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Biomedical subjects

W Murphy

Publications and source records attributed to W Murphy.

At least 19 recordsLinked to original sources
PubMed2000

Host T cells resist graft-versus-host disease mediated by donor leukocyte infusions.

Delayed lymphocyte infusions (DLIs) are used to treat relapse occurring post bone marrow transplantation (BMT) and to increase the donor chimerism in recipients receiving nonmyeloablative conditioning. As compared with donor lymphocytes given early post-BMT, DLIs are associated with a reduced risk of graft-vs-host disease (GVHD). The mechanism(s) responsible for such resistance have remained incompletely defined. We now have observed that host T cells present 3 wk after lethal total body irradiation, at the time of DLI, contribute to DLI-GVHD resistance. The infusion of donor splenocytes on day 0, a time when host bone marrow (BM)-derived T cells are absent, results in greater expansion than later post-BMT when host and donor BM-derived T cells coexist. Selective depletion of host T cells with anti-Thy1 allelic mAb increased the GVHD risk of DLI, indicating that a Thy1(+) host T cell regulated DLI-GVHD lethality. The conditions by which host T cells are required for optimal DLI resistance were determined. Recipients unable to express CD28 or 4-1BB were as susceptible to DLI-GVHD as anti-Thy1 allelic mAb-treated recipients, indicating that CD28 and 4-1BB are critical to DLI-GVHD resistance. Recipients deficient in both perforin and Fas ligand but not individually were highly susceptible to DLI-GVHD. Recipients that cannot produce IFN-gamma were more susceptible to DLI-GVHD, whereas those deficient in IL-12 or p55 TNFRI were not. Collectively, these data indicate that host T cells, which are capable of generating antidonor CTL effector cells, are responsible for the impaired ability of DLI to induce GVHD. These same mechanisms may limit the efficacy of DLI in cancer therapy under some conditions.

Animals↗
PubMed1998

In vivo alloreactive potential of ex vivo-expanded primary T lymphocytes.

BACKGROUND: We are presently investigating the therapeutic potential of herpes simplex-thymidine kinase-expressing donor T cells in the setting of a T cell-depleted allogeneic bone marrow transplantation. The generation, expansion, and selection of the gene-modified T cells require a 12-day ex vivo culture period in high-dose interleukin (IL)-2 that could significantly alter their in vivo alloreactivity. METHODS: We evaluated the alloreactive potential of such cultured cells in a murine allogeneic bone marrow transplantation model. RESULTS: The present studies demonstrate that ex vivo-expanded cultured T cells are capable of strong alloreactivity as evidenced by the occurrence of lethal acute graft-versus-host disease (GVHD). However, GVHD mortality after administration of the cultured T cells occurred later than after the administration of a same number of fresh T cells. Similar kinetics of GVHD-induced mortality between cultured and fresh T cells required a 10-fold increase in the number of cultured T cells, indicating a reduced alloreactive potential of these cells. The addition of a 2-day "resting" period in low-dose IL-2 resulted in T cells with enhanced alloreactive potential identical to the alloreactivity observed with fresh T cells. CONCLUSION: Ex vivo IL-2-expanded T cells are capable of significant in vivo alloreactivity. However, an increase in the number of cultured T cells administered or the introduction of a short resting culture period prior to infusion is necessary in order to achieve in vivo alloreactivity identical to the alloreactivity observed with fresh T cells.

Acute Disease↗
PubMed1997

State-and sex-specific prevalence of selected characteristics--behavioral risk factor surveillance system, 1994 and 1995.

PROBLEM/CONDITION: High-risk behaviors (e.g., cigarette smoking, excessive alcohol consumption, and physical inactivity) and lack of preventive health care (e.g., screening for cancer) are associated with chronic disease- and injury-related morbidity and mortality. States use the Behavioral Risk Factor Surveillance System (BRFSS) to collect data about these modifiable health behaviors and to monitor trends and changes in the prevalence of behavioral risk factors in state populations. BRFSS data also are used to monitor progress toward the year 2000 national health objectives. REPORTING PERIOD: 1994 and 1995. DESCRIPTION OF SYSTEM: The BRFSS is a state-based telephone survey of the civilian, noninstitutionalized, adult (persons > or =18 years of age) population. In 1994, 49 states and the District of Columbia participated in the BRFSS; in 1995, 50 states participated. RESULTS: As in previous years, there were state-specific variations in the prevalences of high-risk behaviors, awareness of certain medical conditions, use of preventive health services, and health-care coverage. Selected findings for 1995 were that 22.4% of adults reported being current cigarette smokers (range: 13.2%-27.8%); the percentage of adults who reported driving after drinking too much alcohol ranged from 0.6% to 5.2% (median: 2.3%); and among adults aged > or =65 years, 36.8% (range: 11.4%-46.6%) reported ever having had a pneumococcal vaccination and 59.2% (range: 44.2%-70.0%) reported having had an influenza vaccination within the past 1 year. INTERPRETATION: State-specific variations in prevalence may reflect differences in population composition, socioeconomic factors, state laws enacted to discourage high-risk behaviors, levels of effort to screen for certain diseases and physiological conditions, and other factors. ACTION TAKEN: States continue to use the BRFSS to monitor risk factors associated with chronic disease- and injury-related morbidity and mortality and to develop public health programs and policies to address these problems. BRFSS data continue to be important in assessing progress toward national year 2000 and state health objectives.

Adult↗
PubMed1996

Magnetic resonance imaging findings in asymptomatic volunteers and symptomatic patients with temporomandibular disorders.

Internal derangement has been suggested to be a cause of temporomandibular disorders. This study compared magnetic resonance imaging findings in 82 asymptomatic volunteers and 263 symptomatic patients. Disk displacement was observed in 33% of the asymptomatic volunteers and 84% of the symptomatic patients. The prevalence of trauma, headache, and other joint problems was more common in symptomatic patients. A history of general anesthesia and orthodontic treatment was not increased in the symptomatic population compared with asymptomatic volunteers. This study suggests that disk displacement is more common in symptomatic subjects.

Cartilage, Articular↗
PubMed1996

Improved analogs and novel delivery systems for somatostatin octapeptides.

Appropriate N-terminus modification can result in somatostatin (SRIF) octapeptide analogs that are both more potent and more selective in vitro for the human SRIF receptor type 2 (hsst2). In addition, these modifications can improve the duration of action and bioavailability of SRIF analogs following parenteral administration, as shown by both pharmacological and distribution studies in vivo with BIM-23190 and BIM-23197 in the rat.

Amino Acid Sequence↗
PubMed1996

Endoscopic injection for bleeding peptic ulcer: a comparison of adrenaline alone with adrenaline plus human thrombin.

BACKGROUND & AIMS: Endoscopic injection therapy improves outcome in bleeding peptic ulcer, but the optimum regimen is unknown. The aim of this study was to compare the efficacy of endoscopic therapy with dilute adrenaline alone vs. adrenaline plus human thrombin in the treatment of patients with major peptic ulcer hemorrhage. METHODS: One hundred forty patients with significant peptic ulcer hemorrhage and active arterial bleeding or a nonbleeding visible vessel were randomized to endoscopic injection with 1:100,000 adrenaline (70 patients; group 1) or to adrenaline plus 600-1000 IU of human thrombin (70 patients; group 2). The two groups were well matched for age, shock, hemoglobin concentration, comorbid disease, endoscopic findings, and consumption of nonsteroidal anti-inflammatory drugs. RESULTS: Fourteen patients from group 1 (20%) and 3 patients from group 2 (4.5%) rebled (P < 0.005). Seven patients from group 1 (10%) but no patients from group 2 died within 30 days of admission (P < 0.013). Patients from group 1 were administered a total of 297 units of blood compared with 219 units in group 2 (P < 0.041). CONCLUSIONS: Endoscopic injection using adrenaline plus human thrombin is superior to injection with dilute adrenaline alone and may represent the best treatment for bleeding peptic ulcers.

Adult↗
PubMed1996

Pylephlebitis: a case report and review of outcome in the antibiotic era.

Pylephlebitis or septic thrombophlebitis of the portal vein, a precursor of hepatic abscesses, is an extremely rare and frequently fatal complication of diverticulitis. The following report describes a patient presenting with pylephlebitis and complicated diverticulitis. Diagnosis was confirmed by computed tomography. The patient had a favorable outcome with medical and surgical therapy, prompting us to evaluate historical treatment of pylephlebitis.

Acute Disease↗
PubMed1995

Angle of the articular eminence in patients with temporomandibular joint dysfunction and asymptomatic volunteers.

OBJECTIVE: The purpose of this study was to compare structural variations of the temporomandibular joint anatomy between symptomatic patients with temporomandibular joint dysfunction and asymptomatic controls. STUDY DESIGN: There were 74 symptomatic patients with temporomandibular joint dysfunction, 29 asymptomatic volunteers with normal joints, and 6 asymptomatic volunteers with disk displacement with reduction included in this study. All subjects had bilateral high resolution magnetic resonance imaging scans performed in the sagittal (closed and opened) and coronal (closed) positions. All subjects had right and left full profile laminagraphs, one in the centric occlusal position, and one with the incisors edge to edge. RESULTS: Student-Newman-Keuls tests demonstrated no significant angular or linear differences for depth of the articular fossa, angle of the articular eminence, horizontal and vertical overlap of the incisor teeth, and linear condylar translation. CONCLUSION: This study concludes that there are no significant differences in angular and linear measurements in the articular fossa of asymptomatic volunteers and symptomatic subjects with temporomandibular joint dysfunction.

Adult↗
PubMed1993

Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis.

The selective 5-hydroxytryptamine3 (5HT3) antagonist ondansetron has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. This double-blind study compared the efficacy and safety of three doses of intravenous ondansetron in the prevention of nausea and vomiting associated with high-dose (> or = 100 mg/m2) cisplatin chemotherapy. A total of 125 patients were randomized (1:1:1) to receive 0.015, 0.15, or 0.30 mg/kg every 4 h for a total of 3 doses. All patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 h following cisplatin administration. The 0.15-mg/kg dose was superior to the 0.015-mg/kg dose with respect to the median number of emetic episodes (P = 0.033) and complete response (no emetic episodes, P = 0.005). No statistically significant difference was found between the 0.15 and the 0.30-mg/kg groups. The most common adverse event was headache. Three 0.15-mg/kg doses of intravenous ondansetron are safe, effective, and adequate for the control of cisplatin-induced emesis.

Adult↗
PubMed1993

Activity of anterior temporalis and masseter muscles during deliberate unilateral mastication.

The reproducibility of electromyographic parameters descriptive of deliberate unilateral chewing (activity, timing, curve symmetry) was investigated in normal asymptomatic volunteers. The best time for the initiation of muscle activity was also examined, with the future aim of staging TMJ internal derangements. The results suggest that activity is the most reliable variable, indicating that it may be helpful in describing muscle incoordination. When time was used in conjunction with another variable, overall reproducibility decreased.

Adult↗
PubMed1992

Apparent lack of synergism between heparin and dihydroergotamine in prevention of deep vein thrombosis after elective hip replacement: a randomised double-blind trial reported in conjunction with an overview of previous results.

We report the results of a double-blind, randomised trial of venous thrombosis (VT) prevention in 117 patients having elective hip replacement where low dose heparin alone (5,000 IU sodium heparin given subcutaneously [sc] 8 hourly until the seventh postoperative day) was compared with low dose heparin plus dihydroergotamine (DHE; 0.5 mg, given 8 hourly by sc injection). The trial end point consisted of VT discovered through bilateral ascending venography done routinely on the seventh postoperative day. VT developed in 34% of patients given heparin/DHE (95% confidence interval = 22% - 47%) compared with 24% in those given low dose heparin alone (95% confidence interval = 14% - 37%; p = 0.34), difference = 10% (95% confidence interval = -7% to +26%). Corresponding figures for the incidence of proximal (above-knee) thrombosis were 17% and 14% (95% confidence intervals = 8% - 29% and 6% - 25% respectively). These results are discussed in the context of a detailed overview of published evidence concerning VT prevention with heparin/DHE after hip replacement and we conclude it is unlikely that heparin/DHE is markedly superior to low dose heparin alone in this clinical setting.

Aged↗