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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 19 recordsLinked to original sources

Mechanically loaded ex vivo bone culture system 'Zetos': systems and culture preparation.

This paper introduces the culture preparation of ovine, bovine and human cancellous bone cores to be used in an explants model Zetos. The three dimensional (3D) bone cores were prepared and evaluated for all three animals. Bone cells in vivo constantly interact with each other, migratory cells, surrounding extracellular matrix (ECM) and interstitial fluid in a microenvironment, which continuously responds to various endogenous and exogenous stimuli. The Zetos system was designed to culture and mechanically load viable cancellous bone explants in their near natural microenvironment. This 3D ex vivo system bridges the current gap between in vitro and in vivo methods. One aim of this work was to compare the macro and micro-architecture of ovine, bovine and human cancellous bone tissue in preparation for culture within the Zetos system in order to determine the optimal source of experimental material. A second aim was to optimise the preparations of the bone cores as well as develop techniques involved during tissue maintenance. Bone core response was visualised using histological and immunohistochemical methods. The results demonstrate that cancellous bone explants vary greatly in trabecular density and bone volume depending on species, age and location. Sheep and human samples displayed the greatest variation between bones cores when compared to bovine. Even cores taken from the same animal possessed very different characteristics. The histology demonstrated normal bone and cell structure after the core preparation. Immunohistochemistry results demonstrated antigen retention after preparation methods.

Aged↗

Orbital based electronic structural signatures of the guanine keto G-7H/G-9H tautomer pair as studied using dual space analysis.

Electronic structural signatures of the guanine-7H and guanine-9H tautomers have been investigated on an orbital by orbital basis using dual space analysis. A combination of density functional theory (B3LYP/TZVP), the statistical average of model orbital potentials (SAOP/TZ2P) method and outer valence Green's function theory (OVGF/TZVP) has been used to generate optimal tautomer geometries and accurate ionization energy spectra for the guanine tautomer pair. The present work found that the non-planar form for both of the guanine keto pair possesses lower energies than their corresponding planar counterparts, and that the canonical form of the guanine-7H tautomer has slightly lower total energy than guanine-9H. This latter result is in agreement with previous experimental and theoretical findings. In the planar guanine pair the geometric parameters and anisotropic molecular properties are compared, focusing on changes caused by the mobile proton transfer. It is demonstrated that the mobile proton only causes limited disturbance to isotropic properties, such as geometry and the energetics, of the guanine keto tautomer pair. The exception to this general statement is for related local changes such as the N((7))-C((8)) and C((8))-N((9)) bond length resonance between the single and double bonds, reflecting the nitrogen atom being bonded with the mobile proton in the tautomers. The mobile proton distorts the electron distribution of the tautomers, which leads to significant changes in the molecular anisotropic properties. The dipole moment of guanine-7H is altered by about a factor of three, from 2.23 to 7.05 D (guanine-9H), and the molecular electrostatic potentials also reflect significant electron charge distortion. The outer valence orbital momentum distributions, which were obtained using the plane wave impulse approximation (PWIA), have demonstrated quantitatively that the outer valence orbitals of the tautomer pair can be divided into three groups. That is orbitals 1a''-7a'' and 18a', which do not have visible alternations in the tautomeric process (which consist of either pi orbitals or are close to the inner valence shell); a second group comprising orbitals 19a'-22a', 25a', 26a', 28a', 29a' and 31a', which show small perturbations as a result of the mobile hydrogen locations; and group three, orbitals 23a', 24a', 27a', 30a' and 32a', which demonstrate significant changes due to the mobile proton transfer and are therefore considered as signature orbitals of the G-7H/G-9H keto tautomeric process.

Guanine↗

Twenty-year audit of percutaneous liver biopsy in a major Australian teaching hospital.

BACKGROUND: To examine the changes in indications, patient characteristics, safety and outcomes in consecutive patients undergoing percutaneous core liver biopsies in a major Australian teaching hospital over a period of two decades. METHODS: A retrospective audit was carried out on all percutaneous core liver biopsies from a single institution between 1996 and 2005. This was combined with 10 years of data already reported on for the years 1986-1995 to detect trends in indications and outcomes. RESULTS: Medical records from 1398 patients were included for analysis. Over a 20-year period, the most common indications for liver biopsy were hepatitis C (37.8%), hepatitis B (26.4%) and abnormal liver function tests (22.2%). Twelve major complications (1.0%) were seen; 10 episodes of haemorrhage, 1 bile leak and 1 visceral perforation. Seven of these patients had an abnormal baseline coagulation profile; a significant risk for major haemorrhage (P < 0.001), resulting in three deaths. All deaths occurred in inpatients with major comorbidities. Minor complications occurred in 13.6% of patients, with multiple passes a significant risk factor. Whereas the overall major and minor complication rates were independent of operator experience inadequate specimens were more frequently obtained by the registrar. CONCLUSION: This large series extending over two decades shows that despite advances in biopsy techniques, the rates of both minor and major complications remain significant. Of particular concern are the procedure-related deaths. Identifying factors that may increase risk requires further scrutiny and careful patient selection needs to be undertaken.

Adolescent↗

Prevalence and spectrum of bacterial co-infection during fungal keratitis.

AIMS: To estimate the propensity of keratomycosis for parallel or secondary bacterial infection and to explore affinities among fungal and bacterial co-isolates. METHODS: A retrospective review of laboratory records over 24 years yielded 152 episodes of culture positive fungal keratitis. After collating 65 corneal specimens having bacterial co-isolates, polymicrobial co-infection was defined as detection of concordant bacteria on smear and culture or on two or more different media. RESULTS: 30 (20%) keratomycoses met laboratory criteria for polymicrobial infection. The risk of bacterial co-infection was 3.2 (95% confidence interval, 1.7 to 5.8) times greater with yeast keratitis than with filamentous fungal keratitis. CONCLUSIONS: Bacterial co-infection occasionally complicates fungal keratitis, particularly candidiasis.

Adult↗

The C-caffeine breath test distinguishes significant fibrosis in chronic hepatitis B and reflects response to lamivudine therapy.

BACKGROUND: The 13C-caffeine breath test is a non-invasive, quantitative test of liver function. AIM: To determine the utility of the 13C-caffeine breath test in chronic hepatitis B virus and its ability to monitor response to lamivudine. METHODS: Forty-eight chronic hepatitis B virus patients and 24 controls underwent the 13C-caffeine breath test. In 28 patients commenced on lamivudine, 13C-caffeine breath tests were performed at 1 week (n = 12) and after 1 year of therapy. RESULTS: Patients with Metavir F0-1 fibrosis (2.30 +/- 1.02 Delta per thousand per 100 mg caffeine) had a 13C-caffeine breath test similar to controls (2.31 +/- 0.85, P = 0.96). However, patients with F2-3 fibrosis (1.59 +/- 0.78, P = 0.047) and cirrhotic patients (0.99 +/- 0.33, P = 0.001) had a decreased 13C-caffeine breath test. Fibrosis correlated best with the 13C-caffeine breath test (r(s) = -0.62, P < 0.001). The 13C-caffeine breath test independently predicted significant (F > or = 2) and advanced (F > or = 3) fibrosis and yielded the greatest area under the receiver operating characteristic curve (0.91 +/- 0.04) for predicting advanced fibrosis. The 13C-caffeine breath test was unaltered by 1 week of lamivudine but improved by 61% (P < 0.001) in responders to long-term lamivudine, whereas in those with viraemia and elevated alanine aminotransferase, values remained stable or deteriorated. CONCLUSION: The 13C-caffeine breath test distinguishes chronic hepatitis B virus-related fibrosis and detects improvement in liver function in response to long-term lamivudine.

Adult↗

Mechanosensitivity of human osteosarcoma cells and phospholipase C beta2 expression.

Bone adapts to mechanical load by osteosynthesis, suggesting that osteoblasts might respond to mechanical stimuli. We therefore investigated cell proliferation and phospholipase C (PLC) expression in osteoblasts. One Hertz uniaxial stretching at 4000 microstrains significantly increased the proliferation rates of human osteoblast-like osteosarcoma cell line MG-63 and primary human osteoblasts. However, U-2/OS, SaOS-2, OST, and MNNG/HOS cells showed no significant changes in proliferation rate. We investigated the expression pattern of different isoforms of PLC in these cell lines. We were able to detect PLC beta1, beta3, gamma1, gamma2, and delta1 in all cells, but PLC beta2 was only detectable in the mechanosensitive cells. We therefore investigated the possible role of PLC beta2 in mechanotransduction. Inducible antisense expression for 24h inhibited the translation of PLC beta1 in U-2/OS cells by 35% and PLC beta2 in MG-63 by 29%. Fluid shear flow experiments with MG-63 lacking PLC beta2 revealed a significantly higher level of cells losing attachment to coverslips and a significantly lower number of cells increasing intracellular free calcium.

Cell Adhesion↗

Basic reactions of osteoblasts on structured material surfaces.

In order to assess how bone substitute materials determine bone formation in vivo it is useful to understand the mechanisms of the material surface/tissue interaction on a cellular level. Artificial materials are used in two applications, as biomaterials alone or as a scaffold for osteoblasts in a tissue engineering approach. Recently, many efforts have been undertaken to improve bone regeneration by the use of structured material surfaces. In vitro studies of bone cell responses to artificial materials are the basic tool to determine these interactions. Surface properties of materials surfaces as well as biophysical constraints at the biomaterial surface are of major importance since these features will direct the cell responses. Studies on osteoblastlike cell reactivity towards materials will have to focus on the different steps of protein and cell reactions towards defined surface properties. The introduction of new techniques allows nowadays the fabrication of materials with ordered surface structures. This paper gives a review of present knowledge on the various stages of osteoblast reactions on material surfaces, focused on basic cell events under in vitro conditions. Special emphasis is given to cellular reactions towards ordered nano-sized topographies.

Biocompatible Materials↗

Simulated laparoscopy using a head-mounted display vs traditional video monitor: an assessment of performance and muscle fatigue.

BACKGROUND: The direction of visual gaze may be an important ergonomic factor that affects operative performance. We designed a study to determine whether a head-mounted display (HMD) worn by the surgeon would improve task performance and/or reduce muscle fatigue during a laparoscopic task when compared to the use of a traditional video monitor display (VMD). METHODS: Surgical residents (n = 30) were enrolled in the study. A junior group, consisting of 15 postgraduate year (PGY) = 1 subjects with no previous laparoscopic experience, and a senior group, consisting of 15 PGY 4 and PGY 5 subjects with experience, completed a laparoscopic task that was repeated four times using the Computer Enhanced Laparoscopic Training System (CELTS). Groups alternated between using the HMD with the task placed in a downward frontal position and the VMD with the task at a 30 degrees lateral angle. The CELTS module assessed task completion time, depth perception, path length of instruments, response orientation, motion smoothness; the system then generated an overall score. Electromyography (EMG) was used to record sternocleidomastoid muscle activity. Display preference was surveyed. RESULTS: The senior residents performed better than the junior residents overall on all parameters (p < 0.05) except for motion smoothness, where there was no difference. In both groups, the HMD significantly improved motion smoothness when compared to the VMD (p < 0.05). All other parameters were equal. There was less muscle fatigue when using the VMD (p < 0.05). We found that 66% of the junior residents but only 20% of the senior residents preferred the HMD. CONCLUSIONS: The CELTS module demonstrated evidence of construct validity by differentiating the performances of junior and senior residents. By aligning the surgeon's visual gaze with the instruments, HMD improved smoothness of motion. Experienced residents preferred the traditional monitor display. Although the VMD produced less muscle fatigue, inexperienced residents preferred the HMD, possibly because of improved smoothness of motion.

Computer Simulation↗

Optimal management of the morbidly obese patient. SAGES appropriateness conference statement.

BACKGROUND: Obesity is a growing health problem that contributes to numerous life-threatening or disabling disorders, including coronary artery disease, hypertension, type 2 diabetes mellitus, hyperlipidemia, degenerative joint disease, and obstructive sleep apnea. Significant weight reduction in the morbidly obese improves or reverses associated illness and benefits well-being. The purpose of the SAGES Appropriateness Conference was to summarize the state of the art for open and laparoscopic operations for the morbidly obese. METHODS: The English literature comparing bariatric procedures was reviewed and grouped by level of evidence by three surgeons (BS, LV, and CC). From more than 1,500 articles, all conference participants were provided with reprints and table summaries of no less than 50 selected manuscripts. Ten experts were requested to present reviews and make evidence-based arguments for and against the open and laparoscopic approaches in written format. An expert panel of six surgeons, including an ethicist and patient, commented on implications of data presented. The finalized statement was e-mailed to all participants for approval and comment. RESULTS: Consensus statements were achieved on various aspects of morbid obesity, including indications for surgery, resolution of comorbid illnesses with significant weight loss, and the importance of committed bariatric program. Our panel of experts agreed, in general, to the advantages of laparoscopic approaches compared to open operations in skilled hands. CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass (RYGB) affords improved short-term recovery compared to open gastric bypass. Laparoscopic adjustable banding can be performed with lower average mortality than either RYGB or any of the malabsorptive operations, and it produces variable degrees of short-term weight loss. Prospective randomized trials are needed to compare gastric bypass, malabsorptive, and restrictive procedures.

Aftercare↗

Laparoscopy alone is superior to peritoneal cytology in staging gastric and esophageal carcinoma.

BACKGROUND: Laparoscopy identifies metastatic disease in patients with upper gastrointestinal malignancies; however, it has been suggested that cytological examination of peritoneal washings may increase the diagnostic yield. We hypothesize that the addition of cytologic washings to a standardized staging laparoscopy is unnecessary for the identification of intraabdominal metastasis in patients with gastric/esophageal cancer. METHODS: Forty patients with gastric/esophageal cancer were prospectively evaluated. Patients successfully underwent a diagnostic laparoscopy protocol (with biopsies) during which peritoneal washings were obtained and processed for cytologic analysis. Laparoscopic versus cytologic identification of intraabdominal metastasis were compared. RESULTS: Forty patients successfully completed laparoscopy with collection of peritoneal washings. Laparoscopic examination of the peritoneal cavity upstaged 21 (52.5%) patients. Laparoscopic examination consistently identified a statistically significant higher number of positive patients than cytologic examination of peritoneal washings (p = 0.001) and examination of cytologic washings alone failed to identify 45% of patients with positive findings and laparoscopy. The addition of cytologic examination added no additional stage IV patients to the laparoscopy-negative group. CONCLUSION: A standardized laparoscopic examination alone is sufficient for the identification of intraabdominal metastatic disease in patients with gastric and esophageal cancer.

Abdominal Neoplasms↗

Intraoperative ultrasound and prophylactic ursodiol for gallstone prevention following laparoscopic gastric bypass.

BACKGROUND: Previous studies have shown that ursodiol decreases gallstone formation from 32% to 2% following open gastric bypass, but no data exist on laparoscopic Roux-en-Y gastric bypass (LRYGB) using intraoperative ultrasound (IOUS) screening. METHODS: LRYGB with IOUS were performed on 195 consecutive patients. Patients with gallstones underwent simultaneous cholecystectomy, and patients without gallstones were prescribed ursodiol, 300 mg twice daily, for 6 month. Follow-up survey and ultrasound. RESULTS: Of 195 patients, 44 (23%) had had a prior cholecystectomy, 21 (11%) underwent a simultaneous cholecystectomy, 129 (66%) had gallbladders left intact, and one (0.5%) false negative IOUS was excluded. Of 69 patients with ultrasound and survey follow-up (mean, 10 months), 19 (28%) developed gallstones seven with symptoms), and 50 (72%) were gallstone free. Forty-one percent of patients were compliant with ursodiol. There was no difference in compliance between patients with and without gallstones. In patients with gallstones, all of the symptomatic patients were noncompliant, whereas none of the compliant patients developed symptoms. Medication side-effects occurred in 17 of 69 patients (25%). CONCLUSIONS: IOUS during LRYGB efficiently screens for gallstones, and selective cholecystectomy followed by prophylactic ursodiol results in low morbidity. Improvements in compliance may lower the incidence of postoperative gallstone formation.

Adult↗

Development of a mechanical testing and loading system for trabecular bone studies for long term culture.

A highly accurate (+/-3%) mechanical loading and measurement system combined with a trabecular bone diffusion culture-loading chamber has been developed, which provides the ability to study trabecular bone (and possibly) cartilage under controlled culture and loading conditions over long periods of time. The loading device has been designed to work in two main modes, either to apply a specific compressive strain to a trabecular bone cylinder or to apply a specific force and measure the resulting deformation. Presently, precisely machined bone cylinders can be loaded at frequencies between 0.1 Hz to 50 Hz and amplitudes over 7,000 microepsilon. The system allows accurate measurement of many mechanical properties of the tissue in real time, including visco-elastic properties. This paper describes the technical components, reproducibility, precision, and the calibration procedures of the loading system. Data on long term culture and mechanical responses to different loading patterns will be published separately.

Animals↗

Clinical predictors of leak after laparoscopic Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: Gastrointestinal leak is a complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Contrast studies may underdiagnose leaks, forcing surgeons to rely solely on clinical data. This study was designed to evaluate various clinical signs for detecting leakage after LRYGB. METHODS: We retrospectively reviewed 210 consecutive patients who underwent LRYGB between April 1999 and September 2001. There were nine documented leaks (4.3%). Clinical signs between patients with leaks (group 1) and those without leaks (group 2) were compared using univariate and multivariate logistic regression analysis. RESULTS: Evidence of respiratory distress and a heart rate exceeding 120 beats per min were the two most sensitive indicators of gastrointestinal leak. Routine upper gastrointestinal contrast imaging detected only two of nine leaks (22%). CONCLUSION: Leak after LRYGB may be difficult to detect. Evidence of respiratory distress and tachycardia exceeding 120 beats per min may be the most useful clinical indicators of leak after laparoscopic Roux-en-Y gastric bypass.

Adult↗

Splenic marginal zone atrophy and progressive CD8+ T-cell lymphocytosis in HIV infection: a study of adult post-mortem spleens from Côte d'Ivoire.

AIMS: Progressive changes have been reported in lymph nodes in HIV infection, but few accounts describe altered splenic histology at different stages of the disease. Investigation of splenic changes accompanying the progressive CD4+ T-cell depletion that occurs in HIV infection could shed light on normal immunological interactions in this organ. Therefore, we assessed the amount and distribution of lymphoid tissue in spleens from adults with documented early or advanced HIV disease. METHODS AND RESULTS: Immunohistochemistry was used to study splenic tissue collected in an extensive autopsy survey of HIV+ adults in West Africa. Compared with post-mortem spleens from HIV- West African adults and control UK spleens, those from HIV-infected patients showed severe atrophy of white pulp B- and T-cell compartments. In early and advanced HIV disease, marginal zone atrophy was significant. Peri-arteriolar lymphoid sheaths contained increased numbers of CD8+/CD45RO+ T-cells in advanced HIV disease. In red pulp, early and advanced cases showed a lymphocytosis of CD8+/CD45RO- T-lymphocytes. CONCLUSIONS: Atrophic changes were more extreme in advanced than early HIV infection. Reduced marginal zone function possibly explains the known predisposition of HIV+ patients to infection by encapsulated bacteria. Possible immunological consequences of these CD8+/CD45RO+ (peri-arteriolar lymphoid sheaths) and CD8+/CD45RO- (red pulp) responses deserve further study. Comparison of West African and UK control spleens indicated that there were no major ethnic differences in spleen structure to prevent extrapolation of our results to European adults.

Adolescent↗

Deterministic photon transport calculations in general geometry for external beam radiation therapy.

A deterministic method is described for performing three-dimensional (3D) photon transport calculations of a LINAC head and phantom/patient geometry to obtain dose distributions for therapy planning. The space, energy, and directional-dependent photon flux density is obtained by numerically solving the Boltzmann equation in general 3D geometry using the method of characteristics. The deterministic transport calculations use similar ray tracing routines as found in Monte Carlo (MC) codes. A special treatment is developed to better represent the impact of scattering from accelerator head components. Equations are presented for computing the water kerma distribution due to the uncollided and collided photon flux density field in the patient region. Kerma results obtained from the deterministic computation are compared to Monte Carlo values for a variety of source spectra and field sizes. The agreement for kerma values in the beam is usually within the MC uncertainties. It is concluded that the deterministic method is a rigorous, first-principles approach that could provide a superior alternative to Monte Carlo calculations for some types of problems. However additional development is needed to provide capability for 3D electron transport calculations.

Algorithms↗

Quantitation of cyclin D1 over-expression using competitive fluorescent reverse transcription polymerase chain reaction: a tool for the differential diagnosis of mantle cell lymphoma.

Mantle cell lymphoma is characterized by the presence of the t(11;14)(q13;q32) translocation that causes over-expression of the BCL-1 gene and consequent overproduction of its gene product cyclin D1. We have developed a competitive fluorescent reverse transcription polymerase chain reaction assay for the detection and semiquantitation of cyclin D1 over-expression. Using this assay a definitive ratio of the expression of cyclin D1 to cyclins D2 and D3 can be determined, provided good quality RNA is available. A single upstream primer derived from a consensus sequence found in cyclins D1, D2, and D3 was labeled at the 5' end using a fluorescent dye. Downstream primers specific to cyclins D1 and D2 were designed and used in conjunction with a previously published D3 specific primer. The fluorescently labeled PCR products were separated by electrophoresis using an ABI 377 DNA sequencer. Fluorescence emitted from each product was used to determine the ratio of expression of cyclin D1 to D2 and D3 by assigning a dosage quotient [D1/(D2+D3)]. The mean dosage quotient recorded from samples representing 29 non-MCL patients was 0.03 (SD +/- 0.03), the maximum value being 0.11. Samples from eight patients with a diagnosis of MCL generated values greater than 2. Calculation of a dosage quotient using this competitive fluorescent reverse transcription polymerase chain reaction assay allows unequivocal identification of patients with over-expression of cyclin D1, providing a new tool for the differential diagnosis of MCL.

Aged↗