ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

1

Electronic Resource

Evaluation of the safety of enalapril in the treatment of heart failure in the very old (1988)

O'Neill, C. J. A. ; Bowes, S. G. ; Sullens, C. M. ; [et al.]

Springer

European journal of clinical pharmacology 35 (1988), S. 143-150

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ISSN: 1432-1041

Keywords: enalapril ; heart failure ; very old ; adverse reactions ; drug safety

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia. Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages. Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up. The benefit to cost ratio of ACE inhibitors might be improved in aged patients by their use at an earlier stage in the natural history of heart failure, when perfusion of essential organs is not grossly impaired, but carefully monitored trials would be necessary to establish this.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00609243

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2

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Therapeutic drug monitoring of digoxin: Help or hindrance? (1986)

Dobbs, R. J. ; Nicholson, P. W. ; Denham, M. J. ; [et al.]

Springer

European journal of clinical pharmacology 31 (1986), S. 491-495

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ISSN: 1432-1041

Keywords: digoxin ; therapeutic drug monitoring

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary A major role of therapeutic drug monitoring services is to advise on the dose of a drug which would be required to bring the concentration in the blood to within specific ‘therapeutic’ limits. Monitoring digoxin usage constitutes a substantial part of the work load. We have examined the potential variability in recommendations for digoxin dosages based on a series of serum digoxin measurements in each of 80 out-patients. In over a third of cases a dose, which seemed to be optimal on the basis of the first assay result, would have produced concentrations outside the conventional therapeutic range when the measurement was repeated. This was despite careful supervision of medication and the timing of the blood sample in relation to its administration. In routine practice the apparent variability in dose requirements would be far greater. Objectives of therapeutic drug monitoring services remain the same, the way forward would seem to lie in their taking on a heavy commitment to counsel and supervise patients before repeated blood sampling. However, effort and resources might be better channelled into producing simple prescribing aids relating the risk of cardiotoxicity directly to the size of the maintenance dose and the individual's renal function.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00613530

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3

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Prescribing digoxin in geriatric units: The unexplained variability in dosage requirements (1987)

Dobbs, R. J. ; Royston, J. P. ; O'Neill, C. J. A. ; [et al.]

Springer

European journal of clinical pharmacology 32 (1987), S. 611-614

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ISSN: 1432-1041

Keywords: digoxin ; geriatrics ; dosage requirements

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary Some physicians regard patients of Geriatric Units as a homogeneous population with respect to digoxin dosage requirements. Others advocate the use of pharmacokinetic models in prescribing digoxin for the elderly. Sixty in-patients of Geriatric Units were studied and the results compared with those previously obtained from 129 patients of other adult Units; all were receiving maintenance digoxin. For each patient the dose required to achieve a mean steady-state serum digoxin concentration of 1.6 nmol·l−1, the standardized dose, was calculated, assuming proportionality between the dose given and the concentration achieved. A mean of four estimates of standardized dose for each individual was used in the analysis. Threefold ranges of standardized dose covered the requirement of approximately 85% of patients both of Geriatric Units (62.5 to 187.5 μg per day) and of other adult Units (125 to 375 μg per day). The variables, serum creatinine concentration, sex, age, and body weight were of relatively little value in predicting the standardized dose for the patients in Geriatric Units. There was a sub-group of these in-patients for whom the standardized dose was extremely large.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF02455997

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4

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Implementing partial least squares (1995)

Denham, M. C.

Springer

Statistics and computing 5 (1995), S. 191-202

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ISSN: 1573-1375

Keywords: regression ; Splus ; Matlab ; Fortran ; orthogonal invariance

Source: Springer Online Journal Archives 1860-2000

Topics: Computer Science , Mathematics

Notes: Abstract Partial least squares (PLS) regression has been proposed as an alternative regression technique to more traditional approaches such as principal components regression and ridge regression. A number of algorithms have appeared in the literature which have been shown to be equivalent. Someone wishing to implement PLS regression in a programming language or within a statistical package must choose which algorithm to use. We investigate the implementation of univariate PLS algorithms within FORTRAN and the Matlab (1993) and Splus (1992) environments, comparing theoretical measures of execution speed based on flop counts with their observed execution times. We also comment on the ease with which the algorithms may be implemented in the different environments. Finally, we investigate the merits of using the orthogonal invariance of PLS regression to ‘improve’ the algorithms.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00142661

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5

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Second messenger role of magnesium in pancreatic acinar cells of the rat (1995)

Singh, Jaipaul ; Wisdom, Denham M.

Springer

Molecular and cellular biochemistry 149-150 (1995), S. 175-182

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ISSN: 1573-4919

Keywords: rat pancreas ; cholecystokinin ; magnesium ; calcium ; acetylcholine ; amylase secretion

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Abstract Application of either acetylcholine (ACh, 10−5 M) or cholecystokininoctapeptide (CCK-8, 10−8 M) to the isolated rat pancreas elicited large increases in amylase secretion, radiolabelled45Ca2+ influx and cytosolic free calcium [Ca2+]i levels in zero and normal (1.1 mM) extracellular magnesium [Mg2+]o. Elevated [Mg2+]o significantly (p〈0.001) reduced the secretagogueevoked secretory responses and Ca2+ mobilisation. Stimulation of pancreatic segments with either ACh (10−5 and 10−6 M) or CCK-8 (10−8 and 10−10 M) resulted in marked elevation in Mg2+ concentration in effluent samples (net efflux). On removal of either ACh or CCK-8, Mg2+ concentration returned to resting level. In pancreatic acinar cells loaded the flourescent dye magfura, ACh and CCK-8 evoked marked reduction in cytosolic free Mg2+ concentration [Mg2+]i compared to the resting value of 0.82±0.03 mM (n=50) in normal medium in the absence of secretagogues. In elevated [Mg2+]o (10 mM) medium, [Mg2+]i rises to 0.98±0.04 mM (n=6). Addition of CCK-8 led to only a small reduction in [Mg2+ i in elevated [Mg2+]o. In Mg2+ loaded pancreatic acinar cells, Mg2+ is released in a time dependent manner and this efflux of Mg2+ was sensitive to sodium, extracellular amiloride (1 mM), dinitrophenol (10 mM) and lidocaine (1 mM). The results indicate that Mg2+ is acting as an intracellular messenger to regulate the mobilisation of Ca2+ which in turn mediates enzyme secretion.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01076575

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6

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The role of magnesium in regulating CCK-8-evoked secretory responses in the exocrine rat pancreas (1996)

Wisdom, Denham M. ; Salido, Gines M. ; Baldwin, Lisa M. ; [et al.]

Springer

Molecular and cellular biochemistry 154 (1996), S. 123-132

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ISSN: 1573-4919

Keywords: rat pancreas ; cholecystokinin-octapeptide ; magnesium ; calcium ; secretion ; cyclic AMP

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Abstract This study investigates the effect of magnesium (Mg2+) on the secretory responses and the mobilization of calcium (Ca2+) and Mg2+ evoked by cholecystokinin-octapeptide (CCK-8) in the exocrine rat pancreas. In the isolated intact perfused pancreas CCK-8 (10−10 M) produced marked increases in juice flow and total protein output in zero and normal (1.1 mM) extracellular Mg2+ [Mg2+]o compared to a much reduced secretory response in elevated (5 mM and 10 mM) [Mg2+]o Similar effects of perturbation of [Mg2+]o on amylase secretion and 45Ca2+ uptake (influx) were obtained in isolated pancreatic segments. In pancreatic acinar cells loaded with the fluorescent bioprobe fura-2 acetomethylester (AM), CCK-8 evoked marked increases in cytosolic free Ca2+ concentration [Ca2+]i in zero and normal [Mg2+]o compared to a much reduced response in elevated [Mg2+]o Pretreatment of acinar cells with either dibutyryl cyclic AMP (DB2 cAMP) or forskolin had no effect on the CCK-8 induced changes in [Ca2+]i. In magfura-2-loaded acinar cells CCK-8 (10−8 M) stimulated an initial transient rise in intracellular free Mg2+ concentration [Mg2+]i followed by a more prolonged and sustained decrease. This response was abolished when sodium Na+ was replaced with N-methyl-D-glucamine (NMDG). Incubation of acinar cells with 10 mM Mg2+ resulted in an elevation in [Mg2+]i. Upon stimulation with CCK-8, [Mg2+]i. decreased only slightly compared with the response obtained in normal [Mg2+]o. CCK-8 caused a net efflux of Mg2+ in pancreatic segments; this effect was abolished when extracellular sodium [Na+]o was replaced with either NMDG or choline. The results indicate that Mg2+ can regulate CCK-8-evoked secretory responses in the exocrine pancreas possibly via Ca2+ mobilization. Moreover, the movement of Mg2+ in pancreatic acinar cells is dependent upon extracellular Na+.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00226780

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