CYP2D6 allelic frequencies in young-onset Parkinson's disease

Parkinson's disease (PD) is thought to develop as a result of interactions between genetic susceptibility factors and environmental exposures. One candidate gene is CYP2D6, which codes for the debrisoquine 4-hydroxylase cytochrome P450. Impairment of debrisoquine 4-hydroxylase activity has been associated with an increased risk of PD in patients with younger age at disease onset. Genotyping studies in patients with an older age at onset have reported modest increases in risk associated with the CYP2D6 B and A alleles; however, the risk for young-onset PD has not been adequately evaluated. We designed a case-control study to investigate the role of nonfunctional CYP2D6 allelic risk factors for young-onset PD in a sizable patient population and compared the distributions of CYP2D6 genotypes between young-onset ( < or = 51 years) PD patients (n = 108) and controls (n = 236). In contrast with the results from genotyping studies conducted among patients with an older age at onset, there were no significant differences in CYP2D6 allelic frequencies between young-onset PD cases and controls. The frequency of the B allele was slightly lower in the young-onset PD cases than in the controls (0.14 versus 0.20) (X2 = 2.66, p = 0.10). The presence of one or more B alleles was not associated with an increased risk of young-onset PD (odds ratio 0.58; 95% CI 0.33 to 1.00), nor was the presence of one or more nonfunctional alleles (i.e., A, B, D, and D2) (odds ratio 0.68; 95% CI 0.41 to 1.13). This study suggests that the young-onset PD population may differ from the older-onset population with respect to risk factors.     

Treatment response of depressed outpatients unresponsive to both a tricyclic and a monoamine oxidase inhibitor antidepressant

BACKGROUND: Data regarding effective treatment options for the minority of patients refractory to initial antidepressant trials are essential to guide therapeutic choices and to sustain the hope of patients and perseverance of clinicians. Few such data are available concerning the treatment of patients refractory to treatment with both a tricyclic antidepressant and a monoamine oxidase inhibitor given singly. METHOD: In a study of mood reactive depressed patients, most of whom met Columbia criteria for atypical depression, 20 patients refractory to vigorous 6-week double-blind trials of both imipramine and phenelzine given singly were given clinician's choice open treatment. A chart review of course in open treatment was conducted. RESULTS: Eleven patients (55%) had a full response to subsequent treatments, principally continued phenelzine and the combination of phenelzine with amitriptyline. Another 6 (30%) had at least moderate benefit from a variety of other treatments. CONCLUSION: These data suggest that even among patients who have failed to respond to two vigorous trials of different antidepressants, at least half appear to benefit from other pharmacologic regimens.     

Determination of potential migrants present in Nylon 'microwave and roasting bags' and migration into olive oil

Two groups of potential migrants were found in Nylon "microwave and roasting bags' (MRBs): volatile compounds were released at cooking temperatures and non-volatile compounds were extracted with methanol and/or water. A dynamic headspace system at 200 degrees C followed by gas chromatography (GC) coupled to mass spectrometry (MS) was used for determination of volatile compounds. Cyclopentanone (31.7 mg/bag), 2-cyclopentyl cyclopentanone (17.4 mg/bag), hexadecane (2.6 micrograms/bag), heptadecane (3.2 micrograms/bag), octadecane (3.0 micrograms/bag) and epsilon-caprolactam (5.0-35.5 mg/ bag) were the main volatile compounds present in the MRBs. High performance liquid chromatography (HPLC) and mass spectrometry were combined for identification and quantification of non-volatile compounds extracted with methanol (46.0 mg/bag). Nylon 6,6 cyclic monomer and cyclic oligomers up to the tetramer and Nylon 6 monomer and cyclic oligomers up to the octamer were identified and quantified, confirming that the plastic was made of Nylon 6,6 and Nylon 6 polymers. The same non-volatile compounds (except Nylon 6 heptamer and octamer) were found to migrate into olive oil at 175 degrees C for 1 h. A total of 0.916 mg/dm2 (19.2 mg/bag) of non-volatile compounds migrated into olive oil (41.8% of those quantified in the plastic material).     

Microvascular free-flap correction of severe hemifacial atrophy

Romberg's disease is a progressive hemifacial atrophy of unknown etiology. Microsurgical reconstruction, focusing on the correction of facial asymmetry and restoration of contour, has become the "gold standard." We report our experience with 15 patients involving 16 free-tissue transfers with a minimum of 1 year of follow-up who were treated from July of 1989 to January of 1993. All patients were classified as having severe atrophy. There were 7 males and 8 females in the series. Distribution of disease was a coup de sabre type or segmental pattern in 6 patients, whereas 9 patients had a hemifacial distribution. Fourteen patients had unilateral disease (7 right and 7 left), and 1 patient had bilateral atrophy. The average age of onset of disease was 11.9 years. The average duration of atrophy was 6.7 years. No patient was operated on with a quiescent interval of less than 2 years. Average age at operation was 28.7 years, with a range from 6 to 46 years. Follow-up ranged from 1 to 4.5 years. Two patients had facial hematomas as the only complication. No flaps were lost. Flap revisions consisting of minor contour corrections were performed in 10 patients. Limited recurrence of facial atrophy was seen in a single patient 2 years postoperatively. All patients rated their improvement as excellent. The deepithelialized extended parascapular flap with large fascial extensions of dorsal thoracic fascia is our procedure of choice. This fascia can be folded into variable thicknesses to correct subtle contour defects of the upper lip, medial canthus, eyelids, and ear that have reportedly been difficult to reconstruct.(ABSTRACT TRUNCATED AT 250 WORDS)     

Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functions

Osteopontin (OPN) is a secreted calcium-binding phosphoprotein produced in a variety of normal and pathological contexts, including tissue mineralization and cancer. OPN contains a conserved RGD (arg-gly-asp) amino acid sequence that has been implicated in binding of OPN to cell surface integrins. To determine whether the RGD sequence in OPN is required for adhesive and chemotactic functions, we have introduced two site-directed mutations in the RGD site of the mouse OPN cDNA, in which the RGD sequence was either deleted or mutated to RGE (arg-gly-glu). In order to test the effect of these mutations on OPN function, we expressed control and mutated mouse OPN in E. coli as recombinant glutathione-S-transferase (GST)-OPN fusion proteins. Control mouse GST-OPN was functional in cell adhesion assays, supporting attachment and spreading of mouse (malignant PAP2 ras-transformed NIH 3T3, and, to a lesser extent, normal NIH 3T3 fibroblasts) and human (MDA-MB-435 breast cancer, and normal gingival fibroblast) cells. In contrast, neither of the RGD-mutated OPN proteins ("delRGD" or "RGE") supported adhesion of any of the cell lines, even when used at high concentrations or for long assay times. GRGDS (gly-arg-gly-asp-ser) peptides inhibited cell adhesion to intact GST-OPN, as well as to fibronectin and vitronectin. In chemotaxis assays, GST-OPN promoted directed cell migration of both malignant (PAP2, MDA-MB-435) and normal (gingival fibroblast, and NIH 3T3) cells, while RGD-mutated OPN proteins did not. Together these results suggest that the conserved RGD sequence in OPN is required for the majority of the protein's cell attachment and migration-stimulating functions.     

Rhinotillexomania: psychiatric disorder or habit?

BACKGROUND: Conditions once considered bad habits are now recognized as psychiatric disorders (trichotillomania, onychopagia). We hypothesized that nose picking is another such "habit," a common benign practice in most adults but a time-consuming, socially compromising, or physically harmful condition (rhinotillexomania) in some. METHODS: We developed the Rhinotillexomania Questionnaire, mailed it to 1000 randomly selected adult residents of Dane County, Wisconsin, and requested anonymous responses. The returned questionnaires were analyzed according to age, sex, marital status, living arrangement, and educational level. Nose picking was characterized according to time involved, level of distress, location, attitudes toward self and others regarding the practice, technique, methods of disposal, reasons, complications, and associated habits and psychiatric disorders. RESULTS: Two hundred fifty-four subjects responded. Ninety-one percent were current nose pickers although only 75% felt "almost everyone does it"; 1.2% picked at least every hour. For 2 subjects (0.8%), nose picking caused moderate to marked interferences with daily functioning. Two subjects spent between 15 and 30 minutes and 1 over 2 hours a day picking their nose. For 2 others, perforation of the nasal septum was a complication. Associated "habits" included picking cuticles (25%), picking at skin (20%), biting fingernails (18%), and pulling out hair (6%). CONCLUSION: This first population survey of nose picking suggests that it is an almost universal practice in adults but one that should not be considered pathologic for most. For some, however, the condition may meet criteria for a disorder-rhinotillexomania.     

Pixel driven implementation of filtered backprojection for reconstruction of fan beam SPECT data using a position dependent effective projection bin length

Filtered backprojection is commonly implemented as a pixel driven algorithm in which the density is reconstructed on an array of grid points that are usually associated with the centres of square image pixels. In fan beam geometry, this conventional pixel driven approach using two-bin linear interpolation leads to an inefficient use of the projection data due to magnification at the projection line. For typical count limited SPECT data, this results in increased reconstructed image noise. We propose an alternative type of pixel driven algorithm that makes efficient use of projection data by averaging over all bins within a position dependent "effective' projection bin interval. The effective bin interval is equivalent to the image pixel length magnified on the projection line. This heuristic method leads to more complete use of the projection data and results in reconstructed images with superior noise properties compared with the conventional method while presenting similar spatial resolution characteristics.     

Strength of silicone breast implants

Rupture and leakage are recognized problems associated with silicone breast implants. Data are scarce about the durability of the silicone shell, and the life span of this device is unknown. The purpose of this study was to investigate the strength of silicone breast implants. Thirty implant shells were subjected to mechanical testing. Twenty-nine of the shells were tested after explanation, and one unused implant served as a control to validate the testing method. Implantation time varied from 4 months to 20 years, and all shells were tested, regardless of condition. Fourteen implant shells were intact, eight were leaking, and seven were ruptured. All ruptured implants had been in place for 10 years or longer. The breaking force of all excised shell specimens ranged from 2.6 to 22.4 N (0.6 to 5.0 lb.). Specimens from the control "high performance" shell required 15.5 to 25.6 N (3.5 to 5.8 lb) of force to fail. The weakest group was from thin-shelled implants between 10 and 16 years of age. More than half these specimens failed with less than 1 lb of force. The average breaking force of ruptured shell material was less than that of intact shells. A comparison of strength data in this study with manufacturers' data suggests that breaking force is dependent on implant type, shell thickness, and implantation time.     

Betacyanins from plants and cell cultures of Phytolacca americana

Betacyanins from cell cultures of Phytolacca americana were characterized and compared with those of the stems and ripening fruits of the plant. Whereas in fruits prebetanin (betanin 6'-O-sulphate) and its isoform predominate, in the stem and cell cultures feruloylated derivatives occur as the major components. These were rigorously identified by various spectroscopic techniques (DAD-HPLC, NMR, LC-MS and electrospray MS-MS) and carbohydrate analyses as betanidin 5-O-[(5"-O-E-feruloyl)-2'-O-beta-D-apiofuranosyl] -beta-D-glucopyranoside, a new betacyanin of higher plants, and betanidin 5-O-(6'-O-E-feruloyl)-beta-D-glucopyranoside (lampranthin II), together with their isoforms.