Organ specificity of LSP.
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Biomedical subjects
Publications and source records attributed to T Poralla.
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It is widely accepted that glyceryl trinitrate (GTN) effectively dilates the smooth muscles of blood vessels. A similar effect has been postulated on the smooth muscles in the gastrointestinal tract. In this study the motility of the sphincter of Oddi and the common bile duct pressure as determined by endoscopic manometry was investigated in nine patients before and after sublingual application of 1.2 mg GTN (nitro group). Eight untreated patients served as controls. Three minutes after application of GTN the papillary contraction amplitude decreased from 69.3 +/- 4.3 mmHg to 36.8 +/- 5.1 mmHg (p less than 0.005) and the papillary baseline pressure fell from 8.9 +/- 0.6 mmHg to 2.9 +/- 0.2 mmHg (p less than 0.005) respectively. The contraction frequency in the nitro group and all motility parameters in the control group remained unchanged. These results indicate that GTN does not influence the sphincter of Oddi motility, but it relaxes very effectively the sphincter of Oddi muscle. Thus, GTN should be taken into account for the treatment of biliary colic. In our endoscopic unit GTN proved to be useful as premedication for endoscopic examinations, particularly for the removal of small and medium size common bile duct stones through the intact papilla.
A simple and safe procedure providing sensitive and reproducible direct measurement of intravascular oesophageal variceal pressure (IOVP) during routine oesophagoscopy is described. The method requires only commercially available equipment. First results were obtained in 16 patients with oesophageal varices caused by liver cirrhosis (Child's A) can be summarised as follows: intravascular oesophageal variceal pressure was nearly identical in different varices of the single patient. Varices grade III exhibited a significantly higher intravascular oesophageal variceal pressure than varices grade II (22.7 +/- 2.5 vs 15.7 +/- 0.6 mmHg, p less than 0.05). After Valsalva's manoeuvre there was a remarkable increase in intravascular oesophageal variceal pressure by 13.6 +/- 1.0 mmHg irrespective of the variceal size. The high intravascular oesophageal variceal pressure values observed in grade III varices during the rise of the intraabdominal pressure may indicate an important risk factor for variceal haemorrhage. Glyceryltrinitrate (1.2 mg sprayed onto the tongues of 14 patients) very effectively lowered the intravascular oesophageal variceal pressure from 22.8 +/- 2.0 to 12.0 +/- 0.4 mmHg in grade III varices, and from 16.3 +/- 0.4 to 10.0 +/- 0.4 mmHg in grade II varices (p less than 0.005 in both groups). We conclude that this method provides a suitable tool to study the effect of drugs with presumed influence on the oesophageal variceal pressure and that the impressive effect of glyceryltrinitrate in lowering intravascular oesophageal variceal pressure warrants further study on the effect of longer acting nitrates on intravascular oesophageal variceal pressure, and the rebleeding rate after oesophageal variceal haemorrhage.
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Cellular cytotoxicity of peripheral blood lymphocytes against autologous hepatocytes was studied in 9 patients with HBeAg positive and 8 patients with anti-HBe positive chronic hepatitis B. In the HBeAg positive group a greatly increased cytotoxicity of 41 +/- 7% (mean +/- SEM) was found, in contrast the moderately increased cytotoxicity in anti-HBe positive cases of 15 +/- 5% was clearly different (p = 0.005). The different cytotoxicity values could not be explained on the basis of the histological classification, but seemed to correlate at least to some degree to the aminotransferase levels. The cytotoxic activity resided in both T cell and non-T cell enriched lymphocyte compartments. Our findings may provide an explanation for the poor prognosis of HBeAg positive patients with chronic hepatitis B in contrast to their anti-HBe positive counterparts.
Using ERC-manometry diameters of the common bile duct (CBD) the common hepatic duct (CHD) as well as CBD pressure before and after opacification were determined in 35 non-cholecystectomized patients without extrahepatic cholestasis. We found a significant rise of both CBD and CHD diameters as well as CBD pressure recorded before the injection of contrast medium with increasing age. (p less than 0.005, less than 0.001 and less than 0.05 respectively). Following the opacification CBD pressure became elevated. Again this increase tended to be more pronounced in older patients although this association was lacking statistical significance. In the presence of comparable age female patients (n = 16) exhibited higher CBD and CHD diameters (n.s.) as well as CBD pressure values (p less than 0.05) than male patients (n = 19). We conclude that in the absence of extrahepatic cholestasis bile duct diameter as well as bile duct pressure rise significantly with increasing age. Furthermore women tend to have higher diameters and pressure values than men.
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A 43-year-old woman with a solitary renal cyst developed polycythaemia. 21 well documented cases of this type have been previously published. In the majority of them a causal connection could be assumed between the renal cyst and polycythaemia: in 13 of the 15 cases (as in the reported one), the polycythaemia disappeared after surgical removal of the cyst. Measurement of serum erythropoietin can help in the differential diagnosis, but exclusion of polycythaemia vera may be difficult in the individual case.
Neurologic manifestations were the sole symptoms of disease in three patients with systemic lupus erythematodes (SLE): one case presented with Brown-Séquard's syndrome, a second with spinal ataxia and polyneuropathy, and a third with polyneuropathy. In all three patients there was a considerable delay in making the diagnosis after onset of neurological symptoms. The diagnosis was established either by demonstration of antinuclear antibodies in combination with antibodies against dsDNA or by the demonstration of antibodies against dsDNA alone. In two patients perivascular deposits of IgG and C3 were seen in skin-muscle biopsies from the calf region.
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We generated monoclonal antibodies after immunization of mice with rabbit liver-specific protein (LSP) preparations. One of these antibodies (2D3) showed an organ-specific and species-specific binding pattern as determined by immunohistological and ELISA techniques. Immunoelectron microscopy studies demonstrated that this antibody is bound exclusively to the liver cell membrane except in the region of the bile canaliculi. We further describe a simple ELISA technique for the detection of anti-LSP antibodies. Our study clearly demonstrates the presence of at least 1 organ-specific liver cell membrane antigen in rabbit LSP and shows antigenic differences between areas of the plasma membrane of hepatocytes.
We tested lymphocyte cytotoxicity against autologous hepatocytes in patients with alcoholic liver disease (ALD). The following cytotoxicity values were found (mean +/- SEM): alcohol-induced steatosis with or without fibrosis 16.5 +/- 2% (n = 29), alcoholic cirrhosis 28 +/- 4% (n = 13), controls with normal liver histology or minimal changes 6 +/- 2% (n = 11). The differences were statistically significant (both forms of ALD versus controls p less than 0.005). T-cell as well as non-T-cell-enriched lymphocyte fractions showed increased cytotoxicity in ALD. We did not observe a correlation between cellular cytotoxicity and the degree of biochemical or histological alterations within the groups tested. Thus, our study demonstrating enhanced cellular cytotoxicity against autologous hepatocytes in ALD further supports the hypothesis that cellular immune reactions are involved in the pathogenesis of ALD, especially of alcoholic cirrhosis.
In a microcytotoxicity assay we tested lymphocyte cytotoxicity against autologous hepatocytes. The following cytotoxicity values were found (given mean +/- SEM): acute non-A, non-B (NANB) hepatitis 45.7 +/- 4.3% (n = 7), chronic NANB hepatitis 32.8 +/- 5.1% (n = 11), chronic active hepatitis B (CAH-B) 27.7 +/- 6.7% (n = 10), toxic lesions 18.1 +/- 4.2% (n = 18), controls with normal liver histology or minimal changes 4.9 +/- 2.5% (n = 8). Thus our study shows enhanced cellular cytotoxicity in acute and chronic NANB hepatitis and indicates that T cells as well as non-T cells have cytotoxic effector functions. These findings are similar to those obtained in CAH-B and suggest that cellular immune reactions play an important role in the course of NANB hepatitis. For comparison we tested cytotoxic reactions in toxic lesions. They were only moderate and well distinguishable from those observed in NANB hepatitis and CAH-B; they even may be unspecific. No correlation was seen between cytotoxicity and aminotransferase concentrations.
In 57 patients undergoing endoscopic retrograde cholangiography (ERC) the magnification of the endoscope was determined by measurement of its diameter depicted on the X-rays. A magnification of 30.2 +/- 10.6% (mean +/- SD) ranging from 8 to 58% in individual patients was recorded. The clinical reliability of the method was confirmed by comparing the diameters of 13 bile duct stones assessed in-situ and after removal respectively. Although the magnification tended to be higher in obese patients, no correlation between body weight and the degree of the magnification could be established. Our data add further doubt to the reliability of the radiologic bile duct measurement if not referred to a reliable standard which can be easily provided by the endoscope. This is particularly important whenever therapeutic interventions are planned which critically depend on exact determination of diameters, like bile duct stone removal with or without endoscopic papillotomy, lithotripsy or introduction of transpapillary enthoprothesis.
We studied the frequency and composition of circulating immune complexes (CIC) in patients with chronic persistent non-A, non-B (NANB) hepatitis and in convalescent persons after an apparently normal recovery from acute NANB hepatitis. 10 of 16 patients with chronic NANB hepatitis and 5 of 11 convalescent persons after acute NANB hepatitis had CIC as detected by the Raji cell technique. CIC in chronic NANB hepatitis were composed of IgG, C3, and in 7 of 10 cases also IgM, while in CIC from convalescent persons IgG and C3 were present, too, but IgM was detected in only 1 case. Viral antigens within the CIC were not detectable in any case while 14 of 16 chronic NANB hepatitis patients were found to have free virus-associated antigen in serum.
spontaneous (SCMC) and antibody-dependent (ADCC) cellular cytotoxicity was studied in patients with aucte viral hepatitis B and chronic active hepatitis (CAH) B and non-A, non-B. Chang cells displaying the liver-specific protein LSP on the plasma membrane were used as target cells. SCMC and ADCC in acute hepatitis B were not different from normal controls. SCMC and ADCC in chronic active hepatitis B as well as in non-A, non-B were significantly elevated in comparison to normal controls. In additional experiments, the influence of patients sera on SCMC and ADCC was studied. Autologous serum from CAH patients significantly reduced cytotoxicity in SCMC and ADCC assays. This inhibitory capacity of patients sera was attributable to immune complexes, as ultracentrifugation studies and determination of immune complexes of fractionated sera demonstrated.
Despite recent improvements of hemodialysis (HD) techniques, symptoms due to secondary hyperparathyroidism (HPT) contribute to longtime complications of HD patients. The aim of the present retrospective study was to determine the incidence and localization of radiological joint and bone lesions in 175 patients on chronic HD. In 108 patients the diagnosis of HPT was made by radiologic criteria. 56% had radiomorphologic lesions of the hands, 45% of the acromio-clavicular (AC) joint, 31% of the shoulder, and 27% of the pelvis. No sex difference was found for prevalence of HPT in these patients, nor was one found for any of the underlying renal diseases. There was a negative correlation between elevated serum parathyroid hormone and serum aluminum concentrations. In 111 patients the history of bone and joint pain was evaluated. 54% of these patients suffered from bone pain, arthralgia, and morning stiffness. Radiological lesions of AC-joint correlated with shoulder pain in 38%. Our data show that even in the predialytic phase of renal insufficiency x-rays of the shoulder are helpful in early diagnosis of HPT. Skeletal manifestations specific for one of the underlying renal diseases do not exist. Elevated PTH levels are a good indicator of HPT in these patients, whereas low levels of PTH do not exclude radiological manifestations. In contrast to beta 2-microglobulin amyloidosis, pain does not occur during rest and is not worsened during HD. Treatment with non-steroidal antiinflammatory drugs led to pain relief in the majority of patients. Pain history in patients on chronic HD provides important information concerning the differential diagnosis of HPT/beta 2-microglobulin amyloidosis.
beta 2-microglobulin amyloidosis is a major complication in chronic hemodialysis patients. Destructive arthropathy, spondylarthropathy, and carpal tunnel syndrome are clinical manifestations of beta 2M amyloid depositions within the joints, intervertebral discs, and tendon sheets. We have investigated the prevalence of beta 2M amyloidosis associated radiological joint lesions in a population of 175 patients on chronic hemodialysis. In 32 of 175 patients the diagnosis of amyloidosis arthropathy and spondylarthropathy was made by radiomorphological criteria. These 32 patients were asked about rheumatic symptoms (localisation and character of pain, synovitis, carpal tunnel syndrome, influence of dialysis membrane on pain) and examined clinically. Bilateral pain of the shoulders or wrists was complained by most of the patients. 24 of the 32 patients had signs of secondary hyperparathyroidism besides beta 2M-amyloidosis. 29 patients had a carpal tunnel syndrome, 23 of whom had to be operated. beta 2M-amyloid was histochemically demonstrated in all of these 23 cases. Renal transplantation led to immediate pain relief in 3 out of 3 patients, a change of the dialysis membrane (high-flux membrane) improved chronic pain in the majority of patients.