Biomedical subjects
J Watson
Publications and source records attributed to J Watson.
Taking telehealth to the bush: lessons from north Queensland.
Networking North Queensland (NNQ) was a two-year project to improve access to health services in rural and remote communities. The project involved email and Internet access in 61 communities, in a region almost three times the size of the UK. Videoconferencing equipment was also installed at 21 sites and a total of 197 h of videoconferencing was recorded at 10 of the remote sites over 12 months. As a result of the project, health consumers enjoyed improved access to medical, specialist, allied health and primary health services. In addition, health service providers had better access to reliable, up-to-date health-care information via intranet and Internet services. Consideration of local issues--local needs and existing resources--was vital to the achievements of the project. Community involvement and community access were also important factors in its success.
Helping the woman with sexual dysfunction.
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Influence of hypoglycaemia, with or without caffeine ingestion, on visual sensation and performance.
Full-field visual evoked potentials and visual information processing were measured in 16 normal, healthy subjects during a hyperinsulinaemic clamp. A randomized cross-over design was used across three conditions: hypoglycaemia and caffeine; hypoglycaemia and placebo; and euglycaemia and caffeine. The latency of the P100 component of the pattern-reversal visual evoked potential increased significantly from rest to hypoglycaemia, but no effect of caffeine was found. Subjects were subsequently divided into two median groups based on the increase in P100 latency in the placebo condition (Group 1, +0.5 ms; Group 2, +5.6 ms). In the absence of caffeine, an inverse correlation between the increase in P100 latency from rest and a deterioration in visual movement detection was found for Group 2, but not for Group 1. Caffeine ingestion resulted in a further increase in P100 latency, from rest to hypoglycaemia, for subjects in Group 2. Hypoglycaemia in the absence of caffeine produces changes in visual sensation from rest to hypoglycaemia. In those subjects most sensitive to the effects of hypoglycaemia (Group 2), the increase in P100 latency was associated with poorer performance in tests of visual information processing. Caffeine ingestion produced further increases in P100 latency in these subjects.
Radiation Therapy Oncology Group. Research Plan 2002-2006. Translational Research Program.
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Signalling pathways regulating the dephosphorylation of Ser729 in the hydrophobic domain of protein kinase Cepsilon upon cell passage.
We have recently demonstrated that in quiescent fibroblasts protein kinase C (PKC) epsilon(95) is phosphorylated at Ser(729), Ser(703), and Thr(566) and that upon passage of quiescent cells phosphorylation at Ser(729) is lost, giving rise to PKCepsilon(87). Ser(729) may be rephosphorylated later, suggesting cycling between PKCepsilon(87) and PKCepsilon(95). Here we show that the dephosphorylation at Ser(729) is insensitive to okadaic acid, calyculin, ascomycin C, and cyclosporin A, suggesting that dephosphorylation at this site is not mediated through protein phosphatases 1, 2A or 2B. We demonstrate that this dephosphorylation at Ser(729) requires serum and cell readhesion and is sensitive to rapamycin, PD98059, chelerythrine, and Ro-31-8220. These results suggest that the phosphorylation status of Ser(729) in the hydrophobic domain at Ser(729) is regulated independently of the phosphorylation status of other sites in PKCepsilon, by a mTOR-sensitive phosphatase. The mitogen-activated protein kinase pathway and PKC are also implicated in regulating the dephosphorylation at Ser(729).
Transverse asymmetry AT' from the quasielastic 3He(e,e') process and the neutron magnetic form factor.
We have measured the transverse asymmetry A(T') in 3He(e,e(')) quasielastic scattering in Hall A at Jefferson Laboratory with high precision for Q2 values from 0.1 to 0.6 (GeV/c)(2). The neutron magnetic form factor G(n)(M) was extracted based on Faddeev calculations for Q2 = 0.1 and 0.2 (GeV/c)(2) with an experimental uncertainty of less than 2%.
Phase 1 trial of a single dose of recombinant human interleukin-12 in human immunodeficiency virus-infected patients with 100-500 CD4 cells/microL.
A phase 1 dose-escalation trial of a single subcutaneous dose of recombinant human (rh) interleukin (IL)-12 was conducted in medically stable human immunodeficiency virus (HIV)-infected patients with 100-500/microL absolute CD4(+) T lymphocytes. Subjects at each dose level were randomly assigned (3:1) to receive rhIL-12 or placebo. Among the 47 subjects enrolled, rhIL-12 was well tolerated at doses of 3-300 ng/kg, but 4 of 5 subjects who received rhIL-12 at 1000 ng/kg had severe adverse events. Dose-related increases in serum interferon-gamma occurred after rhIL-12 administration at doses > or =30 ng/kg. There was no effect of rhIL-12 on plasma HIV RNA or absolute CD4(+) T cell counts. However, dose-related increases in absolute CD8(+) T and NK cells were observed in subjects assigned to rhIL-12 doses of 30-300 ng/kg. Single rhIL-12 doses of 30-300 ng/kg were well tolerated and had biologic activity that could potentially be of benefit in the treatment of HIV disease or its complications.
Regulation of the human fas promoter by YB-1, Puralpha and AP-1 transcription factors.
Fas (CD95/Apo-1) gene expression is dysregulated in a number of diseased states. Towards understanding the regulation of fas gene expression, we previously identified activator and repressor elements within the human fas promoter. Using a combination of expression screening and reporter gene assays, we have identified transcription factors which bind to these elements and thereby regulate transcription of the fas promoter. These are three single-stranded DNA binding proteins, YB-1, Puralpha and Purbeta and two components of the AP-1 complex, c-Fos and c-Jun. c-Jun is a potent transcriptional activator of fas and stimulated expression levels up to 184-fold in reporter gene assays. Co-expression with c-Fos abrogated c-Jun-mediated activation. YB-1 and Puralpha are transcriptional repressors of fas and decreased basal transcription by 60-fold in reporter gene assays. Purbeta was predominantly an antagonist of YB-1/Puralpha-mediated repression. Overexpression of YB-1 and Puralpha in Jurkat cells was shown to reduce the level of cell surface Fas staining, providing further evidence that these proteins regulate the fas promoter. It has been suggested that YB-1 plays a role in cell proliferation as an activator of growth-associated gene expression. We have shown that YB-1 is a repressor of a cell death-associated gene fas. These results suggest that YB-1 may play an important role in controlling cell survival by co-ordinately regulating the expression of cell growth-associated and death-associated genes.
The double helix revisited. The man who launched the Human Genome Project celebrates its success.
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Myxoma involving the atrial valve chordae.
Primary cardiac valve tumors are rare and comprise less than 10% of all cardiac tumors. They are, however, of clinical importance because of their unique locations. We report an unusual case of myxoma involving the tricuspid valve chordae in a young woman presenting with syncope. The myxoma was diagnosed by echocardiography and successfully removed by excision of the involved tricuspid valve chordae with valve preservation. (Curr Surg 57:357-358)
Systematic implementation of an advance directive program in nursing homes: a randomized controlled trial.
CONTEXT: Although advance directives are commonly used in the community, little is known about the effects of their systematic implementation. OBJECTIVES: To examine the effect of systematically implementing an advance directive in nursing homes on patient and family satisfaction with involvement in decision making and on health care costs. DESIGN: Randomized controlled trial conducted June 1, 1994, to August 31, 1998. SETTING AND PARTICIPANTS: A total of 1292 residents in 6 Ontario nursing homes with more than 100 residents each. INTERVENTION: The Let Me Decide advance directive program included educating staff in local hospitals and nursing homes, residents, and families about advance directives and offering competent residents or next-of-kin of mentally incompetent residents an advance directive that provided a range of health care choices for life-threatening illness, cardiac arrest, and nutrition. The 6 nursing homes were pair-matched on key characteristics, and 1 home per pair was randomized to take part in the program. Control nursing homes continued with prior policies concerning advance directives. MAIN OUTCOME MEASURES: Residents' and families' satisfaction with health care and health care services utilization over 18 months, compared between intervention and control nursing homes. RESULTS: Of 527 participating residents in intervention nursing homes, 49% of competent residents and 78% of families of incompetent residents completed advance directives. Satisfaction was not significantly different in intervention and control nursing homes. The mean difference (scale, 1-7) between intervention and control homes was -0.16 (95 % confidence interval [CI], -0.41 to 0.10) for competent residents and 0.07 (95% CI, -0.08 to 0.23) for families of incompetent residents. Intervention nursing homes reported fewer hospitalizations per resident (mean, 0.27 vs 0.48; P = .001) and less resource use (average total cost per patient, Can $3490 vs Can $5239; P = .01) than control nursing homes. Proportion of deaths in intervention (24%) and control (28%) nursing homes were similar (P = .20). CONCLUSION: Our data suggest that systematic implementation of a program to increase use of advance directives reduces health care services utilization without affecting satisfaction or mortality.
Cumulation characteristics of cisatracurium and rocuronium during continuous infusion.
PURPOSE: The dissimilar pharmacokinetic properties of cisatracurium (CIS) and rocuronium (ROC) predict different potential for drug cumulation when these drugs are administered by continuous infusion. A study was therefore undertaken to compare cumulation potential of CIS and ROC during surgical procedures of relatively long duration (2-4 hr). METHODS: Sufentanil/propofol-N2O anesthesia was administered to 40 ASA I and II adults. In a double-blind protocol, patients were randomly allocated to receive a continuous i.v. infusion of either CIS or ROC, titrated in progressive increments or decrements as required to achieve and maintain 95 +/- 5% depression of the T1 response of the adductor pollicis muscle, using a Datex NMT-100 Relaxograph EMG monitor applied at the wrist. At the end of surgery, 60 microg x kg(-1) neostigmine plus 15 microg x kg(-1) atropine were administered for reversal. RESULTS: The duration of infusion was 104 +/- 33 min in group CIS and 110 +/- 23 min in group ROC (P=NS). In both groups, a progressive decrease in potency-adjusted infusion rates was observed after 30 min, then stabilized beyond 60 min. When allowing for an initial period of stabilization, mean potency-adjusted infusion requirements were: CIS 0.81 +/- 0.02 microg x kg(-1) x min(-1) and ROC 5.58 +/- 1.94 microg x kg(-1) x min(-1). There were no differences between groups at any time with regard to potency-adjusted infusion requirements necessary to maintain 90-99% block (P=NS). However, drug costs/hr for maintenance of neuromuscular block were less with CIS ($3.57 +/- 0.09) than with ROC ($6.03 +/- 0.27), P < 0.001. CONCLUSION: When adjusted to equipotency, infusion requirements of CIS and ROC vary at similar rates during general anesthesia. Despite pharmacokinetic differences, neither drug demonstrates cumulation for infusion lasting up to 3.5 hr.
HCV-related fibrosis progression following liver transplantation: increase in recent years.
BACKGROUND/AIMS: The natural history and predictors of HCV-related disease severity post-transplantation are uncertain. The aims of this study were to define the natural history of post-transplantation HCV infection by assessing the rate of fibrosis progression, to determine if the post-transplantation natural history differs from that observed pre-transplantation, and to identify predictors of post-transplantation disease progression. METHODS: Post-transplantation biopsies (mean: 3+/-1.6/patient) from 284 patients were scored according to histologic stage, using the method of Desmet et al. Change in fibrosis score (fibrosis progression/year) post-transplantation was used as the primary outcome. Predictors analyzed included viral factors (genotype and viral load at transplantation), patient demographics, year of transplantation, country of transplantation, pre-transplantation fibrosis progression, immunosuppression and laboratory data. RESULTS: There was a linear association between change in fibrosis score and time from transplantation, with a median rate of fibrosis progression per year of 0.3 (0.004-2.19/year). Using parametric time-to-event analysis, the expected median duration to cirrhosis was 10 years. The rate of post-transplantation fibrosis progression was significantly higher than pre-transplantation (0.2/year (0.09-0.8) p<0.0001), and higher in Spanish than US centers (0.48 (0.01-2.19) vs 0.28 (0.004-2.08); p=0.09) despite similar progression rates prior to transplantation. Variables independently associated with post-transplantation progression included year of transplantation (p=0.0001), race (p=0.02), number of methyl-prednisolone boluses (p=0.03), and HCV RNA levels at transplantation (p=0.01). CONCLUSIONS: HCV-related disease progression is accelerated in immunocompromised compared to immunocompetent patients, with a progressive increase in patients who have recently undergone liver transplantation. Changes in patient management post-transplantation over time and between transplant centers may account for the increase in fibrosis progression observed in recent years.
CPR '98: a practical multimedia computer-based guide to cardiopulmonary resuscitation for medical students.
This paper describes an initiative to build a multimedia computer-based teaching package for cardiopulmonary resuscitation. The project resulted from a perceived gap in the undergraduate medical curriculum allied to concern from medical students. The software application was designed to be networked and used as an adjunct to taught life support courses for undergraduate medical students. The package comprises tutorials and test questions in basic and advanced life support. It incorporates sound, video, graphics and animation to illustrate the techniques involved and is distributed on CD ROM for the PC. The content is based on the 'Advanced Life Support Manual', produced by the Resuscitation Council (UK) and incorporates all changes to the guidelines made during 1997 and 1998. The basic life support section has been networked locally, and has been tested on more than 60 third year medical students attending a local basic life support course. It was found that students who used the package performed significantly better in theoretical assessments than those who did not.
5-HT(1A) receptor agonist-antagonist binding affinity difference as a measure of intrinsic activity in recombinant and native tissue systems.
1. It has been reported that radiolabelled agonist : antagonist binding affinity ratios can predict functional efficacy at several different receptors. This study investigates whether this prediction is true for recombinant and native tissue 5-HT(1A) receptors. 2. Saturation studies using [(3)H]-8-OH-DPAT and [(3)H]-MPPF revealed a single, high affinity site (K(D)approximately 1 nM) in HEK293 cells expressing human 5-HT(1A) receptors and rat cortex. In recombinant cells, [(3)H]-MPPF labelled 3 - 4 fold more sites than [(3)H]-8-OH-DPAT suggesting the presence of more than one affinity state of the receptor. [(3)H]-Spiperone labelled a single, lower affinity site in HEK293 cells expressing h5-HT(1A) receptors but did not bind to native tissue 5-HT(1A) receptors. These data suggest that, in transfected HEK293 cells, human 5-HT(1A) receptors exist in different affinity states but in native rat cortical tissue the majority of receptors appear to exist in the high agonist affinity state. 3. Receptor agonists inhibited [(3)H]-MPPF binding from recombinant 5-HT(1A) receptors in a biphasic manner, whereas antagonists and partial agonists gave monophasic inhibition curves. All compounds displaced [(3)H]-8-OH-DPAT and [(3)H]-spiperone binding in a monophasic manner. In rat cortex, all compounds displaced [(3)H]-MPPF and [(3)H]-8-OH-DPAT in a monophasic manner. 4. Functional evaluation of compounds, using [(35)S]-GTPgammaS binding, produced a range of intrinsic activities from full agonism, displayed by 5-HT and 5-CT to inverse agonism displayed by spiperone. 5. [(3)H]-8-OH-DPAT : [(3)H]-MPPF pK(i) difference correlated well with functional intrinsic activity (r=0.86) as did [(3)H]-8-OH-DPAT : [(3)H]-spiperone pK(i) difference with functional intrinsic activity (r=0.96). 6. Thus agonist : antagonist binding affinity differences may be used to predict functional efficacy at human 5-HT(1A) receptors expressed in HEK293 cells where both high and low agonist affinity states are present but not at native rat cortical 5-HT(1A) receptors in which only the high agonist affinity state was detectable.
A biodialysis system for liver support tested in a porcine hepatic failure model.
BACKGROUND: A practical liver support system for patients in fulminant hepatic failure (FHF) remains a needed therapeutic modality. A new method of bioartificial liver support, the liver biodialysis system (LBDS), is described. METHODS: Porcine hepatocytes, removed from direct contact with the treated subject's circulation, are in culture in a bioreactor which is combined in a dialysis circuit for patient treatment. The LBDS was tested in a porcine ischaemic hepatic failure model. RESULTS: The viable hepatocyte content of the bioreactor was 2.49 +/- 0.72 x 10(10). Cells remained viable in culture throughout the experiments (30 +/- 3 h) without evidence of immunological damage. A decrease in the degree of accumulation in the blood of ammonia (P < 0.02) and of 14 amino acids (P < 0.001) was achieved by the LBDS. Cerebral perfusion pressure was maintained at significantly higher levels in LBDS-treated animals (P < 0.05). CONCLUSIONS: In the LBDS, hepatocytes in large numbers and satisfactory culture conditions in a bioreactor have sustained viability and function. When combined in a dialysis circuit for the treatment of FHF pigs, immune reactions between the blood and hepatocytes were prevented and beneficial metabolic effects were observed.
Driving and insulin--consensus, conflict or confusion?
AIMS: All drivers requiring insulin treatment must be able to demonstrate satisfactory diabetic control and recognition of hypoglycaemic symptoms before being allowed to drive a motor vehicle. Clinicians have a duty to discuss fitness to drive with their patients. However, is the advice given consistent and in line with the regulations published by the Driver and Vehicle Licensing Authority (DVLA)? METHODS: Six 'real-life' case scenarios were posted to clinicians (consultant diabetologists, specialist registrars and diabetes specialist nurses) within Wessex, UK. The identical cases were also sent to the DVLA for their comments. RESULTS: Sixty-six doctors (36 consultants) and 70 diabetes specialist nurses were contacted by postal questionnaire of which replies were received from 17 consultants (47%), 17 specialist registrars (57%) and 39 diabetes specialist nurses (56%). Although there was general agreement in cases of hypoglycaemia unawareness, there was disagreement where patients had or were at risk of unstable control albeit for a short time. CONCLUSIONS: Patients treated with insulin may receive conflicting information concerning their ability to drive.