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S E Jones

Publications and source records attributed to S E Jones.

At least 73 records · Page 4Linked to original sources
PubMed1998

Expression of alphaB-crystallin in a mouse model of inherited retinal degeneration.

AlphaB-crystallin, which is abundantly expressed in the lens but also in a diversity of other tissues, functions as a stress-inducible molecular chaperone and is increased in brain neurodegenerative diseases. We compared retinal alphaB-crystallin expression in a model of inherited retinal degeneration, the rd mouse, and controls. Northern and in situ hybridization analysis showed alphaB-crystallin mRNA to have an altered spatio-temporal pattern with increased levels localized to glial cells in the degenerative state. Immunocytochemistry confirmed increased expression at Müller cells and astrocytes, together with transiently increased localization to the degenerating photoreceptors. These findings suggest that increased alphaB-crystallin expression is associated with glial cell reaction to neuronal damage in the retina, and may comprise part of the retina's overall defensive response to the stress of apoptotic photoreceptor cell death.

Animals↗
PubMed1998

Expression of Pax-6 mRNA in the retinal degeneration (rd) mouse.

The homeobox gene Pax-6 is expressed during eye development in both the retina and lens, and Pax-6 mutations cause ocular abnormalities including retinal defects. We investigated the pattern of Pax-6 gene expression in the rd/rd mouse model of inherited retinal degeneration in comparison with nondegenerative controls, using Northern blot, reverse-transcription (RT)-PCR and in situ hybridization analysis. We observed an increased level of Pax-6 mRNA expression in the degenerative state, which appeared to affect equally the major Pax-6 exon 5a transcriptional splice variants as detected by RT-PCR. By in situ hybridization, Pax-6 mRNA was localized to the inner nuclear and ganglion cell layers of nondegenerative retina, but showed a more diffuse signal pattern in the rd/rd retina. This modulation of Pax-6 mRNA levels and localization is suggestive of activation of expression in retinal glial cells and may reflect reorganization of cellular interactions in response to the degenerative processes.

Animals↗
PubMed1998

Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Arimidex Study Group.

BACKGROUND: This report presents the results of a survival update based on the combined data from two studies that compared the efficacy and tolerability of anastrozole (1 or 10 mg once daily), a selective, nonsteroidal aromatase inhibitor administered orally, and megestrol acetate (40 mg 4 times daily) in the treatment of postmenopausal women with advanced breast carcinoma whose disease had progressed after treatment with tamoxifen. METHODS: Two randomized, parallel-group, multicenter trials were conducted, involving a total of 764 patients. The two trials were identical in design; both were double blind for anastrozole and open label for megestrol acetate. Overview analyses were conducted with the intent of strengthening the interpretation of results from each trial. The median follow-up duration for this survival update was 31 months. RESULTS: At the clinical dose of 1 mg daily, anastrozole demonstrated a statistically significant survival advantage over megestrol acetate, with a hazard ratio of 0.78 (P < 0.025)(0.60 < 97.5% confidence interval [CI] <1.0). The 1 mg anastrozole group also had a longer median time to death (26.7 months) compared with 22.5 months for the megestrol acetate group. The 10 mg anastrozole group also had a survival benefit over the megestrol acetate group, with a hazard ratio of 0.83 (P=0.09, not significant)(0.64 < 97.5% CI < 1.1). Higher 2-year survival rates were observed for both anastrozole treatment groups than for the megestrol acetate group (56.1%, 54.6%, and 46.3% for the groups given 1 mg anastrozole, 10 mg anastrozole, and megestrol acetate, respectively). CONCLUSIONS: This combined analysis of two trials of postmenopausal patients with advanced breast carcinoma has clearly demonstrated that, after disease progression with tamoxifen, treatment with anastrozole 1 mg once daily results in a statistically and clinically significant advantage over a standard treatment, megestrol acetate. This important benefit, in addition to the good tolerability profile of anastrozole, supports the use of this drug as a valuable new treatment option for this patient population.

Aged↗
PubMed1998

Inhibition of the rapid component of the delayed-rectifier K+ current by therapeutic concentrations of the antispasmodic agent terodiline.

Prolongation of the QT interval and malignant ventricular arrhythmia have been observed in patients administered terodiline for urinary incontinence. Since this adverse reaction might be caused by inhibition of delayed-rectifier K+ current (IK), we investigated whether clinically relevant (< or = 10 microM) concentrations of the drug modify IK in guinea-pig ventricular myocytes. Myocytes superfused with normal Tyrode's solution were pulsed from -40 mV to more positive test potentials (V) for 0.2 - 1 s to elicit tail IK on repolarization and measure tail IK-V relationships. IKr was distinguished from IKs by its sensitivity to the selective blocker E4031. Inhibition of IKr by 5 microM E4031 was completely occluded by pretreatment with 3 microM terodiline. In addition, action potential lengthening by E4031 in guinea-pig papillary muscles (29+/-3%) was abolished (3+/-2%) (P<0.001) by terodiline pretreatment. Inhibition of IKr by terodiline appeared to be voltage-independent, and the parameters of the Hill equation describing the inhibition were IC50 = 0.7 microM and nH = 1.6. High concentrations of the drug also affect IKs; in experiments with K+-free Tyrode's, 10 microM terodiline inhibited tail IKs by 27+/-3% (n=5) (P< 0.001). These data suggest that QT lengthening at therapeutic concentrations of the drug (approximately equal to 1.5 microM) is primarily due to inhibition of IKr. Inhibition of other K+ currents such as IKs is likely to be important at higher concentrations.

Action Potentials↗
PubMed1998

Low birth weight and cardiovascular disease: myth or reality?

The Barker hypothesis proposes a link between low birth weight and adulthood cardiovascular disease. Recent studies have cast doubt on this hypothesis whilst others have proposed an effect of maternal birth weight that may extend to future generations. Thus, the debate on the effect of birth weight in cardiovascular disease continues.

Adult↗
PubMed1998

Domiciliary nocturnal intermittent positive pressure ventilation in patients with respiratory failure due to severe COPD: long-term follow up and effect on survival.

BACKGROUND: There is increasing interest in the use of non-invasive nocturnal intermittent positive pressure ventilation (NIPPV) in the management of patients with chronic hypercapnoeic (type II) respiratory failure. Although this treatment enables patients requiring mechanical ventilatory support to the treated more readily at home, few studies have been done to demonstrate its long term benefits in chronic obstructive pulmonary disease (COPD) and the application of NIPPV in these circumstances remains controversial. METHODS: Eleven patients in severe stable chronic type II respiratory failure due to COPD who were unresponsive to conventional treatments experienced symptomatic hypercapnia when receiving sufficient supplementary oxygen to result in an arterial oxygen saturation (SaO2) of > 90%. They were assessed for treatment with NIPPV, and its effects were observed for over two years using arterial blood gas tensions, spirometric parameters and body mass index (BMI), survival, hospital admissions, use of general practitioner resources, and patient satisfaction. RESULTS: Hospital admissions and GP consultations were halved after one year compared with the year before NIPPV and there was a sustained improvement in arterial blood gas tensions at 12 and 24 months when breathing air, despite progressive deterioration in ventilatory function. BMI did not change during the period of observation. The median survival was 920 days, with no patient dying within the first 500 days. CONCLUSIONS: Domiciliary NIPPV results in improvements in arterial blood gas tensions which are sustained after two years of treatment and reduces both hospital admissions and general practitioner visits by patients with severe COPD in hypercapnoeic respiratory failure. It is well tolerated and, although there was no control group, survival appears to be prolonged when these results are compared with those of the NOTT and MRC (LTOT) trials.

Aged↗
PubMed1998

A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer.

PURPOSE: To evaluate the efficacy and safety of docetaxel in patients with paclitaxel-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Docetaxel (100 mg/m2) was administered every 3 weeks to 46 patients registered at four centers. Patients had previously received < or = two chemotherapy regimens for MBC. All patients had progressive disease while receiving paclitaxel therapy. Treatment was repeated until there was evidence of disease progression or for a maximum of three cycles after best response. RESULTS: Objective responses were seen in eight of 44 assessable patients (18.1%; 95% confidence interval [CI], 6.7% to 29.5%). Seven patients had partial responses and one patient responded completely. Response rates were not significantly different by previously received paclitaxel dose or resistance. No responses were seen in 12 patients who had previously received paclitaxel by 24-hour infusion, but the response rate in 32 patients who had received paclitaxel by 1- to 3-hour infusion was 25%. The median response duration was 29 weeks and the median time to disease progression was 10 weeks. Median survival was 10.5 months. Clinically significant (severe) adverse events included neutropenic fever (24% of patients), asthenia (22%), infection (13%), stomatitis (9%), neurosensory changes (7%), myalgia (7%), and diarrhea (7%). CONCLUSION: Docetaxel is active in patients with paclitaxel-resistant breast cancer, particularly in those who failed to respond to brief infusions of paclitaxel. Response rates were comparable to or better than those seen with other therapies for patients with paclitaxel-resistant MBC. This confirms preclinical studies, which indicated only partial cross-resistance between paclitaxel and docetaxel.

Adult↗
PubMed1997

Localization of tissue inhibitor of metalloproteinases-3 in neurodegenerative retinal disease.

Tissue inhibitor of metalloproteinases-3 (TIMP-3) is one of a family of genes whose products are implicated in the regulation of remodelling of the extracellular matrix. The level of mRNA coding for TIMP-3 is increased in retinas affected by the photoreceptor degenerative disease, simplex retinitis pigmentosa (RP), and mutations in TIMP-3 are associated with an inherited form of macular dystrophy. Here we compare TIMP-3 protein expression in normal retina and in those affected by RP and by age-related macular degeneration. Immunoreactive TIMP-3 is present in normal retinal pigment epithelium, and in degenerative retinas particularly at Bruch's membrane and additionally in photoreceptor-retaining regions in simplex RP. The pattern suggests a role for TIMP-3 in normal retinal homeostasis, and, in the disease state, in the modulation of extracellular matrix metabolism and neovascularization.

Aged↗
PubMed1997

A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Arimidex Study Group.

BACKGROUND: Anastrozole is a new oral aromatase inhibitor with highly potent and selective activity for the aromatase enzyme. In a Phase III trial, the efficacy and tolerability of anastrozole, given in doses of 1 and 10 mg orally once daily, and megestrol acetate, given in doses of 40 mg orally 4 times daily, were compared in 386 postmenopausal women with advanced breast carcinoma who progressed after tamoxifen therapy. METHODS: The trial was randomized, double blind for anastrozole, open label for megestrol acetate, parallel group, and multicenter. Patients were randomly assigned to receive anastrozole, 1 mg (n = 128); anastrozole, 10 mg (n = 130); or megestrol acetate (n = 128). The primary efficacy measures were time to progression and tumor response; secondary measures were time to treatment failure, duration of response, quality of life, and time to death. RESULTS: With a median duration of follow-up of 6 months, there was no statistical evidence of a difference between either 1 or 10 mg doses of anastrozole and megestrol acetate for any efficacy endpoint. According to rigid response criteria, 10%, 6%, and 6% of patients in the anastrozole 1 mg, anastrozole 10 mg, and megestrol acetate groups, respectively, had an objective response (complete response or partial response) and 27%, 24%, and 30% of patients in the respective groups had stable disease for a duration of 24 weeks or longer. Quality-of-life assessments revealed that anastrozole in a 1-mg dose was associated with better physical scores and anastrozole in a 10-mg dose with better psychologic scores than megestrol acetate. Both anastrozole and megestrol acetate were generally well tolerated. Among anticipated adverse events, gastrointestinal disturbance was more common among patients in the anastrozole groups, whereas weight gain occurred more frequently among patients in the megestrol acetate groups. Weight increases of 5% or more and 10% or more were more common among megestrol acetate-treated patients; moreover, patients in this group continued to gain weight over time. CONCLUSIONS: Anastrozole, given in doses of 1 and 10 mg once daily, represents a well tolerated and effective therapeutic option for the treatment of postmenopausal women with advanced breast carcinoma who progress after tamoxifen treatment.

Adult↗
PubMed1997

Guidelines for systemic therapy of early stage breast cancer.

Optimal treatment of early stage breast cancer remains an active area of study. An expert multidisciplinary committee reviewed clinical data on systemic therapy for early stage, stage I and II breast cancer. Guidelines for treatment were developed for Texas Oncology. P.A., the largest private practice group of oncologists in the United States. This group of physicians treats approximately 5000 new breast cancer patients each year and has a major impact on oncology care in the state of Texas. These guidelines identify prognostic factors which help the practitioner in choosing treatment for patients. Subsets of patients are identified for whom no systemic therapy is warrented. Standard chemotherapy and hormonal therapy regimens are outlined for patients with early stage disease at increased risk for relapse. Dose intensification for high risk stage II patients is reviewed. Timing of therapy and the sequencing of chemotherapy and radiation therapy is addressed. Strategies for the follow-up of patients with a history of breast cancer are outlined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy.

BACKGROUND: A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim (r-metHuG-CSF) on hematologic recovery following chemotherapy. PATIENTS AND METHODS: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment. Chemotherapy was delivered on days 1-3 of each 21-day cycle with Filgrastim initiated at 5 micrograms/kg/day subcutaneously (SC) beginning on day 4, day 6, or day 8 and continuing until post-nadir neutrophil recovery. RESULTS: During the first cycle of chemotherapy, the duration of neutropenia was similar for all three schedules; however, the pattern of absolute neutrophil count (ANC) recovery differed. In subsequent cycles of treatment, an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy. By contrast, patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one. Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment. CONCLUSION: Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery. Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6. Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery. Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered.

Adult↗
PubMed1997

Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration.

Knowledge of the mutations leading to inherited retinal degenerations provides a foundation for the development of somatic gene therapy in which potentially corrective genes are transferred to the target photoreceptor cells. Towards this end, we have evaluated the efficacy of a recombinant adeno-associated virus (AAV) vector to deliver and express the correct form of the cGMP phosphodiesterase-beta (PDE-beta) gene in the retinas of rd mice, which suffer rapid retinal degeneration due to recessive mutation in the endogenous gene. A truncated murine opsin promoter was used to drive expression of the PDE-beta cDNA. Following intraocular injection of AAV. PDE-beta, increased retinal expression of immunoreactive PDE protein was observed, including within photoreceptor cell bodies. Compared with age-matched controls, treated eyes showed increased numbers of photoreceptors and a two-fold increase in sensitivity to light as measured by in vitro electroretinography. These findings provide evidence that rescue of functional photoreceptor neurons can be achieved by somatic gene therapy.

Animals↗
PubMed1997

Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer.

PURPOSE: To determine the cardioprotective effect of dexrazoxane (DZR) used in a doxorubicin-based combination therapy in advanced breast cancer. PATIENTS AND METHODS: Between November 1988 and January 1991, 534 patients with advanced breast cancer were randomized to two multicenter, double-blind studies (088001 and 088006). Patients received fluorouracil, doxorubicin, and cyclophosphamide (FAC) with either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3 weeks and were monitored with serial multiplegated acquisition (MUGA) scans. RESULTS: The hazards ratio (HR) of PLA to DZR for a cardiac event, which was predefined ejection fraction changes or congestive heart failure (CHF), was 2.63 (95% confidence interval [CI], 1.61 to 4.27; P < .001) for 088001 and 2.00 (95% CI, 1.01 to 3.96; P = .038) for 088006. The objective response rates for 088001 were 46.8% for DZR and 60.5% for PLA, a difference of 14% (95% CI, -25% to -2%; P = .019), and for 088006 were 53.7% for DZR and 49.3% for PLA, a difference of 4% (95% CI, -13% to 22%; P = .63). Time to progression and survival were not significantly different between treatment arms in either study. Toxicities on the DZR arms included lower granulocyte and platelet counts at nadir (P = .009 and P = .004, respectively) and more pain on injection (P = .001), with no difference in the rates of fever, infection, or hemorrhage. CONCLUSION: DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF. One of the two studies (088001) showed a lower response rate with DZR, but time to progression and survival were not significantly different. DZR is the first agent shown to reduce cardiotoxicity from doxorubicin.

Aged↗
PubMed1997

Computers in the operating room: the staff nurse perspective.

Computers and information management are long-standing tools for the Perioperative Manager. As paperless nursing documentation makes its way into the operating room, the staff nurse must become adept at the use of the computer. How to get the staff nurse comfortable with this new role, and concerns the staff nurse may voice are the subject of this article.

Attitude to Computers↗
PubMed1997

Breaking down barriers: multidisciplinary education model.

A pilot project was implemented involving students from three disciplines: dental hygiene, physical therapy, and physician assistant. The purpose was to prepare students to work together in multidiscipline teams utilizing concepts of problem-based learning (PBL) on both simulated and real patients. The project was divided into three phases. Phase I introduced discipline specific information, team concepts, and PBL concepts. Phase II involved students working in multidisciplinary teams solving a simulated patient case in the PBL format. Phase III consisted of students working in small groups and on real patients, performing an extraoral/intraoral and periodontal examination, a problem oriented physical examination, and a neuromuscular assessment. Pre and posttest evaluation of Phase I revealed no difference in knowledge among the three disciplines. Of those students evaluating Phase II and III, 100% felt PBL was an effective means of presenting multidisciplinary material; 93% reported enhanced problem-solving; 98% indicated improvements in working in groups; and 98% felt they had learned more about each other's discipline. This model may provide a viable means to prepare interdisciplinary teams to work effectively together.

Adult↗