PubMed Health⌕ Search

Biomedical subjects

C Murray

Publications and source records attributed to C Murray.

At least 109 records · Page 6Linked to original sources
PubMed1993

The incidence of mania in two areas in the United Kingdom.

The incidence of mania in an inner-city area was estimated by both a casenote search with later interview and a prospective interview method. The incidence was found to be twice as high as that in a more rural area, as estimated by the casenote-based method. Though a high proportion of the inner-city population were from ethnic minorities, particularly Afro-Caribbean, this could not explain the discrepancy. It is suggested that the incidence of mania is related to the mobility of the local population.

Adult↗
PubMed1993

Maternal caffeine consumption and fetal behavior in normal third-trimester pregnancy.

OBJECTIVE: Our aim was to perform a longitudinal cohort study of 20 normal third-trimester pregnancies to observe whether the level of long-term maternal caffeine ingestion influenced fetal behavior. STUDY DESIGN: By dietary history 10 normal pregnant women were categorized as "high" caffeine consumers (> 500 mg/day, group H) and 10 as "low" caffeine consumers (> 200 mg/day, group L). Between 30 and 40 weeks biweekly 2-hour continuous ultrasonographic observations of fetal heart rate; breathing activity; and eye, trunk, and extremity movements were conducted. Maternal caffeine levels were determined at each session, and fetal states were identified and their duration quantified. Data were compared by analysis of variance by means of repeated measures or t tests. RESULTS: When compared with group L fetuses, group H fetuses spent similar mean time in state 1F (quiet sleep), less mean time in state 2F (active sleep), and much greater mean time in state 4F (arousal). The mean time spent in no state decreased significantly in group L, was unchanged in group H, and was similar for both groups at term. Both groups had similar mean numbers of state changes at all gestational ages studied. Mean maternal serum caffeine levels in group H were always significantly higher than those in group L. CONCLUSION: Evolving fetal behavior may be influenced by the level of maternal caffeine consumption during the last trimester.

Adult↗
PubMed1993

State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment.

Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.

Adult↗
PubMed1993

The elevation of plasma beta-endorphin levels in major depression.

Day-time plasma beta-endorphin/beta-lipotrophic hormone (beta-ENDO/beta-LPH), ACTH and cortisol have been determined in 26 patients with major depression and 25 controls. beta-ENDO/beta-LPH and cortisol were significantly elevated in patients, while ACTH was not. Cortisol levels were significantly negatively correlated with age in controls as were beta-ENDO/beta-LPH and ACTH. In patients, by contrast, cortisol levels were positively, albeit not significantly, related to age. Peptide levels were not related to age in the patient group. Instead, beta-ENDO/beta-LPH was negatively correlated with clinical ratings of symptom severity in patients and positively associated with an acute psychosocial precipitant. The findings cast further light on beta-ENDO/beta-LPH as a measure of hypothalamic-pituitary over activity in depressive illness. A negative association with symptom severity suggests that beta-ENDO/beta-LPH responses are, like those of ACTH, down-regulated in the course of depressive illness.

Adrenocorticotropic Hormone↗
PubMed1993

The effect of anxiety induction on the regional uptake of 99mTc-exametazime in simple phobia as shown by single photon emission tomography (SPET).

Ten patients suffering from DSM-III-R simple phobia were studied under two conditions: (a) while listening to a 4 min relaxation tape, and (b) while listening to a 4 min audio tape describing exposure to the phobic stimulus. During each condition, subjects were injected with 99mTc-Exametazime, a marker of regional cerebral blood flow. Subjective and psychophysiological measures indicated a marked effect of the anxiety induction procedure. Ratio analysis of the SPET data revealed reductions in tracer uptake largely confined to posterior cerebral regions bilaterally. Analysis of brain regions of interest normalised to the whole brain slice showed reductions confined to right temporal/occipital regions. In general there was no clear association between subjective and physiological variables and changes in regional uptake of tracer as a consequence of the anxiety induction procedure. The changes in tracer uptake were dissimilar to those previously reported for other cognitive activation paradigms, providing some reassurance that those functional brain changes were not artefacts of non-specific changes in state anxiety. These posterior brain changes may reflect alterations in activation of the GABA/benzodiazepine complex.

Acoustic Stimulation↗
PubMed1993

Combined modality therapy for stage IIIA non-small cell carcinoma of the lung.

53 patients with stage IIIA non-small cell carcinoma of the lung (NSCCL) were treated with multimodality therapy consisting of induction radiotherapy (55.8 Gy) and two cycles of concurrent chemotherapy with cisplatin, 25 mg/m2 for 4 days by continuous infusion and bolus etoposide, 100 mg/m2 on days 2 and 4 of each cycle followed by surgery and adjuvant chemotherapy. Of 53 evaluable patients, 47 achieved clinical responses (9 complete response, 38 partial response) after induction therapy for a response rate of 89%. 47 patients were resectable after induction therapy, but 8 patients refused surgery and 6 patients were not eligible for surgery based on poor pulmonary function (medical contraindications). 33 patients underwent thoracotomy and in 6 patients, resection was technically unfeasible. Thus complete surgical resection was accomplished in 27 patients. After all therapy, 28 patients achieved a complete response (53%) and 19 patients a partial response (36%). Toxicities were mild. At a maximum of 75 months (median, 28 months) of follow-up, the median survival of the entire group is 24 months. The median survival of resected patients has not been reached; their 6-year survival rate is 55%. Unresected patients survived for a median of 11 months. This multimodality regimen is well-tolerated, induces a high response and resectability rate and prolongs survival in resected patients.

Adult↗
PubMed1993

Korsakoff's syndrome, cognition and clonidine.

Eighteen patients suffering from Alcoholic Korsakoff's Syndrome participated in a placebo-controlled double-blind cross-over trial of clonidine 0.3 mg b.d. for two weeks versus matched placebo for two weeks. A detailed neuropsychological assessment was carried out at the end of each treatment phase and staff ratings of behaviour were also obtained. Clonidine treatment resulted in no significant improvement over placebo on any of the cognitive measures employed. The results contradict previous smaller studies which had suggested that chronic treatment with clonidine had a memory-enhancing effect in Korsakoff's syndrome.

Aged↗
PubMed1993

Proactive interference and the neuropsychology of schizophrenia.

Gray, Felden, Rawlins, Hemsley & Smith (1991) have proposed a theoretical model of the neuropsychology of schizophrenia. A major feature of this model is that it is a weakening of the influences of memories of previous input on current perception/learning which is basic to the phenomenon of acute schizophrenia. In the present study, proactive interference (PI) was used as a paradigm to test this hypothesis. PI occurs when new learning is diminished as a consequence of previously learned material. According to our reading of the Gray et al. (1991) model, acutely ill unmedicated patients with schizophrenia should demonstrate reduced PI relative to controls. Ten acutely ill unmedicated patients with schizophrenia, 20 patients suffering from major depressive disorder, and 20 healthy controls were assessed using a PI paradigm. No significant differences in PI emerged between the groups. The results do not support this specific feature of the neuropsychological model of acute schizophrenia proposed by Gray et al. (1991).

Acoustic Stimulation↗
PubMed1993

Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2.

The immunologic consequences of prolonged infusions of rIL-2 in doses that produce physiologic serum concentrations of this cytokine were investigated. rIL-2 in doses of 0.5-6.0 x 10(6) U/m2 per d (3.3-40 micrograms/m2 per d) was administered by continuous intravenous infusion for 90 consecutive days to patients with advanced cancer. IL-2 concentrations (25 +/- 25 and 77 +/- 64 pM, respectively) that selectively saturate high-affinity IL-2 receptors (IL-2R) were achieved in the serum of patients receiving rIL-2 infusions of 10 micrograms/m2 per d and 30 micrograms/m2 per d. A gradual, progressive expansion of natural killer (NK) cells was seen in the peripheral blood of these patients with no evidence of a plateau effect during the 3 mo of therapy. A preferential expansion of CD56bright NK cells was consistently evident. NK cytotoxicity against tumor targets was only slightly enhanced at these dose levels. However, brief incubation of these expanded NK cells with IL-2 in vitro induced potent lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Infusions of rIL-2 at 40 micrograms/m2 per d produced serum IL-2 levels (345 +/- 381 pM) sufficient to engage intermediate affinity IL-2R p75, which is constitutively expressed by human NK cells. This did not result in greater NK cell expansion compared to the lower dose levels, but did produce in vivo activation of NK cytotoxicity, as evidenced by lysis of NK-resistant targets. There was no consistent change in the numbers of CD56- CD3+ T cells, CD56+ CD3+ MHC-unrestricted T cells, or B cells during infusions of rIL-2 at any of the dosages used. This study demonstrates that prolonged infusions of rIL-2 in doses that saturate only high affinity IL-2R can selectively expand human NK cells for an extended period of time with only minimal toxicity. Further activation of NK cytolytic activity can also be achieved in vivo, but it requires concentrations of IL-2 that bind intermediate affinity IL-2R p75. Clinical trials are underway attempting to exploit the differing effects of various concentrations of IL-2 on human NK cells in vivo.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1993

A single photon emission computerised tomography study of regional brain function underlying verbal memory in patients with Alzheimer-type dementia.

Ten patients with Alzheimer-type dementia and nine age-matched normal controls were examined with SPECT, using split-dose 99mTc-labelled exametazime. The baseline condition involved repetition of the word 'yes' or 'no'. The activation condition involved recognition (indicated by a 'yes' or 'no') of words from a previously learned list presented along with distractor words. Patients who performed this task successfully were selected, and efforts were made to match the patients with controls according to their performance on the task, although this was not fully achieved. Uptake of 99mTc-exametazime was estimated at baseline and during the word-recognition task for predetermined regions of interest drawn from a standard neuroanatomical atlas. The baseline task appeared to normalise tracer uptake for frontal, temporal and parietal cortex in the patient group. However, during the recognition task, controls but not patients showed activation effects. These were most prominent in dorsolateral frontal cortex and adjacent anterior cingulate cortex. Among patients, successful performance was correlated with activation of dorsolateral frontal and parietal cortex on the left side. The results confirm the central role of frontal mechanisms in a recognition memory task. The study highlights some of the difficulties of using cognitive challenge tests in clinical groups.

Acoustic Stimulation↗
PubMed1993

High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant.

PURPOSE: To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS). PATIENTS AND METHODS: Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm). RESULTS: Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor. CONCLUSION: Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.

Adolescent↗
PubMed1993

Quality of parenting in families created by the new reproductive technologies: a brief report of preliminary findings.

The creation of families by means of the new reproductive technologies has raised important questions about the consequences for parent-child relationships, particularly where gamete donation has been used to conceive the child. Preliminary findings are presented of a study of the quality of parenting in families created as a result of the two most widely used reproductive technologies, in vitro fertilization and donor insemination, in comparison with a control group of families with a naturally conceived child and a control group of adoptive families. The quality of parenting was assessed using a standardized interview with the mother, and mothers and fathers completed questionnaire measures of stress associated with parenting. The results showed that the quality of parenting in families with a child conceived by assisted conception is superior to that shown by families with a naturally conceived child. The findings are discussed in terms of their implications for understanding the role of genetic ties in parent-child relationships.

Adoption↗
PubMed1993

Monoclonal antibody-purged autologous bone marrow transplantation in adults with acute lymphoblastic leukemia at high risk of relapse.

The prognosis for adults with B lineage ALL who have relapsed after an initial remission is poor. High-dose chemoradiotherapy followed by autologous BMT can induce prolonged clinical remissions in some children with recurrent ALL. In this study, we evaluated the efficacy of autologous BMT in adults. Autologous marrow was treated in vitro with J5 and J2 monoclonal antibodies (CD10/CD9) plus rabbit complement to purge residual ALL cells. Twenty-two adults with B lineage ALL were treated with high-dose chemoradiotherapy followed by infusion of J2/J5 purged autologous BM. The median age was 28 years (range 18-54 years). Twenty-one of 22 patients had experienced at least one relapse prior to BMT. All patients achieved complete hematologic engraftment. Disease-free survival (DFS) in this cohort of patients was 20%, with all survivors alive and free of disease between 2.5 and 7.5 years post-BMT. Age at the time of BMT was an important prognostic factor, with patients < 28 years old faring much better than older individuals (DFS, 45% vs 0%, p = 0.01). Our experience suggests that high-dose chemoradiotherapy followed by infusion of J2/J5 purged autologous marrow is as efficacious in young adults as it is in children and is a reasonable alternative for patients who lack HLA-matched donors. Results in older adults are poor, however, and demonstrate the need for more effective transplant strategies in these individuals.

Adolescent↗
PubMed1993

Adhesion formation and reproductive outcome after myomectomy and second-look laparoscopy.

OBJECTIVES: To evaluate adhesion formation after myomectomy and the reproductive outcome of infertile women with a large leiomyomatous uterus after myomectomy and second-look laparoscopy. METHODS: Twenty-six infertile women with a large leiomyomatous uterus underwent second-look laparoscopy 6 weeks after a myomectomy. At laparoscopy, the degree of adhesions was scored using the American Fertility Society classification of adnexal adhesions, and the adhesions were lysed. The pregnancy rates of these women were evaluated by life table analysis. RESULTS: A myomectomy incision on the posterior wall of the uterus was associated with more adnexal adhesions than that on the fundus or anterior uterine wall (93.7 versus 55.5%; P = .04). The degree of adnexal adhesions was also higher among women who underwent myomectomy with a posterior uterine incision (22.2 +/- 2.3 points) than in those with a fundal or anterior uterine incision (2.7 +/- 1.2 points) (P < .000001). The cumulative pregnancy rate was 33.4% at 6 months and 66.7% at 12 months after the procedures. CONCLUSIONS: Myomectomy incisions on the posterior uterine wall are associated with more and a higher degree of adnexal adhesions than those on the fundus and anterior wall. Conception occurs in the majority of infertile women with a large myomatous uterus who undergo myomectomy and second-look laparoscopy.

Adnexal Diseases↗
PubMed1992

High-dose intravenous zidovudine with 5-fluorouracil and leucovorin. A phase I trial.

BACKGROUND: The inhibition of pyrimidine metabolism by 5-fluorouracil (5-FU) enhances the anti-cancer effects of zidovudine (formerly called AZT) in in vitro and in vivo model systems without additive toxicity. Zidovudine-induced DNA damage correlates with cytotoxicity. METHODS: A Phase I trial of high-dose continuous-infusion intravenous zidovudine therapy in combination with 5-FU and leucovorin therapy was performed. Eighteen patients with advanced malignant tumors were treated with 43 courses of oral leucovorin (50 mg every 4 hours); continuous-infusion 5-FU (800 mg/M2/day) for 72 hours (3 days); and zidovudine, begun 24 hours after the start of 5-FU and leucovorin, for 48 hours, and terminating with the end of the 5-FU infusion. Zidovudine plasma levels and zidovudine-induced DNA damage were assessed. RESULTS: Zidovudine administered in doses of 2-20 g/M2/day, added no obvious toxicity to the basic chemotherapeutic treatment with 5-FU and leucovorin but resulted in a dose-dependent biologic effect manifested by an increase in DNA strand breaks in peripheral blood cells. At doses greater than 15 g/M2/day, altered plasma kinetics of zidovudine were observed; plasma zidovudine levels increased dramatically in relation to the dose of zidovudine. Limitations in drug administration restricted administration of higher intravenous doses without achieving a maximally tolerated dose. No responses were seen in this heavily pretreated population. CONCLUSIONS: Based on the results of preclinical studies, plasma zidovudine levels greater than those achieved at the maximal dose (133 microns) are required for increased anti-cancer activity with 5-FU. Additional studies using a bolus or rapid infusion as a method of achieving higher peak levels are indicated.

Adult↗
PubMed1992

Human bone marrow depleted of CD33-positive cells mediates delayed but durable reconstitution of hematopoiesis: clinical trial of MY9 monoclonal antibody-purged autografts for the treatment of acute myeloid leukemia.

The CD33 antigen, identified by murine monoclonal antibody anti-MY9, is expressed by clonogenic leukemic cells from almost all patients with acute myeloid leukemia; it is also expressed by normal myeloid progenitor cells. Twelve consecutive patients with de novo acute myeloid leukemia received myeloablative therapy followed by infusion of autologous marrow previously treated in vitro with anti-MY9 and complement. Anti-MY9 and complement treatment eliminated virtually all committed myeloid progenitors (colony-forming unit granulocyte-macrophage) from the autografts. Nevertheless, in the absence of early relapse of leukemia, all patients showed durable trilineage engraftment. The median interval post bone marrow transplantation (BMT) required to achieve an absolute neutrophil count greater than 500/microL was 43 days (range, 16 to 75), to achieve a platelet count greater than 20,000/microL without transfusion was 92 days (range, 35 to 679), and to achieve red blood cell transfusion independence was 105 days (range, 37 to 670). At the time of BM harvest, 10 patients were in second remission, one patient was in first remission, and one patient was in third remission. Eight patients relapsed 3 to 18 months after BMT. Four patients transplanted in second remission remain disease-free 34+, 37+, 52+, and 57+ months after BMT. There was no treatment-related mortality. Early engraftment was significantly delayed in patients receiving CD33-purged autografts compared with concurrently treated patients receiving CD9/CD10-purged autografts for acute lymphoblastic leukemia or patients receiving CD6-purged allografts from HLA-compatible sibling donors. In contrast, both groups of autograft patients required a significantly longer time to achieve neutrophil counts greater than 500/microL and greater than 1,000/microL than did patients receiving normal allogeneic marrow. CD33(+)-committed myeloid progenitor cells thus appear to play an important role in the early phase of hematopoietic reconstitution after BMT. However, our results also show that human marrow depleted of CD33+ cells can sustain durable engraftment after myeloablative therapy, and provide further evidence that the CD33 antigen is absent from the human pluripotent hematopoietic stem cell.

Adult↗
PubMed1992

Clinical and immunologic effects of prolonged infusion of low-dose recombinant interleukin-2 after autologous and T-cell-depleted allogeneic bone marrow transplantation.

Bone marrow transplantation (BMT) can produce prolonged clinical remission in some patients with hematologic malignancies. Unfortunately, disease relapse may occur despite BMT. Studies in animal models and clinical experience have provided evidence that immunologic factors play an important role in preventing relapse post-BMT. To stimulate immunologic activity in patients post-BMT, we administered prolonged uninterrupted continuous infusions of low-dose recombinant interleukin-2 (rIL-2). Thirteen marrow recipients (seven autologous BMT, six CD6 T-depleted allogeneic BMT) received rIL-2 at a dose of 2 x 10(5) U/m2/d for a scheduled period of 90 days. rIL-2 was administered through a Hickman catheter with a portable pump beginning a median of 85 days after BMT. Toxicity was minimal and all treatment could be undertaken in the outpatient setting. No patient developed any signs of graft-versus-host disease, hypotension, or pulmonary capillary leak syndrome. Treatment did not affect the absolute neutrophil count or hemoglobin level, but eosinophils increased substantially in most patients. Platelet counts decreased by 20% in 10 of 13 individuals within 2 weeks, but stabilized thereafter. Despite the low dose of rIL-2 administered, significant immunologic changes were noted. Specifically, all 13 patients experienced a marked increase (fivefold to 40-fold) in natural killer (NK) cell number. Phenotypic characterization showed that the majority of NK cells were CD56bright+ CD16+ CD3-. In contrast, a minor increase in T-cell number was noted in only 4 of 13 patients. Low-dose rIL-2 treatment resulted in augmentation of in vitro cytotoxicity against K562 and COLO tumor targets. This cytotoxic activity could be dramatically enhanced by incubation with additional rIL-2 in vitro. The immunologic effects of rIL-2 treatment were similar in both autologous and allogeneic marrow recipients. Our data suggest that prolonged infusion of rIL-2 at low doses is safe and can selectively increase NK cell number and activity after BMT. Further studies to assess the impact these changes may have on disease relapse post-BMT will be undertaken.

Adult↗