Assessing differential functioning in a satisfaction scale.

In this study, an item response theory-based differential functioning of items and tests (DFIT) framework (N. S. Raju, W. J. van der Linden, & P. F. Fleer, 1995) was applied to a Likert-type scale. Several differential item functioning (DIF) analyses compared the item characteristics of a 10-item satisfaction scale for Black and White examinees and for female and male examinees. F. M. Lord's (1980) chi-square and the extended signed area (SA) measures were also used. The results showed that the DFIT indices consistently performed in the expected manner. The results from Lord's chi-square and the SA procedures were somewhat varied across comparisons. A discussion of these results along with an illustration of an item with significant DIF and suggestions for future DIF research are presented.

Phase I trial of the selective mitochondrial toxin MKT077 in chemo-resistant solid tumours.

BACKGROUND: MKT077 is a rhodacyanine dye analogue which preferentially accumulates in tumour cell mitochondria. It is cytotoxic to a range of tumours. In this phase I study, MKT077 was administered as a five-day infusion once every three weeks. PATIENTS AND METHODS: Ten patients, median age 59 (38-70) years, with advanced solid cancers were treated at three dose levels: 30, 40 and 50 mg/m2/day for a total of 18 cycles. 31Phosphorus magnetic resonance spectroscopy (MRS) was used to evaluate the effect of MKT077 on skeletal muscle mitochondrial function. RESULTS: The predominant toxicity was recurrent reversible functional renal impairment (grade 2, two patients). One patient with renal cancer attained stable disease and the remainder progressive disease. There were no MRS changes in the first or second treatment cycles but one patient received 11 treatment cycles and developed changes consistent with a mitochondrial myopathy. Mean values for all pharmacokinetic parameters were at sub micromolar levels and did not exceed IC50 values (> or = 1 microM). CONCLUSIONS: Because of the renal toxicity, and animal studies showing MKT077 causes eventual irreversible renal toxicity, further recruitment was halted. The study shows, however, that it is feasible to target mitochondria with rhodacyanine analogues, if drugs with higher therapeutic indices could be developed.

Potentiation of the hypoglycaemic response to glipizide in diabetic patients by histamine H2-receptor antagonists.

In a randomised placebo controlled study, two groups of six maturity onset diabetic patients stabilised on glipizide were given cimetidine (400 mg) or ranitidine (150 mg) 3 h before a standardised meal. In comparison with placebo, both cimetidine and ranitidine significantly reduced the post-prandial rise in blood glucose by a mean of 40% and 25% respectively producing glucose levels of less than 3 mmol l-1 (lowest 1.5 mmol l-1) in four patients. Both drugs also significantly increased plasma glipizide AUC by approximately 20%. Caution should be exercised when initiating treatment with H2-receptor antagonists in diabetics receiving sulphonylurea hypoglycaemic agents.

Plasma protein binding of lidocaine and warfarin in insulin-dependent and non-insulin-dependent diabetes mellitus.

We examined the plasma protein binding of an acidic drug (warfarin bound to albumin) and a basic drug [lidocaine (lignocaine) bound to alpha 1-acid glycoprotein] in 15 patients with insulin-dependent diabetes mellitus (IDDM) and 15 matched controls. We also examined protein binding of warfarin and lidocaine in 30 patients with non-insulin-dependent diabetes (NIDDM) and 25 controls. Compared with control, the binding of both warfarin (98.81 +/- 0.02 vs 98.57 +/- 0.03%, mean +/- SEM) and of lidocaine (69 +/- 2 vs 58 +/- 2%) was significantly reduced in IDDM. This group had lower concentrations of both albumin and alpha 1-acid glycoprotein (AAG), achieving statistical significance vs control for albumin only. In the patients with NIDDM, who had a similar level of glycosylated haemoglobin, while there was no significant difference in the binding of lidocaine there was a significant increase in warfarin binding compared with the control population (99.01 +/- 0.03 vs 98.82 +/- 0.04%). This study suggests that binding of both acidic and basic drugs is altered in both IDDM and NIDDM.

Quality of life with three antihypertensive treatments. Cilazapril, atenolol, nifedipine.

A multicenter, randomized double-blind study of 6 months' duration was performed in 540 patients (average age 54 years, 57% male) with mild-to-moderate essential hypertension to determine the relative effects on quality of life of cilazapril, atenolol, and nifedipine retard. Quality of life was assessed by using both a self-administered and an interviewer-administered questionnaire; the assessment included a complaint score (symptoms checklist), Health Status Index, assessment of work satisfaction, Psychological General Well-being Index, Profile of Mood States subscales, and life satisfaction assessment. Psychomotor function was measured by the Reitan Trail Making test B. At the end of the trial, diastolic blood pressure had fallen by an average of 15 mm Hg in all three groups, but significantly (p = 0.01) more patients taking cilazapril required the addition of a diuretic (36%) compared with those taking atenolol (25%) or nifedipine retard (24%). No significant differences in quality of life were observed between cilazapril and atenolol during the trial. Symptomatic complaints increased on nifedipine retard (p = 0.02) and contributed to a higher discontinuation rate (21% discontinued treatment compared with 13% and 14% taking atenolol and cilazapril, respectively, p = 0.04). However, a possible improvement in the fatigue subscale (p = 0.04) was also observed on nifedipine retard. The 95% confidence intervals showed that none of the drugs in this trial produced an effect equivalent to that previously reported between captopril and methyldopa in the Psychological General Well Being Index or between captopril and methyldopa or propranolol in Trail Making test B.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium channel blocker drugs and diabetic control.

Calcium channel blockers are now widely used and there have been case reports of hyperglycemia with nifedipine. In a double-blind, randomized, crossover study of the effects of 4 weeks of therapy, each with two dihydropyridine calcium channel blocker drugs, nifedipine and nicardipine, glucose tolerance, plasma insulin levels, and hemoglobin A1 were assessed in 20 patients with non-insulin-dependent diabetes (mean age 59 years). There was no significant difference in glucose tolerance on active therapy (AUC: control, 548.3 +/- 24.8; nifedipine, 559.3 +/- 41.0; and nicardipine, 589.3 +/- 40.3). Similarly, despite producing significant hemodynamic effects, these drugs produced no significant effect on plasma insulin and hemoglobin A1 levels. Calcium channel blocker drugs may be useful alternatives to thiazide diuretics and beta-blockers in the treatment of ischemic heart disease and hypertension, especially in patients with diabetes.

Effect of early treatment with nifedipine in suspected acute myocardial infarction.

In this single centre prospective, double blind study, 98 patients with suspected acute myocardial infarction (AMI) were randomized, within six hours, to nifedipine 10 mg (46 patients) or placebo (52 patients) both administered sublingually. The delay time from onset of chest pain to treatment was 3.33 +/- 0.2 hours (mean +/- SEM) and 3.28 +/- 0.18 hours for the nifedipine and placebo treated groups, respectively. Treatment was continued orally for 3 days. AMI was confirmed in 28 patients given nifedipine and 23 patients given placebo. Infarct sizing by CK-MB isoenzyme release was possible, for technical reasons, in only 23 patients on nifedipine and 17 patients on placebo. CK-MB isoenzyme release was 710 +/- 104 IU l-1 and 655 +/- 118 IU l-1 for the nifedipine and placebo treated groups respectively (P greater than 0.05). In the acute coronary insufficiency (ACI) group--18 patients given nifedipine and 29 patients given placebo--there was no significant difference in duration of admission, urgent cardiac readmission or progression to AMI within one month. Study withdrawal occurred in 15.3%--8 nifedipine and 7 placebo. Overall, one month mortality was 10.2% with 5 deaths in both the nifedipine and placebo treated groups. Early treatment with nifedipine did not reduce enzymatically determined infarct size or one month mortality in patients with AMI, or reduce one month morbidity or mortality in patients with ACI.

Plasma prolactin concentrations following epileptic and pseudoseizures.

Serial plasma prolactin levels were measured following eighteen generalised seizures, ten partial seizures and eight pseudoseizures. Prolactin levels were elevated following generalised seizures, but were normal following the other seizure types. Plasma prolactin levels may, therefore, be helpful in differentiating between generalised and pseudoseizures. The optimal time for estimating the prolactin level was 15-20 minutes following the seizure.

Real-time recording medium: photodichroic KF:LiF.

Laser recording and readout measurements using the photodichroic crystal KF:LiF indicate that the material has potential as an input transducer and an adaptive spatial filter in an optical spectrum analyzer. These crystals are among the most photosensitive recording materials without gain, can be produced in large sizes at relatively low cost, and can be operated close to room temperature using thermoelectric coolers. Experiments using a high precision laser scanner providing 96.6-MHz subnsec pulses at 514 nm show that adequate recording can be accomplished with exposures less than 10 mJ/cm(2). An MTF of 40% at 72 1/mm was measured with uniform readout illumination of the recorded signal, but this is reduced if the signal is recovered by rescanning due to the convolution of the scanning beam profile with the recorded spot profile. The readout is destructive at the recording wavelength but can be read out with a much reduced decay rate by using 488 nm. The linear dynamic range in the Fourier plane was measured to be 40 dB.