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Biomedical subjects

P Knoflach

Publications and source records attributed to P Knoflach.

At least 19 recordsLinked to original sources
PubMed1992

[Malignant lymphomatous polyposis of the gastrointestinal tract].

Two years after endoscopic excision of several polyps of the colon (histological examination revealing infiltration by a malignant non-Hodgkin lymphoma) a 67-year-old man was again found to have blood and mucus in his stool. Because local recurrence was suspected a coloscopy was performed. This revealed multiple polyps throughout the entire colon, predominantly in the sigmoid and rectum. Biopsy showed focal infiltration of the submucosa and mucosa with centrocytic non-Hodgkin lymphoma, compatible with the diagnosis of malignant lymphomatous polyposis of the gastrointestinal tract. Gastroduodenoscopy then demonstrated duodenal polyps and massive coarsening of the gastric folds due to infiltration. For the first time tumour masses were also found in the epipharynx. After 6 chemotherapy cycles according to the CHOP scheme (day 1: cyclophosphamide, 1500 mg, adriblastin, 100 mg and vincristine, 2 mg; days 1-5: prednisolone, 100 mg) all lymphoma infiltrates regressed completely. The patient has been symptom-free for 9 months.

Aged↗
PubMed1992

[Long-term follow-up of Crohn disease].

184 patients diagnosed with Crohn's disease were observed for an average of 5 years and evaluated for clinical pattern and course of disease. The male/female ratio was almost equal (90 m. vs. 94 f.). The peak of disease manifestation was between years 18-32. Familial clustering of inflammatory bowel disease was observed in 2.2%. The pattern of anatomic involvement was ileocolic in 53%, colon in 24%, small bowel in 20% and other locations in 3%. 34% of patients were afflicted with at least one extraintestinal manifestation, 34% developed fistulae. Fistula formation was seen more often in colon involvement than small bowel involvement (69% vs. 32%). 48% of the patients were operated at least once. 3 patients died during the observation period, 2 of them with sepsis. Evolution of carcinoma was not observed. Some of our results are in accordance with the literature, some distinct observations (e.g. low familial clustering) underline the theory of a multifactorial pathogenesis in Crohn's disease.

Abscess↗
PubMed1991

Constrictive pericarditis without typical haemodynamic changes as a cause of oedema formation due to protein-losing enteropathy.

A 41-year-old man presented with physical signs of leg oedema and a laboratory value of decreased serum albumin of 2.4 g.dl-1. Loss of protein via the gastrointestinal tract was demonstrated by an increased faecal excretion of 51-chromium-labelled-albumin and by elevated stool clearance of alpha 1-antitrypsin. No anatomical lesions or intestinal disease were found to explain this protein loss. Constrictive pericarditis was suspected as the cause of protein-losing enteropathy but could not be confirmed by right heart catheterization, in which normal filling pressures and no sign of 'dip and plateau' pressure pattern were found. However, magnetic resonance imaging clearly demonstrated a thickening of the pericardium over the right heart and a tubular-shaped right ventricle as signs of constrictive pericarditis. Peripheral oedema disappeared and serum protein concentration returned to normal after pericardectomy. This demonstrates that moderate pericardial constriction not resulting in discernible pressure abnormalities in the right heart can be associated with protein-losing enteropathy and thus result in hypoproteinaemic peripheral oedema. In this condition a morphological investigation by magnetic resonance imaging is of importance in order not to miss the diagnosis of a potentially treatable disease.

Adult↗
PubMed1991

Comparison of functional and structural brain disturbances in Wilson's disease.

We assessed the functional and structural brain disturbances in Wilson's disease (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI). All the 25 neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or brain atrophy. Our findings indicate that EPs and MRI are sensitive techniques for the evaluation of brain involvement in WD.

Adult↗
PubMed1991

Increased serum osteocalcin levels in patients with lactase deficiency.

Serum levels of osteocalcin, a noncollagenous bone matrix protein, have been found to be a specific biochemical parameter of bone formation. In the literature in subjects with osteoporosis, an increased incidence of lactase deficiency has been described. We therefore determined the serum levels of osteocalcin in 10 patients with lactase deficiency and in 20 control subjects by radioimmunoassay. The patients with lactase deficiency were dietary treated and had a very low daily calcium intake. Serum osteocalcin levels were significantly higher in the patients with lactase deficiency than in the control subjects. In contrast, serum levels of parathyroid hormone, alkaline phosphatase, calcium, and phosphorus were not statistically different in the two groups. Our data suggest an increased rate of bone turnover in patients with lactase deficiency on a low calcium diet; possibly calcium supplementation is indicated in dietary-treated patients with lactase deficiency.

Adult↗
PubMed1990

T-cell activation in Crohn's disease. Increased levels of soluble interleukin-2 receptor in serum and in supernatants of stimulated peripheral blood mononuclear cells.

Serum levels of soluble interleukin-2 receptor were determined in 29 patients with active and quiescent Crohn's disease. In addition, the ability of peripheral blood mononuclear cells of 23 of these patients to generate soluble interleukin-2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin-2 receptor concentrations of patients with active Crohn's disease (n = 19) were significantly elevated (757 +/- 438 U/ml) compared with levels in patients with inactive disease (n = 10; 412 +/- 120 U/ml) and healthy control individuals (n = 40; 375 +/- 102 U/ml; p less than 0.003 and p less than 0.0005, respectively). Serial determinations of serum soluble interleukin-2 receptor concentration in a follow-up of 11 hospitalized patients treated for highly active disease showed a decrease from 1252 +/- 494 U/ml to 527 +/- 193 U/ml (p less than 0.004) that corresponded to clinical improvement, as assessed by Crohn's disease activity index and a reduction of inflammatory parameters. In vitro phytohemagglutinin stimulation of peripheral blood mononuclear cells derived from patients with Crohn's disease resulted in elevated soluble interleukin-2 receptor production not only in patients with active disease (3987 +/- 2439 U/ml), but also in patients with inactive disease (3297 +/- 2282 U/ml), compared with the amount of soluble interleukin-2 receptor produced by mononuclear cells of healthy individuals (1523 +/- 1152 U/ml; p less than 0.005 and p less than 0.02, respectively). In addition, cultivation of mononuclear cells without mitogen resulted in higher soluble interleukin-2 receptor production in patients with active disease than in patients with inactive disease (p less than 0.02). However, patients suffering from active ulcerative colitis also had significantly increased serum levels of soluble interleukin-2 receptor (1080 +/- 400 U/ml) compared with the levels in patients with chronic disease (455 +/- 140 U/ml; p less than 0.0025). In addition, peripheral blood mononuclear cells derived from patients with ulcerative colitis produced significantly more soluble interleukin-2 receptor upon mitogenic stimulation with phytohemagglutinin (2314 +/- 936 U/ml), than cells from healthy controls (1523 +/- 1152 U/ml; p less than 0.05). The finding of elevated soluble interleukin-2 receptor serum levels in patients with active Crohn's disease and its increased production by mononuclear cells of patients with both active and inactive disease is a further example of an alteration of the immune system in this condition; however, this alteration can also be found in other inflammatory bowel diseases.

Adult↗
PubMed1989

Soluble interleukin 2 receptor in acute viral hepatitis and chronic liver disease.

Serum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 +/- 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 +/- 102 units per ml; p less than 0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 +/- 507 units per ml), primary biliary cirrhosis (619 +/- 190 units per ml) or chronic active HBsAg+ hepatitis (941 +/- 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p less than 0.0005 vs. controls, respectively). In vitro mitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2--thus making it a potential immunoregulatory molecule--its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver disease.

Acute Disease↗
PubMed1989

Alpha-fetoprotein-positive adenocarcinoma of the pancreas.

A case of a poorly differentiated ductal adenocarcinoma arising in the body and tail of the pancreas with diffuse intraabdominal metastases in an adult is reported. Serum alpha-fetoprotein (AFP) level was markedly elevated in this patient, but fell transiently when a partial tumor response to combination chemotherapy was achieved. Both the occurrence of biochemical and anatomical responses, and the immunohistochemical finding of AFP in the tumor tissue clearly indicate that oncofetal protein is produced by the tumor cells. The patient survived 10.5 mo after the onset of symptoms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Local texture analysis: an approach to differentiating liver tissue objectively.

The usefulness of local textural analysis in identifying diseases of the liver has been evaluated. In comparing two areas texturally, a random distribution of one or several textural parameters indicates identical tissue, whereas a distinct clustering can be used to discriminate between different tissues. Using this procedure, various diseases of the liver were differentiated accurately whereas different images of the same state of the liver were classified as similar with high accuracy. The consistent results with different patients, sections, sample locations and scanner parameter settings demonstrate that these factors have no impact on the characteristics of the resulting pattern used for discrimination and therefore for the final diagnosis. The overall diagnostic accuracy of this method seems better than conventional sonographic evaluation of parenchymal liver disease and at least competitive with other computerized methods described. The most important result clinically seems to be the high accuracy in differentiating between hepatitis and normal liver, which cannot be achieved by conventional ultrasonography.

Adult↗
PubMed1988

Spontaneous and interferon-induced natural cytotoxicity in Crohn's disease.

Natural killer cell (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) exerted by peripheral blood mononuclear cells (PMNC) were investigated in 53 patients with Crohn's disease (CD). NK activity and ADCC were found to be significantly reduced in patients with CD (p less than 0.0005) as compared to healthy controls. Both effector cell functions increased after in vitro treatment of PMNC with gamma-interferon, but did not reach the levels found in controls (p less than 0.0005). Neither NK activity nor ADCC was significantly influenced by therapy with corticosteroids. Moreover, the reduced serum zinc levels in patients with CD, which have been shown to be associated with impaired immune function, did not influence the lytic effector cell mechanism assayed either. Finally, no association could be found between NK cell activity or ADCC and CD activity index, the extent of the disease and several laboratory parameters of inflammation. We conclude that patients with CD have a reduced lytic effector cell function which remains uninfluenced by corticosteroid treatment and seems to be present independently of disease activity.

Adolescent↗
PubMed1988

Phenotypic and functional analysis of cellular cytotoxicity after splenectomy.

Phenotypic and functional aspects of cellular cytotoxicity were investigated in patients after splenectomy. While assays testing for natural killer cell (NK) activity and antibody-dependent cellular cytotoxicity showed a significantly reduced (p less than 0.005 and p less than 0.025, respectively) activity of the relevant cell populations, lectin-dependent cellular cytotoxicity was either normal or, in one dilution of phytohemagglutinin, even significantly increased (p less than 0.025), as compared to healthy control persons. In a search for a possible explanation for this phenomenon, it was found that the total lymphocyte count was significantly increased (p less than 0.01) in patients after splenectomy, when compared with healthy control individuals. However, neither the absolute cell count nor the percentage of Leu7+ lymphocytes showed significant differences between splenectomized patients and controls. In contrast, the percentages of (Leu7+Leu2)+, OKT11+, OKT4+ and Leu2a+ lymphocytes were significantly decreased (p less than 0.0025, p less than 0.01 and p less than 0.005, respectively) in splenectomized patients with not only the percentage, but also the absolute number of DR+ lymphocytes being significantly increased (p less than 0.005 and p less than 0.05, respectively). We thus conclude that in patients after splenectomy NK activity is decreased which may possibly be due to the lack of a NK subset. In contrast, the overall percentages of T cells (OKT11+), T helper/inducer (OKT4+) and T suppressor cells (Leu2a+) were significantly decreased in patients after splenectomy, although this defect could be compensated by a significant increase in the absolute lymphocyte number.

Adult↗
PubMed1988

[Chemotherapy of advanced pancreatic cancer with 5-fluorouracil, doxorubicin and high-dose methotrexate].

The aim of the present phase II clinical trial was to investigate the therapeutic efficacy and tolerance of a combination chemotherapeutic protocol consisting of 4-weekly intervals of 5-fluorouracil, doxorubicin and high-dose methotrexate (FAMeth-regimen) in patients with advanced measurable pancreatic cancer. After a median treatment duration of 4 (2-12) months, one complete and one partial response were achieved in the 13 evaluable patients. Two additional patients had evidence of objective tumour regression, although response was less than 50% of pretreatment tumor measurements. Stable disease was noted in 3 patients, and the tumour progressed in 6. The median survival of all evaluable patients from start of therapy is 7 (2-17) months. Side-effects associated with FAMeth-chemotherapy were generally mild and reversible and primarily included gastrointestinal symptoms (38%) and leukopenia (62%). There was 1 treatment related death due to pancytopenia and sepsis. Our preliminary data suggest some antitumour activity of the regimen against pancreatic cancer, although final assessment of therapeutic results must await accrural of additional patients.

Adult↗
PubMed1987

Serum antibodies to cow's milk proteins in ulcerative colitis and Crohn's disease.

Serum antibodies of immunoglobulin G, immunoglobulin M, and immunoglobulin A isotypes to five major proteins of cow's milk, casein, bovine serum albumin, alpha-lactalbumin, beta-lactoglobulin A, and beta-lactoglobulin B, were measured using enzyme-linked immunosorbent assay in 51 patients with ulcerative colitis, 49 with Crohn's disease, and 20 age-matched controls. Immunoglobulin G and immunoglobulin M antibodies to cow's milk proteins were significantly elevated in patients with inflammatory bowel disease as compared to controls. In contrast, no significant increase in immunoglobulin A antibodies to 3 of 5 proteins was noted. The increased titers of antibodies to milk proteins seem to be specific and not due to a polyclonal immunoglobulin activation, as naturally occurring blood group antibodies were not elevated in patients with ulcerative colitis and Crohn's disease. A good correlation of disease activity, as measured by serum alpha 1-acid glycoprotein concentrations, and immunoglobulin G and immunoglobulin A antibody titers against certain cow's milk proteins could be demonstrated in Crohn's disease, but not ulcerative colitis. These findings suggest that production of antibodies to cow's milk proteins reflects specific immunization with these antigens. The study of antibody isotypes and correlation with disease activity may provide better insight into the immune response to dietary antigens and its possible role in the pathogenesis of inflammatory bowel diseases.

Adult↗
PubMed1987

[Mercuric chloride-induced enteropathy in the rat: a model of gastrointestinal disease with immunologic pathogenesis].

Protein-loss into the gastrointestinal tract is a feature of many different diseases, a number of which are immunologically mediated, e.g. systemic lupus erythematosus or Crohn's disease. The pathogenic mechanism of protein-losing enteropathy in diseases without obvious enterocyte injury are unknown. Brown-Norway-rats (BN-rats) were gavaged with low doses of HgCl2 for 39 weeks. Within 2 weeks, the intestines showed strong linear staining for IgG and IgA along vascular and intestinal basement membranes. Granular deposits containing IgG and C3 were present along intestinal basement membrane only in the late stages of the experiment; only in these animals increased intestinal protein loss as measured by fecal Cr-51 excretion was found. These findings suggest that immune complex deposition along the intestinal basement membrane can lead to protein-losing enteropathy. This disease may be used as a model for the study of immunologically mediated intestinal disease.

Animals↗
PubMed1986

[Etiology and pathogenesis of Crohn disease and ulcerative colitis].

The aetiology and pathogenesis of Crohn's disease and ulcerative colitis have not yet been clarified. None of the many investigations on the involvement of genetic, microbial, psychological, immunological and environmental factors have been able to identify a single aetiological agent. Nevertheless, all of these factors could play a role in a multifactorial model of the aetiology and pathogenesis of inflammatory bowel disease.

Autoimmune Diseases↗
PubMed1986

Lack of circulating immune complexes in inflammatory bowel disease.

Multi-organ involvement and especially extraintestinal manifestations have suggested an immune complex-mediated pathogenesis of ulcerative colitis and Crohn's disease. Using various techniques controversial data have been reported on the incidence and levels of circulating immune complexes and their correlation to clinical presentation. Sera of 131 patients with inflammatory bowel disease (78 Crohn's disease, 53 ulcerative colitis) representing a wide spectrum of disease activity, treatment and presence or absence of extraintestinal manifestations were tested for circulating immune complexes using Raji cell indirect immunofluorescence assay, Raji cell radioimmunoassay, C1q solid phase assay and polyethylene glycol precipitation coupled with measurements of optical density and subsequent immunoelectrophoresis or radial immunodiffusion. Circulating immune complexes in low concentrations were observed in a small number of patients with inflammatory bowel disease, the frequency and concentrations being slightly higher in patients with Crohn's disease than in those with ulcerative colitis. No association of concentrations of circulating immune complexes with disease activity or presence of extraintestinal manifestations could be demonstrated. These data do not support the claim for a major role of circulating immune complexes in the pathogenesis of inflammatory bowel disease.

Adolescent↗