Epidemiological characteristics of uveitis in Switzerland

Since January 1990, data from uveitis patients have been systematically stored in a computer data bank. During the period from January 1990 to March 1993, 435 new patients (185 female and 250 male, mean age 43 years; range 6–92) were seen at the Uveitis Clinic of the Hopital Jules Gonin. These 435 patients (630 eyes) were subdivided into anterior uveitis (268 patients — 62%), intermediate uveitis (47 patients — 11%), posterior uveitis (89 patients — 20%) and panuveitis (31 patients — 7%). The incidence of uveitis for the referral area considered was calculated to be 17 per 100,000 inhabitants per year. A specifie diagnosis was found in 312 cases (72%). The most frequently diagnosed entities were HLA-B27-associated acute anterior uveitis (67 cases — 15.4%), uveitis associated with acute herpes zoster ophthalmicus (40 cases — 9.2%), toxoplasmosis (39 cases — 9%), typical pars planitis (29 cases — 6.7%), sarcoidosis (29 cases — 6.7%), Fuchs' heterochromic cyclitis (27 cases — 6.2%), herpetic anterior uveitis (21 cases — 4.8%) and acute retinal necrosis (11 cases — 2.5%). Incidence and distribution of most disease entities correspond to those of other European series.     

Hepatectomy in intrahepatic lithiasis

STUDY AIM: The aim of this study was to report the immediate results of a series of 65 hepatic resections for hepatolithiasis performed in Vietnam. PATIENTS AND METHOD: From 1986 to 1998, 44 men and 21 women (mean age: 40 years) underwent hepatic resection for hepatolithiasis. Fourty patients had previously undergone one or several operations for hepatolithiasis. The procedure was performed on emergency in 25 patients. Indications for hepatic resection were: angiocholitis and liver abscess in 22 cases, stones closely inserted in the biliary duct in 20 cases, hemobilia in 12 cases, stones located above a biliary stricture in 8 cases and stones associated with a postoperative biliary fistula in 3 cases. Liver resections (minor in 61 patients, including 55 left lobectomies, and major in 4 patients) were performed through transhepatic approach according to the Ton That Tung technique and followed by an external biliary drainage with a Kehr tube. RESULTS: There were 6 postoperative deaths (9%), 3 due to septic shock, 2 to cachexia, and 1 to liver failure. The 15 patients with complications recovered with conservative therapy. Bile infection was present in 93%, mostly with Escherichia coli and Enterobacter. Pigmented stones were usually found. CONCLUSION: Vietnam is a country with high incidence of hepatolithlasis. Hepatic resection is an adequate treatment for localized intrahepatic bile duct stones when the involved segment including biliary strictures and calculi can be completely removed. The procedure may be performed on emergency for liver abscess, or hemobilia.     

Sentinel lymph node biopsy in breast cancer: unfiltered radioisotope is superior to filtered

BACKGROUND: The combination of gamma-probe radiolocalization and blue-dye mapping of sentinel lymph nodes (SLNs) has been advocated as the most accurate method for staging the clinically negative axilla in breast cancer patients, but the technical aspects of these procedures are not fully characterized in the literature. In this study, we compared the success of SLN localization in 134 consecutive breast cancer patients using blue dye plus two different preparations of radiocolloid. STUDY DESIGN: A retrospective analysis of a prospectively maintained data base was performed to assess SLN localization in two cohorts of patients. Unfiltered technetium-99m (Tc-99m) sulfur colloid (in 77 patients; group I) was compared with filtered Tc-99m sulfur colloid (in 57 patients; group II). All patients had a peritumoral injection of blue dye and isotope, followed immediately by lymphoscintigraphy to confirm radioactivity at the injection site and to image the SLN. Statistical analysis was performed using the Pearson chi-square test. RESULTS: Unfiltered Tc-99m sulfur colloid was superior to the filtered radiocolloid in localizing the SLN (88% versus 73%; p = 0.03). SLN imaging by lymphoscintigraphy was also more successful in the unfiltered group. Using the combination of blue dye and radiolocalization, SLNs were identified in 94% of patients. CONCLUSIONS: For optimal localization of the SLN in breast cancer patients, surgeons should use the combined technique of blue-dye mapping and gamma-probe localization using unfiltered Tc-99m sulfur colloid.     

Alterations in hippocampal and hypothalamic monoaminergic neurotransmitter systems after alcohol exposure during all three trimester equivalents in adult rats

Summary. Animal models of Fetal Alcohol Syndrome (FAS) often rely on exposing the developing organism to alcohol during either the prenatal or postnatal period only. Very few studies have examined brain changes resulting from alcohol exposure during both the prenatal and postnatal period, a period which is equivalent to all three trimesters in humans. In this study, we examined the effects of alcohol exposure during this prolonged period of neural development on hippocampal and hypothalamic neurotransmitters in the rat. Pregnant dams were intubated with alcohol from gestational day (GD) 1 to GD 22 and then their pups were intubated with alcohol from postnatal day (PD) 2 to PD 10. Alcohol-exposed rats of both sexes exhibited increased hippocampal noradrenaline (NE) concentration compared to intubated and nontreated control animals. Within the hypothalamus, alcohol-exposed females but not males exhibited increased NE concentration. Hypothalamic serotonin (5-HT) concentration was reduced in both alcohol-exposed and intubated-control rats compared to nontreated controls. The results suggest that both the hippocampal and hypothalamic NE systems are especially vulnerable to alcohol insult that occurs during a period of neural development that corresponds to the full human prenatal period. Received April 7, 1998; accepted February 2, 1999     

Control of smooth muscle cell proliferation--the role of the basement membrane

In atherogenesis and in response to vessel injury, arterial smooth muscle cells (SMCs) are activated from a quiescent, differentiated state into an actively proliferating and synthetic phenotype which migrate into the intima where the cells participate in the formation of a fibrous plaque or intimal hyperplasia. The mechanisms involved in the control of SMC function are not clear and no preventive therapy against SMC activation is available. Interactions between SMCs and the extracellular matrix have been shown to influence SMC structure and function through integrin-mediated signaling processes. The SMC basement membrane is a specific form of extracellular matrix which seems to be crucial for the maintenance of SMC quiescence and the disruption of these interactions is part of cellular activation after atherogenic or traumatic stimuli. This concept of "negative growth control" may constitute a future target for the development of new strategies in the prevention of SMC activation in atherogenesis and restenosis formation.     

Design, synthesis, and evaluations of substituted 3-[(3- or 4-carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases

Receptor tyrosine kinases (RTKs) have been implicated as therapeutic targets for the treatment of human diseases including cancers, inflammatory diseases, cardiovascular diseases including arterial restenosis, and fibrotic diseases of the lung, liver, and kidney. Three classes of 3-substituted indolin-2-ones containing propionic acid functionality attached to the pyrrole ring at the C-3 position of the core have been identified as catalytic inhibitors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) RTKs. Some of the compounds were found to inhibit the tyrosine kinase activity associated with isolated vascular endothelial growth factor receptor 2 (VEGF-R2) [fetal liver tyrosine kinase 1 (Flk-1)/kinase insert domain-containing receptor (KDR)], fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R) tyrosine kinase with IC(50) values at nanomolar level. Thus, compound 1 showed inhibition against VEGF-R2 (Flk-1/KDR) and FGF-R1 tyrosine kinase activity with IC(50) values of 20 and 30 nM, respectively, while compound 16f inhibited the PDGF-R tyrosine kinase activity with IC(50) value of 10 nM. Structural models and structure-activity relationship analysis of these compounds for the target receptors are discussed. The cellular activities of these compounds were profiled using cellular proliferation assays as measured by bromodeoxyuridine (BrdU) incorporation. Specific and potent inhibition of cell growth was observed for some of these compounds. These data provide evidence that these compounds can be used to inhibit the function of these target receptors.     

4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: a novel, potent, and selective NR1/2B NMDA receptor antagonist.

A structure-based search and screen of our compound library identified N-(2-phenoxyethyl)-4-benzylpiperidine (8) as a novel N-methyl-D-aspartate (NMDA) receptor antagonist that has high selectivity for the NR1/2B subunit combination (IC(50) = 0.63 microM). We report on the optimization of this lead compound in terms of potency, side effect liability, and in vivo activity. Potency was assayed by electrical recordings in Xenopus oocytes expressing cloned rat NMDA receptors. Side effect liability was assessed by measuring affinity for alpha(1)-adrenergic receptors and inhibition of neuronal K(+) channels. Central bioavailability was gauged indirectly by determining anticonvulsant activity in a mouse maximal electroshock (MES) assay. Making progressive modifications to 8, a hydroxyl substituent on the phenyl ring para to the oxyethyl tether (10a) resulted in a approximately 25-fold increase in NR1A/2B potency (IC(50) = 0.025 microM). p-Methyl substitution on the benzyl ring (10b) produced a approximately 3-fold increase in MES activity (ED(50) = 0.7 mg/kg iv). Introduction of a second hydroxyl group into the C-4 position on the piperidine ring (10e) resulted in a substantial decrease in affinity for alpha(1) receptors and reduction in inhibition of K(+) channels with only a modest decrease in NR1A/2B and MES potencies. Among the compounds described, 10e (4-hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperid ine, Co 101244/PD 174494) had the optimum pharmacological profile and was selected for further biological evaluation.     

Resorcinol derivatives from two Ardisia species

Besides a series of known sterols and triterpenoids, 2-methyl-5-(Z-nonadec-14-enyl)resorcinol and 5-(Z-nonadec-14-enyl)resorcinol have been isolated from leaves of Ardisia silvestris. The last mentioned diphenol has also been obtained from roots of Ardisia gigantifolia. The structures of these resorcinol derivatives were elucidated.     

Effects of cyclic enteral nutrition on the immunological status of malnourished patients

The effects of 2 weeks of refeeding by cyclic enteral nutrition on chronically malnourished (mean global nutritional deficiency 19.9 +/- 1.1%) hospitalized patients were assessed in a prospective study with special attention paid to immunological status. All patients were immunodeficient, with cell-mediated immunity being more affected than humoral immunity. After 2 weeks of refeeding, nutritional status had improved by 29.8%. Initially abnormal parameters of humoral immunity (IgM, C3 and C4) improved significantly (P < 0.05) between day 0 and day 15. The following cell-mediated immunity parameters also improved significantly (P < 0.05): CD8, monocyte count, natural killer cell activity and skin tests. Short-term refeeding by cyclic enteral nutrition appears to be a safe and effective way of improving immunodeficiency in chronically malnourished patients, with predictable consequences on infection.