them attractive for structural studies, in vivo imaging, and therapy.

Animals↗

Varix of the facial vein.

The differential diagnosis for a mass overlying the angle of the mandible but not attached to it includes lymphatic masses, benign and malignant parotid lesions, cysts, and vascular malformations. Thrombosis of the facial vein is a rare entity that now must be added to the list. This article details the first English-language description of such a thrombosis presenting as a mass. The possible causes are antecedent trauma, infection, or thrombosis of contiguous venous structures. While the diagnosis could be made preoperatively by selective venography or ultrasonography, it most likely will be made by surgical excisions. The preoperative diagnosis may be suggested by the "turkey wattle sign" (i.e., fluctuation in the size of the mass with bending the head downward). In this article the entity and differential diagnosis are reviewed and discussed.

Humans↗

Vascular and neural changes in the rat optic nerve following induction of diabetes with streptozotocin.

This study was undertaken to determine whether or not changes occur in blood vessels, axons or glia of the optic nerve as the result of streptozotocin-induced diabetes. Diabetes was induced in 4 weeks old Sprague-Dawley rats. At 12 and 16 weeks of age, the rats were killed and the optic nerves prepared for examination. The number and density of blood vessels was found to be significantly increased in the diabetic rats. No alteration in the structure of the blood vessels was noted. A decrease in the percentage volume of axons and an increase in the percentage volume of glial elements accompanied the increase in blood vessels in the diabetic rats. No difference was found in the spectrum of fibre diameters.

Animals↗