A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder

OBJECTIVE: Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with escitalopram. METHOD: A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002. RESULTS: Survival analysis of relapse and time to relapse showed a significant advantage for escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for escitalopram-treated patients (p < .001), resulting in significantly fewer escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with escitalopram and 8.3% for patients treated with placebo. CONCLUSION: Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.     

Immunization with a tetramer derivative of an anti-inflammatory pentapeptide produced by Entamoeba histolytica protects gerbils (Meriones unguiculatus) against experimental amoebic abscess of the liver

Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with several anti-inflammatory properties, including the inhibition of human monocyte locomotion (Monocyte Locomotion Inhibitory Factor (MLIF)). A construct displays the same effects as the native material. It remains to be seen if MLIF is used, or even produced in vivo by the tissue-invading parasite. If MLIF were to be relevant in invasive amoebiasis, immunizing against it could diminish this parasite advantage and prevent lesions. KLH-linked MLIF mixed with Freund's adjuvant was too aggressive an immunizing material to answer this question. However, immunization with a tetramer of MLIF (but not a scrambled version of MLIF) around a lysine core (MLIF-MAPS), that displays increased antigenicity, yet lacks excessive innate immunity activation, completely protects gerbils against amoebic abscess of the liver caused by the intraportal injection of virulent E. histolytica. Liver abscesses caused by Listeria monocytogenes were not prevented. Invasive E. histolytica may produce the parent protein of MLIF in vivo, and if appropriately cleaved, it may play a role in invasive amoebiasis. MLIF may join new vaccination strategies against amoebiasis.     

An anomaly within the Latino epidemiological paradox: the Latino adolescent male mortality peak

OBJECTIVE: To describe the anomaly of the Latino adolescent male mortality peak in relation to the overall Latino epidemiological paradox and in relation to the need for new conceptual models describing the health of a culturally diverse population. DESIGN: Population-based study using California's 1989 to 1997 summary death files for death-related information and the State of California Department of Finance population estimates for population denominators for corresponding years. PARTICIPANTS: California's general population for 1989 to 1997, including California's 15- to 19-year-old and 20- to 24-year-old populations. In 1997, those 2 age groups numbered 4.3 million. MAIN OUTCOME MEASURES: Mortality rates for Latinos and African Americans compared with non-Hispanic whites expressed as relative risk (RR). RESULTS: Overall, the Latino RR of mortality follows the Latino epidemiological paradox in that it is lower (RR, <1.00) than that of non-Hispanic whites for most age groups and both sexes. The anomaly within this paradox is seen in Latino males aged 15 to 19 years (RR, 1.77; 95% confidence interval, 1.55-2.02) and 20 to 24 years (RR, 1.79; 95% confidence interval, 1.58-2.02). CONCLUSIONS: This period of elevated mortality risk is labeled the Latino adolescent male mortality peak, and it is an anomaly within the overall Latino epidemiological paradox.     

Ventilation time of the middle ear in otitis media with effusion (OME) after CO2 laser myringotomy

OBJECTIVE: The aim of this study was to investigate the transtympanic ventilation time, the healing course of the tympanic membrane, the early and late complications, and the recurrence rate of otitis media with effusion (OME) within 6 months after CO2 laser myringotomy with the CO2 laser otoscope Otoscan. STUDY DESIGN: Prospective clinical study. MATERIALS AND METHODS: In this study, laser myringotomy was performed with the CO2 laser otoscope Otoscan in a patient population comprising 81 children (159 ears) with a history of otitis media with effusion (OME) associated with adenoidal and sometimes tonsillar hyperplasia. The procedure on the tympanic membrane was accordingly combined with an adenoidectomy, a CO2 laser tonsillotomy, or a tonsillectomy and therefore performed under insufflation anesthesia. In all ears, approximately 2 mm circular perforations were created in the lower anterior quadrants with a power of 12 to 15 W, a pulse duration of 180 msec, and a scanned area of 2.2 mm in diameter. RESULTS: None of the children showed postoperative impairment of cochleovestibular function such as sensorineural hearing loss or nystagmus. Otomicroscopic and videoendoscopic monitoring documented the closure time and healing pattern of tympanic membrane perforations. The mean closure time was found to be 16.35 days (minimum, 8 days; maximum, 34 days). As a rule, an onion-skin-like membrane of keratinized material was seen in the former myringotomy perforations at the time of closure. At the follow-up 6 months later, the condition of the tympanic membrane of 129 ears (81.1%) could be checked by otomicroscopy and videoendoscopy and the hearing ability by audiometry and tympanometry. The CO2 laser myringotomy sites appeared normal and irritation-free. Two of the tympanic membranes examined (1.6%) showed atrophic scar formation, and 1 (0.8%) had a perforation with a diameter of 0.3 mm. The perforation was seen closed in a control otoscopy 15 months postoperatively. OME recurred in 26.3% of the ears seen intraoperatively with mucous secretion (n = 38) and in 13.5% of the ears with serous secretion (n = 37; P <.05). CONCLUSION: The most important principle in treating OME is ventilation of the tympanic cavity. CO2 laser myringotomy achieves this through a self-healing perforation in which its diameter roughly determines the duration of transtympanic ventilation. Laser myringotomy competes with ventilation tube insertion in the treatment of OME. It may be a useful alternative in the surgical management of secretory otitis media.     

Sesquiterpenoid derivatives from Gonospermum elegans and their cytotoxic activity for HL-60 human promyelocytic cells

Four new compounds, a sesquiterpene, eleganodiol (1), and three sesquiterpene lactones, eleganolactone A (2), eleganolactone B (3), and elegain (4), were isolated from Gonospermum elegans along with 16 known compounds. The structures of 1, 2, and 4 were determined on the basis of MS and NMR studies of their acetate derivatives (1a, 2a, 4a). The structure of the acetate derivative (3a) of 3 was determined on the basis of spectroscopic data interpretation and by single-crystal X-ray diffraction. Compounds 2a and 3a were used to study their biological activities on the HL-60 human promyelocytic leukemia cell line. These compounds induced morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death.