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Biomedical subjects

J Pike

Publications and source records attributed to J Pike.

At least 19 recordsLinked to original sources
PubMed2006

Use of the one-legged hyperextension test and magnetic resonance imaging in the diagnosis of active spondylolysis.

BACKGROUND: Active spondylolysis is an acquired lesion in the pars interarticularis and is a common cause of low back pain in the young athlete. OBJECTIVES: To evaluate whether the one-legged hyperextension test can assist in the clinical detection of active spondylolysis and to determine whether magnetic resonance imaging (MRI) is equivalent to the clinical gold standard of bone scintigraphy and computed tomography in the radiological diagnosis of this condition. METHODS: A prospective cohort design was used. Young active subjects with low back pain were recruited. Outcome measures included clinical assessment (one-legged hyperextension test) and radiological investigations including bone scintigraphy (with single photon emission computed tomography (SPECT)) and MRI. Computed tomography was performed if bone scintigraphy was positive. RESULTS: Seventy one subjects were recruited. Fifty pars interarticulares in 39 subjects (55%) had evidence of active spondylolysis as defined by bone scintigraphy (with SPECT). Of these, 19 pars interarticulares in 14 subjects showed a fracture on computed tomography. The one-legged hyperextension test was neither sensitive nor specific for the detection of active spondylolysis. MRI revealed bone stress in 40 of the 50 pars interarticulares in which it was detected by bone scintigraphy (with SPECT), indicating reduced sensitivity in detecting bone stress compared with bone scintigraphy (p = 0.001). Conversely, MRI revealed 18 of the 19 pars interarticularis fractures detected by computed tomography, indicating concordance between imaging modalities (p = 0.345). There was a significant difference between MRI and the combination of bone scintigraphy (with SPECT)/computed tomography in the radiological visualisation of active spondylolysis (p = 0.002). CONCLUSIONS: These results suggest that there is a high rate of active spondylolysis in active athletes with low back pain. The one-legged hyperextension test is not useful in detecting active spondylolysis and should not be relied on to exclude the diagnosis. MRI is inferior to bone scintigraphy (with SPECT)/computed tomography. Bone scintigraphy (with SPECT) should remain the first-line investigation of active athletes with low back pain followed by limited computed tomography if bone scintigraphy is positive.

Adolescent↗
PubMed2005

Inhibiting estrogen responses in breast cancer cells using a fusion protein encoding estrogen receptor-alpha and the transcriptional repressor PLZF.

Estrogen receptor alpha (ERalpha) is a ligand-inducible transcription factor that acts to regulate gene expression by binding to palindromic DNA sequence, known as the estrogen response element, in promoters of estrogen-regulated genes. In breast cancer ERalpha plays a central role, where estrogen-regulated gene expression leads to tumor initiation, growth and survival. As an approach to silencing estrogen-regulated genes, we have studied the activities of a fusion protein between ERalpha and the promyelocytic leukemia zinc-finger (PLZF) protein, a transcriptional repressor that acts through chromatin remodeling. To do this, we have developed lines from the estrogen-responsive MCF-7 breast cancer cell line in which the expression of the fusion protein PLZF-ERalpha is conditionally regulated by tetracycline and shows that these feature long-term silencing of the expression of several well-characterized estrogen-regulated genes, namely pS2, cathepsin-D and the progesterone receptor. However, the estrogen-regulated growth of these cells is not inhibited unless PLZF-ERalpha expression is induced, an observation that we have confirmed both in vitro and in vivo. Taken together, these results show that PLZF-ERalpha is a potent repressor of estrogen-regulated gene expression and could be useful in distinguishing estrogen-regulated genes required for the growth of breast cancer cells.

Animals↗
PubMed2005

Design and development of a mobile system for supporting emergency triage.

OBJECTIVES: Our objective was to design and develop a mobile clinical decision support system for emergency triage of different acute pain presentations. The system should interact with existing hospital information systems, run on mobile computing devices (handheld computers) and be suitable for operation in weak-connectivity conditions (with unstable connections between mobile clients and a server). METHODS: The MET (Mobile Emergency Triage) system was designed following an extended client-server architecture. The client component, responsible for triage decision support, is built as a knowledge-based system, with domain ontology separated from generic problem solving methods and used for the automatic creation of a user interface. RESULTS: The MET system is well suited for operation in the Emergency Department of a hospital. The system's external interactions are managed by the server, while the MET clients, running on handheld computers are used by clinicians for collecting clinical data and supporting triage at the bedside. The functionality of the MET client is distributed into specialized modules, responsible for triaging specific types of acute pain presentations. The modules are stored on the server, and on request they can be transferred and executed on the mobile clients. The modular design provides for easy extension of the system's functionality. A clinical trial of the MET system validated the appropriateness of the system's design, and proved the usefulness and acceptance of the system in clinical practice. CONCLUSIONS: The MET system captures the necessary hospital data, allows for entry of patient information, and provides triage support. By operating on handheld computers, it fits into the regular emergency department workflow without introducing any hindrances or disruptions. It supports triage anytime and anywhere, directly at the point of care, and also can be used as an electronic patient chart, facilitating structured data collection.

Acute Disease↗
PubMed2004

CT-guided suprascapular nerve blocks: a pilot study.

OBJECTIVE: The objective of this study was to describe the suprascapular nerve block using CT guidance and to evaluate the short- and medium-term efficacy in a range of shoulder pathologies. DESIGN AND PATIENTS: CT-guided infiltration around the suprascapular nerve was performed with bupivacaine and Celestone Chronodose on 40 consecutive patients presenting with chronic shoulder pathologies unresponsive to conventional treatment. Patients were interviewed using the Shoulder Pain and Disability Index (SPADI) before the procedure, 30 min after the procedure and at 3 days, 3 weeks and 6 weeks afterwards. RESULTS: Within 30 min of the block overall pain scores decreased from a mean (+/-SEM) pain score of 7.0 (+/-0.4) to 3.5 (+/-0.5) ( n=39, P<0.001). At 3 days after the procedure, the mean overall improvement of the pain and disability scores were 20.4% (+/-4.9, P<0.001) and 16.8% (+/-4.8, P=0.004) respectively. Sustained pain relief and reduced disability were achieved in 10 of 35 (29%) patients at 3 weeks and longer. Patients suffering from soft tissue pathologies were the most likely patients to benefit from the injection. No serious side effects were noted. CONCLUSIONS: In some patients with chronic soft tissue pathologies who do not respond to conventional treatment, a CT-guided suprascapular nerve block can provide safe short- and medium-term relief from pain and disability.

Adult↗
PubMed2004

MR imaging of thumb carpometacarpal joint ligament injuries.

This study describes the MR imaging appearances of the supporting ligaments of the thumb carpometacarpal joint in asymptomatic volunteers and in a group of patients following joint injury. Fourteen patients with 11 acute and three chronic injuries underwent MR imaging. The anterior oblique ligament was the most commonly injured ligament, usually on the metacarpal side where it was disrupted, or allowed dislocation because of subperiosted stripping from the base of the thumb metacarpal. The dorsal radial ligament was occasionally avulsed or partially torn from the trapezoid. Following chronic injury, MR imaging can evaluate ligamentous laxity, ganglion cyst formation or osteoarthritis. Accurate evaluation of ligament injury may identify patients who would benefit from surgery.

Adult↗
PubMed2001

Early Oligocene initiation of North Atlantic Deep Water formation.

Dating the onset of deep-water flow between the Arctic and North Atlantic oceans is critical for modelling climate change in the Northern Hemisphere and for explaining changes in global ocean circulation throughout the Cenozoic era (from about 65 million years ago to the present). In the early Cenozoic era, exchange between these two ocean basins was inhibited by the Greenland-Scotland ridge, but a gateway through the Faeroe-Shetland basin has been hypothesized. Previous estimates of the date marking the onset of deep-water circulation through this basin-on the basis of circumstantial evidence from neighbouring basins-have been contradictory, ranging from about 35 to 15 million years ago. Here we describe the newly discovered Southeast Faeroes drift, which extends for 120 km parallel to the basin axis. The onset of deposition in this drift has been dated to the early Oligocene epoch ( approximately 35 million years ago) from a petroleum exploration borehole. We show that the drift was deposited under a southerly flow regime, and conclude that the initiation of deep-water circulation from the Norwegian Sea into the North Atlantic Ocean took place much earlier than is currently assumed in most numerical models of ancient ocean circulation.

Animals↗
PubMed2001

Delineation of functional regions within the subunits of the Saccharomyces cerevisiae cell adhesion molecule a-agglutinin.

a-Agglutinin from Saccharomyces cerevisiae is a cell adhesion glycoprotein expressed on the surface of cells of a mating type and consists of an anchorage subunit Aga1p and a receptor binding subunit Aga2p. Cell wall attachment of Aga2p is mediated through two disulfide bonds to Aga1p (Cappellaro, C., Baldermann, C., Rachel, R., and Tanner, W. (1994) EMBO J. 13, 4737-4744). We report here that purified Aga2p was unstable and had low molar specific activity relative to its receptor alpha-agglutinin. Aga2p co-expressed with a 149-residue fragment of Aga1p formed a disulfide-linked complex with specific activity 43-fold higher than Aga2p expressed alone. Circular dichroism of the complex revealed a mixed alpha/beta structure, whereas Aga2p alone had no periodic secondary structure. A 30-residue Cys-rich Aga1p fragment was partially active in stabilization of Aga2p activity. Mutation of either or both Aga2p cysteine residues eliminated stabilization of Aga2p. Thus the roles of Aga1p include both cell wall anchorage and cysteine-dependent conformational restriction of the binding subunit Aga2p. Mutagenesis of AGA2 identified only C-terminal residues of Aga2p as being essential for binding activity. Aga2p residues 45-72 are similar to sequences in soybean Nod genes, and include residues implicated in interactions with both Aga1p (including Cys(68)) and alpha-agglutinin.

Agglutinins↗
PubMed2000

Biodistribution and genetic stability of the novel antitumor agent VNP20009, a genetically modified strain of Salmonella typhimurium.

VNP20009 is a genetically modified strain of Salmonella typhimurium possessing an excellent safety profile, including genetically stable attenuated virulence (a deletion in the purI gene), reduction of septic shock potential (a deletion in the msbB gene), and antibiotic susceptibility. VNP20009 is genetically stable after multiple generations in vitro and in vivo. In mice, VNP20009 is rapidly cleared from the blood from a peak level of 1x104 cfu/mL to undetectable levels in 24 h. In tumor-bearing mice, VNP20009 accumulates preferentially in tumors over livers at a ratio of 1000&rcolon;1. In nonhuman primates, VNP20009 was also rapidly cleared from the blood, from a peak level of 1.0x106 cfu/mL to undetectable levels in 24 h. VNP20009 was detected in the liver, spleen, and bone marrow of monkeys; the amount decreased over time, and VNP20009 was cleared from all organs by day 41; no VNP20009 could be detected in the urine or feces of the monkeys. VNP20009 is genetically stable after many generations of growth (>140) both in vitro and in vivo.

Animals↗
PubMed1999

Prophylactic plating of the donor site of osteocutaneous radial forearm flaps.

We carried out a retrospective study of fracture morbidity of radial forearm osteocutaneous donor sites. During a period of three-and-a-half years, 12 patients had had composite flaps taken, and 5 of them had subsequently fractured the radius. We then elected to plate the radius prophylactically and found that over a period of just over two years, none of the 8 patients who had had prophylactic plating at the original harvesting operation had subsequently fractured the radius.

Adult↗
PubMed1999

Design of a clinical notification system.

We describe the requirements and design of an enterprise-wide notification system. From published descriptions of notification schemes, our own experience, and use cases provided by diverse users in our institution, we developed a set of functional requirements. The resulting design supports multiple communication channels, third party mappings (algorithms) from message to recipient and/or channel of delivery, and escalation algorithms. A requirement for multiple message formats is addressed by a document specification. We implemented this system in Java as a CORBA object. This paper describes the design and current implementation of our notification system.

Algorithms↗
PubMed1996

A phase I study of bi-weekly paclitaxel/cisplatin as initial therapy for advanced ovarian cancer. A study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Given the potential for improved outcomes, a phase I trial was initiated to develop a paclitaxel/cisplatin regimen that could be delivered every two weeks to women with newly diagnosed advanced ovarian cancer. PATIENTS AND METHODS: From 1992 to 1994, 29 (28 eligible) patients were enrolled in a dose-seeking trial. All received 60 mg/m2 of cisplatin preceded by paclitaxel infused over three hours. The paclitaxel dose was excalated from an initial level of 90 mg/m2 by 10 mg/m2 increments in successive cohorts of patients. RESULTS: At 120 mg/m2 of paclitaxel, the dose-limiting toxicity was granulocytopenia which prevented retreatment on time. The recommended dose level was therefore paclitaxel 110 mg/m2 infused over three hours with cisplatin 60 mg/m2, repeated bi-weekly for eight cycles. CONCLUSION: This bi-weekly schedule of paclitaxel/cisplatin provides no advantage in terms of dose-intensity nor total dose of paclitaxel in comparison to more common regimens given tri-weekly.

Adolescent↗
PubMed1995

Genetics of a-agglutunin function in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae cell adhesion protein a-agglutinin is composed of an anchorage subunit (Aga1p) and an adhesion subunit (Aga2p). Although functional a-agglutinin is expressed only by a cells, previous results indicated that AGA1 RNA is expressed in both a and alpha cells after pheromone induction. Expression of the Aga2p adhesion subunit in alpha cells allowed a-agglutinability, indicating that alpha cells express the a-agglutinin anchorage subunit, although no role for Aga1p in alpha cells has been identified. Most of the a-specific agglutination-defective mutants isolated previously were defective in AGA1; a single mutant (La199) was a candidate for an aga2 mutant. Expression of AGA2 under PGK control allowed secretion of active Aga2p from control strains but did not complement the La199 agglutination defect or allow secretion of Aga2p from La199, suggesting that the La199 mutation might identify a new gene required for a-agglutinin function. However, the La199 agglutination defect showed tight linkage to aga2::URA3 and did not complement aga2::URA3 in a/a diploids. The aga2 gene cloned from La199 was nonfunctional and contained an ochre mutation. The inability of pPGK-AGA2 to express functional Aga2p in La199 was shown to result from an additional mutation(s) that reduces expression of plasmid-borne genes. AGA2 was mapped to the left arm of chromosome VII approximately 28 cM from the centromere.

Base Sequence↗
PubMed1995

Targeted eradication of ovarian cancer mediated by intracellular expression of anti-erbB-2 single-chain antibody.

OBJECTIVE: Overexpression of the tyrosine kinase receptor erbB-2 is important in the pathogenesis of a variety of neoplasms including ovarian cancer. As a strategy to selectively eradicate erbB-2-overexpressing tumor cells, an anti-erbB-2 single-chain immunoglobin (sFv) gene was constructed to direct expression of intracellular anti-erbB-2 antibody. The purpose of this study is to establish the antitumorigenicity of this strategy in in vitro and in vivo models. METHODS: An anti-erbB-2 sFv construct containing an endoplasmic reticulum (ER)-directed leader sequence was transiently expressed in the human ovarian carcinoma cell line SKOV3 using the adenovirus-polylysine vector. SKOV3 cells transfected with a non-ER form of an anti-erbB-2 sFv construct or an irrelevant plasmid DNA served as controls. Antitumorigenicity, as measured by anchorage-independent growth in soft agar and subcutaneous (sc) tumor formation, was analyzed. The ability to achieve a biological effect with relevant sFv in murine orthotopic xenograft models and in primary human ovarian cancer cells was also evaluated. RESULTS: The ER form of anti-erbB-2 sFv was found to exert a marked antineoplastic effect on the SKOV3 cell line resulting in an arrest of anchorage-independent growth. A significant increase in sc tumor volume was noted in animals challenged with control constructs. In marked contrast, complete tumor eradication was noted at necropsy 80 days after sc transplantation in the group challenged with the ER-directed anti-erbB-2 sFv gene. Intraperitoneal treatment of malignant ascites in human tumor xenograft models with the ER form of the anti-erbB-2 sFv gene resulted in profound downregulation of cell surface erbB-2 in retrieved ovarian cancer cells. The ER-directed anti-erbB-2 sFv also elicited a significant cytotoxic effect in transfected primary ovarian cancer cells obtained from a patient with malignant ascites. CONCLUSION: The ability to selectively "knock out" erbB-2 demonstrates that this strategy can induce a significant antineoplastic effect in ovarian cancer cells overexpressing this growth factor receptor. In addition, the ability to accomplish selective abrogation of erbB-2 expression in animal treatment models and to transfect and eradicate primary ovarian cancer cells justifies further investigation of this novel strategy in ovarian cancer patients.

Animals↗
PubMed1995

Audit of post-operative auto-transfusion of shed blood in hip arthroplasty.

Auto-transfusion of shed blood for joint arthroplasty has several theoretical advantages: availability, compatibility, avoidance of transmission of infection and cost. The clinical records of 92 primary hip arthroplasties were reviewed to investigate the effect of auto-transfusion on the use of the National Blood Transfusion Service both in terms of blood ordered and subsequently used. Overall, post-operative auto-transfusion had no significant effect on blood ordering or usage and was very expensive. The majority of patients were over transfused.

Blood Loss, Surgical↗
PubMed1995

Effect of vitamin and trace element supplementation on immune indices in healthy elderly.

Aging is associated with a progressive decline in the immune system and a greater susceptibility to infection. This double-blind, placebo-controlled study, examined the effect of a vitamin and trace element supplement on immune responses of healthy, noninstitutionalized elderly subjects. Forty-seven subjects aged 61-79 years were randomly assigned to receive placebo or micronutrient supplementation for one year. Thirty-five individuals completed the one-year study. Immune function was assessed before and after the period of supplementation. Cell-mediated immune function assessed by the number of T cells and subsets remained constant in the supplemented group and there was a significant increase in CD57 natural killer cells. In contrast, a significant decrease in T cells, CD4 cells, and CD4: CD8 ratio was noted in the placebo group. Supplementation with micronutrients can play a crucial role in the maintenance of normal immune function in the elderly.

Aged↗