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Biomedical subjects

D Hartmann

Publications and source records attributed to D Hartmann.

At least 19 recordsLinked to original sources
PubMed2003

[New nondispersive infrared spectrometry in 13C-urea breath tests].

BACKGROUND AND OBJECTIVE: 13C-urea breath tests have become clinical routine in the diagnosis of Helicobacter pylori infection. For the analysis of the 13CO2/12CO2 enrichment in breath, less expensive alternatives to the expensive mass spectrometry (IRMS) have been developed, based on isotope-selective infrared spectroscopy (NDIRS). In this prospective study we tested under clinical conditions a simplified and thus less expensive NDIR-spectrometer by comparing it with mass spectroscopy. METHODS: 100 patients (53 men, 47 women, mean age 59+/-14 years) with dyspeptic symptoms were tested for Helicobacter pylori infection using the 13C-urea breath test. The isotope ratio analysis of the breath samples was performed in duplicate, both using IRMS and NDIRS. RESULTS: The results of the baseline-corrected 13CO2 -exhalation values between IRMS and NDIRS were in excellent agreement. The mean difference between both methods was 0.05+/-1.16 . Evaluating the qualitative urea breath test results in reference to IRMS as the reference, the NDIRS had a sensitivity of 95 % and a specificity of 99 %. CONCLUSION: This newly developed isotope-selective nondispersive infrared spectroscopy is going to become a reliable, and low-cost alternative to expensive isotope ratio mass spectrometry in the analysis of 13C-breath tests. All these characteristics make NDIRS particularly suitable for laboratories where the daily number of assays is small or for use in the doctor's office

Adult↗
PubMed2003

[Symptomatic pericardial effusion as initial manifestation of gastric signet ring cell carcinoma].

HISTORY: A 78-year-old woman presented at our hospital with palpitation, tachycardia and progressive dyspnea. The health history included the diagnosis of diabetes mellitus and chronic obstructive pulmonary disease. INVESTIGATIONS: The ECG showed atrial fibrillation, later changing with sinus rhythm and low voltage. The echocardiography revealed pericardial effusion. The cytology showed signet ring cells from the stomach. Endoscopic study revealed a 3 cm tumor in the posterior wall of the upper part of the body. The histopathological examination diagnosed cancer of diffuse type according to Lauren, with signet-ring cells. TREATMENT AND CLINICAL COURSE: After treating the atrial fibrillation a pericardial drainage was performed. The pericardiocentesis yielded 500 ml of serous fluid. In an echocardiogram after pericardial drainage, pericardial effusion was no longer present. During the clinical course the patient suffered a stroke and the chemotherapy could not be initiated. The patient died 2 months after diagnosis. CONCLUSION: Cardiac involvement with clinical manifestations and pericardial effusion may be associated with a malignant neoplasm. Echocardiography and pericardiocentesis are helpful for the diagnosis of cardiac metastases.

Aged↗
PubMed2003

[Diagnosis of a high-grade B-cell lymphoma of the small bowel by means of wireless capsule endoscopy].

Wireless capsule endoscopy is a new diagnostic procedure to detect diseases of the small bowel, in particular in patients with obscure gastrointestinal bleeding. We report on a 76-year-old patient who presented at our hospital with signs of gastrointestinal bleeding and hypochromic anaemia. Bidirectional endoscopy, push enteroscopy, angiography as well as small bowel barium enema rendered no pathologic findings. Wireless capsule endoscopy demonstrated a polypous space in the cantral area of the small bowel. Subsequent intraoperative endoscopy revealed a subtotal stenosing tumour of the upper jejunum which was resected. Based on the histology a high-grade B-Cell lymphoma was diagnosed. The postoperative staging examinations did not indicate any further extranodal involvement.

Aged↗
PubMed2003

Capsule endoscopy versus push enteroscopy in patients with occult gastrointestinal bleeding.

BACKGROUND: Wireless capsule endoscopy is a new method enabling non-invasive diagnostic endoscopy of the entire small intestine. In this study we prospectively examined the diagnostic precision of capsule endoscopy compared with push enteroscopy in patients with occult gastrointestinal bleeding. METHODS: Between July 2001 and October 2002 we examined 48 patients with suspected disorders of the small intestine using capsule endoscopy. 33 patients with obscure bleeding (19 men, 14 women, mean age 58 +/- 23 years) were prospectively examined using capsule endoscopy and push enteroscopy. RESULTS: On average, the patients had been suffering from chronic gastrointestinal bleeding for 30 +/- 36 (1-120) months. The lowest haemoglobin level was 6.5 +/- 1.6 g/dl (2.3-9.6) and on average 9 +/- 10 (0-50) blood units were transfused. Each patient underwent 4 +/- 2 (1-10) hospitalisations, with a mean 9 +/- 4 (5-17) diagnostic procedures before capsule endoscopy was used. Definitive bleeding sites were diagnosed by push enteroscopy in 7 patients (angiodysplasia [n = 5], ulcers [n = 1], multiple jejunal diverticula [n = 1]). Capsule endoscopy showed a bleeding source in 25 cases (76 %) (angiodysplasias [n = 15], Meckel's diverticulum [n = 1], ulcers [n = 7], ileum diverticulosis [n = 1], B-cell lymphoma [n = 1]). Push enteroscopy localised an additional bleeding source in comparison with capsule endoscopy (multiple jejunal diverticula) in one patient. Both methods of examination were safe and showed no complications. DISCUSSION: The present study shows that capsule endoscopy had the highest diagnostic yield and was superior to push enteroscopy in patients with chronic gastrointestinal bleeding. By using the capsule at an early stage the subsequent therapeutic procedure could be considerably shortened and diagnostic processes could possibly be optimised.

Adolescent↗
PubMed2003

[Cellular culture of osteoblasts and fibroblasts on porous calcium-phosphate bone substitutes].

PURPOSE OF THE STUDY: Calcium phosphate ceramics are synthetic bone substitutes able to fill in bone destruction as a support of the bone growth. This work consisted in an in vitro assessment of osteoblasts and fibroblasts cultures on macroporous calcium-phosphate bone substitutes to analyze the interaction between cells and bone substitute. MATERIALS AND METHODS: The macroporous ceramic was composed of 70% hydroxyapatite and 30% tri-calcium phosphate with known mechanical and physico-chemical properties. Three compounds were processed with different size of macropore and with or without microporosity on their surface. Cells were seeded on discs measuring 10 mm in diameter and 2 mm in thickness. Cellular viability was evaluated by the MTT test for every stage of observation. An histological study to observe the invasion in the depth of discs was performed. Scanning electron microscopy was used to analyze the cellular comportment in contact with the surface of substitutes. RESULTS: An exponential cellular growth was effective on each substitute with the two cellular types. Cells spread on the surface of the compounds covering macropores and colonized the depth of the discs. A size of macropore of 300 microm or more seemed to support this invasion. 15 microm sized interconnections appeared to be effective to allow cell migration between macropores. The cell proliferation was similar on substitutes with or without microporosity. CONCLUSION: Biomaterials currently used as bone substitute are more or less osteoconductive but they have no osteoinductive property. A hybrid association of calcium-phosphate ceramic with osteogenic cells should promote the development of a calcium phosphate compound with osteoinductive capacity.

Biocompatible Materials↗
PubMed2002

[Endoscopy of the small intestine without tube or enema? A video capsule makes it possible].

The diagnosis of unclear bleeding in the small bowel remains a gastroenterological problem. To date, the diagnostic approach routinely employed has been roentgen Sellink. With such newer techniques as magnetic resonance tomography (MRT) substantially more diagnostic information can now be obtained. A recent new development is capsule endoscopy, which is intended for use when conventional endoscopic examinations fail to identify the source of bleeding. Using this new option in the Ludwigshafen Klinikum the small bowel lesions were discovered in 81% of the 26 patients in whom they had been previously remained undetected. At present, the patients have to bear the cost of this examination themselves.

Capsules↗
PubMed2002

[Endometriosis of the transverse colon--a rare localization].

HISTORY: A 65-year-old woman with no complaints came to our hospital for a colonoscopy because of a family history of a colorectal carcinoma. Because of postmenopausal complaints she had been undergoing estrogen therapy for the past five years. INVESTIGATIONS: Colonoscopy revealed a 2 x 2 cm polyp like structure with central tissue proliferation in the transverse colon. Neither chromoendoscopy with indigocarmine nor multiple biopsies indicated an adenomatous glandular proliferation. Miniendosonography revealed the image of a tumour located in the muscularis propria. DIAGNOSIS AND CLINICAL COURSE: As a malign process could not definitely be excluded, a colon segment resection was carried out by laparoscopy. In the operative specimen there was a 2 x 2 cm large tumour growing under the mucosa. Histologically it was an intramural manifestation of an extragenital endometriosis in the area of the muscularis propria with resulting nodular proliferation of the local muscle system. The ectopic endometrial glands in the area of the endometriosis revealed a complex hyperplasia without atypical features, an image suggesting oestrogen stimulation. CONCLUSION: In many cases the diagnosis of an intestinal endometriosis can not be made through a non-invasive diagnostic method such as colonoscopy with biopsy because of the intramural localisation in the muscularis propria. In order to safely rule out a malignant lesion, in unclear cases a resection should be aimed at.

Adenomatous Polyposis Coli↗
PubMed2002

Stromal cell-derived factor 1 is secreted by meningeal cells and acts as chemotactic factor on neuronal stem cells of the cerebellar external granular layer.

The cerebellar external granular layer (EGL) is an unusually long-lasting neural proliferative zone positioned immediately beneath the pial surface. Its position and stability critically depend on meningeal cells, as their selective destruction leads to its rapid dispersal, creating massive cortical ectopia. Similar ectopias have recently been described as a side effect of deficiency for stromal cell-derived factor 1 (SDF-1), a chemoattractant for haematopoietic precursor cell migration. Here we show that SDF-1 is present in meningeal cells in vivo and in vitro, where it is secreted in functionally relevant concentrations into the medium. Correspondingly, the SDF-1 receptor (termed CXCR4) can be demonstrated on stem cells of the external granular layer, but is absent on postmitotic cells commencing their final inward migration. We show that SDF-1 is concentrated by heparan sulphate proteoglycans highly expressed in the EGL in a laminar fashion, which thus might act to locally restrict SDF-1 action to the EGL in a kind of step gradient. In vitro, SDF-1 chemotactically attracts neuronal cells isolated from the external, but not from the internal granular layer, in a Boyden chamber assay in concentrations found in meningeal cell-conditioned medium. Selective removal of SDF-1 from conditioned media by immunoprecipitation abolishes their chemoattractive action, which can be reconstituted again by the addition of recombinant SDF-1. Meningeal cells are thus an important source for the expression of SDF-1 during brain development, which--comparable to its role in haematopoiesis--appears to be a key factor attracting precursor cells to their proliferative compartment.

Animals↗
PubMed2002

Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations.

Arylsulfatase A (ASA) knockout mice represent an animal model for the lysosomal storage disease metachromatic leukodystrophy (MLD). Stem cell gene therapy with bone marrow overexpressing the human ASA cDNA from a retroviral vector resulted in the expression of high enzyme levels in various tissues. Treatment partially reduces sulfatide storage in livers exceeding 18 ng ASA/mg tissue, while complete reduction was observed in livers exceeding 50 ng ASA/mg tissue. This corresponds to about 80% and 200% of normal enzyme activity. Similar values seem to apply for kidney. A partial correction of the lipid metabolism was detectable in the brain where the galactoerebroside/sulfatide ratio, which is diminished in ASA-deficient mice, increased upon treatment. This partial correction was accompanied by amelioration of neuropathology; axonal cross-sectional areas, which are reduced in deficient mice, were significantly increased in the saphenic and sciatic nerve but not in the optic nerve. Behavioral tests suggest some improvement of neuromotor abilities. The gene transfer did not delay the degeneration occurring in the acoustic ganglion of ASA-deficient animals. The limited success of the therapy appears to be due to the requirement of unexpected high levels of ASA for correction of the metabolic defect.

Animals↗
PubMed2002

[Surgical therapy of inflammatory bowel diseases. Rational diagnosis--endoscopy, contrast media administration, CT? Indications for operation].

Some 10 to 25 percent of all patients with diverticulosis will come down with diverticulitis in the course of their lives. Apart from physical examinations, sonography and--if results are still unclear--computer tomography are seen as the most important diagnostic devices. 75 percent of patients with acute diverticulitis can initially be treated conservatively, and only one in four ever falls ill again with another inflammation. According to those numbers a conservative method is justified when dealt with a primary uncomplicated diverticulitis. If a second attack occurs, should an elective resection be considered. An increased mortality and morbidity exists among young and immunocompromised patients so that elective surgery is recommended already after the first incident.

Contrast Media↗
PubMed2002

[Colonic carcinoma--state of the art. Primary and secondary prevention].

Considering the high incidence and mortality rate of colorectal cancer, great efforts are made for primary and secondary prevention. By doing so, primary prophylaxis includes the use of protective measures in order to prevent the development of adenomas and carcinomas. Epidemological studies have shown that nutrition or medication (e.g. NSAID) have an immediate influence on the pathogenesis of colorectal carcinomas. Secondary prevention includes early diagnosis and treatment of precursors of carcinomas. Considering this, colonoscopy is the cheapest and gentlest method and therefore the screening method of choice.

Colonic Polyps↗
PubMed2002

[Adenoma of Vater's ampulla: what is the value of endoscopic diagnosis and therapy?].

The method of choice to detect tumors of the papilla of Vater is endoscopic diagnosis. However, no definite decision on the dignity can be made through the macroscopic appearance itself. Only the combination of various diagnostic methods (side view duodenoscopy with biopsy, endosonography, ERCP, IDUS) allows a reliable statement on the local growth of tumors and the dignity. If there are no signs for local infiltration, histological indications for a carcinoma or distant metastasis, the endoscopic resection in specialized centers is recommended.

Adenoma↗
PubMed2001

The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein.

We showed previously that PrPc undergoes constitutive and phorbol ester-regulated cleavage inside the 106-126 toxic domain of the protein, leading to the production of a fragment referred to as N1. Here we show by a pharmacological approach that o-phenanthroline, a general zinc-metalloprotease inhibitors, as well as BB3103 and TAPI, the inhibitors of metalloenzymes ADAM10 (A disintegrin and metalloprotease); and TACE, tumor necrosis factor alpha-converting enzyme; ADAM17), respectively, drastically reduce N1 formation. We set up stable human embryonic kidney 293 transfectants overexpressing human ADAM10 and TACE, and we demonstrate that ADAM10 contributes to constitutive N1 production whereas TACE mainly participates in regulated N1 formation. Furthermore, constitutive N1 secretion is drastically reduced in fibroblasts deficient for ADAM10 whereas phorbol 12,13-dibutyrate-regulated N1 production is fully abolished in TACE-deficient cells. Altogether, our data demonstrate for the first time that disintegrins could participate in the catabolism of glycosyl phosphoinositide-anchored proteins such as PrPc. Second, our study identifies ADAM10 and ADAM17 as the protease candidates responsible for normal cleavage of PrPc. Therefore, these disintegrins could be seen as putative cellular targets of a therapeutic strategy aimed at increasing normal PrPc breakdown and thereby depleting cells of the putative 106-126 "toxic" domain of PrPc.

ADAM Proteins↗
PubMed2001

Bone marrow stem cell gene therapy of arylsulfatase A-deficient mice, using an arylsulfatase A mutant that is hypersecreted from retrovirally transduced donor-type cells.

Arylsulfatase A (ASA)-deficient mice represent an animal model for the fatal lysosomal storage disease metachromatic leukodystrophy, which is characterized by widespread intralysosomal deposition of sulfatide. Bone marrow stem cell gene therapy in mice, using a retroviral vector mediating expression of wild-type human ASA, has the potential to ameliorate the visceral pathology, but improves the prevailing brain disease and neurologic symptoms only marginally. One factor that influences the efficacy of bone marrow transplantation therapy in lysosomal storage diseases is the secretion level of the therapeutic enzyme from donor-type cells. Here we test the potential of a hypersecreted glycosylation variant of ASA. Although this mutant lacks mannose 6-phosphate residues it is taken up by cells by a mannose 6-phosphate receptor-independent pathway and causes partial metabolic correction of ASA-deficient mouse cells. Retrovirally mediated transfer of the mutant cDNA into ASA-deficient mice results in the sustained expression of the transgene. Serum levels argue for an increased secretion of the glycosylation mutant also in vivo. Tissue levels were reduced to 2% in liver and up to 40% in kidney compared with animals treated with the wild-type enzyme, indicating reduced endocytosis. Thus, the limited uptake of the variant enzyme outweighs the putative advantageous effect of improved supply. Although the mutant enzyme is able to correct the metabolic defect partially, histological examinations did not reveal any reduction of sulfatide storage in treated animals. Surprisingly, analysis of neurologic symptoms indicated a significant improvement of the gait pattern.

3T3 Cells↗
PubMed2001

[Phenprocoumon-induced necrotizing hepatitis].

CLINICAL PRESENTATION: A 52-year-old female patient presented at our hospital with right upper abdominal pain and impaired general condition. During the previous 7 months, the patient had received anticoagulation treatment with phenprocoumon due to a prosthetic aortic valve replacement. TESTS: Serological tests for virologic, autoimmune or metabolic causes of hepatitis were negative. The histologic examination of liver biopsies showed necrotizing hepatocellular injury in zone 3 of the acinus without relevant fibrosis. Initially, a lymphocyte transformation test with phenprocoumon was negative. A second test after one week turned out to be positive. DIAGNOSIS AND CLINICAL COURSE: After withdrawal from phenprocoumon therapy and switching to anticoagulation with a low molecular weight heparin, liver tests gradually became normal. Aminotransferase levels rapidly increased when phenprocoumon treatment was resumed. Phenprocoumon-associated necrotizing hepatitis was diagnosed by clinical course, liver histology and the positive lymphocyte transformation test. After immunosuppressive treatment with prednisolone was started again, liver enzymes gradually normalized. Anticoagulation was further performed with low molecular weight heparin. CONCLUSION: This case stresses the fact that an adequate and detailed history on concomitant medication is mandatory in patients who present with cryptic hepatitis. Though severe hepatic adverse effects of phenprocoumon are rare, physicians should consider coumarin derivatives as a potential source of hepatitis.

Anti-Inflammatory Agents↗
PubMed2001

Lysosomal sulfoglycolipid storage in the kidneys of mice deficient for arylsulfatase A (ASA) and of double-knockout mice deficient for ASA and galactosylceramide synthase.

The inherited deficiency of arylsulfatase A (ASA) causes lysosomal accumulation of sulfoglycolipids (mainly sulfo-galactosylceramide, S-GalCer ) and leads to metachromatic leukodystrophy in humans. Among visceral organs, kidneys are particularly affected. In the present study, the regional distribution and temporal development of sulfoglycolipid storage in kidneys of ASA-/- mice was investigated histochemically (alcian blue) and ultrastructurally. Furthermore, the sulfoglycolipid storage was examined in kidneys of double-knockout mice, which are incapable of: (a) degrading any sulfolipids (ASA-/-) and (b) synthesizing the major sulfolipid S-GalCer because of deficiency for galactosylceramide synthase (CGT), with the aim to search for additional ASA substrates. In ASA-/- mice, the nephron segments could be ranged in the order of decreasing sulfolipid storage: thin limbs of long-looped nephrons approximately thick ascending limbs > distal convoluted tubules > collecting ducts approximately short thin limbs. Macula densa and proximal tubules were unaffected. In ASA-/-/CGT-/- mice, the long thin limbs and distal convoluted tubules resembled those of ASA-/-/CGT+/+ mice, while the other segments showed less storage. The results suggest that the turnover of sulfolipids in general is highest in the distal nephron except macula densa, and that long thin limbs and distal convoluted tubules are the main sites for turnover of a minor sulfolipid species, which is known to be synthesized in the kidney of CGT-/- mice.

Animals↗