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Biomedical subjects

J Murphy

Publications and source records attributed to J Murphy.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

Electric Stimulation Therapy↗
PubMed2000

The inflammatory response within Dukes' B colorectal cancers: implications for progression of micrometastases and patient survival.

OBJECTIVES: The aim of this study was to determine the relationship between the inflammatory response in primary colorectal carcinomas, patient outcome, and the fate of bone marrow micrometastases. METHODS: The populations studied were a) 155 consecutive patients with Dukes' B colorectal cancer and follow-up for a mean of 5 yr, from the Mercy Hospital, Cork, and b) 260 consecutive patients with rectal carcinoma Dukes' B and follow-up for >10 yr, from St. Mark's Hospital, London. The primary tumor was assessed for the Jass and "Crohn's-like" lymphoid reactions. In 36 consecutive patients, bone marrow aspirates were examined for micrometastases before and > or = 6 months postoperatively. RESULTS: The relationship between prognosis and the inflammatory reactivity in the tumors was similar in both populations. In the Mercy group there were two deaths among 40 patients who had coexistent Jass and Crohn's-like infiltrates. This contrasted with 25 deaths among 58 patients in whom both infiltrates were absent (p < 0.005). Results were intermediate in cases in which either type of inflammatory reaction was present alone. In the St. Mark' s patients similar prognostic differences were sustained for up to 10 yr. Bone marrow micrometastases were present in 12/36 patients preoperatively and in 14/36 postoperatively. Seven of 12 patients with preoperative micrometastases were negative postoperatively, indicating clearance of tumor cells. Nine of 24 who tested negative preoperatively had micrometastases postoperatively. The clearance and presence of postoperative micrometastases was related to the immunological responses in the primary tumor. CONCLUSIONS: These results demonstrate an association between the inflammatory reaction, prognosis, and clearance of micrometastases, indicating a systemic antitumor reaction that confers a survival advantage.

Aged↗
PubMed2000

Development of a brief screening instrument: the HANDS.

BACKGROUND: The present study was designed to develop a briefer screening scale of approximately 10 items which maintained the validity of the Zung Self-Rating Depression Scale in a sample similar to that attending National Depression Screening Day (NDSD), as well as a more general audience. METHODS: We first administered 70 items from a variety of existing rating scales to 40 subjects who answered an ad for depressed subjects and 55 who answered an ad for non-depressed subjects, all of whose diagnoses were confirmed by the Structured Clinical Interview for DSM-IV (SCID). Based on the correlation between each item and the diagnostic criterion, we reduced the number of items to 17 which we then administered to another 45 subjects who answered an ad similar to that used for NDSD and also underwent a SCID interview. Based on these results, we arrived at the final 10-item Harvard Department of Psychiatry/NDSD scale (HANDS) with the assistance of the item-response theory. The items are scored for frequency of occurrence of each symptom over the past 2 weeks. Total scores range from 0 to 30. RESULTS: The 10-item scale (HANDS) has good internal consistency and validity: a cutpoint score of 9 or greater gave sensitivity of at least 95% in both studies. Although specificity was lower for all scales in the self-selected population, the HANDS performed at least as well as the 20-item Zung Scale, the 21-item Beck Depression Inventory-II and the 15-item Hopkins Symptom Depression Checklist. CONCLUSION: The 10-item HANDS performs as well as other widely used longer self-report scales and has the advantage of briefer administration time.

Adolescent↗
PubMed2000

Effects of gonadal steroids in women with a history of postpartum depression.

OBJECTIVE: Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression. METHOD: The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales. RESULTS: Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline. CONCLUSIONS: The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.

Adult↗
PubMed2000

Evaluation of the predictive value of Her-2/neu overexpression and p53 mutations in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE: To ascertain the predictive value of Her-2/neu overexpression and p53 mutations, assessed by immunohistochemistry, in high-risk primary breast cancer (HRPBC) treated with high-dose chemotherapy (HDCT). PATIENTS AND METHODS: We obtained paraffin-embedded tumor blocks from 146 HRPBC patients previously enrolled at our program onto clinical trials of HDCT for four to nine involved axillary lymph nodes, > or = 10 involved axillary nodes, or inflammatory carcinoma. All patients received the same HDCT regimen, with cyclophosphamide, cisplatin, and carmustine (STAMP-I), followed by autologous stem-cell transplantation. Median follow-up was 42 months (range, 5 to 90 months). The same pathologist, blinded to clinical outcome, reviewed all immunostained slides. RESULTS: Positive results for Her-2/neu and p53 were found in 44.5% and 34% of the patients, respectively. Positivity for Her-2/neu was significantly associated with increased risk of relapse and death. No correlation was found between p53 mutations and relapse-free survival (RFS) or overall survival (OS). Multivariate analyses included Her-2/neu overexpression and the following variables previously identified as independent predictors of outcome in this population: tumor size, nodal ratio (number of involved nodes/number of dissected nodes), and hormone receptor status. All four variables had independent value. CONCLUSION: Her-2/neu overexpression is an independent negative predictor of RFS and OS in HRPBC treated with HDCT. Its inclusion in our previously described predictive model increases the predictive capacity of this model for the low-risk subgroup. In contrast, p53 mutations lack predictive value in this setting.

Adult↗
PubMed2000

Improved platelet counting using two-dimensional laser light scatter.

Clinical management of platelet disorders depends on accurate platelet counts. We evaluated a new analytic approach for platelet counting based on improved platelet discrimination. Current automated counting methods provide accurate platelet counts for most samples but often are unable to discriminate platelets accurately from nonplatelet particles such as microcytic RBCs, RBC fragments, and cellular debris that may falsely elevate platelet counts. The new approach measures 2 light-scatter angles of platelets and nonplatelet particles as they pass through a laser beam. The volume and refractive index of each platelet and particle are derived from the light-scatter measurements using the Mie scattering theory. Together, these 2 measurements provide improved platelet discrimination compared with 1-dimensional methods. With its improved discrimination, 2-dimensional platelet analysis provides more accurate platelet counts in samples containing interfering particles and may contribute to more effective clinical management of patients with platelet disorders.

Blood Platelet Disorders↗
PubMed2000

Testing control of radiation-induced diarrhea with a psyllium bulking agent: a pilot study.

Sixty cancer patients who were undergoing radiation therapy to the pelvis of at least 4,000 cGy in 20 fractions over four weeks were randomized to take or not take Metamucil. Results were analyzed for the presence of radiation-induced diarrhea in two groups: patients taking Metamucil (n = 30) or not taking Metamucil (n = 30). The Murphy Diarrhea Scale was developed to assist in the synthesis of data collected in daily patient-reported diaries. Results were analyzed using ANOVA F-tests. Metamucil significantly decreased the incidence (p = 0.049) and severity (p = 0.030) of diarrhea and showed a strong trend in reducing the use of anti-diarrhea medication (p = 0.062). According to this pilot study, Metamucil was an effective method of controlling radiation-induced diarrhea. Results of this pilot study have implications for clinical practice and nursing research.

Aged↗
PubMed2000

A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma.

The use of interleukin-2 (IL-2) and interferon-alpha (IFNalpha) in combination with chemotherapy for the treatment of advanced malignant melanoma has generated considerable interest. In particular, the relatively high number of durable complete responses has suggested this may be a significant advance in the treatment of malignant melanoma. We report our experience at the University of Colorado in 43 patients, including many with poor prognostic factors. Patients received cisplatin 20 mg/m2 on days 1-4, vinblastine 1.6 mg/m2 on days 1-4, dacarbazine 800 mg/m2 on day 1, IL-2 9 x 10(6) IU/m2 per day intravenously over 24h on days 1-4 and IFNalpha 5 x 10(6) IU/m2 per day subcutaneously on days 1-5 every 3 weeks. The median follow-up for all patients was 34 months. Responses were seen in 20 patients (47%, 95% confidence interval 31-62%) and comprised five complete responses (CRs) (12%) and 15 partial responses (PRs) (35%). Two patients achieving a CR remain disease free at 45 and 47 months follow-up. In addition three patients who obtained a surgical CR and another with only minor residual changes on computed tomography scan have not progressed at 27, 30, 40 and 27 months, respectively. Toxicity was manageable, but all patients had at least one grade 3 or 4 toxicity, predominantly hypotension and neutropenia. There were no treatment-related deaths. In conclusion, the response rate and duration is within the range previously reported for biochemotherapy. The results of ongoing randomized studies are awaited to better define the value of biochemotherapy in the treatment of advanced melanoma.

Abdominal Neoplasms↗
PubMed2000

A phase I/II trial of paclitaxel, carboplatin, and gemcitabine in untreated patients with advanced non-small cell lung cancer.

Paclitaxel and carboplatin is widely used in the treatment of patients with advanced non-small cell lung cancer (NSCLC); however, median survival remains < 1 year. One strategy to improve survival is to add a third active drug with a differing mechanism of action. Gemcitabine is a novel antimetabolite with considerable activity in NSCLC. The primary objective of this Phase I/II study was to determine the maximally tolerated dose of gemcitabine administered with fixed doses of paclitaxel and carboplatin in untreated patients with advanced NSCLC.

Adenocarcinoma↗
PubMed2000

Pathogenesis I: interactions of host cells and fungi.

The interactions of host cells and fungi during infection represent a complex interplay. Although T helper 1 (Th1)-mediated immunity is primarily responsible for acquired resistance to Paracoccidioides brasiliensis, studies have demonstrated that polymorphonuclear neutrophils play a critical role in providing an early resistance to this organism. One study has shown that the invasiveness of Candida albicans requires adherence, particularly to endothelial cells, which in turn are stimulated to express various cell-markers and pro-inflammatory cytokines as part of a proactive resistance to invasion. Somewhat in contrast to infection with C. albicans, it has been shown that the capsular glucuronoxylomannan of Cryptococcus neoformans causes the shedding of host-cell adherence molecules (L-selectins) needed for the migration of host-inflammatory cells to sites of infection and likely explains, in part, the reduced host inflammatory response to this organism. Resistance to aspergillosis is often associated with the immune status of the host. In one set of studies, it has been demonstrated that lymphocytes have little direct effect on the organism, but that antigen-presenting dendritic cells stimulate the production of Th1 cytokines, suggesting a positive role for the dendritic cell in host-response. Similarly, another study has shown that among the regulatory cytokine networks that Th2-associated cytokines (e.g., interleukin-10) likely play a detrimental role in the resistance of the host to Aspergillus fumigatus.

Animals↗
PubMed1999

Preparative chromatographic resolution of enantiomers using polar organic solvents with polysaccharide chiral stationary phases.

The preparative chromatographic resolution of racemic mixtures is rapidly becoming a standard approach for the generation of enantiomers in pharmaceutical research and development. This paper will discuss the optical resolution of numerous pharmaceutical intermediates and final products using polar organic solvents with polysaccharide chiral stationary phases. The advantages of this approach compared to more traditional mobile phases for preparative separations will be presented. In addition the ability to reverse elution order using polar organic solvents will be presented.

Chromatography, High Pressure Liquid↗
PubMed1999

Is radical trachelectomy a safe alternative to radical hysterectomy for patients with stage IA-B carcinoma of the cervix?

BACKGROUND: The prognosis associated with lymph node negative, early stage carcinoma of the cervix is excellent, with 5-year survival rates greater than 90%. Radical trachelectomy in combination with pelvic lymph node dissection (RVT + LPL) has emerged as an alternative to radical hysterectomy (RH) for these patients who desire preservation of fertility. However, there are limited data to support its efficacy and safety. METHODS: All patient information was collected prospectively and was subsequently extracted from the cervical cancer surgery database of the Division of Gynecologic Oncology at the University of Toronto. Patients treated by RVT + LPL for fertility preservation were compared with two groups of patients treated by RH. One control group was matched for age, tumor size, histology, depth of invasion, presence of capillary lymphatic space involvement, lymph node metastases, and use of adjuvant radiation. The other control group consisted of patients with tumor sizes </=2 cm, negative pelvic lymph nodes who had not received adjuvant radiation therapy. RESULTS: Thirty of 32 patients treated by RVT + LPL between March 1994 and November 1998 were matched. The only statistically significant difference in prognostic factors between the patients who underwent RVT + LPL and unmatched controls (556 patients) was the median depth of invasion in the adenocarcinomas (2. 0 mm vs. 4.0 mm, respectively; P < 0.02). The 2-year actuarial recurrence free survival was 95%, 100%, and 97% for the patients who underwent RVT + LPL, matched controls, and unmatched controls, respectively. The actuarial conception rate at 12 months was 37%. CONCLUSIONS: Acknowledging the small numbers and short follow-up, RVT + LPL appears to be similar in efficacy to RH. If longer follow-up with more patients confirms the above, this procedure will represent an acceptable alternative to RH for patients with early Stage I carcinoma of the cervix who desire preservation of fertility.

Adenocarcinoma↗
PubMed1999

Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak.

BACKGROUND: The largest number of adult cases of haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) during an Escherichia coli O157 outbreak occurred in 1996 in central Scotland. Adults who develop HUS/TTP induced by E. coli O157 tend to be elderly and have a historical mortality rate of almost 90% when treated conservatively. Therefore the decision was made to treat adults who developed HUS/TTP during this outbreak with therapeutic plasma exchange (TPE). We report our outcome with this controversial treatment. METHODS: A case definition for HUS/TTP was developed at the beginning of the outbreak. All cases meeting this definition were considered for TPE. Information on demographics, clinical features, treatment and outcome of patients was obtained by retrospective case note review. FINDINGS: 22 adults developed HUS/TTP. They had a mean age of 71 years. 16 cases received TPE. Six cases had contraindications to TPE or died before the procedure could be done. Ten of the 22 (45%) adults with HUS/TTP died. Five of the 16 (31%) TPE-treated cases died, four of eight aged over 70 years compared with one of eight aged less than 70 years. Premorbid illness, neurological features, treatment with ciprofloxacin or prostacyclin, and the laboratory severity of HUS/TTP were not associated with death; the number of cases, however, was too small to allow statistical conclusion. INTERPRETATION: The mortality rate is high in adults who develop HUS/TTP induced by E. coli O157. TPE appears to be a promising treatment that was well tolerated in our elderly patients. A national register of adult cases of HUS/TTP induced by E. coli O157 should be established.

Adolescent↗
PubMed1999

Treatment of early epithelial ovarian cancer with chemotherapy and abdominopelvic radiotherapy: results of a prospective treatment protocol.

PURPOSE: To test the hypothesis that the combination of adjuvant chemotherapy and abdominopelvic radiation (APRT) improves the outcome of patients with early ovarian cancer compared to treatment with APRT alone. METHODS AND MATERIALS: Between 1991 and 1994, 93 patients with Stage I to III, optimally cytoreduced, invasive, epithelial ovarian cancer were treated with sequential chemotherapy and APRT. Treatment was assigned using a prognostic classification that was derived from previous cohorts of patients. Low-risk patients (n = 9) received APRT alone, intermediate-risk patients (n = 66) received two courses of cisplatin followed by APRT, and high-risk patients (n = 18) received 6 courses of cisplatin and cyclophosphamide followed by APRT. RESULTS: Disease recurred in 22 patients, and was confined to the pelvis or abdomen in 15. Nine patients died and the remainder were alive with disease after receiving salvage chemotherapy. The 3-year disease-free and overall survivals were 78% and 91%, respectively. The prognostic classification used to assign treatment was the only factor that predicted disease-free survival (83% and 59% at 3 years for low/intermediate- and high-risk patients, respectively; p = 0.03). There was no detectable difference in outcome between the present series and an historical control group treated with APRT alone. Treatment was well tolerated and only 2 patients (2.5%) developed serious complications. CONCLUSION: APRT is an effective adjuvant treatment for carefully selected patients with early ovarian cancer. The addition of chemotherapy as used in this study to APRT does not significantly improve outcome compared to APRT alone.

Adult↗
PubMed1999

Nutrition survey in an elderly population following admission to a tertiary care hospital.

BACKGROUND: Malnutrition in elderly patients in institutions has become an issue of clinical concern, but it remains largely unrecognized in acute care hospitals. The demonstrated benefits of intervention emphasize the need for routine nutritional assessment. The objectives of this study were to determine the prevalence of malnutrition in elderly patients admitted to a tertiary care centre and to test the sensitivity and specificity of 3 nutrition screening tools. METHODS: Between July and November 1996 patients 65 years and older were consecutively recruited from the general medicine, orthopedics, general surgery and neurosciences services of The Ottawa Hospital--General Campus within 72 hours of admission. They were interviewed using 3 nutritional screening tools: one developed by Chandra and colleagues (Chandra), the Nutrition Screening Initiative (NSI) and the Mini Nutritional Assessment (MNA). A detailed nutrition assessment was then undertaken, which included anthropometric assessment, laboratory tests, determination of risk factors and assessment of dietary intake. A dietitian blinded to the screening results classified each patient as being well nourished, at risk for malnutrition or malnourished. The prevalence of malnutrition was assessed, and screening results were compared with the results of the detailed nutrition assessment for sensitivity and specificity. RESULTS: In total, 160 patients (86 women) were recruited. Detailed nutrition assessments were completed for 152 patients, of which 62 (40.8%) were found to be well nourished, 67 (44.1%) at moderate risk for malnutrition and 23 (15.1%) malnourished. Matched comparisons showed that, of the 23 malnourished patients, 1 was found to be at high risk for malnutrition using the Chandra screening tool, 9 using the NSI and 4 using the MNA, giving sensitivities of 32%, 54% and 57%, and specificities of 85%, 61% and 69%, respectively. INTERPRETATION: Given the high rate of malnutrition or risk of malnutrition in this study, admitting physicians need to be aware of this problem and its scope. The 3 screening tools tested performed poorly in comparison with the detailed nutrition assessment. This may have been because the score thresholds for the screening tools were set for screening purposes and because the screening tools were designed for different settings and a wider population.

Aged↗
PubMed1999

Phosducin, beta-arrestin and opioid receptor migration.

Internalization of G protein-coupled opioid receptors depends on multiple criteria, including the affinity of drugs to their receptors and the state of the receptor-G protein interaction. Most recent studies reveal that cytosolic components like phosducin and arrestin interfere with receptor internalization, that is phosducin impairs receptor phosphorylation and arrestin enhances endocytosis by uncoupling the receptor from its G protein. This study was designed to examine the mutual effect phosducin and arrestin exert on receptor endocytosis. Neuronal NG 108-15 hybrid cells transiently expressing the mu-opioid receptor, which has been fused to green fluorescence protein, were employed to study internalization of the fluorescent mu-opioid receptor construct in living cells by means of confocal laser scanning microscopy. Fluorescent mu-opioid receptors were detected in drug-naive cells both at the cell membrane and at cell surface protrusions, most likely filopodia, microspikes and retraction fibres. The opioid receptors present in the cell membrane internalize upon etorphine (1 nM) exposure, a process clearly blocked in cells overexpressing phosducin. However, coexpression of both phosducin and beta-arrestin 1 reverses this blockade. In contrast to etorphine, morphine fails to internalize mu-receptors expressed in NG 108-15 cells. When arrestin is overexpressed in these cells, morphine gains the ability to induce endocytosis, and this process is left unaffected by phosducin. The findings suggest that endocytosis of activated mu-opioid receptors primarily depends on arrestin-triggered uncoupling of the receptor from its G protein complex. Drug-induced receptor phosphorylation appears of subordinate significance for receptor internalization.

Analgesics, Opioid↗