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Biomedical subjects

C Farrell

Publications and source records attributed to C Farrell.

At least 37 records · Page 2Linked to original sources

The benefits of a partnership approach to disability management.

Taking a partnership approach to disability management and fostering a return-to-work culture can significantly reduce disability costs for employers and help disabled employees successfully return to work. Two rehabilitation case managers from ReliaStar Life Insurance Company share their perspective and experience, including three case studies that illustrate successful case management intervention and return-to-work strategies.

Cost-Benefit Analysis↗

Rapid identification of a novel chondrocyte-specific gene by RNA differential display.

Differential display or RNA fingerprinting is a novel approach for the isolation of differentially expressed genes. Here we describe the application of the RNA differential display technique to the analysis of the genes expressed in chick embryonic sternal chondrocytes, fibroblasts and BrdU-treated chondrocytes, which dedifferentiate back to mesenchymal-like phenotype. Parallel display among the genetags allowed us to isolate seven clones with differential expression patterns. Nucleotide sequencing of one of these clones revealed that it is a novel developmentally regulated gene with no significant homology to those reported previously. An RT-PCR analysis, using primers derived from this novel clone, confirmed the presence of the corresponding RNA only in the untreated chondrocytes, and not in the BrdU-treated chondrocytes or fibroblasts. This confirmation of the expression pattern given by the differential display reinforces the reliability of this approach. These results indicate that the differential display analysis provides a rapid and effective way to identify novel differentially expressed genes during chondrogenesis.

Animals↗

Treatment of purpura fulminans in meningococcemia with protein C concentrate.

OBJECTIVE: To evaluate the clinical and laboratory effects of protein C concentrate as an adjunct to conventional therapy in the treatment of meningococcemia with purpura fulminans. DESIGN: Case series (pilot study). SETTING: Intensive care unit in a tertiary care pediatric hospital. PATIENTS: Four children (aged 3 months to 15 years) requiring intensive treatment for meningococcemia with shock, disseminated intravascular coagulation, and purpura fulminans. INTERVENTION: Intravenous administration of a protein C concentrate (100 IU/kg every 6 hours). MAIN OUTCOME MEASURES: Plasma protein C amidolytic activity, fibrinogen, and D-dimers; evolution of skin and limb lesions. RESULTS: Treatment with protein C concentrate led to a rise in plasma protein C activity levels to within normal limits in all patients, associated with an increase in plasma fibrinogen and a bimodal decrease in D-dimers. No adverse effects were noted. All patients had reversal of organ dysfunction despite the severity of the initial illness. Two patients recovered completely with no sequelae; two required amputations. CONCLUSIONS: These encouraging clinical and laboratory results and the absence of side effects warrant the initiation of a double-blind, randomized controlled multicenter trial to determine the role of protein C replacement in the treatment of meningococcemia-associated purpura fulminans.

Adolescent↗

Cytotoxic T lymphocyte precursor frequency does not correlate with either the incidence or severity of graft-versus-host disease after matched unrelated donor bone marrow transplantation.

BMT from matched unrelated donors or mismatched family members is associated with an increased risk of graft-versus-host disease (GVHD) compared with HLA-identical sibling donors. It has been suggested that the level of patient-specific CTL precursors (CTLp) present in matched unrelated donors correlates with the incidence and severity of GVHD after BMT. This study group consisted of 17 patients who all received unmanipulated bone marrow from an HLA-A,B,DR-matched unrelated donor. Patient-specific CTLp frequencies were estimated in the donor before transplant. The CTLp frequencies were then compared with the incidence and severity of GVHD experienced by the patient after transplantation. Statistical analysis revealed no correlation between donor precursor frequencies and the patient developing clinically significant acute GVHD after transplantation (X2 = 1.16). This study suggests that caution should be used before the inclusion of the CTLp frequency result in the clinical decision of selecting the most suitable matched unrelated donor for BMT. CTLp frequency does not correlate with either the incidence or severity of GVHD after matched unrelated donor BMT.

Bone Marrow Transplantation↗

Enzyme linked immunosorbent assay for ceftazidime in airborne samples.

A simple and rapid enzyme linked immunosorbent assay (ELISA) method for the cephalosporin, ceftazidime, has been developed for the quantification of this antibiotic in solutions that have been eluted from filters following the capture of air samples in the workplace. The assay has the specificity, sensitivity and precision necessary for its use in determining airborne concentrations of ceftazidime in the workplace as part of an occupational health and hygiene programme.

Air Pollutants, Occupational↗

Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes.

Tight junctions between endothelial cells of brain capillaries are the most important structural elements of the blood-brain barrier. Cultured brain endothelial cells are known to loose tight junction-dependent blood-brain barrier characteristics such as macromolecular impermeability and high electrical resistance. We have directly analyzed the structure and function of tight junctions in primary cultures of bovine brain endothelial cells using quantitative freeze-fracture electron microscopy, and ion and inulin permeability. The complexity of tight junctions, defined as the number of branch points per unit length of tight junctional strands, decreased 5 hours after culture but thereafter remained almost constant. In contrast, the association of tight junction particles with the cytoplasmic leaflet of the endothelial membrane bilayer (P-face) decreased continuously with a major drop between 16 hours and 24 hours. The complexity of tight junctions could be increased by elevation of intracellular cAMP levels while phorbol esters had the opposite effect. On the other hand, the P-face association of tight junction particles was enhanced by elevation of cAMP levels and by coculture of endothelial cells with astrocytes or exposure to astrocyte-conditioned medium. The latter effect on P-face association was induced by astrocytes but not fibroblasts. Elevation of cAMP levels together with astrocyte-conditioned medium synergistically increased transendothelial electrical resistance and decreased inulin permeability of primary cultures, thus confirming the effects on tight junction structure and barrier function. P-face association of tight junction particles in brain endothelial cells may therefore be a critical feature of blood-brain barrier function that can be specifically modulated by astrocytes and cAMP levels. Our results suggest an important functional role for the cytoplasmic anchorage of tight junction particles for brain endothelial barrier function in particular and probably paracellular permeability in general.

Animals↗

Thalidomide, pregnancy and renal failure.

A 26-year-old woman with upper limb phocomelia as a result of thalidemide embryopathy developed renal failure that required dialysis during pregnancy. The pregnancy was complicated by dialysis difficulties, uncontrollable hypertension and deteriorating renal function resulting in fetal loss at 26-weeks' gestation. The patient was left with end-stage renal failure and recently has undergone cadaveric renal transplantation. This case highlights the widespread effects, including urinary-tract abnormalities, that thalidomide may have and illustrates the peculiar difficulties in managing such a patient during and after pregnancy.

Adult↗

The Na+-Ca2+ exchange system in vascular smooth muscle cell membrane vesicles isolated from cultured cells and from tissue is similar.

The existence of a Na+-Ca2+ exchange system was investigated in sarcolemmal vesicles isolated from cultured cells of dog mesenteric artery. When Na+-loaded membrane vesicles were suspended in a Na+-free KCl medium to create an outwardly directed Na+ concentration gradient across the membrane, a time-dependent uptake of Ca2+ was observed. This uptake of Ca2+ was drastically reduced when the vesicles were suspended in NaCl medium to eliminate the Na+ concentration gradient across the membrane. Monensin also decreased Ca2+ uptake in Na+-loaded vesicles. The apparent Km for Ca2+ was 2.97 microM and the apparent maximum velocity was 4.27 nmol/min per mg protein. The data indicate that a Na+-Ca2+ exchange system exists in sarcolemmal membranes isolated from cultured cells and that it is similar to the system in membranes isolated from the tissue.

Animals↗

Surveillance for stage I non-seminomatous germ cell tumours of the testis: the optimal protocol has not yet been defined.

Forty-six patients with clinical stage I testicular non-seminomatous germ cell tumours were followed up according to a protocol of active surveillance between 1979 and 1987. The median follow-up time was 40+ months. Thirteen patients (28%) relapsed, predominantly in retroperitoneum and/or lung. Ten of these relapses (76%) occurred within 8 months of orchiectomy. Relapses occurred in 7/35 T1 tumours and 5/10 T2 to T4 tumours. No correlation was detected between the histological type and relapse rate. Three late relapses were diagnosed at 23, 29 and 36 months. Eleven of the relapsed patients remain in prolonged complete remission after PVB chemotherapy +/- surgery; one patient, who initially refused treatment at the time of relapse, has died. Another relapsed with predominant elements of rhabdomyosarcoma intermingled with malignant teratoma in a bone metastasis. He had a partial response to PVB chemotherapy but subsequently died. Thirty-four patients (74%) did not undergo lymphography (LG) and had a higher relapse rate (11/34) than those who had LG (2/12); this was not a statistically significant difference in this small series. The policy of active surveillance is not yet the "state of the art" and should be under constant scrutiny with respect to safety and practice.

Adult↗