Cyclosporin A in the ocular fluids of uveitis patients following long-term systemic administration

BACKGROUND/AIMS: To determine the levels of cyclosporin A (CsA) in tears and the anterior segment of the eye following long-term oral intake for autoimmune diseases. METHODS: Subjects taking oral CsA to treat relapsing autoimmune ocular inflammation were included in this study. All of the patients had been quiescent for at least 6 months. In patients scheduled for cataract extraction (group A), the CsA levels in the blood, aqueous humour and anterior capsule of the lens were determined. In subjects not requiring surgical intervention (group B), CsA was measured in tears and blood. The samples were analysed using turbulent flow chromatography coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: There were 19 subjects in group A and 43 subjects in group B. CsA was detectable in all of the tear samples with a mean value of 22.4 +/- 20.2 ng/ml and there was a significant positive correlation between the CsA levels in tears and blood (P = 0.012). CsA was not detected in any of the surgical samples. CONCLUSION: LC-MS/MS proved very sensitive for detecting CsA in low-volume biological samples. CsA was present in human tears in proportion to the blood level after an average of 12 hours from the last oral intake.     

Therapeutic studies in NZB/W mice. I. Synergy of azathioprine,cyclophosphamide and methylprednisolone in combination

This study compares different immunosuppressive regimens in the treatment of the lupus-like nephritis of NZB/W mice. Groups of 5-month-old female NZB/W mice were given azathioprine, cyclophosphamide and methylprednisolone in all one-, two- and three-drug regimens, each drug in the relatively low dose of 1.5 mg/kg/day. Treatment for 3 months with one or two drugs resulted in modest suppression of NZB/W disease. Mice receiving all three drugs had significantly less proteinuria, lower titers of anti-DNA antibody and less severe, histologically evident renal involvement than mice treated with one or two drugs. Survival at 1 year was 10% for untreated controls, 44% for one-drug-treated, 37% for two-drug-treated and 86% for the three-drug-treated mice. The survival for the three-drug regimen was significantly longer than any other group (P < 0.01). The three-drug regimen was synergistic, since mice treated with each drug at three times the dose had significantly more proteinuria after 3 months of treatment and lowered 1 year survival (33%). The beneficial effects of triple-drug therapy were attained without increased toxicity. This study represents the first controlled evaluation of single versus combination therapy in a model of autoimmune disease. Based on these results, a controlled evaluation of triple-drug therapy in human systemic lupus erythematosus appears warranted.     

Pharmacological evidence of catecholaminergic involvement in the behavioral effects of luteinizing hormone releasing hormone in rats

The influence of L-DOPA on the behavioral effects of LHRH was studied in male rats. Subcutaneous administration of LHRH (100 micrograms/kg) caused a significant disruption in the acquisition of a conditioned avoidance response (CAR) and a significant increase in head shaking behavior (HSB). Pretreatment with this hormone antagonized the stimulatory action of amphetamine (1 mg/kg, IP) in acquisition of CARs, spontaneous motor activity (SMA) and rearing behavior (RB). L-DOPA (100 mg/kg, IP), administered after LHRH, stimulated SMA, RB and HSB. In addition L-DOPA antagonized the effect of LHRH on acquisition of CARs and counteracted the antagonism between LHRH and amphetamine in acquisition of CARs and SMA. These findings indicate that LHRH could exert its behavioral effects through an inhibitory action upon brain catecholamine synthesis. The suppression of CARs may be the response to DA antagonism and the interaction with amphetamine could be mediated by an inhibition of both DA and NE activities. The possibility of an interaction between LHRH and central serotonin mechanisms is also discussed.     

Fatal Ingestion of Plastic Resin Catalyst

A 46-year-old man ingested approximately 50 ml of a plastic resin catalyst He developed persistent gastrointestinal bleeding, renal and hepatic failure, pneumonitis, and septicemia, and died four weeks later. Autopsy revealed chronic esophagitis and gastritis with massive intraluminal gastrointestinal hemorrhage. This case emphasizes the potential danger of ingestion of such substances.     

Electrical stimulation versus extracorporeal magnetic innervation for urinary incontinence after radical prostatectomy

Nurses use several conservative methods for treating urinary incontinence after radical prostatectomy. Functional electrical stimulation (FES) has a recognized role, while extracorporeal magnetic innervation (ExMI) is still under evaluation in the international guidelines. Few data are available in literature, regarding comparisons between these two treatments. The aim of the study is to compare electrical stimulation and magnetic innervation for treating urinary incontinence after radical prostatectomy. Twenty‐two patients treated with ExMI and 18 treated with FES were enrolled in a retrospective study. ExMI was available for 6 weeks; the number of times ExMI was required by the patients to reduce their leakages to 10 g/d or less was compared. The groups had comparable age and body mass index. Initial leakages showed clinically relevant differences (median = 80 g/d in the ExMI patients and 150 g/d in the FES group). After 6 weeks, 71·9% of ExMI patients and 29·2% of FES patients had completed rehabilitation. The difference was statistically significant even after adjusting the analyses for initial leakages (p = 0·008). Six patients treated with ExMI had already undergone FES, with no clinically relevant results after five sessions (leakages reduction <50 g/d). The difference remained even after removing the data of these patients from the analysis (p = 0·004). Both FES and ExMI produce muscle strengthening, which is just one step of rehabilitation. Our findings suggest the possibility of using ExMI instead of FES to reduce the times required to improve muscular performance. Pelvic muscle exercises remain essential to develop the ability to automatically perform the contractions needed to avoid leakages.     

Comparison of cleansing methods in preparation for colonic surgery

Golytely, an oral gut lavage solution, was compared with a standard bowel cleansing preparation in patients undergoing elective colonic surgery. Sixty patients were randomly assigned to either a one-day preparation with Golytely and bisacodyl or a standard method using a three-day clear liquid diet, cathartics, and enemas. Colon cleansing was better with Golytely (100 percent optimal cleansing vs. 64 percent, P less than 0.05). Patients receiving Golytely had less weight loss and found this preparation more tolerable. Quantitative stool cultures before and after preparation and intraoperatively were not significantly different between the two preparations. In this surgical bowel preparation study, Golytely and Bisacodyl were found to be safe, rapid, and effective. The preparation was well tolerated by patients and has become our preferred method of colonic cleansing.