Secretion of dilevalol in breast milk.

The pharmacokinetics of unchanged and total (unchanged plus Glusulase [Biotechnology Systems, Boston, MA]) released dilevalol and secretion into human breast milk was studied in six healthy breast-feeding female volunteers administered a single 400-mg dilevalol hydrochloride capsule. In plasma, the mean Cmax for unchanged dilevalol, 485 ng/mL was reached at 0.8 hour (tmax) and the AUC(48 hours) was 1435 hr X ng/mL. Pharmacokinetic analysis of unchanged dilevalol in plasma showed that dilevalol was distributed and eliminated with half-lives of 0.9 and 8.2 hours, respectively. Breast milk concentrations of unchanged dilevalol as a function of time, paralleled those of plasma but were consistently lower. The milk Cmax, 149 ng/mL, occurred during the 0 to 2 hour collection interval; the AUC(42 hours) for unchanged dilevalol in milk was 663 hr X ng/mL. The mean milk to plasma concentration ratio was 0.46. The unchanged dilevalol plasma concentrations were 12 to 18% those of total drug suggesting that the drug is extensively conjugated. By contrast, the concentrations of unchanged dilevalol in breast milk, based on Cmax and AUC data were 63 to 94% those of total drug, indicating that very little conjugated drug is secreted into breast milk. Through 48 hours, a mean of only 27 micrograms dilevalol or 0.007% of the administered dose was secreted into breast milk, which is much less than that reported for other beta blockers.

Pharmacokinetics and bioavailability of dilevalol in normotensive volunteers.

The bioavailability and pharmacokinetics of dilevalol following oral and intravenous administration were investigated in 12 healthy male volunteers. Dilevalol HCl was administered as a 200-mg oral tablet and a 50-mg intravenous infusion using a randomized cross-over design. Blood and urine samples were collected over 60 hours and analyzed for unchanged and total (unchanged plus Glusulase-released) dilevalol using a high performance liquid chromatography (HPLC) assay. After intravenous administration, total body clearance and volume of distribution of unchanged dilevalol were determined to be 23.2 mL/min/kg and 24.6 L/kg, respectively. After oral administration, a mean maximum concentration of 62 ng/mL was reached at an average peak time of 1.4 hours. Drug was eliminated with a half-life of 8.3 hours after oral administration and 12 hours after intravenous administration. Based on plasma levels and urinary excretion of total dilevalol, the drug was completely absorbed; however, due to first-pass metabolism, the absolute bioavailability of unchanged drug was 11 to 14%.

Small cell lung cancer associated with anti-Hu paraneoplastic sensory neuropathy and peripheral nerve microvasculitis: case report and literature review.

A 53-year-old man presented with an 8-week history of upper and lower limb paraesthesia. Neurological examination revealed a glove and stocking distribution of sensory loss. Sural nerve biopsy showed severe axonal neuropathy associated with microvasculitis. Positron-emission tomography and thoracic computed tomography helped in localising the underlying malignancy. A transbronchial biopsy confirmed the diagnosis of small cell lung carcinoma (SCLC). Neuroimmunological studies identified anti-Hu antibodies and confirmed a paraneoplastic aetiology for his neuropathy. Treatment of small cell lung cancer with carboplatin and etoposide resulted in significant improvement of neurological symptoms. We report a case of a patient with SCLC and anti-Hu paraneoplastic sensory neuropathy with microvasculitis, and discuss the literature on prognosis of patients with SCLC with paraneoplastic neurological syndromes compared with patients with SCLC only.

99mTechnetium-mercaptoacetyltriglycine scintigraphy with full bladder in patients with severe bladder dysfunction.

PURPOSE: We evaluated 99mtechnetium-mercaptoacetyltriglycine scintigraphy for detecting threshold bladder volume at which upper tract obstruction occurs in patients with bladder dysfunction. MATERIALS AND METHODS: A total of 24 patients 19 to 74 years old with severe bladder dysfunction who underwent 99mtechnetium-mercaptoacetyltriglycine scintigraphy and videocystometrogram in a 4-year period were selected for retrospective study. 99mTechnetium-mercaptoacetyltriglycine scintigraphy was done with a full bladder with a mean instilled volume of more than 850 ml saline. In patients in whom an obstructed renal outflow pattern was observed saline was drained at a rate of 100 ml every 5 minutes while dynamic imaging was performed. If results were abnormal, the study was repeated with an empty bladder. Differential function, parenchymal transit time index and outflow efficiency were calculated. RESULTS: Of the 24 patients 15 had an obstructed outflow pattern with a full bladder, which was relieved at a bladder volume of less than 390 ml (median 300, range 250 to 600). Only 2 of these 15 patients had a normal vesical end filling pressure of less than 20 cm H2O. There was no obstruction in 9 patients, of whom 5 had increased vesical end filling pressures. Followup in patients who had normal tracer outflow on a full bladder showed no decrease in renal function, while a small decrease was seen in patients who had obstructed outflow on a full bladder. CONCLUSION: This novel, full bladder 99mtechnetium-mercaptoacetyltriglycine scintigraphic technique provides the ability to detect bladder volumes at which obstructive outflow patterns develop in patients with severe bladder dysfunction.

Impact of combined (18)F-FDG PET/CT in head and neck tumours.

To compare the interobserver agreement and degree of confidence in anatomical localisation of lesions using 2-[fluorine-18]fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and (18)F-FDG PET alone in patients with head and neck tumours. A prospective study of 24 patients (16 male, eight female, median age 59 years) with head and neck tumours was undertaken. (18)F-FDG PET/CT was performed for staging purposes. 2D images were acquired over the head and neck area using a GE Discovery LS PET/CT scanner. (18)F-FDG PET images were interpreted by three independent observers. The observers were asked to localise abnormal (18)F-FDG activity to an anatomical territory and score the degree of confidence in localisation on a scale from 1 to 3 (1=exact region unknown; 2=probable; 3=definite). For all (18)F-FDG-avid lesions, standardised uptake values (SUVs) were also calculated. After 3 weeks, the same exercise was carried out using (18)F-FDG PET/CT images, where CT and fused volume data were made available to observers. The degree of interobserver agreement was measured in both instances. A total of six primary lesions with abnormal (18)F-FDG uptake (SUV range 7.2-22) were identified on (18)F-FDG PET alone and on (18)F-FDG PET/CT. In all, 15 nonprimary tumour sites were identified with (18)F-FDG PET only (SUV range 4.5-11.7), while 17 were identified on (18)F-FDG PET/CT. Using (18)F-FDG PET only, correct localisation was documented in three of six primary lesions, while (18)F-FDG PET/CT correctly identified all primary sites. In nonprimary tumour sites, (18)F-FDG PET/CT improved the degree of confidence in anatomical localisation by 51%. Interobserver agreement in assigning primary and nonprimary lesions to anatomical territories was moderate using (18)F-FDG PET alone (kappa coefficients of 0.45 and 0.54, respectively), but almost perfect with (18)F-FDG PET/CT (kappa coefficients of 0.90 and 0.93, respectively). We conclude that (18)F-FDG PET/CT significantly increases interobserver agreement and confidence in disease localisation of (18)F-FDG-avid lesions in patients with head and neck cancers.

Comparison of plant cytoplasmic ribosomal proteins by two-dimensional polyacrylamide gel electrophoresis.

The electrophoretic mobilities of the cytoplasmic ribosomal proteins of several species of plants were compared using two-dimensional electrophoresis. The total number of proteins as well as the number of acidic and basic proteins in individual species varied markedly. Of the species examined, Triticum aestivum had the highest number of basic cytoplasmic ribosomal proteins and Hordeum vulgare had less than half as many. However, marked similarities were noted in the electrophoretic mobilities of many of the proteins, especially for wheat, rye, and barley and for peas and beans. There was a statistically significant positive correlation between the numbers of basic proteins in the species and their chromosome number.