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Biomedical subjects

S J Williams

Publications and source records attributed to S J Williams.

At least 109 records · Page 6Linked to original sources
PubMed1987

Peptide histidine-methionine immunoreactivity in plasma and tissue from patients with vasoactive intestinal peptide-secreting tumors and watery diarrhea syndrome.

The presence of peptide histidine-methionine (PHM)-like peptides has been determined in plasma and tumor specimens from patients with vasoactive intestinal peptide (VIP)-secreting tumors and the watery diarrhea syndrome. All patients had strikingly elevated plasma concentrations of PHM immunoreactivity (median, 1800; range, 500-6800 pmol/liter; n = 12), which were higher than those of VIP (median, 235; range, 50-580 pmol/liter). In patients with other endocrine and nonendocrine pancreatic tumors, plasma PHM concentrations were not significantly different from normal (median, 20; range, 5-60 pmol/liter; n = 28). Plasma samples from patients with diarrhea due to other illnesses also had PHM concentrations that were not significantly different from normal (median, 40; range, 10-80 pmol/liter; n = 23). The gel chromatographic profiles of plasma and tumor extracts from patients with VIP-secreting tumors revealed the presence of at least two molecular forms that reacted with an antiserum directed to the N-terminus of PHM (SY1). The later peak (Kav, 0.50-0.53) corresponded in position to synthetic PHM and also reacted with the PHM-specific antiserum (SY2). The earlier peak (Kav, 0.30-0.37), not reactive with antiserum SY2, corresponded to a large molecular form of PHM-like immunoreactivity previously identified as the predominant form in normal human stomach and plasma, though not in the rest of the intestinal tract. The neuroendocrine nature of the tumors was confirmed by the demonstration of immunostaining with a battery of antisera to neuroendocrine markers. Immunocytochemistry revealed the presence of both VIP and PHM in tumor cells. The presence of high circulating concentrations of PHM-like immunoreactivity in patients with VIP-secreting tumors, as measured with a PHM N-terminus-directed antiserum, SY1, suggests that use of this type of antiserum may provide valuable information in the diagnosis of such tumors. The contribution of the PHM-like peptides to the features of this syndrome is not known.

Adenoma, Islet Cell↗
PubMed1987

Clinical evaluation of SMS 201-995. Long-term treatment in gut neuroendocrine tumours, efficacy of oral administration, and possible use in non-tumoural inappropriate TSH hypersecretion.

Long-acting somatostatin analogues such as SMS 201-995 (Sandoz) are being evaluated in a wide range of clinical indications, including gut neuroendocrine tumours and acrogemaly. Long-term continuous SMS 201-995 treatment has achieved useful symptomatic improvement in diarrhoea in 4 patients with metastatic VIPomas who had relapsed following previous treatment. Clinical improvement has outlasted suppression of VIP secretion (suggesting an additional direct antisecretory action of SMS 201-995) and has occurred despite expansion of hepatic metastases. In 6 patients with tumours secreting gastrin and/or glucagon, secretion of these peptides was acutely inhibited by SMS 201-995. However, endocrine and clinical responses to chronic treatment have been less consistent. SMS 201-995 is active orally at doses of 4-8 mg and when given thrice-daily to 6 patients with active acromegaly, suppressed mean 24-h growth hormone levels by 51-88%. Despite significantly reduced plasma insulin concentrations, glucose tolerance did not deteriorate. SMS 201-995 was also effective in suppressing thyroid-stimulating hormone (TSH) and thyroid hormone secretion in a patient with mild thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion. In all cases SMS 201-995 treatment has been well tolerated and has few side-effects.

Acromegaly↗
PubMed1987

Characterization of in vivo chemistry of cations in the heart.

A variety of laboratory procedures can be used to define the chemistry and pharmacokinetics of myocardial cationic imaging agents. These methods are utilized to define the in vivo chemistry of cationic heart agents, in order to understand the kinetics and mechanisms of: tissue and cellular transport, subcellular distribution, and intracellular localization. Transport across cell membranes can be active, passive or facilitated. Studies performed in erythrocytes, heart cells, slices and isolated perfused hearts using methods for separation of metabolites have shown a high degree of myocardial specificity for [99mTc]hexakis alkyl isonitrile by an uptake mechanism different from 201Tl. These studies demonstrate the importance of in vivo chemistry and pharmacokinetics in the development of new radiopharmaceuticals.

Animals↗
PubMed1986

Secretion of pancreatic polypeptide in patients with pancreatic endocrine tumors.

Pancreatic polypeptide is often secreted by pancreatic endocrine tumors and is considered a marker for such tumors. To investigate the diagnostic value of this marker, we studied 323 patients with proved pancreatic endocrine tumors. We found plasma concentrations of pancreatic polypeptide to be elevated (more than 300 pmol per liter) in 144 patients (diagnostic sensitivity, 45 percent). However, plasma levels of pancreatic polypeptide can also be elevated in the absence of a pancreatic tumor. To ascertain whether the administration of atropine could distinguish between normal and tumor-associated polypeptide secretion, we studied 30 patients with pancreatic tumors and high plasma levels of pancreatic polypeptide, 18 patients without tumors who had elevated levels of pancreatic polypeptide, and eight normal controls. Polypeptide levels in the 18 patients without tumors were substantially lower than in the 30 patients with tumors. Atropine (1 mg intramuscularly) did not suppress polypeptide levels in patients with tumors, but did suppress plasma levels by more than 50 percent in all subjects without tumors. Thus, although its diagnostic sensitivity is low, pancreatic polypeptide appears to be a useful adjunctive marker of many pancreatic endocrine tumors, and the atropine suppression test can be used to distinguish normal from tumor-related secretion of the polypeptide. Identification of the type of pancreatic endocrine tumor still requires measurement of the hormone that is specific for the tumor.

Adenoma, Islet Cell↗
PubMed1986

Remission of symptoms during long term treatment of metastatic pancreatic endocrine tumours with long acting somatostatin analogue.

Five patients with metastatic pancreatic endocrine tumours injected a long acting somatostatin analogue (SMS 201-995) 50 micrograms subcutaneously every 12 hours and were followed up for three to six months. Treatment aimed at controlling excess secretion of hormone by the tumours thereby bringing symptomatic relief. Four patients showed a significant reduction in tumour related hormone concentrations but in none did values return to normal. All five patients, however, noted definite symptomatic improvement and in one this was dramatic (disappearance of life threatening diarrhoea and correction of metabolic acidosis and hypokalaemia within 48 hours). Mild worsening of symptoms and increasing fasting tumour related hormone concentrations after three to six months of treatment were reversed by doubling the 12 hourly dose. The treatment was well tolerated and had no deleterious effect on fasting blood glucose concentrations. This somatostatin analogue seems a promising non-invasive treatment for metastatic pancreatic endocrine tumours.

Adult↗
PubMed1986

Factors related to the use of ambulatory mental health services in three provider plans.

The use of ambulatory mental health (MH) services by adults was studied in three provider plans: Blue Cross (BC), Group Health Cooperative (GHC) and United Healthcare (UHC), an experimental new plan in which a patient's primary care physician managed all of his care. Approximately 8.3% of the enrollees in each plan had some MH use in the 18 months of the study. We studied correlates of MH use (yes/no). Sex was not a significant predictor of MH use. In general, worse health and lower socioeconomic status (SES) were correlated with having at least one MH visit, but better health and higher SES were correlated with a higher quantity of use for those who had some MH use. The three insurance plans did not differ significantly in the proportion of people who had any MH services, but BC users of MH services had 2-3 times more MH visits and higher costs than GHC and UHC users. This suggests that the reliance on primary care providers in UHC and GHC may have changed the nature of MH care as compared to Blue Cross. The effects of income, MH need and symptom sensitivity on MH use were different among the three plans.

Ambulatory Care↗
PubMed1986

Chronic upper extremity ischemia: current concepts in management.

As a rule, the few innominate or subclavian obstructions that are symptomatic produce neurologic and extremity symptoms that are easily reversed by an extrathoracic surgical approach. Balloon angioplasty is seeing some utility for this problem also. Concomitant carotid disease may be more significant in that its correction may not only prevent stroke but also mitigate symptoms of subclavian steal. The reconstruction of lesions distal to the vertebral artery frequently results in dramatic and durable improvement. Sympathectomy has a valuable role to play in those cases in which restoration of perfusion cannot be complete.

Angioplasty, Balloon↗
PubMed1986

Inhibition of antipyrine metabolism by interferon.

Antipyrine clearance was measured before and 1 day after administration of a single intramuscular dose of recombinant human leukocyte alpha A interferon. In the nine patients studied, antipyrine clearance was reduced after interferon from 0.49 (0.21-1.13) ml kg-1 min-1 (median (range)) to 0.41 (0.20-1.07) ml kg-1 min-1, P less than 0.01. In individual patients, the decrement in antipyrine clearance was variable, ranging from 5-47% (median, 16%). This study provides the first direct evidence that interferon inhibits hepatic oxidative drug metabolism in humans and alerts clinicians to the possibility of potentially toxic drug-drug interactions.

Adult↗
PubMed1986

Effect of abdominal binders on breathing in tetraplegic patients.

We studied the effect on breathing of a conventional and a newly designed abdominal binder in seven patients with complete tetraplegia. The indices of respiratory ability used were the transdiaphragmatic pressure on maximal sniff (sniff Pdi), the maximum static inspiratory mouth pressure (PImax), and the vital capacity (VC). These were measured in patients with and without binders, in the supine position, raised up to 70 degrees on a tilt table, and seated upright. When patients were raised from the supine to the 70 degrees tilt and to the seated posture, sniff Pdi and VC decreased. Both binders improved VC in the seated position and at 70 degrees tilt, and sniff Pdi at 70 degrees tilt. The new binder was as effective as but no better than the conventional binder. PImax was too variable to be a valuable index of inspiratory power. These findings support the view that abdominal binders assist breathing in tetraplegic patients who are seated or raised to near vertical positions.

Abdominal Muscles↗
PubMed1986

Production of pituitary protein 7B2 immunoreactivity by endocrine tumors and its possible diagnostic value.

7B2 is a protein originally isolated from pituitary, which has been shown to be present in the central nervous system and in certain peripheral tissues, with very high concentrations in pancreatic islets. Endocrine and nonendocrine tumors from 185 patients were investigated by RIA for the presence of immunoreactive pituitary protein 7B2. The highest mean concentration of 7B2 immunoreactivity was found in insulinomas [452 +/- 174 (+/- SEM) pmol/g wet wt tissue; n = 16], which was significantly higher than the concentration in normal adult pancreatic tissue (28.3 +/- 4.4 pmol/g; n = 7). High concentrations of 7B2 immunoreactivity also were found in other endocrine tumors. The cellular localization of 7B2 was studied in normal pancreas, pancreas with hyperplastic islets, and endocrine tumors. 7B2 immunoreactivity was localized to B-cells in the normal pancreas and to variable proportions of cells in islet cell hyperplasias, B-cell tumors, and pheochromocytomas. Plasma concentrations of 7B2 immunoreactivity also were determined in 255 patients with established diagnoses of endocrine or nonendocrine tumors. The proportion of patients with elevated plasma concentrations (arbitrarily set at more than 4 SD above the mean) were 42 of 72 with pancreatic islet cell tumors, 7 of 11 with midgut carcinoid tumors, and 5 of 13 with medullary carcinomas of the thyroid. Especially high values were found in patients with glucagonomas (14 of 20), vipomas (12 of 13), and pancreatic polypeptide-producing tumors (5 of 6). Thus, 7B2 immunoreactivity is produced by a variety of different tumors and may serve as a tumor marker, especially in patients with certain pancreatic islet tumors.

Adult↗
PubMed1985

Use of outpatient somatic health services by patients who use or need mental health services in three provider plans.

A major topic in mental health (MH) research addresses the problem that patients who use mental health services have inappropriately high levels of somatic use, and examines whether provision of mental health services can decrease the inappropriate use (the so-called offset effect). However, the research showing higher somatic use by mental health patients has usually been unable to control for the patients' health status, or for their mental health status. In this paper we examine use of somatic health services by enrollees in three provider plans as a function of both mental health use and mental health need. In two of the provider plans (an HMO and a prepaid independent practice association), MH users used significantly more outpatient somatic services than non-MH patients, after control for age and sex, and after control for the number of chronic conditions they had. People with MH need, however, did not use significantly more MH services than those without MH need. In the third plan, a Blue Cross/Blue Shield type of plan, results were different; MH users did not have significantly higher somatic utilization after control for chronic conditions, and those with MH need did have significantly higher somatic utilization after control for age and sex, but not after control for the number of chronic conditions. These results suggest that the form of inappropriate use of outpatient somatic services, and the nature of an offset effect, may be specific to the type of insurance provided.

Adult↗
PubMed1985

Changing concepts of ocular irritation evaluation: pitfalls and progress.

A series of studies has been carried out to evaluate methods of modifying existing ocular test protocols with the aim of reducing the numbers of animals used and lessening the severity of the response with the minimum effect on the predictive value of the tests. Initial studies showed that when the dose administered is reduced from 100 to 10 microliter, the severity of the response is reduced but the rank order of severity of a series of test compounds is unchanged. This series of studies also demonstrates that the greatest source of variability in obtaining irritation scores is in the rabbit population and that the numbers of rabbits used per test can be chosen on the basis of the required degree of accuracy. In a related study it is shown that direct corneal application of the test material (10 microliter) increases the corneal response but has no effect on the conjunctival response in comparison with reactions after application in the conjunctival cul-de-sac. Finally, a retrospective study was performed to determine whether severe skin irritation is predictive of a similar level of response in the eye. Of 60 compounds known to be severe skin irritants, only 39 are severe eye irritants whereas 15 are mild to non-irritants. The remainder were found to cause moderate responses in the eye. These data demonstrate that existing ocular irritation test protocols can be modified to use fewer animals under less extreme conditions without significant compromise of predictability. However, dermal irritation, determined using current test protocols, does not appear to be directly predictive of ocular irritation potential.

Animals↗
PubMed1985

Lowered ultraviolet minimal erythema dose in hemiplegia.

In view of recent reports of increased tanning in hemiplegic limbs, we have investigated ultraviolet (u.v.) minimal erythema dose (MED) in hemiplegia using the bilateral comparison technique. Seven of 10 patients had a lower MED in the hemiplegic arm compared to the normal side, the mean reduction being 16% (range 0-33%, P = 0.003). No patients had a higher MED in the hemiplegic arm. We review the literature regarding other non-neurological features of hemiplegia, in particular asymmetry of temperature, oedema, and finger clubbing, and we propose a vasomotor or trophic aetiology for these findings.

Erythema↗
PubMed1985

Contribution of the rib cage to breathing in tetraplegia.

In tetraplegia there is often paradoxical inward motion of the rib cage during inspiration. The volume of this negative contribution is difficult to estimate but can be obtained by optical mapping. The partitioning of ventilation between the rib cage and abdomen in six normal subjects, 10 stable tetraplegic patients, and one tetraplegic patient at intervals during rehabilitation has been studied by this technique. In normal subjects the tidal volume and the vital capacity were the sum of positive contributions from the rib cage and abdomen. In stable tetraplegic subjects with similar neurological levels, the rib cage contribution varied widely but the total chest wall displacement could not be predicted from the vital capacity. In the patient studied sequentially rib cage paradox reversed with time after injury, and this was associated with an absolute increase in vital capacity and an improvement in the action of the diaphragm.

Adolescent↗
PubMed1984

Interactions of heavy metals with the pulmonary metabolism of [3H]benzo[a]pyrene.

To test the hypothesis that the inhalation of heavy metal aerosols from polluted air or cigarette smoke could alter the metabolism of polycyclic aromatic hydrocarbons, isolated, ventilated, and perfused rat lungs were used to study the effects of NiCl2, CdCl2, and CoCl2 on the pulmonary metabolism of [3H]benzo[a]pyrene [( 3H]BAP). Five minutes prior to removing the lungs from a rat, 100 microliter of isotonic sucrose containing 1 mumole of NiCl2, CdCl2, or CoCl2 was instilled intratracheally. The lungs were placed in the perfusion system and washed free of blood. After 10 min, 5 nmole of [3H]BAP dissolved in 100 microliter of dimethylsulfoxide was introduced in the arterial circulation. After 45 min, the lungs were homogenized and the homogenates and perfusates were extracted with ethyl acetate:acetone (2:1, v/v) for analysis by HPLC. Binding of [3H]BAP metabolites to lung tissue was also determined. The metabolism of [3H]BAP was found to be inducible by pretreatment of rats with beta-naphthoflavone (80 mg/kg) and to be inhibited by the inclusion of metyrapone (1.0 mM) or indomethacin (0.1 mM) in the perfusate. Instillation of NiCl2 resulted in a slight inhibition of metabolism. In the presence of CdCl2, 20% more of the parent compound was metabolized compared to sucrose-treated controls, but the fraction of organic solvent extractable metabolites increased to 213% of controls. CoCl2 was without effect on [3H]BAP metabolism. In all cases, the extent of covalent binding to lung macromolecules was proportional to the extent of metabolism of the [3H]BAP. Since heavy metals and polycyclic aromatic hydrocarbons coexist in the same atmospheric aerosols, heavy metal exposure from polluted urban or occupational air or cigarette smoking may have profound effects upon the bioactivity of a common organic carcinogen.

Animals↗
PubMed1984

Prediction of ocular irritancy potential from dermal irritation test results.

In a survey of the test files of Haskell Laboratory, it was found that of the materials that had been tested on rabbit skin for primary irritation or corrosivity, 60 were severe irritants or corrosive on the skin and had also been tested for ocular irritancy. Of these 60 materials only 39 were severe eye irritants, while 15 were mild irritants or non-irritants and the remainder were considered to be moderate irritants. Thus, to suggest that materials are eye irritants solely on the basis of their skin-irritation properties may be misleading, even when severe dermal irritants are considered.

Animals↗
PubMed1984

Ambulatory mental health services utilization in three provider plans.

This article examines the use of mental health services in three insurance plans: Blue Cross (BC), a health maintenance organization (HMO), and an independent practice association (IPA) in which the primary care physician was to manage all care for an individual. Approximately 7.3% of the enrollees in all three plans used some mental health care in the 18-month study period. The percent of enrollees with mental health utilization was lower in BC than in the other two plans, but the total quantity of mental health care use per enrollee and per user was much higher in BC than in the HMO and the IPA. Use was highest in the 19-44-year-old age group, and there were no significant differences between men and women in use of mental health services. There were substantial differences by race in all three plans: white persons were more likely to use any mental health care and had more visits than nonwhite persons after seeking mental health use. A similar study was conducted in the early 1970s on a poverty-level population enrolled in BC and the HMO. The findings of this study are similar, except that in the low-income study mental health care use was lower, and males used less mental health care than females. These differences might be attributable to the difference in enrollees' socioeconomic status in the two studies or to the increasing acceptability of mental health care utilization, particularly for males.

Adolescent↗