'Out-patient' albumin dialysis for cholestatic patients with intractable pruritus.

BACKGROUND: Intractable pruritus is a major problem for some patients with cholestasis. Albumin dialysis has been shown to ameliorate pruritus, but long-term outcome data are limited. AIM: To evaluate the safety and efficacy of 'out-patient' albumin dialysis using the molecular adsorbent recirculating system (MARS) in the treatment of intractable pruritus in cholestatic patients referred for liver transplantation for symptomatic relief. METHODS: Fifteen patients who failed to respond to standard medical therapy to control pruritus were included. Three MARS (6 h) sessions were performed per admission, and were repeated, if necessary. The intensity and severity of itch was quantified using itch severity and visual analogue scales (ISS and VAS). RESULTS: Molecular adsorbent recirculating system treatment was safe and associated with immediate and complete response in 11 patients; two patients had a partial response and two patients had no response. Thirty-four treatments were performed during a follow-up period of 15.7 months (3-46) with patients requiring a mean of two admissions (1-6). The mean VAS and ISS improved significantly (both P < 0.001) with improvement in the patient's perception of their quality of life. The duration of acceptable relief in responders was 3.3 months (range 2-5). No serious adverse events were recorded, but the platelet count and haemoglobin were reduced significantly. CONCLUSION: Molecular adsorbent recirculating system therapy delivered in an 'out-patient' setting is safe and effective with a high degree of patient acceptability. Albumin dialysis can be considered a viable therapeutic option for patients with severe intractable pruritus, in whom, the only other effective treatment option is liver transplantation.

Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

The potential of robotic technology applied to meet requirements for tools to support microsurgery and cellular surgery.

Microsurgery and processes involving cell manipulation or cell surgery are clinical practices where the operator works at or beyond the threshold of human dexterity. Current tools available are conventional in their design, and this limits consistency and the level of reliability and achievement. Surgical robotic devices have been explored to improve precision in minimal access surgical procedures to augment control of tool points in tissues, and have enabled feedback of sensory data from which the operator is able to deduce information on the tool at the working site. In this paper, relevant technologies are described that can be harnessed to improve perception of tool point interaction with tissues at the working site and to improve tool control at the small scale required in clinical practice for microsurgery and for cell surgery.

Reversible meiotic abnormalities in azoospermic men with bilateral varicocele after microsurgical correction.

Because of a possible relationship between microenvironmental disturbances and meiotic abnormalities and of a straight relationship between lower-quality semen in patient carrying a varicocele and first meiotic non-disjunction, bilateral bipolar testicular biopsies are realized according the thermic differential gradient described in varicocele. Systematic meiotic studies of multiple testicular biopsies from 65 azoospermic men with bilateral varicocele were done in a multi-centric study on microsurgical correction of bilateral varicocele with microthermic intra-operative evaluation using minimally invasive thermal microsensors (Betatherm 10K3MCD2). In the present study abnormal temperature raising, histomorphometric abnormalities (spermatocyte arrest) and meiotic abnormalities (class IIC) are strongly correlated. In the ten patients submitted to another testicular biopsy procedure six months after surgery for TESE, normal thermal differential is registered and no meiotic abnormalities recurrences are found.

Stable reversal of pathologic signs of primitive intestinal lymphangiectasia with a hypolipidic, MCT-enriched diet.

We report on a patient with protein-losing enteropathy due to primitive intestinal lymphangiectasia with an early reversal of clinical and biochemical signs and a stable late reversal of pathologic signs after treatment with a hypolipidic diet enriched with medium-chain triacylglycerols.

A case of sclerosing cholangitis managed by a percutaneous approach.

In 1992, a 61-year-old man who complained of recurrent episodes of fever and jaundice was diagnosed as having sclerosing cholangitis. In the three years that followed, the clinical picture progressively worsened; and, in 1995, the patient was hospitalized again for biliary obstruction. A liver transplantation was excluded because of concomitant severe coronary heart disease. A percutaneous transhepatic cholangiogram showed several critical strictures of the intrahepatic biliary tree and a temporary internal-external biliary drainage was placed to relieve the obstruction. After 40 days, a two-step percutaneous biliary balloon dilation was performed followed by topical steroid treatment through the catheter. After 45 days, the catheter was removed and steroid treatment tapered orally. In the three years that followed, the patient was well. He experienced only about 1-2 episodes of ascending cholangitis per year requiring antimicrobial therapy. Laboratory analysis showed a gradual improvement in hepatic chemistry, serum bilirubin, and erythrocyte sedimentation rate (ESR). In our patient, the association of percutaneous balloon dilation and topical steroid treatment improved both the clinical and radiological picture, without significant side-effects. This approach should be considered a valuable and cost-effective option in primary sclerosing cholangitis, mainly for patients not eligible for liver transplantation.

Histamine plasma levels and elimination diet in chronic idiopathic urticaria.

OBJECTIVE: The aim of this study was to evaluate the effects of an oligoantigenic and histamine-free diet on patients affected with chronic idiopathic urticaria (CIU). DESIGN: Ten patients with chronic idiopathic urticaria were prescribed an oligoantigenic and histamine-free diet for 21 days, followed by serial and controlled reintroduction of foods during a further 70 days. Modification in clinical illness as well as histamine plasma levels, post-heparin plasma diamine oxidase (DAO) and intestinal permeability were evaluated. RESULTS: The oligoantigenic and histamine-free diet induced a significant improvement of symptoms (P<0.05). Moreover, CIU patients on free diet showed higher histamine plasma levels (P<0. 05 vs post-diet and vs controls) that fell to control levels during the oligoantigenic and histamine-free diet. Post-heparin plasma diamine oxidase values were slightly reduced and were unchanged during the diet as well as intestinal permeability, which was always normal in all patients. CONCLUSIONS: These data suggest that histamine plays a major role in chronic idiopathic urticaria. The finding of normal intestinal permeability suggests that a morphological damage of intestinal mucosa should be excluded in these patients. However, the presence of low levels of post-heparin plasma diamine oxidase may indicate a subclinical impairment of small bowel enterocyte function that could induce a higher sensitivity to histamine-rich or histamine-producing food. European Journal of Clinical Nutrition (2000) 54, 155-158

Accumulation of 5 alpha-reduced androgen glucosiduronates associated with impaired removal in young male hemodialysis patients.

Hypothalamic-pituitary gonadal function is commonly altered in dialysis patients. Even though an improvement in general status and well-being has been noted after recombinant human erythropoietin supplementation, no significant changes were observed in the sex hormone profile. Pituitary gonadal axis as well as 5 alpha-reduced androgen glucosiduronates (i.e. 5 alpha-androstane,3 alpha,17 beta-diol and androsterone) profiles were studied in 23 young male stable dialyzed patients and compared to an age-matched group of healthy subjects. 5 alpha-Reduced androgen glucosiduronates are products of peripheral testosterone (T) metabolism and seem to be a useful tool in assessment of the male androgen status. Their polarity facilitates their urinary excretion, and their clearance is similar to the glomerular filtration rate in healthy men. We observed 1) a pituitary-Leydig cell dysfunction supported by normal serum estradiol and T levels, low free T, and increased LH levels; 2) an alteration of the dehydroepiandrosterone (DHEA) sulfate-DHEA interconversion, reflected by a dramatic decrease in DHEA while DHEA sulfate levels remained in the normal range; 3) an accumulation of 5 alpha-reduced androgen glucosiduronates, whose removal was impaired as shown by their very low sieving coefficients (< 0.012). Taken together, the above observations are consistent with alteration of spermatogenesis with respect to dialysis duration in which earlier elevated baseline serum LH levels indicate a primary defect in Leydig cell function.

Hypergastrinemia in rats with azoxymethane-induced colon cancers.

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.

Cell kinetics and polyamine enzymes in the intestinal mucosa of rats with azoxymethane induced tumours.

We studied the proliferative activity and the modifications in ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of rats with azoxymethane induced tumours. Fifty rats were treated with six weekly injections of 15 mg/kg body weight azoxymethane (AOM). Six rats died during the treatment. All the surviving rats developed intestinal tumours; tumour incidence was 93.1% (41/44) in the left colon, 40.9% (18/44) in the right colon and 45.4% (20/44) in the small bowel. In the normal-appearing mucosa close to intestinal tumours we found an extension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthesizing cells from the basal region to the middle and upper third (stage II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly higher than the normal mucosa of control rats (small bowel: 1.01 +/- 0.26 vs 0.42 +/- 0.15, P < 0.01; right colon: 1.32 +/- 0.34 vs 0.25 +/- 0.02, P < 0.001; left colon: 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). We also detected a significant decrease of DAO activity in the mucosa of the small bowel and right colon of treated rats compared to controls (0.86 +/- 0.09 vs 4.39 +/- 0.85, P < 0.01; 1.04 +/- 0.43 vs 3.80 +/- 0.91, P < 0.01, respectively), while DAO activity in the left colon was unchanged. The lower incidence of tumours in the small bowel and right colon suggests the presence of factors protecting these segments from carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Testicular ectopy. Current concepts]. / L'ectopie testiculaire. Notions actuelles.

Testicular descent is a complex mechanism influenced by hormonal and anatomical factors. Whatever the age of the patient or the descent technique used for either one or both testes, there is a risk of degeneration and sterility counts. Anatomical studies and the results of sperm are important, hence the importance of establishing a precise anatomical and therapeutic classification.

Postheparin plasma diamine oxidase values in the follow up of patients with small bowel Crohn's disease.

Measurement of postheparin plasma diamine oxidase (PHD) activity has been proposed to assess mucosal integrity in several diseases of the small intestine. In Crohn's disease, PHD values identify a group of patients with predominantly small bowel mucosal damage. To determine the role of mucosal involvement in the progression of small bowel Crohn's disease and whether different PHD values can predict different outcomes the changes in PHD values in 41 patients with small bowel Crohn's disease admitted consecutively to our department were investigated. The test was performed during periods of active disease and after either medical or surgical treatment had resulted in improvement. PHD values were significantly lower than in normal subjects (normal range 3.7-7.7 U/ml). In 35 patients with active disease (Crohn's disease activity index (CDAI) greater than 150) two groups were identified by choosing a cut off value of 2 U/ml: 93% of the 15 patients with PHD values lower than 2 U/ml (mean (SD) 1.36 (0.46) U/ml) relapsed at least once in the following year, while only the 20% of the 20 whose values were higher than 2 U/ml (mean (SD) 3.69 (1.50)) relapsed in the same period. The data were statistically significant (Yates's corrected chi 2 = 15.63; p less than 0.0001). The positive and negative predictive values of the test were 93% and 80%, respectively. During relapses, PHD values were consistently lower than previous values, and increased significantly after effective medical or surgical treatment. In the six patients in whom there were no changes in disease activity (CDAI persistently less than 150), there was no change in PHD values. This test may be useful for identifying Crohn's disease patients who are likely to relapse. Furthermore, the data indicate that mucosal damage is common in active small bowel Crohn's disease and improves at least in part after treatment.

Polyamine uptake by human colon carcinoma cell line CaCo-2.

The intracellular concentrations of the polyamines are highly regulated and high polyamine concentrations are associated with rapidly proliferating cells. Hormones, nutrients and growth factors that stimulate the proliferation of the intestinal epithelium, increase the intracellular polyamine concentration mainly by activating ODC expression. Other cell types stimulated to proliferate satisfy their requirement for polyamines by increasing polyamine uptake. In the present study, we investigated polyamine uptake by a human colon carcinoma cell line, CaCo-2. Uptake of putrescine, spermidine and spermine by CaCo-2 cells was saturable and temperature dependent and all polyamines appear to share a common carrier. The carrier of differentiated cells had an apparently higher affinity and lower activity than the carrier of replicating cells. Culture of CaCo-2 cells on porous filters showed that polyamine accumulation occurred mainly through the basolateral membrane in replicating cells, while an increase in the rate of apical uptake was observed after differentiation. A significant increase in polyamine uptake and in ODC expression resulted from fresh medium replacement, a well-known stimulus to proliferation; no change in uptake occurred after ODC inhibition by DFMO. We conclude that CaCo-2 cells are able to increase their polyamine concentration by both enhanced synthesis and increased polyamine uptake.

Regulation of diamine oxidase expression by ornithine decarboxylase in isolated rat small bowel enterocytes.

Ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, are highly expressed by small bowel enterocytes. Modulation of ODC expression is mediated through cellular concentration of polyamines that inhibits the enzyme synthesis and also induces the synthesis of an inhibitory protein, the antizyme, which in turn binds to ODC and inhibits its activity. DAO is an important regulator of intracellular concentration of polyamines because it catalyzes the degradation of putrescine into gamma-aminobutyraldehyde. Change in intracellular polyamine concentration has been suggested to represent a regulatory factor for DAO expression. In order to investigate a possible regulation of DAO expression by ODC, we studied the effect of difluoromethylornithine (DFMO), a selective, irreversible inhibitor of ODC, on DAO activity in isolated rat small bowel enterocytes. Our data demonstrate that in isolated small bowel enterocytes ODC inhibition by 10 mM DFMO reduced DAO activity by 53%, suggesting that, in our experimental conditions, ODC plays a regulatory role on DAO expression.

The pull-through technique for the advancement of the unfolded epididymal tubule and the tubulo-deferential telescopic reconstruction.

A new reconstructive microsurgical model of the epididymo-deferential complex was performed in the rat to study the plastic adaptation of the distal epididymal tubule in transposition and/or substitution procedures. The model consists of three steps: endoluminal stripping of the mucosa of the proximal half of the vas deferens; pull-through technique for the advancement of the unfolded epididymal tubule of the "zone 9" into the stripped vas deferens; end-to-end tubulo-deferential telescopic reconstruction.

[Reorganization of the electrical activity of the transverse colon after cholecystectomy. Study in humans with implanted electrodes]. / Réorganisation de l'activité électrique du côlon transverse après cholécystectomie. Etude chez l'homme porteur d'électrodes implantées.

Electrical activity of the colon was investigated in the postoperative period in 12 patients, 1 to 6 days after cholecystectomy. The polygraphic records are obtained during 2 hours each day late in the morning (10-12 h) in a preprandial situation from serosal implantation of bipolar copper wires inserted into each circular and longitudinal layer in narrow portion of the middle part of the transverse colon. The time presence diagrams was built up after recognition of the basic patterns activity previously definite by Sarna as follows: Electro-Control-Activity, with it slow waves (ECA), Electro-Response-Activity (ERA) with Discrete bursts (DERA) or Continuous ones (CERA). In the former postoperative period 1 to 3 days ECA is present with a low range frequency 1-5 c/min. The higher frequency (10-12 c/min) activity arises sporadically, in this case associated with DERA bursts. From the 4th day all activities ECA and DERA increase significantly. The continuous response activity CERA may be observed in all periods but more frequently from the 3rd day with the same mean duration (12.4 +/- 1.85 s for the circular fibers and 21.6 +/- 2.56 s for the longitudinal ones); the predominance of longitudinal activity duration is significative (p = .001). The complex CEC (26-40 c/min) associated with CERA is observed only in 3% of the time recording. Thus after the onset of colonic motility with DERA and CERA in the 3th day, the normalization is obtain the 6th day with the predominant rythm of 1-2 c/min.

[Relationship between taenia coli electric activity and circular fibers. Study of the human transverse colon]. / Relations entre les activités électriques du taenia coli et des fibres circulaires. Etude sur le côlon transverse chez l'homme.

First results of the comparison between the electrical activity of taenia coli and circular muscle are described. Experimental techniques consisted in recording electrical activity for 83 h in 12 patients during the post-operative period after cholecystectomy. Bipolar wire electrodes were surgically inserted in each muscle of the transverse colon's median portion. Statistical treatment leads to the principal conclusion as follows: Whatever type of muscles we have investigated, always could be found slow rhythmic components (called electro-control activity, ECA) in frequency ranges of 1-5 c/min and 9-12 c/min. Major part of taenia coli ECA is in frequency range between 1-5 c/min. ECA in this frequency range can be found in 21% of circular ECA, 23% of taenia coli ECA and 9% of common ECA (% means percents of total recording time). Higher frequencies are found in 7% of circular ECA, 4% of taenia coli ECA and 3% of common ECA. Using long time constant (more than 2 s) the bursts of spikes (10-50 microV) meaning active responses are always accompanied with slower components of important amplitude (greater than or equal to 100 microV): In the discrete mode of activity (DERA) short bursts (during 1-2.5 s) always follow the ECA, whereas in the continuous mode of activity (CERA) mostly longlasting bursts (up to 30 s) could be found. The bursts represent 14% of total time, namely in 8% of longitudinal ECA, 4% of circular ECA and 2% of common ECA. ECA of taenia coli in the case of common ECA is always prolonged. Typical slow waves of greater amplitude (greater than or equal to 500 microV) different from ECA are frequently recorded probably due the intensive contractile process.