Maxillofacial manifestations of acquired immunodeficiency syndrome

46 cases of acquired immunodeficiency syndrome permit the authors to detail the particular aspects of the oral and facial lesions in AIDS. In patients at risk, a lymphadenopathic syndrome is thought to represent a prodromic phase of the illness. The authors insist upon the differences between the classic Kaposi's sarcoma and that associated with the AIDS (mean age and initial sites of tumor). One third of these sarcomas is completed by a digestive candidiasis. The review of the literature reveals squamous cell carcinoma and Burkitt's lymphoma with the AIDS. We must be aware of early diagnosis and transmission factors in the individuals at risk with tumors and opportunistic infection.     

Hypercalcaemia-induced acute renal failure as a presenting feature of T-cell leukaemia

A 14-year-old patient presented with hypercalcaemia-induced acute renal failure. Investigation yielded a diagnosis of T-cell leukaemia. Chemotherapy resulted in complete remission, a return of serum calcium levels to normal and consequent improvement of renal function.Abbreviations ARF acute renal failure - PTH parathormone     

Quantitative determination of n-propane, iso-butane, and n-butane by headspace GC-MS in intoxications by inhalation of lighter fluid

This report describes a fully elaborated and validated method for quantitation of the hydrocarbons n-propane, iso-butane, and n-butane in blood samples. The newly developed analytical procedure is suitable for both emergency cases and forensic medicine investigations. Its practical applicability is illustrated with a forensic blood sample after acute inhalative intoxication with lighter fluid; case history and toxicological findings are included. Identification and quantitation of the analytes were performed using static headspace extraction combined with gas chromatography-mass spectrometry. In order to reconcile the large gas volumes injected (0.5 mL) with the narrowbore capillary column and thus achieve preconcentration, cold trapping on a Tenax sorbent followed by flash desorption was applied. Adequate retention and separation were achieved isothermally at 35 degrees C on a thick-film capillary column. Sample preparation was kept to a strict minimum and involved simply adding 2.5 microL of a liquid solution of 1,1,2-trichlorotrifluoroethane in t-butyl-methylether as an internal standard to aliquots of blood in a capped vial. Standards were created by volumetric dilution departing from a gravimetrically prepared calibration gas mixture composed of 0.3% of n-propane, 0.7% of iso-butane, and 0.8% of n-butane in nitrogen. In the forensic blood sample, the following concentrations were measured: 90.0 microg/L for n-propane, 246 microg/L for iso-butane, and 846 microg/L for n-butane.     

Plasma concentration response to drinks containing beta-carotene as carrot juice or formulated as a water dispersible powder

Summary. Background: Bioavailability of β-carotene is highly variable and depends on the source, the formulation and other nutritional factors. Objective: It was the aim of the study to compare β-carotene plasma response to b-carotene dosing with two commercially available drinks, containing β-carotene from carrot juice or as water dispersible β-carotene powder. Design In a randomized, parallel group study design, 4 volunteers per group received daily β-carotene doses of 6–7 or 18–22 mg of either drink over 6 weeks. Blood samples for determination of carotenoid and vitamin A plasma concentrations were collected before supplementation and over the dosing period. Results: Apparent steady-state β-carotene concentrations were attained after 40 days of supplementation. Consumption of the beverage containing β-carotene as a water dispersible powder resulted in a higher response of β-carotene plasma concentrations with increments of 3.84 ± 0.60 μmol/L (p < 0.05, dose: 7.2 mg/d) and 5.04 ± 0.72 μmol/L (p < 0.05, dose: 21.6 mg/d), respectively, in comparison to the carrot juice-based drink with increments of 0.42 ± 0.33 μmol/L (dose: 6 mg/d) and 1.71 ± 0.55 μmol/L (dose: 18 mg/d), respectively. β-carotene was cleared from the plasma with an apparent half-life of 6–11 days. Plasma concentrations of α-carotene, β-cryptoxanthin, lutein, zeaxanthin, and lycopene remained almost unchanged, whereas retinol plasma concentrations increased slightly. By contrast, with the exception of elevated 13-cis-retinoic acid in one group (21.6 mg/d, water dispersible powder), the concentrations of all-trans-retinoic acid, and the oxo-derivatives or retinoic acid were not significantly affected by b-carotene supplementation. Conclusions: The results confirm that the relative bioavailability of β-carotene depends largely on the source of b-carotene and demonstrate the superior bioavailability of β-carotene powder in comparison to that in carrot juice. Received: 7 May 2002, Accepted: 22 August 2002 This work was supported by a grant from F. Hoffmann-La Roche Ltd., Vitamins and Nutrition Research, Basle, Switzerland. Correspondence to: Prof. Dr. med. Petra A. Thürmann     

Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease

Carbamate derivatives of N-propargylaminoindans (Series I) and N-propargylphenethylamines (Series II) were synthesized via multistep procedures from the corresponding hydroxy precursors. The respective rasagiline- and selegiline-related series were designed to combine inhibitory activities of both acetylcholine esterase (AChE) and monoamine oxidase (MAO) by virtue of their carbamoyl and propargylamine pharmacophores. Each compound was tested for these activities in vitro in order to find molecules with similar potencies against each enzyme. Compounds with such dual AChE and MAO inhibitory activities are expected to have potential for the treatment of Alzheimer's disease. The observed SAR also offers insight into the requirements of the active sites on these enzymes. A carbamate moiety was found to be essential for AChE inhibition, which was absent in the corresponding hydroxy precursors. The propargyl group caused 2-70-fold decrease in AChE inhibitory activity (depending on the position of the carbamoyl group) of Series I, but had little or no effect in Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were either equipotent to, or slightly (2- to 5-fold) less active as AChE inhibitors than, the corresponding compounds in Series II, while the 4-carbamyloxyphenyls were more potent. The presence of the carbamate moiety in 6- and 7-carbamyloxyphenyls of Series I, considerably decreased MAO-A and -B inhibitory activity, compared to that of the parent hydroxy analogues, while the opposite was true for Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were 2-3 orders of magnitude weaker MAO inhibitors while the 4- carbamyloxyphenyls were equipotent with the corresponding compounds in Series II. In both series, N-methylation of the propargylamine enhanced the MAO (A and B equally) inhibitory activities and decreased the AChE inhibitory activity. Two candidates belonging to the indan and tetralin ring systems (24c, 27b) and one phenethylamine (53d) were identified as possible leads for further development based on the following criteria: (a) comparable AChE and MAO-B inhibitory activities, (b) good to moderate AChE inhibitory activity, and (c) lack of strong MAO-A selectivity. However, it is likely that these compounds will be metabolized to the corresponding phenols, with inhibitory activities against AChE and/or MAO-A or -B, different from those of the parent carbamates. Thus, the apparent enzyme inhibition will be a result of the combined inhibition of all of these individual metabolites. The results of our ongoing in vivo screening programs will be published elsewhere.     

Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence

PURPOSE: We evaluated the efficacy and safety of an oxybutynin transdermal delivery system (TDS) in a general population of patients with overactive bladder and urge or mixed urinary incontinence. MATERIALS AND METHODS: Following symptom stabilization or treatment withdrawal 520 adult patients were randomized to 12 weeks of double-blind daily treatment with 1.3, 2.6 or 3.9 mg. oxybutynin TDS or placebo administered twice weekly, followed by a 12-week open-label, dose titration period to assess efficacy and safety further. Evaluations included patient urinary diaries, incontinence specific quality of life and safety. RESULTS: A dose of 3.9 mg. daily oxybutynin TDS significantly reduced the number of weekly incontinence episodes (median change -19.0 versus -14.5, p = 0.0165), reduced average daily urinary frequency (mean change -2.3 versus -1.7, p = 0.0457), increased average voided volume (median change 24 versus 6 ml., p = 0.0063) and significantly improved quality of life (Incontinence Impact Questionnaire total score, p = 0.0327) compared with placebo. Average voided volume increased in the daily 2.6 mg. group (19 ml., p = 0.0157) but there were no other significant differences between 1.3 and 2.6 mg. oxybutynin TDS and placebo. The most common adverse event was application site pruritus (oxybutynin TDS 10.8% to 16.8%, placebo 6.1%). Dry mouth incidence was similar in both groups (7.0% versus 8.3%, p not significant). In the open-label period a sustained reduction of nearly 3 incontinence episodes per day was reported for all groups. CONCLUSIONS: Doses of 2.6 and 3.9 mg. oxybutynin TDS daily improve overactive bladder symptoms and quality of life, and are well tolerated. Transdermal oxybutynin is an innovative new treatment for overactive bladder.     

Lateral frontal cortex oxygenation changes during translation and language switching revealed by non-invasive near-infrared multi-point measurements

The organisation of language in the brain of multilingual people remains controversial. Using a high temporal resolution 12-channel near-infrared continuous wave spectroscopy system, we have demonstrated that it is possible to monitor non-invasively, comfortably and, without the interferences due to intrinsic limitations of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), cortical oxygenation changes in the Broca's area in response to translation of short sentences and language switching. Eight Dutch students proficient in English translated aloud from their native language into English or vice versa or alternating (switching) short visually presented sentences. These tasks provoked, in the left inferior frontal cortex which includes the Broca's area, a consistent and incremental rise in oxyhaemoglobin accompanied by a smaller decrease in deoxyhaemoglobin. The investigated cortical areas surrounding the Broca's area showed no uniform and consistent oxygenation changes upon the three different translation tasks. These results confirm that Broca's area is involved in the translation process and its so called activation is unaffected by the direction of the translation. In addition, these results strengthen the role of near-infrared multi-point measurements as a powerful tool for investigating the spatial and temporal features of the cortical oxygenation changes during language processing.