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Biomedical subjects

P Hildebrand

Publications and source records attributed to P Hildebrand.

At least 19 recordsLinked to original sources

Surgery for right-sided colonic diverticulitis: results of a 10-year-observation period.

INTRODUCTION: In contrast to sigmoid diverticular disease, right colonic diverticulitis is a rare disease in Western countries. The clinical presentation is often similar to acute appendicitis. OBJECTIVE: The aim of this study was to analyze surgical challenge in right-sided diverticulitis. MATERIALS AND METHODS: All patients who underwent resection for both right-sided and sigmoid diverticular disease were registered prospectively in a database (observation period, 1996-2005). A retrospective analysis of all patients who underwent resection for right-sided colonic diverticulitis (ileocolic resection, right colectomy) was performed. Special focus was set on incidence, clinical symptoms, indication, procedure, clinical outcome, and histopathologic findings including immunohistochemistry. RESULTS: From a total of 593 patients treated surgically for recurring or acute complicated diverticular disease, the majority (97.8%) suffered from sigmoid diverticulitis (n = 580), whereas 2.2% (n = 16) underwent surgery for right-sided diverticulitis (including three patients with combined sigmoid and cecal diverticulitis). Related to the total number of appendectomies (n = 1167), this represented an incidence of 1.4%. In five of 16 patients, acute appendicitis was presumed preoperatively. Most common diagnostic was ultrasonography. In the group of patients with right-sided diverticulitis, the most common procedure was right hemicolectomy (n = 10), followed by ileocolic resection (n = 3) and combined right colonic resection with sigmoid resection (n = 3). Histopathological investigation confirmed complicated diverticulitis of the cecum with local perforation or abscess in 75% of the patients (12/16). Hypoganglionosis or aganglionosis was diagnosed in seven of the 16 resected specimens. DISCUSSION: As right-sided diverticulitis is a rare colonic disease in Western countries, the differentiation from acute appendicitis may be difficult. In general, there is no difference in the treatment of right-sided diverticulitis compared to left-sided diverticulitis. As most cases will remain clinically unimminent, surgery is only indicated in complicated right-sided cases. Resection of the inflamed colonic segment with primary anastomosis is safe and can be performed laparoscopically. It can only be speculated whether hypoganglionosis or aganglionosis is a causative factor in the etiology of right-sided diverticulitis.

Adult↗

Laparoscopic ultrasound navigation in liver surgery: technical aspects and accuracy.

The functional-anatomic structure of the liver according to Couinaud classification based on the intrahepatical course of the vascular structures is the basis of all modern liver surgery. Consequently, the use of intraoperative ultrasound is an undisputed requirement for every liver resection. Exact following of the planned resection plane can be realized only with the application of permanent online navigation based on intraoperative ultrasound during the dissection of the hepatical tissue. Now that the authors have established ultrasound navigated resection in open liver surgery using a navigated parenchymal dissecting instrument, they intend to transfer this technique from open to laparoscopic liver surgery. A special adapter was developed to connect an ultrasound-based navigation system to laparoscopic instruments. The authors present the first results in terms of technical aspects and feasibility.

Equipment Design↗

Influence of operator experience in radiofrequency ablation of malignant liver tumours on treatment outcome.

AIMS: Radiofrequency ablation is gaining popularity as the interventional therapy of choice for unresectable hepatic malignancies. However, little attention has been paid to the importance of operator experience in this therapy. This study aims to evaluate the results of RFA treatment dependent on operator experience and learning curve. PATIENTS AND METHODS: Between 2/2000 and 11/2004 we have undertaken 116 RFA procedures to ablate 404 unresectable primary or metastatic liver tumours in 84 patients. The clinical data of all patients were recorded prospectively and treatment results of the first 42 patients (group I) and the second 42 patients (group II) were compared. All patients were treated by the same surgeon or interventional radiologist. RESULTS: RFA was performed percutaneously in 44 procedures (group I n = 35, group II n = 9), via laparotomy in 64 procedures (group I n = 27, group II n = 37) and via laparoscopy in eight procedures (group I n = 1, group II n = 7). The complication rate was comparable in both groups with 7.9% in group I and 7.5% in group II. Group II had a higher complete ablation rate (96.2 vs 93.7%) than group I. One- and two-year survival rates of 92 and 89% in group II were significantly higher than in group I with 69 and 46% (p = 0.015). CONCLUSION: By the experience conditional optimization of indication and performance by a specialized RFA team the results could be improved significantly. The data on hand speak for a considerable learning curve in the RFA and demonstrate the importance of the experience of the therapist for the outcome of the patients.

Adult↗

[Diagnostic laparoscopy in acute abdomen].

Acute abdomen is not a disease in itself but a description of a complex of symptoms combined with severe abdominal pain developed within a time frame of less than 24 h. All strategies for the management of acute abdomen underline the need for an interdisciplinary approach to diagnosis and therapy. This requires focused and intelligent use of efficient diagnostic procedures. Diagnostic laparoscopy may be a key to solving the diagnostic dilemma of unspecific acute abdomen. Furthermore, it allows not only direct inspection of the abdominal cavity but also surgical intervention, if needed. In particular the rate of negative laparotomies can be reduced.

Abdomen, Acute↗

[Surgical therapy in right-sided diverticulitis].

INTRODUCTION: Left-sided diverticulitis is a common disease in Western countries, whereas right-sided diverticultitis is rare and symptoms are often similar to the clinical signs of an acute appendicitis. It was the aim of this study to analyse surgical experience in right-sided diverticulitis. METHODS: All patients who underwent resectional surgery for both right-sided and sigmoid diverticular disease were entered prospectively in a registry database (8-year observation period, 1996-2003). For the current study, a retrospective analysis of all patients who underwent ileocolic resection or right colectomy for right-sided colonic diverticulitis was performed, specifically focussing on incidence, clinical symptoms, indication for surgery, type of procedure, and histopathological parameters including immunohistochemistry, and outcome in right-sided diverticulitis. RESULTS: Within eight years, 481 patients were treated surgically for chronically recurrent or acute complicated diverticular disease: 468 patients with sigmoid diverticulitis, 12 patients with right-sided diverticulitis, and 1 patient with combined right-sided and sigmoid diverticular disease. This corresponds to an incidence of right-sided diverticulitis of 2.5 % related to the total number of resections for diverticulitis, and an incidence of 1.3 % in relation to the appendectomies in our patients. In 4 patients, acute appendicitis was presumed preoperatively. Most common diagnostic tool was ultrasonography. Right colectomy was performed in 9 patients with complicated cecal diverticulitis, whereas ileocolic resection was performed in 2 patients and simultaneous ileocolic and sigmoid resection was carried out in one patient. Postoperatively, no morbidity occurred. Histopathological assessment showed local perforation in 75 % (9/12). Hypoganglionosis or aganglionosis was detected in 5 of 12 resected specimen. DISCUSSION: As right-sided diverticulitis is a rare colonic disease in Western countries, the differentiation from acute appendicitis can be difficult. In general, there is no difference in the treatment of right-sided diverticulitis compared to left-sided diverticulitis, and surgery is only indicated in complicated right-sided diverticulitis. Resection of the inflamed colon with primary anastomosis is safe and can be performed by laparoscopy in experienced centers. At present, it can only be speculated whether hypoganglionosis or aganglionosis are causative factors in the etiology of right-sided diverticulitis.

Acute Disease↗

Diabetes mellitus in Tropical Chronic Pancreatitis Is Not Just a Secondary Type of Diabetes.

AIMS: In chronic calcific pancreatitis of the tropics, etiology and relationship to developing diabetes mellitus are unknown. Some consider these cases a straightforward secondary type of diabetes, while others suggest selective beta-cell impairment. Testing pancreatic function, we investigated whether selective beta-cell impairment triggers diabetes associated with tropical pancreatitis. METHODS: At a Bangladeshi research institute, 8 chronic tropical pancreatitis and no diabetes mellitus subjects, 14 fibrocalculous pancreatic diabetics and 27 matched healthy controls underwent arginine (endocrine pancreatic function) and secretin (exocrine pancreatic function assessment) stimulation tests. RESULTS: All patients with clinically-diagnosed, chronic pancreatitis demonstrated pronounced exocrine pancreatic dysfunction with beta-cell functioning differing significantly between the two groups. Compared to controls, patients having tropical pancreatitis and no diabetes showed normal plasma C-peptide values at baseline and after arginine stimulation, while fibrocalculous pancreatic diabetics demonstrated a typical diabetic pattern for plasma C-peptide levels. In contrast, pancreatic alpha-cell functioning (glucagon response to arginine) was preserved in both pancreatitis groups. CONCLUSION: A preserved pancreatic alpha-cell function in diabetics with advanced chronic pancreatitis of the tropics supports the concept of two different pathogenic mechanisms, one eliciting chronic pancreatitis and the other selective pancreatic beta-cell impairment and subsequent diabetes mellitus.

Adult↗

[Present state of radio frequency ablation of liver tumors in Germany].

INTRODUCTION: Radio frequency ablation (RFA) represents a new technique for local destruction of liver tumors. Indication and procedure are poorly validated at present. METHOD: To record the actual nationwide RFA application in Germany, a survey of 2026 hospitals with standardized questionnaires was conducted. RESULTS: With a respond rate of 17.5%, results from 58 hospitals covering 1700 ablated patients were analyzed. In 25.9% of them, RFA is already used in potentially curative resectable tumors, in 22.4% even when incomplete ablation for tumor mass reduction is expected. Of the 58 hospitals, 75% combine resection and RFA to reach a so-called R-0 situation. The maximal tumor sizes they quoted for achieving complete ablation ranged from <3 cm to 11 cm. In contraindications for RFA, the tumor size, number of tumors, critical localization of the tumor, and disorders of liver function were mentioned the most. CONCLUSION: This survey documents significant discrepancies in indication, application, procedure, and results in RFA for liver tumors. The lack of general standards and an overestimation of the method may lead to uncritical application, neglect of standard therapy, or unsatisfying results.

Chemotherapy, Adjuvant↗

Uretero-iliac artery fistula--a rare cause of massive hematuria.

Uretero-arterial fistulae are rare. Immediate diagnosis and treatment are crucial in this life-threatening disorder and thus a uretero-arterial fistula in a patient with persistent hematuria should be taken into consideration. The authors report a case of a fistula between the right ureter and right common iliac artery.

Aged↗

[Ultrasound-guided interventions using magnetic field navigation. First experiences with Ultra-Guide 2000 under operative conditions].

AIM: Ultrasound-guided interventions are presently performed as free-hand-type procedures or using biopsy transducers. In this article we report on our experience with a new navigation-system for sonographically guided interventional procedures under OR-conditions. METHODS: The US-Guide 2000 trade mark is an electromagnetic guidance system that assists physicians in ultrasound-guided interventional procedures. This system accommodates both in-plane and out-of-plane needle placement. We evaluated this system for the first time under OR-conditions. Overall, for 39 interventional procedures (23 thermoablations of malignant liver lesions, 16 diagnostic punctures) were performed. RESULTS: All targets were reached successfully without any complications. No interactions with other OR-devices were seen. CONCLUSION: The US-Guide 2000 trade mark as a virtual needle-guiding system allows a safe and accurate sonographically assisted intervention. The major advantage is the possibility of out-of-plane needle placement and the combination of flexibility of free-hand-type procedures with the accuracy of a biopsy transducer. This increases the safety of punctures especially when lesions are difficult to reach and/or are situated next to vulnerable structures. It also reduces the interventional trauma.

Biopsy, Needle↗

Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit.

BACKGROUND & AIMS: This study was designed to characterize [D-F(5)Phe(6)D-Ala(11)]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5-500 microg. kg(-1). h(-1)) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. METHODS: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. RESULTS: Intravenous BIM26226 potently inhibited gastric lag time (114 +/- 7 vs. 41 +/- 6 minutes [control]) and gastric emptying rate (0.11 +/- 0.02%/min vs. 0.26 +/- 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 +/- 41 vs. 262 +/- 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t(50%), 35 +/- 4 minutes), which BIM26226 inhibited significantly (t(50%), 64 +/- 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. CONCLUSIONS: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.

Adult↗

Recrudescence and reinfection with Helicobacter pylori after eradication therapy in Bangladeshi adults.

BACKGROUND & AIMS: In developing countries where Helicobacter pylori infection is widespread, posttherapeutic recurrence rates may be high. Many of the limited studies available have methodological problems and show varied recurrence rates. We determined late recrudescence rates, true reinfection, and ulcer recurrence. METHODS: One hundred five Bangladeshi patients with H. pylori infection and duodenal ulcer disease were treated with a triple therapy. Follow-up included 13C-urea breath tests, endoscopy, and biopsy-based tests. In reinfected patients, genomic typing compared pretherapeutic and posttherapeutic strains. RESULTS: Recrudescence, associated with nitroimidazole-based treatment, occurred in 15 of 105 patients (14%) within the first 3 months, but only 8 of 105 patients tested positive 4 weeks after therapy ended. True reinfection was diagnosed in 11 of 105 patients between 3 and 18 months after therapy. The annual reinfection rate was 13%, based on a total follow-up of 84.7 patient years. Ulcer relapse occurred in 2 of 15 (13%) recrudescence cases and in 6 of 11 (55%) reinfection cases, but also in 4 of 73 (5%) H. pylori-negative patients. CONCLUSIONS: In Bangladesh, late recrudescence of H. pylori after eradication therapy occurs within the first 3 months. The reinfection rate is high and might influence cost-benefit analyses for determining diagnostic and therapeutic procedures.

Adult↗

Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblasts.

Lung fibrosis is a fatal condition of excess extracellular matrix (ECM) deposition associated with increased transforming growth factor beta (TGF-beta) activity. Although much is known about its pathological features, our understanding of the signal transduction pathways resulting in increased ECM and collagen deposition in response to TGF-beta is still incompletely defined. We have previously reported that a JunD homodimer of the transcription factor AP-1 is specifically activated by TGF-beta in lung fibroblasts. Here we demonstrate that JunD is also specifically required for TGF-beta-induced effects. Antisense against JunD, but not c-fos or c-jun, significantly inhibited collagen deposition in response to TGF-beta in primary human lung fibroblasts. We then investigated the ability of pharmacological agents to inhibit TGF-beta-induced signaling and collagen deposition. Cs-A and IFN-gamma, but not glucocorticoids, cyclophosphamide, or azathioprine, inhibited TGF-beta-induced signaling, as assessed by luciferase reporter gene assays, and collagen deposition. TGF-beta antagonism by Cs-A was associated with direct inhibition of JunD activation, as demonstrated by electrophoretic mobility shift analyses. In contrast, the effects of IFN-gamma required signal transducer and activator of transcription (STAT)-1. We thus identify the JunD isoform of AP-1 as an essential mediator of TGF-beta-induced effects in lung fibroblasts. TGF-beta-induced signaling and collagen deposition are efficiently antagonized by Cs-A and IFN-gamma treatment, both of which exhibit distinct molecular mechanisms of action. These observations therefore offer novel targets for future therapy of fibrotic lung disease.

Cells, Cultured↗

Helicobacter pylori eradication treatment does not benefit patients with nonulcer dyspepsia.

OBJECTIVES: The aim of this study was to assess the still controversial role of treatment of Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. METHODS: We conducted a double-blind, randomized, placebo-controlled, multicenter trial comparing the efficacy of 7 days of eradication treatment (lansoprazole 15 mg b.i.d., amoxicillin I g b.i.d., and clarithromycin 500 mg b.i.d.) with a control treatment (lansoprazole 15 mg b.i.d. and placebo) in H. pylori-infected patients with nonulcer dyspepsia. 13C breath tests were performed at baseline and during follow-up. We assessed patient symptoms, health status (based on the SF-12 questionnaire), patient satisfaction, drug consumption, health care consultation behavior, and absenteeism related to dyspepsia over a 1-yr period. RESULTS: A total of 74 patients randomized to eradication treatment and 70 patients randomized to placebo were compared. The rate of eradication of H. pylori infection was 75% in the active treatment group and 4% in the placebo group (p < 0.005). The symptom score improved to a similar extent in the group receiving active treatment (-4.0; 95% CI = -5.0 to -3.0) and placebo (-3.6; 95% CI = -4.5 to -2.7). Treatment response was not related to the severity or duration of initial symptoms or to the severity of gastritis on histology. Quality of life scores were comparable at 12 months. There was no significant difference in dyspepsia-related absenteeism or satisfaction with management of NUD. Patients receiving active treatment were more likely not to have had to use any dyspepsia treatment over the 12 months (60.8% vs 44.3%; p = 0.047). CONCLUSIONS: This study did not demonstrate any substantial benefit of curing H. pylori infection in patients with nonulcer dyspepsia. The study adds further evidence that H. pylori is not the main pathogenetic or therapeutic target in these patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist.

BACKGROUND AND AIMS: The main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to determine if endogenous GRP is a physiological regulator of gastric acid secretion and gastrin release. METHODS: Our study consisted of three parts. In part I, subjects received saline or BIM26226 followed by graded doses of intravenous human GRP in a four period crossover design. In part II, subjects received BIM26226 or saline during oral meal ingestion or modified sham feeding. In part III, subjects received an acidified meal in the presence and absence of BIM26226 in a two period crossover design. In addition, gastrin and somatostatin mRNA were measured in biopsy specimens during saline and BIM26226 infusion. RESULTS: BIM26226 dose dependently inhibited GRP induced acid output. Acid secretion after oral liquid meal intake and sham feeding was significantly inhibited by BIM26226 (p<0.01) whereas plasma gastrin release remained unchanged. Gastrin and somatostatin mRNAs were not significantly different after saline or BIM26226. CONCLUSIONS: BIM26226 is a potent GRP antagonist in humans. Endogenous GRP may be a physiological regulator of gastric acid secretion. Gastrin release does not seem to be under the control of GRP.

Adult↗

Prospero's paper.

The writer proposes that the interplay between the hermeneutics of psychoanalysis and literature can illuminate understanding of the transference and countertransference at large in an analytic treatment. Writing about the work with a young woman who had been persistently sexually abused as a child and who developed anorexia in her adolescence so severe that her life was endangered both by the illness and by attempts at suicide, the author finds his reading of Shakespeare's The Tempest a powerful informant to the work. Interpreting the object relations represented by Prospero and Miranda and the process of their integration into new mental structures lends the analytic work an additional level of understanding, in particular in relation to the oedipal bond between patient and analyst. When the analyst is confronted by the imminence of his own death towards the end of the analysis, his reading of Prospero's relinquishment of his magical powers and his release of his daughter into sexual maturity and independence helps the patient to replace her destructive inner objects with more reparative and benign ones as she develops a capacity for concern and mourning.

Adult↗

Defective Jak-STAT signal transduction pathway in melanoma cells resistant to growth inhibition by interferon-alpha.

Advanced malignant melanoma is an aggressive malignancy with poor prognosis. Current therapeutic strategies have a modest success rate. The most promising treatment consists of a combination of chemotherapy with interferon-alpha, but complete response rates remain less than 15%. Interferon-alpha is also effective in adjuvant therapy for non-advanced melanoma treated surgically. The molecular mechanisms leading to loss of growth restraints and gain of growth-promoting functions during carcinogenesis of malignant melanoma are not understood in detail. Here, we studied 9 human melanoma cell lines with regard to growth inhibition by interferon-alpha and defects in intracellular signal transduction through the Jak-STAT pathway. In 3 cell lines, we found a complete loss of growth restraint by interferon-alpha. In all of them, different components of the Jak-STAT pathway were defective. Since signal transduction through the Jak-STAT pathway is necessary for antiviral and antiproliferative effects of interferons, we conclude that defects in this pathway may be one of the mechanisms that lead to cancer progression through loss of growth-restraining functions. Moreover, our results indicate that a subgroup of melanomas could be completely resistant to interferon-alpha and should therefore not be treated with this cytokine.

Cell Division↗

Interaction between CCK and a preload on reduction of food intake is mediated by CCK-A receptors in humans.

Cholecystokinin (CCK) interacts with neural signals to induce satiety in several species, but the mechanisms are unclear. We therefore tested the hypothesis that alimentary CCK (CCK-A) receptors mediate the interaction of CCK with an appetizer on food intake in humans. CCK octapeptide (CCK-8, 0.75 microgram infused over 10 min) or saline (placebo) with concomitant infusions of saline (placebo) or loxiglumide, a specific CCK-A antagonist, was infused into 16 healthy men with use of a double-blind, four-period design. All subjects received a standard 400-ml appetizer (amounting to 154 kcal) but were free to eat and drink thereafter as much as they wished. The effect of these infusions on feelings of hunger and satiety and on food intake was quantified. CCK-8 induced a reduction in calorie intake (P < 0.05) compared with saline. Furthermore, a decrease in hunger feelings (P < 0.05, saline-CCK-8 vs. all other treatments) and an increase in fullness were observed. These effects were antagonized for hunger and fullness by loxiglumide. We conclude that CCK-8 interacts with an appetizer to modulate satiety in humans. These effects are mediated by CCK-A receptors.

Adult↗