Prospective intervention trial of a screening protocol to identify fetal trisomy 18 using maternal serum alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotropin.

Two prenatal centres in New England, routinely using a screening protocol for fetal Down syndrome that included maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG) measurements in combination with maternal age, adopted a separate screening protocol for trisomy 18. That protocol identified a pregnancy as being at high risk when AFP, uE3, and hCG measurements all fell at or below specified cut-offs (0.75, 0.60, and 0.55 multiples of the median, respectively), regardless of maternal age. Among the first 19,491 women screened, 98 (0.5 per cent) were found to have values which placed them in the high-risk category. Four of these women were subsequently found not to be pregnant. In two others, samples from non-pregnant individuals were found to have been incorrectly submitted for analysis in place of the samples from the pregnant women. All of the remaining 92 women were counselled and offered amniocentesis and fetal karyotyping. Eighty-eight (96 per cent) accepted. Karyotypes or birth outcomes were available on all 92 pregnancies. Six cases of trisomy 18 and one case of Turner syndrome were identified by karyotype. One case of trisomy 18 was identified for every 14 unaffected pregnancies offered amniocentesis. In the present prospective study, an estimated 85 per cent of the cases of trisomy 18 were identified. However, given the small number of cases (six), the 95 per cent confidence interval for the detection rate is broad (40-95 per cent).     

Mosquito collections following local transmission of Plasmodium falciparum malaria in Westmoreland County, Virginia

A 63-year-old woman from Colonial Beach, Westmoreland County, VA, was diagnosed with Plasmodium falciparum malaria on July 19, 1998. The woman had no history of international travel, intravenous drug use, blood transfusion, or other risk factor for contracting the disease. She seldom left the county and generally spent her evenings indoors, leading to the conclusion that she had been bitten locally by an infected mosquito. Colonial Beach is host to a population of migrant agricultural laborers from areas in which malaria occurs, but a blood survey of 89 Haitians and Mexicans failed to find Plasmodium parasites, specific antibodies, or clinical cases of malaria. Mosquito surveys were conducted during 2 days (July 22 and 28, 1998) with carbon-dioxide-baited light traps, larval and pupal collections, and landing collections. Thirteen species of mosquitoes were identified morphologically, including 4 potential vectors: Anopheles crucians, An. punctipennis, An. smaragdinus (new state record), and An. quadrimaculatus s.s. (new state record). Identifications of the latter 2 species were confirmed by sequencing of the ITS2 DNA region from adults reared from locally collected larvae. Anopheles smaragdinus was the most common biting species among the potential vectors, although An. crucians was the most abundant in other kinds of collections. In addition, Ae. albopictus was collected in Westmoreland County for the 1st time.     

Biological Mechanisms,Cerebrovascular Alterations and Pharmacological Targets in the Pathology of Dementia

In response to stimulation, information is stored in the brain when synapses are simultaneously active. Interestingly, a physiological continuum may exist between processes of memory formation and brain injury, as many of the molecular mechanisms involved in memory encoding are the same as those activated during excitotoxic events in neurons. However, how brain injury leads to long lasting impairments in memory and/or dementia is still open for debate. Furthermore, evidence now suggests that cerebrovascular alterations and the pathology seen in dementia from Alzheimer's disease are mechanistically linked. Investigations have generated a wealth of information on mechanisms that become disturbed in dementia. However, there is still no cure for dementia of the Alzheimer's type. Undaunted by failures or drugs that have only modest effects, hundreds of drug discovery programs across the world continue to look for promising and more effective treatments for the disease. (c) 2002 Prous Science. All rights reserved.     

Design,synthesis, and SAR of tachykinin antagonists: modulation of balance in NK(1)/NK(2) receptor antagonist activity

Through optimization of compounds based on the dual NK(1)/NK(2) antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK(1) and NK(2) potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK(1) potency and thus afforded NK(1) preferential antagonists. Alterations of the piperidine region could then increase NK(2) potency to restore dual NK(1)/NK(2) selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK(1)/NK(2) antagonists, and the third is an NK(1) preferential antagonist. In this paper, the factors affecting the balance of NK(1) and NK(2) selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.     

Methylphenidate bioavailability from two extended-release formulations

OBJECTIVE: The objective of these studies was to compare the rate and extent of absorption of d,l-threo-methylphenidate (MPH) from two extended-release products--a capsule formulation containing coated beads and an OROS tablet formulation--in healthy male and female subjects under fasted conditions. MATERIALS: Metadate CD (methylphenidate HCl, USP) Extended-Release Capsules and Concerta (methylphenidate hydrochloride) Extended-Release Tablets. METHODS: Two studies were conducted: (1) A single dose, randomized, two-way crossover study in 36 adults comparing a 20 mg capsule and an 18 mg tablet, and (2) a single dose, randomized, four-way crossover study in 24 adults comparing 2 x 20 mg capsules, one 36 mg tablet, 3 x 20 mg capsules and one 54 mg tablet. Blood samples were collected over 24 hours and MPH plasma concentrations were used to calculate pharmacokinetic parameters for each treatment. Equivalence of pharmacokinetic parameters for comparable doses of the formulations was concluded if the 90% confidence intervals (CI) for the ratio between test and reference means were within the 80-125% equivalence criterion. RESULTS: Both formulations exhibited biphasic plasma concentration-time profiles and were equivalent in terms of total exposure (AUC(0-last) and AUC(0-infinity)). However, early exposure (AUC(0-4) and AUC(0-6), the first maximum measured plasma concentration (C(max-1), and early plasma MPH concentrations (1.5, 3 and 4 hours) were greater with the capsule formulation, while later plasma MPH concentrations (8, 10 and 12 hours) were greater with the tablet formulation (the CIs were outside the 80-125% required for equivalence and p < 0.001 for all). Similar results were obtained whether or not the data were normalized for the difference in total dose. CONCLUSIONS: The two formulations are not bioequivalent. The capsule fonnulation produces greater exposure to MPH and higher MPH concentrations during the first 6 hours following dosing. MPH is frequently used in school children, and this period would correspond to a major part of the school day.     

Plastische Ohrmuschelverkleinerung bei beidseitiger Makrotie

We present the rare case of a bilateral reduction of macrotic ears by a helical advancement according to Davis. It is a quite simple and reliable technique, that permits to hide the scars in the relief of the pinna.     

Whole-brain atrophy in multiple sclerosis measured by two segmentation processes from various MRI sequences

Recent MRI and pathologic studies have drawn attention to the destructive nature of the multiple sclerosis (MS) disease process, including the early occurrence of axonal and neuronal loss, leading to macroscopic brain and spinal cord atrophy. Measurement of brain atrophy from MRI has emerged as a potential outcome measure and marker of disease severity in MS and neurodegenerative diseases such as Alzheimer's. However, the optimal method for quantifying atrophy has not been established, including the choice of pulse sequence and segmentation algorithm employed. Using two different MRI scanners to ensure generalizability of results, we compared the reproducibility of four pulse sequences and two analysis methods (fully automated [FA] and semi-automated [SA]) when obtaining brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, in patients with MS (n=13) and normal controls (n=2). In order to ensure the validity of our fully automated analysis technique, we also used it to evaluate the atrophy rate over nine months in 57 MS patients from the placebo arm of a clinical trial.All pulse sequences were capable of yielding reproducibility of around 1% coefficient of variation (CoV) or better. The best reproducibility was obtained using 2D multi-slice sequences (conventional spin echo [SE] and fluid-attenuated inversion recovery [FLAIR]), with fully automated analysis. Fully automated analysis of the longitudinal data (conventional spin echo) showed an atrophy rate of -0.5% change in BPF per year, in line with previous findings from a similar cohort of patients.In conclusion, BPF measurement is affected by both pulse sequence and segmentation method. Automated measurement has high reproducibility especially when 2D sequences are used. Semi-automated measurement may have increased accuracy, but with a decreased efficiency and reliability.