Pyridoxal-5′-phosphate and pyridoxal biokinetics in aging Wistar rats

Biokinetic parameters of plasma pyridoxal-5′-phosphate (PLP) and pyridoxal (PL) disposition were studied in male Wistar rats aged 8 and 27 months kept from weaning on a purified diet containing 250 g casein and 6 mg pyridoxine·HCl per kg. Baseline plasma PLP concentration was lower in the older animals (514 ± 56 nmol/L for young and 317 ± 124 nmol/L for old animals), whereas baseline plasma PL concentration did not differ between age group (average 235 nmol/L for both young and old animals). We hypothesized lower baseline plasma PLP in the older animals was caused by an increased PLP elimination rate, a decreased PLP synthesis rate, or a combination of these processes. Observations from earlier in vitro experiments suggest age-related changes occur in vitamin B-6 metabolizing enzyme activities. In the in vivo experiments described here no age-related difference in plasma PLP elimination rate nor in plasma PLP synthesis rate was observed to explain the observed decrease in plasma PLP concentration with age.     

The inside-out Bankart procedure

Bankart capsulorraphy for recurrent shoulder instability produces predictable results. Time-consuming, technically demanding details of the procedure, however, discourage its use. A simplified technique and new instrumentation solving these limitations was used in 69 procedures, all performed by the same surgeon. Seventy-eight percent of these procedures were reviewed independently at a minimum of 2 years followup: 77% were asymptomatic, 12% had minimal symptoms, and 11% had residual problems. Instability recurred in six patients and was associated with a significant traumatic event in five. Thus, the inside-out Bankart modifications were effective.     

Patient education and the physician-patient relationship

Noncompliance is a major problem that patient education aims at resolving. The emphasis in patient education upon didactic strategies, educational content, and materials distracts from perhaps the most important factor in the success of patient education, that is, the quality of the physician-patient relationship. In the context of the physician-patient relationship many of the patient's psychological needs, wishes, and fears will be revealed, and these factors have bearing upon compliance and the ability to make use of patient education. When the physician develops a psychotherapeutic attitude characterized by empathic attunement to the patient and his or her underlying psychological reasons for resistance to medical advice, the likelihood of accepting patient education increases.     

Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

Background  

Estimates suggest that up to 30% of colorectal cancers (CRC) may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV) (Roche NimbleGen, 385 000 oligo CGH array) in microsatellite stable (MSS) tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53) and 17 elderly patients with median age 79 years (range: 69-87). Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list.     

Antimicrobial Susceptibility and Resistance Patterns among Helicobacter pylori Strains from The Gambia,West Africa

Helicobacter pylori is a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four Gambian H. pylori strains were tested for antibiotic susceptibility. The role of rdxA in metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 μg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P = 0.0031). Representative Mtz-resistant (Mtz^r) strains were rendered Mtz susceptible (Mtz^s) by transformation with a functional rdxA gene; conversely, Mtz^s strains were rendered Mtz^r by rdxA inactivation. Many mutations were found by Gambian H. pylori rdxA sequencing; mutations that probably inactivated rdxA in Mtz^r strains were identified and explained using RdxA protein''s structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety of rdxA mutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen.     

MR‐based measurements and simulations of the magnetic field created by a realistic transcranial magnetic stimulation (TMS) coil and stimulator

Transcranial magnetic stimulation (TMS) is an emerging technique that allows non‐invasive neurostimulation. However, the correct validation of electromagnetic models of typical TMS coils and the correct assessment of the incident TMS field (B_TMS) produced by standard TMS stimulators are still lacking. Such a validation can be performed by mapping B_TMS produced by a realistic TMS setup. In this study, we show that MRI can provide precise quantification of the magnetic field produced by a realistic TMS coil and a clinically used TMS stimulator in the region in which neurostimulation occurs. Measurements of the phase accumulation created by TMS pulses applied during a tailored MR sequence were performed in a phantom. Dedicated hardware was developed to synchronize a typical, clinically used, TMS setup with a 3‐T MR scanner. For comparison purposes, electromagnetic simulations of B_TMS were performed. MR‐based measurements allow the mapping and quantification of B_TMS starting 2.5 cm from the TMS coil. For closer regions, the intra‐voxel dephasing induced by B_TMS prohibits TMS field measurements. For 1% TMS output, the maximum measured value was ~0.1 mT. Simulations reflect quantitatively the experimental data. These measurements can be used to validate electromagnetic models of TMS coils, to guide TMS coil positioning, and for dosimetry and quality assessment of concurrent TMS‐MRI studies without the need for crude methods, such as motor threshold, for stimulation dose determination.