Impairment of renal function following liver transplantation.

BACKGROUND: Although renal insufficiency following liver transplantation is not infrequent, only limited reports describe the incidence and progression of the kidney disease. METHODS: This single-centre retrospective analysis after successful liver transplantation between January 1985 and March 2002 defined the baseline serum creatinine at 50 days after liver transplantation to represent the renal function. The primary end-point was an increase of serum creatinine by more than 50% above the baseline. RESULTS: Long-term data were available for 162 patients (84 women, 78 men) who received 167 liver transplants. The median serum creatinine level at 50 days after liver transplantation was 1.0 mg/dL (range 0.5-3.5 mg/dL). The median serum creatinine increased to 1.2 mg/dL (0.4-9.8 mg/dL) at the end of follow-up. Six patients (4%) experienced end-stage renal failure. Forty-one patients (25%) showed a 50% increase in the serum creatinine. Kaplan-Meier analysis revealed that 43% and 48% of patients had a deterioration of renal function at 10 and 15 years after liver transplantation, respectively. Patients at risk showed an increase of serum creatinine by 0.25 mg/dL/y. Only the recipient age was an independent risk factor for deterioration of renal function. CONCLUSIONS: Although there is a high risk for the impairment of renal function after liver transplantation, progression of renal disease is slow and rarely results in end-stage renal failure within 10-15 years. However, patients at risk should be identified early to prevent further decline in renal function.

Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions.

The clinical management of pancreatic disease is often hampered by a lack of tissue diagnosis. Endoscopic pancreatography offers the opportunity to investigate exfoliated cells. However, the significance of mere cytological investigation is compromised by an insufficient sensitivity. The evaluation of the molecular background of carcinogenesis hopefully is capable of providing more sensitive diagnostic markers. The p16INK4a-/retinoblastoma tumour-suppressive pathway has been shown to be involved in the development of near to all pancreatic neoplasms. p14ARF is another tumour suppressor located in the immediate neighbourhood of p16INK4a. Promoter methylation has been demonstrated to be a major inactivating mechanism of both genes. We sought to further evaluate the role of the gene locus INK4a methylation status in the endoscopic differentiation of chronic inflammatory and neoplastic pancreatic disease. Pancreatic fluid specimens of 61 patients with either pancreatic carcinoma (PCA: 39), chronic pancreatitis (CP: 16) or a normal pancreatogram (NAD: 6) were retrieved. In order to detect methylation of either the p14ARF or the p16INK4a promoter a methylation-specific PCR protocol was applied. While 19 out of 39 patients with PCA showed p16 promoter methylation (49%), none of the 16 patients with CP revealed p16 promoter methylation. p14ARF methylation was found in a lower percentage of PCA specimens and in none of the samples of patients with CP. These results suggest a specific significance of INK4a for the development of malignant pancreatic disease. Our data further indicate a potential role for INK4a methylation as a diagnostic marker in the endoscopic differentiation of benign and malignant pancreatic disease.

Parameters predicting response to alpha-interferon treatment in chronic hepatitis C.

BACKGROUND/AIMS: Sustained response to alpha-interferon treatment for chronic hepatitis C is seen in only 25% of cases. Therefore, it is desirable to define pretreatment factors predicting responders. MATERIALS AND METHODS: Forty-nine patients with chronic hepatitis C were treated with a standard alpha-interferon regimen (3 x 3 MU s.c./week). Demographic, biochemical and immunological parameters, and HCV genotypes were obtained prior to initiation of treatment and evaluated for their value in predicting response to alpha-interferon therapy. RESULTS: Response, as defined by normalization of ALT, was 71% during interferon therapy and sustained response after discontinuation of interferon 24.5%. Patients infected with HCV-genotype 1b had significantly more often "community-acquired" disease. Their outcome was worse with a response rate of 44% during therapy and a sustained response of 12.5%, as compared to 87% and 27% respectively in patients infected with genotypes other than 1b. On multivariate analysis, absence of cirrhosis, HCV-genotype other than 1b, higher ALT levels and higher numbers of CD8 positive liver infiltrates were found to be predictors of response during alpha-interferon therapy. CONCLUSION: Response to alpha-interferon therapy seems to be influenced both by viral virulence factors and by the intensity of the host immune response to HCV.

Incidence of local CMV infection and acute intestinal GVHD in marrow transplant recipients with severe diarrhoea.

Intestinal biopsy samples derived from 22 consecutive patients with severe diarrhoea (> 1.5 1/day for 3 or more consecutive days) following allogeneic BMT were analysed for the local presence of cytomegalovirus (CMV) and histological and immunohistological alterations described as typical for acute graft-versus-host disease (GVHD). Seventeen patients showed extensive histopathological lesions typical for acute intestinal GVHD grade > I, 14 marked GVHD-related immunohistological alterations. In intestinal biopsies from 10 of these 22 patients CMV-DNA was detected using PCR- and in situ hybridisation techniques. In 7 of these 10 CMV-DNA positive samples CMV protein expression and in 5 cytomegalic cells were demonstrated. CMV could predominantly be shown in biopsies obtained from the ascending colon and/or the terminal ileum. All 10 patients with local CMV infection showed severe histopathological and immunohistological alterations described as typical for acute intestinal GVHD. Five of seven patients with a CMV-positive intestinal biopsy showed marked improvement of lower gastrointestinal tract disease on antiviral therapy. Five of seven patients lacking local presence of CMV but with severe histopathological lesions responded to therapy with high-dose steroids. Thus, PCR screening for CMV and histopathological analysis may help to treat lower intestinal disease in the marrow transplant recipient early and effectively.

Cytomegalovirus in liver biopsies of marrow transplant recipients: detection methods, clinical, histological and immunohistological features.

In a retrospective analysis liver biopsy specimens obtained from 44 marrow transplant recipients were studied to evaluate the frequency of local presence of human cytomegalovirus (CMV) and graft-versus-host disease (GvHD)-like histological and immunohistological alterations in patients with and without liver dysfunction following bone marrow transplantation (BMT). In 22 of 28 patients with marked liver dysfunction after BMT and histopathological alterations described as typical for acute GvHD CMV could be detected in the liver biopsy specimen. The polymerase chain reaction (PCR) technique revealed the highest sensitivity for CMV detection in liver biopsy samples, but in 20 of 22 PCR-positive specimens CMV infection could be confirmed by at least one additional technique. All the liver biopsies obtained from 16 patients with normal liver function lacking histopathological signs of GvHD were CMV negative. In all 3 patients with CMV-positive liver biopsy started on antiviral therapy liver function improved and no generalized CMV disease occurred. All the 4 patients without local presence of CMV started on severe immunosuppressive therapy showed an improvement of liver dysfunction without occurrence of CMV infection. Local CMV infection of the liver could not be differentiated from hepatic GvHD by clinical and histopathological features, nor by immunohistological analysis of the bile duct epithelium. In contrast, only in liver biopsy with local viral presence could an increase in HLA class II- and ICAM-1 expression be demonstrated on hepatocytes. Thus, especially the high negative predictive value of the PCR technique helps to manage the patient with liver dysfunction after BMT.

[The chemoembolization of hepatocellular carcinoma: the computed tomographic findings and clinical results in prospective repetitive therapy]. / Chemoembolisation des hepatozellulären Karzinoms: computertomographische Befunde und klinische Resultate bei prospektiv repetitiver Therapie.

Between April 1989 and March 1993 162 transarterial chemoembolizations (TACE) were performed repeatedly (mean interval: 2.9 months) in 52 patients with hepatocellular carcinoma (HCC): An emulsion of Lipiodol and epirubicin was injected as selectively as possible in a dosage proportional to liver function and tumour size. Before and after each TACE the size of tumours and ratio of tumour volume containing Lipiodol (RTVCL) were determined in CT and the grade of tumour vascularisation was assessed angiographically. The RTVCL increased from 58% after the first treatment to 73% after the third treatment. RTVCL and Lipiodol retention were higher in responders than in non-responders. Tumours with expansive growth pattern showed a higher response rate (56%) than infiltrating tumours (20%). Mean survival of these patients was different (19 and 8 months; p < 0.01), respectively. Survival rates of all patients were 54, 22, and 11% after 1, 2 and 3 years, respectively. Repeated TACE shows local effectiveness. Three treatments during a period of one year are recommended for patients with Child-Pugh class A cirrhosis.

Endoscopic laser therapy in a case of gastric antral vascular ectasia (watermelon stomach).

We report the case history of a 75-year-old female patient suffering from extensive gastric antral vascular ectasia (watermelon stomach) with portal hypertension in alcoholic liver cirrhosis. Iron deficiency anaemia, due to chronic blood loss from the antral lesions, required repeated transfusions. Conservative treatment failed, but a surgical intervention (antrectomy) was discarded in view of concomitant diseases. Endoscopic laser photocoagulation therapy with a Nd:YAG-laser eradicated the characteristic antral lesions, which was accompanied by a significant reduction of transfusion requirements. No relapse has been observed since then. Endoscopic laser photocoagulation appears to be an efficacious and safe alternative in the treatment of gastric antral vascular ectasia.

Flashlamp exited pulsed dye laser and electrohydraulic lithotripsy: in vitro study on tissue effects.

Intracorporal lithotripsy has gathered momentum in the management of gallstone disease due to the increasing sophistication of technical equipment for the percutaneous, as well as the retrograde-endoscopic route. Laser-induced shock wave lithotripsy (LISL) and electrohydraulic lithotripsy (EHL) have proved feasible by allowing reliable fragmentation of biliary calculi. Evaluation of therapeutic risks, e.g., effects of accidental irradiation of the gallbladder wall, has been performed in small sample sizes only. We investigated the effects of LISL and EHL on multiple sets of human and porcine gallbladders under in vitro conditions. Gallbladders were freshly harvested, mounted, and immersed in different mediums (normal saline, blood, bile). They were swiftly exposed to LISL (Pulsolith¿) and EHL (Lithotron EL 23¿) under differing experimental conditions (energy setting, pulse mode, exposition time, medium, probe pressure) and subjected to standard procedures for morphometric evaluation (Bioquant¿). Tissue effects were described by the depth (d) and width (w) of the cratered lesions, as well as the extension of the damage in the surrounding tissue(s). Serial cuts of the exposed areas yielded 894 section for morphometric analysis. Multivariate analysis of variance (MANOVA) revealed a significant effect of laser energy (p[d] less than 0.002, p[w] < 0.05, p[s] < 0.05), medium (p[d] less than 0.03, p[w] < 0.001, p[s] < 0.04, and exposition time (p[d] less than 0.001, p[s] < 0.001) on the degree of tissue lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

AL amyloidosis mimicking a preferentially autonomic chronic Guillain-Barré syndrome.

We report a case history of a patient whose diagnosis of AL amyloidosis remained elusive until postmortem examination. Exhaustive autonomic neuropathy mimicking a chronic Guillain-Barré syndrome dominated the clinical picture. The problems in establishing the definitive diagnosis of AL amyloidosis even in the face of strong clinical evidence are discussed.

[A fistula between the rectosigmoid junction and the ileum as a complication of highly malignant AIDS-associated lymphoma]. / Fistel zwischen rektosigmoidalem Ubergang und Ileum als Komplikation eines AIDS-assoziierten hochmalignen Lymphoms.

A 29-year-old man, a known heroin addict until 1984 in whom HIV antibodies had been first demonstrated in 1985, was hospitalized because of fever, nocturnal sweating, weight loss and treatment-resistant diarrhoea. An opportunistic infection of the gastrointestinal tract was excluded microbiologically and serologically. Coloscopy and biopsy revealed a highly malignant gastrointestinal B-cell lymphoma, which had caused a spontaneous rectosigmoid-ileum fistula. Lymphoma infiltrations were also found in the duodenum, jejunum, left lung and brain. Because the underlying disease was far progressed (CD4/CD8 ratio: 0.04) and the patient was in a poor general condition neither surgery nor chemotherapy was undertaken. He died of cerebral lymphoma involvement. Gastrointestinal lymphoma should be included in the differential diagnosis of chronic diarrhoea in HIV-positive patients.

Muscle PO2 in the initial phase of increased local oxygen demand (rhythmical muscle contraction) in rats with portacaval shunt (PCA).

The influence of a hyperdynamic syndrome caused by PCA on PO2 distribution in skeletal muscle of rats during the initial phase of muscle activity was examined. Rhythmical muscle contraction of the m. biceps femoris was induced by direct electrical stimulation. Tissue PO2 of the contracting muscle was recorded continuously from the start of the 210 s-long activity period up to 140 s after the last contraction using a multiwire surface electrode. In comparison with controls no different behaviour of mean muscle PO2 in the initial phase of contraction was found. After muscle activity mean PO2 decreased to a lower level in rats with PCA than in controls. This might be a further indication of the disturbing influence of a hyperdynamic syndrome on the regulating mechanisms of the microcirculation.

Circadian course of PO2-oscillations in skeletal muscle of intact and portacaval shunted (PCA) rats.

In rats several circadian rhythms such as heart rate, body temperature, and locomotor activity are known. Several authors found a loss of day-night-rhythm (locomotor activity, EEG) after portacaval shunting (PCA). The aim of this study was to evaluate whether muscle PO2 oscillations are circadian and whether they are altered after time-limited hypercirculation caused by PCA. 126 days after operation tissue PO2 of m. rectus abdominis of 9 rats with PCA and 10 controls was measured with a multi-wire surface electrode. All animals were kept under constant conditions and each animal was measured 6 times at intervals of 4 hours in order to get a circadian PO2 course. In controls the circadian course of mean muscle PO2 resembled a sine oscillation with high values at night and low values in the afternoon. In PCA-rats the time course of mean muscle PO2 showed 3 oscillations with different amplitudes, each with a period length of 24 hours. Our results indicate that oscillations of muscle PO2 are determined principal by circadian locomotor activity and that time-limited hypercirculation influences the circadian course of mean muscle PO2.

Influence of normovolemic hemodilution with 10% HES 200 on tissue PO2 in the M. tibialis ant. of 7 male volunteers.

The aim of the present study was to investigate the effect of normovolemic hemodilution with a middle molecular HES solution on oxygen supply and PO2 pressure distribution in the extremity muscles of healthy male subjects. In addition to a significant reduction of the hematocrit (Hct) by hemodilution from about 44% to about 37% and unchanged arterial blood gas values, an increase of the mean muscle PO2 from about 16 mmHg (before hemodilution) to about 27 mmHg (30 minutes after having reached normovolemia) was observed. The increase of the mean tissue PO2 is demonstrable already 30 minutes after the start of infusion (t = 30) (see Table 2). The markedly raised level of the tissue PO2 in the M. tibialis anterior as compared with the initial value is demonstrable both during and after normovolemic hemodilution. In addition to this dilution-related increase of the mean tissue PO2, a marked change of configuration of the PO2 histograms is found. There is an increase filling of the PO2 classes in the pressure ranges above 40 mmHg. The conspicuous increase of the intra-individual dispersion of PO2 mean values during and after infusion of HES 200 cannot be interpreted for the moment. Similar observations were, for example, reported by Landgraf and Ehrly in 1985 when measuring the muscular tissue oxygen pressure in patients with intermittent claudication before, after and during infusion of 0.9% saline solution. This could be interpreted as an increased perfusion of certain areas of the muscular capillary system.(ABSTRACT TRUNCATED AT 250 WORDS)