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Biomedical subjects

R Smallwood

Publications and source records attributed to R Smallwood.

At least 19 recordsLinked to original sources

Duck hepatitis B virus replication in primary bile duct epithelial cells.

Primary cultures of intrahepatic bile duct epithelial (IBDE) cells isolated from duckling livers were successfully grown for studies of duck hepatitis B virus (DHBV). The primary IBDE cells were characterized by immunohistochemistry using CAM 5.2, a cytokeratin marker which was shown to react specifically to IBDE cells in duck liver tissue sections and in primary cultures of total duck liver cells. Immunofluorescence assay using anti-duck albumin, a marker for hepatocytes, revealed that these IBDE cultures did not appear to contain hepatocytes. A striking feature of these cultures was the duct-like structures present within each cell colony of multilayered IBDE cells. Normal duck serum in the growth medium was found to be essential for the development of these cells into duct-like structures. When the primary cultures of duck IBDE cells were acutely infected with DHBV, dual-labeled confocal microscopy using a combination of anti-DHBV core proteins and CAM 5.2 or a combination of anti-pre-S1 proteins and CAM 5.2 revealed that the IBDE cell colonies contained DHBV proteins. Immunoblot analysis of these cells showed that the DHBV pre-S1 and core proteins were similar to their counterparts in infected primary duck hepatocyte cultures. Southern blot analysis of infected IBDE preparations using a digoxigenin-labeled positive-sense DHBV riboprobe revealed the presence of hepadnavirus covalently closed circular (CCC) DNA, minus-sense single-stranded (SS) DNA, double-stranded linear DNA, and relaxed circular DNA. The presence of minus-sense SS DNA in the acutely infected IBDE cultures is indicative of DHBV reverse transcriptase activity, while the establishment of a pool of viral CCC DNA reveals the ability of these cells to maintain persistent infection. Taken collectively, the results from this study demonstrated that primary duck IBDE cells supported hepadnavirus replication as shown by the de novo synthesis of DHBV proteins and DNA replicative intermediates.

Animals↗

Effect of nucleoside analogue therapy on duck hepatitis B viral replication in hepatocytes and bile duct epithelial cells in vivo.

BACKGROUND: Recent studies have implicated bile duct epithelial cells (BDEC) as a reservoir of hepatitis B virus (HBV) infection that may be particularly important in the development of post-liver transplant recurrence of hepatitis B. The aim of this study was to compare the effects of antiviral therapy on duck HBV (DHBV) expression in hepatocytes and BDEC and to determine if this was affected by biliary hyperplasia. METHODS: Ducklings congenitally infected with DHBV received penciclovir (10 mg/kg per day) treatment from 9 days of age. In order to mimic the biliary hyperplasia that often accompanies severe post-liver transplant HBV recurrence, half the animals underwent bile duct ligation. Duck HBV-DNA in serum was measured at day 1, and serum and liver DHBV-DNA were determined when the animals were killed on day 17. Intrahepatic expression of viral preS1 antigen and DHBV-DNA was measured by immunohistochemistry and in situ hybridization, respectively. RESULTS: Viraemia became undetectable in the penciclovir-treated animals at day 17, following 8 days of therapy. Examination of liver tissue revealed that all hepatocytes and the majority of BDEC contained DHBV preS1 antigen and DHBV-DNA. Penciclovir greatly reduced the intrahepatic viral burden, but there was no antiviral effect on viral markers within BDEC. Despite the increased number of BDEC after bile duct ligation, the same proportion of BDEC was seen to be infected, and this was unaffected by antiviral therapy. CONCLUSIONS: In the duck model with and without biliary hyperplasia, penciclovir controls DHBV replication and reduces viral burden in hepatocytes, but not in BDEC. The BDEC appear to be an important reservoir of virus that is relatively unaffected by antiviral treatment, and may play an important role in disease persistence and relapse following cessation of therapy.

Acyclovir↗

Can we optimize electrode placement for impedance pneumography?

In this paper, we discuss issues involved in defining an optimum placement of four electrodes for impedance pneumography. We observed a general trend where the change in impedance (delta Z) decreased while the sensitivity (delta Z/Z) increased with distance between the drive and receive electrode pairs. However, the theoretical study indicated that delta Z/Z should decrease with distance. The scatter of points in the plots indicated that sensitivity was influenced by factors other than distance. The correlation coefficient between the theoretical and measured delta Z/Z was low, but significant. This suggested that the best electrode configuration can be derived from the theoretical data. High delta Z/Z was obtained when the drive and receive electrode pairs were placed close to the lungs and in different horizontal planes.

Adult↗

Virtual arthroscopy training: do the "virtual skills" developed match the real skills required?

The purpose of the study is to validate the training efficacy of the PC-based Sheffield Knee Arthroscopy Training System (SKATS, as described in MMVR6). Based on a task analysis of real arthroscopy, an evaluation module has been designed to test the core psycho-motor skills used in arthroscopy. The evaluation simulates a joint inspection and triangulation task, which is used to assess the research hypothesis that experienced arthroscopists will perform significantly better on the virtual arthroscopy simulator, than a trainee arthroscopist group and a control group. A group of experienced arthroscopic knee surgeons, a trainee surgeon group and a control group were tested on the simulator. The preliminary results indicate that experienced surgeons performed best with fewer instrument collisions and faster task-completion times. The results indicate that the core skills of arthroscopy used on the SKATS simulator are similar to those used in real arthroscopy. Further validation work is required to assess the training transfer effects. Once the simulator has been validated fully, it may prove beneficial in minimising patient risk.

Arthroscopy↗

Anorectal function in patients with complete spinal transection before and after sacral posterior rhizotomy.

BACKGROUND/AIMS: The implantation of spinal stimulators to facilitate defecation in patients with complete spinal transection involves division of the posterior sacral nerve roots. The aim of this study was to investigate the role of spinal reflexes in anorectal function. METHODS: Anorectal manometry and electromyography were performed in 14 patients with supraconal spinal cord transection (C6-T12) before and after complete sacral posterior rhizotomy and in 30 normal controls. RESULTS: Patients with spinal transection lost conscious control of the external anal sphincter. Reflex responses to intra-abdominal pressure and to rectal distention were eliminated after rhizotomy, indicating that they are spinal reflexes. Rhizotomy also eliminated giant rectal contractions induced by rectal distention in these patients. In contrast, the exaggerated sphincter relaxation induced by rectal distention was not influenced by rhizotomy. Discriminant rectal sensation was lost, but patients with thoracic cord lesions perceived a dull pelvic sensation during rectal distention even after rhizotomy. CONCLUSIONS: The exaggerated anorectal smooth muscle responses and absent conscious control of the anorectum may explain why patients with complete spinal transection experience uncontrollable reflex defecation, and the persistence of external anal sphincter contraction during straining may impair fecal expulsion. The elimination of these responses after posterior rhizotomy prevented reflex defecation while facilitating manual evacuation.

Adult↗

Risk factors for development of flucloxacillin associated jaundice.

OBJECTIVES: To identify risk factors predisposing to the development of flucloxacillin associated jaundice. DESIGN: Case-control study. Medical records of cases and controls were reviewed and information recorded on standard data collection forms. SETTING: Alfred Hospital recruiting subjects from Melbourne, Sydney, and Brisbane. SUBJECTS: Cases were defined as patients who had developed jaundice within eight weeks of stopping flucloxacillin, biochemical test results suggesting cholestasis, normal calibre bile ducts, and not been taking recognised hepatotoxic drugs. 51 of the 53 patients referred were included in the study. Four controls for each case were randomly selected from the patient register of the prescribing doctor. These were defined as patients who had been prescribed flucloxacillin without developing jaundice. MAIN OUTCOME MEASURES: Demographic characteristics, medical history, indication for flucloxacillin, dose, route and duration of treatment, other drugs, smoking, and previous drug allergies or use of flucloxacillin. RESULTS: Increasing age and a prolonged duration of flucloxacillin treatment were found to be risk factors for the development of jaundice. Patients aged over 55 years had an odds ratio of 18.61 (95% confidence interval 5.16-67.17) compared with patients under 30. The odds ratio for patients prescribed flucloxacillin for over 14 days was 7.13 (2.90 to 17.58) compared with patients treated for 14 days or less. Dose and route of administration were not related to the risk of jaundice. CONCLUSIONS: Older patients and those receiving flucloxacillin for longer than two weeks are at a substantially greater risk of jaundice. Careful consideration of the risk-benefit ratio is required when flucloxacillin is used in these settings.

Adult↗

Ribotyping of Helicobacter pylori from clinical specimens.

Ribotyping is a method used to type strains of bacteria by analyzing the restriction enzyme digestion patterns of the rRNA genes. This method was applied to 126 strains of Helicobacter pylori from 100 unrelated symptomatic patients who had endoscopies done and to 15 strains from 15 infected subjects from seven families. Analysis of the rRNA gene patterns revealed 77 distinct ribotypes from the 100 patients. From 15 of these subjects, isolates were recovered from antral mucosal biopsies at follow-up endoscopy. All follow-up isolates from the same patient, with one exception, yielded identical digest patterns. This patient had strains with two distinct digest patterns obtained from a set of three isolates cultured from biopsy specimens taken at different times. Five patients who had isolates recovered from different sites in the stomach (antrum, gastric body, duodenum, and pyloric channel) showed ribotyping patterns which were identical for each patient yet distinct between patients. In seven family groups studied, identical digest patterns were detected in members of two families, with variability in strains detected among members of the remaining families. This study demonstrates that ribotyping provides a useful, reliable, reproducible, and highly discriminatory typing scheme for the study of H. pylori infection.

Bacterial Typing Techniques↗

Anorectal function in patients with complete supraconal spinal cord lesions.

Anorectal manometry and sphincter electromyography were performed in 23 patients with complete supraconal traumatic spinal injuries and 30 age and sex matched control subjects. Basal pressures in the spinal group were similar to those in normal subjects but conscious control of sphincter activity was abolished in all spinal patients. Discriminant rectal sensation was also abolished during rectal distension, but 40% of patients experienced a dull pelvic ache at maximum levels of distension. Phasic rectal contraction and anal relaxation were present but exaggerated and induced at lower distending volumes than in normal subjects. The configuration of the rectal pressure/volume relationship was linear in patients compared with a reversed 'S' shape in normal subjects. The external anal sphincter response to rectal distension was noticeably attenuated, reinforcing the view that this spinal reflex is heavily modulated by supraspinal centres under normal circumstances. The external anal sphincter response to increases in abdominal pressure was also attenuated, and the anal pressures were strongly correlated with the level of the lesion and the abdominal pressure the patient could generate. No spinal patient showed a decrease in external anal sphincter activity during straining 'as if to defecate.' The exaggerated anorectal smooth muscle responses to rectal distension and the attenuated external sphincter response explain why patients with complete supraconal spinal lesions experience uncontrollable reflex defecation, while the persistance of external and sphincter contraction and the absence of any external anal sphincter relaxation during straining 'as if to defecate' might explain the difficulty that these patients have in consciously expelling rectal contents.

Adolescent↗

Comparative evaluation of three selective media and a nonselective medium for the culture of Helicobacter pylori from gastric biopsies.

Plating on solid media is the standard technique used in most laboratories for the isolation of Helicobacter pylori from gastric biopsies. Recently, various selective media were developed for this purpose. We compared and evaluated three selective media, Skirrow's, Dent's CP, and modified Glupczynski's Brussels campylobacter charcoal media, and chocolate agar medium for the isolation of H. pylori. Gastric biopsies taken from a total of 203 patients were plated in parallel on all four media. An isolation rate of 51% (104 of 203) was obtained with a combination of all four media. Of the 104, 92 (88%) were positive with Dent's medium and with modified Glupczynski's medium. Skirrow's medium gave the highest isolation rate, 96% (100 of 104). However, growth of H. pylori was scant (only one to five colonies) when growth occurred on Skirrow's medium alone. Overall, modified Glupczynski's medium provided significantly heavier growth. Chocolate agar medium yielded a 76% (79 of 104) positivity rate. We recommend the use of a combination of two selective media for the maximum recovery of H. pylori from antral biopsies.

Bacteriological Techniques↗

Control of defecation in patients with spinal injuries by stimulation of sacral anterior nerve roots.

OBJECTIVE: To observe the effects of stimulation of the sacral anterior roots on anorectal and low colonic pressures and to programme implanted stimulators to produce defecation. DESIGN: Prospective study of 12 consecutive patients. SETTING: Spinal injuries unit and university gastrointestinal physiology department. PATIENTS: 12 Patients with complete supraconal spinal cord lesions. Their injuries had been sustained at least two years before the study. INTERVENTIONS: A Brindley-Finetech intradural sacral anterior root stimulator was implanted in all patients. Three months postoperatively the stimulator settings were adjusted after measurement of simultaneous anorectal and low colonic pressures. MAIN OUTCOME MEASURES: Full defecation. RESULTS: Six patients achieved complete rectal evacuation of faeces using the implant and subsequently did not require manual help for defecation. For all but one of the patients the total time taken to complete defecation was reduced, and all were free from constipation, the most prevalent gastrointestinal symptom in patients with spinal injuries. CONCLUSIONS: Sacral anterior root stimulators can be programmed to achieve complete unassisted defecation and can considerably improve the quality of life of patients with spinal injuries.

Adult↗

Liver transplantation for acute hepatic failure?

In the absence of definitive medical treatment for severe fulminant hepatic failure, liver transplantation may be appropriate in selected patients. However, uniform and easily applicable criteria for diagnosis of severity and analysis of results are needed to prevent unnecessary transplantation and to ensure that patients who may benefit are appropriately treated. Previous regimens for treatment of fulminant hepatic failure were often advocated, on the basis of data from historical controls, for several years until controlled trials failed to show any benefit. To obtain reliable information more rapidly than achieved before, a controlled trial between specialist liver transplant units is needed to establish the role of emergency hepatic transplantation in patients with fulminant hepatic failure.

Acute Disease↗