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Biomedical subjects

D Bush

Publications and source records attributed to D Bush.

At least 37 records · Page 2Linked to original sources

An investigation of lower oesophageal redox potentials in gastro-oesophageal reflux patients and healthy volunteers.

Oesophageal electrical properties are thought to be important in the development of gastro-esophageal reflux. This study simultaneously monitored the intraoesophageal pH and redox potentials in 18 patients with gastro-oesophageal reflux symptoms and 15 asymptomatic controls, for a 24 h period. The pH and redox electrodes were positioned 5 cm proximal to the lower oesophageal sphincter, the position of which had been determined by manometry. Since significantly different behaviour was observed during the day and night, the data were divided into periods of waking and sleeping. Data were analysed for acid reflux (pH < 4) and transients in the redox potential-time curve. Both patients and normal subjects showed negative redox transients which were more frequent and pronounced at night than during the day, and which were uncorrelated with acid reflux. The only parameter which was significantly different between normal and refluxing groups was the amount of nocturnal redox activity, which was lower in refluxing subjects than in normals. Some possible hypotheses for these observations, and the origin of the redox species, are discussed.

Adult↗

Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics.

The complete 1,751,377-bp sequence of the genome of the thermophilic archaeon Methanobacterium thermoautotrophicum deltaH has been determined by a whole-genome shotgun sequencing approach. A total of 1,855 open reading frames (ORFs) have been identified that appear to encode polypeptides, 844 (46%) of which have been assigned putative functions based on their similarities to database sequences with assigned functions. A total of 514 (28%) of the ORF-encoded polypeptides are related to sequences with unknown functions, and 496 (27%) have little or no homology to sequences in public databases. Comparisons with Eucarya-, Bacteria-, and Archaea-specific databases reveal that 1,013 of the putative gene products (54%) are most similar to polypeptide sequences described previously for other organisms in the domain Archaea. Comparisons with the Methanococcus jannaschii genome data underline the extensive divergence that has occurred between these two methanogens; only 352 (19%) of M. thermoautotrophicum ORFs encode sequences that are >50% identical to M. jannaschii polypeptides, and there is little conservation in the relative locations of orthologous genes. When the M. thermoautotrophicum ORFs are compared to sequences from only the eucaryal and bacterial domains, 786 (42%) are more similar to bacterial sequences and 241 (13%) are more similar to eucaryal sequences. The bacterial domain-like gene products include the majority of those predicted to be involved in cofactor and small molecule biosyntheses, intermediary metabolism, transport, nitrogen fixation, regulatory functions, and interactions with the environment. Most proteins predicted to be involved in DNA metabolism, transcription, and translation are more similar to eucaryal sequences. Gene structure and organization have features that are typical of the Bacteria, including genes that encode polypeptides closely related to eucaryal proteins. There are 24 polypeptides that could form two-component sensor kinase-response regulator systems and homologs of the bacterial Hsp70-response proteins DnaK and DnaJ, which are notably absent in M. jannaschii. DNA replication initiation and chromosome packaging in M. thermoautotrophicum are predicted to have eucaryal features, based on the presence of two Cdc6 homologs and three histones; however, the presence of an ftsZ gene indicates a bacterial type of cell division initiation. The DNA polymerases include an X-family repair type and an unusual archaeal B type formed by two separate polypeptides. The DNA-dependent RNA polymerase (RNAP) subunits A', A", B', B" and H are encoded in a typical archaeal RNAP operon, although a second A' subunit-encoding gene is present at a remote location. There are two rRNA operons, and 39 tRNA genes are dispersed around the genome, although most of these occur in clusters. Three of the tRNA genes have introns, including the tRNAPro (GGG) gene, which contains a second intron at an unprecedented location. There is no selenocysteinyl-tRNA gene nor evidence for classically organized IS elements, prophages, or plasmids. The genome contains one intein and two extended repeats (3.6 and 8.6 kb) that are members of a family with 18 representatives in the M. jannaschii genome.

Anaerobiosis↗

Polyprenylphosphate-pentoses in mycobacteria are synthesized from 5-phosphoribose pyrophosphate.

Polyprenylphosphate-arabinose (in which the polyprenyl unit is found both as decaprenyl and octahydroheptaprenyl) is a donor of mycobacterial cell wall arabinosyl residues. Because of this important role, its biosynthetic pathway, and that of the related lipid, polyprenylphosphate-D-ribose, was investigated. Surprisingly, phosphoribose pyrophosphate was shown to be a key intermediate on the pathway to both polyprenylphosphate-D-pentoses. Thus, incubation of 5-phospho-D-[14C]ribose pyrophosphate with membranes prepared from Mycobacterium smegmatis resulted in the presence of organic-soluble radioactivity that was shown to be, in part, polyprenylphosphate-[14C]arabinose and polyprenylphosphate-[14C]ribose. Two additional intermediates, polyprenylphosphate-5-phospho[14C]ribose and polyprenylphosphate-5-phospho[14C]arabinose, were identified. Further experiments showed that the mature polyprenylphosphate-ribose is formed from phosphoribose pyrophosphate via a two-step pathway involving a transferase to form polyprenylphosphate-5-phosphoribose and then a phosphatase to form the final polyprenylphosphateribose. Polyprenylphosphate-arabinose is formed by a similar pathway with an additional step being the epimerization at C-2 of the ribosyl residue. This epimerization occurs at either the level of phosphoribose pyrophosphate or at the level of polyprenylphosphate-5-phosphoribose.

Carbon Radioisotopes↗

Knowledge of junior doctors regarding the New Deal.

Junior doctors' knowledge of the content and local implementation of the New Deal for junior doctors was surveyed in one English region. Data were analysed from 254 replies (response rate 60%); a majority (86%) knew that the initiative was intended to reduce their working hours, but detailed knowledge was lacking. Less than half could identify the correct limits on contracted hours for full or partial shift working patterns, while 73% knew that they should not be contracted for more than 72 hours per week for an on-call pattern, the most common and traditional pattern worked. Only 20% knew that hours actually worked should not exceed 56 per week. Only 13 of 114 doctors who believed their posts conformed to the New Deal knew the correct hours limits. Only 11% knew any member of the hospital local implementation group for the New Deal. The results of the survey indicate that junior doctors are not well informed about the details of the New Deal, or its local implementation-four years into the New Deal, this situation needs to be improved, especially as junior doctors are now to be asked to validate the progress of the initiative.

Attitude of Health Personnel↗

The effect of TCPL devices on tissue-implant interface analysis using adult sheep as a model.

Inflammatory response and the subsequent fibrous capsule formation are often used as a screening method to determine biocompatibility of an implanted material. In this study, porous implants of tricalcium phosphate-lysine (TCPL) delivery devices were implanted subcutaneously in adult rams. The fibrous capsule surrounding the implant was studied histochemically to determine the resorbability rate of the device. Fibrous capsular tissues were carefully dissected away from the capsule noting the tissue closest to the implanted material. Evaluation of the sections (5um, H&E) collected from various areas of the implants (n = 127) revealed that: vascularity, macrophages, multinucleated giant cells and plasma cells at the TCPL implant-interface were evident after the first month. Persistence of these cell types and progressive angiogenesis in subsequent months was apparent in all tissues collected from experimental animals. The formation of distinct cell layers was remarkable at the six and twelve month phases. After the first month, macrophages were the predominant cell type at the interface and as the tissue progressed away from the implant the presence of fibroblast and plasma cells were observed. The layer of tissue furthest from the implant mostly consisted of structured collagen fibers with minimal number of microvasculature. The presence of inflammatory cells at the interface sites in all phases was further evidenced by immunohistochemical analysis (IL-1 and IL-6). The inflammatory cells seen at the interface along with the formation of a structured fibrous tissue resembles a normal repair process and supports our previous observations regarding the biocompatibility and biodegradability of TCPL delivery device.

Animals↗

An open multicenter trial of Sinemet CR in levodopa-naive Parkinson's disease patients.

It has been proposed that initiation of anti-Parkinson therapy with continuous release formulations of Sinemet might prevent or delay the development of adverse effects associated with chronic levodopa therapy employed in standard formulations. In anticipation of a prospective study comparing Sinemet to Sinemet CR in previously untreated Parkinson's disease patients, we evaluated Sinemet CR as primary therapy in 45 levodopa-naive Parkinson's disease patients in a 12 week, open-label, multi-center study. At the conclusion of the study, optimal results were obtained with levodopa administered as Sinemet CR in a total daily dose of 497 mg divided into 2.4 doses per day. Statistically significant improvement compared to baseline was observed for total Parkinson's score as well as each of rigidity, tremor, bradykinesia, gait and postural stability. Statistically significant improvement was also noted in total disability as well as in each of its components. Adverse experiences were mild and transient and no significant laboratory abnormalities were encountered. We conclude that a daily dose of 1 to 1.5 tablets b.i.d. of Sinemet CR as primary therapy for patients with Parkinson's disease is well tolerated and provides effective therapy.

Aged↗

Pulsatile flow index for qualitative measurements of blood flow with duplex ultrasound. An experimental study.

We determined the accuracy of Doppler blood flow measurements in an experimental investigation using a tissue-simulating phantom, pulsatile flow pumps and heparinized blood. A new index for qualitative assessment of blood flow, the pulsed flow index (PFI) is described. The PFI takes advantage of the area under the flow velocity curve between the true zero line and the diastolic baseline. Under conditions of continuous flow, the PFI ranged from 0.82 to 0.94 (mean value 0.90). The PFI was found to be relatively independent of the transducer/vessel angle (+/- 8%) and the inter/intra-operator variation was small (+/- 7.5%, or +/- 7%, respectively).

Blood Flow Velocity↗

Transient atrial dysfunction after conversion of chronic atrial fibrillation to sinus rhythm.

Although conversion of atrial fibrillation (AF) to sinus rhythm can usually be accomplished by electrical or drug therapy, effective atrial systole may not be restored. To investigate the return of atrial transport function and its relation to the duration of the arrhythmia, Doppler echocardiography was performed after conversion in 18 patients with acute AF (less than or equal to 1 week duration), 14 patients with chronic AF (greater than 1 week duration) and 15 control patients. Flow velocities during rapid filling (E wave) and atrial systole (A wave) were measured in both left and right ventricles. Patients in the acute AF group had left ventricular A waves (49 +/- 4 cm/s) and A/E ratios (0.97 +/- 0.1) similar to those of the control patients (55 +/- 7 cm/s, 0.87 +/- 0.08, respectively). In contrast, patients in the chronic AF group had much smaller A waves (19 +/- 5 cm/s) and A/E ratios (0.30 +/- 0.08) than those in the other 2 groups (p less than 0.001). Five patients with chronic AF (36%) had complete left atrial paralysis (A/E = 0) despite normal sinus P waves. Measurements in the right ventricle showed similar differences among the groups. Patients with chronic AF who maintained sinus rhythm showed an increase in A/E ratio to control levels, from 0.45 +/- 0.1 to 0.93 +/- 0.1 (p = 0.003) at 48 days (average) after conversion. Thus, atrial transport function is normal after brief periods of AF, but reduced or absent when conversion is achieved after the arrhythmia has been sustained greater than 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Sonographic evaluation of the kidney following extracorporeal shock wave lithotripsy.

We investigated the value of real-time sonography for determination of pelvicaliceal dilatation 24-48 h after extracorporeal shock wave lithotripsy (ESWL) in 369 patients (419 treated kidneys). A varying degree of hydronephrosis was present in 121/419 (29%) kidneys. Fragmented stones post-ESWL were demonstrable in 346/419 kidneys (82%), but were missed by ultrasound in three kidneys (less than 1%). In four kidneys (1%), stone fragments which were shown to be present by ultrasound were not detectable on radiographs. In 25/419 kidneys (6%), evidence of renal trauma caused by ESWL was demonstrated by ultrasound. The most important incidental finding was a small renal cell carcinoma of the contralateral (untreated) kidney.

Diagnosis, Differential↗

Immunity to Eimeria separata (Apicomplexa: Eimeriina): expose-and-challenge studies in rats.

Oocyst production of Eimeria separata of the rat was determined in initial and challenge infections. The total number of oocysts produced was no higher at 100 oocysts than at 1,000, 10,000, or 100,000 in initial infections. In 2 experiments, the reproductive index with 100 oocysts was 17,000 and 34,000, respectively. On challenge with 10,000 oocysts, there was 91% protection at 100 oocysts. There was slightly lower protection at 10,000 and 100,000 oocysts, 72% and 81%, respectively, and t-values suggest lower protection at these higher inocula.

Animals↗