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Biomedical subjects

C Murray

Publications and source records attributed to C Murray.

At least 127 records · Page 7Linked to original sources
PubMed1992

Refining the biophysical profile with a risk-related evaluation of test performance.

OBJECTIVE: Our objective was to determine the ability of biophysical profile variables to predict bad perinatal outcome in high-risk third-trimester pregnancy. STUDY DESIGN: The outcomes of 1146 fetuses were correlated with abnormal single or multiple variables occurring in biophysical profile done within 72 hours of delivery. Theoretic risks of poor outcomes for different combinations of abnormal variables, calculated with Shortlife's formula, were compared with the actual risks observed (chi 2 tests). RESULTS: Two hundred forty-six fetuses had at least one abnormal biophysical profile variable with the risk of bad outcome, for a single abnormal variable, ranging from 8% (body movements) to 100% (tone) and increasing from 14% (any variable abnormal) to 63% (all variables abnormal). In most (57%) observed combinations of biophysical profile variables, significant differences between theoretic and actual risks of bad outcomes were found. By stepwise logistic regression the best predictive model contained all variables except fetal movement. CONCLUSIONS: Dynamic biophysical profile variables appear to be interdependent. Not all combinations of abnormal variables occur and specific combinations improve prediction of poor outcome. Risk-related scales for biophysical profile outcomes might prove superior to more conventional scoring systems.

Biophysics↗
PubMed1992

Nifedipine for treatment of preterm labor: a historic prospective study.

OBJECTIVES: The purpose of this study was to ascertain whether adverse fetal and/or neonatal effects occurred during nifedipine treatment of preterm labor and to assess maternal tolerance of nifedipine therapy in patients intolerant of a beta-sympathomimetic agent. STUDY DESIGN: We undertook historic prospective review of medical records of 102 women admitted to an antepartum ward for treatment of preterm labor who received nifedipine. Data were collected regarding maternal side effects, fetal surveillance, and neonatal outcome. RESULTS: The number and severity of reported maternal side effects were significantly reduced when patients were switched from terbutaline to nifedipine. No discontinuance of nifedipine occurred because of maternal side effects. Fetal surveillance testing and neonatal outcome data failed to reveal deleterious in utero effects of nifedipine. CONCLUSIONS: Nifedipine was a well-tolerated and safe tocolytic in this population and warrants further investigation.

Embryonic and Fetal Development↗
PubMed1992

Prevention of graft-versus-host disease by selective depletion of CD6-positive T lymphocytes from donor bone marrow.

PURPOSE: Acute and chronic graft-versus-host disease (GVHD) continues to be the major causes of morbidity and mortality after allogeneic bone marrow transplantation (BMT). In this study, we have evaluated the clinical effects of selective in vitro T-cell depletion of donor allogeneic bone marrow by using a single monoclonal antibody ([MoAb] anti-T12, CD6) and rabbit complement. This antibody recognizes mature T cells, but not other cellular elements such as natural-killer (NK) cells, B cells, and myeloid precursors. PATIENTS AND METHODS: From August 1983 to April 1991, 112 consecutive adult patients with hematologic malignancies underwent BMT with bone marrow from HLA-identical sibling donors. Marrow was harvested and depleted of mature T lymphocytes ex vivo by the use of three rounds of incubation with an anti-T12 antibody and rabbit complement. The preparative regimen consisted of cyclophosphamide and fractionated total body irradiation (TBI) in 108 patients. No patients received prophylactic immune suppression post-BMT. Purgation by anti-T12 was used as the only method for the prevention of GVHD. RESULTS: Twenty patients (18%) developed acute GVHD (grade 2 to 4); only eight patients developed chronic GVHD. The incidence of GVHD did not increase significantly with age. Only three of 112 patients (2.7%) exhibited acute graft failure. One patient developed late graft failure that was associated with cytomegalovirus (CMV) infection. Within the subset of 50 patients who had not previously undergone unsuccessful conventional therapy (acute leukemia in first remission or chronic myelogenous leukemia [CML] in stable phase), we estimated by the Kaplan-Meier method that the probability of disease-free survival was 50% at 3 years post-BMT, with a median follow-up of 44 months. The treatment-related mortality rate in this group was only 14% and was independent of patient age. CONCLUSIONS: We conclude that selective in vitro T-cell depletion with an anti-T12 monoclonal antibody effectively reduces the incidence of both acute and chronic GVHD after allogeneic BMT without compromising engraftment. Moreover, depletion of CD6-positive cells from donor marrow obviates the need to administer immune suppressive medications to the majority of patients. This approach reduces the morbidity and mortality of allogeneic BMT and permits the BMT of older patients.

Adult↗
PubMed1992

Induction of neointima formation by platelet derived angiogenesis fraction in a small diameter, wide pore, PTFE graft.

Enhancement of endothelialization and patency of a small diameter (2 mm), wide pore, PTFE graft was attempted by coating the luminal surface with a platelet derived angiogenesis fraction (PDAF) and implanting it in a rat model. PDAF was delivered to the grafts by combining it with a carrier polymer. PDAF-treated grafts were initially implanted in the retroperitoneum for 21 days followed by removal of one for histology and in situ end to side bypass to the infrarenal aorta for the other. Vascularized grafts were examined at 14 days for patency and 100 days for patency and histology. Significant differences were noted in transmural ingrowth of capillaries and tissue at 21 days post implantation in PDAF-treated versus untreated grafts. Similarly, near significance was noted in capillary ingrowth and significance was noted in tissue ingrowth at 100 days in PDAF-treated grafts. Despite favorable trends particularly early in the time course, no significant differences in graft patency, endothelialization, or hydroxyproline content was demonstrated between PDAF-treated and untreated grafts. Results of this preliminary study are encouraging for further study of PDAF-treated PTFE grafts and the potential that rapid vascularized neointima formation results improved in graft patency rates.

Animals↗
PubMed1992

The prediction of "controlled" uterine rupture by the use of intrauterine pressure catheters.

OBJECTIVE: To determine whether uterine activity, assessed by either fluid-filled or solid pressure catheters, changes with uterine incision at cesarean delivery. METHODS: Uterine activity was recorded continuously during low transverse cesarean delivery in ten parturients using fluid-filled pressure catheters and in ten women with solid pressure catheters. Visual analyses were performed of the last 30 minutes of uterine recording before uterine incision and of the period after incision; the analyses were then compared within and between the catheter groups for mean uterine tone and contraction amplitude, frequency, and duration. Oxytocin use, anesthesia method, mean gestational age, birth weight, length of labor, duration of monitoring, and uterine incision-to-delivery time were compared between the groups. RESULTS: All obstetric end points were similar in both catheter groups except for a higher mean birth weight in the solid-catheter group. The mean (+/- standard deviation) duration of post-incision monitoring was 4.7 +/- 0.94 minutes. After uterine incision, mean tone and contraction amplitude were unchanged, whereas mean contraction frequency and duration decreased significantly. CONCLUSIONS: Though intrauterine monitoring was brief, this model allows a unique view of "controlled" uterine rupture. Spontaneous uterine rupture may evolve more gradually; however, neither catheter type would be likely to aid its early recognition.

Adult↗
PubMed1991

Regional cerebral blood flow and cognitive function in patients with chronic liver disease.

Subtle impairments of cognitive function may be an important cause of occupational and psychosocial morbidity in patients with chronic liver disease. Correlation of structural brain abnormalities with cognitive deficits has yielded inconsistent results. 10 patients with cirrhotic liver disease were compared with 10 age, education, and intelligence matched control subjects. Neuropsychological assessment revealed significant overall cognitive impairments in cirrhotic patients compared with controls (p = 0.02). Regional cerebral blood flow was measured by single photon emission computed tomography (SPET or SPECT) and showed increased uptake of radiotracer in the right and left posterior parts of the basal ganglia and right occipital lobe, together with reduced uptake in the right anterior cingulate region. The degree of cognitive impairment was directly correlated with functional abnormalities in the basal ganglia and limbic cortex (p less than 0.05). Our results suggest that impaired cognitive status may be associated with abnormalities of regional brain function in patients with chronic liver disease. Since these deficits are clinically inapparent, our findings have important implications for identification and management of patients with chronic liver disease.

Analysis of Variance↗
PubMed1991

Antibody reactivities of Mycobacterium paratuberculosis infected sheep as analyzed by enzyme-linked immunosorbent assay and western blotting.

Antibody reactivities in sera from Mycobacterium paratuberculosis (M. ptb) infected and vaccinated sheep were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western (immuno)blotting using a sonicate antigen from M. ptb. Both methods allowed good differentiation between infected/vaccinated animals and noninfected controls. Removal of nonspecific crossreactive antibodies by absorption with a M. phlei sonicate antigen coupled to Sepharose reduced ELISA reactivities of positive sera by 50% and those of noninfected serum by 85%. Immunoblotting analysis revealed that reduction by M. phlei absorption was due to lower reactivities of M. ptb antigens in the range of 30 to 45 kDa. However, one protein with a molecular mass of approx. 27 kDa seemed to be specific for M. ptb since it reacted similarly with nonabsorbed and absorbed serum but not with antibodies which were eluted from M. phlei-Sepharose after absorption. Our findings indicate that M. ptb and M. phlei share a number of common antigens of potential pathogenic importance and that only a smaller part of proteins (i.e. the 27 kDa protein) might be specific for M. ptb.

Animals↗
PubMed1991

Clustering of hepatocellular carcinoma in Alaska Native families.

Alaska Natives have a high incidence of hepatocellular carcinoma (HCC), with regional, ethnic, village, and familial clustering. During 1969-1988, 15 of the 45 incident cases of HCC in Alaska Natives occurred in 5 families. This report presents epidemiologic, virologic, and immunogenetic data on these 5 families. The results of hepatitis B virus (HBV) serologic testing indicates that HBV infection was an important factor in 4 of the 5 families. Human lymphocyte antigen (HLA) testing was performed in 3 families. The HLA results are reviewed in relationship to the familial clustering of HCC.

Adolescent↗
PubMed1991

Hepatic dysfunction following T-cell-depleted allogeneic bone marrow transplantation.

We reviewed the medical records of 97 patients undergoing T cell-depleted allogeneic bone marrow transplantation at our institution from 1984 to 1990 to determine the incidence of hepatic dysfunction, including venoocclusive disease of the liver following BMT. All patients received allogeneic marrow that had been purged with monoclonal antibody to the CD6 surface antigen (T12) and rabbit complement as the sole method of graft-versus-host disease prophylaxis. No additional immunosuppressive agents were routinely administered to these patients. Overall, 55% of patients in our series developed two-fold elevations in serum bilirubin, SGOT, or alkaline phosphatase within the first 30 days following BMT. A five-fold elevation in any liver function test was noted in only 19% of patients. Logistic regression analysis revealed that the presence of GVHD, female sex, and administration of amphotericin B all were independently associated with laboratory evidence of hepatic dysfunction. While LFT abnormalities were common in our series, they were generally mild, and the development of VOD was rare. Only three patients (3.1%) fulfilled clinical criteria sufficient to establish a diagnosis of VOD. Among the 86 patients whose ablative regimen consisted of cyclophosphamide (60 mg/kg x2) and total-body irradiation (1200-1400 cGy in 200 cGy fractions), only 1 patient (1.2%) developed VOD. Our experience suggests that patients undergoing allogeneic BMT are at low risk for VOD and other serious hepatic complications when they receive high-dose cyclophosphamide, fractionated TBI, and T cell-depleted marrow without hepatotoxic medications for GVHD prophylaxis.

Adolescent↗
PubMed1991

Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states.

Adult↗
PubMed1991

An improved radionuclide technique for the detection of altered pulmonary permeability.

Technegas, an ultra-fine dry aerosol with prolonged retention in the lungs, can be modified by altering the atmosphere in which the carbon particles are generated. The modified Technegas has much faster clearance from the lung. The half-time pulmonary clearances with modified Technegas were compared to those obtained with conventional 99mTc DTPA aerosol in 50 patients. Interstitial lung disease was suspected in 12 while 38 were infected with the human immunodeficiency virus and suspected of having opportunistic lung infection. In 22 nonsmokers in whom no evidence of active pulmonary pathology was demonstrable, the mean half-time with DTPA was 52.5 min whereas the mean half-time with modified aerosol was 10.1 min. The mean half-time in 14 smokers in whom there was also no evidence of active pulmonary disease was 28.3 min with DTPA and 7.0 min with the modified method. In the 14 patients in whom altered pulmonary permeability was demonstrated by a short DTPA half-time (mean 4.8 min) there was also an accelerated half-time with modified Technegas (mean 2.5 min). It is concluded that the modified Technegas procedure offers a simple but accurate method of identifying individuals having opportunistic infection or other diffuse lung pathology.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation.

Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT.

Adolescent↗
PubMed1990

Natural history of mixed chimerism after bone marrow transplantation with CD6-depleted allogeneic marrow: a stable equilibrium.

Mixed hematopoietic chimerism (MC) is a common finding after allogeneic bone marrow transplantation (BMT), but the natural history of this phenomenon remains unclear. To understand the evolution and the implications of this finding, we performed a prospective analysis of the development of mixed chimerism in 43 patients with hematologic malignancies who received bone marrow (BM) from human leukocyte antigen (HLA)-identical sibling donors. T-cell depletion in vitro with anti-T12 (CD6) monoclonal antibody and rabbit complement was used as the only method of graft-versus-host disease (GVHD) prophylaxis. Overall, MC was identified in peripheral blood (PB) and BM in 22 of 43 (51%) patients evaluated. MC was found by restriction fragment length polymorphism (RFLP) analysis in 21 of 40 (53%) patients, by cytogenetic analysis in 6 of 29 (21%) patients, and by red blood cell phenotyping in 4 of 9 (44%) patients. RFLP studies were performed at 0.5, 1, 3, 6, 9, and 12 months post-BMT and then every 6 months, and showed a high probability of developing MC in the first 6 months after BMT followed by stabilization after 12 months. Cytogenetic analysis was less sensitive in detecting MC. Once MC was detected after BMT, the percentage of recipient cells increased very slowly over more than 3 years of follow-up, and no patient reverted to complete donor hematopoiesis (CDH). Thus, recipient and donor cells remained in a relative state of equilibrium for prolonged periods that seemed to favor recipient cells over donor cells. Patient's disease, remission status, or intensity of the transplant preparative regimen did not influence the subsequent development of mixed chimerism. Early immunologic reconstitution was the only factor that correlated with the subsequent chimeric status of the patients. The percentage and absolute number of T3 (CD3) and T4 (CD4) positive cells at day 14 after BMT were significantly higher in the patients who maintained CDH but NK cell reconstitution was similar in both groups, suggesting that early reconstitution with T cells may play a role in preventing recovery of recipient cells after BMT. GVHD was also associated with maintenance of CDH, but the probability of relapse, survival, and disease-free survival was identical in patients with MC and CDH.

Antigens, CD↗
PubMed1990

Vibroacoustic stimulation and fetal behavioral state in normal term human pregnancy.

Vibroacoustic stimulation may affect human fetal behavior. Continuous graphic records of simultaneous ultrasonographic observations of fetal activities and electronic fetal heart rate tracings of 30 normal term fetuses were examined visually for the occurrence of behavioral state 30 minutes before and after 3 seconds of vibroacoustic stimulation. After vibroacoustic stimulation, the total time spent in state 1 decreased significantly, that spent in state 4 increased significantly, and times spent in state 2 and indeterminate state (no state established for at least 3 minutes) were unchanged. No fetus exhibited state 3 before or after vibroacoustic stimulation. State 4 occurred in 22 fetuses after vibroacoustic stimulation with a duration of at least 30 minutes in four fetuses, and was noted in all fetuses in pre-vibroacoustic stimulation state 1 and 11 of 16 fetuses in pre-vibroacoustic stimulation state 2. Fetal heart rate accelerations occurred within 10 seconds after vibroacoustic stimulation in 94% of the fetuses studied regardless of their prior behavioral state. The variation in the onset and duration of behavioral state responses in most fetuses after vibroacoustic stimulation may depend on previous behavioral state and could be important for interpretation of antenatal assessment that uses this stimulus.

Acoustic Stimulation↗