Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n=7; E-LAVAGE, n=5) or bolus (I-BOLUS, n=8; E-BOLUS, n=5), or went untreated (CONTROL, n=4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO₂ were observed in the lavage groups compared to the bolus groups and the controls. PaO₂ (mmHg) at 240 min posttreatment: I-LAVAGE=297±54, E-LAVAGE= 280±57; I-BOLUS=139±31; E-BOLUS=152±29; C=119±73 (mean± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.     

The Role of Pleural Fluid-Serum Gradient of Tumor Necrosis Factor-α Concentration in Discrimination Between Complicated and Uncomplicated Parapneumonic Effusion

In a previous preliminary study an excess of tumor necrosis factor- (TNF) was found in pleural fluid of patients with complicated parapneumonic effusion (CPPE), and its levels in pleural fluid of these patients were shown to be significantly higher than those in patients with uncomplicated parapneumonic effusion (UCPPE). This larger population study was undertaken to investigate, for the first time, the role of pleural fluid-serum gradient of TNF (TNFgradient) in discrimination between UCPPE and CPPE. Using a commercially available high sensitivity ELISA kit, levels of TNF were measured in serum and pleural fluid of 51 patients with UCPPE and 30 patients with nonempyemic CPPE. The mean±SEM values of serum TNF (TNFserum), pleural fluid TNF (TNFpf), and TNFgradient in the UCPPE group were 6.65±0.48 pg/mL, 10.85±0.74 pg/mL, and 4.2±0.38 pg/mL respectively, and in the CPPE group they were 7.59±0.87 pg/mL, 54.02±5.43 pg/mL, and 46.43±5.34 pg/mL, respectively. While no significant difference was found between the two groups regarding levels of TNFserum (p=0.31), a highly significant difference between these two groups was found regarding levels of TNFpf and TNFgradient (p < 0.0001 for both variables). A significant correlation was found between levels of TNFserum and levels of TNFpf in the UCPPE group (r=0.89, p < 0.0001), but not in the CPPE group (r=0.18, p < 0.33). TNFgradient at an optimal cut-off level of 9.0 pg/mL was found to be a good marker for discrimination between UCPPE and CPPE (sensitivity, 96.7%, specificity, 98%, accuracy, 97.5%, and p < 0.0001). In conclusion, levels of TNFpf but not TNFserum are significantly higher in CPPEs than those in UCPPEs where TNFgradient at an optimal cut-off level of 9.0 pg/mL is a good marker for discrimination between UCPPE and CPPE.     

Sampling Airway Surface Liquid: Non-Volatilesin the Exhaled Breath Condensate

Exhaled breath condensate (EBC) samples contain molecules that have no appreciable vapor pressure; such molecules likely derive from droplets of airway fluid. We analyzed EBC gathered from a total of 62 healthy volunteers in order to quantify the volume of airway liquid that was the source of the non-volatiles; saliva was analyzed as a reference secretion. EBC urea averaged 0.52±0.12 mol/L (n=18), an 8,600-fold dilution from predicted blood urea nitrogen levels. Protein averaged 2.3±0.3 g/ml (n=31), three orders of magnitude less than in saliva (1.4±0.1 mg/ml, n=15). EBC ammonia was 6.6±0.6 mmol/L (1/15 that of saliva) and EBC ammonium ion was 0.90±0.19 mol/L, concentrations that are incompatible with an 8,600-fold dilution from a biological source. Thus, urea-derived dilution factors may be used to interpret EBC non-volatile molecules, but not EBC volatiles.     

Burden of musculoskeletal pain in Japan

Based on the prevalence of musculoskeletal pain in the context of interference with daily activities (IDA) and treatment for musculoskeletal disorders in the study population (n = 3188), we estimated the prevalence and years lived with disability (YLD) of musculoskeletal pain in Japan. The total of 42287 thousand (41.2%) of Japanese adult people was estimated to suffer from musculoskeletal pain. Among them, 9127 thousand was estimated to interfere with daily activities due to the pain. Overall YLD for musculoskeletal pain in Japan were estimated at 1297843.7 (1263.6 per 100000). The YLD for Pain without IDA were 33159.3 (32.3 per 100000) and the YLD for Pain with IDA were 1264684.4 (1231.3 per 100000). One-way sensitivity analysis showed that the YLD of musculoskeletal pain might increase to 4421844.0 (4305.2 per 100000) with the increased disability weight for Pain without IDA of 0.1, while they might inversely decrease to 1018875.0 (992.0 per 100000) with the increased treatment rate in Pain with IDA of 100%. Musculoskeletal pain imposes a substantial burden on the Japanese adult population. To allow the population to keep their health-related quality of life, health professionals should pay more attention to musculoskeletal pain and make positive efforts to improve prevention and control of musculoskeletal pain.     

Efficacy of mizoribine treatment in patients with SjÖgren’s syndrome: an open pilot trial

The aim of this study was to evaluate the efficacy and safety of mizoribine in patients with SjÖgrens syndrome. Forty patients with sicca syndrome, whose conditions were definitely diagnosed as SjÖgrens syndrome, were given mizoribine orally at a dosage of 150mg/day for 12 months. The percentage change in salivary secretion after 3, 6, and 12 months of the therapy increased to +112.2% (P 0.001), +119.9% (P 0.01), and +147.3% (P 0.001), respectively, compared with the baseline. Serum IgG levels decreased significantly throughout the study, and the level was 1969.4 ± 620.0mg/dl after treatment for 12 months compared with the pretreatment value of 2094.3 ± 746.6mg/dl (P 0.05). The patients assessment of clinical signs and symptoms on a 10-cm visual analog scale improved significantly from 7.2 ± 2.3cm at the start of the treatment to 5.0 ± 1.9cm after 12 months (P 0.001). There was a similar improvement in the physicians assessment using the 10-cm visual analog scale: 7.1 ± 1.6cm at the start of the treatment and 5.2 ± 1.9cm after 12 months (P 0.001). With regard to safety, no serious adverse reactions were observed. Although a controlled study would be required to clarify the efficacy of mizoribine, these preliminary observations indicate its efficacy for ameliorating glandular symptoms through improvements in immune abnormalities in patients with SjÖgrens syndrome.     

Ultrasonic tissue characterization in patients with dilated cardiomyopathy: comparison with findings from right ventricular endomyocardial biopsy

Aim: The clinical usefulness of integrated backscatter (IB) imaging was compared with right ventricular endomyocardial biopsy for assessing myocardial damage in patients with dilated cardiomyopathy (DCM). Methods: We examined 15 patients with DCM and 20 healthy controls. In addition to the conventional M-mode echocardiographic parameters, we determined the cyclic variation in IB values (CV-IB) obtained from parasternal short axis views of the left ventricle just under the transducer for both the interventricular septum (IVS) and the left ventricular posterior wall (PW). The per cent fibrosis area (%) and the transverse diameter of myocytes (m) were measured in right ventricular endomyocardial biopsy specimens by computer image analysis. To analyze the relationship between pathological findings and CV-IB, we divided patients into four subgroups on the basis of the pathological characteristics of endomyocardial biopsy specimens as follows: degeneration dominant group (n=5), fibrosis dominant group (n=5), dilated phase hypertrophic cardiomyopathy (n=2), and mixed type (n=3). Results: CV-IB in the IVS and the PW was lower in patients with DCM (8.8 ± 2.9, 8.3 ± 2.7dB, respectively) than in normal subjects (14.4 ± 2.9, 13.6 ± 2.6dB, respectively). Biopsy findings showed a mean per cent fibrosis area of 24.0 ± 12.3%, and a mean myocyte diameter of 14.3 ± 2.9m in patients with DCM. CV-IB was correlated with both of these findings: per cent fibrosis area (r=–0.56 in IVS, r=–0.56 in PW) and myocyte diameter (r=0.67 in IVS, r=0.71 in PW). CV-IB was decreased in all DCM subgroups compared with normal subjects, but there was no significant difference between subgroups. Conclusions: CV-IB was correlated with both the extent of fibrosis in myocardial tissue and the myocyte diameter. These findings suggest that ultrasonic tissue characterization is a good indicator of the severity of fibrosis and myocyte atrophy in patients with DCM.     

Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice

Background d-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor- (TNF-) plays a pivotal role. We examined the effects of a highly selective adenosine A_2A receptor agonist (ATL-146e) on GalN/LPS-induced fulminant hepatic failure.Methods Mice were given an intraperitoneal dose of GalN (800mg/g body weight)/LPS (100ng/g body weight) with and without ATL-146e (0.01µg/kg) treatment. Liver injury was assessed biochemically and histologically. Also, TNF- levels in the serum were determined.Results The serum liver enzyme (ALT) level in vehicle-treated mice was 20960 ± 2800IU/ml and was reduced by 63% to 7800 ± 1670IU/ml by treatment with 0.01µg/kg per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum TNF- and greatly reduced inflammation assessed by histopathologic examination compared with control mice treated with GalN/LPS. ATL-146e also reduced lethality at 12h from 65% to 13%.Conclusion The present findings suggest that the highly selective adenosine A_2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF- secretion.     

Increased uptake of low density lipoprotein by SV40-transformed smooth muscle cells

We compared the metabolism of low density lipoprotein (LDL) in SV40-transformed smooth muscle cells (TSMCs) to that in nontransformed smooth muscle cells (SMCs). When SMCs were incubated in medium with 100 g/ml LDL for 24 hours, they did not accumulate sudanophilic lipid droplets. On the other hand, when TSMCs were incubated in medium containing more than 100 g/ml LDL, they accumulated a large amount of lipid droplets in their cytoplasm. When cells were incubated with 200 g/ml LDL for 24 hours, cholesteryl ester levels significantly increased in TSMCs (18.3±3.53 g/mg protein), as compared with SMCs (2.40±0.85 g/mg protein). However, there was no difference in the cellular level of free cholesterol between the TSMCs and SMCs. Although the TSMCs and SMCs had a similar number of binding sites for LDL, the TSMCs demonstrated a markedly higher uptake of LDL labeled with 1,1-dioctadecyl-3,3,3,3-tetramethyl indocarbocyanine perchlorate (Dil-LDL), compared with the SMCs. SMCs that had been pretreated with 100 g/ml of unlabeled LDL for 24 hours showed a decreased uptake of Dil-LDL. In contrast, TSMCs incorporated Dil-LDL independently of the preincubation with 100 g/ml LDL. The presence of brefeldin A, which may block the transport of glycoproteins from the ER to Golgi apparatus, had less of an effect on the uptake of LDL in the TSMCs than in the SMCs. These results suggest that SV40-transformed smooth muscle cells show an increased uptake of LDL independent of the cellular cholesterol level, which may induce the accumulation of lipid droplets in their cytoplasm. A LDL receptor-independent pathway may be related to the increased uptake of LDL in SV40-transformed smooth muscle cells.     

Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease

Canavan disease, an inherited leukodystrophy, is caused by mutationsin the aspartoacylase (ASPA) gene. It is most common among children of Ashkenazi Jewish descent but has been diagnosed in many diverse ethnic groups.Two mutations comprise the majority of mutant alleles in Jewish patients, while mutations in the ASPA gene among non-Jewish patients are different and more diverse. In the present study, the ASPA gene was analysed in 22 unrelated non-Jewish patients with Canavan disease, and 24 different mutations were found. Of these, 14 are novel, including five missense mutations (E24G, D68A, D249V, C152W, H244R), two nonsense mutations (Q184X, E214X), three deletions (923delT, 33del13, 244delA), one insertion mutation (698insC), two sequence variations in one allele ([10T>G; 11insG]), an elimination of the stop codon (941A>G, TAGTGG, X314W), and one splice acceptor site mutation (IVS1–2A>T). The E24G mutation resulted in substitution of an invariable amino acid residue (Glu) in the first esterase catalytic domain consensus sequence. The IVS1–2A>T mutation caused the retention of 40 nucleotides of intron 1 upstream of exon 2. The results of transient expression of the mutant ASPA cDNA containing these mutations in COS-7 cells and assays for ASPA activity of patient fibroblasts indicated that these mutations were responsible for the enzyme deficiency. In addition, patients with the novel D249V mutation manifested clinically at birth and died early. Also, patients with certain other novel mutations, including C152W, E214X, X314W, and frameshift mutations in both alleles, developed clinical manifestations at an earlier age than in classical Canavan disease.     

Microemboli at the Different Stages of Percutaneous Transluminal Carotid Angioplasty and Stenting in Patients with Post–carotid Endarterectomy Restenosis Compared to Primary Stenosis

Microembolization to cerebral arteries during percutaneous transluminal carotid angioplasty (PTCA) and stenting is well described, as well as different mural pathology in primary versus post–carotid endarterectomy (CEA) restenosis lesions. The purpose of this study is to investigate possible different patterns of embolization in regards to number and distribution of microembolic signals (high-intensity transient signals (HITS)) in patients with primary carotid stenosis and restenosis after CEA. We used transcranial Doppler (TCD) to monitor the ipsilateral middle cerebral artery (MCA) of 13 patients (13 procedures) with restenosis after CEA and six patients (seven procedures) with primary stenosis of the internal carotid artery (ICA) during PTCA and stenting. All the procedures were performed without protection devices. The total number of HITS recorded in all patients was 2692, including 1563 microemboli in patients with restenosis and 1129 in patients with primary stenosis. The mean number of microemboli per procedure was 120.2±65 and 161.3±70 (p=0.05) respectively. The average number of microembolic signals during the various stages of PTCA and stenting in the two groups was as follows: 1. Crossing the stenotic region with the guidewire and positioning the balloon inside the stenosis 33±6.9 and 73.4±9.4 (restenosis patients versus primary–stenosis patients, respectively, (p=0.011); 2. angioplasty, balloon inflation and deflation, 19.l±6.9 and 38.9±9.4 (restenosis versus primary lesions, respectively, p=0.09); 3. stent deployment, 39.5±6.9 and 27.3±9.4 (restenosis versus primary lesions, respectively, p=0.3); and 4. Post-stent dilatation, 29±6.9 and 21.7±9.4 (restenosis versus primary lesions, respectively, p=0.53). Microembolic signals are detected through all stages of PTCA and stenting in patients with primary or post-CEA-restenosis lesions. The number of HITS was significantly higher in patients with primary stenosis than with restenosis of ICA in stages prior to stenting. This probably stems from the difference in pathomorphologic structure between the lesions. There was no significant difference between groups during stent deployment and post-stent dilatation. The clinical significance of the phenomenon of microembolism during carotid stenting is still not clear, but our results suggest the importance of using protection devices to reduce the incidence of these events in both primary and post-CEA lesions.     

Pulsed Doppler tissue imaging can help to identify patients with right ventricular infarction

This study was planned to assess whether tissue Doppler imaging is a useful method for the detection of the right ventricular myocardial infarction. Forty-eight patients with acute inferior myocardial infarction and 24 age- and sex-matched healthy controls were included in this study. Twenty-four patients had electrocardiographic signs of inferior myocardial infarction without right ventricular infarction (group I), and the other 24 patients had electrocardiographic signs of inferior myocardial infarction with right ventricular infarction (group II). From the echocardiographic apical four-chamber view, peak systolic, early diastolic, and late diastolic velocities of the tricuspid annulus at the right ventricular free wall were recorded with the use of pulsed-wave Doppler tissue imaging. The tricuspid annular peak tissue Doppler imaging systolic velocity was significantly lower in group I (14.03 ± 2.57cm/s, P 0.005) and in group II (8.50 ± 0.84cm/s, P 0.005) than in controls (16.63 ± 2.31cm/s). The tricuspid annular peak systolic (8.50 ± 0.84cm/s vs 16.63 ± 2.31cm/s) and peak early diastolic (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) velocities were significantly lower in group II than in group I, as compared with controls (P 0.001). Peak early diastolic velocity of tricuspid annulus (10.99 ± 3.28cm/s vs 19.39 ± 4.3cm/s) was significantly lower in group I than in controls (P 0.001); however, late diastolic velocity was significantly lower in group II (15.98 ± 5.08cm/s, P 0.05) than in group I (18.21 ± 2.63cm/s, P 0.05) and in controls (19.02 ± 5.29cm/s). The results of this study indicate that tricuspid annular peak systolic and early diastolic velocities are reduced in patients with right ventricular infarction. The velocity of the tricuspid annulus by tissue Doppler imaging is simple and can be used to distinguish whether patients with inferior myocardial infarction have right ventricular infarction.This study was presented at the XXIII. Congress of the European Society of Cardiology, Stockholm, Sweden, 1–5 September 2001     

Vigorous achalasia with high-amplitude esophageal body contractions: a case report

A 25-year-old woman presented with dysphagia and chest pain in November 1999. Esophagography revealed esophageal stasis with spindle-shaped tapering at the cardia without dilatation of the lower esophagus. Manometry showed a hypertonic sphincter with incomplete relaxation on swallowing. Esophageal body contractions were simultaneous with an amplitude in excess of 200mmHg with tertiary contractions. These findings were not compatible with classic achalasia, but with vigorous achalasia. The patient underwent pneumatic dilatation with immediate relief of her symptoms. However, improvement in dysphagia and chest pain was temporary, necessitating four sessions of dilatation over three and a half years. The literature on this rare esophageal motility disorder is reviewed.     

Anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus investigated with a three-dimensional electroanatomical mapping system

We studied the anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus in humans with a three-dimensional electroanatomical mapping system (CARTO, Biosense, Haifa, Israel). Fifteen patients with atrial flutter were studied. Thirteen patients had underlying heart disease. We investigated the anatomical structure of the isthmus with cross sections made from the three-dimensional right atrial map. The cross sections of the isthmus showed a concave shape in 7 patients (47%: group A), convex shape in 2 (13%: group B), and complex shape in 6 (40%: group C). The distance between the IVC and TA was 34 ± 17mm (group A), 25 ± 2mm (group B), 34 ± 16mm (group C), and 32 ± 15mm (Total), respectively. The distance between the top and bottom was 6 ± 5mm (group A), 3mm (group B), 6 ± 3mm (group C), and 6 ± 4mm (total), respectively. Seven of 15 patients exhibited an uneven surface of more than 5mm in depth and 4 of 15 patients had one of more than 10mm. The anatomical structure of the isthmus varies. To carry out precise catheter ablation, these variations should be taken into consideration to ensure an effective procedure.     

Interferon monotherapy for patients with chronic hepatitis C and normal serum aminotransferase levels at commencement of treatment

Background Approximately 30% of patients with chronic hepatitis C have normal serum alanine amino transferase (ALT) levels. While interferon (IFN) monotherapy is approved for patients with chronic hepatitis C infection, the effectiveness of such therapy for chronic hepatitis C patients with normal ALT levels at commencement of treatment remains poorly understood.Methods Ninety-four individuals (M/F, 54:40; median age, 46 years) with normal ALT levels (<50IU/l) at the commencement of treatment who were positive for both anti-hepatitis C virus (HCV) and serum HCV-RNA were studied. Among this group, 18 individuals (M/F, 9:9; median age, 50 years) had had persistently normal ALT levels for at least 3 months prior to treatment. All patients received their first course of IFN therapy in this study.Results Forty-three (45.7%) of 94 individuals had lost serum HCV-RNA at 6 months after cessation of therapy (complete response; CR). The proportion of patients with genotype 2a and HCV-RNA level over 1Meq/ml who showed CR was significantly lower in those with normal ALT levels than in those with elevated ALT levels (23.8% vs 55.6%; P = 0.0189). Two patients who had persistently normal ALT levels and HCV-RNA level over 1Meq/ml were nonresponders (NR) and had ALT flare-ups after IFN therapy. Patients with HCV-RNA levels of less than 1Meq/ml did not show differential responses based on ALT levels.Conclusions Our data suggest that IFN therapy is effective for patients with normal ALT levels and less than 1Meq/ml HCV-RNA. Thus, such patients should be considered for curative IFN therapy.     

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.     

PBC-AIH overlap syndrome with concomitant ITP and Hashimoto’s disease with positivity for anti-centromere antibody

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimotos disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimotos disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6g/dl; -globulin (glb), 35.9%; total bilirubin (T-bil), 9.41mg/dl; direct bilirubin (D-bil), 7.52mg/dl; aspartate aminotransferase (AST), 957U/l; alanine aminotransferase (ALT), 651U/l; alkaline phosphatase (ALP), 595U/l; -guanosine triphosphate (GTP), 129U/l; IgG, 2620mg/dl; IgM, 223mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimotos disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.     

Granulocyte Elastase in Cirrhotic Patients with Spontaneous Bacterial Peritonitis

Granulocyte elastase (GE) is a powerfulproteolytic enzyme that is released by PMNs whendegranulated in infectious processes. The aim of thisstudy was to measure GE in ascites and plasma ofcirrhotic patients with spontaneous bacterial peritonitis(SBP). We studied 29 cirrhotic patients, 17 of themhaving SBP (group A). Twelve patients with noninfectedascites formed the control group (group B). At the time of diagnosis of SBP, GE levels inascites (183.17 ± 86.11 g/liter) and plasma(114.6 ± 35.99 g/liter) were higher in groupA than in group B (27.41 ± 11.54 g/liter, P< 0.00001 and 82.54 ± 20.52 g/liter, P = 0.01,respectively). Levels of GE in ascites had a high valuefor discriminating between patients with and withoutSBP. In the patients who responded to the initialantibiotic treatment, these values significantly decreasedin ascites (67.69 ± 54.22 g/liter, P = 0.003)and plasma (67 ± 22.39 g/liter, P = 0.01) 48hr after therapy was started, in parallel with thedecrease of PMN in ascites. In patients who did notrespond, the production of GE remained elevated.Patients who developed renal insufficiency following SBPhad more marked elevation of GE in plasma (144.8± 33.43 g/liter) than those with normal renalfunction (99.5 ± 27.53 g/liter, P = 0.02).These results suggest that the measurement of GE may behelpful for the diagnosis of SBP in patients withcirrhosis and for assessing the efficacy of therapy. Inaddition, the release of GE into plasma may contributeto the impairment of renal function that follows SBP insome patients.     

Characteristics of ischaemic human myocardium: a transoesophageal echocardiographic and voltammetric microelectrode study

Delayed local myocardial power development (primary asynchrony) has been suggested as a marker of ischaemic ventricular dysfunction in humans. However, to prove this, microcirculatory perfusion, microcirculatory oxygenation, and intrinsic mechanical function of the same asynchronous myocardial segment should be studied simultaneously before and after revascularisation. We performed a prospective intraoperative study of 15 patients (age 67 [SD 5] years) at baseline and 30min after left anterior descending artery grafting. Local tissue perfusion and oxygenation of the anterior left ventricular wall were quantified with a voltammetric microelectrode technique. Transesophageal M-mode echocardiograms and simultaneous high-fidelity left ventricular pressure were measured. Eight patients showed primary asynchrony and 7 did not. Patients with primary asynchrony had local mechanical depression with lower resting values of myocardial work and peak power which increased with surgery. In this group, resting perfusion consistently increased with surgery (32.1 [13] to 54 [31]mlmin^–1 100g^–1, P < 0.05). In the remaining patients, local work and power were normal, and resting perfusion was consistently higher (90 [9]Mlmin^–1 100g^–1, P < 0.05 vs primary asynchrony), and fell with surgery. Local tissue oxygen tension was similar in both groups (38 vs 44mmHg) and did not change with surgery. In patients with chronic coronary artery disease, microcirculatory perfusion, but not pO₂, is reduced in regions showing primary asynchrony and impaired mechanical function. Abnormalities in both mechanical function and perfusion normalise within 30min of revascularisation. These data provide further evidence that primary asynchrony is not only a marker of chronic ischemic ventricular dysfunction, but is associated with a modified contraction pattern in which normal oxygen tension coexists with reduced perfusion.     

Beneficial effects of N-acetylcysteine on sodium taurocholate-induced pancreatitis in rats

Background Acute pancreatitis (AP) is a complex disease associated with significant complications and a high rate of mortality. Although several mechanisms are put forward, oxidative stress seems the most important early event in the pathophysiology of AP. Therefore, we evaluated the beneficial effects of N-acetylcysteine (NAC), a strong antioxidant, in experimental AP.Methods Forty-nine Sprague-Dawley rats were used. Acute pancreatitis (AP) was induced by the intraductal infusion of sodium taurocholate. Rats were divided into seven groups (each containing seven rats): control, sham-operated (saline-treated, 3.5 and 12h), non-treated AP (3.5 and 12h) and NAC-treated AP (3.5 and 12h). Treated rats received intraperitoneal (i.p.) NAC 1000mg/kg 24h before and just before the induction of pancreatitis.Results Rats with AP had extensive parenchymal and fat necrosis and NAC treatment at 12h reduced tissue necrosis significantly (P 0.05). NAC treatment at 12h reduced leukocytic infiltration significantly (P 0.05). Edema and hemorrhage were significantly increased in the AP groups when compared to controls (P 0.001). NAC treatment reduced edema and hemorrhage at both 3.5 and 12h slightly but not significantly. The total pathological mean score was significantly increased in the AP groups (P 0.05) and it was reduced by NAC treatment (P 0.05). NAC treatment decreased plasma amylase and lipase levels significantly (P 0.05). While glutathione peroxidase (GPx) activity of pancreatic tissue was similar in the NAC-treated and AP groups, hepatic tissue GPx activity was lower in the AP groups, and NAC treatment restored it (P 0.05). NAC had no effect on pancreatic superoxide dismutase level. In the NAC-treated rats, the serum NO₂/NO₃ (nitrite/nitrate) level was significantly increased in the 3.5-h group when compared to the respective AP group (P 0.05). NAC treatment also significantly reduced the serum concentration of the lipid peroxidation product, malondialdehyde, at 12h (P 0.05).Conclusions NAC treatment had beneficial effects in sodium taurocholate-induced AP in rats. It reduced pancreatic tissue necrosis and lipid peroxidation. In our study, the mechanism underlying the beneficial effects of NAC seemed to be its antioxidant activity, either by increasing hepatic GPx activity, or by a direct scavenging effect on free radicals, thus enhancing the production of and/or inhibiting the degradation of nitric oxide.Presented at the 1st National Experimental Surgery Meeting, January 5–6, 2002, Ankara, Turkey     

Effects of Piclamilast,a Selective Phosphodiesterase-4 Inhibitor,on Oxidative Burst of Sputum Cells From Mild Asthmatics and Stable COPD Patients

Oxidative stress associated with increased presence of neutrophils is an important feature of inflammatory airways diseases like asthma or chronic obstructive pulmonary disease. We studied the in vitro effect of piclamilast (RP73401), a selective phosphodiesterase (PDE)-4 inhibitor, compared to theophylline and prednisolone, on respiratory burst of sputum cells from mild asthmatics and COPD patients. Sputum cells were harvested from mild asthmatics and stable COPD patients and treated with piclamilast, theophylline or prednisolone. Respiratory burst was assessed by luminol-dependent chemoluminescence after stimulation with 10 M n-formyl-met-leu-phe (FMLP). Piclamilast inhibited FMLP-induced respiratory burst of sputum cells in a concentration-dependent manner (asthma: EC₅₀ approximately 100 nM, max. inhibition: 97.5±5% at 100 M; COPD: EC₅₀ approximately 1 M, max. inhibition: 70.6±4.5% at 100 M), whereas maximal inhibition observed with theophylline (asthma: max. inhib. 27±15%; COPD: 6±2%, both p < 0.05 vs. piclamilast) and prednisolone (asthma: 16±6%; COPD: 7.8±6.2%, both p < 0.05 vs. piclamilast) was weaker. Inhibition by piclamilast was largely reversed through pretreatment of cells with the adenylcyclase inhibitor SQ22536. We concluded that piclamilast, a selective PDE-4 inhibitor, attenuates the respiratory burst of sputum cells from mild asthmatics and COPD patients in vitro. These data underline the potential of PDE-4 inhibition as a novel therapeutic approach to inflammatory airway diseases like asthma or COPD.