Biomedical subjects

N Runkel

Publications and source records attributed to N Runkel.

At least 19 recordsLinked to original sources

PubMed2000

Expression and function of endothelial Ca(2+)-activated K(+) channels in human mesenteric artery: A single-cell reverse transcriptase-polymerase chain reaction and electrophysiological study in situ.

Ca(2+)-activated K(+) (K(Ca)) channels have been suggested to play a role in the control of endothelial functions such as regulation of vascular tone and cell proliferation. We established a method for single-cell reverse transcriptase-polymerase chain reaction analysis in combination with the patch-clamp technique to characterize K(Ca) channel expression and function in single endothelial cells (ECs) within the endothelial monolayer of intact human mesenteric arteries (MAs) and in disease states. We tested whether endothelial K(Ca) channel expression and function are altered in MAs obtained from patients with colonic adenocarcinoma (CA) compared with those in MAs from non-cancer patients with inactive diverticulitis. Expression of the intermediate-conductance K(Ca) channel (hIK1) was detected in non-cancer and CA patients. In whole-cell patch-clamp measurements, only ECs expressing hIK1 exhibited corresponding K(Ca) currents, whereas respective K(Ca) currents were missing in hIK1-negative ECs. This heterogeneity of hIK1 expression patterns is indicative of a specialized subset of ECs within the endothelial monolayer. In CA patients, compared with non-cancer patients, a 2.5-fold increase in hIK1-expressing ECs per MA was observed (P:<0.05). However, K(Ca) current densities in hIK1-expressing ECs of both groups were similar. In addition to hIK1, expression of the large-conductance K(Ca) channel (hSlo) was detected in single ECs from CA patients. The increased K(Ca) channel expression in CA patients resulted in a 2. 7-fold increase of bradykinin-induced endothelial hyperpolarization compared with controls (P:<0.05). This increased expression and function of K(Ca) channels might indicate an altered functional state of the endothelium in cancer patients and could play a role in tumor angiogenesis.

Adenocarcinoma↗

PubMed2000

[Radiotherapeutic strategies in the multimodal therapy of resectable and nonresectable pancreatic carcinoma].

BACKGROUND: The prognosis of patients with adenocarcinoma of the pancreas remains poor. Only patients with small tumors and complete resection have a curative chance. The value of combined radio-chemotherapy adjuvant or even palliative in case of unresectable tumors is controversial due to the short median survival times of all patients ranging from 8 to 15 months. Within the last years, significant new treatment modalities were introduced into the multimodality approach. Even the intraoperative boost therapy (IORT) with fast electrons remains still controversial. MATERIAL AND METHODS: Since the publication of the results of the historic GITSG study, in the US postoperative adjuvant radio-chemotherapy with 5-FU remains the treatment of choice. Successor studies of the ESPAC and the EORTC have been closed or are recruiting patients, the results are still pending. Neoadjuvant treatment modalities were investigated within the last 3 years, mostly in case of primary operable but also in unresectable tumors. Using 3-D-treatment planning, the total dose of radiotherapy was increased from 40 up to 45 to 50 Gy. In centers with great experience, an IORT was added to these combined modalities. More modern chemotherapeutic agents like gemcitabine or the taxanes are under investigation, using combined radio-chemotherapy in phase-II protocols in patients with unresectable tumors. RESULTS: In case of both, adjuvant or neoadjuvant radio-chemotherapy following or before pancreaticoduodenectomy, median survival times range from 15 to 25 months. The neoadjuvant radio-chemotherapy seems to reduce the rate of positive surgical margins and the rate of patients with positive lymph nodes. For the moment, there is no proven survival advantage or increase of local control (about 80% in both cases) for patients treated with neoadjuvant radio-chemotherapy compared with adjuvant radio-chemotherapy. However, about 25% of the patients don't receive adjuvant therapy due to the perioperative morbidity. Because prolongation of survival with adjuvant therapy is only 5 to 10 months, in Europe adjuvant radio-chemotherapy is not accepted as the treatment standard. Combined radio-chemotherapy in patients with unresectable tumors results in significant improvement of survival. 5-FU continuous infusion with 250 mg/m2 seems to be the treatment of choice. IORT is effective in achieving long-term local control and an effective pain palliation. More modern chemotherapeutic agents seem to be effective in vitro as radio-sensitizers. In first reported results, the MTD was not found. Toxicity seems not to be increased with single radiotherapy doses of 1.8 to 2 Gy. However, higher single doses should not be used. CONCLUSIONS: Due to the worse prognosis of patients with adenocarcinoma of the pancreas, new combined treatment modalities as adjuvant and neoadjuvant radio-chemotherapy, particularly with more modern chemotherapeutic agents, for patients with resectable and unresectable tumors are under investigation. For some reasons, the neoadjuvant setting seems to be better. However, these results are not proven by prospective randomized clinical trials. Therefore, these trials are necessary to define the treatment of choice in these patients. IORT is a helpful tool to improve local control. However, these aggressive multimodality approaches are only indicated in a minority of patients. In patients with unresectable tumors and good condition, combined radio-chemotherapy remains the treatment of choice.

Chemotherapy, Adjuvant↗

PubMed2000

The insertion of the lesser and greater gastric omenta and its significance for the T classification of gastric carcinomas (UICC).

The problem of T classification of proximal gastric carcinomas is becoming increasingly important due to a rise in the incidence of these tumors. The aim of this study was to examine the gastric insertion of the lesser and greater omenta and its role in the T classification of gastric carcinomas. The stomach and greater and lesser omenta were removed from 76 fixed cadavers and 12 measurements each were done in defined localizations. The lesser omentum extended to the gastric wall in 98% of the cases. This junction as well as the omental thickness and thus the retroperitoneal part are especially pronounced in the cardiac region. According to the current UICC classification, even advanced tumors extending into the gastric wall can be classified T2 as long as they do not penetrate the visceral peritoneum. This results in "understaging" and a seemingly poorer prognosis for cardiac carcinomas. Our study results support the recommendation of Hermanek and Wittekind [5] to subdivide the T2 stage of gastric carcinomas on the basis of infiltration depth.

Cadaver↗

PubMed1999

Manometric analysis of anal sphincter damage after ileal pouch-anal anastomosis.

A constant reduction in anal sphincter pressure follows an ileoanal pouch procedure for ulcerative colitis and familiar adenomatous polyposis. We analyzed whether this reduction is more likely due to neurogenic damage or to direct sphincter trauma. Three-dimensional vector volume manometry was performed in 75 patients prior to the ileoanal pouch procedure and 3 months thereafter. Resting pressure was significantly reduced from 83.5 +/- 24.4 to 58.1 +/- 18.0 mmHg and squeezing pressure from 204.7 +/- 63.3 to 173.4 +/- 50.6 mmHg. Moreover, significant vector volume reductions were recorded postoperatively, and the asymmetry index increased significantly (resting: 11.5 +/- 4.1% to 18.4 +/- 7.4%; squeezing: 9.6 +/- 3.1 to 13.0 +/- 6.7%). Functional anal sphincter length at the high-pressure zone remained unchanged. Thus, there was no local damage to proximal or distal anal sphincter segments, which suggests that the postoperative impairment of sphincter function is secondary to neurogenic rather than morphological damage.

Adenomatous Polyposis Coli↗

PubMed1999

The prognostic significance of tumor vascularization in patients with localized colorectal cancer.

Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a x200 field in the area of the most dense neovascularization. Vascular density was found to be 75+/-27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (>75) than in those of less vessel density (<75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.

Adenocarcinoma↗

PubMed1999

Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis.

BACKGROUND & AIMS: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis (UC) was performed. METHODS: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy. RESULTS: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 omega3. cm2, which in conventional analysis is masked by an increase in subepithelial resistance from 14 +/- 1 to 36 +/- 3 omega3. cm2 caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 +/- 0.25 to 4.76 +/- 0.47 at the surface and from 7.26 +/- 0.31 to 5.46 +/- 0.37 in the crypts. CONCLUSIONS: The inflamed colonic mucosa in UC has an impaired barrier function that is much more pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC.

Chloride Channels↗

PubMed1999

Co-expression of renin-angiotensin system genes in human adipose tissue.

OBJECTIVE: The renin-angiotensin system plays a central role in blood pressure regulation, both by affecting renal function and by modulating vascular tone and structure. Recent studies in rodents demonstrated the existence of several components of this system in adipose tissue. The activity of the renin-angiotensin system appears to be regulated by food intake, suggesting that it may be involved in obesity-associated hypertension. Few data are available on the presence of renin-angiotensin system components in human adipose tissue. MATERIALS AND METHODS: In order to explore the expression of renin-angiotensin system genes in human adipose tissue and adipocytes, total RNA was isolated from whole adipose tissue (subcutaneous and omental) or cultured adipocytes (mammary) and subjected to reverse-transcriptase polymerase chain reaction with primers specific for human angiotensinogen, renin, renin-binding protein, angiotensin converting enzyme, chymase and type 1 and type 2 angiotensin receptors. RESULTS: Angiotensinogen, angiotensin converting enzyme and type 1 angiotensin receptor genes were widely expressed, both in human adipose tissue and in cultured human adipocytes. Furthermore, we found expression of the chymase and renin-binding protein genes in these samples. CONCLUSIONS: Our findings suggest the presence of a local renin -angiotensin system in human adipose tissue, with adipocytes being an important part of this system, and prompt speculation that this local renin-angiotensin system may be involved in obesity-related disorders, including hypertension and the metabolic syndrome.

Adipose Tissue↗

PubMed1999

[Cavernous hemangioma of the rectum--a rare differential per anal hemorrhage diagnosis].

A 19-year-old woman suffered from recurrent peranal hemorrhage. Over a period of five years she was treated under the suspicion of ulcerative colitis. After a sigmoid resection with a colostomy, proctectomy with an end colostomy followed due to recurrent intractable peranal hemorrhage. Histology of the specimen showed surprisingly a hemangioma of the rectum. Thereafter reconstruction was performed by colopouchanal anastomosis. Afterwards the patient was free of disease and had a good stool-continence. Stool-frequency was twice daily. The second case consisted in a 27-year-old woman who underwent emergency sigmoidectomy due to massive peranal hemorrhage. Here as well diagnosis was a hemangioma of the sigmoid. One year after the first operation the patient had a recurrence of peranal bleeding again due to rectal hemangioma. Since endoscopy and endosonography confirmed a rectal hemangioma a rectal exstirpation with a colopouchanal reconstruction was performed successfully. The reviewed literature shows including the two presented cases a total of 81 cases with rectal hemangiomas. Because of the good results concerning function and morbidity the therapy of choice is rectal exstirpation with colopouchanal reconstruction.

Adult↗

PubMed1998

[Duodeno-caval fistula: a rare cause of upper gastrointestinal hemorrhage].

Non-traumatic duodenocaval fistulae are rare, but may be the source of massive gastrointestional bleeding with associated fever and sepsis. These fistulae result from penetrating duodenal peptic ulcers or right nephrectomy and subsequent radiation to the upper abdomen. The outcome depends on early diagnosis and surgery before a potentially fatal hemorrhage occurs. The therapy of choice includes closure of the fistula and repair of the duodenum and inferior vena cava. We describe the seventh case with radiogenic duodenal ulcer. Gastrointestinal bleeding occurred 10 years after radical nephrectomy and radiation (60 Gy). The patient survived following partial pancreatoduodenectomy (Whipple).

Adult↗

PubMed1998

Extent of surgery and recurrence rate of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic fistula- and abscess-forming disease of the cutis and subcutis of unknown etiology. Disease recurrence is frequent and may cause severe complications. We analyzed patients with HS who underwent surgery between 1976 and 1997. The operative procedures were divided into drainage procedures (n = 6), limited regional (n = 14), and radical wide excisions (n = 11). The extent of surgery was examined in terms of the clinical course and late postoperative sequelae of HS. At a mean follow-up of 72 months, we found developed locoregional recurrent HS in 45% of patients. There was 100% recurrence after drainage, 42.8% after limited, and 27% after radical excision (P < 0.05). HS recurred after a median interval of 3 months for drainage, 11 months for limited excision, and 20 months for radical excision (P < 0.05). The disease-free interval continued up to 35 months. Long-term sequelae included penile amputation and a case of fatal squamous cell carcinoma. Although radical wide excision of the HS-affected cutis is associated with the lowest recurrence rate, it is still considerable and warrants long-term follow-up.

Adult↗

PubMed1998

Pouchitis: pathophysiology and treatment.

Pouchitis is a potential complication after proctocolectomy and restorative ileoanal anastomosis. It is more frequent in UC than in familial polyposis. Little is known about the etiopathology of pouchitis. Risk factors include the presence of extraintestinal manifestations, primary sclerosing cholangitis, cessation of smoking, and previous course of disease. A host of pathophysiological pathways have been identified as potential mechanisms of pouchitis, which include inflammatory mediators, adhesion molecules, oxygen radical species, p-ANCA, and short-chain fatty acids. The microflora in the pouch may also be an important factor in causing inflammation. The risk of developing cancer in cases of pouchitis has not been established as clearly as in those of UC. Particular attention should be paid to patients who have remaining anorectal mucosa after pouch construction. Experience in the treatment of chronic relapsing and chronic refractory pouchitis is limited. The continuation of conventional anti-inflammatory treatment is successful only in a small percentage of patients. New biological response-modifying therapies which target novel immunoregulatory molecules in IBD will also have impact on the systemic and topical treatment of pouchitis.

Colitis, Ulcerative↗

PubMed1998

Radical resection in obstructing colorectal carcinomas.

Emergency resections of obstructing colorectal carcinomas usually involve only limited rather than radical lymphadenectomy, which may contribute to the poor long-term survival of these patients. Thirty patients with ileus due to colorectal cancer have been included in a prospective follow-up study since January 1995. Seventeen of these underwent potentially curative resections with radical locoregional lymphadenectomy according to current standards of elective oncological surgery; 2 had radical right and 15 had radical left hemicolectomies. Postoperative morbidity was 18%. An 89-year-old patient died following postoperative bleeding from the colostomy site. During the same period, 13 patients with a metastasizing colorectal carcinoma underwent palliative emergency surgery with a resection rate of only 38%. Morbidity and mortality were 69% and 46%, respectively. These results suggest that emergency radical resections can be safely performed in the majority of patients with obstructing colorectal cancer without increasing the complication rate.

Adult↗

PubMed1998

Surgical training and vocal-cord paralysis in benign thyroid disease.

INTRODUCTION: Operations performed by a trainee surgeon should not result in a higher risk of complications. However, there is little information about identifying risk factors for primary surgery of benign, non-autoimmune goiter. METHODS: This study correlates experience of the surgeon and other potential risk factors with palsy rates of the recurrent laryngeal nerve over an 18-month period. Radical removal of all nodular thyroid tissue and principal nerve identification were standard procedures. RESULTS: Of a total of 405 operations per side, 55.8% were subtotal resections, 11.8% extended subtotal (near total) resections and 33.1% lobectomies. The overall initial and permanent palsy rates of "nerves at risk" were 8.9% and 1.2%, respectively. Patients' age, gender and weight, as well as endocrine activity of the thyroid gland were not associated with increased complications. CONCLUSION: The risk of nerve damage increased significantly and independently with size of goiter and extent of resection, but did not correlate with the surgical experience. In conclusion, the training of surgeons is safe if cases are carefully selected and the surgeons in training are supervised.

Clinical Competence↗

PubMed1998

Serum cardiac troponin T as a prognostic marker in early sepsis.

STUDY OBJECTIVE: Sepsis is the leading cause of death in the noncardiologic ICU. Maldistributed nutritive blood flow and altered convective and diffusive oxygen transport during sepsis can lead to organ dysfunction and multiple organ failure. One of the causes of myocardial dysfunction is thought to be myocardial ischemia in sepsis; however, conventional biochemical parameters to detect myocardial ischemia lack sensitivity and specificity. Serum cardiac troponin T (S-TnT) was reported to have higher sensitivity and specificity in diagnosing minor myocardial injury. The aim of this study was to investigate if and how often S-TnT is pathologically elevated in patients with sepsis and to evaluate whether S-TnT might be a prognostic marker in early sepsis. DESIGN: Prospective study. SETTING: Surgical ICU. PATIENTS: Twenty-six patients with sepsis were included in this study within 24 h of the onset of sepsis. The patients were allocated a priori to a high S-TnT group (S-TnT > or = 0.2 microg/L) and a low S-TnT group (S-TnT<0.2 microg/L). MEASUREMENT: Blood samples for the determination of S-TnT and conventional myocardial ischemia markers as well as for adhesion molecules were drawn. Hemodynamic measurements were performed every 4 h during the first 24 h and then once per day over 7 days. S-TnT was determined by enzyme-linked immunosorbent sandwich assay. RESULTS: Eighteen patients had pathologically high S-TnT values. High S-TnT values were associated with an increased mortality rate (15/18 in the high S-TnT group vs 3/8 in the low S-TnT group; p=0.02). Significant differences between the two groups were found in the norepinephrine dosages at maximum values of S-TnT. Soluble intercellular adhesion molecule-1 was significantly elevated in the high S-TnT group. CONCLUSIONS: As high S-TnT values were associated with an increased mortality rate, it seems reasonable to further evaluate S-TnT as a prognostic marker of myocardial ischemia in patients with sepsis under different therapeutic regimens.

Adult↗

PubMed1998

[Lack of effect of EGF on epithelial barrier function in experimental TNBS colitis].

This study tested the hypothesis that EGF has a protective effect on the intestinal barrier function in experimental TNBS-induced colitis. EGF was given intraperitoneally one hour before and 24 hours after induction of colitis. The rats were killed 48 hours after induction of colitis: The distal colon was resected and mounted into Ussing chambers. Flux measurements were performed for Na+ and mannitol, and epithelial and subepithelial resistances were determined. A semiquantitative histological score was used to grade acute and chronic inflammation. Compared to controls, TNBS caused a 3-fold increase in both fluxy, indicating enhanced paracellular permeability. There rates was a severe reduction of total and epithelial resistances indicating a dramatic defect of epithelial barrier function. EGF failed to improve the electrophysiologic and histologic parameters. Therefore, EFG has no protective effective in experimental TNBS colitis.

Animals↗

PubMed1998

[Zinc acts as a protective agent on the mucosal barrier in experimental TNBS colitis].

The aim of this study was to analyze the effect of enterally given zinc on the impaired epithelial barrier function in experimental TNBS colitis in rats. Rats in therapy group were zinc-fed in therapeutic dose. 48 hours after induction of TNBS colitis the rats were killed, the distal colon was resected and mounted into an Ussing chamber. The following electrophysiological measurements were carried out: 1. Flux measurements for Na+ and mannitol as a parameter of paracellular permeability, 2. Resistance measurements of the colon, distinguishing between pure epithelial resistance and resistance of the subepithelial tissue. In TNBS colitis we found a marked increase of both fluxes as a parameter of enhanced paracellular permeability (factor 3). Further there was a drastic reduction of total resistance, and especially of pure epithelial resistance indicating a massive epithelial barrier defect. In rats treated by zinc the increase of paracellular permeability was increased only by a factor of 2, and there was only a moderate decrease of resistance. For the first time we demonstrated zinc to have a protective effect on damaged mucosal barrier function in TNBS colitis. These results confirm the data collected in guinea pigs with malnutrition, whose intestinal integrity could be improved by zinc. Further studies are necessary in order to test whether this protective effect of zinc on mucosa barrier in experimental colitis may be relevant also in human ulcerative colitis.

Administration, Oral↗

PubMed1998

[Different mechanisms in intestinal paralysis in edematous and necrotizing pancreatitis of the rat].

The influence of experimental pancreatitis on bowel motility was measured in vivo with the propulsion technique and in vitro as contractility of isolated ileum muscle strips. In edematous pancreatitis, propulsion was reduced but contractility was normal. Both, propulsion and contractility were reduced in necrotizing pancreatitis. The intravenous saline infusion normalized propulsion in edematous pancreatitis but was of no benefit in necrotising pancreatitis. These results indicate that extraintestinal (neuroendocrine) regulation pathways were effected in edematous pancreatitis. Necrotising pancreatitis appears to have an additional profound influence on the intrinsic, intramural regulation of motility.

Animals↗

PubMed1998

[Changes in permeability after ileoanal pouch anastomosis and in pouchitis].

The aim of the present study was to determine the changes in permeability and mucosal function after ileo-pouchanal anastomosis (IPAA) in patients with ulcerative colitis. We examined 24 patients (m: f = 15:9; Age = 35.2 +/- 12.5) prior to colectomy (pre IPAA), prior to closure of ileostomy (pre CIS), after closure of ileostomy (post CIS), in case of pouchitis and 5 controls. With a miniaturizised Ussing-chamber electrophysiological parameters of permeability and resorptive isotope-fluxes for mannitol were measured. Total resistance could be differenciated into epithelial and subepithelial resistance by using alternating current impedance measurements. Active Na(+)-glucose-Cotransport was measured by detection of the maximal short-curcuit-current under stepwise addition of glucose and active Cl(-)-secretion was measured by the increase in short-curcuit-current after stimulation with Theophillin and PGE2. Epithelial resistance of pouchitis was slightly raised towards controls but did not differ from the others. Subepithelial resistance post CIS and pouchitis was significantly increased versus controls and pre CIS (21.2 +/- 22.4 vs. 10.7 +/- 13.3 omega cm2) Whereas Cl-secretion of pouchitis was significantly reduced vs. post CIS and controls (38.6 vs. 120.9 +/- 113.9 microA cm-2). In the same way Na(+)-glucose Cotransport of pouchitis was significantly reduced vs. post CIS and controls(41.8 vs. 138.4 +/- 264.4 microA cm-2). Increasing subepithelial resistance post CIS and in pouchitis is a hint for an adaptive thickening of the subepitheal layer. Concerning the functional analysis pouchitis and terminal ileum prior to IPAA show a reduced secretion and resorption whereas the mucosal barrier towards Mannitol remains unchanged.

Biopsy↗