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Biomedical subjects

W Bennett

Publications and source records attributed to W Bennett.

At least 37 records · Page 2Linked to original sources

Efficacy of area under the curve cyclosporine monitoring in renal transplantation.

Previous studies suggest that area-under-the-curve (AUC) pharmacokinetic monitoring is superior to trough level monitoring for proper cyclosporin A (CSA) dosing, but AUC monitoring is expensive and unwieldy. The utility of a simplified AUC monitoring method was evaluated for predicting AUC on the basis of three timed levels. CSA pharmacokinetic profiles were studied in 27 renal transplant patients at steady state early (days), late (months), and in some patients, serially posttransplantation. Whole-blood RIA levels were obtained at 2, 4, 6, 10, 12, 14, and 24 h after a once-daily CSA dose. The 6- and 24-h levels were the best single-level predictors of AUC (r = 0.77 and 0.76, respectively). The best model predictive of AUC curves used three time points at 2, 6, and 24 h postdose: AUC predicted = 8.6 x (24 h) + 1.4 x (2 h) + 6.2 x (6 h) + 1.57 mg x h/L; r2 = 0.986, P = 0.00001. The greatest pharmacokinetic variability occurred between 0 and 10 h postdose (absorption and distribution) between patients and even within individual patients monitored serially over time. The 12- to 24-h postdose portion (elimination) of the curve was consistently flat and uniform among patients. AUC were not consistent in individual patients over time. An AUC of more than 13 mg x h/L correlated with nephrotoxicity, whereas a value of 8 mg x h/L correlated with protection from rejection in first-transplant recipients. This AUC, however, was not able to prevent rejection in reengrafted or highly sensitized patients.

Adult↗

A novel keratan sulphate proteoglycan from a human embryonal carcinoma cell line.

We describe here the purification and partial characterization of a 200 kDa keratan sulphate proteoglycan found in the pericellular matrix of human embryonal carcinoma cells. Previously we have shown that this molecule is recognized by a monoclonal antibody (GCTM-2). The antigen was isolated using ion-exchange chromatography and gel filtration, purification being monitored by e.l.i.s.a. using GCTM-2. Metabolic labelling of GCT 27 C-4 embryonal carcinoma cells with sodium [35S]sulphate resulted in the incorporation of [35S]sulphate into the purified molecule. Throughout the purification procedure, the peaks of 35S radioactivity were coincident with the peaks of immunoreactivity, and this label was released both by digestion with keratanase and chondroitinase, confirming the proteoglycan nature of the antigen. The intact molecule ran as a single broad band of 200 kDa, which has been identified by silver staining and immunoblotting following gel electrophoresis. Amino acid analysis of the purified antigen indicated a high content of serine, glycine and aspartic acid/asparagine residues. Visualization by rotary-shadowing electron microscopy suggests that the purified material forms large aggregates, even under denaturing conditions. Deglycosylation of this preparation with trifluoromethanesulphonic acid yielded a major band of 55 kDa and a minor band of 48 kDa. The biochemical nature of the molecule described here, along with tissue distribution studies using GCTM-2, indicates that the antigen is not related to previously described keratan sulphate proteoglycans.

Amino Acids↗

Review of the American College of Radiology--National Electrical Manufacturers' Association standards activity.

The American College of Radiology and the National Electrical Manufacturers' Association published the ACR-NEMA Digital Imaging and Communications Standard in 1985. Implementations are just now becoming available. During this time, working groups of the committee responsible for the standard have been very active. An expanded version of the standard was published in 1988 and a third version, to be known as Digital Imaging and Communications in Medicine (DICOM), is being prepared for publication in 1992. This paper briefly reviews the history of the standard, describes recent activities, outlines the extensions planned for the DICOM standard, and describes the participation of the committee in international radiological imaging standards activities.

Diagnostic Imaging↗

Management of nephrotic syndrome in childhood.

Nephrotic syndrome is defined as proteinuria sufficiently severe to result in hypoalbuminaemia, oedema and hyperlipidaemia. The early modern history of this illness was characterised by the serendipitous development of renal biopsy technique at approximately the same time as the use of corticosteroids for nephrotic syndrome. The coincidence of these events set the stage for evaluating therapeutic response to corticosteroids and cytotoxic agents in relation to renal histology and ultimate clinical outcome. The International Study of Kidney Disease in Children (ISKDC) was initiated in the 1960s as a multicentre study examining these relationships in children. Over the next decade this study, as well as contributions from other investigators, helped define optimum therapy for these children. It was determined that a child with nephrotic syndrome under the age of 6 years, who did not present with hypertension, azotaemia, hypocomplementaemia or signs of systemic illness, had an approximately 85% chance of responding to corticosteroid therapy. If only those children who had minimal change histology on biopsy were considered, 94% responded. The original regimen which is still used today, was 60 mg/m2 bsa/day prednisone administered on a 3 times per day dosage schedule for 4 weeks, followed by an additional 4 weeks of therapy at a dose of 40 mg/m2 bsa given as a single oral dose every other day. Of those who respond roughly one-third will have no relapses, while almost half will have frequent relapses (greater than or equal to 2 in 6 months) and the rest will have infrequent relapses. Patients in relapse are treated as at presentation but are usually converted to the 40 mg/m2 bsa dose when the urine has been free of protein for 3 days, and are then tapered off or maintained on this dose for several weeks, depending on the individual's history of relapses and incidence of side effects from corticosteroids. For those children who are suffering frequent relapses and severe corticosteroid side effects (e.g. growth failure, morbid obesity, aseptic necrosis of bone), cytotoxic agents were identified as providing long term remission. After inducing remission with conventional corticosteroid dosages, cyclophosphamide is administered at a dose of 2 mg/kg/day given as a single dose for 8 weeks. This regimen was shown to lead to approximately 70% of patients being in remission 2 years after completion of this course of therapy. Chlorambucil given at a dose of 0.2 mg/kg/day as a single oral dose has been equally efficacious.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗

Reliability of three clinical measures of muscle tone in the shoulders and wrists of poststroke patients.

Muscle tone was tested at the shoulders and wrists of 49 randomly selected poststroke patients with the use of resting joint position (SJP and WJP), resistance to passive movement or stiffness (SRM and WRM), and angle of appearance of resistance (SAR and WAR). Subjects were tested while seated with their arm supported in a suspension sling adapted for free movement. Five of the first and immediately repeated measurement pairs showed strong correlations and interrater reliability (SJP, .839; WJP, .900; SRM, .886; WRM, .904; SAR, .884 [p less than .05]). The sixth (WAR) showed moderate reliability (.618, p less than .05). Resting joint position measurements were most reliable among subjects with higher tone. The joint first measured had a slight order effect on SRM among subjects with higher muscle tone. Its second measurements were slightly increased over the first among those subjects whose shoulders were measured first and slightly reduced when measured immediately after the wrist. Reliable means of clinical evaluation of muscle tone at the shoulder and wrist are available if the influence of level of tone and the mutual influence of muscles tested are prudently considered.

Aged↗

Primary liver tumors: diagnosis by MR imaging.

MR features of 153 proved primary liver tumors (95 malignant, 58 benign) in 55 patients with hepatocellular carcinoma (21), cholangiocarcinoma (seven), carcinosarcoma (one), hepatoblastoma (one), hemangioma (16), hepatic adenoma (four), focal nodular hyperplasia (three), leiomyoma (one), and hemangioendothelioma (one) were studied retrospectively to determine which techniques are most reliable for lesion detection and which criteria are most useful for differential diagnosis. MR data were correlated with histologic features such as fatty degeneration, fibrosis, and peritumoral edema. Unlike metastatic cancer, hepatocellular carcinoma was best detected (p less than .01) with T2-weighted pulse sequences. The mean tumor-liver T2 difference was 34.4%, while the mean T1 difference was only 21.8%. A tissue-specific diagnosis of hepatocellular carcinoma was possible in 14 of 21 patients by identification of fatty degeneration of the tumor (eight of 17), tumor capsule (five of 21), and/or vascular invasion (six of 21). MR features of peritumoral edema, present in six of 21 patients with hepatocellular carcinoma and in seven of 25 patients with metastases, were exclusively associated with malignant tumors. The large variation in tissue characteristics (relaxation times and proton density) seen in primary liver tumors necessitates the use of multiple pulse sequences to maximize lesion detection. However, the combined use of T1- and T2-weighted spin-echo and T2-weighted phase-contrast images had the advantage of distinguishing benign from malignant primary liver tumors in 48 of 55 patients in this series.

Adenoma↗

Studies of renal function in animals chronically treated with apomorphine.

Based on the observation that orally administered apomorphine may induce nephrotoxicity, we studied the renal effects of a two-week subcutaneous infusion of apomorphine in rats. Drug-treated rats did not exhibit any change in renal cortical uptake of an organic cation (tetraethyl ammonium), organic anion (para-hippuric acid), creatinine clearance, or fractional excretion of sodium and potassium. Renal histology showed no change specific to drug. A small increase in urinary N-acetylglucosaminidase, a tubular enzyme, was measured but a second tubular enzyme showed no change. We conclude that parenterally administered apomorphine is not associated with renal toxicity.

Animals↗

Epithelioid sarcoma with diffuse bone marrow metastases and associated leukemoid reaction. A case report and brief literature review.

A patient with a recurrent epithelioid sarcoma of the hand was observed for five years with a diagnosis of nodular fasciitis. Eventually, the patient had a pulmonary metastasis and diffuse bone marrow spread, which was associated with a leukemoid reaction. Bone marrow dissemination by sarcoma is unusual, and its production of a leukemoid reaction very rare; this is its first reported occurrence in epithelioid sarcoma that the authors have been able to identify in the literature.

Adult↗

Dietary treatments of obesity.

Dietary treatment of obesity is based on one or another of two premises: that the obese eat too much or that they eat the wrong things. The first is a tautology lacking explanatory power. The second is a meaningful and promising hypothesis but has yet to be effectively applied. At present, virtually all outpatient treatments of obesity, including behavior modification, are based on the first premise and consist of strategies for reducing the subject's caloric intake. Most such interventions produce short-term weight loss. Regain after the end of treatment remains the usual outcome. A survey of studies published in the period 1977-1986 and reporting on dietary or behavioral treatment of obesity reveals that the maximum percentage of body weight lost is, on average, 8.5 percent--no different from the value, 8.9%, in similar studies from 1966-1976, as reviewed by Wing and Jeffery. The principal determinant of success in such programs appears to be the intake weight of the subjects: the higher the intake weight, the more successful the intervention will appear to be. The goals and research methods of studies on dietary treatments for obesity are overdue for ethical as well as scientific reevaluation. The same may be said for the numerous programs providing such treatment outside the context of research.

Animals↗

Primary leptomeningeal gliomatosis and "numb, clumsy hands": a case report.

A 48-year-old man presented with the numb, clumsy hand syndrome. Evaluation revealed a high cervical cord lesion. Surgical exploration discovered leptomeningeal gliomatosis with no discernible intraparenchymal component. The clinical features of the case, the neuroimaging studies including magnetic resonance scanning, and the most unusual pathological nature of the lesion are discussed.

Astrocytoma↗

Gallium-67 scintigraphy in well-differentiated lymphocytic lymphoma of the skin.

Skin lymphomas are now divided into "T" or thymic cell lymphomas (mycosis fungoides being the principal type) and "B" cell lymphomas after the bursa of Fabricius. The "T" cell lymphomas all are identified by the thymic or cerebriform cell. Those lymphomas of the skin which do not contain these characteristic cells are derived from the bursa cells and are termed "B" cell lymphomas. A large percentage of these non "T" cell lymphomas have been histologically diagnosed as lymphocytic lymphoma of the skin (1). The authors had an opportunity to scan a patient with histologically proven lymphocytic lymphoma of the skin with Ga-67 and obtained on excellent correlation between gallium accumulation in the skin lesions and histologic confirmation of lymphocytic lymphoma.

Gallium Radioisotopes↗

The nicotine fix.

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Adolescent↗