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Biomedical subjects

L R Smith

Publications and source records attributed to L R Smith.

At least 109 records · Page 6Linked to original sources
PubMed1990

Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass.

We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age-matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/- 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ml/100 g/min (p = 0.001) at normothermia and rose from 0.60 +/- 0.27 to 1.49 +/- 0.35 ml/100 g/min (p = 0.0005) in the controls. Thus, despite temperature-mediated changes in oxygen consumption, diabetic patients did not increase cerebral blood flow as metabolism increased. Arteriovenous oxygen saturation gradients and oxygen extraction across the brain were calculated from arterial and jugular bulb blood samples. The increase in arteriovenous oxygen difference between temperature conditions in diabetic patients and controls was significantly different (p = 0.01). These data reveal that diabetic patients lose cerebral autoregulation during cardiopulmonary bypass and compensate for an imbalance in adequate oxygen delivery by increasing oxygen extraction.

Brain↗
PubMed1989

The relation of flow cytometry to clinical and biologic characteristics in women with node negative primary breast cancer.

Flow cytometry (FC) analysis including DNA index (ploidy status) and cell kinetics (%S and %S + G2/M) was done on frozen tissue of the primary lesions of 101 women with node negative (N-) breast cancer who were studied prospectively. Currently, 19% (19/101) of the patients have recurred. No significant relations have been found between recurrence or survival and age, estrogen/progesterone receptor status, tumor size, and tumor type. The DNA index (ploidy) was not related to any clinical variable, time to recurrence, or survival. Aneuploid tumors did, however, have significantly higher %S phase activity. Patients with %S activity less than or equal to the median value were significantly different from those patients with %S above the median. They were older and had a higher frequency of ER/PR positive and well- or moderately differentiated tumors. Patients with %S + G2/M greater than the median value showed shorter time to recurrence (P = .055) and shorter survival (P = .006), whereas %S alone was significantly associated only with survival. Multivariate analysis showed that neither DNA index nor cell kinetics was significantly associated with time to relapse. DNA index was not significantly associated with survival; %S was of borderline significance whereas %S + %G2/M was a significant independent predictor of survival. Although FC data may provide independent information related to survival in N-women, additional research in a larger number of patients is needed to define its precise role in patient management.

Breast Neoplasms↗
PubMed1989

Preliminary crystallographic data and primary sequence for anti-peptide Fab' B13I2 and its complex with the C-helix peptide from myohemerythrin.

Crystals of the Fab' fragment from the monoclonal anti-peptide antibody B1312 and of the Fab'-peptide antigen complex have been characterized. The monoclonal antibodies were raised against a synthetic homologue of the C-helix of myohemerythrin (residues 69-87 in myohemerythrin). The Fab'-peptide complex crystallizes in space group P6322 with unit cell dimensions a = b = 142.5 A, c = 101.5 A, alpha = beta = 90 degrees, gamma = 120 degrees, and Z = 1. The native Fab' crystallizes in space group P212121 with unit cell dimensions a = 98.0 A, b = 151.7 A, c = 80.8 A, alpha = beta = gamma = 90 degrees, and Z = 2. Both crystal forms diffract to beyond 2.6 A resolution. We also report the cDNA and predicted amino acid sequences for the variable regions of both the light and heavy chains of this anti-peptide antibody.

Amino Acid Sequence↗
PubMed1989

Thyrotropin: an endogenous regulator of the in vitro immune response.

We have previously shown that thyrotropin (TSH), which is produced by lymphocytes in response to the T cell mitogen staphylococcal enterotoxin A, enhances in vitro antibody production to T cell-dependent and independent Ag (SRBC and trinitrophenylated Brucella abortus [BA-TPN], respectively) as determined by a direct plaque-forming cell assay. As a result of these studies, experiments were designed to examine the possible immunoregulatory function of thyrotropin-releasing hormone (TRH) on the in vitro antibody response to the T cell-independent Ag BA-TNP. Our studies demonstrate that TRH at very low concentrations (pM) enhances the in vitro plaque-forming cell response to BA-TNP and also induces splenocyte production of TSH. Other hypothalamic-releasing factors were without effect. This enhancement effect by TRH was specifically blocked by rabbit antisera to the TSH-beta subunit, whereas addition of normal rabbit sera had no effect. These data suggest that TRH specifically enhances the in vitro antibody response via production of immunoreactive TSH.

Adjuvants, Immunologic↗
PubMed1989

Influence of particulate trap oxidizers on emission of mutagenic compounds by diesel automobiles.

Diesel exhaust particles are known to contain mutagenic and carcinogenic chemicals. The aim of this study was to determine whether, and to what extent, catalytic particulate trap oxidizers on light-duty diesel engines may reduce the emission of particle-associated mutagenic chemicals into the environment. Exhaust particles were collected from Mercedes Benz and Volkswagen diesel automobiles, equipped with or without the manufacturer's exhaust traps, while running on a chassis dynamometer under specified load conditions. Exhaust particles were collected from a dilution tunnel onto 20" X 20" Teflon-coated fiberglass filters. Mutagenesis tests of dichloromethane (DCM) extracts of the particles were conducted using the Ames Salmonella bacterial test system. The mutation rate was calculated in terms of histidine revertants per mile of travel during a set of standard test cycles. With both vehicles the traps produced an 87-92% reduction in the total amount of particulate material collected by the filters. There was no significant change in the specific mutagenic activity (revertants per microgram of DCM particle extract) with or without the traps. These studies support the notion that installation of exhaust traps which reduce particulate emission on diesel-powered vehicles will also reduce the emission of particle-associated mutagenic and carcinogenic materials into the environment.

Air Pollution↗
PubMed1989

Interleukin-2 induction of ACTH secretion: presence of an interleukin-2 receptor alpha-chain-like molecule on pituitary cells.

Pituitary cells were shown to release corticotropin (ACTH) in response to interleukin-2 (IL-2) and to express a protein that is related to the alpha-chain of the IL-2 receptor (IL-2R). The alpha-chain-like molecule was bound by a rat monoclonal antibody to the murine IL-2 receptor as well as to IL-2. Sodium dodecylsulfate-polyacrylamide gel electrophoretic analysis of the affinity-purified material from pituitary cells demonstrated a protein which was similar to that which was isolated from activated splenocytes. Thus, IL-2 and its receptor may be one of several hormone-receptor pairs utilized by both the immune and neuroendocrine systems for intersystem communication.

Adrenocorticotropic Hormone↗
PubMed1989

Current management of mitral valve incompetence associated with coronary artery disease.

At a time when hospital mortality for adult cardiac operations is continuing to fall, the combined mitral valve coronary bypass subset remains at relatively high risk. Efforts to improve results should be directed toward a more general application of mitral reconstruction in this population, tailoring the type of repair to the pathological anatomy of valve dysfunction. Other promising therapeutic measures include the liberal use of reperfusion therapy in the acute papillary muscle dysfunction group, better selection patients for operation, and perhaps operative recommendation to a greater proportion of the more stable patients that previously were treated medically. Finally increasing the general awareness of this problem should hasten the development of improved management strategies.

Coronary Artery Bypass↗
PubMed1989

Ischemic mitral regurgitation.

At a time when hospital mortality for adult cardiac operations is continuing to fall, the ischemic mitral regurgitation subset remains at relatively high risk. Based on analysis of available data, efforts to improve results might be directed toward a more general application of mitral valve reconstruction in this population. Other promising therapeutic measures include the liberal use of reperfusion therapy in the acute papillary muscle dysfunction group, better selection of patients for operation, and, perhaps, operative recommendation to a greater proportion of the more stable patients who previously were treated medically. Incorporating these therapeutic concepts into routine clinical practice may improve the overall prognosis of this difficult subgroup.

Actuarial Analysis↗
PubMed1989

The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children.

Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.

Blood Pressure↗
PubMed1989

Effects of cardiopulmonary bypass on cerebral blood flow in neonates, infants, and children.

Cardiopulmonary bypass (CPB) management in neonates, infants, and children requires extensive alterations in temperature, pump flow rate, and perfusion pressure, with occasional periods of circulatory arrest. The effect of these alterations on cerebral blood flow (CBF) are unknown. This study was designed to determine the relation of temperature and mean arterial pressure to CBF during hypothermic CPB (18 degrees-32 degrees C), with and without periods of total circulatory arrest. CBF was measured before, during, and after hypothermic CPB with xenon-clearance techniques in 67 pediatric patients, aged 1 day-16 years. Patients were grouped based on different CPB techniques: group A, repair during moderate-hypothermic bypass at 25 degrees-32 degrees C; group B, repair during deep-hypothermic bypass at 18 degrees-22 degrees C; and group C, repair with total circulatory arrest at 18 degrees C. There was a significant correlation of CBF with temperature during CPB. CBF significantly decreased under hypothermic conditions in all groups compared with prebypass levels under normothermia. In groups A and B, CBF returned to baseline levels in the rewarming phase of CPB and exceeded baseline levels after bypass. In group C, no significant increase in CBF was observed during rewarming after total circulatory arrest (32 +/- 12 minutes) or after weaning from CPB. During moderate-hypothermic CPB (25 degrees-32 degrees C), there was no association between CBF and mean arterial pressure. However, during deep-hypothermic CPB (18 degrees-22 degrees C), there was an association between CBF and mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

The speech regulating system: temporal and aerodynamic responses to velopharyngeal inadequacy.

Temporal and respiratory responses to a loss of velar resistance were measured in 107 subjects demonstrating varying degrees of velopharyngeal inadequacy. The subject data were compared to data generated by a mechanical model representing a passive system. The pressure-flow technique was used to estimate velopharyngeal orifice size and measure respiratory and temporal characteristics of aerodynamic events associated with the production of the nasal-plosive blend /mp/ in the word "hamper". Subjects were categorized as having adequate closure (less than 0.05 cm2), adequate/borderline closure (0.05-0.09 cm2), borderline/inadequate closure (0.10-0.19 cm2) and inadequate closure (greater than or equal to 0.20 cm2). The data revealed that intraoral pressure fell 10-fold in the model as velopharyngeal orifice area changed from adequate closure to inadequate. The subject data demonstrated only a 1.4-fold drop in pressure. Airflow data indicated that there was a 10-fold increase in respiratory volume in the subject data corresponding to the change from adequacy to inadequacy. When respiratory and temporal responses were assessed together, the findings revealed that airflow and temporal changes minimized the fall of pressure as velar resistance declined across groups.

Adolescent↗
PubMed1989

Assessment of left ventricular functional preservation during isolated cardiac valve operations.

To evaluate intraoperative changes in myocardial performance during valvular operations, ventricular functional measurements were obtained in 16 patients before and after elective cardiac valvular replacement. Six patients had mitral regurgitation, four had mitral stenosis, and six had calcific aortic stenosis; all patients underwent isolated mitral or aortic valve replacement. Cold potassium crystalloid cardioplegia, topical hypothermia, and low-flow systemic hypothermia were employed uniformly. Just before and 10 minutes after cardiopulmonary bypass was discontinued, left ventricular pressure and volume data were recorded at four to five different steady-state levels of filling produced by blood infusion or withdrawal from the aortic cannula (mean end-diastolic pressure range, 10-22 mm Hg; mean end-diastolic volume range, 120-168 ml). Portable first-pass radionuclide ventriculography and simultaneous micromanometry were used for construction of left ventricular pressure-volume loops from which stroke work and end-diastolic volume were calculated. Two-dimensional transesophageal echocardiograms also were recorded, and epicardial pacing maintained heart rate as constant as possible. As compared with prebypass measurements, echocardiographic left ventricular wall volume changed insignificantly after the valvular procedures (178-181 ml/m2, p greater than 0.5). The stroke work-end-diastolic volume relationship before and after operation was highly linear in all studies (mean = 0.97). The slope and x intercept of this relationship did not change significantly after operation, indicating a stable level of left ventricular function (from 12.7 x 10(4) to 10.0 x 10(4) ergs/ml and from 67 to 57 ml, respectively; p greater than 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Bypass↗
PubMed1989

Screening of velopharyngeal inadequacy by differential pressure measurements.

Warren (1979) described an approach for screening velopharyngeal inadequacy using a device (PERCI) that measures orifice differential pressure (P). The PERCI score is based on the relationship between velopharyngeal orifice (VPO) area and velopharyngeal orifice differential pressure. The purpose of this study was to test the original assumptions, which were based on modeling experiments and a small sample size. The sample in this study included 515 subjects who demonstrated various degrees of velopharyngeal inadequacy. The pressure-flow technique was used to estimate velopharyngeal orifice size and to measure orifice differential pressure. The data demonstrate that differential pressures greater than 3.0 cm H2O generally predict adequacy of closure, whereas differential pressures less than 3.0 cm H2O usually indicate inadequacy. These findings support the use of orifice differential pressure as a simple screening of velopharyngeal function.

Humans↗
PubMed1989

The effect of age on cerebral blood flow during hypothermic cardiopulmonary bypass.

Cerebral blood flow was measured in 20 patients by xenon 133 clearance methodology during nonpulsatile hypothermic cardiopulmonary bypass to determine the effect of age on regional cerebral blood flow during these conditions. Measurements of cerebral blood flow at varying perfusion pressures were made in patients arbitrarily divided into two age groups at nearly identical nasopharyngeal temperature, hematocrit value, and carbon dioxide tension and with equal cardiopulmonary bypass flows of 1.6 L/min/m2. The range of mean arterial pressure was 30 to 110 mm Hg for group I (less than or equal to 50 years of age) and 20 to 90 mm Hg for group II (greater than or equal to 65 years of age). There was no significant difference (p = 0.32) between the mean arterial pressure in group I (54 +/- 28 mm Hg) and that in group II (43 +/- 21 mm Hg). The range of cerebral blood flow was 14.8 to 29.2 ml/100 gm/min for group I and 13.8 to 37.5 ml/100 gm/min for group II. There was no significant difference (p = 0.37) between the mean cerebral blood flow in group I (21.5 +/- 4.6 ml/100 gm/min) and group II (24.3 +/- 8.1 ml/100 gm/min). There was a poor correlation between mean arterial pressure and cerebral blood flow in both groups: group I, r = 0.16 (p = 0.67); group II, r = 0.5 (p = 0.12). In 12 patients, a second cerebral blood flow measurements was taken to determine the effect of mean arterial pressure on cerebral blood flow in the individual patient. Changes in mean arterial pressure did not correlate with changes in cerebral blood flow (p less than 0.90). We conclude that age does not alter cerebral blood flow and that cerebral blood flow autoregulation is preserved in elderly patients during nonpulsatile hypothermic cardiopulmonary bypass.

Aged↗
PubMed1988

The relationship between nasal airway size and nasal-oral breathing.

Most clinicians agree that impaired nasal breathing results in obligatory mouth breathing. Some believe that mouth breathing influences dentofacial growth; others disagree. The term mouth breathing is confusing because total mouth breathing rarely occurs. A combination of nasal and oral breathing is more usual. The purpose of the present study involving 116 adult subjects was to (1) assess the relationship between nasal impairment and nasal-oral breathing, (2) determine the switching range from nasal to nasal-oral breathing, and (3) quantify the term mouth breathing. The pressure-flow technique was used to estimate nasal airway size; inductive plethysmography was used to assess nasal-oral breathing in normal and impaired breathers. Analysis of the date showed a Pearson rank correlation of 0.545 (P less than 0.001) between nasal area and nasal-oral respiration. Ninety-seven percent of subjects with a nasal size less than 0.4 cm2 were mouth breathers to some extent. About 12% of subjects with an adequate airway were assumed to be habitual mouth breathers. The findings indicate that the switching range from nasal to nasal-oral breathing is very narrow (0.4-0.45 cm2). These results also confirm our contention that in adults an airway less than 0.4 cm2 is impaired.

Adult↗
PubMed1988

Production of immunoreactive growth hormone by mononuclear leukocytes.

In the present study, we evaluated whether mononuclear leukocytes could synthesize and secrete growth hormone (GH) in vitro. By using RNA slot blot analysis, we detected maximum spontaneous levels of specific GH mRNA in the cytoplasm of rat leukocytes after a 4-h incubation. Northern gel analysis demonstrated that the specific leukocyte GH RNA was polyadenylated and had a molecular mass of 1.0 kb. Further studies using immunofluorescence, antibody affinity chromatography, and Sephacryl gel filtration indicate that leukocytes secrete a high molecular weight (greater than 300,000) and a low molecular weight (approximately 22,000) immunoreactive GH (irGH). A substantial amount of the high molecular weight irGH can be converted to the lower molecular weight form after reduction with mercaptoethanol. The irGH appeared to be de novo synthesized because it could be radiolabeled with tritiated amino acids and its production could be blocked by previous incubation of leukocytes with cycloheximide. The replication of Nb2 rat node lymphoma cells was stimulated by affinity-purified human lymphocyte-derived irGH. The growth stimulation was blocked by specific antibodies to hGH. We conclude that lymphocytes produce an irGH that is similar to if not identical to pituitary GH in terms of bioactivity, antigenicity, and molecular weight. The findings demonstrate a potential regulatory loop between the immune and neuroendocrine tissues.

Animals↗
PubMed1988

Phase II trial of high-dose cytosine arabinoside and cisplatin in recurrent squamous carcinoma of the head and neck. A Piedmont Oncology Association Study.

Fifteen patients with recurrent squamous carcinoma of the head and neck received high-dose cytosine arabinoside (ara-C) (3 g/m2) and cisplatin (100 mg/m2) every 3 weeks in an attempt to explore the dose-dependent synergy between these two agents. A partial response was attained in one patient; there were no complete responses. The major toxicity was myelosuppression. With the current schedule, high-dose ara-C failed to improve the response rate achieved with cisplatin alone.

Adult↗