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Biomedical subjects

C J Watson

Publications and source records attributed to C J Watson.

At least 55 records · Page 3Linked to original sources

Determinants of clinical performance in a physical therapy program.

In admission decisions, allied health programs evaluate various factors that may include overall grade-point average (GPA), science GPA, GPA in the most recent 60 hours of course work, volunteer/work experience, and performance during an admission interview. Most use mathematical formulas based on these parameters, but the rationale for weighting each factor is not always clear. To determine whether pre-admission variables can differentiate between good and poor clinical performances, the authors compared pre-admission data from 118 graduates of a physical therapy (PT) baccalaureate program with their clinical performances. GPA in the PT curriculum was included to determine whether it was related to clinical performance, which was taken as the average of overall performance scores assigned to each student by his or her instructors at four clinical education sites. The students were divided into quartiles by clinical scores. One-way ANOVA was used to identify differences between quartiles for each variable (alpha level of p < 0.05). The interview score was the only pre-admission variable that differentiated between students who did and did not perform well in the clinic (p < 0.003). Those who performed better in the clinic also had higher PT GPAs (p < 0.0001). The interview format and scoring system used may easily be adapted for other programs. Recommendations are made regarding how to utilize interview scores in the admission decision.

Adult↗

Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3.

Mammary gland involution is characterized by extensive apoptosis of the epithelial cells. At the onset of involution, Stat3 is specifically activated. To address the function of this signaling molecule in mammary epithelial apoptosis, we have generated a conditional knockout of Stat3 using the Cre-lox recombination system. Following weaning, a decrease in apoptosis and a dramatic delay of involution occurred in Stat3 null mammary tissue. Involution is normally associated with a significant increase in IGFBP-5 levels. This was observed in control glands, but not in the absence of Stat3. IGFBP-5 has been suggested to induce apoptosis by sequestering IGF-1 to casein micelles, thereby inhibiting its survival function. Our findings suggest that IGFBP-5 is a direct or indirect target for Stat3 and its upregulation is essential to normal involution. No marked differences were seen in the regulation of Stat5, Bcl-x(L), or Bax in the absence of Stat3. Precocious activation of Stat1 and increases in levels of p53 and p21 occurred and may act as compensatory mechanisms for the eventual initiation of involution observed in Stat3 null mammary glands. This is the first demonstration of the importance of a Stat factor in signaling the initiation of physiological apoptosis in vivo.

Animals↗

A 3 to 4 year study of single tooth hydroxylapatite coated endosseous dental implants.

OBJECTIVE: To evaluate the clinical effectiveness, common complications and maintenance associated with hydroxylapatite (HA) coated cylindrical implants when used to support single crowns. DESIGN: A prospective medium term clinical study of the Calcitek HA-coated implant. SETTING: Implant placement, crown fabrication and follow-up procedures were carried out at the Leeds Dental Institute, between 1990 and 1998. SUBJECTS AND METHOD: 26 patients (33 implants) participated in the trial. They were referred from general dental practitioners because of their suitability for single tooth implant placement. MAIN OUTCOME MEASURES: The implants were assessed using recognised clinical review procedures e.g. radiographs and soft tissue assessments. RESULTS: At exposure there was 100% implant integration. The cumulative survival rate over 4 years was 100%. In five implants there was cervical bone loss of more than 4 mm and these were classified as failing. This gave an overall cumulative success rate of 58% by year 4. CONCLUSION: The Calcitek HA-coated single tooth implant shows exceptionally high initial integration however, the longer term results suggest that the cervical bone level adjacent to the implant failed to establish a steady state. Doubts remain regarding the long-term prognosis of these cylindrical HA-coated implants.

Adult↗

Sirolimus: a potent new immunosuppressant for liver transplantation.

BACKGROUND: Sirolimus (rapamycin) is a new immunosuppressant that appears to be synergistic with cyclosporine in kidney transplantation, but with a different side-effect profile. This pilot study evaluated sirolimus in liver transplantation. METHODS: Patients undergoing orthotopic liver transplantation for primary tumors (8), and later for nonmalignant disease (7), received one of three sirolimus-based immunosuppressive regimens. Protocol A comprised sirolimus, microemulsion cyclosporine (target whole blood concentration: 100 ng/ml), and prednisolone; protocol B omitted prednisolone; and protocol C was sirolimus alone. By 3 months after transplantation, all patients were receiving sirolimus as monotherapy. RESULTS: Fifteen patients were treated with a follow-up of 117-806 days. Rejection was more common on monotherapy than double therapy, and absent on triple therapy. The drug was generally well tolerated, with only three patients discontinuing sirolimus: one for hyperlipidemia, one for pneumocystis pneumonia, and one for inability to tolerate the taste of the drug. Two patients discontinued cyclosporine early, both as a result of neurological complications; they continued on sirolimus monotherapy. Five patients died; one suffered a cardiac arrest, and four died from sepsis in association with graft-versus-host disease, recurrent tumor, a paralyzed right hemidiaphragm, and primary nonfunction. CONCLUSIONS: Sirolimus combined with cyclosporine provided potent immunosuppression of liver allografts, and sirolimus monotherapy was adequate and well tolerated as maintenance therapy. Side effects of sirolimus over the short period of follow-up were uncommon and reversible with dose reduction or cessation of therapy.

Adult↗

DNA chip technology.

A mini-revolution is sweeping the world of science and medicine. DNA chip or microarray technology will have a more profound impact than other recent major advances, including DNA sequencing and the polymerase chain reaction (PCR). This mini-review explains the technology, its scope, and impact on science and medicine, as well as its cost and possible limitations.

Chromosome Mapping↗

Implications for space radiation environment models from CREAM & CREDO measurements over half a solar cycle.

Flight data obtained between 1990 and 1997 from the Cosmic Radiation Environment Monitors CREAM & CREDO carried on UoSAT-3, Space Shuttle, STRV-1a (Space Technology Research Vehicle) and APEX (Advanced Photovoltaic and Electronics Experiment Spacecraft) provide coverage over half a solar cycle. The modulation of cosmic rays and evolution of the South Atlantic Anomaly are observed, the former comprising a factor of three increase at high latitudes and the latter a general increase accompanied by a north-westward drift. Comparison of particle fluxes and linear energy transfer (LET) spectra is made with improved environment & radiation transport calculations which account for shield distributions and secondary particles. While there is an encouraging convergence between predictions and observations, significant improvements are still required, particularly in the treatment of locally produced secondary particles. Solar-particle events during this time period have LET spectra significantly below the October 1989 event which has been proposed as a worst case model.

Atlantic Ocean↗

NF-kappaB and apoptosis in mammary epithelial cells.

A number of transcription factors have been identified as regulators of mammary development, including Stat5 and C/EBPbeta (1-3). In this review we summarize evidence which suggests that the NF-kappaB family of transcription factors also has a role in mammary gland development. NF-kappaB was originally described as a mediator of inflammatory reactions and cellular responses to viral pathogens. More recently it has been shown to possess an anti-apoptotic effect in a variety of cell types by regulating apoptosis-related genes. In the light of this function in other tissues, and the observation that aberrant activation of NF-kappaB can be associated with mammary tumors, we discuss the potential role of this transcription factor in modulating mammary epithelial apoptosis and involution of the mammary gland.

Animals↗

Apoptosis: the germs of death.

From the initial recognition that programmed cell suicide existed, to the elucidation of the underlying death and survival pathways at the molecular level, the story of apoptosis has unfolded rapidly. But much still remains to be discovered.

Animals↗

Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): specific up-regulation by tumour necrosis factor-alpha (TNF-alpha) in synovial fluid.

This study was designed to investigate VEGF production from peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) compared with healthy controls and to identify the predominant cellular source in PBMC isolated from RA patients. The regulation of PBMC VEGF production by cytokines and synovial fluid (SF) was studied. PBMC were isolated from RA patients and healthy controls and stimulated with lipopolysaccharide (LPS), IL-1beta, IL-4, IL-6, IL-8, IL-10, TNF-alpha and transforming growth factor-beta (TGF-beta) isoforms for varying time points up to 72 h at 37 degrees C/5% CO2. The effect of SF on VEGF secretion by PBMC was also studied. Supernatant VEGF levels were measured using a flt-1 receptor capture ELISA. RA patients had significantly higher spontaneous production of VEGF compared with controls, and monocytes were identified as the predominant cellular source. RA PBMC VEGF production was up-regulated by TGF-beta isoforms and TNF-alpha and down-regulated by IL-4 and IL-10, with no effect observed with IL-1beta, IL-6 and IL-8. Antibody blocking experiments confirmed that TNF-alpha and not TGF-beta isoforms in SF increased VEGF secretion by RA PBMC. These results emphasize the importance of monocytes as a source of VEGF in the pathophysiology of RA. Several cytokines known to be present in SF can modulate the level of VEGF secretion, but the predominant effect of SF in VEGF up-regulation is shown to be dependent on TNF-alpha.

Arthritis, Rheumatoid↗

A survey of U.K. centres on implant failures.

This study investigated the experience of endossoseus implants in the U.K. - how success rates compare with other countries; the common causes of failure; early detection, definition and treatment of the failing implant. Information was gathered by means of a questionnaire sent to 120 centres in the U.K. Thirty-nine centres responded to the survey, reporting on a total of 5328 implants which had been placed over an average time period of 6.5 years. A mean failure rate of 4.3% was reported in the mandible with 16% in the maxilla. The survey showed that 11 different implant systems were in use and that implants were used to support an overdenture in 56% of cases, and bridgework in 26%. The definition of the failing implant and the causes of failure were unclear, with a wide range of opinions given. A combination of methods were used to treat the failing implant including surgical techniques and chemotherapeutic agents, but the long-term success of these treatments was uncertain. Failure rates especially in the maxilla at some of the centres appear higher than have been previously suggested in the U.K. or abroad. Universal agreement on the criteria for 'success' and 'failure' of fixtures is needed along with agreed treatment protocols for the failing implant.

Clinical Protocols↗

Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome.

BACKGROUND: An uncharacterized circulating factor that increases vascular permeability has previously been described in childhood steroid-sensitive nephrotic syndrome (SSNS). The aim of this study was to determine whether this factor is vascular endothelial growth factor (VEGF), the recently described endothelial cell mitogen and enhancer of vascular permeability. METHODS: Plasma and urine VEGF levels were measured in children with SSNS in both relapse and remission and in normal age- and sex-matched controls. Semiquantitative reverse transcriptase-polymerase chain reaction studies investigating VEGF mRNA expression were performed on peripheral blood mononuclear cells isolated from children with SSNS in relapse and controls. In two experimental models (one-hour and three-day follow-up postinfusion), Sprague-Dawley rats were intravenously administered 50 microg rVEGF to determine whether this induced either proteinuria or glomerular histologic change. RESULTS: Plasma VEGF levels and urine VEGF/creatinine ratios were not elevated in SSNS relapse compared with remission and control samples. Peripheral blood mononuclear cell VEGF mRNA expression was no different in SSNS patients compared with controls. The administration of VEGF to rats induced an acute reversible fall in systemic blood pressure but did not result in the development of either proteinuria or glomerular histologic change. CONCLUSION: Increased circulating VEGF levels are not responsible for the proteinuria observed during relapses of SSNS. Further studies are warranted to investigate intrarenal VEGF expression.

Adrenal Cortex Hormones↗

Reliability of McConnell's classification of patellar orientation in symptomatic and asymptomatic subjects.

STUDY DESIGN: Test-retest reliability study with blinded testers. OBJECTIVES: To determine the intratester reliability of the McConnell classification system and to determine whether the intertester reliability of this system would be improved by one-on-one training of the testers, increasing the variability and numbers of subjects, blinding the testers to the absence or presence of patellofemoral pain syndrome, and adhering to the McConnell classification system as it is taught in the "McConnell Patellofemoral Treatment Plan" continuing education course. BACKGROUND: The McConnell classification system is currently used by physical therapy clinicians to quantify static patellar orientation. The measurements generated from this system purportedly guide the therapist in the application of patellofemoral tape and in assessment of the efficacy of treatment interventions on changing patellar orientation. METHODS AND MEASURES: Fifty-six subjects (age range, 21-65 years) provided a total of 101 knees for assessment. Seventy-six knees did not produce symptoms. A researcher who did not participate in the measuring process determined that 17 subjects had patellofemoral pain syndrome in 25 knees. Two testers concurrently measured static patellar orientation (anterior/posterior and medial/lateral tilt, medial/lateral glide, and patellar rotation) on subjects, using the McConnell classification system. Repeat measures were performed 3-7 days later. A kappa (kappa) statistic was used to assess the degree of agreement within each tester and between testers. RESULTS: The kappa coefficients for intratester reliability varied from -0.06 to 0.35. Intertester reliability ranged from -0.03 to 0.19. CONCLUSION: The McConnell classification system, in its current form, does not appear to be very reliable. Intratester reliability ranged from poor to fair, and intertester reliability was poor to slight. This system should not be used as a measurement tool or as a basis for treatment decisions.

Adult↗

How well are complete dentures copied?

OBJECTIVE: To assess how accurately the same set of complete dentures could be copied by 12 different laboratories. DESIGN: A prospective study. SETTINGS: Completed by commercial laboratories used by GDPs in England (1996). Results were analysed and controlled by a university department. SUBJECTS (MATERIALS) AND METHODS: The master set was constructed to include a midline diastema and a bilateral posterior crossbite. Twelve sets of silicone moulds of the master denture were prepared. GDPs selected commercial laboratories of their choice to receive the work. MAIN OUTCOME MEASURES: All stages of the work were compared with the master dentures by returning them to a specially adapted articulator. Analysis was completed using preset criteria. RESULTS: Only five of the returned copies were considered to have both good quality acrylic resin work and clear details of the teeth in wax. Only four cases reproduced the diastema. After processing, the occlusal vertical dimension had been increased in eight of the cases and the bilateral crossbite had been eliminated in all cases. CONCLUSIONS: None of the final copy dentures were considered an accurate copy of the master dentures. There is considerable scope for further training of dental technicians in this important technique.

Acrylic Resins↗

Characterization of a nucleoside/proton symporter in procyclic Trypanosoma brucei brucei.

Adenosine transport at 22 degrees C in procyclic forms of Trypanosoma brucei brucei was investigated using an oil-inhibitor stop procedure for determining initial rates of adenosine uptake in suspended cells. Adenosine influx was mediated by a single high affinity transporter (Km 0.26 +/- 0.02 microM, Vmax 0.63 +/- 0.18 pmol/10(7) cells s-1). Purine nucleosides, with the exception of tubercidin (7-deazaadenosine), and dipyridamole inhibited adenosine influx (Ki 0.18-5.2 microM). Purine nucleobases and pyrimidine nucleosides and nucleobases had no effect on adenosine transport. This specificity of the transporter appears to be similar to the previously described P1 adenosine transporter in bloodstream forms of trypanosomes. Uptake of adenosine was Na+-independent, but ionophores reducing the membrane potential and/or the transmembrane proton gradient (monitored with the fluorescent probes bis-(1,3-diethylthiobarbituric acid)-trimethine oxonol and 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester, respectively) inhibited adenosine transport. Similarly, an increase in extracellular pH from 7.3 to 8.0 reduced adenosine influx by 30%. A linear correlation was demonstrated between the rate of adenosine transport and the protonmotive force. Adenosine uptake was accompanied by a proton influx in base-loaded cells and was also shown to be electrogenic. These combined results indicate that transport of adenosine in T. brucei brucei procyclics is protonmotive force-driven and strongly suggest that the adenosine transporter functions as an H+ symporter.

Adenosine↗

Activated human neutrophils express vascular endothelial growth factor (VEGF).

The neutrophil (PMN) influx in the acute inflammatory response is associated with a local increase in vascular permeability and oedema. Vascular endothelial growth factor (VEGF), a growth factor known to have potent vascular permeability-enhancing properties in addition to being an endothelial cell mitogen and a chemo-attractant for mononuclear cells, has previously been shown to be expressed by mononuclear cells and platelets, though PMN VEGF expression has not been reported. PMNs isolated from healthy adult volunteers (n = 16) were incubated for 4 h at 37 degrees C in the presence of tumour necrosis factor alpha (TNF-alpha) (5 ng/ml) and serum opsonized zymozan (SOZ) (500 micrograms/ml). Supernatant VEGF levels were measured using a sandwich antibody capture immuno-assay. Median (interquartile range) VEGF levels were significantly increased in PMN supernatants following stimulation with both TNF-alpha [347 pg/ml (264-385 pg/ml)] and SOZ [506 pg/ml (407-593 pg/ml)] compared with control values [78 pg/ml (78-87 pg/ml)]. Time course experiments with SOZ stimulated PMNs showed that the majority of VEGF production occurred within the first hour (1 h mean VEGF level 318 pg/ml, 4 h mean VEGF level 451 pg/ml). RT-PCR studies showed that PMNs express mRNA for the two common VEGF splice variants, VEGF121 and VEGF165. PMN VEGF production may be central to the classic acute phase response to injury and the chemo-attraction of other leukocytes to the source of injury.

Adult↗

The low earth orbit environment observed using CREAM and CREDO.

The Cosmic Radiation Environment and Dosimetry experiment (CREDO) has been operational on board the Advanced Photovoltaics & Electronics Experiment Spacecraft since August 1994. Extensive measurements of cosmic ray linear energy transfer spectra (using data to January 1996) and total dose (using data to November 1994) have been made, and compared with predictions of standard models. Detailed consideration of spacecraft shielding effects have been made. Predictions are shown to overestimate the measured linear energy transfer spectra. The CREAM experiment was flown on STS-63 in the SpaceHab module. Results show penetration of high energy electrons into the SpaceHab module.

Atlantic Ocean↗

Estimates of distance by claudicants and vascular surgeons are inherently unreliable.

Claudication distance and maximum walking distance are both measures of disability. Estimates of the distances which a patient with intermittent claudication can walk are commonly used by vascular surgeons as surrogate measures of handicap. We studied how accurately distance was estimated by 70 patients with intermittent claudication, and by 100 British vascular surgeons. Patients and vascular surgeons estimated actual distances of 30 m and 34 m, respectively. Estimates were 46 m median (range 2.7-402 m) for claudicants, and 46 m median (range 15.2-186 m) for vascular surgeons, median over estimates of 52% and 34% respectively. Claudicants' errors can easily be eliminated by accurate and appropriate measurement of claudication and maximum walking distances but interpretation of the data by surgeons is dependent on their own ability to estimate distance. Flawed perceptions by patients and their surgeons of the disability of reduced walking distance illustrates the need for reliable measures of handicap on which to base therapeutic decisions in patients with intermittent claudication.

Disability Evaluation↗