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S Fischer

Publications and source records attributed to S Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2002

[Anticoagulation in pregnant women after artificial heart valve replacement: is low-molecular-weight heparin an alternative?].

We report on the case of a 24-year-old pregnant woman with acute mechanical mitral valve thrombosis due to a treatment failure of low molecular weight heparin (LMWH) for permanent anticoagulation following mechanical valve replacement. Initially, our patient was put on oral warfarin for anticoagulation, but when her pregnancy was perceived the anticoagulation regimen was switched to daily subcutaneous administration of LMWH in order to minimize the risk of warfarin-induced embryopathy. During her 24th week of gestation she developed acute life-threatening pulmonary edema and hemodynamic instability, which was caused by an acute thrombosis of her artificial mitral valve. In an emergency operation the thrombozed valve was replaced by a porcine biological heart valve. The patient recovered uneventfully and gave birth to a healthy child in her 35th gestational week by cesarean section. In addition we discuss the rationale of different anticoagulation regimens with regard to maternal and fetal outcome with special consideration of LMWH as an alternative strategy to oral anticoagulation during pregnancy in women with mechanical heart valves.

Anticoagulants↗
PubMed2002

Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass.

In obese people, an increase of plasma leptin levels is well-known and is seen as a consequence of the increased body fat mass. Moreover, a relationship between fasting concentrations of leptin and insulin has been described. Hyperinsulinemia is considered to be indicative of insulin resistance. We aimed at elucidating the interrelations between leptin, insulin and insulin resistance in type 2 diabetic patients. Under metabolic ward conditions, we investigated 21 moderately overweight men with type 2 diabetes. The patients had a mean age of 49.1 years, a mean body mass index (BMI) of 26.8 kg/m(2), and a mean diabetes duration of 82.5 months. All patients were treated with diet alone. We measured fasting leptin and insulin levels, body composition by determination of total body water, and insulin resistance by euglycemic hyperinsulinemic clamp technique. At univariate analysis, fasting leptin level significantly and positively correlated with BMI (r=0.49, p=0.02) and with fasting insulin (r=0.69, p=0.001), while it negatively correlated with the glucose disposal rate (r=-0.62, p=0.002). Furthermore, leptin was inversely correlated with HDL-cholesterol (r=-0.45, p=0.04). When excluding the influence of body fat mass or of BMI in partial correlation analysis, the correlations between leptin and insulin or insulin sensitivity remained significant. The relationship between insulin resistance (as measured directly in the clamp experiments) and leptin concentrations was also shown by subdividing the diabetic patients according to tertiles of insulin sensitivity. The highest fasting leptin levels were observed in those patients with the most expressed insulin resistance. Our data point to a functional relationship between insulin resistance and leptin concentrations in insulin-resistant type 2 diabetic men, independently of body composition. This relationship is believed to be mediated by insulin.

Adipose Tissue↗
PubMed2002

Different effects of acarbose and glibenclamide on proinsulin and insulin profiles in people with Type 2 diabetes.

AIM: In a double-blind, placebo-controlled study, we compared the effect of acarbose (A) and glibenclamide (G) on post-prandial (pp) and 24-h profiles of proinsulin and insulin. METHODS: Twenty-seven patients with Type 2 diabetes mellitus insufficiently controlled with diet alone were randomised to receive acarbose, 100 mg thrice daily, glibenclamide, 1 mg thrice daily, or placebo. Before and after 16 weeks of treatment, 24-h profiles of proinsulin, insulin and glucose (fasting, 1 h after breakfast and every 3-h for a 24-h period) were measured under metabolic ward conditions with standardised meals. RESULTS: With acarbose, a reduced 24-h level of proinsulin was observed compared with glibenclamide (AUC 1096 +/- 118 vs. 1604 +/- 174 pmol/l per h, P<0.05) at 16 weeks. The breakfast increment of proinsulin was lower with acarbose than glibenclamide (6.8 vs. 19.3 pmol/l, P<0.05) as was the level at that time (37.3 +/- 5.3 vs. 56.4 +/- 7.5 pmol/l, P<0.05). A lower AUC of insulin after treatment was also observed with acarbose than glibenclamide (7.9 +/- 0.9 vs. 14.8 +/- 4.5 nmol/l per h, P<0.05), as also for 1-h increment (81 +/- 26, vs. 380 +/- 120 pmol/l, P<0.01) and 1-h level (325 +/- 30 vs. 621 +/- 132 pmol/l, P<0.01). Acarbose reduced 1-h breakfast glucose increment (baseline 6.3 +/- 0.6, 16-week 3.5 +/- 0.6 mmol/l, P<0.01) and 1-h glucose level (18.1 +/- 1.1 and 14.5 +/- 1.3 mmol/l, P<0.01), whereas glibenclamide did not (6.6 +/- 0.7 vs. 5.4 +/- 0.6 mmol/l and 18.9 +/- 1.5 vs. 15.3 +/- 1.3 mmol/l). CONCLUSIONS: Measurement of circadian excursions of proinsulin and insulin reveals distinct differences in meal-time proinsulin and insulin increment and level between acarbose and glibenclamide whereas fasting levels of these insulin fractions remained unaffected.

Acarbose↗
PubMed2002

Insulin resistance and metabolic parameters in type 2 diabetic patients.

Background: The importance of insulin resistance in type 2 diabetes mellitus has been generally accepted. Only very few data about the degree of insulin resistance in a representative group of type 2 diabetic patients are available. The aim of this study was to ascertain the degree of insulin resistance and its relation to metabolic parameters in type 2 diabetic patients. Methods: We studied 96 type 2 diabetic patients. The inclusion criteria were type 2 diabetes according to WHO criteria and HbA(1c) between 6.8% and 10.5%. Insulin resistance was estimated in a euglycemic hyperinsulinemic clamp. Blood parameters like lipids, insulin, glucose, fatty acids, and leukocytes were also studied. Results: The insulin sensitivity of 71 of the type 2 diabetic patients was markedly lower than that of the controls. Twenty-five diabetic patients had an M(c) value within the range of the controls. The M(c) values, as a measure of insulin resistance, of the diabetic patients were between 0.3 and 5.2 mg/(kg min insulin), whereas the M(c) range of the controls was from 2.6 to 10.8 mg/(kg min insulin). Conclusions: Approximately 75% of the type 2 diabetic patients were insulin-resistant. Hence, type 2 diabetes mellitus was not equivalent to insulin resistance in every case.

Journal Article↗
PubMed2002

Triple valve replacement in a patient with severe carcinoid heart disease.

We report on the case of a 34-year-old male patient suffering from end-stage carcinoid heart disease with severe tricuspid, pulmonary and mitral valve regurgitation. In addition, a persisting foramen ovale was present. The primary carcinoid tumor was never discovered. However, urine 5-hydroxy-indole-acetic-acid (5-HIAA) were consistently elevated after the first diagnosis of carcinoid disease and after eight years of medication with Octreotide and Interferon alpha-2b our patient developed significant cardiac insufficiency mainly due to severe valvular dysfunction. Ultimately, mechanical tricuspid, mitral and pulmonary valve replacement was performed. Twelve hours following the operation the patient had to be returned to the operating room for persisting intrathoracic hemorrhage. He recovered uneventfully and was discharged from hospital on day 37. Twelve months following triple valve replacement the cardiac status recovered from preoperative NYHA-IV to NYHA-I.

Adult↗
PubMed2002

EEG synchronization upon reward in man.

OBJECTIVES: It was tested whether reward in humans is associated with EEG synchronization similar to that seen in animals. METHODS: In two experiments (I and II) the EEG was recorded from frontal, central, and parietal positions before, during, and after drinking or oral stimulation. In Experiment I, subjects (n=11) who had either been thirsty for 16h or had quenched thirst before recordings, drank 400ml of water. In Experiment II, thirsty subjects (n=11) either drank 400ml of water or sucked on a soother. The recording epochs included a 3min baseline, an interval of about 5min during which subjects drank or sucked on the soother, and a 7min post-drinking interval. RESULTS: During the drinking epoch, beta band-power (12-30Hz) was enhanced in both conditions of Experiment I and II, respectively. In Experiment I, after drinking, lower alpha power (8-10Hz) was higher when subjects were thirsty than when they were not. Lower alpha was also enhanced in the post-drinking interval of both conditions of Experiment II, and after sucking, lower alpha synchronization was in addition accompanied by increased theta activity (4-8Hz). CONCLUSIONS: Increased beta activity during drinking and sucking in thirsty subjects presumably reflects non-specific activation related to the motivational strength of sensorimotor regulation during consumatory behavior. The thirst dependent lower alpha synchronization after drinking, generated not only by water consumption but also by surrogate oral stimuli, can be considered a reflection of the drive reducing and rewarding qualities of oral stimulation and consumatory behavior.

Adult↗
PubMed2002

[Differential type 2 diabetes therapy based on pathophysiological aspects].

Type 2 Diabetes is characterized by a deficit in early insulin secretion and increased insulin resistance. Based on the measurement of fasting and 2 h postprandial blood glucose a simple typing of hyperglycemia is possible in isolated fasting hyperglycemia (IFH), isolated postprandial hyperglycemia (IPH) and combined hyperglycemia (CH). IFH is predominantly associated with insulin resistance whereas in IPH a more pronounced insulin deficit is found. This and other simple parameters such as BMI, comorbidities and age are the basis of differential therapy with OAD if best efforts with life style modification fail to reach the target values of the lipid triad. Patients with IFH profit particularly from metformin and long acting sulfonylureas (glimepiride, glibenclamide). Patients with IPH are candidates for prandial antidiabetics (AGI, nateglinide, repaglinide). Antihyperglycemic agents such as metformin and AGI bear no risk of hyperglycemia and reduce body weight. Prandial insulin secretagogues have lower risk of weight gain and hypoglycemia than long acting sulfonylureas. They are therefore beneficial in obese patients and the elderly. The same principles are valid for combination treatment. With exception of insulin secretagogues all OAD can be combined if monotherapy fails to reach the target levels of the gluco-triad. Instead of a stepwise treatment algorithm an individualized therapy based on pathophysiology and comorbidities taking into account the global risk seems to be beneficial.

Blood Glucose Self-Monitoring↗
PubMed2002

[Monitoring of naevus density--an approximate marker of previous UV exposure--in children at school enrollment as a method to detect shifts in melanoma risk in the population].

OBJECTIVE: Naevus density in children depends both on constitutional factors (see below) and on previous (solar) UV exposure, which is a well-known risk factor for malignant melanoma. Secular trends of childhood UV exposure - e. g., due to intervention programmes - can be monitored by repeated, standardised cross-sectional studies assessing naevus density in children. METHODS: The 'CMONDE-Study (childhood monitoring of naevus density)' appears as a suitable instrument, introduced into the process of school enrollment for children of the years 1999 and 2000 in Göttingen. RESULTS: Analyses are based on 3883 children. Median age was 6.25 years, the proportion of girls 47 %. Median naevus density was 5.8/m(2), with an increase of density from 'Fitzpatrick skin type' IV to II, but marked decrease in type I. Similarly, naevus density increased with increasing lightness of hair colour, but was very low in red-haired individuals. While the number of freckles was also strongly associated with naevus density, the association between iris colour and skin darkness, respectively, was weak. CONCLUSION: To meet the objective of continual monitoring, further comparative cross-sectional studies are needed.

Child↗
PubMed2002

Endothelial anatomy of the human heart: immunohistochemical evaluation of endothelial differentiation.

OBJECTIVES: Endothelial cells play a significant role in cardiovascular physiology and the pathogenesis of numerous cardiovascular diseases. Essential phenomena such as hemostasis, inflammation and immunity require close interactions between immunocompetent and endothelial cells. However, many questions of endothelial heterogeneity regarding function and morphology at various vascular sites remain unanswered. In this study, we have created an immunohistochemical map of endothelial adhesion molecule expression at different vascular sites of the healthy human heart. The main focus was to analyze endothelial expression patterns and whether they are distinctive regarding their function at these vascular sites. We also tried to build up a relation between clinical and immunohistochemical findings. PATIENTS AND METHODS: Tissue samples from eleven different vascular locations of healthy human hearts were analyzed using immunohistochemistry. Endothelial adhesion molecules of the selectin, immunoglobulin supergene, and integrin families, some complementary cellular adhesion molecules, and von Willebrand factor were analyzed. RESULTS: Endothelial adhesion molecule expression was found to be characteristic for all vascular sites investigated. Thus, molecules involved in inflammatory reactions were predominantly expressed within the myocardial microvasculature, whereas molecules serving endothelial anchorage towards extracellular matrix components could be observed especially on endocardial and valvular surfaces. Apart from that, a parallel expression of immunologically relevant as well as integrin molecules was found to be characteristic for coronary arteries. CONCLUSIONS: To our knowledge, this is the first report on site-specific expression characteristics for all vascular sites of the human heart. Thus, our data provide important novel information, which will ultimately help to bring some light into the field of cardiac physiology.

Antibodies, Monoclonal↗
PubMed2002

In vitro engineering of heart muscle: artificial myocardial tissue.

INTRODUCTION: Myocardial infarction followed by heart failure represents one of the major causes of morbidity and mortality, particularly in industrialized countries. Engineering and subsequent transplantation of contractile artificial myocardial tissue and, consequently, the replacement of ischemic and infarcted areas of the heart provides a potential therapeutic alternative to whole organ transplantation. METHODS: Artificial myocardial tissue samples were engineered by seeding neonatal rat cardiomyocytes with a commercially available 3-dimensional collagen matrix. The cellular engraftment within the artificial myocardial tissues was examined microscopically. Force development was analyzed in spontaneously beating artificial myocardial tissues, after stretching, and after pharmacologic stimulation. Moreover, electrocardiograms were recorded. RESULTS: Artificial myocardial tissues showed continuous, rhythmic, and synchronized contractions for up to 13 weeks. Embedded cardiomyocytes were distributed equally within the 3-dimensional matrix. Application of Ca(2+) and epinephrine, as well as electrical stimulation or stretching, resulted in enhanced force development. Electrocardiographic recording was possible on spontaneously beating artificial myocardial tissue samples and revealed physiologic patterns. CONCLUSIONS: Using a clinically well-established collagen matrix, contractile myocardial tissue can be engineered in vitro successfully. Mechanical and biologic properties of artificial myocardial tissue resemble native cardiac tissue. Use of artificial myocardial tissues might be a promising approach to reconstitute degenerated or failing cardiac tissue in many disease states and therefore provide a reasonable alternative to whole organ transplantation.

Animals↗
PubMed2002

Impact of n-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery.

In various diseases n-3 fatty acids exert anti-inflammatory properties. These effects seem to be related to the uptake and incorporation of eicosapentaenoic acid (EPA) into the cellular substrate pool after dietary intake of EPA, which is contained in fish oils (FO). In the state of inflammation EPA is released to compete with arachidonic acid (AA) for metabolism at the cyclo-oxygenase and the 5-lipoxygenase level. The metabolites of EPA have less inflammatory and chemotactic potency than the substances derived from AA. In addition to positive effects, early studies pointed towards prolonged bleeding times after dietary intake of n-3 fatty acids. This study was undertaken to address the issue of potential coagulation disturbances associated with postoperative parenteral FO administration. This was a prospective, randomised, double blinded clinical trial, carried out in two operative intensive care units (13 and 16 beds) in a university hospital. Forty-four patients undergoing elective major abdominal surgery participated in the trial. Patients were randomly assigned to receive total parenteral nutrition (TPN) supplemented with either soybean oil (SO, Lipovenoess 10% PLR; 1.0 g/kgBW per day; n = 20) for five days or with a combination of FO and SO (FO, Omegaven; 0.2 g/kgBW per day plus SO, Lipovenoes 10% PLR; 0.8 g/kgBW per day, n = 24), respectively. Blood samples were taken preoperatively (day -1), prior to (day 1) during (days 2-5) and after TPN (day 6). The coagulation parameters thromboplastin time (Quick), activated partial thromboplastin time (aPTT), fibrinogen and antithrombin III were measured. To differentially assess activation levels of extrinsic and intrinsic coagulation pathway, factors VIIa and XIIa were quantified. Moreover platelet function was determined by resonance thrombography. Baseline values of coagulation and platelet function were comparable in both groups, but coagulation activity dropped after surgery. Over the observation period of 6 days, however, physiological levels were regained. No clinically significant differences were observed between the SO- and SO + FO- group. These findings suggest that infusion of fish oil in doses up to 0.2 g/kgBW per day is safe regarding coagulation and platelet function.

Aged↗
PubMed2001

Prostaglandin E1 protects lung transplants from ischemia-reperfusion injury: a shift from pro- to anti-inflammatory cytokines.

INTRODUCTION: Prostaglandin E1 (PGE1) has been demonstrated to reduce ischemia-reperfusion (IR) injury following lung transplantation. However, the cytoprotective mechanisms remain largely unknown. The purpose of this study was to determine whether the mechanism through which PGE1 improves IR injury is related to the level of apoptosis or the release of inflammatory cytokines. METHODS: In a rat single-lung-transplant model, animals were randomly allocated into four groups of five animals each. Group 1 received normal saline (NS) in the preservation solution and during the 2-hr reperfusion period. Group 2 received NS in the preservation solution and PGE1 during the reperfusion period. Group 3 received PGE1 in the preservation solution and NS during the reperfusion period. Group 4 received PGE1 in the preservation solution and during the reperfusion period. RESULTS: The two groups that received PGE1 during the reperfusion period had a significantly higher partial pressure of oxygen (PaO2), lower wet-dry weight ratio, and lower peak airway pressure at the end of the reperfusion period than did the two groups that received NS. In the two groups that received PGE1 during the reperfusion period, we observed significantly higher levels of interleukin (IL)-10 in the transplanted lung tissue and plasma and significantly lower levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and IL-12 in lung tissue. The levels of IL-4 and macrophage inflammatory protein-2 (MIP-2) were not significantly different between groups. The number of apoptotic cells and the expression of Bcl-2 were not significantly different between groups. CONCLUSIONS: PGE1 does not decrease the amount of apoptosis after reperfusion and does not significantly upregulate Bcl-2. We have demonstrated that PGE1 administered during the reperfusion period reduces IR injury and improves lung function through a mechanism that is likely mediated by a shift between pro- and anti-inflammatory cytokine release.

Alprostadil↗
PubMed2001

The use of oral washes to diagnose Pneumocystis carinii pneumonia: a blinded prospective study using a polymerase chain reaction-based detection system.

Pneumocystis carinii pneumonia (PCP) can be diagnosed by direct microscopic examination of induced sputum or by bronchoalveolar lavage (BAL). However, many institutions have little diagnostic success with induced sputum, and BAL is invasive and expensive. This prospective, blinded study assessed oral washes as a more convenient specimen than either sputum or BAL fluid and used a dissociation-enhanced lanthanide fluoroimmunoassay time-resolved fluorescent hybridization polymerase chain reaction (PCR) detection system that is feasible for clinical laboratories. The study assessed 175 oral washes, each paired with either an induced sputum that was positive for Pneumocystis or a BAL sample. The PCR test based on the Pneumocystis major surface glycoprotein primers had a sensitivity of 91% and a specificity of 94%, compared with a test based on mitochondrial large subunit rRNA primers, which had a sensitivity of 75% and a specificity of 96%. These results suggest that oral washes can provide a useful sample for diagnosis of PCP when a sensitive PCR detection system is used.

Bronchoalveolar Lavage↗
PubMed2001

Practising evidence-based medicine: the design and implementation of a multidisciplinary team-driven extubation protocol.

BACKGROUND: Evidence from recent literature shows that protocol-directed extubation is a useful approach to liberate patients from mechanical ventilation (MV). However, research evidence does not necessarily provide guidance on how to implement changes in individual intensive care units (ICUs). We conducted the present study to determine whether such an evidence-based strategy can be implemented safely and effectively using a multidisciplinary team (MDT) approach. METHOD: We designed a MDT-driven extubation protocol. Multiple meetings were held to encourage constructive criticism of the design by attending physicians, nurses and respiratory care practitioners (RCPs), in order to define a protocol that was evidence based and acceptable to all clinical staff involved in the process of extubation. It was subsequently implemented and evaluated in our medical/ surgical ICU. Outcomes included response of the MDT to the initiative, duration of MV and stay in the ICU, as well as reintubation rate. RESULTS: The MDT responded favourably to the design and implementation of this MDT-driven extubation protocol, because it provided greater autonomy to the staff. Outcomes reported in the literature and in the historical control group were compared with those in the protocol group, and indicated similar durations of MV and ICU stay, as well as reintubation rates. No adverse events were documented. CONCLUSION: An MDT approach to protocol-directed extubation can be implemented safely and effectively in a multidisciplinary ICU. Such an effort is viewed favourably by the entire team and is useful in enhancing team building.

Adult↗
PubMed2001

Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques.

BACKGROUND: Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques. METHODS AND RESULTS: The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd(3+) atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL. s(-1). pmol(-1) (10% Gd-DTPA nanoparticles) to 0.54 mL. s(-1). pmol(-1) for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was approximately 118+/-21, and that between the targeted clot and the control clot was 131+/-37. CONCLUSIONS: These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.

Animals↗
PubMed2001

[Brugada syndrome].

BACKGROUND: A high take-off descending ST segment associated with right bundle branch block is the typical ECG criterion of the Brugada-Brugada syndrome. It leads to ventricular fibrillation or syncopes in case of a familiar disposition. CASE REPORT: We describe a 56-year-old man in whom oral prajmalium bitartrate therapy previously prescribed for symptomatic ventricular extrasystoles unmasked an electrographic pattern characteristic of a Brugada syndrome. After the ongoing invasive diagnostic a right ventricular dysplasia in the same case is possible. The patient was treated with an ICD pacemaker.

Anti-Arrhythmia Agents↗
PubMed2001

In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia-reperfusion injury and improves early posttransplant graft function in the rat.

We examined the effect of adenovirus-mediated transtracheal transfer of the human interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injury, which is the insult due to hypothermic preservation plus graft reperfusion, and posttransplant lung function in Lewis rat lungs. Thirty rats were divided into 6 groups (n = 5). Groups 1 and 4 received 5 x 10(9) PFU of Ad5E1RSVhIL-10, groups 2 and 5 received 5 x 10(9) PFU of Ad5BGL2 ("empty" vector), and groups 3 and 6 received 3% sucrose (diluent). After 24 hr of in vivo transfection, lungs were stored at 4 degrees C (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr (groups 4-6) before transplantation. After 2 hr of reperfusion, lung function was assessed by oxygenation (FIO2, 1.0), airway pressure (AwP), and wet-to-dry (W/D) weight ratios. Rat tumor necrosis factor alpha (rTNF-alpha), interferon gamma (IFN-gamma), IL-10, and hIL-10 were measured in graft tissue and recipient plasma by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen (PaO2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector and diluent groups (PaO2, 530 +/- 23 vs. 387 +/- 31 and 439 +/- 27 mmHg, respectively, p < 0.05). IL-10 rats after 24 hr of CIT showed higher PaO2 levels (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmHg) lungs (p < 0.05). AwP and W/D ratios were reduced in hIL10 lungs (p < 0.05) compared with the other groups. rTNF-alpha and INF-gamma were reduced in tissue and plasma in groups 1 and 4 (p < 0.05). rIL-10 was reduced in the tissue of hIL-10 lungs (p < 0.05). IHC showed equal distribution of cytokines in tissue and abundant transgene expression in large and small airway epithelium in hIL-10 lungs.

Adenoviridae↗