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Biomedical subjects

D A Adams

Publications and source records attributed to D A Adams.

At least 37 records · Page 2Linked to original sources

Determination of human hepatic cytochrome P4501A2 activity in vitro use of tacrine as an isoenzyme-specific probe.

Oxidative metabolism of the cognition activator tacrine (1,2,3,4-tetrahydro-9-aminoacridine) is thought to be catalyzed by cytochrome P4501A2 (CYP1A2). In this study, the use of tacrine as a specific substrate to measure CYP1A2 activity in vitro was investigated. Tacrine metabolism was assessed in 16 human liver microsomal samples. Initially, the percentage conversion of tacrine to stable metabolites (i.e. 1-, 2-, 4-, and 7-hydroxytacrine) at a single time point was correlated with levels of CYP1A2 apoprotein. Apoprotein was detected by immunoquantification using a monospecific CYP1A2 antipeptide antibody. Significant correlations were seen between CYP1A2 content and the degree of 1-hydroxylation (r = 0.81, p < 0.001), 7-hydroxylation (r = 0.70, p < 0.001), and metabolism to all stable products (r = 0.82, p < 0.001). The major metabolite formed in all livers was 1-hydroxytacrine. The conversion of tacrine to this metabolite was examined in more detail. The rate of formation varied from 19.2 pmol min-1 mg-1 to 101.0 pmol min-1 mg-1. There was a significant correlation (r = 0.84, p < 0.001) between the rate of formation and CYP1A2 levels. Tacrine metabolism was also compared with the rate of formation of 3-methylxanthine, from theophylline, a reaction previously shown to be catalyzed by CYP1A2. Significant correlations were found between 3-methylxanthine formation and all quantified tacrine metabolites. The rate of 3-methylxanthine generation also correlated with CYP1A2 apoprotein levels. It is concluded, therefore, that tacrine is a valuable probe for the determination of human hepatic CYP1A2 activity in vitro.

Amino Acid Sequence↗

In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging.

The goal of this study was to investigate myelin phospholipids in vivo in multiple sclerosis lesions and normal-appearing white matter by evaluating the spectral broad component from phosphorus 31 magnetic resonance spectroscopic imaging data. The phospholipid broad component was reduced nearly 35% (p < 0.001) in both lesions and in normal-appearing white matter in multiple sclerosis subjects compared to control subjects, suggesting reduced myelin phospholipid concentration or altered relaxation times.

Adult↗

Explaining information technology use with the usefulness scale: a comparison with user age.

Understanding and predicting the use of information technology is an important problem in healthcare management. The relationships among user characteristics and information technology have generally been weak. This paper describes a recently developed scale that measures perceived usefulness of information technology. Following this description, the scale is compared with user age in ability to explain information technology use. The results suggest perceived usefulness explains a significant proportion of the variance in use (r2 = .13, p < or = 0.0001), while age was not a significant predictor. Implications and suggestions for use of the usefulness scale are discussed.

Adult↗

Purified Pasteurella multocida protein toxin reduces acid phosphatase-positive osteoclasts in the ventral nasal concha of gnotobiotic pigs.

To study the in vivo response of conchal (turbinate) osteoclasts to Pasteurella multocida toxin, four gnotobiotic pigs (7 days of age) were inoculated subcutaneously with 0.2 microgram/kg of purified toxin. One toxin-treated pig along with one control pig were necropsied at 2, 5, 9, and 14 days postinoculation. The entire length of nasal concha from the nasal planum toi ethmoid region was removed, blocked by transverse cuts into five areas, decalcified, sectioned, and then stained with tartrate-resistant acid phosphatase (TRAP) to identify osteoclasts. In each section, total area of concha, total osteoclast cytoplasmic area, and number of osteoclasts were determined using an image analysis morphometric unit. Also collected from pigs were blood and serum for complete blood counts, electrolyte levels, liver enzymes, and TRAP levels. Conchal atrophy increased in severity with time after 2 days postinoculation. In general, the ventral conchae from toxin-treated pigs at 9 and 14 days postinoculation had decreased surface area, osteoclast cytoplasmic area, and numbers of osteoclasts. Serum levels of TRAP were mildly elevated when compared with age-matched controls. No other significant alterations in blood cells or chemistries occurred and no lesions were present histologically in tissues (liver, kidney, lung, heart, and spleen) other than concha. This study shows that the P. multocida toxin induces rapid bone resorption and increases serum levels of acid phosphatase but leads to diminished acid phosphatase expression and presumably, numbers of osteoclasts.

Acid Phosphatase↗

Transsphenoidal adenomectomy for growth hormone-secreting pituitary adenomas in acromegaly: outcome analysis and determinants of failure.

The results of transsphenoidal adenomectomy for growth hormone (GH)-secreting pituitary adenomas in acromegaly performed over a 17-year period were analyzed retrospectively to determine which preoperative factors significantly influenced the long-term surgical outcome. These variables were then used to develop a logistic regression model to determine the probability of surgical failure. The series consisted of 103 patients. Long-term follow-up study (mean duration 102 +/- 64 months) was performed to derive outcome analysis and determinants of failure. Surgical control was defined as a long-term postoperative serum basal GH level of less than 5 micrograms/liter, a long-term postoperative serum somatomedin C (SM-C) level of less than 2.2 U/ml, and a favorable clinical response. Eighteen (17.5%) patients did not meet these criteria. The overall control rate by the GH criteria was 81.3% and by the SM-C criteria 76.2%. By multivariate logistic regression analysis, tumor stage was the strongest predictor of outcome (p < 0.05). The preoperative GH level, tumor grade, and preoperative SM-C level were significant univariate predictors (p < 0.05). There were statistically significant differences in mean preoperative GH and SM-C levels (p < 0.05, t-test) and tumor stage (p < 0.05, chi-squared test) between patients whose acromegaly was controlled by surgery and those whose acromegaly was not. Furthermore, estimates were derived of the probability of surgical failure based on preoperative GH level, preoperative SM-C level, and tumor grade and stage. The authors believe these findings will enhance clinical decision-making for neurosurgeons considering transsphenoidal microsurgery in patients with acromegaly.

Acromegaly↗

Otological manifestations of a new familial polyostotic bone disorder.

Fifty members of a family with a unique autosomal dominant bone disease were investigated. Nineteen of the family members were either known to have, or were strongly suspected of having the disease. All but one of these had a hearing loss which was conductive in the younger age group and mixed in the older members. The common finding in those who had middle ear surgery was replacement of the long process of incus by a fibrous band. The histological features were similar to those found in Paget's disease. The age of onset, distribution of lesions and radiographic findings, however, were not typical of this disorder.

Adult↗

Pituitary adenoma: correlation of half-dose gadolinium-enhanced MR imaging with surgical findings in 26 patients.

Sellar magnetic resonance imaging studies obtained with half doses of gadopentetate dimeglumine (0.05 mmol/kg) were prospectively interpreted and retrospectively rated in 26 patients who subsequently underwent transsphenoidal sellar surgery for suspected pituitary adenoma. Studies included a sagittal scout view followed by a non-contrast-material-enhanced, an immediate postcontrast, and a delayed postcontrast T1-weighted image (obtained at 1.0 or 1.5 T). Ten of 11 confirmed microadenomas were identified prospectively; all were identifiable in retrospect. Macroadenomas (12 cases) were well demonstrated. The high signal intensity of the posterior pituitary and of intrasellar hemorrhage was obscured on postcontrast studies. Delayed images proved unnecessary. This prospective evaluation suggests that a half-dose study is comparable to retrospective studies in which full-dose techniques were used for detection of micro- and macroadenomas. Imaging times are reasonably short, and cost of contrast material is potentially reduced. Confirmation with larger studies is required, and careful endocrinologic and clinical follow-up of nonsurgical patients is necessary.

Adenoma↗

Cushing's disease: results of transsphenoidal microsurgery with emphasis on surgical failures.

From 1977 to 1988, 56 patients with a preoperative diagnosis of Cushing's disease were treated by transsphenoidal microsurgical exploration of the pituitary gland. In 42 patients, a discrete tumor was found and a selective adenomectomy was performed. Total hypophysectomy was performed in nine patients. In an attempt to preserve pituitary function, a technique of subtotal hypophysectomy was utilized in the remaining five patients. Regular and adequate follow-up results were obtained in 53 patients. A sustained remission was obtained in 45 of these 53 patients for a remission rate of 84.9%. Eight patients were classified as therapeutic failures. The causes for failure included: 1) invasive tumor; 2) hyperplasia mistaken for an adenoma; 3) a presumed ectopic source of adrenocorticotropic hormone; 4) misdiagnosis; 5) atypical tumor; and 6) recurrence of disease after remission. In cases of therapeutic failure, the original diagnosis of Cushing's disease must be reevaluated and treatment continued until sustained remission is achieved. Necessary measures to help avoid surgical failures and an approach for further diagnostic and therapeutic maneuvers in these cases are discussed.

Adrenalectomy↗

Respiratory syncytial viral infection in infants: nursing implications.

Respiratory syncytial viral infection is the leading cause of acute lower respiratory tract disease in infants and young children. Presenting symptoms include rhinorrhea, nasal congestion, a low grade fever, and a cough. Hypoxemia and respiratory acidosis are the most common presentation for infants requiring intensive care. Critical care nurses must skillfully assess the infant's clinical status and response to medical treatment, implement and enforce isolation procedures, and remain sensitive to the emotional and psychologic needs of RSV-infected infants and their families. They must be knowledgeable regarding the latest research and recommendations concerning isolation policies and safe administration of ribavirin therapy in order to maximize the care for infants experiencing acute respiratory distress caused by RSV infection.

Child, Preschool↗

A comparison between coupler gain and insertion gain of hearing aids as used in partially hearing units in five schools in Belfast.

A group of 30 school-children attending partially hearing units at ordinary schools had their hearing aids assessed with reference to coupler gain and insertion gain. The results showed no statistically significant difference between the coupler and insertion gain at 250, 500 and 1000 Hz, but a small statistically significant difference with insertion gain greater at 2000, 4000 and 5000 Hz. A large individual variation in results is noted, which would suggest that a standard 2 cm3 coupler is of little use in predicting the output of an aid in a specific child's ear. The presence of wax in the ear canals seems to affect the insertion gain in a positive fashion but this is not statistically significant and further investigation is warranted.

Audiometry↗

Familial expansile osteolysis. A new dysplasia.

We report 40 cases in one family of an autosomal dominant bone dysplasia, which, though similar in some aspects to Paget's disease, seems unique in some features and in its natural history. The disease shows both general and focal skeletal changes, the latter being mainly in the limbs with an onset from the second decade. Progressive osteoclastic resorption is accompanied by medullary expansion which leads to pain, severe deformity and a tendency to pathological fracture. The serum alkaline phosphatase and urinary hydroxyproline are variably elevated, while other biochemical indices are normal. Most patients had an associated deafness of early onset and loss of dentition. No previous description of this disease has been found in the literature.

Deafness↗

Dietary fatty acid modulation of murine B-cell responsiveness.

These studies were designed to determine how dietary fat concentration and degree of saturation influence antibody response to a T-dependent antigen. In vivo fatty acid manipulation did not affect the total number of nucleated spleen cells or IgM or IgG-bearing cells. After primary immunization with sheep red blood cells (SRBC), the number of splenic IgM and IgG antigen specific plaque-forming cells (PFC) was lower in mice fed a diet containing a high level of polyunsaturated fat (PUF, safflower oil) than in mice fed a diet containing minimal essential fatty acids (EFA, 0.5% corn oil). Mice fed a high level of saturated fat (SF, coconut oil) exhibited greater IgM PFC responses than the control. After secondary immunization, the number of IgG-producing cells followed a similar response pattern. These differences were also reflected in the serum anti-SRBC IgM and IgG levels as determined by solid-phase radioimmunoassay. Although the level of linoleic acid in whole lymphocytes has been previously reported to change in direct relation to the serum fatty acid level, no differences in the fatty acid composition of isolated lymphocyte plasmalemma were observed. Thus, changes in the number of antibody-forming cells appear to be inversely related to the levels of linoleic acid in other cell compartments. Fluorescence polarization measurements of the lipopholic probe, 1, 6-diphenyl-1,3,5-hexatriene (DPH), in the purified lymphocyte plasmalemma from mice fed a diet high in PUF indicated an increase in mobility. Polarization values for lymphocyte plasmalemmas from mice receiving diets high in SF were not significantly different from the controls. We conclude that dietary fat modulation of splenic B-cell responses was manifested through changes in the number of cells producing antibody and level of antibody produced, not through total splenic B-cell numbers. This B-cell response can be modified, depending upon the fatty acids available to the cell, and may be related to differential effects upon plasma membrane structure.

Animals↗

Radioimmunotherapy of human lymphoma in athymic, nude mice as monitored by 31P nuclear magnetic resonance.

Human B cell lymphoma (Raji) growing in athymic, nude mice has been successfully treated with a single pulse dose of 131I-labeled monoclonal antibody (Lym-1) specific for this tumor. Sequential in vivo measurements of phosphate metabolites in the tumors by 31P surface coil nuclear magnetic resonance showed a significant initial decrease of phosphocreatine following radioimmunotherapy. Diminution of relative ATP to Pi peak area ratio suggesting tissue damage occurred within 3-4 days. The contribution from metabolites resonating at ca 3.8 ppm (putative sugar phosphate region) increased. There was no significant change in pH either as a function of tumor volume or treatment. The sequence of alterations of nuclear magnetic resonance spectra from tumors of treated mice were strikingly different from sequential nuclear magnetic resonance spectra obtained from tumors of control mice. These observations lead us to conclude that 31P surface coil nuclear magnetic resonance is a promising non-invasive method for assessing and predicting the efficacy of radioimmunotherapy. Further spatial discrimination of the region of tissue observed by the surface coil nuclear magnetic resonance experiment is under exploration in an effort to increase the utility of these methods.

Adenosine Triphosphate↗

31P surface-coil NMR analysis of metabolic status in KHJJ tumors.

Noninvasive monitoring of the effects of treatment on cancer tissue is fundamental to the development of rational radioimmunotherapy (RIT) schemes employing radiolabeled monoclonal antibodies or antibody fragments specific for human cancer. Recent advances in nuclear magnetic resonance spectroscopy make it an attractive candidate for sequential, topical monitoring by 31P NMR of metabolic events during RIT. Preliminary to this effort, we examined the metabolic competence of the well-characterized, murine KHJJ tumor in situ in BALB/c mice using 31P surface-coil NMR. The ATP/Pi ratio in tumor volumes ranging from 100 to 800 mm3 showed that tumors over this range of sizes were able to maintain high levels of ATP relative to Pi. As the tumor volume increased above 1 cm3, ATP/Pi levels indicated poor metabolic competence. This lack of metabolic competence was correlated with histological evidence of tissue necrosis and vascular disintegration. The T1 values of assigned phosphorus metabolites were established. Intracellular pH, as determined from the chemical shift of Pi, was found to vary in these tumors from 7.1 in rapidly metabolizing tissue to 6.6 in necrotic tumors.

Adenocarcinoma↗

Plasma membrane isolation and fatty acid analysis of membrane lipids from murine lymphocytes.

Plasma membranes have been isolated in high yield by a novel method from splenic lymphocytes of BALB/c mice. These membranes were purified in predominantly envelope form, essentially right-side out, by zinc stabilization and sucrose density gradient centrifugation. A simple, rapid method was used for derivatization and analysis of fatty acids in plasma membrane lipids.

Animals↗