Body weight in patients with Parkinson's disease.

There is some evidence suggesting that Parkinson's disease (PD) patients exhibit lower body weight when compared to age-matched healthy subjects. Low body mass index (BMI) is correlated with low bone mineral density, both of which are major risk factors for hip fractures. Possible determinants of weight loss in PD patients include hyposmia, impaired hand-mouth coordination, difficulty chewing, dysphagia, intestinal hypomotility, depression, decreased reward processing of dopaminergic mesolimbic regions, nausea, and anorexia as the side effects of medication, and increased energy requirements due to muscular rigidity and involuntary movements. It is unclear whether PD patients in general, or only a subgroup of those affected, definitely show lower BMI in the advanced stages of the disease. We therefore recommend that the body weight of PD patients be monitored monthly as the disease progresses, and that a patient's nutrition should be supplemented with sufficient amounts of vitamin D and calcium to reduce the risk of hip fractures and strengthen bone density. Because meal times may coincide with unpredictable off periods associated with akinesia and impaired hand-mouth coordination, PD patients also need flexible food schedules that accommodate the associated symptoms of this disease.     

Optimizing the efficiency of high-field multivoxel spectroscopic imaging by multiplexing in space and time.

A new strategy to yield information from the maximum number of voxels, each at the optimum signal-to-noise ratio (SNR) per unit time, in MR spectroscopic imaging (MRSI) is introduced. In the past, maximum acquisition duty-cycle was obtained by multiplexing in time several single slices each repetition time (TR), while optimal SNR was achieved by encoding the entire volume of interest (VOI) each TR. We show that optimal SNR and acquisition efficiency can both be achieved simultaneously by multiplexing in space and time several slabs of several slices, each. Since coverage of common VOIs in 3D proton MRSI in the human brain typically requires eight or more slices, at 3 T or higher magnetic fields, two or more slabs can fit into the optimum TR (approximately 1.6 s). Since typically four or less slices would then fit into each slab, Hadamard encoding is favored in that direction for slice profile reasons. It is demonstrated that per fixed examination length, the new method gives, at 3 T, twice as many voxels, each of the same SNR and size, compared with current 3D chemical shift imaging techniques. It is shown that this gain will increase for more extensive spatial coverage or higher fields.     

A Decade of Change in Obesity Surgery

Background: The International (formerly National) Bariatric Surgery Registry began collecting data in January 1986. The aim of this study was to examine changes in the practice of surgical treatment of severe obesity that occurred during the decade of 1986 through 1995, as observed in the IBSR data. Methods: All data submitted to the IBSR during the decade were transferred to the IBM mainframe computer for analysis. Characteristics of operative type populations were compared over time using analysis of variance (ANOVA) for age, body mass index (BMI), operative weight and Chi-square (χ²) test for gender. Results: There has been a steady increase over the decade in mean patient weight. The operations used have changed from predominantly ‘simple’ operations to more frequent use of ‘complex’ operations. Within the categories of ‘simple’ and ‘complex’, an increase in the variety of operations occurred. As a group, patients with ‘simple’ operations have been heavier, more often male and public pay patients than those who have undergone ‘complex’ operations. One year weight loss was greater for Roux-en-Y gastric bypass (RGB) than vertical banded gastroplasty (VBG), but follow-up rates were too low to study the relative merits of the operations used. The reported incidence of operative mortality and serious complications (leak with peritonitis, abscess and pulmonary embolism) remained low. Conclusions: These observations and their implications can be summarized in three statements which relate to action for improved patient care in the beginning of the new century: (1) increasing weight of candidates for surgical treatment during this decade indicates the need for earlier use of operative treatment before irreversible complications of obesity can develop; (2) low risk of obesity surgery, decreasing postoperative hospital stay, and early weight control support the continued and increased use of surgical treatment; (3) continued widespread use of both ‘simple’ and ‘complex’ operations with increased modifications of standard RGB and VBG procedures emphasizes the need for standardized long-term data and analyses regarding both weight control and postoperative side-effects.     

Contribution of genetic factors for melanoma susceptibility in sporadic US melanoma patients

Abstract:  The risks of developing malignant melanoma (MM) include ultraviolet irradiation and genetic factors. To examine the contribution of rare and common variation within known MM genes in sporadic US MM patients, coding regions of known MM susceptibility genes [cyclin-dependent kinase inhibitor 2A ( CDKN2A ), cyclin-dependent kinase 4, melanocortin 1 receptor ( MC1R ) and tyrosinase ( TYR )] were resequenced in 109–135 MM cases. The significance of variants was examined by comparing their frequencies in 390 cancer-free controls. Potential deleterious mutations in CDKN2A were found in two patients and two others had variants of unknown significance. Cases were more likely than controls to harbour the MC1R 'R' variants known or predicted to alter its function ( P  = 0.002), particularly the R160W variant ( P  = 0.0035). The associated TYR R402Q variant (rs1126809*A) was found in 29% of cases, similar to what has been described previously. One MM patient with a family history of MM, who had developed other skin cancers, was homozygous for a novel TYR variant (P406L) of unknown significance. Hence, rare variants in TYR may be important risk factors for skin cancer.     

Synthesis and teratogenic action of n-hydroxythalidomide

N-Hydroxythalidomide (1d), a potential metabolite of thalidomide (1a), was synthesized from N-phthalyglutaminic acid anhydride (1b) and O-tetrahydropyraline hydroxylamine, followed by deprotection. The teratogenicity of 1d was studied using the Hen's-Egg-Test model which had been found applicable for 1a. 1d was more teratogenic to chicken embryos compared to 1a. The percentage of teratogenic malformations in the 1d groups was 28-46%, whereas the percentage in the 1a groups was 20-23%. The oxygen protected precursor N-hydroxythalidomide (1c) was less teratogenic (11-15%).     

1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) is a more potent dopaminergic neurotoxin than MPTP in mice

The administration to mice of 1-methyl-4-(2'-methylphenyl)-1,2,3, 6-tetrahydropyridine (2'-CH3-MPTP), a substituted analog of the dopaminergic neurotoxin MPTP caused even more dopaminergic toxicity than MPTP itself. Under conditions in which MPTP was relatively ineffective (i.e. two injections per day of 0.113 mmol/kg at an interval of 6 h for one or two days), 2'-CH3-MPTP caused a very large decrement in the neostriatal content of dopamine and its metabolites and a corresponding decrement in the capacity of a neostriatal synaptosomal preparation to take up [3H]dopamine. Moreover, 2'-CH3-MPTP administration (as few as four injections) caused a virtually complete loss of nerve cells in the zona compacta of the substantia nigra. This compound, like MPTP, may prove to be a valuable research tool.