Effect of oral and inhaled cetirizine in allergen induced bronchoconstriction

Cetirizine is a potent, selective H₁ histamine receptor antagonist. The effect of oral and inhaled eetirizine was assessed on the early bronchoconstrictor response to inhaled allergen in 10 mild atopie asthmatic patients in a double-blind, randomized, plaeebo controlled trial. All were sensitive to Dermatophagoides pleronyssinus and this was used as the provoking allergen. The geometric mean PD20 FEV] values obtained at allergen challenge were measured as cumulative breath units (c.b.u.) and following oral cetirizine, inhaled cetirizine and placebo were 124–5, 75–7 and 76–7 c.b.u. respectively. These did not differ significantly. We conclude that neither oral nor inhaled cetirizine significantly attenuates the early response to inhaled allergen in atopie asthmatic subjects. However, the method of repeated allergen challenge is likely to be relatively insensitive. Clinical and Experimental Allergy, [o]. 23, pp. 528–531.     

Current oral contraceptive use instructions: an analysis of patient package inserts.

Oral contraceptive use instructions contained in manufacturers' patient package inserts (PPIs) are often inconsistent or conflicting, both among manufacturers and among different brands and regimens from the same manufacturer. Instructions on what to do about missed pills are often incomplete or inadequate, as are instructions on backup contraceptive use when pills are missed. The format of many PPIs is confusing and makes instructions difficult to find and read. Comprehending the PPIs requires the user to read at a 10th-12th-grade level, far higher than the generally accepted 5th-6th grade level considered standard for health education materials.     

Fluorescence polarization immunoassay and HPLC assays compared for measuring monoethylglycinexylidide in liver-transplant patients.

We compared fluorescence polarization immunoassay (FPIA, x) and HPLC (y) for measuring monoethylglycinexylidide (MEGX) concentrations in 119 serum samples from 61 liver-transplant donors and recipients. The correlation between the two methods was y = 1.48 micrograms/L + 0.8x (r = 0.89). The bias (mean difference) was 12 micrograms/L (0.055 mumol/L) through the MEGX concentration range measured (0-250 micrograms/L, 0-1.136 mumol/L). We observed a major difference between the two methods in samples from four recipients and one donor. Cross-reactivity in FPIA with lignocaine and two of its metabolites (glycinexylidide and 2,6-xylidine) was < 3%. Samples with high bilirubin concentrations (> 200 mumol/L) required dilution before assay of MEGX by FPIA. Although there was an increase in apparent MEGX concentrations in some samples with increased bilirubin concentrations, the relationship was not constant. Increased plasma concentrations of cholesterol and triglyceride resulted in relatively small increases in apparent MEGX concentrations.     

The influence of anaesthetic techniques and type of delivery on peripartum serum interleukin-6 concentrations

Background: Interleukin-6 is a pleiotropic cytokine with a wide range of physiological activities. It plays an important role in the immuno-neuro-humoral axis during stress and surgery.
Methods: Serum interleukin-6 in parturients was measured on hospital admission, immediately after birth and 12 and 24 hours later. All parturients had uncomplicated pregnancies, and delivered vaginally without (n=31) or with (n=20) epidural analgesia, or underwent Caesarean section under epidural (n=20) or general (n=10) anaesthesia.
Results: Serum interleukin-6 assayed immediately following Caesarean section was low, but peaked 12 hours later, irrespective of the anaesthetic technique or other foetomaternal characteristics. Patients who delivered vaginally showed the highest interleukin-6 levels immediately after delivery. These were positively correlated with serum interleukin-6 on admission and duration of labour. Serum interleukin-6 was significantly higher in parturients who had epidural analgesia, and was significantly lower in those receiving intravaginal prostaglandins compared to those without prostaglandins.
Conclusion: The interleukin-6 response after Caesarean section can be explained by a generalized acute phase response to surgery, with no anaesthetic, maternal or neonatal interference. The rapid increase in peripartum serum interleukin-6 levels after vaginal delivery reflects, in part, cervical ripening or labour, their physiological triggers and psychological or physical stress. Regional anaesthesia, duration of labour and exogenous prostaglandin administration can modulate the peripartum interleukin-6 response and subsequently the physiological effects of this cytokine.     

Measurement of short-term 11C-thymidine activity in human head and neck tumours using positron emission tomography (PET).

Tumour uptake of 11C-thymidine labeled in the methyl position was assessed after intravenous injection in 13 patients with head and neck tumours. This activity was compared to other tracers such as C15O, 13NH3 and C15O2. In every single case a 'positive' tumour image after injection of 11C-thymidine was obtained. Time-activity curves showed the initial activity to be followed by a rapid decrease over the first 10-15 min with an apparent plateau thereafter. A similar level of uptake was found in normal salivary gland regions and myocardium, while higher activities were noted in liver and kidney parenchyma. It is suggested that both blood flow and cellular metabolism can influence 11C-thymidine imaging in this class of human tumours.     

Acute cardiovascular effects of tranylcypromine: correlation with plasma drug, metabolite, norepinephrine, and MHPG levels

BACKGROUND: Recent case reports, small series, and uncontrolled, unblinded studies have suggested that tranylcypromine may produce pressor reactions in some patients. However, the physiologic mechanism underlying this cardiovascular change is unknown. METHOD: The authors studied the acute cardiovascular effects of tranylcypromine in 13 patients and attempted to correlate these changes with plasma measures of parent drug, possible pressor metabolites, norepinephrine, and 3-methoxy-4-hydroxyphenylglycol. RESULTS: Significant elevations in supine blood pressure occurred after administration of tranylcypromine and correlated with tranylcypromine dose. Similar changes were not observed in standing blood pressure measurements. In fact, an orthostatic decrease in blood pressure and increase in heart rate were observed. Amphetamine-like metabolites were not found. CONCLUSIONS: The authors speculate on possible mechanisms underlying these opposite cardiovascular effects.     

Development of a high performance zinc-62/copper-62 radionuclide generator for positron emission tomography.

Clinical utilisation of positron emission tomography could be enhanced by the availability of short-lived radionuclides derived from generator systems. The zinc-62/copper-62 combination is one such system which could be used as a source for a number of copper-62 radiopharmaceuticals. We have developed and optimised a high activity (5.6 GBq, 150 mCi) zinc-62/copper-62 generator to provide 62Cu in a form that is suitable for direct labelling of pyruvaldehyde-bis-(N4-methylthiosemicarbazone)-copper(II), Cu(PTSM). The distribution coefficients of Zn(II) and Cu(II) between anion-exchange resin and various hydrochloric acid/organic solvent mixtures were measured. Based on these measurements a generator eluent of 0.3 M HCl/40% ethanol provided 62Cu in greater than 90% yield in a 3-ml volume. A very low 62Zn breakthrough of less than 3 x 10(-7)% was achieved. Copper-PTSM was successfully labelled with the no-carrier-added 62Cu eluent directly from the generator with 94% radiochemical yield.     

Studies on the relationship between transaldolase activity and testosterone synthesis in Leydig cells of pubertalmice

Objective: To study the relationship between transaldolase activity, protein expression and testosterone synthesis in Leydig cells of pubertal mice. Methods: Leydig cells were cultured for 2 hours and 8 hours, to the Stimulation Group, hCG was added and to the Controls, only the vehicle. The testosterone concentration was then determined by enzyme-linked immunoadsordent assay (ELISA) and the transaldolase activity and protein expression by Western blot. Results: (1) Both the testosterone concentration and the transaldolase activity in both Stimulation Groups were significantly higher than those in the corresponding Controls (2 h: p<0.05-0.01; 8 h: P<0.001); (2) The ratios of the A isoform, the B isoform and the total transaldolase protein to β-actin between the Stimulation and Control Groups did not differ signifi-cantly. Conclusion: hCG stimulates the transaldolase activity as well as the testosterone synthesis in the Leydig cells of pubertal mice, indicating a positive relationship between them.     

Scintigraphic visualization of intrathecal liposome biodistribution

Background: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h.
Methods: We administered ⁹⁹Tc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37°C in vitro.
Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.
Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.     

Free vascularized jejunum interposition for pharyngoesophageal reconstruction after total laryngopharyngectomy

The records of 28 patients who underwent free jejunal graft reconstruction after resection for cancer involving the pharynx were analysed. Seven patients had a T₃ carcinoma, 15 patients T₄ and six patients recurrence after laryngectomy. Ten patients had received radiotherapy in the past. Post-operatively, 15 patients (54%) had complications and two patients (7%) died. No significant difference was observed in the complication rate between the group that received radiotherapy in the past and those who did not. Nineteen patients received post-operative radiotherapy. Nine patients had no radiotherapy on the basis of complete resection or because of serious complications. For the whole group the 2-year recurrence free period and survival were 42% and 51% respectively. The postoperative radiotherapy group had a significantly better survival (73%) and recurrence free period (63%) than the group without post-operative radiotherapy (0%). Thus, post-operative radiotherapy seems indicated irrespective of resection margins.