Evidence for opioid modulation and generation of prostaglandins in sulphur dioxide (SO)2-induced bronchoconstriction.

BACKGROUND: Inhalation of sulphur dioxide (SO2) provokes bronchoconstriction in asthmatic subjects. Cholinergic mechanisms contribute, but other mechanisms remain undefined. The effect of morphine, an opioid agonist, on the cholinergic component of SO2-induced bronchoconstriction was investigated, and the effect of indomethacin, a cyclooxygenase inhibitor, on SO2-induced bronchoconstriction and tachyphylaxis was studied. METHODS: In the first study 16 asthmatic subjects inhaled either ipratropium bromide or placebo 60 minutes before an SO2 challenge on days 1 and 2. On day 3 an SO2 challenge was performed immediately after intravenous morphine. In the second study 15 asthmatic subjects took either placebo or indomethacin for three days before each study day when two SO2 challenges were performed 30 minutes apart. The response was measured as the cumulative dose causing a 35% fall in specific airways conductance (sGaw; PDsGaw35). RESULTS: Ipratropium bromide significantly inhibited SO2 responsiveness, reducing PDsGaw35 by 0.89 (95% CI 0.46 to 1.31) doubling doses. This effect persisted after correction for bronchodilatation induced by ipratropium bromide. The effect of ipratropium bromide and morphine on SO2 responsiveness also correlated (r2 = 0.71). In the second study SO2 tachyphylaxis developed with PDsGaw35 on repeated testing, being reduced by 0.62 (95% CI 0.17 to 1.07) doubling doses. Indomethacin attenuated baseline SO2 responsiveness, increasing PDsGaw35 by 0.5 (95% CI 0.06 to 0.93) doubling doses. CONCLUSIONS: These results suggest that opioids modulate the cholinergic component of SO2 responsiveness and that cyclooxygenase products contribute to the immediate response to SO2.     

Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.     

The Use of Cervicography in the Follow-up of Cervical Intraepithelial Neoplasia Treated by CO2 Laser

Summary: After treatment for cervical intraepithelial neoplasia (CIN) the follow-up of patients would be simplified if colposcopy could be safely omitted. A study of 50 patients was performed to determine the feasibility of such an approach. Cervical cytology, cervicography and colposcopy, with or without biopsy, was performed in each patient. From the results the following criteria for colposcopy were adopted: (a) patients thought to have CIN on cytology or cervicography, (b) inadequate cervicography picture (vagina covering cervix or poor quality photograph), (c) high-risk factors present (immunosuppression, after cone biopsy, postmenopausal). In this study the number of colposcopies would have been reduced from 50 to 11 if these criteria were adopted. Cervical cytology combined with cervicography is a reasonable alternative to colposcopy and we feel this is a technique worth pursuing for the follow-up of patients treated for CIN.     

Advances in development of medications for alcoholism treatment

 Over the past decade, research on medications to treat alcohol problem has flourished. Naltrexone and acamprosate are tangible fruits of such endeavors and each has now earned approval in a large number of countries. Recent studies on naltrexone indicate that patient compliance is important if full benefits are to be achieved. Several laboratory studies with human subjects are beginning to elucidate the mechanisms underlying efficacy of naltrexone, as well as explaining variability of response among subpopulations of drinkers. In addition to these two agents, recent investigations have also demonstrated that the antidepressants desipramine, imipramine, and fluoxetine reduce mood-related symptoms and, to some extent, drinking itself in alcoholics who are depressed. Research to date suggests that opioid antagonists and selective serotonin reuptake inhibitors are more effective in reducing alcohol intake when used in combination. Clinical issues, methodology, and directions for future research are also reviewed in this article. In particular, issues addressed include alternative dosage regimens, necessary duration of treatment, employment of medications in combination, integration of pharmacologic agents with behavioral interventions, enhancement of patient compliance, and concurrent treatment of psychiatric comorbidity. Received: 16 December 1997 / Final version: 15 April 1998     

Psychosocial Adjustment of Children With Isolated Growth Hormone Deficiency

Fifty-six children with isolated growth hormone deficiency (IGHD) and their families completed self-report instruments about behavioral, social, and emotional adjustment of the children. Results show that children with IGHD may experience significant behavioral and social adjustment problems. Social and emotional adjustment was best predicted by the relative height discrepancy between an individual and their normal-sized peers. Adjustment varied depending on the type of adjustment under consideration, the relative height discrepancy of the individual, the age and gender of the child, and the amount of time in treatment. Discussion addresses the need for an interdisciplinary approach to effective patient management of children with IGHD.     

Oral mucosal reactions to cinnamon-flavored chewing gum

Oral lesions induced by contact with cinnamon flavoring agents are relatively uncommon, and are probably unrecognized as such by many clinicians. Ten patients with these lesions seen during the past 6 years are described in this report. Most patients had a "burning sensation" as their primary symptom. Clinically, lesions appeared as erythematous patches with varying degrees of superimposed keratosis or ulceration, or both. The lesions were usually confined to the buccal mucosa and lateral border of the tongue. The offending agent was almost always cinnamon-flavored chewing gum, and symptoms typically resolved within 1 to 2 days of discontinuing the product containing cinnamon.     

Retroperitoneal versus transperitoneal approach for repair of abdominal aortic aneurysms

We, as well as other authors, believe that the retroperitoneal approach is an excellent alternative to the transperitoneal route for the repair of abdominal aortic aneurysms. This approach is associated with a significant decrease in pulmonary and cardiac complications and therefore can be used in selected high-risk patients with expanding aneurysms. A well-controlled randomized multicenter trial should answer the question: "Is this approach the surgical access of choice for the elective repair of abdominal aortic aneurysms?"     

Monocytes and other infiltrating cells in human colorectal tumours identified by monoclonal antibodies

Monoclonal antibodies have been used to examine the patterns of infiltrating cells in colorectal tumours staged according to Dukes' classification. MAbs reacting with monocytes, but not tissue Mph, revealed a six-fold increase in monocytes in metastasizing C tumours compared to normal gut. The non-metastasizing B tumours could be divided into one group containing increased numbers of monocytes, and a second group comparable to control gut. T-cell numbers were increased in all tumour stages by an average 1.4-fold, which disguised the lack of consistent pattern in T-cell subset ratios in the tumour stromal tissue. However, in the tumour epithelium, there was a constant decrease in the Ts + c cell subset and a subsequent alteration in T-cell subset ratio in favour of Th + i cells. With the progression from Dukes' Stage B to C, there was an increase in the proportion of monocytes and T cells which were activated as detected by mAbs to the C3b receptor and IL-2 receptor, respectively. These observations suggest that an immune response is in progress in these colorectal tumours and that it is most active in the metastasizing Dukes' C tumours. Whether this response is elicited by the tumour or other elements, whether it is detrimental to tumour growth, or whether it is actively assisting tumour growth and possibly dissemination, are matters of conjecture.