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Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

At least 145 records · Page 8Linked to original sources

[The benefits and risks of percutaneous transhepatic cholangioscopy].

Percutaneous transhepatic cholangioscopy (PTCS) was undertaken in 101 patients (for diagnostic reasons in 64 and/or therapeutic reasons in 56) out of 167 consecutive patients (56 women, 45 men; mean age 64.2 [27-95] years) in whom percutaneous transhepatic drainage had been instituted. In all but one of 64 patients PTCS clearly defined stenoses which had been unclear in the cholangiogram. There was a 90% accuracy of histological diagnosis of biopsies obtained under vision in 60 cases. A malignant stenosis was seen in 19 of 25 cases (sensitivity 76%). Severe stenosis, not passable by contrast medium, were recanalized cholangioscopically in 14 of 15 cases. Biliary tract stones were completely removed by PTCS in 40 of 41 patients, by mechanical means (n = 4) or intracorporeal lithotripsy (n = 37). There were no complications from PTCS. It is concluded that PTCS can be performed safely and reliably in patients with functioning percutaneous transhepatic drainage. It provides the diagnosis of previously unclear cholangiographic findings as well as treatment of difficult biliary tract stenoses and/or ductal stones.

Adult↗

Molecular analysis of ependymins from the cerebrospinal fluid of the orders Clupeiformes and Salmoniformes: no indication for the existence of an euteleost infradivision.

Ependymins represent the predominant protein constituents in the cerebrospinal fluid of many teleost fish and they are synthesized in meningeal fibroblasts. Here, we present the ependymin sequences from the herring (Clupea harengus) and the pike (Esox lucius). A comparison of ependymin homologous sequences from three different orders of teleost fish (Salmoniformes, Cypriniformes, and Clupeiformes) revealed the highest similarity between Clupeiformes and Cypriniformes. This result is unexpected because it does not reflect current systematics, in which Clupeiformes belong to a separate infradivision (Clupeomorpha) than Salmoniformes and Cypriniformes (Euteleostei). Furthermore, in Salmoniformes the evolutionary rate of ependymins seems to be accelerated mainly on the protein level. However, considering these inconstant rates, neither neighbor-joining trees nor DNA parsimony methods gave any indication that a separate euteleost infradivision exists.

Amino Acid Sequence↗

Granulocyte colony-stimulating factor treatment of leucopenia during fractionated radiotherapy.

11 patients suffering from an isolated leucopenia during fractionated radiotherapy were treated with granulocyte colony stimulating factor (G-CSF). 4 of the patients received radiotherapy alone, and 7 patients received concomitant chemotherapy. G-CSF treatment was initiated at the occurrence of leucopenia and maintained for the duration of radiotherapy. The applied daily dose was 5 micrograms/kg subcutaneously. 10 of the 11 treated patients reacted with an increased leucocyte count, from an average of 1342 leucocytes per microliter (+/- 502/microliters) to 24,568 leucocytes per microliter (+/- 950/microliters). Neutrophil counts increased on average from 64.9% (+/- 13.9%) to 91.1% (+/- 2.3%) (n = 7). In 1 patient thrombocytopenia occurred during the continued radiotherapy. 1 other patient reacted with an unexplained fall of leucocytes after two doses of G-CSF and one fraction of mediastinal irradiation. Side-effects observed during G-CSF treatment consisted of mild bone pain (1/11) and transient increases of serum alkaline phosphatase levels (4/11). Our observations indicate that G-CSF treatment is well tolerated during continuous fractionated radiotherapy. Therefore, we conclude that G-CSF can be used clinically to alleviate neutropenia caused by radiotherapy or by combined radio-chemotherapy.

Adult↗

The P-domain or trefoil motif: a role in renewal and pathology of mucous epithelia?

By analogy with epidermal growth factor and EGF-like repeats, the P-domain, or trefoil motif, is a characteristic shuffled module containing six invariant cysteine residues that forms the basic unit for a family of mucin-associated peptides. These P-domain peptides are potential modulators of cell growth and they are also expressed under certain pathological conditions. Furthermore, P-domains have been found as components of extracellular mosaic proteins including certain mucins, where they are thought to play a role either in protein-protein or in lectin-like interactions.

Amino Acid Sequence↗

Laser lithotripsy of difficult bile duct stones under direct visual control.

Biliary laser lithotripsy was performed under direct visual control in 35 consecutive patients not amenable to routine endoscopy. The patients had 1-50 (median 1) bile duct stones with the greatest diameter of the largest stone being 9-42 mm (median 20 mm). Conventional endoscopic treatment had failed because of an inaccessible papilla (16 patients), biliary strictures (seven patients), and impaction or large size of calculi (12 patients). Twelve patients, depending on their anatomical condition, underwent peroral cholangioscopy by means of a mother-babyscope system. Percutaneous cholangioscopy was initially carried out in 23 patients, 7-20 days (median 10 days) after creation of a transhepatic fistula. Pulsed dye laser (32 patients) or alexandrite laser (three patients) lithotripsy was applied under an appropriate direct visual control in all cases. Complete stone disintegration succeeded in 33 of 35 patients. All resultant fragments passed the papilla within a mean number of 1.3 treatment sessions. Peroral cholangioscopic lithotripsy failed in two cases. One patient successfully underwent percutaneous laser treatment and the other patient was referred to surgery. Fever, temporary haemobilia, or a subcapsular liver haematoma were seen in a total of eight patients during establishment of the cutaneobiliary fistula. A 95 year old patient who had been admitted with septic cholangitis died because of cardiorespiratory failure 5 days after bile duct clearance. It is concluded that laser lithotripsy performed under a direct visual control is an effective and safe procedure for the non-surgical treatment of difficult bile duct stones. Ductal clearance can usually be achieved in a single treatment session when the papilla and the stones are accessible by the peroral route. Percutaneous cholangioscopic lithotripsy is more time consuming but highly effective even in patients with a difficult anatomy, bile duct strictures, or intrahepatic calculi. This approach should be limited, however, to cases not amenable to retrograde procedures because the creation of the cutaneobiliary fistula is not without risks.

Aged↗

Ultrasound diagnosis of splenic lymphoma: ROC analysis of multidimensional splenic indices.

To assess the efficacy of splenic size in the sonographic diagnosis of lymphomatous involvement of the spleen, the authors studied 31 patients with splenic lymphoma (Hodgkin's disease, 17 and non-Hodgkin's lymphoma, 14) and 218 individuals without evidence of splenic disease. All subjects were studied with both a linear and a sector transducer. The longitudinal, transverse and diagonal diameters of the spleen were measured, and two- and three-dimensional splenic indices were calculated. The analysis of the diagnostic performance of these criteria, compared by means of receiver-operating characteristic (ROC) curves, revealed that diagnosis of splenic involvement by malignant lymphoma was considerably more reliable with a sector than with a linear scanner. If the longitudinal diameter was measured with a sector scanner, sensitivities were 66% and 74%, at specificities of 95% and 90% respectively (cut-off points: 12.5 cm and 11.3 cm, respectively). For the sector scanner, there was no advantage in using other diameters or multidimensional indices. Additional ROC analysis of recently published data indicating excellent discrimination capacity of a computed tomography index revealed that these results were largely owing to patient selection. In contrast, our data suggest that the potential of current non-invasive assessment of splenic lymphoma is limited. However, ultrasound may eventually help to eliminate staging laparotomy in selected cases, e.g. in patients with low risk of abdominal disease and with increased surgical risk.

Adult↗

Radium-226-contaminated drinking water: hypothesis on an exposure pathway in a population with elevated childhood leukemia.

A recent epidemiological survey on childhood malignant disease in the region of Ellweiler, Rheinland-Pfalz, Germany, revealed a significantly increased incidence of childhood leukemia, but observed incidences of lymphoma and solid tumors were normal. Established risk factors such as individual exposure to chemicals as well as hereditary genetic disorders were ruled out in interviews with the patients or their families. The general population in the region, however, is subjected to considerable doses of ionizing radiation due to high levels of external gamma radiation and high activities of indoor radon. Radiation-specific chromosome aberrations were found in one of two healthy siblings and one father of leukemia patients as well as in any of three probands living in houses with high indoor radon activities. Radon and natural gamma radiation, however, cannot explain the geographical pattern of the cases. Four out of seven cases were observed in two particular villages near a uranium processing plant. The drinking water of these villages partly came from a small river that was contaminated with radium-226 washed out from the dumps of the uranium plant. Only sparse measurements of 226Ra are available, but derived red bone marrow doses for children in the two villages obtained from a simple radio-ecological model show the significance of the drinking water pathway. Prenatal 226Ra exposure of fetuses due to placental transfer and accumulation may have led to significant doses and may explain the excess cases of childhood leukemia in the region even in quantitative terms.

Adolescent↗

[Laser therapy and tube implantation for palliative treatment of inoperable esophageal and cardia cancer].

Laser photocoagulation and intubation are effective measures for palliation of the unresectable esophago-cardial malignancy. Laser therapy is especially useful for short strictures and noncircular and proximal lesions. Intubation usually leads to a rapid relief of dysphagia especially in patients with extensive tumor involvement of the esophagus; for esophago-bronchial fistula special tubes are available. By using the newly developed metal endoprotheses, the higher complication rates of the plastic tubes as compared with laser therapy could probably be decreased. Nowadays, endoscopic palliation of esophageal carcinoma is usually applied as part of multimodal oncological treatment concepts.

Cardia↗

[Hilar bile duct cancer: diagnostic and therapeutic strategies].

Hilar bile duct carcinoma is difficult to diagnose and requires high standards of a curative or palliative therapy. The tumor staging is performed by means of transabdominal sonography, CT scan, endoscopic retrograde cholangiography, and/or percutaneous transhepatic cholangiography and angiography. The value of cholangioscopy and endosonography must be evaluated in further studies. These procedures could improve the preoperative selection of completely resectable tumors. In addition, the mapping of tumor extension into individual hepatic segments facilitates curative operations with the smallest necessary hepatic resection which is associated with low early mortality rates and good long-term results. Nevertheless, the majority of patients can only be treated by palliation with operative, percutaneous, or endoscopic drainage. The decision of the selection of the method is individual, since there are no controlled trials for the hilar bile duct carcinoma.

Adenocarcinoma↗

[The role of endoscopic retrograde cholangiopancreatography in complications after laparoscopic cholecystectomy].

Endoscopic retrograde cholangiography (ERC) following conventional as well as laparoscopic cholecystectomy is a suitable method in the case of residual calculi and biliary leakage. This is due to the fact that this method enables an exact diagnosis and, in most patients, a prompt and effective therapy. Problems due to bile duct injuries frequently arise with a time-lag after surgery. Even in these cases ERC and, in certain anatomical conditions, percutaneous transhepatic cholangiography (PTC) enable the accurate delineation of changes which are the basis of further therapy. Concerning stenoses of the biliary tract the question awaits evaluation as to what extent an endoscopic or radiologic intervention will be a sound alternative to surgery. First results are encouraging.

Biliary Fistula↗

[The clinical picture and therapy of aggressive fibromatosis (desmoids)].

Desmoid tumors are accounted among histologically benign soft tissue tumors. Though metastases do not occur the clinical course of the disease with their tendency to grow locally aggressive and to relapse after curative intended surgery is similar to sarcomas. After surgical excision adjuvant therapy of desmoid tumors is necessary in such cases, where a radical excision with a wide margin is not possible, or must be doubted or after the surgical excision of a locally recurrent tumor. Radiation doses of 50 to 60 Gy reduce the risk of local recurrence of desmoid tumors to 18%. In such cases, where surgery and radiotherapy have been leading to incomplete responses, systemic therapy with hormones (tamoxifen or progesterone), with alkylating agents (e. g. ifosfamide) or with prostaglandin antagonists (indomethacin) is possible. The published data on therapeutic responses to the treatment of desmoid tumors are scarce. We are reporting on seven of our own cases, treated with surgery and radiotherapy (four) or with a combination of surgery, radiotherapy, hormones and chemotherapy (three).

Adult↗

P-domains as shuffled cysteine-rich modules in integumentary mucin C.1 (FIM-C.1) from Xenopus laevis. Polydispersity and genetic polymorphism.

A new frog integumentary mucin (FIM-C.1) has been discovered by molecular cloning. This mucin contains at least six typical P-domains as cysteine-rich modules. Shuffled P-domains have previously been detected in FIM-A.1, and they also form the basis of various P-domain peptides, which presumably have growth-modulating activities. Furthermore, FIM-C.1 contains at least three threonine-rich clusters, which consist of semi-repetitive cassettes. Various polydisperse transcripts have been characterized. They originate from two genes only and differ by deletions/insertions that are congruent with the semi-repetitive cassettes. Thus, polydispersities are probably generated by alternative splicing. Southern analysis revealed genetic polymorphism between different individuals. Furthermore, a specific antiserum was generated against a synthetic peptide deduced from the COOH-terminal end of FIM-C.1 and used for Western analysis.

Amino Acid Sequence↗

Ependymins from the cerebrospinal fluid of salmonid fish: gene structure and molecular characterization.

So far, ependymins (Epds) have been sequenced only from cypriniform fish, and in the past all attempts have failed to characterize, on a molecular level, homologous Epd proteins in higher vertebrates. Therefore, rainbow trout (Oncorhynchus mykiss) Epds, which represent the predominant proteins of the cerebrospinal fluid, have been N-terminally sequenced and the encoding cDNA subsequently cloned using the polymerase chain reaction. Surprisingly, only 40-42% of the amino acids are identical with the corresponding sequences from goldfish (Carassius auratus), and no convincing immunological cross-reactivity is observed with an antiserum raised against purified Epds from C. auratus. O. mykiss possesses two highly homologous genes encoding Epds (Om-I, Om-II), a feature typical of a quasi-tetraploid species. Western analysis, using two specific antibodies against Epds from O. mykiss, revealed a variety of different glycosylation variants. In contrast to C. auratus, Epds from O. mykiss probably do not form disulfide-linked dimers. The structure of one Epd gene and its flanking regions have been determined for the Atlantic salmon (Salmo salar). Six exons were deduced by comparison with the corresponding cDNA sequence from O. mykiss (almost 98% homology with Om-II).

Amino Acid Sequence↗

xP2, a new member of the P-domain peptide family of potential growth factors, is synthesized in Xenopus laevis skin.

Similarly to epidermal growth factor (EGF) and EGF-like repeats, the "P-domain" represents a cysteine-rich module that has been detected in the past in a variety of polypeptides, as well as in high molecular weight proteins. Here, a precursor for a secretory polypeptide (xP2) is characterized that consists of two P-domains. xP2 has been discovered in Xenopus laevis with the help of the polymerase chain reaction. In contrast to all other P-domain peptides, it is synthesized in the skin but not in the stomach or the pancreas. By this and other criteria, it cannot be considered simply as the X. laevis homologue of recently described P-domain peptides, viz. the spasmolytic polypeptides (PSP/hSP/mSP). Furthermore, a polyclonal antiserum was generated against the deduced C-terminal end of xP2. Due to its immunoreactivity with granular glands, as well as with the epidermis, the possibility of a growth factor activity for xP2 in the germinal layer is discussed.

Amino Acid Sequence↗

The polymorphic integumentary mucin B.1 from Xenopus laevis contains the short consensus repeat.

The frog integumentary mucin B.1 (FIM-B.1), discovered by molecular cloning, contains a cysteine-rich C-terminal domain which is homologous with von Willebrand factor. With the help of the polymerase chain reaction, we now characterize a contiguous region 5' to the von Willebrand factor domain containing the short consensus repeat typical of many proteins from the complement system. Multiple transcripts have been cloned, which originate from a single animal and differ by a variable number of tandem repeats (rep-33 sequences). These different transcripts probably originate solely from two genes and are generated presumably by alternative splicing of an huge array of functional cassettes. This model is supported by analysis of genomic FIM-B.1 sequences from Xenopus laevis. Here, rep-33 sequences are arranged in an interrupted array of individual units. Additionally, results of Southern analysis revealed genetic polymorphism between different animals which is predicted to be within the tandem repeats. A first investigation of the predicted mucins with the help of a specific antibody against a synthetic peptide determined the molecular mass of FIM-B.1 to greater than 200 kDa. Here again, genetic polymorphism between different animals is detected.

Amino Acid Sequence↗

Goldfish ependymins: cerebrospinal fluid proteins of meningeal origin.

Ependymins are unique secretory proteins from the goldfish brain which have calcium binding capacity. They are synthesized in the leptomeninx and appear subsequently as the predominant protein constituents in the cerebrospinal fluid (CSF). In contrast, the serum is nearly devoid of ependymins. The perimeningeal fluid (PMF) between the meninx and the skull represents a mixture of CSF and serum. The different composition of PMF and CSF implies that there is no open communication between these two compartments. Separation is probably achieved by an arachnoid-like meningeal barrier as proposed from ultrastructural studies. This basic CSF system of fish is compared with that of higher vertebrates.

Animals↗

Laser lithotripsy of pancreatic and biliary stones via 3.4 mm and 3.7 mm miniscopes: first clinical results.

The pulsed dye laser is safe and effective in lithotripsy of biliary and pancreatic ductal stones, however delivery of the laser energy to the site of the calculi is technically difficult. A 3.4 mm miniscope inserted through a standard duodenoscope was used for transpapillary laser application under direct vision in one patient with an impacted pancreatic stone and in three patients with bile duct stones not amenable to treatment by routine endoscopy. Lithotripsy and ductal clearance was achieved in 3 of the 4 patients within a single treatment session. Percutaneous transhepatic laser lithotripsy via a 3.7 mm miniscope succeeded in the patient in whom the peroral approach had failed and in two further patients with bile duct stones not accessible by a retrograde approach. There were no major complications. The miniscopes provide an appropriate direct visual control for laser lithotripsy of pancreatobiliary calculi. This approach using miniscopes seems to be an effective, minimally invasive and time-saving alternative to conventional endoscopic laser lithotripsy.

Adult↗