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Biomedical subjects

E Farrell

Publications and source records attributed to E Farrell.

At least 19 recordsLinked to original sources
PubMed2006

Influence of strong static magnetic fields on primary cortical neurons.

Intense uniform magnetic fields, such as those used in magnetic resonance imaging (MRI), are thought to exert little influence at the cellular level. Here we report modifications of the signaling cascades in rat cortical neurons cultured for 1 h in magnetic fields of up to 5 Tesla. The activation of c-Jun N-terminal kinase (JNK) increases monotonically with field strength, with a maximal activation of approximately 10% at 5 T, whereas the activation of extra cellular-regulated kinase (ERK) shows a maximum at 0.75 T ( approximately 10%). Since ERK is involved in cellular differentiation, these results indicate a magnetic induction of the signaling events associated with differentiation. However, the cells respond to further increases in field strength by evoking a stress response, since JNK is a stress-activated protein kinase. Three possible mechanisms are discussed and of these, the most plausible is magnetic field induced change in the membrane rest potential, a microscale magnetohydrodynamic effect. This mechanism most likely involves the activation of voltage dependent Ca(2+) channel opening; since intracellular Ca(2+) concentration was also found to be modified by the static magnetic field.

Animals↗
PubMed2005

Influence of different hormonal regimens on endometrial microvascular density and VEGF expression in women suffering from breakthrough bleeding.

BACKGROUND: The aim of this study was to quantify blood vessel density (BVD) and immunoreactive vascular endothelial growth factor (VEGF) levels in endometrial biopsies taken from women suffering breakthrough bleeding (BTB) under different exogenous hormonal regimes. METHODS: Endometrial biopsies from women in Melbourne with BTB were divided into four groups: combined-continuous hormone therapy (HT) (estrogen and progestin taken daily), cyclical HT (daily estrogen with progestin for 14 days each cycle), progestin-only, or no HT. Subjects from Barcelona were using the Mirena intrauterine levonorgestrel-releasing system for contraceptive purposes, with menstrual diaries for classification into four groups (amenorrhea, infrequent, regular and prolonged). Control biopsies from Melbourne were included in the study. Endometrial samples were immunostained for VEGF and blood vessel localization using an antibody to CD34. RESULTS: Results showed that BVD was significantly reduced in the progestin-only treated group compared with the other three treatment groups (P = 0.028). In addition, all four Mirena BTB groups had significantly reduced BVD compared with controls. Considerable heterogeneity was observed in VEGF immunostaining within and between individual samples with no major differences between HT or Mirena. CONCLUSION: These results provide strong evidence that unopposed progestins reduce endometrial BVD and that there is no link between VEGF immunostaining and BVD or BTB.

Adult↗
PubMed2005

Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet.

AIMS: The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring (ESTring) to that of a vaginal estradiol tablet (Vagifem) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency. Quality of life and acceptability of treatment delivery were also assessed. STUDY DESIGN: A prospective, randomized study in which women were assigned in a 2:1 ratio to ESTring and Vagifem and followed for 12 months. The primary endpoint was endometrial safety, based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48. Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3, 12, 24, 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline, 12 and 48 weeks. In addition, pelvic floor strength, vaginal cytological evaluation and pH, bacteruria and patient acceptability were assessed. Quality of life was assessed using a menopause-specific quality-of-life questionnaire and a 2-day bladder diary at baseline and 12 and 48 weeks. The comparability of the two groups was assessed using ANOVA, chi2 or Fisher's exact tests. RESULTS: A total of 126 women were randomized to ESTring and 59 to Vagifem. There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency. Maturation indices increased in both groups, from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks. After 48 weeks of treatment, there was no statistically significant difference in endometrial thickness between the two groups. A statistically smaller proportion of bleeding/spotting occurred in the ESTring group (n = 0) compared to the Vagifem users (n = 4). Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range. General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups. Bladder diary variables showed no differences between treatment groups. CONCLUSION: Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet.

Administration, Intravaginal↗
PubMed2004

Outcome after primary hemiarthroplasty for fracture of the head of the humerus. A retrospective multicentre study of 167 patients.

We have examined 167 patients who had a hemiarthroplasty for three- and four-part fractures and fracture-dislocations of the head of the humerus in a multicentre study involving 12 Austrian hospitals. All patients were followed for more than a year. Anatomical healing of the tuberosity significantly influenced the outcome as measured by the Constant score and subjective patient satisfaction. With regard to pain, the outcome was generally satisfactory but only 41.9% of patients were able to flex the shoulder above 90 degrees. The age of the patient and the type of prosthesis significantly influenced the healing of the tuberosity, but bone grafting did not. Achievement of healing of the tuberosity was inferior in institutions at which less than 15 hemiarthroplasties had been performed (Mann-Witney U test, p = 0.0001).

Adolescent↗
PubMed2001

Computed tomography and magnetic resonance imaging of the equine head.

Horses are frequently presented with clinical conditions warranting diagnostic imaging of the head. Unfortunately, evaluation of the equine head can be difficult using conventional radiography. The anatomic complexity and superimposition of the osseous, dental, and soft tissue structures complicate radiographic interpretation and diagnoses. Multiple radiographic projections may be necessary to image specific regions, and side-to-side comparison is often essential.

Animals↗
PubMed2001

Effect of hormone replacement therapies and selective estrogen receptor modulators in postmenopausal women with uterine leiomyomas: a literature review.

This systematic review examines current literature relating to clinical studies of hormone replacement therapy (HRT) and tibolone, including selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene, and their usage in postmenopausal women with fibroids. After a MEDLINE search, 28 relevant articles were found in total, of which five concerned randomized controlled trials. The results from class I studies and class II studies are evaluated in the categories of those that involved tibolone only, those that involved HRT only, and those that involved SERMs such as tamoxifen and raloxifene. In conclusion, tibolone has no significant effect on myoma size in postmenopausal women. There is myoma growth in postmenopausal women taking HRT. However, this does not appear to cause clinical symptoms.

Animals↗
PubMed2000

The number of CD34+ cells mobilized into the peripheral blood can predict the quality of subsequent collections.

PBPC were mobilized using a variety of chemotherapy regimens plus G-CSF in a group of 126 consecutive patients. Data are presented that show a close correlation between the number of CD34+ cells mobilized into the peripheral blood (PB) and the number of CD34+ cells subsequently collected by leukapheresis (R = 0.904). On the basis of this correlation, a regression formula was calculated that could give an estimate of the total number of CD34+ cells likely to be collected by leukapheresis from a given number of CD34+ cells per microliter PB. An easy-to-read table has been compiled to show how this type of analysis can be applied to predict the likely dose of CD34+ cells that will be obtained by leukapheresis over a wide range of patient weights.

Antigens, CD34↗
PubMed1997

CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens.

We have previously demonstrated that CD34+ cells, selected from peripheral blood progenitor cells (PBPC), can be expanded in ex vivo culture and can be infused in tandem with unmanipulated PBPC with little or no toxicity. In this study, four patients (two non-Hodgkin's lymphoma (NHL), two multiple myeloma (MM)) received myeloablative conditioning prior to stem cell rescue using ex vivo expanded cells alone. The two patients with NHL received cyclophosphamide and total body irradiation (CY/TBI) and the two patients with MM, busulphan and melphalan (Bu/M). One case received an inadequate CFU-GM dose, despite expansion, and in one case the expanded cells were contaminated. No definitive conclusions may therefore be drawn concerning engraftment in these two cases. However, the other two cases received high doses of committed progenitors. Following infusion of the expanded material, all four patients failed to show sustained neutrophil engraftment and none showed evidence of platelet engraftment. Back-up, unmanipulated PBPC were therefore infused on days 14, 34, 32 and 28 and subsequently all four cases achieved satisfactory engraftment of both neutrophils and platelets. In conclusion, we feel that, CD34+ cells, expanded ex vivo using the conditions described in this report, may not provide durable engraftment following fully myeloablative conditioning.

Adult↗
PubMed1997

CD34+ cells can be selected efficiently from cryopreserved peripheral blood progenitor cells and can retain their proliferative potential.

Hematopoietic stem and progenitor cells express the CD34 antigen. Techniques have been developed that enable purified populations of CD34+ cells to be selected from hematopoietic tissues. These selected CD34+ cells have several potential applications, including CD34 selection to obtain a tumor purging effect in autologous transplantation studies and using CD34+ cells as the starting cells for ex vivo expansion studies and as a vehicle for gene transduction protocols. We have investigated the feasibility of using cryopreserved peripheral blood progenitor cells (PBPC) for CD34 selection. Cells could be recovered from cryopreservation with good yields and high viability. After CD34 selection, the final product was, on average, 84% pure, with a recovery of 54%. These cells retained extensive proliferative potential, as demonstrated by ex vivo expansion culture. We believe that cryopreserved PBPC could be thawed, and CD34+ cells could be selected and used for transplantation following high-dose chemotherapy.

Blood Cell Count↗
PubMed1997

Peripheral blood progenitor cell mobilisation in patients with multiple myeloma following oral idarubicin and dexamethasone (Z-Dex) induction therapy.

Difficulties associated with current intensive induction regimens for multiple myeloma and uncertainty as to how to achieve optimal peripheral blood progenitor cell mobilisation (PBPC) prompted this study of an oral induction regimen, Z-Dex (oral idarubicin and dexamethasone) followed by PBPC mobilisation using four different regimens. Thirty-patients received Z-Dex (median age 56 years, range 46-66 years) including 24 patients with previously untreated disease. The overall response rate was 75% with a CR rate of 16.7% and PR rate of 75.7% in patients with previously untreated disease. We compared four mobilisation regimens: low-dose (LD) cyclophosphamide, high-dose (HD) cyclophosphamide, cis-platin/VP16 and cis-platin, Ara-C and dexamethasone (DHAP). Failure to mobilise optimal numbers of PBPCs (>1.0 x 10(6) CD34+ cells/kg and >20 x 10(4) CFU-GM/kg) was seen in two patients who received LD cyclophosphamide, in two patients who received HD cyclophosphamide and three patients who received cis-platin/VP16. No patient failed to mobilise adequate numbers of PBPCs following DHAP. In previously untreated patients, DHAP mobilised significantly more PBPC than LD cyclophosphamide (P=0.02), HD cyclophosphamide (P=0.0015) and cis-platin/VP16 (P=0.021). This study demonstrates the efficacy of Z-Dex in inducing tumour responses in patients with multiple myeloma without limiting PBPC mobilisation in subsequent dose-intensive schedules. Furthermore, we also demonstrate that DHAP is superior to cyclophosphamide (low- and high-dose) and cis-platin/VP16 in mobilising PBPCs and demonstrated a degree of tumour control.

Administration, Oral↗
PubMed1996

CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity.

PURPOSE: The objectives of this phase I study were to assess the feasibility of using cryopreserved peripheral-blood progenitor cells (PBPC) for large-scale CD34 selection and subsequent expansion, and the safety of their use for reinfusion following chemoradiotherapy. PATIENTS AND METHODS: For 10 patients with nonmyeloid malignancy, an aliquot from a PBPC harvest was recovered from liquid nitrogen, and CD34 selected using the Isolex system (Baxter Healthcare, Newbury, United Kingdom) and expanded for 8 days ex vivo in a medium free of animal proteins but supplemented with autologous serum, stemcell factor (SCF), interleukin-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin. RESULTS: The mean increase for cell number was 21-fold, for colony-forming units-granulocyte/macrophage (CFU-GM) 139-fold, and for burst-forming units-erythroid (BFU-E) 114-fold. The expanded cells were reinfused in tandem with unmanipulated material (> or = 25 x 10(4) CFU-GM/kg). The patients did not experience any adverse effects immediately on cell infusion or within 48 hours. The 10 index patients were compared with 10 historical controls for parameters of myelosuppressive morbidity. In this small study, there were no differences in either neutrophil or platelet recovery between the patients who received expanded cells and historical controls. CONCLUSION: These data demonstrate that CD34 cells can successfully be selected from cryopreserved material, expanded ex vivo on a large scale, and safely reinfused following myeloablative conditioning regimens.

Adolescent↗
PubMed1993

Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation.

OBJECTIVE: Although numerous trials have demonstrated the efficacy of exogenous surfactant for prophylaxis or treatment of neonatal respiratory distress syndrome (RDS), optimum timing of administration remains controversial. One previous study showed that administration of calf lung surfactant extract immediately following birth, to neonates born before 30 weeks postconceptional age, was preferable to delaying administration until after development of RDS. The current study was designed to test a similar hypothesis for babies born between 29 and 32 weeks gestational age. DESIGN: One thousand three hundred ninety-eight neonates with obstetric estimates of 29 through 32 weeks' gestation were randomized to receive CLSE at birth or to wait until development of mild RDS. After exclusions for malformations and other factors, data from 1248 were analyzed. RESULTS: Prophylaxis was associated with less development of moderate RDS (7% vs 12%), less need for retreatment (5% vs 9%), less need for mechanical ventilation or supplemental oxygen during the first 4 days, and fewer deaths or less requirement for supplemental oxygen at 28 days (5% vs 9%). Although 1-minute Apgar scores were significantly lower in the prophylaxis group, the difference disappeared by the 5-minute score and there was no difference in the incidence of asphyxia-related complications. Sixty percent of the neonates assigned to early treatment received endotracheal intubation and 43% received calf lung surfactant extract at a median age of 1.5 hours. When data were analyzed by gestational age and birth weight subgroups, most of the differences could be attributable to babies born at 30 weeks or less or weighing less than 1500 g, probably because of the higher incidence of surfactant deficiency in this more immature subgroup.

Drug Administration Schedule↗
PubMed1992

Treatment options and menopause regimens.

Treating a woman with menopausal or perimenopausal problems is rewarding nd challenging, aided these days by the range of hormones, hormone combinations and delivery systems available. Keeping the following points in mind should improve treatment outcomes: Careful pretreatment assessment. Explanation of benefits and risks. Individualise therapy. Allow about 6 months to stabilise therapy. Regular follow up. Oestrogen only therapy for the woman with a uterus. Combined continuous oestrogen-progestogen therapy await further studies. Continue progestogen therapy for 2 to 3 years after ceasing implant therapy in a woman with a uterus. Severe side effects of progestogen may necessitate oestrogen-only therapy, with regular yearly endometrial biopsy. Duration of therapy is variable, but it may be long term for maximal prevention.

Administration, Oral↗