Biomedical subjects
Publications and source records attributed to E Pike.
A 28-year-old woman with uncomplicated psoriasis vulgaris presented with spinal hyperostosis and osteitis. The absence of peripheral arthritis, sacroiliitis, and diffuse idiopathic skeletal hyperostosis (DISH) raised the possibility that the spinal lesion was an extracutaneous manifestation of psoriasis. We review the association between uncomplicated psoriasis vulgaris and skeletal involvement.
The Participative Decision-making Scale for Nurses was administered before and after a six-week interval to 30 nursing students in the final semester of their programme. Reliability coefficients for the four subscales, with the exception of the clinical subscale, were of reasonable magnitude (range .42 to .62).
This paper reports on the initial stage of a research program that examines decisions nurses expect to participate in and the methods by which they expect to participate. This stage of the research focuses on the development of a scale, the Participative Decision Making Scale for Nurses (PDMSN), to measure expectations for participative decision making (PDM) among graduating nurses. It has four subscales that measure expectations for participation in clinical, unit, hospitalwide, and strategic decisions. The PDMSN was administered to two groups of graduating nursing students. Results indicate that the subscales of the PDMSN have high internal consistency; alpha coefficients in Study 1 and Study 2 ranged from .70 to .85 and from .76 to .90, respectively. Patterns of correlations among the subscales and significant correlations with an alternative scale measuring PDM indicate that it is a valid instrument.
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The cholinesterase (ChE) activities were measured in-season and out-season in a total of 204 greenhouse workers and 360 non-exposed controls. No seasonal ChE variation were observed in the controls, whereas an in-season depression was seen in the workers, indicating an uptake of anti-cholinesterase agents during cultivation of greenhouse flowers in the intervals between sprayings (p = 0.0001). The anti-ChE agents applied seem to persist in the greenhouses and cause continued subtoxic uptake for weeks since last application. Wearing of protective gloves did not prevent the uptake. Thus, chronic percutaneous and oral uptake occurs as a result of cultivation of greenhouse flowers.
The dietary intake of anticholinesterase (anti-ChE) agents was estimated in 331 schoolteachers during the spraying season. Summer plasma-cholinesterase (ChE) activity was compared with the baseline value obtained during winter. Intraindividual plasma-ChE activity varied independently of factors such as drugs, non-malignant diseases, alcohol and smoking. A depressed mean plasma-ChE, indicating an intake of anti-ChE agents (P = 0.04), was observed in individuals who consumed exclusively agriculturally-grown fruits and vegetables without an additional intake of unsprayed, home-grown products. It remains to be determined whether a subclinical but chronic intake of anti-ChE agents in the diet can be hazardous to humans.
Unusual lung tumors are not simply pathological curiosities. They demonstrate features of major significance in diagnosis, treatment, and prognosis. Six of these tumours are discussed: (1) Carcinosarcoma is rarely found in the lung. The histogenis of the lesion is unclear and the prognosis is poor. (2) Only three cases of pleomorphic adenoma have previously been described. Differentiation from other "mixed tumours" of the lung is essential. (3) A rare case of bronchial adenoma producing ectopic ACTH is described. Early recognition of these polypeptide hormone-secreting tumours is stressed. (4) Oat cell carcinoma with the myasthenic (Eaton-Lambert) syndrome shows the clinical features which should permit early tumour diagnosis. The hazards of muscle relaxants must be recognized. (5) Prostatic carcinoma with endobronchial metastases is is discussed. The importance of localization of the primary tumour is emphasized. (6) An example of double primary carcinoma is presented. The rarity of this finding may be related to the poor prognosis of patients with bronchogenesis carcinoma.
The relative role of lipoproteins, albumin and orosomucoid in the serum binding variation of various drugs was examined by separate removal of these proteins. Lipoproteins were removed from serum by ultracentrifugation, albumin by affinity chromatography and orosomucoid by immunoprecipitation. Removal of the lipoproteins did not affect the serum binding of the acidic (phenytoin) and neutral (digitoxin) drugs tested, nor the basic drugs disopyramide, quinidine or propranolol. A reduction in binding of amitryptyline, nortriptyline, doxepin and desmethyldoxepin was observed. Removal of albumin did, with some exception for nortriptyline, not affect the serum binding of the basic drugs tested. A pronounced reduction in the binding of phenytoin and digitoxin was observed. Removal of orosomucoid did not affect the binding of the acidic and neutral drugs tested. A reduction in the binding of all the basic drugs tested was observed, especially for disopyramide whose binding almost disappeared. Quinidine, propranolol, phenytoin and digitoxin all bound to isolated lipoproteins, but the removal of lipoproteins had no effect on the total serum binding for these drugs. Hence, the use of deficient sera provides valuable information as to the quantitative role of the various proteins in drug binding, whereas studies using purified proteins are often necessary to examine the mechanisms of the drug protein interactions.
The importance of variation in plasma binding in the uncertain correlation between total plasma concentration and the antidepressive effect of amitriptyline (AT) and its active metabolite nortriptyline (NT) was examined. Plasma binding of AT and NT in 131 plasma samples from 87 patients was analyzed by equilibrium dialysis at 37 degrees for 3 hr. There was a twofold variation in percent unbound AT and NT (range 3.5% to 8.6% and 5.4% to 11.3%) and there was no correlation between percent and unbound drug and total drug concentration (range 54 to 6910 nmol/l and 77 to 3420 nmol/l for AT ant NT). The correlation coefficient relating unbound drug concentration of AT and NT to total concentration in plasma was 0.99 for the whole group and 0.16 for the NT therapy control patients, with total plasma concentrations within the therapeutic range. At therapeutic concentration AT was 66.6% and 63.5% bound to purified isolated orosomucoid (alpha 1-acid glycoprotein) and albumin, at physiologic concentrations. The binding to isolated lipoproteins was not examined, but no correlation was found between percent unbound AT and NT and plasma concentration of triglycerides, cholesterol, or orosomucoid.
Using isotope technique, the serum binding of amitriptyline (AT), nortriptyline (NT), and quinidine (Q) was measured by equilibrium dialysis in sera containing varying amounts of lipoproteins. Sera were obtained from 10 fasting subjects with normal to grossly elevated levels of cholesterol, triglycerides, or both. When the lipoproteins were removed from eight of the sera by a standard ultracentrifugation technique, the ratio bound/unbound (B/F) AT decreased an average of 47% (range 30% to 68%), NT an average of 54% (range 39% to 67%), and Q an average of 6% (range 0 to 16%). This decrease in the ratio B/F correlated linearly with the sum of serum concentrations of cholesterol and triglycerides for AT (r = 0.88) and NT (r = 0.82), but not for Q (r = 0.15). In three lipoprotein-depleted sera resuspended with lipoproteins at eight different concentrations ranging from 0 to 100% of the original content, there was a linear correlation between the ratio B/F for AT and NT and the lipoproteins, as evidence by cholesterol or triglycerides concentrations (r = 0.97 to 0.99), but not for Q (r = -0.17 to 0.36). Finally, in the original 10 serum samples, there was a linear correlation between the ratio B/F and the serum lipoproteins (sum of cholesterol and triglycerides) for AT (r = 0.89) and NT (r = 0.68), whereas there was no such relationship for Q (r = -0.15). These data indicate that basic drugs differ in binding characteristics (probably depending on lipophility).
1 Measuring total plasma levels of disopyramide (DP) and the main metabolite mono-N-dealkyldisopyramide (MND) in patients on maintenance therapy with DP has shown concentrations of MND comparable with those of DP, with wide intersubject variations. 2 A method which permits simultaneous measurement of unbound fraction of DP and MND has been developed. 3 In healthy subjects the unbound fraction of both DP and MND was concentration dependent, i.e. increased with higher concentrations of DP or MND. 4 The plasma protein binding of DP is altered by varying concentrations of MND. Clinically relevant concentrations of MND may increase the unbound fraction of DP approximately twofold. 5 The plasma protein binding of MND is also altered by varying concentrations of DP. Variation in the concentration of DP from the lower to the upper part of the therapeutic range may cause a 1.5-fold increase in the unbound fraction of MND. 6 In the assumed therapeutic range of 6-15 mumol DP/L, the interpatient variance of unbound DP concentration might be ten-fold or even higher. The present findings indicate the need for monitoring unbound drug concentrations in any attempt to establish plasma concentration/effect relationship.
A 30-year-old man with recurrent sinopulmonary infections, eventually fatal, was found to have common variable immunodeficiency. In addition to low serum immunoglobulin concentrations he also had lymphopenia and cell-mediated immunodeficiency as shown by cutaneous anergy and a poor lymphocyte response to phytohemagglutinin (PHA) in vitro. However, intradermal injection of PHA produced a vigorous cutaneous response, showing that some cell-mediated responsiveness remained. The responsiveness of his lymphocytes to PHA was restored towards normal (confirmed by chromosome studies) by the addition of a small number of normal leukocytes to cultures; thus a reversible functional defect in his T-lymphocytes was revealed. Experiments indicated that the defect was cellular and not due to serum factors and it was concluded that normal leukocytes restored a missing factor to the patient's T-lymphocytes. Although counts of macrophage precursor cells in the bloodstream were low, thus contributing to the immunodeficiency, this could not have caused the reduced PHA response. Several relatives of this patient had lymphoma; two cousins had common variable immunodeficiency.
The binding of the basic drugs quinidine, propranolol and amitriptyline, the neutral drug digitoxin and the acidic drug phenytoin to heparinised normal plasma, to orosomucoid (alpha 1-acid glycoprotein)-deficient plasma and to purified orosomucoid and albumin was studied in both the presence and absence of tris (2-butoxyethyl)-phosphate (TBEP) and de-(2-ethylhexyl)-phthalate (DEHP). The addition of TBEP and DEHP to heparinised plasma in concentrations up to 2.5 mmol/L markedly increased the unbound fractions of quinidine and propranolol, but the increase was less for amitiriptyline, TBEP being the most potent displacer. In orosomucoid-deficient plasma, which was prepared by immunoprecipitation, the free fraction of quinidine was similar to that of normal plasma in which maximal displacement with TBEP was obtained. The addition of the displacers to orosomucoid-deficient plasma caused no further reduction in the binding, nor was the plasma binding of digitoxin and phenytoin significantly affected. When combining purified albumin and orosomucoid in concentrations found in normal plasma, quinidine binding approached that of heparinised normal plasma. This study confirms the dominant role of orosomucoid in the variable plasma binding of basic drugs, and underlines the value of using immunologically prepared orosomucoid-deficient plasma and TBEP or DEHP as model displacers.