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Biomedical subjects

T McAuliffe

Publications and source records attributed to T McAuliffe.

15 recordsLinked to original sources
PubMed1996

Recombinant human interferon-beta (rHuIFN-beta) and radiation therapy for inoperable non-small cell lung cancer.

Fifteen patients with stage II, IIIA, and IIIB non-small cell lung cancer (NSCLC) received subcutaneous (s.c.) recombinant, glycosylated, human interferon-beta 1a (Rebif; rHuIFN-beta 1a) on each day of conventionally fractionated radiation therapy (RT) given in 2.0 Gy fractions to 60 Gy in 6 weeks. The rHuIFN-beta 1a was generated in CHO cells by recombinant DNA technology and is identical to natural IFN-beta produced by fibroblasts in primary sequence and glycosylation. Cohorts of three patients each were treated with escalating doses of rHuIFN-beta 1a: 1.5, 3, 6, 12, and 24 MIU/m2 per treatment day. Acute toxicity was assessed according to modified WHO criteria; late toxicity was graded using RTOG late toxicity criteria. The maximum tolerated dose (MTD) of rHuIFN-beta 1a was defined as the dose level immediately below that in which dose-limiting toxicity occurred in > or = two of six patients. Immunomodulatory effects and antigenicity of rHuIFN-beta 1a were assessed by 2-5A synthetase, beta 2-microglobulin, and neopterin levels and by measurement of anti-rHuIFN-beta antibodies, respectively. Fourteen of fifteen patients experienced grades 1-3 acute (early) toxicity (< or = 90 days), which was primarily gastrointestinal: dysphagia/esophagitis (14/15), nausea/vomiting (12/15), anorexia (7/15), and liver transaminasemia (6/15). One of three patients treated with 24 MIU/m2 per treatment day (total rHuIFN-beta 1a dose 672 MIU) died of complications secondary to pneumonia, sepsis, adult respiratory distress syndrome (ARDS), and radiation pneumonitis. Twelve patients were evaluable for late toxicity (> 90 days). Maximum toxicity was grade 0 in five patients, grade 1 in four patients, and grade 5 in one patient (radiation pneumonitis). Clinical responses from the combination were 1/15 CR, 6/15 PR, 6/15 stable disease, and 1/15 progressive disease. The MTD of rHuIFN-beta 1a has been estimated at 12 MIU/m2 per treatment day when given daily during conventional RT to 60 Gy in 6 weeks. Biologic response by rHuIFN-beta 1a alone was reflected by significant and dose-related increases in 2-5A synthetase, beta 2-microglobulin, and neopterin. Radiation therapy alone had no effect on these immune response parameters and did not diminish their augmentation by rHuIFN-beta 1a. There was no association of biologic modulation with clinical response or survival.

Adult↗
PubMed1996

An empirical investigation of the relationship between spirituality, coping, and emotional distress in people living with HIV infection and AIDS.

Evaluates levels of psychological distress, coping mechanisms, and their relationship with the religious beliefs and spiritual practices of people (N=65) living with HIV and AIDS. Results of the research indicate a strong relationship for spiritual dimensions with mental health, psychological adjustment, and coping. Concludes that a blending of spiritual traditions and mental health approaches are needed to facilitate the coping of people living with HIV and AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Inhibition of nitric oxide production is associated with enhanced weight loss, decreased survival, and impaired alloengraftment in mice undergoing graft-versus-host disease after bone marrow transplantation.

The pathophysiologic role of nitric oxide (NO) in graft-versus-host disease (GVHD) was investigated in a murine bone marrow (BM) transplantation model where donor and recipient were H-2-matched but differed at multiple minor histocompatibility antigens. Host AKR/J (H-2K) mice received lethal total body irradiation as pretransplant conditioning followed by transplantation of donor B10.BR (H-2K) BM cells with or without spleen cells as a source of GVH-reactive T cells. NO production, as assessed by serum nitrate and nitrite levels, was increased for up to 3 weeks posttransplant in animals undergoing both moderate and severe GVHD. Administration of NG-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide synthase, to animals undergoing GVHD resulted in effective suppression of NO production when compared with saline-treated GVHD control animals. Suppression of NO production by L-NMA in GVHD animals was associated with enhanced weight loss early posttransplant and decreased overall survival. Histologic analysis of tissues from L-NMA-treated and saline-treated GVHD animals showed that early weight loss was not because of an exacerbation of GVHD, indicating that NO did not appear to play an immunosuppressive role in this experimental model. L-NMA-treated animals with enhanced weight loss were observed to have splenic atrophy, decreased extramedullary hematopoiesis, and a reduction in BM cellularity when compared with GVHD control mice that were weight-matched before transplant. Analysis of T-cell chimerism in the spleen showed that L-NMA treatment impaired donor T-cell repopulation. In vitro colony-forming unit (CFU) assays were performed to further assess the role of NO on BM progenitor cell growth. L-NMA added directly into culture had no effect on CFU-granulocyte/macrophage (CFU-GM) formation in normal murine BM. In contrast, total CFU-GM from L-NMA-treated animals were significantly reduced when compared with GVHD controls or BM control animals who did not develop GVHD. Collectively, these data indicate that inhibition of NO impairs hematopoietic reconstitution and support the premise that NO appears to play a novel role in the facilitation of alloengraftment posttransplant.

Amino Acid Oxidoreductases↗
PubMed1994

Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia.

Between January 1988 and March 1993, 48 patients received T-cell-depleted marrow grafts from unrelated donors as treatment for chronic myelogenous leukemia (CML). The median age of the population was 31.7 years (range 5.4 to 53) with 17 of 48 patients greater than 40 years of age. Twenty-seven patients were transplanted in chronic phase, 17 in accelerated phase, and 4 in blast crisis. All patients received a standardized preparative regimen of cyclophosphamide, high-dose cytosine arabinoside, methylprednisolone, and total body irradiation. Marrow grafts were depleted of mature T cells with the alpha beta T-cell receptor antibody T10B9 as graft-versus-host disease (GVHD) prophylaxis. All patients also received posttransplant cyclosporine therapy. Twenty-eight of 48 patients were mismatched with their donors for one or more HLA-A, B, DR, or DQ loci by either serology or high-resolution oligonucleotide genotyping. Nine of 28 were mismatched at multiple HLA loci. Durable engraftment was achieved in 94% (45/48) of patients. The actuarial probability of developing grades II to IV and grades III to IV acute GVHD were 39.6% (95% confidence interval (CI) 26.9 to 53.0) and 8.3% (95% CI 6.1 to 10.9) for the entire cohort. There was no difference in the incidence of grades II to IV acute GVHD between patients receiving matched (36.8%) or mismatched (41.4%) marrow grafts (P = .77). The actuarial probability of relapse at 2 years was 8.8% (95% CI 2.1 to 21.6) for the entire cohort and 18% (95% CI 4 to 41) for patients transplanted in either the accelerated or blast crisis phase (advanced disease). One cytogenetic relapse has occurred among patients transplanted in the chronic phase. The probability of disease-free survival at 2 years was 52% (95% CI 24 to 70) for patients transplanted in chronic phase and 46% (95% CI 25 to 73) for patients transplanted with advanced disease. No difference in disease-free survival was observed between patients receiving matched (49%) or mismatched (51%) marrow grafts (P = .90). This study shows that patients receiving unrelated T-cell-depleted marrow grafts for CML can achieve durable engraftment with a low incidence of severe GVHD and apparent preservation of graft-versus-leukemia reactivity. These data also suggest that T-cell depletion may allow patients who might otherwise experience unacceptable toxicity from GVHD-related complications caused by older age or increased HLA disparity to benefit from unrelated marrow grafts.

Adolescent↗
PubMed1994

Impact of regulation on benzodiazepine prescribing to a low income elderly population, New York State.

On 1 January 1989, in an effort to reduce diversion of benzodiazepines for illicit use and reduce inappropriate prescribing, a regulation was implemented requiring the reporting of all benzodiazepine prescriptions to the New York State Department of Health. To assess the impact of the regulation on prescribing practices to the elderly, we followed the number of benzodiazepines and other central nervous system medications prescribed to a cohort of participants in an elderly pharmaceutical insurance program. Benzodiazepines were prescribed for 4652 (22%) of the 20,944 patients studied. By the last quarter of 1989, benzodiazepines were prescribed for 3120 (15%) patients, a decrease of 33%. The number of prescriptions of benzodiazepines decreased by 5010 (45%), from 11,123 to 6113. Decreases in the number of prescriptions were similar across benzodiazepine brands (range 40-56%). Statistically significant (p < 0.05) decreases were seen in all sex, age, race and marital status groups. Increases in number (and percent increases) of prescriptions for miscellaneous anxiolytics (i.e. hydroxyzine (399, 69%), meprobamate (299, 149%), buspirone (263, 111%), chloral hydrate (138, 265%), antidepressants (658, 19%), barbiturates (150, 29%), and tranquilizers (198, 19%), some of which may be more toxic or less effective, were noted. New York State's reporting regulation was effective in reducing both the number of patients being prescribed benzodiazepines and the number of prescriptions given to those who remain on benzodiazepines in the elderly population studies.

Aged↗
PubMed1994

Increasing incidence of adenovirus disease in bone marrow transplant recipients.

Adenovirus infections in 201 bone marrow transplant (BMT) recipients over 4 years were retrospectively reviewed. Forty-two patients (20.9%) had positive adenovirus cultures after BMT. There was a higher incidence of adenovirus infections in pediatric patients than in adults (31.3% vs. 13.6%, P = .003). In addition, the time of onset of adenovirus infection after transplant was earlier in pediatric patients (mean, < 30 days) than in adults (> 90 days). Adenovirus type 35 was the most common serotype identified. One-third of adenovirus-positive patients had definite or probable adenovirus disease. Moderate to severe acute graft-versus-host disease and isolation of adenovirus from two or more sites were significant risk factors for adenovirus disease. This report documents a higher incidence of both adenovirus infection and disease than do previous studies. Adenovirus may emerge as a more frequent pathogen as more high-risk BMT transplants are done.

Adenovirus Infections, Human↗
PubMed1993

Vitamin K1 metabolism and the production of des-carboxy prothrombin and protein C in the term and premature neonate.

This study investigated the incidences of undercarboxylated (protein induced by vitamin K absence: PIVKA) prothrombin and protein C in 496 neonates across a wide range of gestational ages. These findings are related to vitamin K1 levels (an indicator of cofactor availability) and vitamin K1 epoxide levels (a measure of the efficiency of the hepatic vitamin K cycle). PIVKA protein C was present in at least trace amounts in 27% of infants; whereas, PIVKA prothrombin was present in 7% of infants. PIVKA prothrombin and protein C were present at high plasma concentrations in 2% to 3% of term and preterm neonates and both PIVKA protein C and prothrombin increased with gestational age. Despite elevated plasma concentrations of PIVKA protein C and diminished levels of normally carboxylated protein C, clinical thrombosis was not observed. The mean (+/- SD) vitamin K1 level in the study population was 0.009 +/- 0.02 nmol/L (adult reference interval: 0.3 to 2.6 nmol/L) with no clear relationship between vitamin K1 levels and production of PIVKA protein C or prothrombin. By comparison with adults, the epoxide form of the vitamin comprised an abnormally high proportion of total vitamin K1; this suggests possible inefficiencies in hepatic reductase cycling.

Biomarkers↗
PubMed1991

The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.

Cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation. We sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension. We randomized 18 rabbits to receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5), or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral blood flow, intracranial pressure, and infarct size. Following the intracarotid administration of an autologous clot, cerebral blood flow in all groups fell to less than 5 ml/100 g/min during induced hypotension. After restoration of baseline blood pressure, mean cerebral blood flow in neutropenic animals recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control animals rose steadily to a final value of 241% of baseline, while a much smaller increase (148% of baseline) was noted in the thrombocytopenic group; no change from baseline was evident in the neutropenic group. Infarct size was significantly (p less than 0.05) reduced in the neutropenic group but not in the thrombocytopenic group. These results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle.

Animals↗
PubMed1990

Effects of age and level of physical activity on plasma norepinephrine kinetics.

We examined the effects of age and physical activity on plasma norepinephrine (NE) kinetics in active and inactive older and younger men. NE kinetics were estimated by calculation of the rates of NE appearance and clearance during infusion of tritiated norepinephrine [( 3H]-NE). Older active men had the highest level of plasma NE (pg/ml) and NE appearance (microgram.min-1.FFW-1, where FFW is fat-free weight) relative to younger men and inactive older men. NE clearance (l.min-1.FFW-1) was not influenced by age or physical activity. No significant associations were noted between percent body fat, supine blood pressure with resting levels of NE, NE appearance, and NE clearance. We concluded that 1) chronic participation in physical activity by older men, but not younger men, is associated with higher resting levels of plasma NE and NE appearance and 2) the degree of adiposity does not influence plasma NE kinetics in healthy younger and older men. The level of physical activity is an influencing factor on plasma NE and NE appearance into circulation in healthy older men.

Adult↗
PubMed1990

Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke.

Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean +/- SEM) was immediately reduced from 55.2 +/- 7.7 to 8.5 +/- 2.5 in the control group and from 61.8 +/- 14.8 to 10.0 +/- 3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6 +/- 10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3 +/- 8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4 +/- 5.6% in control animals to 8.8 +/- 5.6% in treated animals (mean +/- SEM, p less than 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke.

Animals↗
PubMed1990

The 24-hour pattern of the levels of serum progesterone and immunoreactive human chorionic gonadotropin in normal early pregnancy.

The purpose of this study was to characterize the levels of progesterone and hCG and the variability of those levels over 24 h in early pregnancy. Venous blood sampling was performed every 30 min during the first trimester of a subsequently normal pregnancy in 19 women. The variability in each progesterone and hCG data series was evaluated by three methods: 1) comparing the coefficient of variation (CV) of each individual hormone data set to the respective assay CV, 2) examining each data set for pulses, and 3) relating changes in hormone levels to the ingestion of a meal. The CV for each individual progesterone data set was greater than the assay CV (CV progesterone, 3.7%) in all subjects (range, 5.58-21.90%). The CV for each individual hCG data set was greater than the assay CV for hCG (CV hCG, 4.3%) in 17 of 19 subjects (range, 3.27-10.95%). Mean (+/- SE) progesterone and hCG peak frequencies were 2.4 +/- 0.3 and 1.7 +/- 0.3/24 h, respectively. When postprandial levels of progesterone were normalized to a percentage of preprandial levels, there were maximum decreases in mean progesterone levels of 15.4 +/- 2.6% and 13.1 +/- 1.9% 1 h after initiation of the lunch and dinner meals, respectively (P less than 0.05). Postprandial hCG levels decreased by 2.3 +/- 1.9% and 0.4 +/- 1.6% during this same time period (P greater than 0.05). These findings suggest that 1) both progesterone and hCG levels fluctuate during a 24-h period in early pregnancy; 2) this variability of both hormones is greater than inherent assay variability and can be resolved into a short term pattern of pulses, suggesting alterations in episodic secretion, metabolic clearance, or volume of distribution of the hormone; and 3) a portion of the variability in the progesterone time set may be due to the ingestion of meals.

Adult↗
PubMed1985

In vitro cellular cytotoxicity for a human colon cancer cell line by mucosal mononuclear cells of patients with colon cancer and other disorders.

In vitro cellular cytotoxicity of mononuclear cells of intestinal mucosa and peripheral blood for a colon cancer cell target was measured in patients with colon cancer and other disorders requiring resection. Four- and 24-hour cytotoxicity assays were conducted using selenium 75 (75Se)-labeled RPMI-4788 human colon cancer target cells grown in culture. In the cancer group mean cytotoxicity was 30.4% at 24 hours for peripheral blood effectors and 8.0% for effectors from normal mucosa. Values in patients with Crohn's disease were 10.4% for blood and 17.2% for effectors from normal mucosa, and 13.6% and 18.5%, respectively, for blood and abnormal mucosa. Values in patients with other diseases were 25% for blood and 14.7% for mucosa. Mean cytotoxicity at 4 hours did not exceed 6.4% for any group, and assays in autologous serum gave results similar to tests in calf serum. In additional studies, K 562 chronic leukemia cells were somewhat more sensitive to lysis than RPMI-4788 by blood mononuclear cells, but there was no lysis of K 562 by mucosal populations that were cytotoxic for RPMI-4788. There was no competitive inhibition by either target cell for the other. It was concluded that 75Se RPMI-4788 colon cancer cells are suitable targets for evaluating in vitro cytotoxicity by intestinal mucosal cells and that mucosal cytotoxicity in patients with colon cancer is depressed compared to cytotoxicity by peripheral blood effectors.

Adolescent↗
PubMed1980

Treatment of surgical emergencies with and without an algorithm.

A patient care algorithm was developed for resuscitation of patients entering the surgical emergency department with hypotension. The diagnostic workup, monitoring, and therapy were progressively excalated according to admission blood pressure and responses to therapeutic interventions. The branching-chain logic is ideally suited for rapid decision making in emergency conditions where the need is most urgent, the time constraints are most severe, and the potential improvements in terms of patient salvage are greatest. Preliminary results from these ongoing clinical trials indicate that (1) physicians can and will use an algorithm for emergency medical service resuscitation; (2) in a university hospital with a large emergency service and a commitment to emergency care, the physicians using the aigorithm performed as well as and in some instances better than those not using the algorithm; and (3) the use of the algorithm may prevent delays in resuscitation and lead to less morbidity and mortality. Thus, we conclude that the algorithm helps to organize emergency care, establish standards, and improve care.

Adult↗
PubMedDate not supplied

The precision and accuracy of a portable heart rate monitor.

A device that would comfortably and accurately measure exercise heart rate during field performance could be valuable for athletes, fitness participants, and investigators in the field of exercise physiology. Such a device, a portable telemeterized microprocessor, was compared with direct EKG measurements in a laboratory setting under several conditions to assess its accuracy. Twenty-four subjects were studied at rest and during light-, moderate-, high-, and maximal-intensity endurance activities (walking, running, aerobic dancing, and Nordic Track simulated cross-country skiing. Differences between values obtained by the two measuring devices were not statistically significant, with correlation coefficient (r) values ranging from 0.998 to 0.999. The two methods proved equally reliable for measuring heart rate in a host of varied aerobic activities at varying intensities.

Adult↗