Different HLA class IA region complotypes for HLA-A29.2 and -A29.1 antigens, identical in birdshot retinochoroidopathy patients or healthy individuals

PURPOSE: Birdshot retinochoroidopathy (BSCR) is a rare posterior uveitis characterized by distinctive, multiple, hypopigmented choroidal and retinal lesions. At least 96% of patients, if not all, share the major histocompatibility antigen HLA-A29. Although it was hypothesized earlier that more frequently the A*2902 subtype was closely associated with BSCR, new patients were found to share the A*2901 subtype and were further investigated. The present study was designated to check patients' HLA-A*2901 subtyping and the polymorphisms available in the HLA region in patients and control subjects sharing the A*2901 and A*2902 subtypes. METHODS: HLA-A29 was assessed and subtyped by molecular biology. cDNA from one patient (HLA-A*2901) was sequenced. A29.1 antigenic expression on peripheral blood lymphocytes was checked by microlymphocytotoxicity (MLCT). Four homozygous A29.2 and 4 heterozygous A29.2 patients, 3 homozygous A29.2 healthy subjects, 3 heterozygous A29.1 patients, and 11 heterozygous A29.1 healthy subjects were tested for the microsatellite alleles MOGa, -b, -c, and e (of the myelin oligodendrocyte glycoprotein [MOG]gene), D6S265, D6S510, RF, C5_4_5, D6S105, and D6S276 and the mutation H63D of the familial hemochromatosis gene (HFE). RESULTS: The patients' cDNA sequences and MLCT reactivities of HLA-A29.1 subtypes were found to be identical with published data from healthy individuals. Surprisingly, though A*2901 and A*2902 differed only by a single mutation (G376C/ D102H) two strong A*2901 and A*2902 complotypes were observed in patients and control subjects, the polymorphisms being identical at all loci near HLA-A, whereas more distant loci exhibited some diversity. CONCLUSIONS: Susceptibility to BSCR thus appeared to be located between the left and right remote markers C5_4_5 and D6S276, if not relying on the HLA-A29 molecule itself.     

Dacryoadenitis associated with subcutaneous Sweet's syndrome in a patient with acute myeloid leukemia

A 26-year-old woman presented with a painful skin eruption which led to the diagnosis of acute myeloid leukemia. During chemotherapy, she developed an unusual orbital inflammation. Careful observation of the clinical course, computed tomography, and orbital biopsy were necessary to establish the diagnosis of dacryoadenitis associated with subcutaneous Sweet's syndrome. The skin eruption and the dacryoadenitis resolved rapidly with corticosteroid therapy. This is the first report of dacryoadenitis in the course of subcutaneous Sweet's syndrome.     

Psychopharmacological profile of the alkaloid psychollatine as a 5HT2A/C serotonin modulator

Behavioral effects of psychollatine, a new glycoside indole monoterpene alkaloid isolated from Psychotria umbellata, was investigated in models of anxiety, depression, memory, tremor, and sedation related to 5-HT and/or GABA neurotransmission. The GABA antagonist picrotoxin and the 5-HT2 antagonist ritanserin were used to examine the role of GABA and 5-HT2 receptors in psychollatine-induced effects. In the light/dark and hole-board models of anxiety, diazepam (0.75 mg/kg) and psychollatine (7.5 and 15 mg/kg) showed anxiolytic-like effect at doses that do not increase sleeping time nor alter spontaneous locomotor activity. The anxiolytic effect of psychollatine was prevented by prior administration of ritanserin, but not of picrotoxin, indicating that 5-HT2 but not GABA receptors are implicated. In the forced swimming model of depression, psychollatine (3 and 7.5 mg/kg) effects were comparable to the antidepressants imipramine (15 mg/kg) and fluoxetine (20 mg/kg). Psychollatine suppressed oxotremorine-induced tremors in all doses. In the step-down learning paradigm, diazepam (0.85 mg/kg), MK-801 (0.15 mg/kg), and psychollatine 100 mg/kg impaired the acquisition of learning and memory consolidation, without interfering with retrieval. It is concluded that the effects of psychollatine at the central nervous system involve serotonergic 5HT2(A/C) receptors.     

Use of Pavo cristatus feather extract for the better management of snakebites: neutralization of inflammatory reactions

In Indian traditional medicine, peacock feather in the form of ash (Bhasma) or water extract are used against snakebite and to treat various problems associated with lungs. This study was aimed to evaluate the water extract of peacock feather (PCF) against the local tissue damage caused due to snakebite. PCF water extract showed inhibition towards phospholipase A2 enzyme activity from snake venom (Naja naja and Vipera russelii), inflammatory fluids (synovial, pleural, ascites) and normal serum in a dose-dependent manner. Hyaluronidase and proteases are other major enzymes in snake venoms responsible for local tissue damage. PCF water extract inhibited hyaluronidase and proteolytic enzyme activities from Vipera russelii, Naja naja and Trimeresurus malabaricus venom. The active principle is a hydrophilic molecule easily extractable in water or polar solvents. PCF water extract gave positive results for the presence of protein and secondary metabolites like carotenoids and steroids. Analysis of metal ions revealed that iron is the major ion (> 20-fold). Other metal ions detected in smaller amount are copper, chromium, zinc and nickel. The least amount of ion detected is gold. Co-injection of PCF water extract with snake venom and inflammatory PLA2 enzymes neutralize the edema inducing activity of all the PLA2 enzymes studied. Since it inhibits hyaluronidase and proteases enzyme activity from snake venom PCF water extract is a powerful neutralizing agent, which has therapeutic application against venom toxicity.     

Interstitial brachytherapy of periorificial skin carcinomas of the face: a retrospective study of 97 cases

PURPOSE: To analyze outcomes after interstitial brachytherapy of facial periorificial skin carcinomas. PATIENTS AND METHODS: We performed a retrospective analysis of 97 skin carcinomas (88 basal cell carcinomas, 9 squamous cell carcinomas) of the nose, periorbital areas, and ears from 40 previously untreated patients (Group 1) and 57 patients who had undergone surgery (Group 2). The average dose was 55 Gy (range, 50-65 Gy) in Group 1 and 52 Gy (range, 50-60 Gy) in Group 2 (mean implantation times: 79 and 74 hours, respectively). We calculated survival rates and assessed functional and cosmetic results de visu. RESULTS: Median age was 71 years (range, 17-97 years). There were 29 T1, 8 T2, 1 T3, and 2 Tx tumors in Group 1. Tumors were <2 cm in Group 2. Local control was 92.5% in Group 1 and 88% in Group 2 (median follow-up, 55 months; range, 6-132 months). Five-year disease-free survival was better in Group 1 (91%; range, 75-97) than in Group 2 (80%; range, 62-90; p = 0.23). Of the 34 patients whose results were reassessed, 8 presented with pruritus or epiphora; 1 Group 2 patient had an impaired eyelid aperture. Cosmetic results were better in Group 1 than in Group 2 with, respectively, 72% (8/11) vs. 52% (12/23) good results and 28 (3/11) vs. 43% (10/23) fair results. CONCLUSIONS: Brachytherapy provided a high level of local control and good cosmetic results for facial periorificial skin carcinomas that pose problems of surgical reconstruction. Results were better for untreated tumors than for incompletely excised tumors or tumors recurring after surgery.     

A screening questionnaire for voice problems after treatment of early glottic cancer

PURPOSE: After treatment for early glottic cancer, a considerable number of patients end up with voice problems interfering with daily life activities. A 5-item screening questionnaire was designed for detection of voice impairment. The purpose of this study is to assess psychometric properties of this questionnaire in clinical practice. METHODS AND MATERIALS: The questionnaire was completed by 110 controls without voice complaints and 177 patients after radiotherapy or laser surgery for early glottic cancer. RESULTS: Based on normative data of the controls, a score of 5 or less on at least 1 of the 5 questions was considered to state overall voice impairment. Reliability of the questionnaire proved to be good. Voice impairment was reported in 44% of the patients treated with radiotherapy vs. 29% of the patients treated with endoscopic laser surgery. CONCLUSIONS: The questionnaire proved to be a reliable, valid, and feasible method to detect voice impairment in daily life. The questionnaire is easy to fill in, and interpretation is straightforward. It is useful for both radiation oncologists and otorhinolaryngologists in their follow-up of patients treated for early glottic cancer.     

Selective estrogen receptor modulators with conformationally restricted side chains. Synthesis and structure-activity relationship of ERalpha-selective tetrahydroisoquinoline ligands

We disclose herein the discovery of estrogen receptor alpha (ERalpha) selective estrogen receptor modulators (SERMs) of the tetrahydroisoquinoline series that incorporate novel conformationally restricted side chains as replacement of the aminoethoxy residue typical of SERMs. Molecular modeling studies used in conjunction with the X-ray crystal structure of the ERalpha ligand binding domain (LBD) with raloxifene (7) suggested a diazadecaline moiety as a viable mimic of the SERM side chain. On the basis of this knowledge, the piperidinylethoxy moiety of our lead compound 60 was replaced by a diazadecaline subunit, providing the novel tetrahydroisoquinoline 29. In addition to exhibiting a binding affinity to ERalpha and antagonistic properties in the estrogen response element and MCF-7 assays similar to those of the parent compound 60, ligand 29 showed a reduced agonist behavior in the MCF-7 assay in the absence of 17beta-estradiol. These data point toward the fact that 29 may have a potential for breast cancer prevention/treatment in vivo, a feature which is particularly attractive in the quest for safe alternatives to hormone replacement therapy. In a pharmacokinetic experiment carried out in rats, 29 displayed an interesting profile, with a bioavailability of 49%. We also disclose the X-ray crystal structure of 29 in complex with ERalpha-LBD, which reveals the preferred configurations of 29 at the two chiral centers and the details of its interactions with the receptor. Finally, our structure-activity relationship studies show that other analogues bearing constrained side chains retain potency and antagonist activity and that a 3-OH substituted phenyl D-ring increases the selectivity of a set of piperazinyl-containing ligands in favor of ERalpha over ERbeta.     

Molecular characterisation and mechanisms of resistance of multidrug-resistant human Salmonella enterica serovar Typhimurium isolated in Amiens (France)

Antimicrobial resistance patterns of Salmonella enterica serovar Typhimurium isolates obtained during the study period were examined. The molecular epidemiology and the mechanisms of resistance to ampicillin, chloramphenicol and tetracycline were investigated. Resistance to ampicillin increased from 59% between 1996 and 1999 to 62.5% in 2000 and to 66.6% in 2001. Of 51 S. Typhimurium isolates studied, 100% were resistant to ampicillin (minimum inhibitory concentration (MIC)>256 mg/L) and sulphonamide (MIC range, 128 to >256 mg/L). Ninety-eight percent of isolates were resistant to streptomycin (MIC range, 48-256 mg/L), 92.2% to tetracycline (MIC range, 32 to >256 mg/L), 88.2% to chloramphenicol (MIC>256 mg/L), 21.5% to sulphamethoxazole/trimethoprim (MIC>32 mg/L), 5.8% to amoxicillin/clavulanic acid (MIC, 32 mg/L) and 1.9% to cefalothin (MIC, 64mg/L). Six resistance phenotypes were found (a-f), with phenotypes a (47%) and b (27.5%) being predominant. Twenty-five (49%) of 51 isolates produced a single beta-lactamase, among which 48% produced PSE-1, 44% produced TEM-1 and 8% produced OXA-1. Among 26 of the 51 isolates, 10 produced PSE-1+OXA-1, 7 produced TEM-1+PSE-1+OXA-1, 6 produced TEM-1+PSE-1, and 3 produced TEM-1+OXA-1. Forty-eight (94.1%) of the 51 isolates had the plasmid-mediated resistance gene flo(ST) to chloramphenicol and tetracycline. Combining enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) and pulsed-field gel electrophoresis (PFGE), 16 distinct patterns were identified, among which patterns IA (35.3%) and IF (27.4%) were considered as epidemic patterns. The dendrogram obtained from S. Typhimurium pulsotypes allowed five clones (S1-S5) to be identified, with two prevalent clones comprising 47.8% (S2) and 27.3% (S4) of the isolates.     

Continuous renal replacement therapy after cardiac surgery. Review of 85 cases

BACKGROUND/AIMS: To evaluate the outcome of patients who require continuous renal replacement therapy (CRRT) following cardiac surgery. METHODS: All patients who received CRRT after cardiac surgery over more than 4 years at the Surgical Intensive Care Unit of the Montreal Heart Institute were reviewed. Among 5,564 consecutive patients, 85 underwent CRRT postoperatively. RESULTS: The mean delay between surgery and CRRT initiation was 5 days, and the duration of CRRT was 9 days, without a difference between survivors and non-survivors. Delivered clearances with CRRT were estimated at 25-28 ml/min (approximately 40 liters/day), 29-32 ml/min (approximately 46 liters/day) and 17 ml/min (approximately 25 liters/day) for continuous veno-venous hemofiltration, continuous veno-venous hemodiafiltration and continuous veno-venous hemodialysis, respectively. In-hospital mortality was 43.5%. No difference in mortality was observed between patients with normal renal function at baseline and those with pre-operative renal dysfunction. Mortality was 33.3% after a coronary artery bypass graft (CABG), 57.1% after CABG and valve surgery, 60% after valve surgery, and 72.7% for redo-CABG or redo-valve surgery. 79% of survivors and 86% of non-survivors had received a cardiopulmonary bypass (p = NS). The Simplified Acute Physiology Score II upon intensive care unit (ICU) admission and the requirement of an intra-aortic balloon pump were higher in non-survivors (p < 0.05). The mean length of ICU and hospital stay was 27.4 and 34.2 days for survivors and 17.9 and 22.3 days for non-survivors, respectively (p < 0.05). CONCLUSIONS: Renal impairment is relatively common after cardiac surgery. The mortality of patients who required CRRT after cardiac surgery was 43.5% and was particularly influenced by the type of surgery.