Eledoisin and lacrimal secretion in the rabbit

Eledoisin has been tried as a possible treatment for dry eye based on the hypothesis that it pharmacologically stimulates tear secretion when topically applied to the eye. To determine if topically applied eledoisin pharmacologically stimulates orbital lacrimal secretion, the orbital lacrimal gland excretory duct of normal rabbits was cannulated, and eledoisin was applied topically with and without prior administration of proparacaine. To determine if topically applied eledoisin stimulated accessory lacrimal gland secretion, isotonic buffer with and without eledoisin was tested in a rabbit model with only accessory lacrimal tissue remaining after the administration of proparacaine. Topically applied eledoisin did not pharmacologically stimulate lacrimal secretion but rather increased lacrimal gland secretion only in non-anesthetized eyes through a sensory reflex mechanism that is blocked by proparacaine.     

Chorioretinal folds and a macular hole secondary to craniofacial surgery

Chorioretinal folds have been reported as a result of many intraocular and extraocular inflammatory processes or tumors. Visual loss is usually secondary to a combination of the underlying process and chorioretinal folds involving the macula. We report a patient who developed decreased vision, metamorphopsia, chorioretinal folds, and a lamellar macular hole secondary to global compression by a bone fragment. The chorioretinal folds regressed and his vision stabilized following surgical decompression. Chorioretinal folds and lamellar macular hold formation are previously unrecognized complications of reconstructive craniofacial surgery.     

Phase I evaluation of diaziquone in childhood cancer

Summary We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly × 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M²×4 for patients with a solid tumor, and is 30 mg/M²/week × 4 for children with acute leukemia.     

Ritanserin in the treatment of alcohol dependence – a multi-center clinical trial

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT₂ receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence. Received: 30 April 1996/Final version: 3 July 1996     

Practice setting and physician influences on judgments of colon cancer treatment by community physicians.

OBJECTIVE. This article compares judgments about the treatment of Dukes' B2 and C colon cancer made by general surgeons to those of internists and family practitioners. Physician and practice variables were specialty, affiliation with a Community Clinical Oncology Program (CCOP) hospital, time in practice, professional centrality (level of participation in cancer information networks), solo practice, and number of colon cancer patients. DATA COLLECTION METHODS. Data are combined from national probability samples of CCOP- and non-CCOP-affiliated physicians. This study focused on 1,138 internists, family physicians, and general surgeons who participated in decision making for patients diagnosed with Dukes' B2 or C stage colon cancer. Judgments were elicited using brief vignettes. METHODS OF ANALYSIS. Judgments of adjuvant therapy are classified as (a) consistent with the National Institutes of Health Consensus Conference recommendations (experimental for Dukes' B2, accepted for Dukes' C); (b) accepted treatment for both stages; or (c) experimental for both stages. Multinomial logit analyses were used to examine the association of practice setting and physician characteristics to judgments of treatment. RESULTS. Surgeons and CCOP-affiliated physicians were more likely to endorse the NIH consensus conference position. Surgeons, younger physicians, and those in group practice were more likely to approve of chemotherapy for both cancer stages. The most common position (chemotherapy experimental) was more likely from nonsurgeons, solo practitioners, and non-CCOP physicians. CONCLUSION. Physician and practice setting characteristics, including organized structures such as the CCOP, are possible mediating structures that can facilitate dissemination of standards of treatment.     

Induction of endothelium-dependent relaxation in the rat aorta by IRL 1620, a novel and selective agonist at the endothelin ETB receptor.

1. The effects of a novel and selective agonist at the endothelin ETB receptor, IRL 1620 (Suc-[Glu9, Ala11,15] endothelin-1 (8-21)), were examined in the isolated aorta of the rat. 2. IRL 1620 (1-300 nM) changed neither the resting tone nor the cytosolic Ca2+ level ([Ca2+]i) of the aorta without endothelium. In the presence of endothelium, however, IRL 1620 increased endothelial [Ca2+]i with little effect on the muscle tone. In the absence of external Ca2+, IRL 1620 still induced a transient increase in endothelial [Ca2+]i. 3. Noradrenaline (100 nM) increased both muscle [Ca2+]i and tension. IRL 1620 (1-300 nM) relaxed the muscle with an increase in endothelial [Ca2+]i only in the presence of endothelium. An inhibitor of nitric oxide synthase, 100 microM NG-monomethyl-L-arginine, inhibited the relaxant effect of IRL 1620 but not the increase in endothelial [Ca2+]i. 4. In resting and noradrenaline-stimulated aorta, the effects of IRL 1620 were inhibited by a selective antagonist of the ETB receptor, IRL 1038 (0.3-3 microM), although a selective antagonist of the ETA receptor, BQ-123 (3 microM), was ineffective. Verapamil (10 microM) did not alter the effects of IRL 1620. 5. A muscarinic receptor agonist, carbachol (1 microM), also induced endothelium-dependent relaxation with an increase in endothelial [Ca2+]i. However, the effects of carbachol were not inhibited by the ETB antagonist, IRL 1038 (3 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

The scope of the cataract problem in the Middle East and the Mediterranean

The region is characterized by diversity in cultural, political, economic and health conditions. Blindness in the region varies from 6.4% to 0.2% with cataract ranking highly as an underlying cause. There is a need to develop national policies to deliver affordable, technically suitable, and cost effective management plans to reduce cataract. Economic, demographic, health, and manpower statistics are essential information to be considered in formulating such policies.     

Role of intracortical mechanisms in the late part of the silent period to transcranial stimulation of the human motor cortex

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the human motor cortex produce a silent period (SP) following motor evoked potentials (MEPs). The early part of the SP can be explained by decreased alpha motor neuron excitability, whereas the late part is presumably due to suprasegmental mechanisms. In order to determine the level of the suprasegmental contribution to the generation of SPs, we recorded excitatory and inhibitory responses to TMS, TES, and percutaneous electrical brainstem stimulation (PBS) in the voluntarily activated first dorsal interosseous muscle of the hand. Stimulus intensities were set so that PBS and TES induced MEPs with areas equal to or larger than those of MEPs obtained with TMS. This procedure revealed that SPs were 49% and 83% shorter with TES and PBS, respectively, than with TMS. As TMS is more effective than TES or PBS in activating cortical interneurons, these findings support the idea that a significant component of the SP arises from intracortical mechanisms.     

Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor V beta-specific monoclonal antibodies.

Felty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) beta chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR V beta chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared V beta usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation.