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Biomedical subjects

C L Leach

Publications and source records attributed to C L Leach.

At least 37 records · Page 2Linked to original sources
PubMed1994

Liquid ventilation: it's not science fiction anymore.

Liquid ventilation is, by all initial considerations, an unconventional concept. Decades of research, however, have found that by using perfluorocarbons, which are capable of holding high concentrations of critical gases such as oxygen and carbon dioxide, gas exchange optimal enough to support life is possible with no known toxic effects. The earliest method of liquid ventilation, tidal liquid breathing, involved infusion and active removal of tidal volumes of perfluorocarbons by a liquid ventilator for gas exchange. Recently, a new method of partial liquid breathing, called perfluorocarbon-associated gas exchange, makes the process of liquid ventilation simpler by using conventional gas ventilators. Current research is showing great promise in the use of liquid ventilation for patients with pulmonary pathology. Critical care nurses should become knowledgeable of this new mode of ventilation and be prepared to meet the special needs of this unique population.

Critical Care↗
PubMed1993

Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome: a prospective, randomized, controlled study.

OBJECTIVE: To determine the efficacy of perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome. DESIGN: Prospective, randomized, controlled study. SETTING: State University of New York at Buffalo, School of Medicine and Biomedical Sciences. SUBJECTS: Eleven premature lambs with respiratory distress syndrome, delivered by cesarean section. INTERVENTIONS: Five lambs were supported by conventional mechanical ventilation alone. Six lambs were switched to perfluorocarbon-associated gas exchange after 60 to 90 mins of conventional mechanical ventilation. Perfluorocarbon-associated gas exchange was accomplished by instilling a volume of liquid perfluorocarbon equivalent to normal functional residual capacity (30 mL/kg) into the trachea, performing 3 to 4 mins of tidal liquid ventilation, and, at end-expiration, with liquid functional residual capacity of 30 mL/kg remaining in the lung, reconnecting the animal to the volume ventilator for gas tidal volumes. MEASUREMENTS AND MAIN RESULTS: Serial arterial blood gases and lung mechanics were measured. While receiving conventional ventilation, all animals developed progressive hypoxemia, hypercarbia, and acidosis. However, in the perfluorocarbon-associated gas exchange group, within 5 mins of the initiation of perfluorocarbon-associated gas exchange, mean PaO2 increased four-fold, from 59 +/- 6 torr (7.9 +/- 0.8 kPa) during conventional ventilation to 250 +/- 28 torr (33.3 +/- 3.7 kPa; p < .05) during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (268 +/- 38 torr; 35.7 +/- 5.1 kPa; p < .05). Mean PaCO2 decreased progressively from 62 +/- 4 torr (8.3 +/- 0.5 kPa) during conventional ventilation to 38 +/- 3.3 torr (5.1 +/- 0.4 kPa) at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean pH concomitantly increased. Dynamic compliance increased three-fold within 15 mins of instituting perfluorocarbon-associated gas exchange, from 0.31 +/- 0.02 mL/cm H2O during conventional ventilation to 0.90 +/- 0.11 mL/cm H2O during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean peak expiratory flow and mean expiratory resistance were essentially unchanged during perfluorocarbon-associated gas exchange as compared with conventional ventilation in the same group. CONCLUSIONS: We conclude that perfluorocarbon-associated gas exchange, which employs liquid functional residual capacity and gas tidal volumes delivered by a conventional ventilator, can facilitate oxygenation and CO2 removal, and dramatically improve lung mechanics in the premature lamb with respiratory distress syndrome.

Airway Resistance↗
PubMed1992

Pathophysiology of congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH.

Exogenous surfactant therapy (EST) in surfactant-deficient premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Reports have demonstrated that newborns with congenital diaphragmatic hernia (CDH) have lung compliance, pressure-volume curves, and hyaline membrane formation resembling those changes seen in surfactant deficient premature newborns. We hypothesize that EST may also benefit infants with CDH. All high risk cases of prenatally diagnosed CDH at Children's Hospital of Buffalo from November 1988 to February 1991 were prospectively evaluated for EST. In those families who chose to participate, the surfactant preparation, Infasurf (100 mg/kg), was instilled into the newborn's lungs prior to the first breath. The remainder of the perinatal, neonatal, and surgical care was performed in a routine manner. Three high-risk prenatally diagnosed newborns with left CDH were treated with EST. All showed signs of decreased pulmonary compliance, but could still be adequately oxygenated and ventilated. Surgical correction was performed after stabilization and all required patch closures. Two of the three infants suffered no life-threatening episodes of pulmonary hypertension and all survived. These infants had many known indicators for poor outcome in CDH with an expected survival of less than 20%. We believe that EST in these neonates with CDH contributed to their survival with minimum morbidity. These results suggest that surfactant replacement for the high-risk neonate with CDH warrants further consideration and a randomized clinical trial is being planned.

Adult↗
PubMed1992

Pathophysiology of congenital diaphragmatic hernia II: the fetal lamb CDH model is surfactant deficient.

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and pulmonary hypertension. We hypothesize that a surfactant deficiency may in part be contributing to the pathophysiology of CDH. This study documents the functional, quantitative, and qualitative aspects of the surfactant status of the alveolar air-liquid interface and the type II pneumocyte in the fetal lamb CDH model. Ten lamb fetuses (gestational age, 80 days) had a CDH created via a left thoracotomy and then were allowed to continue in utero development until term. Three litter mates and three nonoperated time-dated fetuses served as controls. At term, pressure-volume curves were performed to measure pulmonary compliance and total lung capacity. Alveolar lavage was then performed to measure the quantitative and the qualitative aspects of pulmonary surfactant. Finally, isolation of type II pneumocytes allowed quantification of phospholipid synthesis. When compared with controls (N = 6), the CDH lambs (N = 5) had significantly smaller lungs (P = .009), decreased total lung capacity (P less than .001) and compliance (P less than .001), reduced total lavaged phospholipids (P = .006), and decreased percent phosphatidylcholine (P = .02). CDH lambs also had increased total lavaged proteins (P = .05) and higher minimum dynamic surface tension (P less than .001). A surfactant deficiency may be contributing to the pathophysiology of CDH. Surfactant replacement therapy in premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Exogenous surfactant may also benefit infants with CDH.

Animals↗
PubMed1990

The abused woman and her family of origin.

The abuse of women in significant heterosexual relationships is an important societal problem in the United States. Structural family therapy offers a useful perspective to nurse therapists working with abused women who have left the abusive relationship to rejoin their families of origin. Common errors are avoided if the abused woman and her family are diagnosed within the system's context of structural family therapy. Dysfunctional transactional patterns that originated in the abused woman's childhood or adolescent years can be challenged at their source.

Family Therapy↗
PubMed1989

Lung injury induced by short-term intermittent trimellitic anhydride (TMA) inhalation.

We have developed a rat model of lung injury with interstitial pneumonitis, lung hemorrhage, and a systemic and pulmonary immune response to trimellitic anhydride (TMA)-haptenized proteins induced by TMA inhalation for 10 days. The present studies explored the induction of lung injury induced by short-term intermittent TMA inhalation, a model more likely to simulate short-term industrial exposures during inadvertent spills of TMA. Sprague-Dawley rats inhaled TMA powder (500 micrograms/m3) on days 1, 5, and 10, and were necropsied on day 30, 18 hours after a 6-hour TMA-inhalation challenge on day 29. Rats were bled every second day and at necropsy. Serum IgG, IgA, and IgM antibody to trimellityl rat serum albumin was measured by ELISA. There was a rise in IgM and IgA antibody to trimellityl rat serum albumin starting at day 5 that peaked at day 20 with a decline in IgM by day 30. IgG antibody rose at day 7, peaked at day 20, and plateaued. The IgG antibody level was 10 times higher than the IgA or IgM level. In a second experiment, 18 rats were administered TMA-inhalation exposure on days 1, 5, and 10, and a TMA challenge on day 22. The number of hemorrhagic foci, lung weights, and lung-displacement volumes at necropsy on day 23 were highly correlated with IgG, IgA, and IgM serum-antibody levels. In a final experiment, rats developed a mean of 112 hemorrhagic foci per lung on day 30 after receiving only two TMA-inhalation exposures on days 1 and 5 with a rechallenge on day 29. (ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1989

Immunologic tolerance in rats during 13 weeks of inhalation exposure to trimellitic anhydride.

Trimellitic anhydride (TMA) causes several immunologically based pulmonary syndromes in humans. We developed a rat model representative of some of those syndromes whereby rats exposed for 2 weeks to TMA by inhalation developed hemorrhagic lung foci and pneumonitis accompanied by the appearance of TMA-specific serum antibody. The purpose of the study reported here was to examine the long-term, low-dose effects of TMA inhalation. Rats were exposed to target concentrations of 0, 2, 15, or 50 micrograms/m3 TMA 6 hr/day, 5 days/week for 13 weeks. The study included an interim 6.5-week termination and two recovery periods of 3 and 38 weeks, each with and without a final TMA inhalation challenge. Additional rats were bled regularly throughout the study and monitored for the appearance of TMA-specific antibody; other rats were terminated periodically during the 13-week exposure and examined for lung lesions. These serially terminated rats showed that TMA-induced lung lesions reached a maximum after approximately 2 weeks of exposure, but began to diminish thereafter. Rats bled regularly showed increasing TMA-specific antibody titers through the first 6 weeks of exposure, after which antibody titers diminished. Serum antibody levels rose sharply after the 13-week exposure ended and tapered off throughout the recovery period. Rats terminated after 6.5 weeks of exposure showed a dose-dependent increase in lung lesions and serum antibody. However, rats exposed to TMA for 13 weeks showed greatly reduced lung lesions and antibody titers. Rats exposed for 13 weeks and allowed to recover for 3 weeks showed increased antibody titers but few lesions, even after a TMA challenge. Rats exposed for 13 weeks and allowed to recover 38 weeks had reduced but still significant antibody titers; however, no lung lesions were noted even after a TMA inhalation challenge prior to termination. These results indicated that rats became tolerant to TMA and that 13 weeks of exposure to TMA did not produce lesions of any type, even after 38 weeks of recovery.

Administration, Inhalation↗
PubMed1989

Marfan's syndrome, pregnancy, and the cardiac surgeon.

Marfan's syndrome in a pregnant woman appears to be particularly hazardous because of the increased risk of aortic rupture. The first reported case report of replacement of the ascending aorta in a pregnant woman with a successful outcome for mother and fetus is presented. The literature is reviewed with regard to Marfan's syndrome and pregnancy as well as to open heart surgery during pregnancy.

Adult↗
PubMed1988

Antibody response to trimellityl hemoglobin in trimellitic anhydride-induced lung injury.

Sprague-Dawley rats were exposed to trimellitic anhydride by inhalation, and the antibody response to trimellityl (TM)-conjugated hemoglobin (HB) and TM rat serum albumin (RSA) was compared. Groups of rats were exposed to trimellitic anhydride by inhalation 6 hours per day for 2, 6, or 10 days at 100 micrograms/m3 and compared to a control group exposed to filtered air. The IgG antibody response to TM-HB in both serum and bronchoalveolar lavage (BAL) fluid was measured with ELISA. IgG antibody levels to TM-HB rose significantly throughout the exposure. A positive correlation was found between IgG to TM-HB in serum and BAL fluid. In addition, this response in both serum and BAL fluid correlated with the IgG antibody response to TM-RSA. Cross-inhibition studies indicated the existence of shared antigenic determinants on TM-RSA and TM-HB. The IgG antibody to both antigens was specific for new antigenic determinants and not for the TM hapten.

Animals↗
PubMed1988

Reducing the number of rabbits in the Draize eye irritancy test: a statistical analysis of 155 studies conducted over 6 years.

The Draize eye irritancy test in rabbits has been the focus of recent efforts to reduce the use of live animals in toxicity testing. A suitable alternative is not yet available; therefore, we studied the adequacy of reducing the number of rabbits used per test. Data generated from 6-rabbit eye irritation tests of 155 various materials were used to determine the ability of irritation scores from all possible combinations of 5-, 4-, 3-, or 2-rabbit subsets to predict the Draize score derived from six rabbits. There are 930, 2325, 3100, and 2325 possible combinations of 155 studies for the 5-, 4-, 3-, and 2-rabbit subsets, respectively. We classify materials using a four-level adjectival rating system based on (among other factors) the Draize score. Comparisons indicated that 5-, 4-, 3-, and 2-rabbit scores were in 98, 96, 94, and 91% agreement, respectively, with the classification assigned on the basis of the 6-rabbit score. The correlation coefficients for randomly selected subsets of 5-, 4-, 3-, and 2-rabbit scores versus the Draize score for six rabbits were 0.998, 0.996, 0.992, and 0.984, respectively. This study confirms the findings of an earlier report by De Sousa et al. (1984), and indicates that a high level of accuracy can be obtained with reduced numbers of rabbits per test.

Animals↗
PubMed1988

Evidence of immunologic control of lung injury induced by trimellitic anhydride.

Trimellitic anhydride (TMA) is a chemical intermediate that has been shown to cause immunologically mediated respiratory syndromes in humans. We developed a rat model in which lung lesions accompanied by TMA-specific antibody resembled effects seen in humans. Two sets of experiments were undertaken to determine if TMA lung injury was primarily controlled by the immune system. Experiment 1: Rats were exposed to 95 micrograms/m3 of TMA 6 h/day, 5 days/wk for 2 wk during which time they received daily injections of either the immunosuppressant cyclophosphamide or saline. The TMA-exposed/saline control rats exhibited the usual TMA-induced lung lesions accompanied by TMA-specific antibody. However, the TMA-exposed/cyclophosphamide rats showed no lesions and no antibody. The spleen cells from all rats were subjected to lymphocyte blastogenesis assays using T- and B-cell mitogens. Results confirmed that cyclophosphamide-treated rats showed very little if any blastogenic response, whereas saline-treated rats gave the normal immune response. Thus, cyclophosphamide eliminated T- and B-cell function, which in turn prevented the occurrence of TMA lesions. Experiment 2: An initial passive transfer experiment showed that serum from TMA-sensitized rats could be adoptively transferred into naive recipient rats, which when given a single TMA inhalation challenge exhibited TMA-induced lesions. Similar attempts to transfer spleen cells or spleen cells plus serum did not predispose recipients for lesions. A second modified passive transfer of sensitized serum using a larger number of recipient rats, followed by a TMA challenge, resulted in lesions in 14 of the 16 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A serial immunologic and histopathologic study of lung injury induced by trimellitic anhydride.

Trimellitic anhydride (TMA) can induce immunologic lung disease in exposed workers. We have developed a rat model of TMA lung injury characterized by lung hemorrhage and an immune response to trimellityl (TM) haptenized lung proteins. The model is similar to the pulmonary disease-anemia syndrome (PDA) seen in workers exposed to TMA fumes. Sprague-Dawley rats, 15 per exposure period, inhaled micronized TMA powder, 100 micrograms/m3, 6 h/day, for 2,6, or 10 days and were sacrificed. At each time period, total, IgG, IgA, and IgM antibody to TM-rat serum albumin (TM-RSA) were measured by radiolabeled antigen binding and enzyme-linked immunosorbent assay (ELISA) in serum and bronchoalveolar lavage fluid (BAL). Hemorrhagic lung foci, weight, and displacement volume were determined, and lungs were examined by light and electron microscopy. There was no lung injury or antibody response at 2 days. There was minimal lung injury at 6 days with low levels of antibody in BAL and serum. At 10 days, there was a marked increase in hemorrhagic foci and in BAL and serum antibody levels. BAL antibody levels at 6 and 10 days had higher correlations with measures of lung injury than corresponding serum levels. There was minimal ultrastructural change at 6 days. By Day 10, there was marked intraalveolar hemorrhage, alveolar septal inflammatory nodules, abundant alveolar macrophages, and evidence of endothelial and epithelial cell injury. These results indicate that the immune response to inhaled TMA occurs parallel with the development of lung lesions, and antibody levels in BAL and serum are highly correlated with lung injury.

Animals↗
PubMed1987

The pathologic and immunologic response to inhaled trimellitic anhydride in rats.

Trimellitic anhydride (TMA) is a chemical intermediate used in the paint and plastics industry. Inhalation of TMA can induce four types of syndromes in TMA workers; three are immunologically based whereas the fourth, an irritant syndrome, is nonimmunologic. To evaluate the potential inhalation hazard of TMA under controlled conditions, Sprague-Dawley rats were exposed 6 hr/day via inhalation to target concentrations of 0, 10, 30, 100, and 300 micrograms/m3 for varying durations. Two sets of rats received either 5 or 10 exposures and were terminated. A third set received 10 exposures, and was held 12 days and terminated. A fourth set received 10 exposures, and was held 12 days, challenged with a single 6-hr exposure, and terminated. A fifth set received 10 exposures, and was held 12 weeks and terminated. There were no effects after 5 exposures; however, after 10 exposures the following parameters were increased in a concentration-related manner: absolute and relative lung weights, external hemorrhagic lung foci, alveolar macrophage accumulation, alveolar hemorrhage, pneumonitis, and lung and mediastinal lymph node nonspecific IgG and complement (C3). The rats exposed and rested 12 days were nearly recovered from these effects; however, rats rested 12 days and subsequently challenged exhibited lesions similar to those seen immediately following exposure. Exposed rats rested 12 weeks were completely normal in all of the above parameters. The timing and nature of the lung lesions, along with the presence of lung IgG and complement, are consistent with some of the known aspects of TMA-induced lesions in humans, and are reflective of results obtained from other hypersensitivity pneumonitis models.

Administration, Inhalation↗
PubMed1987

Levels and specificity of antibody in bronchoalveolar lavage (BAL) and serum in an animal model of trimellitic anhydride-induced lung injury.

A study was undertaken to characterize the antibody response in rats exposed to trimellitic anhydride (TMA) by inhalation. Total antibody levels directed to trimellitic rat serum albumin (TM-RSA) from TMA-exposed rats were assayed by an ammonium sulfate technique. Total antibody levels in bronchoalveolar lavage (BAL) and the matched serum were compared by correction for the albumin content of each. An ELISA was developed to detect IgG, IgA, and IgM directed toward TM-RSA in BAL and serum and to compare class-specific antibody levels in BAL and serum by normalizing for albumin content. The specificity of the rat IgG response was determined by ELISA inhibition with TM-RSA and TM-human serum albumin (TM-HSA) and compared with reciprocal inhibition studies with serum from TMA-exposed workers. The levels of total antibody in BAL were three to 15 times greater than the levels found in the matched serum pair. IgG, IgA, and IgM antibodies were detected in the BAL and the serum of TMA-exposed rats but not in control rats. In each of the four rats tested, all antibody classes were present in equal or greater amounts in the BAL than in the serum. Complete inhibition of the rat IgG binding in ELISA was observed when TM-RSA or TM-HSA were added as inhibitors. Human IgG was inhibited in ELISA only by TM-HSA. In an animal model of human lung disease, the levels of total antibody as well as class-specific antibodies directed against TM-RSA were greater in BAL than in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The pathologic and immunologic effects of inhaled acrolein in rats.

Four groups of 40 male Sprague-Dawley rats each were exposed by inhalation to target concentrations of 0, 0.1, 1.0, and 3.0 ppm of acrolein 6 h/day, 5 days/week for 3 weeks. Subsequent changes in local pulmonary immunity were determined by examining the number of antibody plaque-forming cells in the lung-associated lymph nodes following intratracheal immunization with sheep red blood cells. Separate groups of rats were evaluated for blastogenic responsiveness to phytohemagglutinin-P and Salmonella typhimurium antigen using spleen- and lung-associated lymph node cells. In vivo resistance was evaluated utilizing acrolein-exposed rats subsequently challenged with intravenous Listeria monocytogenes. Local pulmonary antibody responsiveness was not affected by acrolein exposure. Lymphocyte blastogenesis and resistance to Listeria challenge were not altered. Body weights and spleen weights were decreased in the 3 ppm-exposed group only. Microscopic examination of the nasal turbinates revealed acrolein-induced exfoliation, erosion, and necrosis of the respiratory epithelium as well as squamous metaplasia, however, lung histology was not affected. Thus at environmental concentrations, acrolein toxicity appeared to be confined to local nasal pathologic changes with no alterations in lung histology or immune function.

Acrolein↗
PubMed1987

A model of immunologic lung injury induced by trimellitic anhydride inhalation: antibody response.

We studied lung injury induced in Sprague-Dawley rats by trimellitic anhydride (TMA) inhalation. Groups of 40 male and 20 female rats were exposed to TMA by inhalation at target concentrations of 0, 10, 30, 100, and 300 micrograms/m3, 6 hours per day, 5 days per week, for 2 weeks. Rats in each exposure group were sacrificed after 10 exposures or rested for 12 days and either sacrificed or received a 6-hour TMA challenge at their initial exposure levels and sacrificed at 24 hours. At each sacrifice, serum antibody to radiolabeled trimellityl rat serum albumin (RSA-TM) was measured by an ammonium sulfate technique, and lung pathology was determined. After 10 days of exposure, external hemorrhagic lung foci were directly related to the exposure concentration of TMA. Serum antibody binding of RSA-TM correlated with exposure concentration, hemorrhagic lung foci, and lung weight. There was healing of lung lesions 12 days after exposure with a return of lung lesions only 18 hours after the 6-hour inhalation challenge. A correlation between serum antibody to RSA-TM, hemorrhagic foci, and lung weight existed after challenge. This model clarifies two clinical entities observed in exposed workers, the late respiratory systemic and the pulmonary disease-anemia syndromes.

Administration, Inhalation↗
PubMed1978

Local anesthesia for mediastinoscopy: experience with 450 consecutive cases.

Mediastinoscopy has been widely applied in the evaluation of patients with suspected bronchogenic carcinoma over the past decade. Though there remain those who feel that such findings should not play a significant role in determining resectability, we have found a number of patients who have been saved from exploratory thoracotomy in obviously incurable situations. We have had a relatively high degree of success in the diagnosis of benign diseases. Wtih no mortality and a morbidity of 1.1%, we feel that mediastinoscopy under local anesthesia is applicable in many clinical circumstances in which the requirement for general anesthesia would preclude such evaluation. Though it is not necessary that local anesthesia be exclusively applied, we feel that our experience with over 450 cases in the last six years has demonstrated safety and efficacy in universal application of local anesthesia for cervical mediastinal exploration.

Anesthesia, Local↗