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Biomedical subjects

B Kreft

Publications and source records attributed to B Kreft.

At least 55 records · Page 3Linked to original sources

[Sensorimotor polyneuropathy and systemic amyloidosis as paraneoplastic symptoms of a carcinoid-like well differentiated carcinoma of the breast].

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman was admitted because of weakness and paraesthesias in both legs. 15 years earlier a chest radiogram had shown numerous round foci of uncertain cause. Physical examination confirmed muscular weakness in all limbs, especially the legs, as well as abnormal superficial and deep sensory perception. INVESTIGATIONS: Electromyography registered a patchy pattern of intentional muscular activity and marked denervation activity but largely normal nerve conduction. There was no evidence of inflammatory disease in the laboratory tests, including the CNS. DIAGNOSIS, COURSE AND TREATMENT: The neurological findings indicated progressive axonal sensorimotor polyneuropathy. A paraneoplastic cause was suspected, but search for a primary tumour was unsuccessful. The patient developed a urinary infection from which she died in septic shock. A carcinoid-like well-differentiated carcinoma of the breast with hematogenous metastases to liver, spleen and lung was discovered at autopsy. It also revealed severe systemic AA-type amyloidosis, involving liver, spleen heart and kidneys. In addition there was a severe progressive axonal neuropathy and marked neurogenic atrophy of the peripheral skeletal musculature. No amyloid deposition was seen. CONCLUSION: In case of amyloidosis and polyneuropathy of uncertain cause a paraneoplastic pathogenesis should be considered in the differential diagnosis, even in the absence of proven malignancy.

Aged↗

p53 mutagenesis in Klatskin tumors.

Mutagenesis of the p53 tumor-suppressor gene represents the most common genetic alteration in human malignancies but has not yet been investigated in Klatskin tumors. Cancerous and normal liver tissues were obtained from 12 patients after surgical resection of Klatsin tumors. Genomic DNA was extracted and served as a template for PCR amplification and sequencing of a 1,574-bp fragment of the p53 gene comprising the exons 5 through 8. Immunohistochemical expression analysis was performed using five different antibodies. Missense mutations were detected in 2 of 12 patients--one transversion on codon 273 (Arg --> Leu) and a transition on codon 168 (His --> Arg). In all specimens, immunohistochemistry was negative regarding a nuclear overexpression. An apparent clinicopathologic impact of p53 mutations was not observed. This report on mutagenesis of the p53 gene in Klatskin tumors shows that the most commonly mutated tumor suppressor gene in human cancers is also mutated in a subset of patients with Klatskin tumors. Assessment of a clinical or pathological impact of p53 mutagenesis on Klatskin tumors requires evaluation in larger studies.

Adult↗

[MRI, CT and CT arterial portography in the diagnosis of malignant liver tumors in liver cirrhosis].

PURPOSE: To determine the value of magnetic resonance imaging (MRI), computed tomography (CT) and CT arterial portography (CTAP) in detecting malignant liver lesions in cirrhosis patients. MATERIALS AND METHODS: The radiological examinations (CT, MRI and CTAP) of 47 patients suffering from cirrhosis having undergone an orthotopic liver transplantation (OLTX) were analysed retrospectively. The number of detected liver lesions was compared with the results of the histopathological findings after OLTX. RESULTS: 13/21, 11/18 and 7/12 of the malignant lesions were detected by MRI, CT and CTAP respectively. In MRI one false positive case was shown, two in CT and three in CTAP. Almost the same lesions were identified by all three procedures. The examination of the liver with MRI and CT and CTAP did not bring additional information. Most of the lesions that were missed were less than 2 cm in diameter. CONCLUSIONS: The rate of detection of HCC in patients with cirrhosis was about 60%. MRI and CT yielded similar results.

Adult↗

Adherence of Staphylococcus aureus isolated in peritoneal dialysis-related exit-site infections to HEp-2 cells and silicone peritoneal catheter materials.

BACKGROUND: Peritoneal catheter exit-site infections cause a relevant morbidity in peritoneal dialysis patients and are frequently caused by Staphylococcus aureus. We tested the hypothesis that adherence of exit-site-derived S. aureus to epithelial cells and peritoneal catheter silicone tubes discriminates virulent and less virulent strains. METHODS: The binding of isolated S. aureus to an epithelial cell line (HEp-2) and to silicone tubes was analyzed using light-microscopy or radioactive labeling of bacteria. RESULTS: Of 378 exit-site swabs, 99 (26%) were positive for microbial growth. S. aureus was cultured in 25 of 99 positive swabs; three of 13 swabs taken in exit-site infections grade 3 and 4 that had tested positive for S. aureus. Adherence of S. aureus from exit-site infections grade 2, 3 and 4 to Hep-2 cells did not differ from adherence of bacteria isolated from asymptomatic or moderately inflamed catheter exit sites (grade 0-2). However, binding of S. aureus to silicone tubes was enhanced in grade 0/1 compared with grade 2-4 exit-site isolates. CONCLUSIONS: Staphylococcus aureus is an important pathogen in CAPD-related exit-site infection being isolated in about 6.6% of all exit-site swabs (and in 25% of all positive swabs). Silicone-adhesive strains may be of more clinical significance in peritoneal dialysis patients since adhesion to silicone was increased in S. aureus strains isolated in more severe exit-site infections.

Bacterial Adhesion↗

Diagnostic value of a superparamagnetic iron oxide in MR imaging of chronic liver disease in an animal model.

OBJECTIVE: The enhancement characteristics and the diagnostic value of a cell-specific superparamagnetic contrast agent (NSR 0430) in different degrees of liver fibrosis and cirrhosis were experimentally studied in an animal model. MATERIALS AND METHODS: Chronic liver damage was induced in rats either by oral administration of carbon tetrachloride (CCl4) for 15 weeks (n = 37) or by oral administration of thioacetamide (TAA) in drinking water for 24-26 weeks (n = 48). Twenty-six animals served as control subjects. T1 and T2 relaxation times for the liver and the spleen were measured in vitro with a spectrometer at 40 MHz. In vivo MR imaging at 1.5 T also was performed using T2-weighted turbo spin-echo sequences before and 1 hr after administration of NSR 0430. All data were correlated with the histologic degree of liver fibrosis and cirrhosis and the amount of connective tissue in the liver, which was measured morphometrically. RESULT: CCl4 produced liver fibrosis in most of the animals, and TAA predominantly caused liver cirrhosis. NSR 0430 caused a T2 relaxation time decrease in the control animals by 49%; in the CCl4 group with light and moderate liver fibrosis, by 25%; in the CCl4 group with severe liver fibrosis or cirrhosis, by 16%; and in the TAA group with cirrhosis, by 30%. On the T2-weighted turbo spin-echo sequences, liver signal-to-noise ratios (SNRs) decreased after contrast agent administration in the control animals by 81% and 79%, depending on the TE parameter. In the CCl4 group, liver SNRs decreased by 96% and 61% in animals with light or moderate fibrosis and by 44% and 55% in animals with severe fibrosis or cirrhosis, depending on the TE parameter. In the TAA group, liver SNR decreased by 61% and 67%, depending on the TE parameter. CONCLUSION: Enhancement of the superparamagnetic contrast agent NSR 0430 is decreased in the presence of liver fibrosis and cirrhosis in an animal model. However, the reduced enhancement is not directly related to the degree of chronic liver damage, which limits the diagnostic value of superparamagnetic contrast agents in the assessment of chronic liver disease.

Animals↗

[Symptomatic heterotopic splenic tissue in the adrenal gland area].

We report on a 33-year-old man with symptomatic heterotopic suprarenal splenic tissue. Heterotopic splenic tissue can often be found after posttraumatic splenectomy. It is a result of autotransplantation induced by trauma (splenosis). Additionally it can grow during embryogenic development. Such an accessory spleen is found in 10-44% of all autopsies. In this case report the patient was treated by resection due to increasing flank pain and suspected neoplasm.

Adrenal Gland Diseases↗

[Primary non-Hodgkin lymphoma of the ovary].

A young female patient was admitted for clarification of a space-occupying ovarian situation. Histological analysis gave the finding of a highly malignant NHL of the Burkitt type. In the further course of the disease bicytopenia developed. Bone mark analysis revealed a B-AII. FAB L3 which can be considered as the leukemic equivalent of the Burkitt lymphoma. In spite of chemotherapy the patient died as a consequence of a sepsis.

Adolescent↗

LI-cadherin-mediated cell-cell adhesion does not require cytoplasmic interactions.

The adhesive function of classical cadherins depends on the association with cytoplasmic proteins, termed catenins, which serve as a link between cadherins and the actin cytoskeleton. LI-cadherin, a structurally different member of the cadherin family, mediates Ca2+-dependent cell-cell adhesion, although its markedly short cytoplasmic domain exhibits no homology to this highly conserved region of classical cadherins. We now examined whether the adhesive function of LI-cadherin depends on the interaction with catenins, the actin cytoskeleton or other cytoplasmic components. In contrast to classical cadherins, LI-cadherin, when expressed in mouse L cells, was neither associated with catenins nor did it induce an upregulation of beta-catenin. Consistent with these findings, LI-cadherin was not resistant to detergent extraction and did not induce a reorganization of the actin cytoskeleton. However, LI-cadherin was still able to mediate Ca2+-dependent cell-cell adhesion. To analyze whether this function requires any interaction with proteins other than catenins, a glycosyl phosphatidylinositol-anchored form of LI-cadherin (LI-cadherin(GPI)) was constructed and expressed in Drosophila S2 cells. The mutant protein was able to induce Ca2+-dependent, homophilic cell-cell adhesion, and its adhesive properties were indistinguishable from those of wild type LI-cadherin. These findings indicate that the adhesive function of LI-cadherin is independent of any interaction with cytoplasmic components, and consequently should not be sensitive to regulatory mechanisms affecting the binding of classical cadherins to catenins and to the cytoskeleton. Thus, we postulate that the adhesive function of LI-cadherin is complementary to that of coexpressed classical cadherins ensuring cell-cell contacts even under conditions that downregulate the function of classical cadherins.

Actins↗

Effect of cytochrome P450 induction on phosphorus metabolites and proton relaxation times measured by in vivo 31P-magnetic resonance spectroscopy and 1H-magnetic resonance relaxometry in human liver.

Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by 31P magnetic resonance (MR) spectroscopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic studies in humans are lacking. Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented induction of oxidative metabolism as measured by an increase in urinary 6-beta-hydroxycortisol output in all volunteers (P = .0004). 31P-MR spectroscopy and 1H-MR relaxometry were performed before and after hepatic P450 induction. As shown by 31P-MR spectroscopy, the median phosphomonoester concentration (PME) relative to nucleoside triphosphate (NTP) increased by 21% from 0.63 (range, 0.40-0.89) before induction to 0.76 (0.49-1.67) after induction (P = .0451). The median level of phosphodiesters (PDE) relative to NTP increased by 28% from 4.82 (3.41-6.67) before induction to 6.18 (4.63-11.63) after induction (P = .0091). An increase in the level of inorganic phosphates (Pi) relative to NTP was observed, but changes were not significant. As shown by 1H-MR relaxometry, a nonsignificant trend of the liver parenchyma to shorter relaxation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo 31P-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with 31P-MR spectroscopy must take into account the potential effects of P450-inducing agents.

Adult↗

Low efficiency of active immunization against diphtheria in chronic hemodialysis patients.

Recent epidemiological studies indicate a low immunity to diphtheria in adults in industrialized countries. In the light of the epidemic increase of diphtheria in countries such as Russia and the Ukraine, systematic vaccination against this disease is recommended. We analyzed the immunity to diphtheria of 228 hemodialysis patients and the efficiency of single versus triple vaccination against diphtheria. Antibodies against diphtheria toxoid were determined by enzyme immunoassay in sera of 228 adult hemodialysis patients. Fifty-four patients were triple vaccinated against diphtheria and were followed for six months; 17 patients were single immunized and antitoxoid titers were determined 1 and 12 months later. The overall protection rate against diphtheria was 22% and equal in male and female patients. After triple immunization, only 35% of the patients developed protective antibody concentration (> 0.1 i.e./ml) six months after the third vaccination. A single vaccination caused protective titres twelve months later in 41% of the patients. There was no difference between responders and non-responders in the duration, intensity or modality of hemodialysis treatment or the response to previous vaccinations against hepatitis-B. We suggest to monitor antibodies against diphtheria toxoid in vaccinated hemodialysis patients at risk for diphtheria since protective titers are often not attained by the standard vaccination protocol.

Adult↗

[Indirect MR arthrography in the diagnosis of lesions of the labrum glenoidale].

PURPOSE: It has been shown that intravenous administration of contrast media produces an MR arthrographic effect without the need for intraarticular injection. This is the first study evaluating this new technique of indirect MR arthrography in the diagnosis of glenoid labrum tears. METHODS: 28 patients with clinically suspected labral injuries were prospectively investigated (1.5 Tesla, flexible surface coil). A plain MR examination of the shoulder (transverse and oblique-coronal orientation, T1-weighted spin- [TE/TR 15/675], proton density- and T2*-weighted gradient echo [TE/TR/Flip 14,32/600/30 degrees] sequences) and indirect MR arthrography (transverse and oblique-coronal orientation, fat-suppressed T1-weighted spin-echo sequences [TE/TR 15/675], intravenous injection of gadopentetate dimeglumine [0.1 mmol/kg], followed by 10-15 min of joint movement) were performed. Results were confirmed by arthroscopy and/or open surgery. RESULTS: Indirect MR arthrography significantly improved delineation of the glenoid labrum and hyaline cartilage (p < 0.05). Sensitivity and specificity of indirect MR arthrography in the diagnosis of labral injuries were 90% and 89%, compared to 79% and 67% of the native MR examination. CONCLUSION: Indirect MR arthrography is a promising non-invasive technique in the evaluation of the glenoid labrum.

Adult↗

[The therapy of a macroprolactinoma with the intramuscular application of a long-acting bromocriptine preparation].

HISTORY AND CLINICAL FINDINGS: Three years ago, a now 26-year-old woman with secondary amenorrhoea was found to have a prolactinoma which was treated with bromocriptine. However, because of side effects and psychosocial problems she took the drug only irregularly. There were no neurological symptoms and the visual fields were normal. Her weight was 97 kg and her height 168 cm. INVESTIGATIONS: Without treatment the serum prolactin concentration was 6978 microU/ml, while other endocrine parameters were unremarkable. Cranial computed tomography showed a suprasellar adenoma (craniocaudal diameter 1.0 cm). TREATMENT AND COURSE: Renewed treatment with bromocriptine (5 mg three times daily) brought prolactin concentration to within normal limits, but then rose again to at least 52,600 microU/ml when the patient took the drug irregularly, and the tumour grew to 2.8 cm. As the obesity (her weight now 120 kg) made neurosurgical intervention very risky a treatment trial with long-acting bromocriptine preparation (50 mg bromocriptine every 28 days intramuscularly), was undertaken. Serum prolactin concentration, measured at the end of the 28-day period, rapidly fell (6470 microU/ml after 3 months). Radiological examination indicated significant tumour shrinkage ( < 1.0 cm after 2 years). CONCLUSION: Repeated intramuscular administration of bromocriptine was an effective, well tolerated alternative (but not yet licensed in Germany) to oral dopamine agonists in the treatment of macroprolactinoma.

Adult↗

Dysregulated transforming growth factor-beta in neonatal and adult autoimmune MRL-lpr mice.

Transforming growth factor- beta (TGF- beta) is a cytokine that promotes inflammatory processes and prevents tissue injury. Autoimmune destruction of the kidney in MRL-lpr mice is spontaneous, rapid, fatal and consists of glomerular damage and an influx of lymphocytes surrounding vessels and in the interstitium. In MRL-lpr mice, cytokine dysregulation is apparent in neonates and continues throughout the life span. Circulating levels of tumour necrosis factor (TNF- alpha) and colony stimulating factor-1 (CSF-1) are detected in neonatal mice and progressively increase in proportion to the loss of renal function. We now report elevated intracellular expression of distinct isoforms of TGF- beta (TGF- beta 3, TGF- beta 2, and TGF- beta 1) detected immunohistochemically in MRL-lpr kidneys and other tissues including the liver and thymus. Enhanced TGF- beta 3 and TGF- beta 2 isoforms are detectable in neonatal mice within the renal tubular epithelial cells (TEC) and vascular smooth muscle cells (VSMC). In MRL-lpr mice 4-6 months of age, TGF- beta 2 and TGF- beta 1 are detected in TEC, VSMC, glomerular epithelial cells (GEC) and in perivascular infiltrating cells. By comparison, TGF- beta is minimally detectable in the normal kidneys of age and sex matched MRL(-)+2 or C3H/Fej mice. Paradoxically, in vitro cultured TEC and VSMC from MRL-lpr mice secrete less TGF- beta than TEC and VSMC isolated from MRL(-)+2 or C3H/FeJ mice. TNF- alpha, but not IL-6, CSF-1, or IFN- gamma stimulated the secretion of TGF- beta in TEC and VSMC. Our data demonstrate the dysregulation of TGF- beta isoforms in neonatal and adult MRL-lpr mice prior to and after the onset of autoimmune renal disease. We suggest that TNF- alpha and/or other molecules increase TGF- beta expression in MRL-lpr mice. We speculate that enhanced expression of TGF- beta promotes autoinmune renal injury in MRL-lpr mice.

Aging↗

Intraarterial hepatic chemotherapy with fluorouracil, fluorodeoxyuridine, mitomycin C, cisplatin or methotrexate as single-agent anticancer drugs for a transplanted experimental liver tumor in rats.

A prospective, controlled and standardized animal experiment was performed to study the influence of various anticancer drugs. The Novikoff hepatoma transplanted into male Sprague-Dawley rats was treated with fluorouracil (FUra), mitomycin C, methotrexate, cisplatin and fluorodeoxyuridine (FdUrd) at equi-effective dosage, in terms of side effects (weight loss), in comparison to a control group (0.9% saline solution) by locoregional application via the hepatic artery. The tumor multiplication factor (TMF = tumor volume day 12/tumor volume day 5) served as the parameter to compare the tumor growth of the various groups. All drugs showed a significant (P < 0.05) effect on the tumor growth. In comparison to the control group (mean TMF 9.66), FdUrd (3.78) and FUra (3.03) only limited the tumor growth, mitomycin C (0.96) produced stable tumor, cisplatin (0.64) and methotrexate (0.15) significantly reduced (P < 0.01) the tumor size. We suggest that, in addition to the established (FUra, FdUrd, mitomycin C) drugs, methotrexate and cisplatin should be considered in further studies of the treatment of primary and secondary liver malignancies.

Angiography↗

Subdural hemorrhage as an initial sign of glutaric aciduria type 1: a diagnostic pitfall.

The case of a 9-month-old girl with glutaric aciduria type 1 (GA 1) is reported. On initial presentation at 6 months of age, the patient demonstrated bilateral subdural hemorrhages and widening of the basal cisterns. After neurosurgical intervention the subdural effusions regressed; their etiology remained unclear. At the age of 9 months the patient presented again because of progressive loss of psychomotor abilities and a dystonic movement disorder. Cerebral MRI revealed regressive subdural hematoma, but marked frontotemporal atrophy as well. Because of a suspected metabolic disorder, urinary analysis of organic acids was performed. This repeatedly showed marked excretion of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid, indicating a diagnosis of GA 1. Considering our patient's history, we recommend the inclusion of GA 1 in the differential diagnosis of patients with unexplained subdural hematoma and neurological deficits.

Amino Acid Metabolism, Inborn Errors↗