Access schedules of oral cocaine and ethanol in rats.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
T O'Connor
Publications and source records attributed to T O'Connor.
12 hour shifts begin in Dunedin.
Explore the source record for details and available documents.
Humans↗
myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens.
We studied 107 specimens (38 tumors and 69 tumor cell lines) from 90 patients with small cell lung cancer to determine the characteristics and clinical situations of patients from whom tumor cell lines could be established and the myc family DNA copy number. The proportion of extensive stage small cell lung cancer patients from whom a tumor cell line could be established prior to the initiation of therapy increased during the 10 years of the study (P less than 0.001). Amplification of one of the myc family genes occurred in 3 of 40 (8%) of the untreated patient specimens compared to 19 of 67 (28%) of the treated patient specimens (P = 0.01). The myc family DNA amplification occurred in 17 of 54 (31%) of the specimens from patients treated with cyclophosphamide-based combinations and 2 of 13 (15%) of the specimens from patients treated with etoposide/cisplatin (P = 0.25). Both tumors and tumor cell lines were obtained from 17 patients with small cell lung cancer and the myc family DNA copy number was similar in 16 of the 17 patients. We conclude that: (a) myc family DNA amplification occurs more commonly in specimens from treated than untreated patients (b) there are no prominent differences in the frequency of amplification following treatment with different chemotherapy regimens; and (c) myc family DNA amplification is similar in tumors and tumor cell lines from the same patients.
Antineoplastic Combined Chemotherapy Protocols↗
Intermolecular cross-links mediate aggregation of phospholipid vesicles by pulmonary surfactant protein SP-A.
As the most abundant glycoprotein component of pulmonary surfactant, SP-A (Mr = 30,000-36,000) plays a central role in the organization of phospholipid bilayers in the alveolar air space. SP-A, isolated from lung lavage, exists in oligomeric forms (N = 6, 12, 18, ...), mediated by collagen-like triple helices and intermolecular disulfide bonds. These protein-protein interactions, involving the amino-terminal domain of SP-A, are hypothesized to facilitate the alignment of surfactant lipid bilayers into unique tubular myelin structures. SP-A reorganization of surfactant lipid was assessed in vitro by quantitating the calcium-dependent light scattering properties of lipid vesicle suspensions induced by SP-A. Accelerated aggregation of unilamellar vesicles required SP-A and at least 3 mM free calcium. The initial rate of aggregation was proportional to the concentration of canine SP-A over lipid:protein molar ratios ranging from 200:1 to 5000:1. Digestion with bacterial collagenase or incubation with dithiothreitol (DTT) completely blocked lipid aggregation activity. Both treatments decreased the binding of SP-A to phospholipids. The conditions used in the DTT experiments (10 mM DTT, nondenaturing Tris buffer, 37 degrees C) resulted in the selective reduction and 14C-alkylation of the intermolecular disulfide bond involving residue 9Cys, whereas the four cysteines found in the noncollagenous domain of SP-A were inefficiently alkylated with [14C]-iodoacetate. HPLC analysis of tryptic SP-A peptides revealed that these four cysteine residues participate in intramolecular disulfide bond formation (138Cys-229Cys and 207Cys-221Cys). Our data demonstrate the importance of the quaternary structure (triple helix and intermolecular disulfide bond) of SP-A for the aggregation of unilamellar phospholipid vesicles.
Amino Acids↗
Hyporegenerative anemia associated with intrauterine transfusion in rhesus hemolytic disease.
Serial erythropoietin and ferritin levels were monitored in a fetus and newborn requiring three intravascular transfusions (in utero) for severe Rh disease. The newborn had a hematocrit of 37% at birth; however a hyporegenerative transfusion-dependent anemia developed and lasted approximately 3 months. The prolonged hyporegenerative anemia may be caused in part by erythropoietin suppression as a result of the fetal intravascular transfusions. In addition, anti-D antibody may also contribute to this anemia by a direct toxic effect on erythroid precursors and by peripheral hemolysis of reticulocytes.
Adult↗
Does intensive glycemic control in diabetic pregnancies result in normalization of other metabolic fuels?
Intensive treatment of insulin-dependent diabetes mellitus during pregnancy often normalizes plasma glucose levels. However, it is unclear whether this adversely affects other metabolic fuels that are essential to normal fetal growth and development. Metabolic studies were conducted after the subjects ingested a standardized mixed meal during each trimester in 7 normal and 15 insulin-dependent diabetic pregnant women. The latter were treated with continuous subcutaneous insulin infusion or multiple injections, which were adjusted to achieve strict glucose control throughout pregnancy. Insulin, alanine, branched-chain amino acids, triglycerides, free fatty acids, and ketones were measured every 15 to 30 minutes before a standardized breakfast and for 150 minutes after the breakfast. Patients with insulin-dependent diabetes mellitus were studied while they received their unusual insulin dosages. Fasting glucose levels (87 +/- 7 mg/dl) and glucose levels 150 minutes after the meal (112 +/- 11 mg/dl) were near normal. However, normoglycemia was achieved at the expense of increased plasma insulin levels (area under insulin response curves, p less than 0.01, vs nondiabetic curves). Nevertheless, fasting and post-prandial plasma branched-chain amino acids, alanine, and free fatty acids were similar in both groups. Fasting cholesterol, triglyceride, and ketone levels were also normalized. We conclude that normalization of circulating amino acids and lipids in conjunction with correction of hyperglycemia may contribute to favorable outcomes in infants of intensively treated diabetic mothers.
Adult↗
Is the pressure rate quotient a predictor or indicator of myocardial ischemia as measured by ST-segment changes in patients undergoing coronary artery bypass surgery?
Perioperative myocardial ischemia is associated with an increased risk of perioperative myocardial infarction (PMI). Several attempts have been made to define intraoperative hemodynamic predictors of myocardial ischemia. In a canine preparation with coronary stenosis, a pressure rate quotient (PRQ = mean arterial pressure/heart rate) less than one (PRQ less than 1) indicated subendocardial myocardial ischemia. The authors tested this hypothesis in patients undergoing elective coronary artery bypass graft operation (CABG), using electrocardiogram (ECG) ST-segment changes (leads II/V5) to diagnose myocardial ischemia. Sixty (n = 60) patients having CABG surgery were prospectively studied before initiation of cardiopulmonary bypass. Calibrated ECG leads II and V5 (diagnostic mode) were monitored continuously and recorded with the use of a Hewlett-Packard computer ST-segment analyzer. In addition, arterial and pulmonary artery pressures were monitored. Ischemia was defined as new-onset ST deviation (greater than or equal to 1 mm from the baseline ECG). ECG and hemodynamic data were stored at 2-min intervals for subsequent computer analysis. Serial creatinine phosphokinase (CPK) X MB (%) determinations and 12-lead ECGs were collected for the initial 3 postoperative days. Of the 3,463 intervals (2 min) available for study, 3,322 (96%) were satisfactorily recorded for 60 patients. Ischemia occurred during 65 intervals in 9 patients (9 of 60), of which only 34% (22 of 65) were associated with a PRQ less than 1 (P less than 0.01). In contrast, there were 466 intervals during which PRQ was less than 1, but without ECG evidence of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Continuous infusion of interleukin-2 and cyclophosphamide as treatment of advanced cancers: a National Biotherapy Study Group Trial.
We have evaluated the effect of Interleukin-2 [IL-2] after Cyclophosphamide (C) chemotherapy in 41 patients with metastatic cancer. IL-2 was given as a continuous infusion priming cycle 36 hours after C at 1 gm/m2 intravenously. In 39 evaluable patients, there were no complete remissions [CR], 2 partial remissions [PR], and 1 had a minor response [MR]. Stable disease for 30 days was seen in 16 patients whereas 20 progressed. The durations of partial and minor responses were brief, ranging from 1-6 months. Grade 3-4 neutropenia was seen in 41%. This was more severe than seen with IL-2 alone or IL-2 combined with lower doses of C. The marrow suppression was due to the chemotherapy. This combination of IL-2 and C appears to be reasonably well tolerated by patients, but toxicity is greater and the response rate is no better than results achieved by IL-2 alone. Responses of 26 patients with renal cancer appear to be inferior to our historical data using IL-2/LAK cells without C. Immune monitoring demonstrated changes expected with C chemotherapy (i.e., a non-selective decline in immune function). C induced no further differences in IL-2 induced changes in immune function.
Adult↗
Tumor cell lines established in vitro: an independent prognostic factor for survival in non-small-cell lung cancer.
OBJECTIVE: To determine the relation between in-vitro establishment of tumor cell lines and survival in patients with non-small-cell lung cancer. DESIGN: Cohort study. SETTING: Single-institution tertiary care center. PATIENTS: One hundred twenty-three consecutive patients with non-small-cell lung cancer from whom a viable tumor specimen could be obtained. INTERVENTION: Tumor tissue was removed at the time of entry into a therapeutic protocol. The tumor tissue was processed in the laboratory for attempted cell-line establishment. Patients classified as potentially curable (stages I, II, and IIIA) were treated with surgical resection, radiation therapy, or a combination. Patients suitable for palliative therapy only (stages IIIB and IV) were treated with radiation therapy with or without chemotherapy. Chemotherapy was based on in-vitro drug sensitivity when available. Cell-line establishment was correlated to clinical outcome. MEASUREMENTS AND MAIN RESULTS: Univariate analysis of survival was done using the log-rank test; multivariate analysis was done by Cox modeling step-up and step-down techniques. Cell lines were established from the tumor specimens of 25 patients (20%). Those patients experienced a median survival of 7 months compared with 18 months in patients from whom cell lines could not be established (P less than 0.001). In the 61 patients with potentially curable disease, 8 patients (13%) with cell lines established had a median survival of 8 months compared with 32 months for those without cell lines established (P = 0.001). In the 62 palliative group patients, the median survival of the 17 patients (27%) from whom tumor cell lines were established was 5 months compared with 7 months for those without cell lines (P = 0.15). Multivariate analysis in both groups showed cell-line establishment to be a significant indicator of prognosis (P less than 0.0001 for curable group; P less than 0.01 for palliative group). CONCLUSION: In-vitro tumor growth is related to decreased patient survival, which in turn reflects the biologic aggressiveness of cancers giving rise to these tumor cell lines.
Analysis of Variance↗
Comparing methods of measurement: an alternative approach.
Explore the source record for details and available documents.
Humans↗
Biochemical and immunological characterization of the major structural proteins of feline immunodeficiency virus.
Feline immunodeficiency virus (FIV) structural proteins were identified using sera obtained from experimentally inoculated cats. Proteins analysed by both radioimmunoprecipitation and Western blotting were specific for FIV infection and failed to cross-react with either antisera to feline leukaemia virus of feline syncytium-forming virus. Western blot analysis of purified virus revealed immunoreactive proteins with apparent Mr of 65K, 50K, 40K, 32K, 24K, 15K and 10K. The major core structural proteins of the virus were isolated by reverse phase HPLC and the aminoterminal sequences of p10 and p24 were determined. Monoclonal antibodies specific for p24 suggested the presence of a precursor protein that could be detected in 35[S]methionine/cysteine-labelled, virus-infected cell extracts. This putative precursor protein possessed an apparent Mr of 50K (Pr50gag). Further analysis revealed the presence of two additional proteins of 130K and 40K. Experiments utilizing tunicamycin, endoglycosidase H and glycopeptidase F revealed that p130 and p40 exhibited properties characteristic of glycoproteins. Our studies also indicated that FIV is immunologically related to other lentiviruses.
Amino Acid Sequence↗
Emergency tracheal intubation in the postanesthesia care unit: physician error or patient disease?
Inadequate airway maintenance has been a major factor in perioperative morbidity. To determine the incidence and etiology of emergency tracheal intubations in the postanesthesia care unit (PACU), we retrospectively reviewed 13,593 consecutive admissions to our PACU from October 1986 through October 1988. Twenty-six patients (26/13,593 = 0.19%) required the insertion of an endotracheal tube while in the PACU. Seventy-seven percent (20/26) of the intubations occurred within 1 h of extubation and/or admission to the PACU. Intubation was more common at the extremes of age; 54% of those intubated were more than 60 yr old (P = 0.003); 19% were less than 3 yr old (P less than 0.05). Twenty-three percent of the intubated patients had undergone otolaryngologic procedures (P = 0.008). Interestingly, 73% of the intubations occurred during the months of January through June (P = 0.016). Median PACU admission scores were lower for the intubated group (P less than 0.001). There was no association between intubation and gender (P = 0.74), anesthetic technique (P = 0.41), or anesthetic agent (P = 0.49). Of the 26 intubations, 18 (69%) were considered to be directly related to anesthetic management. Despite the extremely low incidence of emergency tracheal intubation in a heterogeneous group of patients admitted to our PACU, preventable anesthesia-related etiologic factors including excessive sedative or anesthetic effect, inappropriate fluid management, persistent muscle relaxant effect, and upper airway obstruction contributed to the majority of these intubations.
Adolescent↗
Survival in children with perinatally acquired human immunodeficiency virus type 1 infection.
We describe our experience at Jackson Memorial Hospital in Miami, Florida, with 172 children who were given diagnoses of perinatally acquired infection with human immunodeficiency virus type 1 (HIV-1). The 146 mothers of the children acquired HIV-1 through heterosexual contact (69 percent), intravenous drug use (30 percent), or blood transfusion (1 percent). The children presented with symptomatic disease at a median age of eight months; only 21 percent presented after the age of two years. The most common first manifestations of disease were lymphoid interstitial pneumonia (in 17 percent), encephalopathy (in 12 percent), recurrent bacterial infections (in 10 percent), and candida esophagitis (in 8 percent), for which the median survival times from diagnosis were 72, 11, 50, and 12 months, respectively. Nine percent of the children had Pneumocystis carinii pneumonia at a median age of five months and had a median survival of only one month. The median survival for all 172 children was 38 months from the time of diagnosis. Mortality was highest in the first year of life (17 percent), and by proportional-hazard analysis the probability of long-term survival is low. In multivariate analyses, early age at diagnosis and the first identifiable pattern of clinical disease were found to be independently related to survival. We conclude that children with perinatally acquired HIV-1 infection have a very poor prognosis and that most become symptomatic before one year of age. Early diagnosis is important, since there is only a short interval in which to initiate prophylactic or antiviral treatment before progressive disease begins.
Acquired Immunodeficiency Syndrome↗
Mechanism of DNA strand nicking at apurinic/apyrimidinic sites by Escherichia coli [formamidopyrimidine]DNA glycosylase.
Escherichia coli [formamidopyrimidine]DNA glycosylase catalyses the nicking of both the phosphodiester bonds 3' and 5' of apurinic or apyrimidinic sites in DNA so that the base-free deoxyribose is replaced by a gap limited by 3'-phosphate and 5'-phosphate ends. The two nickings are not the results of hydrolytic processes; the [formamidopyrimidine]DNA glycosylase rather catalyses a beta-elimination reaction that is immediately followed by a delta-elimination. The enzyme is without action on a 3'-terminal base-free deoxyribose or on a 3'-terminal base-free unsaturated sugar produced by a beta-elimination reaction nicking the DNA strand 3' to an apurinic or apyrimidinic site.
Apurinic Acid↗
Diagnosis of gestational diabetes by use of a glucose polymer.
The oral glucose tolerance test is the recommended method for the assessment of carbohydrate metabolism in pregnancy. However, available glucose drinks are often associated with varying degrees of gastrointestinal symptoms that might preclude meaningful studies. Polycose (Ross Labs, Columbus, Ohio) is a glucose saccharide polymer mixture containing 3% glucose, 7% maltose, 5% maltotriose, and 85% polysaccharide of 4 to 15 glucose units, with an osmotic load one fifth that of glucose. We assessed the efficacy of this glucose polymer in the performance of a 3-hour carbohydrate tolerance test with glucose and glucose polymer used 3 to 5 days apart in each patient tested. After 2 days of 300 gm carbohydrate-enriched diets, 48 patients underwent 3-hour carbohydrate tolerance tests at a mean gestational age of 30 +/- 3 weeks. Statistical analysis revealed a moderate level of agreement (kappa = 0.45, p less than 0.001) between the results of both carbohydrate tolerance test preparations. Patients experienced fewer gastrointestinal symptoms with the glucose polymer than with glucose. These preliminary data suggest that glucose polymer may be effectively used in the performance of a 3-hour carbohydrate tolerance test.
Blood Glucose↗
Envelope cross-reactivity in Western blot for HIV-1 and HIV-2 may not indicate dual infection.
Serological identification of infection with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) by western blot alone may not be sufficient to diagnose dual infection. Extensive cross-reactions (eg, to envelope glycoprotein antibody) are seen on heterologous western blots. The use of other techniques, in this case competitive enzyme-linked immunosorbent assays, indicates that blot patterns previously thought to demonstrate simultaneous dual infections should be interpreted with caution.
Acquired Immunodeficiency Syndrome↗
Human retroviral infections in The Gambia: prevalence and clinical features.
The prevalence of infection with human immunodeficiency virus type 1 (HIV 1) is lower in west Africa than in other parts of Africa. Human immunodeficiency virus type 2 (HIV 2) has been isolated from west African patients and may be transmitted by heterosexual contact. The prevalence of antibodies to HIV 1 and HIV 2 was studied by enzyme linked immunosorbent assay (ELISA) among various groups of subjects in The Gambia, west Africa--namely, prostitutes, blood donors, patients with suspected infection with HIV, patients attending clinics for sexually transmitted diseases, and patients with tuberculosis. Four cases of the acquired immune deficiency syndrome (AIDS) due to infection with HIV 1 were detected, of which three had been acquired abroad. No other subject was found to be positive for antibodies to HIV 1. The prevalence of antibodies to HIV 2 among the patients attending clinics for sexually transmitted diseases was found to have increased from 0/117 in 1984 to 10/185 (5%) in the last six months of 1986. One out of 278 blood donors was positive for antibodies to HIV 2 as were 10 out of 80 patients with suspected AIDS. HIV 2 seems to be transmitted sexually, and, although it has been present for only a short time, it seems to be endemic in The Gambia and is pathogenic.
Acquired Immunodeficiency Syndrome↗