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Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

At least 19 recordsLinked to original sources
PubMed1999

Differential behavioral effects of TFF peptides: injections of synthetic TFF3 into the rat amygdala.

TFF peptides (formerly named P-domain peptides or trefoil factors) are also released from the brain as well as being secreted typically by mucin producing cells. The amygdala, besides the hypothalamus, represents a defined neuronal locality of TFF3 synthesis. In a passive avoidance test synthetic TFF3/monomer or 0.9% sodium chloride (control) was injected bilaterally into the basolateral nucleus of the amygdala of male rats either immediately (consolidation test) or 23 h after a footshock (retrieval test). Application of a low TFF3 dose (2 x 6 pg) decreased avoidance latency in a time dependent manner. In contrast, a high dose (2 x 60 pg) increased avoidance latency. Maximal effects of TFF3 were observed about 24 h after the injection. This bidirectional effect was also observed using the elevated plus-maze test. The locomotor activity on the open arms was significantly increased 24 h after a low dose injection of TFF3 into the amygdala. In contrast, a high-dose injection significantly decreased the activity on the open arms. The results of both tests can be explained by an anxiolytic effect at a low dose and an anxiogenic effect at a high dose of synthetic TFF3/monomer.

Amygdala↗
PubMed1999

Localization of TFF3, a new mucus-associated peptide of the human respiratory tract.

Trefoil factor family (TFF)-domain peptides (formerly P-domain peptides, trefoil factors) represent major mucin-associated peptides of the gastrointestinal tract. Here, the first localization studies on TFF3 in the lower respiratory tract of human material are presented. Immunohistochemistry revealed significant accumulation of TFF3 to mucous cells in the acini of submucosal glands and varying amounts in goblet cells at the ductular portions and the surface epithelium. TFF3 appears also as a component of the mucus, for example from patients with chronic bronchitis. Expression of TFF3 was also shown by use of the polymerase chain reaction. In contrast, TFF1 and TFF2 transcripts were hardly detectable in the human respiratory tract. Thus, a structural function of TFF3 for the airway mucus is discussed, possibly together with the mucins MUC5B and MUC5AC.

Blotting, Western↗
PubMed1998

Differential expression of the TFF-peptides xP1 and xP4 in the gastrointestinal tract of Xenopus laevis.

TFF-peptides (formerly P-domain peptides, trefoil factors) represent major secretory products of the mammalian gastrointestinal tract. A molecular cloning approach revealed the existence of two TFF-peptides, xP1 and xP4, also in the stomach of Xenopus laevis. Here, the localization of these two peptides by Western blot analysis as well as immunohistochemistry is presented. xP1 is found predominantly in the surface mucous cells of the stomach, whereas xP4 is mainly localized to a specific population of goblet cells in the esophagus, to mucous neck cells of the stomach, and to closely resembling cells in antral glands. xP4 in the esophagus and in the stomach differ by their N-glycosylation patterns. Compared to mammalian TFF-peptides, xP1 obviously represents the frog homologue of human TFF1 (formerly pS2) and xP4 seems to be the amphibian equivalent of human TFF2 (formerly hSP).

Animals↗
PubMed1998

Permanent junctional re-entry tachycardia. A multicentre long-term follow-up study in infants, children and young adults.

AIMS: Permanent junctional re-entry tachycardia is a relatively uncommon form of re-entry tachycardia with antegrade conduction occurring through the atrioventricular node and retrograde conduction over an accessory pathway usually located in the postero-septal region. It was the aim of the study to investigate the course of permanent junctional re-entry tachycardia with particular regard to the effectiveness of pharmacological treatment and ablation procedures; evaluation was performed with respect to the patient's symptoms, tachycardia rate, frequency of the tachycardia and left ventricular function. METHODS AND RESULTS: The long-term follow-up of 32 patients with permanent junctional re-entry tachycardia was evaluated. The first presentation with supraventricular tachycardia occurred between the 27th week of gestation and 27 years. The tachycardia rate ranged from 100 to 250 beats.min-1. During Holter-ECG, permanent junctional re-entry tachycardia was documented as present for over 50% of the time in 24 h in 22 patients (69%). Left ventricular performance was impaired in nine patients (28%) due to a tachycardia-related cardiomyopathy. Symptoms or signs of heart failure were mild to moderate in eight and severe in four patients; 20 patients showed no clinical impairment. Follow-up time was 1 to 31 (mean 10) years; current age of the patients ranged from 1.5 months to 35 (mean = 15 x 3) years. Four patients needed no therapy because of the infrequency of permanent junctional re-entry tachycardia episodes. Twenty-five patients initially received antiarrhythmic drugs, which were effective or partially effective in 14 (56%). Eight of them are still on medical therapy; in five treatment was discontinued because of absence of symptoms. Eleven patients had ablation of the accessory pathway during follow-up, three underwent ablation as a primary procedure. CONCLUSION: Permanent junctional re-entry tachycardia in our experience is an arrhythmia with a large variety of clinical symptoms. Patients with a slow tachycardia rate and infrequent episodes of tachycardia may never develop symptoms and therefore do not need any therapy. Patients with frequent permanent junctional re-entry tachycardia, a fast tachycardia rate and impaired left ventricular function need effective therapy. In infancy and early childhood medical therapy is recommended as a first option, whereas in older and symptomatic patients catheter ablation is an effective and safe procedure.

Adolescent↗
PubMed1998

Mitomycin C-related hemolytic uremic syndrome in cancer patients.

In rare cases mitomycin C (MMC) may induce cancer-associated hemolytic uremic syndrome, which is characterized by hemolytic anemia, thrombocytopenia and progressive renal failure. Treatment possibilities of this multisystem disease up to now remain disappointing. We report a case of MMC-related hemolytic uremic syndrome, and discuss the etiologic parameters, clinical aspects, prognosis and treatment modalities of this severe syndrome.

Adenocarcinoma↗
PubMed1998

Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate.

PURPOSE: To compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables up to 33 months of follow-up evaluation and for survival up to 45 months. RESULTS: Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain. CONCLUSION: The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens.

Administration, Oral↗
PubMed1998

Radiation-induced gastrointestinal toxicity. Pathophysiology, approaches to treatment and prophylaxis.

BACKGROUND: Gastrointestinal toxicity is frequently observed during radiotherapy of malignancies in the abdomen and pelvis. The proposed pathophysiology of radiation enteritis is complex and a variety of different treatment strategies have been suggested for the management of acute radiation-induced diarrhea. MATERIAL AND METHODS: Data are presented from an extensive review of the current literature. RESULTS: Radiation-induced diarrhea results from a variety of different pathophysiological mechanisms including malabsorption of bile salts and lactose, imbalances in local bacterial flora and changes in the intestinal patterns of motility. Up to date acute radiation diarrhea is predominantly treated symptomatically using opioide derivates (loperamide) or adsorbants of bile salts such as smectite. Clinical trials have been performed using L. acidophilus, smectite or sucralfate for diarrhea prophylaxis with moderate reduction of acute symptoms. CONCLUSIONS: Further evaluation of strategies for diarrhea prophylaxis is warranted. Due to the complex nature of radiation enteritis a multimodal approach taking into account alterations in intestinal motility patterns, malabsorption of bile salts and an imbalance of mucosal bacterial flora may offer new perspectives.

Abdominal Neoplasms↗
PubMed1997

[Role of sodium selenite as an adjuvant in radiotherapy of rectal carcinoma].

BACKGROUND: In various epidemiologic studies an association of low selenium blood levels and reduced glutathione peroxidase with an increased risk of cancer incidence was described. The antitumoral therapy and a suboptimal nutrition could intensify this deficiency. Every reduction of disease related and therapeutic caused symptoms may improve life quality. APPLICATION: We report our preliminary experiences in the adjuvant radiochemotherapy of advanced rectal cancer (UICC II/III) corresponding to the NCl recommendation. An oral selenium supplementation was carried out with 2000 micrograms Na2SeO3 after every course of fluorouracil chemotherapy and daily 400 micrograms Na2SeO3 after irradiation of tumor region and lymph nodes. A weekly life quality assessment was explored with special interest in diarrhea, dysurie, pain, appetite, nausea and emesis. CONCLUSION: Damages to normal tissue specially to DNA enzymes and membranes caused by free radicals is one mechanism in tumorgenesis, tumor progression and therapeutic consequence. A radioprotective effect of selenium is verified by in vitro and in vivo data. Our data show that oral selenium intake in rectal cancer patients is easily tolerated with no side effects. Improving life quality and secondary cancer prevention with supplementation of selenium has to be proven in prospective randomized studies.

Antioxidants↗
PubMed1997

Radiotherapy and concomitant weekly 1-hour infusion of paclitaxel in the treatment of head and neck cancer--results from a Phase I trial.

PURPOSE: To define the maximum tolerated dose (MTD) by describing the dose-limiting toxicity (DLT) of weekly paclitaxel (PAC) given as a 1-h I.V. infusion in patients with head and neck cancer concomitant to irradiation. METHODS AND MATERIALS: Patients with unresectable or incompletely resected head and neck cancer were enrolled into a prospective, dose-escalating Phase I study. Toxicity was graded according to the WHO toxicity score. MTD dose was defined when two out of six patients developed DLT. The starting dose of PAC was 20 mg/m2 once weekly I.V. over 60 min, with a subsequent dose escalation of 10 mg/m2 in cohorts of three new patients. Radiation therapy was administered in three field technique over 6-7 weeks in 2.0 Gy/daily fractions for 5 consecutive days/week up to total doses of 60-70 Gy. RESULTS: From 1994-1996, 18 patients completing three dose levels were included into the study. Altogether, 101 courses of chemotherapy were evaluable for toxicity. On the second dose level (30 mg/m2) one of three patients experienced DLT with Grade IV mucositis. On the next dose level with 40 mg/m2 PAC weekly one patient experienced DLT being prolonged Grade III mucositis. From the following three patients required, two patients showed no DLT. The third patient showed mucositis of WHO Grade 4 and died from hemorrhage caused by a rupture of the a pharyngeal wall. Dose level 2 (30 mg/m2) was repeated and one of the three newly treated patients again suffered from mucositis WHO Grade 4. CONCLUSION: When PAC is given weekly as a 1-h infusion concomitant to radiotherapy, MTD is 30 mg/m2 with mucositis being DLT; hematological and further nonhematological toxicity is mild.

Adult↗
PubMed1997

Rolling in the clover: trefoil factor family (TFF)-domain peptides, cell migration and cancer.

Trefoil factor family (TFF)-domain peptides 1-3 are mucin-associated molecules, largely found in epithelia of gastrointestinal tissues. Structurally similar, resistant to enzymatic degradation, they are up-regulated around areas of epithelial damage such as ulcers. Transgenic expression or exogenous peptide ameliorates or prevents gastric mucosal damage due to indomethacin and some are rapidly up-regulated after cryogenic burns. A role in promoting cell migration is strongly suggested. Knockout mice lacking TFF1 or TFF3 show significant pathology, with the former developing gastric tumours. A recent Conference Philippe Laudat agreed upon a new nomenclature for these peptides.

Animals↗
PubMed1997

Similarities of integumentary mucin B.1 from Xenopus laevis and prepro-von Willebrand factor at their amino-terminal regions.

Frog integumentary mucin B.1 (FIM-B.1) contains various cysteine-rich modules. In the past, a COOH-terminal "cystine knot" motif has been found that is similar to von Willebrand factor; this region is generally known to be responsible for dimerization processes. Furthermore, a "complement control protein" motif is present as an internal cysteine-rich domain in FIM-B.1. We characterize here the missing 75% toward the NH2 terminus of the FIM-B.1 precursor by molecular cloning. Analogous to prepro-von Willebrand factor, four elements with considerable similarity to D-domains are present (i.e. D1-D2-D'-D3). These domains have been described as essential for the multimerization of von Willebrand factor. Thus, the general structure of FIM-B.1 resembles that of the human mucin MUC2 as well as prepro-von Willebrand factor; these three molecules at least seem to share common structural elements allowing similar multimerization mechanisms.

Amino Acid Sequence↗
PubMed1997

Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium.

pS2-TFF 1 is expressed in breast cancers and has been investigated as a potential prognostic factor reflecting oestrogen dependence. The relationship to the expression of other trefoil peptides, human spasmolytic polypeptide (hSP-TFF 2) and intestinal trefoil factor (hITF/hPI.B-TFF 3) is documented here. Fifty-seven breast specimens were selected from surgical pathology archives and included five normal breasts (two lactating), seven benign proliferative lesions, 11 ductal carcinomas in situ (DCIS), three lobular carcinomas in situ (LCIS), 24 invasive ductal carcinomas (IDC), and seven invasive lobular carcinomas (ILC). The comparative distribution of trefoil mRNAs was assessed by in situ hybridization using 35S-labelled riboprobes and immunohistochemical staining for pS2-TFF 1 and hSP-TFF 2. pS2-TFF 1 and hITF/hPI.B-TFF 3 mRNA were focally present at low signal intensity in normal and benign breast. Both pS2-TFF 1 and hITF/hPI.B-TFF 3 were expressed in all DCIS, LCIS and ILC, and 21/24 IDC. Overall, expression patterns of pS2-TFF 1 and hITF/hPI.B-TFF 3 coincided, but hITF/hPI.B-TFF 3 mRNA was usually found in a greater proportion of cells. Expression of hSP-TFF 2 peptide or mRNA was not detected in any of these cases. MCF 7 breast carcinoma cells also expressed hITF/hPI.B-TFF 3 and pS2-TFF 1 mRNAs but not hSP-TFF 2. hITF/hPI.B-TFF 3 co-expression with pS2-TFF 1 may act as a prognostic factor, but also raises questions about the regulatory pathway for pS2-TFF 1 hITF/hPI.B-TFF 3. Trefoil factors have effects on cell motility and spreading in vitro, and co-expression of hITF/hPI.B-TFF 3 with pS2-TFF 1 could be functionally significant if they form a heterodimer or compete for receptor binding. Absence of hSP-TFF 2 expression may be of equal relevance to tumour cell biology.

Blotting, Northern↗
PubMed1997

[The use of sucralfate in radiation oncology].

PURPOSE: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. PATIENTS AND METHOD: The results of available studies are analysed and discussed. RESULTS: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. CONCLUSION: Nevertheless sucralfate is a safe, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation.

Head and Neck Neoplasms↗