Impact of comprehensive pulmonary rehabilitation on anxiety and depression in hospitalized COPD patients.

To prospectively evaluate the effect of inpatient pulmonary rehabilitation (iPR) on anxiety and depression as outcome measures in patients with COPD, we studied 149 consecutive adults COPD referred to our iPR after an exacerbation. Patients were divided according to the GOLD staging into: Group 1 (stage 2a, n = 48, FEV1 63 +/- 9% pred.), Group 2 (stage 2b, n = 53, FEV1 42 +/- 6% pred.) and Group 3 (stage 3, n = 48, FEV1 25 +/- 7% pred.). The iPR consisted of twelve 3-hours daily sessions. Hospital Anxiety Depression (HAD) Scale as well as 6-minute walk (6MWD) with evaluation of dyspnea (D) and leg fatigue (F) at rest and end of effort, and health related quality of life by means of St. George Respiratory Questionnaire (SGRQ) were assessed before (T0) and after (T1) the iPR. 6MWD, D and F at end of effort and SGRQ total score similarly improved (p < 0.001) in all groups after iPR. The mean level of HAD-anxiety (from 9.1 +/- 4.0 to 7.7 +/- 3.5, from 9.0 +/- 4.6 to 7.2 +/- 4.6 and from 8.1 +/- 4.1 to 6.7 +/- 4.3 in group 1,2 and 3 respectively) and HAD-depression (from 9.4 +/- 3.5 to 8.2 +/- 3.5, from 9.1 +/- 4.2 to 8.2 +/- 4.5 and from 9.0 +/- 4.0 to 7.4 +/- 4.5 respectively) similarly changed (p < 0.0001) over time in all groups. The total percentage of patients with abnormal score (> 10) of HAD-anxiety (from 31% to 21%) and HAD-depression (from 30% to 22%) significantly decreased (p < 0.05) after the iPR. Inpatient pulmonary rehabilitation may improve levels of anxiety and depression as well as symptoms, exercise capacity and health related quality of life in moderate to severe COPD patients after an acute exacerbation.

Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients.

Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT Three patients with no history of previous liver diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients.

Polynucleotide:Adenosine glycosidase is the sole activity of ribosome-inactivating proteins on DNA.

Polynucleotide: adenosine glycosidases (PNAG) are a class of plant and bacterial enzymes commonly known as ribosome-inactivating proteins (RIP). They are presently classified as rRNA N-glycosidases in the enzyme nomenclature [EC 3.2.2.22]. Several activities on nucleic acids, other than depurination, have been attributed to PNAG: in particular modifications induced in circular plasmids, including linearisation and topological changes, and cleavage of guanidinic residues. Here we describe a chromatographic procedure to obtain nuclease-free PNAG by dye-chromatography onto Procion Red derivatized Sepharose((R)). Highly purified enzymes depurinate extensively pBR322 circular, supercoiled DNA at neutral pH and exhibit neither DNase nor DNA glycolyase activities, do not cause topological changes, and adenine is the only base released from DNA and rRNA, even at very high enzyme concentrations. A scanning force microscopy (SFM) study of pBR322 treated with saporin-S6 confirmed that (i) this PNAG binds extensively to the plasmid, (ii) the distribution of the bound saporin-S6 molecules along the DNA chain is markedly variable, (iii) plasmids already digested with saporin-S6 do not appear fragmented or topologically modified. The observations here described demonstrate that polynucleotide:adenosine glycosidase is the sole enzymatic activity of the four ribosome-inactivating proteins gelonin, momordin I, pokeweed antiviral protein from seeds and saporin-S6. These proteins belong to different families, suggesting that the findings here described may be generalized to all PNAG.

[Fulminant liver failure: etiopathogenesis and therapy]. / Insufficienza epatica fulminante: eziopatogenesi e terapia.

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by the development of encephalopathy within eight weeks from the onset of the first symptoms, in the absence of previous hepatic disease. It is an uncommon but not rare disease, often fatal but potentially reversible. This article looks at the diverse aetiologies, clinical features, and current medical management, including orthotopic liver transplantation, and auxiliary orthotopic or eterotopic liver transplantation, that are the most recently adopted surgical procedures. Clinical experience with bio-artificial liver support systems of two of the most active research Groups in this field, concludes the paper.

[Acute and fulminant liver failure: experimental models]. / Insufficienza epatica acuta e fulminante: modelli sperimentali.

Fulminant hepatic failure (FHF) is a complex clinical syndrome, with an invariably high mortality rate, that follows many possible and different infectious, pharmacologic and surgical liver injuries. The appearance of the syndrome is similar whatever the etiology, but the mechanisms which lead to the development of FHF are greatly varied. In order to understand the possible pathways which drive to FHF, experimental animal models have been used for a long time. Six requirements should be fulfilled by any FHF animal model: 1) reversibility; 2) reproducibility; 3) death from liver failure; 4) the presence of a therapeutic window; 5) the need of large laboratory animal; 6) minimal hazard to personnel involved in the study. In the present paper a number of models are reported and described, and advantages and disadvantages are discussed. It is concluded that with respect to the aforementioned criteria, no available experimental model is yet as satisfactory as expected.

[In vitro experimentation of a new model of radial flow bioreactor containing isolated hepatocytes]. / Sperimentazione in vitro di un nuovo modello di bioreattore a flusso radiale contenente epatociti isolati.

Hepatocyte based artificial liver support systems are under investigation to support acute liver failure patients. The main purpose of such systems is to serve as a bridge to liver transplantation, or to promote spontaneous liver recovery. Limitation in mass-transfer capacity makes hollow-fiber bioreactors unsuited for long-term functioning of hybrid devices. We developed a novel radial-flow bioreactor in which the fluid perfuses the module from the center to the periphery, after having diffused through a space occupied by a three-dimensional structure filled with the hepatocytes. Five grams of freshly isolated porcine hepatocytes were seeded into uncoated, woven-non woven, hydrophilic polyester fabric, overlaid by two polyethersulfone membranes. Liver cells were perfused with 37 degrees C-warm, oxygenated, serum-free tissue culture medium, in which NH4Cl and Lidocaine were added at the final concentration of 1 mM and 60 micrograms/ml, respectively. Ammonium chloride removal, urea synthesis, monoethylglycinexylide (MEGX), pO2, pCO2, and pH were measured throughout the 14 day duration of the study. In a separate set of experiments, a scaled-up version of the radial flow bioreactor containing 150 grams of cells was perfused for 7 h with recirculating human plasma and MEGX production was monitored. During the 2 weeks of the study, an increasing production of urea was paralleled by constant ammonium removal. MEGX concentration after Lidocaine addition increased throughout the 14 days of perfusion with tissue culture medium, as well as after 7 hour perfusion with human plasma. Under transmission and scanning electron microscopy cells appeared attached to the polyester and one to each other, displaying ultrastructural features typical of functioning hepatocytes. Our study showed that liver cells were metabolically active when perfused into the radial-flow bioreactor. This configuration allowed close contact between media, or plasma, and cells at a physiological flow rate, by equalizing the concentration of the perfusing components, including O2, throughout the module. Our results suggest a potential use of this system for temporary extracorporeal liver support in acute hepatic failure patients.

Portal decompression using the inferior mesenteric vein.

We report five patients with variceal hemorrhage, in three cases secondary to diffuse thrombosis of the portal, superior mesenteric and splenic veins. Mesenteric angiography demonstrated patency of the inferior mesenteric vein (IMV) in each, and successful portal decompression by anastomosis of the IMV to the left renal vein (n = 4) or the inferior vena cava (n = 1) was accomplished. Bleeding was permanently controlled: four patients have survived from one to eight years post-operatively. Because shunt procedures utilizing the IMV are technically straightforward, subtotally decompress the portal system and avoid the right upper quadrant, they may be advantageous in certain clinical settings.

Polynucleotide:adenosine glycosidase activity of ribosome-inactivating proteins: effect on DNA, RNA and poly(A).

Ribosome-inactivating proteins (RIP) are a family of plant enzymes for which a unique activity was determined: rRNAN-glycosidase at a specific universally conserved position, A4324in the case of rat ribosomes. Recently we have shown that the RIP from Saponaria officinalis have a much wider substrate specificity: they are actually polynucleotide:adenosine glycosidases. Here we extend studies on substrate specificity to most known RIP: 52 purified proteins, both type 1 (single-chain) and type 2 (two chain, an enzymatic chain and a lectin chain) were examined for adenine release on various substrates including RNAs from different sources, DNA, and poly(A). All RIP depurinated extensively DNA and some released adenine from all adenine-containing polynucleotides tested. From experimental evidence the entire class of plant proteins, up to now called ribosome-inactivating proteins, may be classified as polynucleotide:adenosine glycosidases. The newly identified substrates may be implicated in the biological role(s) of RIP.

Polynucleotide: adenosine glycosidase activity of saporin-L1: effect on DNA, RNA and poly(A).

The ribosome-inactivating proteins (RIPs) are a family of plant enzymes for which a unique activity has been determined: rRNA N-glycosidase, which removes adenine at a specific universally conserved position (A4324 in the case of rat ribosomes). Here we report that saporin-L1, a RIP from the leaves of Saponaria officinalis, recognizes other substrates, including RNAs from different sources, DNA and poly(A). Saporin-L1 depurinated DNA extensively and released adenine from all adenine-containing polynucleotides tested. Adenine was the only base released from DNA or artificial polynucleotides. The characteristics of the reactions catalysed by saporin-L1 have been determined: optimal pH and temperature, ionic requirements, and the kinetic parameters Km and kcat. The reaction proceeded without cofactors, at low ionic strength, in the absence of Mg2+ and K+. Saporin-L1 had no activity towards various adenine-containing non-polynucleotide compounds (cytokinins, cofactors, nucleotides). This plant protein may now be classified as a polynucleotide: adenosine glycosidase.

Activities associated with the presence of ribosome-inactivating proteins increase in senescent and stressed leaves.

The ribosome-inactivating proteins (RIPs) from Hura crepitans and Phytolacca americana release adenine from herring sperm DNA. Leaf extracts from these plants show the same enzymatic activities as the RIPs. The translation inhibitory activity and the activity on DNA are both increased in the leaves of both plants during senescence or when subjected to heat or osmotic stress. It is proposed that a physiological role of RIPs could be to intervene in the death of plant cells.

Production of ribosome-inactivating protein from hairy root cultures of Luffa cylindrica (L.) Roem.

Transformed root lines of Luffa cylindrica (L.) Roem. (Cucurbitaceae) were established by inoculation of in vitro grown plantlets with wild type Agrobacterium rhizogenes strain 1855. Cloned lines of hairy roots were tested for the presence of ribosome-inactivating proteins; crude extracts inhibited protein synthesis in a reaction mixture based on rabbit reticulocyte lysate. Inhibitory activity increased during culture period, reaching a maximum value in the stationary phase. No activity could be detected in the culture medium, nor in extracts from callus and/or suspension cultures. A ribosome-inactivating protein having specific activity of 62,100 U mg protein(-1) and a molecular mass of 26-28,000 Da was purified to homogeneity. The protein showed N-glycosidase activity on rat liver ribosomes. The results demonstrate that hairy root cultures can be successfully utilized for the in vitro production of ribosome-inactivating proteins.

Increased sinusoidal wall permeability and liver fatty change after two-thirds hepatectomy: an ultrastructural study in the rat.

Accumulation of lipids in the hepatocyte cytoplasm after partial hepatectomy (PH) has long been recognized, but the mechanism behind this phenomenon is still poorly understood. In this study, rats subjected to a standard two-thirds PH showed early and marked increase in portal venous pressure (P < .01). On scanning electron microscopy, the regenerating liver fixed by portal perfusion under hemodynamic conditions identical to that found in vivo during the first 24 hours showed a significant (P < .01) 10-fold increase in the sinusoidal wall porosity (percentage open area by fenestrations). This was paralleled by the disappearance of the sieve-plate arrangement of small fenestrations and by a significant decrease in the number of fenestrations per micrometers squared of sinusoidal surface at 6 (P < .01) and 12 hours (P < .05). In addition, there were major changes in the frequency and distribution of all three classes of fenestrations. At 6 and 12 hours, there was a marked decrease of small class 1 fenestrations and a marked increase of intermediate class 2 fenestrations and large class 3 fenestrations (P < .0001). A concurrent accumulation of lipid droplets in the hepatocyte cytoplasm produced a 20-fold increase in the hepatocyte total lipid volume. A statistically significant linear correlation (r = 0.907; P < .01) was found between the amount of intracellular lipids and the data quantitating the changes in porosity of liver sinusoids at 24 hours. It is concluded that an increased sinusoidal wall permeability to lipids may be the primum moves in the pathogenesis of transient liver fatty change after PH in the rat.

[Benign obstruction of the common bile duct: what is the current role of transduodenal sphincteroplasty?]. / Ostruzione benigna del coledoco: è ancora attuale la papillosfinteroplastica transduodenale?

This paper is a critical review of the clinical records of 20 patients who underwent a Transduodenal Sphincteroplasty (PSP), from October 1990 to January 1992 at our Department (General Surgery). The age was 64.9 (14.2) years (mean and standard deviation), but 14 (70%) of those patients were older than 60 (range: 63 to 89) and 9 (45%) were in the 8th up to 9th decade of their lives. In 16 patients PSP was performed at the same time as cholecystectomy. Common bile duct (CBD) exploration was decided in 11 patients only on the basis of the intraoperative cholangiographic findings (evidence of CBD stones and/or benign stenosis of the Papilla of Vater) as demonstration of the permanent role of this examination in biliary surgery. Among the patients who underwent PSP some time after cholecystectomy, one had a lesion of the choledochus, sustained when he was cholecystectomized 15 days before. Because of the fact that recovery was prompt and definitely uneventful, PSP together with the infusion of somatostatin (SMTN) can be considered a useful approach to the treatment of the biliary fistula.

[Transduodenal sphincterotomy and type II Mirizzi syndrome]. / Papillosfinteroplastica transduodenale e sindrome di Mirizzi di tipo II.

This paper describes the clinical course of a 76-year-old woman surgically treated in our department (General Surgery) for obstructive jaundice in Mirizzi syndrome (II). Ultrasonography and ERCP failed to demonstrate the pathological situation at the level of the biliary tree. When laparotomy was decided because of the progressive worsening of the general clinical conditions of the patient, intraoperative cholangiography showed the presence of a cholecystocholedochal fistula with multiple residual stones eroded into the common bile duct. Surgical management consisted of partial cholecystectomy, removal of the stones, choledochoplasty and exploration of the distal part of the common bile duct by a transduodenal sphincteroplasty. The post-operative period was uneventful and the patient was discharged from our department nine days after surgery. Even though the surgical approach to Mirizzi syndrome generally includes procedures other than papillosphincteroplasty+partial cholecystectomy, our experience seems to substantiate the efficacy of the previously mentioned treatment under suitable conditions.

Abdominal aortic aneurysmectomy associated with a native iliac kidney. Case report.

Abdominal aortic aneurysm (AAA) repair associated with a pelvic kidney is extremely rare. To date only 14 cases have been reported in the literature. The main problem during aortic cross clamping is kidney preservation. The purpose of this article is to record and additional case of AAA repair associated with a native pelvic kidney. The preservation has been successfully achieved by a distal aortic double clamping.

Conservative management of traumatic chylothorax: a case report.

A case is presented of a right traumatic chylothorax, secondary to thoracic trauma with bilateral posterior eleventh rib fracture, treated by total parenteral nutrition and pleural drainage, with resolution within 2 weeks. On the basis of this clinical report and of a review of the literature, it is concluded that adequate conservative management should be initially the treatment of choice. Surgical treatment should be reserved to the cases in which clinical improvement does not occur within 2 weeks, and should consist of supradiaphragmatic thoracic duct ligation. Thoracoscopic fibrin glue injection has recently been described as a possible alternative treatment.

[A case of retroperitoneal leiomyosarcoma]. / Su di un caso di leiomiosarcoma retroperitoneale.

Leiomyosarcoma is a rare malignant tumour originating from the smooth muscular tissue in any part of the organism, including retroperitoneum where it is particularly aggressive. It is nearly always characterized by a silent development causing diagnostic delay. The results of the primary therapy, which is always surgical, are limited because of the tumoral mass extension and the high local aggressiveness. The Authors present a clinical case which was under their observation and seize the opportunity of making a revision of the literature about it.