Differences in social participation between individuals who do and do not attend brain injury drop-in centres: a preliminary study.

OBJECTIVE: To compare social participation for individuals with traumatic brain injury (TBI) ≥1 year post-injury who attend brain injury drop-in centres (BIDCs) with individuals who do not attend but were identified as potentially benefitting from attending. RESEARCH DESIGN: Cross-sectional study with 23 individuals attending BIDCs and a comparison group of 19 individuals not attending. KEY OUTCOME MEASURES: Community Integration Questionnaire, Social Provisions Scale and Adult Subjective Assessment of Participation. MAIN RESULTS: The comparison group was found to consist of 12 participants who stated that they would attend a BIDC ('Yes sub-group') and seven participants who stated that maybe they would attend a BIDC but for the most part were too busy ('Maybe sub-group'). The BIDC group was found to have statistically significantly higher levels of social participation than the comparison group and particularly the 'Yes sub-group'. CONCLUSIONS: Findings provide support that attendance at BIDCs may benefit social participation. Future directions for research are suggested.

Endoscopic ultrasound in the localisation of pancreatic islet cell tumours.

The role of endoscopic ultrasound (EUS) in the evaluation of entero-pancreatic endocrine tumours has evolved in conjunction with advances in other imaging methods. The high spatial resolution of this technique allows the detection of very small lesions and their precise anatomical localisation. In patients with biochemically proven insulinoma, EUS can be effectively used as a first line investigation, with a sensitivity of 94%. Combined with thin section CT, the sensitivity rises to 100%. There is also high sensitivity in diagnosing intrapancreatic gastrinomas but lower for those arising in the duodenal wall which require detailed duodenal evaluation at surgery. EUS in conjunction with Somatostatin Receptor Scanning (SRS) has a combined sensitivity of 93% for gastrinomas. EUS is recommended for screening of asymptomatic patients with genetically proven MEN1. There is a limited role for EUS guided biopsy in pancreatic endocrine tumours.

Optimization of scanning parameters for CT colonography.

To determine the optimal collimation, pitch and reconstruction interval for CT colonography, 10 spherical polyps between 1 mm and 10 mm diameter and made of tissue equivalent material with a CT number of 40 Hounsfield units (HU) were placed in the colon of an anthropomorphic phantom. The phantom was scanned at slice thicknesses of 3 mm, 5 mm and 7 mm and pitches of 1.0, 1.3, 1.5, 1.7 and 2.0 on an IGE Hispeed advantage system. Images were reconstructed for each scanning parameter at the minimum intervals allowed along the z-axis. The optimum scanning protocol was assessed by measuring maximum contrast between the polyp and air, sensitivity for detection of each polyp along the z-axis, and relative radiation dose. In addition, images were reviewed separately by two radiologists who graded polyp conspicuity as: 0, not seen; 1, faintly seen; 2, well seen. It was found that varying the scanning parameters caused a marked alteration in the maximum contrast between each polyp and air. For example, for the 5 mm polyp, the range of contrasts from best to worst case was 910-490 HU. It was noted that with contrasts of less than 500 HU, polyps were only faintly seen. A slice thickness of 3 mm with a pitch of 2 offers optimal polyp conspicuity with a relatively low radiation dose, we conclude that scanning parameters can be optimized for threshold contrast, radiation dose and subjective conspicuity. We propose an optimal parameter of 3 mm slice thickness and pitch 2.

Novel direct curve comparison metrics for bioequivalence.

PURPOSE: The object of this work was to devise four new direct curve comparison (DCC) metrics and examine each metric's distribution properties and performance characteristics. METHODS: DCC metrics, Cmax, and AUCi were calculated from two bioequivalence studies of three sustained release carbamazepine formulations, where a range of profile similarity was observed. DCC metric values and their confidence intervals were compared to Cmax and AUCi. RESULTS: The DCC metrics rho, rhom, deltaa, and deltas, exhibited more favorable distributions than Cmax and AUCi ratios, which were frequently skewed. The DCC metrics performed differently than Cmax and AUCi ratios in profile comparisons due to the nature of the DCC metrics. Unlike Cmax and AUCi, the DCC metrics utilize all data points to directly compare entire profiles. Each DCC metric appears to measure "exposure" in a single assessment. Possible bioequivalence acceptance criteria are: p < or =1.40, rhom, < or =0.35, deltaa, < or =0.27, and deltas < or =0.102. CONCLUSIONS: These DCC metrics, particularly rhom, are promising bioequivalence metrics for "exposure."

Determination of dihydroergotamine in human plasma by high-performance liquid chromatography with fluorescence detection.

Dihydroergotamine, a 5-hydroxytryptamine antagonist, is used for the treatment of vascular headaches. A high-performance liquid chromatography assay with fluorescence detection is described for the determination of dihydroergotamine in plasma. The assay was validated over the concentration range 0.1-10 ng/ml plasma and applied to the analysis of plasma samples from subjects treated intramuscularly and intranasally with 2 mg of dihydroergotamine.

The influence of plasma butyrylcholinesterase concentration on the in vitro hydrolysis of cocaine in human plasma.

In humans, the plasma enzyme butyrylcholinesterase, BChE (EC 3.1.1.8), mediates the in vivo plasma hydrolysis of cocaine to the pharmacologically inactive metabolite ecgonine methyl ester, EME. This enzyme has been purified from human plasma to investigate the potential as a treatment for cocaine intoxication. Cocaine (2.1 micrograms mL-1) was incubated in plasma with a BChE concentration in the normal range (3.02 micrograms mL-1) and in plasma with enhanced BChE concentrations of 9.14, 20.8 and 37.8 micrograms mL-1, respectively for time periods up to 120 min. Cocaine and the hydrolytic products, ecgonine methyl ester and ecgonine, were quantified simultaneously by gas chromatography-mass spectrometry (GC-MS). The enhancement of plasma BChE concentration resulted in a dramatic increase in the rate of hydrolysis of cocaine. There was a stoichimetric conversion of cocaine to the inactive hydrolysis product, ecgonine methyl ester. Accordingly, the half-life of cocaine in plasma decreased significantly with enhanced BChE concentration. At plasma BChE concentrations of 3.02, 9.14, 20.8 and 37.8 micrograms mL-1, half-life values of 116, 35.8, 21.4 and 9.0 min, respectively were observed. The marked reduction in cocaine half-life provides evidence supporting the potential therapeutic use of BChE for the treatment of cocaine intoxication.

Pharmacokinetic evaluation of twice-daily extended-release carbamazepine (CBZ) and four-times-daily immediate-release CBZ in patients with epilepsy.

PURPOSE: A new capsule dosage form of carbamazepine (CBZ) has been developed, consisting of three different types of beads (immediate-release, extended-release, and enteric-release) that may be taken sprinkled on food or swallowed for easy administration. We compared the pharmacokinetics of the extended-release dosage form of CBZ (Carbatrol capsules) twice daily with the conventional immediate-release formulation of CBZ four times daily. METHODS: The randomized, double-blind, two-way, cross-over study was conducted at two sites, with a planned sample size of 24 adult patients with epilepsy. Each treatment was administered for 2 weeks. At the end of the 2-week period, blood samples were obtained hourly for a 24-h period. RESULTS: The 90% confidence intervals (CI) of the ratio of the means of the extended-release formulation twice daily to the immediate-release formulation four times daily were within the range of 0.80-1.25 for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ and CBZ-epoxide (CBZ-E). There was no difference in the frequency of seizures between treatment (p = 0.103). CONCLUSIONS: Our results demonstrate that extended-release CBZ twice daily was bioequivalent to immediate-release CBZ four times daily, with regard to CBZ levels and summation of CBZ and CBZ-E levels, based on the pharmacokinetic parameters evaluated. Substituting one formulation for the other did not cause patients to have a significant change in seizure frequency.

Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones.

The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P less than 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P less than 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P less than 0.05) and residual volume was 17.7 vs. 6.5 mL (P less than 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P less than 0.05) and residual volume was 17.2 vs. 5.0 mL (P less than 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P less than 0.001; residual volume, 3.7 mL, P less than 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects.

Stability of diltiazem in different biological fluids.

The hydrolysis of diltiazem in biological fluids: whole blood, plasma, and gastric fluid was investigated under conditions considered close to the physiological situation. The most significant rate of hydrolytic degradation was found in whole blood (half-life of 27 h), followed by plasma (half-life of 88 h), while the least significant degradation rate was observed in gastric fluid (half-life 153 h). The kinetic profiles of diltiazem hydrolysis indicate that hydrolytic degradation in the biological fluids makes a minimal contribution to the clearance and disposition of the drug.

Application of a variance-stabilizing transformation approach to linear regression of calibration lines.

A variance-stabilizing transformation (VST) was applied to the linear regression of calibration standards of different drugs in plasma. This transformation involved the normalization of the dependent variable peak height or peak area ratio (Y), and the independent variable, plasma drug concentration (C). This transformation led to a constant variance in the regression error term across the measured concentration range and allowed the evaluation of the unbiased slope and y intercept with minimum variance. The utility of the VST procedure in comparison with the ordinary least squares (OLS) approach, routinely used in pharmaceutical studies for constructing calibration lines, is described. The principal advantage of the VST approach is allowing a lower minimum level of drug quantification while using a single calibration line over a wide range of drug concentrations. The VST method is especially useful to quantify drug plasma levels in pharmacokinetic evaluation of sustained-release dosage forms, where the precise quantification of low levels of drug is critical. The application of the VST method was explored and evaluated in comparison with the OLS method for pharmacokinetic assays of diltiazem, gallopamil, nitroglycerin, and nicotine.

Diagnostic and therapeutic efficacy of barium meal examination: a prospective evaluation in general practice.

OBJECTIVE: To assess the efficacy of barium meal examinations in managing patients with dyspepsia in general practice. DESIGN: Prospective study by questionnaires completed by general practitioners before and within three to six months after the barium meal examination. Information was requested about the patients' symptoms, current treatment, reason for requesting the examination, and the working diagnosis, including degree of certainty and, after the examination, about any change in diagnosis, diagnostic confidence, or management and to determine whether the examination was judged to be helpful or not. SETTING: Inner city health district. PATIENTS: 133 Patients with dyspepsia referred by general practitioners for outpatient barium meal examination, 31 of whom failed to attend for the examination, or refused it on arrival, or did not have fully completed questionnaires. Two patients were not available for follow up. MAIN OUTCOME MEASURES: Prevalence of radiological abnormalities and the influence of the examination result on management, particularly changes in drug treatment. RESULTS: Fully completed pairs of questionnaires were available for 100 patients, 58 of whom were aged below 50. Most of the barium meal reports (64) were to confirm the clinical diagnosis; only 22 were to exclude serious disease. Ninety nine patients were already receiving treatment, with 39 taking an H2 receptor antagonist. Fifty eight barium meal examinations showed abnormalities (31 major abnormalities); there were no cancers and in only 18 patients was the working diagnosis changed as a result of the findings. Although the barium meal result increased management confidence (63 patients) and allayed patients' anxiety (46), changes in management attributed directly to the examination occurred in only 22 patients. Management changes were minor, usually comprising interchange of antacids and H2 receptor antagonists. CONCLUSIONS: Young patients (aged below 50) with dyspepsia are still being overinvestigated. Although barium meal examination improves diagnostic confidence and allays patients' anxiety, fully utilising communication skills at the initial consultation might allay anxiety more economically.

Jejunal dilatation in Crohn's disease. Intestinal obstruction or intestinal edema?

Although dilatation of the jejunum is a well-recognized feature of Crohn's disease there has been no systematic inquiry as to whether this is related simply to distal intestinal obstruction or to other factors such as hypoalbuminemia and mucosal disease. Barium follow-up examinations of 21 patients with Crohn's disease who had serum albumin concentrations of 2.1-4.4 g/dl were reviewed. Fourteen of these patients (67%) had increased mean jejunal width. All patients with direct radiologic evidence of a stricture (six patients) had increased jejunal caliber, but this only accounted for 43% of patients with this abnormality. Of the remaining eight patients, six had hypoalbuminemia, three of whom had serum albumin concentrations less than or around 2.7 g/dl, the previously determined "albumin threshold" for jejunal dilatation. We conclude that increased jejunal caliber in Crohn's disease not only occurs in association with distal intestinal stenosis but also with severe hypoalbuminemia in the absence of obstruction. We were unable to define a cause of jejunal dilatation in 36% of these patients, but propose that functional obstruction due to distal nonstenosing inflammatory disease may be a factor.

High-performance liquid chromatographic (HPLC) assay using fluorescence detection for the simultaneous determination of gallopamil and norgallopamil in human plasma.

Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.

General practice and teaching hospital use of barium meal examinations in the City and Hackney Health District.

The value of barium meal examination in the management of younger patients with dyspepsia has been seriously questioned as diagnostic yield is reported to be low with only minor abnormalities detected. Our 9 month survey of general practice and hospital out-patient use of barium meal examination in the City and Hackney Health District during 1983-84 shows that 51% of patients investigated were less than 50 years and 20% less than 30 years of age, suggesting that clinicians have not heeded these warnings. However, 30% of the younger patients had barium meal mucosal abnormalities. Over all age groups abnormalities were more prevalent in men and in general practice rather than hospital out-patient referrals (59% vs 45%; P less than 0.02). Previous studies may therefore have underestimated the prevalence of barium meal abnormalities in younger patients, and continued use of this examination in such patients may indicate that clinicians have found the results helpful in patient management.

Malabsorption in Marfan (Ehlers-Danlos) syndrome.

A patient with somatic features of both Marfan and Ehlers-Danlos syndromes presented with severe intestinal malabsorption. Functional intestinal abnormalities were thought to be due to bacterial overgrowth associated with small intestinal hypomotility and giant jejunal diverticula. The structural intestinal defects are presumed to be the result of defective collagen synthesis in these hereditary connective tissue disorders.

Interactions of apomorphine with serum and tissue proteins.

Physical and covalent interactions of apomorphine with serum and tissue proteins could influence the drug's disposition and pharmacological activities in mammals. Ultrafiltration, equilibrium dialysis, and ultraviolet spectrophotometric methods have been used to study the reversible binding of apomorphine to bovine, human, rat, and swine plasma proteins. The degree of binding was generally greater than 90%, but variations were noted in some instances on the basis of drug concentrations and pH over the range of 6.8-7.8. Incubation of [8,9-3H2]apomorphine with bovine serum albumin led to retention of radioactivity and a stoichiometrically controlled released of tritium which arose from the reaction of an electrophilic drug oxidation product and protein, producing drug-protein conjugates. In vitro experiments with mouse striatal brain preparations indicated parallel covalent binding reactions. In vivo experiments in mice indicated accumulation of radioactivity in brain regions and other tissues following daily injections of [8,9-3H2]apomorphine for 14 days. The physical and covalent interactions of apomorphine with mammalian tissue proteins could be the cause of longer disposition half-lives in mammals than those previously reported. The covalent interactions, in particular, may be important in elucidating the mechanism of apomorphine-induced behavioral effects in mice.

Prone compression with the pneumatic paddle during barium studies.

Prone compression with the pneumatic paddle is easy to perform, effective with high-density suspensions and less uncomfortable for the patient than other methods of compression. It provides accurate graduated compression over a wide field with an unimpeded view. Its routine use is recommended in double-contrast barium meals and all types of small-bowel examinations.