Biomedical subjects

G Späth

Publications and source records attributed to G Späth.

At least 19 recordsLinked to original sources

PubMed2005

[Vaginal foreign body -- cause for a rectovaginal fistula].

A case of 56-year-old patient is presented with the diagnosis "carcinoma of the cervix". She suffered from brown, bad smelling vaginal discharge since half a year without any pain. Three weeks before she had noticed a postmenopausal bleeding. At the examination under anaesthesia with cysto- and rectoscopy we saw a rectovaginal fistula. In the vagina a white plastic object was found which could not be removed. Some days later a hysterectomy with extraction of the foreign body (aerosol cap) was done and the fistula was treated together with the surgeons. There was no evidence of a carcinoma. The patient suffers from multiple sclerosis since 20 years. On asking she told us that the foreign body was in place since about two years. She was not willing to relate any other information.

Female↗

PubMed2000

The role of phosphoglycans in Leishmania-sand fly interactions.

Leishmania promastigotes synthesize an abundance of phosphoglycans, either attached to the cell surface through phosphatidylinositol anchors (lipophosphoglycan, LPG) or secreted as protein-containing glycoconjugates. These phosphoglycans are thought to promote the survival of the parasite within both its vertebrate and invertebrate hosts. The relative contributions of different phosphoglycan-containing molecules in Leishmania-sand fly interactions were tested by using mutants specifically deficient in either total phosphoglycans or LPG alone. Leishmania donovani promastigotes deficient in both LPG and protein-linked phosphoglycans because of loss of LPG2 (encoding the Golgi GDP-Man transporter) failed to survive the hydrolytic environment within the early blood-fed midgut. In contrast, L. donovani and Leishmania major mutants deficient solely in LPG expression because of loss of LPG1 (involved in biosynthesis of the core oligosaccharide LPG domain) had only a slight reduction in the survival and growth of promastigotes within the early blood-fed midgut. The ability of the LPG1-deficient promastigotes to persist in the midgut after blood meal excretion was completely lost, and this defect was correlated with their inability to bind to midgut epithelial cells in vitro. For both mutants, when phosphoglycan expression was restored to wild-type levels by reintroduction of LPG1 or LPG2 (as appropriate), then the wild-type phenotype was also restored. We conclude, first, that LPG is not essential for survival in the early blood-fed midgut but, along with other secreted phosphoglycan-containing glycoconjugates, can protect promastigotes from the digestive enzymes in the gut and, second, that LPG is required to mediate midgut attachment and to maintain infection in the fly during excretion of the digested blood meal.

Agglutinins↗

PubMed1998

Microbial translocation and impairment of mucosal immunity induced by an elemental diet in rats is prevented by selective decontamination of the digestive tract.

OBJECTIVE: To assess the effect of selective decontamination of the digestive tract (SDD) on intestinal secretory immunoglobulin A (sIgA) concentrations in a model of intestinal bacterial overgrowth and bacterial translocation induced by an elemental diet in rats. DESIGN: Laboratory study. SETTING: University hospital, Germany. MATERIAL: 45 specific pathogen free female Crl:CD(R) BR rats. INTERVENTIONS: For 7 days, 3 groups of rats were fed orally with standard chow (n = 15), total parenteral nutrition solution (ORAL-TPN, n = 15), or ORAL-TPN plus tobramycin (20 mg/L) and polymyxin E (25 mg/L) (ORAL-TPN + SDD). MAIN OUTCOME MEASURES: Bacterial translocation to mesenteric lymph nodes (MLN), numbers of gram negative enterobacteria and total aerobic bacteria in the caecum, and intestinal concentrations of sIgA. RESULTS: The incidence of bacterial translocation was significantly increased in the group given ORAL-TPN (8/15, 53%) compared with the group given chow (1/15, 7%, p < 0.01). Supplementation of ORAL-TPN with SDD reduced translocation to 0/15. The ORAL-TPN group had a pronounced overgrowth of aerobic bacteria in the caecum, mainly by gram negative enterobacteria, which was prevented by the SDD. The concentrations of intestinal sIgA were significantly reduced in the ORAL-TPN group. SDD resulted in both the soluble and insoluble sIgA fractions in the gut being within the reference ranges. CONCLUSION: SDD prevents gram negative caecal overgrowth and translocation to MLN in rodents fed on ORAL-TPN. The significantly reduced mucosal immunity caused by ORAL-TPN alone is restored by SDD, although one might have expected a further reduction in sIgA concentrations with lower microbial populations than in the ORAL-TPN group. Not only does SDD not seem to affect the mucosa associated immune system adversely, but also depressed mucosal immunity was restored.

Administration, Oral↗

PubMed1998

Phenotypic effects of the forced expression of HNF4 and HNF1alpha are conditioned by properties of the recipient cell.

Tagged versions of HNF4 or HNF1alpha cDNAs in expression vectors have been introduced by transient and stable transfection into three cell lines of hepatic origin that all fail to express these two liver-enriched transcription factors and hepatic functions. C2 and H5 cells are dedifferentiated rat hepatoma variants and WIF12-E cells are human fibroblast-rat hepatoma hybrids with a reduced complement of human chromosomes. Transfectants were analyzed for the expression state of the endogenous genes coding for these transcription factors and for hepatic functions. Each cell line showed a different response to the forced expression of the transcription factors. In C2 cells, no measurable effect was observed, either upon transitory or stable expression. H5 cells reexpressed the endogenous HNF4 gene only upon transient HNF1alpha transfection, and the endogenous HNF1alpha gene only in stable HNF4 transfectants. WIF12-E cells responded to the forced transient or stable expression of either HNF1alpha or HNF4 by cross-activation of the corresponding endogenous gene. In addition, the stable transfectants reexpress HNF3alpha and C/EBPalpha, as well as all of the hepatic functions examined. Hybrid cells similar to WIF12-E had previously been observed to show pleiotropic reexpression of the hepatic phenotype in parallel with loss of human chromosome 2. For the stable WIF12-E transfectants, it was verified that reexpression of the hepatic phenotype was not due to loss of human chromosome 2. The demonstration of reciprocal cross-regulation between HNF4 and HNF1alpha in transient as well as stable transfectants implies that direct effects are involved.

Animals↗

PubMed1997

Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes.

Hepatocyte growth factor induces proliferation, motility and differentiation of epithelial cells through the tyrosine kinase receptor encoded by the MET protooncogene. The cytoplasmic portion of Met (referred to as cyto-Met) is activated but only weakly transforming. In order to determine the effect of activated Met on hepatocytes, we have targeted truncated Met expression to the liver by incorporating the cDNA into a vector carrying the entire human alpha-1-antitrypsin transcriptional unit. Transgenic expression in the liver of truncated human Met, containing the regulatory and the catalytic cytoplasmic domains, renders hepatocytes constitutively resistant to apoptosis and reproducibly permits immortalization. The emerging stable cell lines are not transformed and maintain a highly differentiated phenotype judged by the retention of epithelial cell polarity and the expression of hepatocyte-enriched transcription factors as well as hepatic products.

Animals↗

PubMed1997

Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients.

OBJECTIVE: To determine if early postoperative feeding of patients with upper gastrointestinal malignancy, using an enteral diet supplemented with arginine, dietary nucleotides, and omega-3 fatty acids (IMPACT, Sandoz Nutrition, Bern, Switzerland) results in an improved clinical outcome, i.e., reduced infectious and wound complications and decreased treatment costs when compared with an isocaloric, isonitrogenous control diet. DESIGN: A prospective, randomized, placebo-controlled, double-blind, multicenter trial of the clinical outcome and a retrospective cost-comparison analysis. SETTING: Surgical intensive care units in three different German university hospitals. PATIENTS: Of 164 patients enrolled in the study, 154 patients were eligible for analysis. They were admitted to the intensive care unit after upper gastrointestinal surgery for cancer and they received an enteral diet via needle catheter jejunostomy. Infectious complications were defined as sepsis or systemic inflammatory response syndrome, pneumonia, urinary tract infection, central venous catheter sepsis, wound infection, and anastomotic leakage. The complication events were prospectively divided into two groups: early (postoperative days 1 to 5) and late (after the fifth postoperative day) postoperative complications. The treatment costs of each complication were analyzed and compared in both groups. INTERVENTIONS: Patients were randomized to receive either the immunonutritional diet (n = 77) or an isocaloric and isonitrogenous placebo diet (n = 77). Enteral feeding was initiated 12 to 24 hrs after surgery, starting with 20 mL/hr and advanced to a target volume of 80 mL/hr by postoperative day 5. MEASUREMENTS AND MAIN RESULTS: Clinical examination and adverse gastrointestinal symptoms were recorded on a daily basis. Both groups tolerated early enteral feeding well, and the rate of tube feeding-related complications was low. Postoperative complications occurred in 17 patients in the immunonutrition group vs. 24 patients in the control group (NS). Further, in the early phase (postoperative day 1 to 5), complications occurred to a similar extent in both groups (12 patients in the immunonutritional group vs. 11 patients in the control group). However, in the late phase (after postoperative day 5), considerably fewer patients in the experimental diet group experienced complications compared with the control group (5 vs. 13, p < .05). In addition, the frequency rate of complicating events were recorded in each group. In the experimental diet group, a total of 22 complicating events were recorded vs. a total of 32 events in the placebo diet group (NS). However, the occurrence of late complicating events, i.e., complicating events after the fifth postoperative day, was significantly reduced in the immunonutrition group when compared with the control group (8 vs. 17 events, p < .05). The total costs for the treatment of the complications were 83,563 German marks in the experimental diet group vs. 122,430 German marks in the control group, resulting in a cost-reduction of 38,867 German marks. (At the end of December 1995, the conversion rate from German marks to U.S. dollars was 1.4365 German marks to $1.00.) CONCLUSIONS: Early enteral feeding with an arginine, dietary nucleotides, and omega-3 fatty acids supplemented diet, as well as an isonitrogenous, isocaloric control diet (placebo) were well tolerated in patients who underwent upper gastrointestinal surgery. In patients who received the supplemented diet, a significant reduction in the frequency rate of late postoperative infectious and wound complications was observed. Thereby, the treatment costs were substantially reduced in the immunonutrition group as compared with the control group.

Adolescent↗

PubMed1996

"High-dose" radioiodine therapy in advanced differentiated thyroid carcinoma.

UNLABELLED: There is yet no consensus concerning the appropriate regimen of the application of [131I]sodium iodine (Nal) activities to patients suffering from advanced differentiated thyroid carcinoma. We report on a total of 167 applications of [131I]Nal, including 78 applications of 11.1 GBq. Response to high-activity radioiodine therapy (RIT) is correlated to the course of the disease as well as to the reaction of thyreoglobulin and acute/subacute side effects of radiation. METHODS: Following radioablation of thyroid remnants using 1.85 to 3.7 GBq[131I]Nal, 26 patients with advanced differentiated thyroid carcinoma (follicular, 11; papillary, 4;mixed-cell thyroid carcinoma, 11) were treated with repeated activities of 11.1 GBq[131I]Nal. Initial tumor staging according to UICC showed T4 in 54%, T3 in 19%, T2 in 19% and was not obtained in 8%. Differentiated thyroid carcinoma was multifocal in 23% of patients. Applied accumulated activities ranged from 14.8 to 99.9 GBq with a mean of 55.5 GBq per patient. RESULTS: Mean post-diagnostical follow-up was 73 mo, mean follow-up after diagnosis of metastatic spread was 48 mo. Follicular thyroid carcinoma remained as stable disease in 7 of 11 patients, 6 of whom showed metastatic disease after a mean of 20 mo, and only 1 complete remission was achieved using high-dose therapies, with progressive disease in the remaining patients. Overall, 73% of follicular thyroid carcinoma had progressive disease without major response to high-activity RIT. In contrast, only 20% of papillary thyroid carcinoma/mixed-cell thyroid carcinoma showed progressive disease, and complete remission was achieved in 47% of patients. Pulmonary and lymph node metastases in the majority of patients showed good response to therapy, whereas local recurrences and bone metastases showed minor reactions to RIT. After low-activity therapies 8% of patients showed WHO grade I hematotoxic reactions. After high-activity therapies, 38% of patients had WHO I, 8% WHO II and one patient had WHO III toxicity (4%). CONCLUSION: Use repetitive high-activity RIT with a maximum of 44.4 GBq applied during 1 yr and a maximum of 99.9 GBq accumulated activity resulted in a significant increase of hematotoxicity. However, during the follow-up period (mean, 4 yr), no clinical symptoms possibly related to low blood counts were seen in patients with advanced differentiated thyroid carcinoma. Initiation of high-activity RIT in reaction to metastatic tumor outspread to achieve complete remission was found to be useful in treating papillary thyroid carcinoma and mixed-cell thyroid carcinoma, but only in a minority of follicular thyroid carcinoma patients.

Adenocarcinoma, Follicular↗

PubMed1995

[Scintigraphy of the parathyroid glands with 99mTc-MIBI].

AIM: Since about 3 years 99mTc-MIBI is used instead of 201Tl/99mTc subtraction scintigraphy for the localization of parathyroid involvement in hyperparathyroidism (HPT). The sensitivity of the new method was evaluated. PATIENTS AND METHODS: 24 patients aged between 28 and 83 years with surgically confirmed primary HPT were studied. Planar images were acquired 15 minutes and 3 hours after tracer injection. Additionally, in 9 patients dynamic images were obtained for 2 hours to study tracer kinetics. RESULTS: 19 out of 24 adenomas (79%) were identified correctly with 99mTc-MIBI. CONCLUSION: The sensitivity of the scintigraphy using 99mTc-MIBI is in the range of the 201Tl/99mTc subtraction scintigraphy. Because of the superior logistic and the lower radiation exposure, 99mTc-MIBI can replace the 201Tl/99mTc scintigraphy in the preoperative diagnostic assessment.

Adenoma↗

PubMed1995

[Can selective decontamination of the digestive tract as a routine procedure on intensive care units be recommended?].

After giving an overview on the epidemiological and microecological background, the applicable drugs, and the necessary microbiological surveillance for Selective Decontamination of the Digestive tract (SDD), the results of 2 new metaanalyses of 22 and 25 individual randomized studies are discussed. A 50%-reduction of the pneumonia incidence results in an only marginal reduction of the mortality rate in the subgroup of topically plus for the first few days systemically treated patients in mixed intensive care units. Facing the weak prognostic relevance of ventilator pneumonia, the reduction of microbial translocation from the lower GI tract as a major goal for SDD is discussed. The chance and the need to confirm a mortality benefit in multicentre trials enrolling large numbers of homogeneous surgical patients are explained. At the present time, SDD as a routine can not (yet) be recommended.

Anti-Bacterial Agents↗

PubMed1994

[Changes in the blood picture after radioiodine therapy of thyroid cancer].

AIM: In this study the effect of radioiodine which was administered because of thyroid carcinoma on blood count and various other parameters was examined. PATIENTS AND METHODS: In 567 patients who had been treated because of a thyroid carcinoma between 1980 and 1990 with radioiodine, changes of hemoglobin, RBC, WBC, platelets, potassium, uric acid, gamma GT, GOT, GPT and AP were measured in correlation with the totally administered dose. RESULT: In low doses (< 18.5 GBq [500 mCi]), which are sufficient in most cases with clinical course without complications, relevant changes of blood count (hemoglobin: < or = 9.0/10.5 g/dl, RBC: < or = 3.1/3.5 10(12)/l (female/male), WBC: < or = 2.5 10(9)/l, platelets: < or = 0.5 10(11)/l) were observed in only 5 out of 469 cases. After moderate doses (> or = 18.5 GBq [500 mCi] and < 37 GBq [1000 mCi]) we found in only 1 out of 77 cases relevant changes. After very high doses (> or = 37 GBq [1000 mCi]), which are used to treat metastases and/or recurrences, thrombopoesis is most sensitive to the radiation exposure of the bone marrow. Relevant decrease of RBC and WBC were observed in 2 out of 21 patients. Pancytopenia (hemoglobin: < or = 12.0/13.5 g/dl, RBC: < or = 3.9/4.3 10(12)/l [female/male], WBC: < or = 3.5 10(9)/l, platelets: < or = 1.4 10(11)/l) occurred in 4 cases. CONCLUSION: In high-dose therapy with radioiodine frequent (monthly, but in any cases before each therapy) controls of blood count are necessary. In patients without metastases or recurrence no relevant changes can be expected in most cases.

Adolescent↗

PubMed1994

[Microbial translocation from the gastrointestinal tract--pathophysiologic phenomenon or catalyst for multiple organ failure?].

The constant passage of intestinal microorganisms and endotoxin into the gut associated immune system is an important physiological process for its optimal function. Under the conditions of disturbed microflora homeostasis, impaired mucosal permeability, and immunocompromisation, translocation is pathologically increased both in the animal experiment and in man. The clinical relevance of increased translocation is not yet definitively established. But from lots of evidence it seems that in the immunocompromised critically ill with systemic inflammatory response syndrome/sepsis, microbial translocation plays an important role for the eventual outcome towards multiple-organ-failure. Our therapeutic efforts have to concentrate on protection of the gut mucosa by maintaining adequate splanchnic blood flow and providing early enteral nutrition.

Acute-Phase Reaction↗

PubMed1992

Arterial, portal or combined arterio-portal regional chemotherapy in experimental liver tumours?

The most appropriate route for regional administration of chemotherapeutic drugs to liver tumours was studied in a standardized rodent model: cells of Novikoff hepatoma were transplanted into the central liver lobe of Sprague-Dawley rats. From day 5 to day 12 after transplantation, the liver was continuously perfused with 420 mg/kg 5'-fluoro-2-deoxyuridine by subcutaneous osmotic micropumps via the hepatic artery (n = 20), the portal vein (n = 20) or both vessels together (n = 12). The tumour multiplication factor (TMF) and the vascularization of the tumour were evaluated. Arterial and combined infusion led to a highly significant reduction in TMF, but combined infusion was not more effective than arterial alone. Portal infusion had no significant effect. There was no correlation between vascularization and tumour response in arterial infusion, but a strong correlation in portal infusion. Thus chemotherapy via the portal route may be effective in selected tumours with considerable portal vascularisation.

Animals↗

PubMed1990

[Massive hemorrhage from an "esophageal tumor": thoracic aortic aneurysm rupturing into the esophagus].

We report on an arteriosclerotic aneurysm of the descending aorta penetrating into the esophagus. On endoscopy it mimicked a bleeding esophageal tumour. The typical clinical course of aortoesophageal fistulas (AEF) exhibits Chiari's triad of midthoracic pain, sentinel arterial hemorrhage, usually hematomesis, and final exsanguination after a symptom-free interval. The various causes of AEF are discussed together with the respective diagnostic and therapeutic problems.

Aged↗

PubMed1988

[Magnesium in cardiology. A challenge for new studies].

Magnesium has been a controversial issue in cardiology for a long time. The following facts are now known: Magnesium plays a decisive role in the treatment of malign ventricular rhythm disturbances; this is especially true for Torsade pointes, which is connected with post-depolarisation and frequently causes sudden cardiac death. In the critical infarction phase intravenous magnesium therapy results in a reduction of malign rhythm disturbances and of the mortality rate. Magnesium plays a role in glycoside intolerance in patients with congestive heart failure. Magnesium deficiency is an important but rather neglected intermediary factor for the occurrence of (avoidable) side effects of renal, ototoxic and cardiac nature, emerge when using cytostatics, immunosuppressives and antibiotics. In several types of poisoning, but also in many other emergency situations with high levels of catecholamine (tetanus, phaeochromocytoma) magnesium can be used as an antidote. Clinically significant situations in which the role of magnesium has been either demonstrated or is still to be determined include diabetes (frequent deficiency demonstrated, significance for late complications under review), alcohol abuse (frequent deficiency of magnesium and its significance for rhythm disturbances demonstrated, correlations with other complications under review), tetanic syndrome, numerous psychiatric-neuromuscular disturbances, including generalized convulsive attacks, transitional syndromes, thromboembolic complications, lipometabolism disturbances, TIAS, PRINDS and loss of hearing.

Arrhythmias, Cardiac↗

PubMed1988

Continuous or bolus chemotherapy with 5-fluoro-2'-deoxyuridine in transplanted experimental liver tumors?

The effect of continuous and discontinuous locoregional chemotherapy with Floxuridine (FUdR) was studied in a standardized and controlled animal model, using the transplantable Novikoff hepatoma in Sprague-Dawley rats. The liver was perfused after transplantation with a total of 420 mg/kg FUdR, via a fully implanted osmotic minipump or miniport and catheter in the hepatic artery, either continuously (n = 22) from day 5 to day 12, or discontinuously (n = 28) on days 5 and 8. Viable tumor volume and peritumorous cell infiltration were measured. No reduction in tumor volume was attained using discontinuous therapy, in contrast to a highly significant reduction using continuous therapy (P less than 0.001). Significantly less cell infiltration was found after discontinuous than after continuous therapy. In conclusion, continuous locoregional chemotherapy with FUdR was the superior administration method on measurable tumor effect, when compared to discontinuous infusion.

Animals↗

PubMed1987

Complications and efficacy of transsternal thymectomy in myasthenia gravis.

Between January 1977 and September 1985, 75 patients in our department underwent elective surgery for myasthenia gravis through a median sternotomy. The main prerequisite was optimal stabilization by medical treatment with the best possible vital capacity. The Osseman types were as follows: type I (22), type IIa (19), type IIb (26), type III (7), and type IV (1). All patients, except for 3 who were mechanically ventilated for a few hours after surgery, were immediately extubated at the end of the operation. The most frequent histologic finding was thymic hyperplasia (36%); 21.3% of the patients had thymomas. No surgery-related deaths occurred. Wound healing was impaired in 6.7% of the patients, including one patient with complete sternal instability, while 5.3% developed pneumonia. The most serious complications were myasthenic (9.3%) and cholinergic (2.7%) crises. Paresis of the phrenic (2.7%) and recurrent laryngeal (1.3%) nerves occurred only in the thymoma patients, who also had a higher frequency of all other complications. The effect on the myasthenic symptoms 3 months after surgery was as follows: 7.5% of the patients were in complete remission, 61.2% had improved, 9% had deteriorated. In a logistic regression model, the parameters age, sex, duration of disease, Osserman type, histology, pre-operative antibody titer to acetylcholine receptors, and post-operative change in titer were examined with respect to their influence on the effect of surgery. Only thymic histology had an appreciable influence (p = 0.057). The effect of these parameters on the success of surgery as well as the type and frequency of complications in relation to perioperative procedure are discussed in detail.

Adolescent↗

PubMed1987

[Thymoma--a retrospective study of 48 cases].

Of the 48 thymomas operated on between 1968 and 1985 50% were associated with myasthenia gravis, in 25% diagnosis was made due to accidental X-ray findings. In the staging according to Masaoka et al. [10] the following distribution was noted: I:22, II:5, III:18, IV:3. The 5-year survival rate of the 37 curatively resected patients was 78.5% (stage I: 88.6%, stage III: 55.6%). No stage III patient with residual tumor survived more than 2 years. Predominantly epithelial tumors had a significantly worse prognosis as compared to those with lymphocytic predominance. None of the 4 patients with category II thymoma survived more than 15 months. Association with myasthenia proved to have a negative prognostic influence in stage I and II patients. Frequency of local recurrences and metastases is documented. The value of irradiation and chemotherapy is discussed.

Adolescent↗

PubMed1986

[Clinical course following thymoma extirpation].

The authors report on 48 thymomas operated on between 1968 and 1985. The survival curve of the 37 (77.1%) totally resected patients showed a marked decrease during the first year postoperatively to 85.8%. The 5-year-survival-rate was 78.5%. Predominantly epithelial thymomas had a significantly worse prognosis than those with lymphocytic predominance. Associated myasthenia gravis (21 of the totally resected patients) as well as invasion beyond the capsule proved to be of negative prognostic significance. Even in cases of gross invasion into neighbouring organs a curative resection was followed by a markedly better prognosis than a mere biopsy or partial resection plus radiotherapy.

Follow-Up Studies↗