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Biomedical subjects

A Holstege

Publications and source records attributed to A Holstege.

At least 37 records · Page 2Linked to original sources

Association of esophageal dysfunction and pulmonary function impairment in systemic sclerosis.

OBJECTIVE: The aim of this study was to investigate the relationship between esophageal dysfunction and pulmonary involvement in patients with systemic sclerosis (SSc). METHODS: Pulmonary function parameters were compared between groups of patients with and without manometric evidence for SSc-induced esophageal dysmotility. RESULTS: Twenty-six of 43 patients (60.5%) exhibited a marked hypo- or aperistalsis of the smooth muscle portion of the esophagus. Total lung capacity, inspiratory vital capacity, and forced vital capacity were significantly lower in patients with esophageal dysfunction compared with those with normal esophageal peristalsis (p < 0.001). Patients with the diffuse form of SSc (n = 20) had significantly lower values for total lung capacity and inspiratory vital capacity compared with patients with the limited type of SSc (n = 23; p < 0.05). CONCLUSION: There is a significant association of esophageal dysmotility with reduced lung volumes in SSc. Possible explanations for these findings are pulmonary damage due to increased gastroesophageal reflux and, more likely, simultaneous involvement of the lungs and the esophagus in the disease process.

Esophageal Motility Disorders↗

Association of autonomic nervous dysfunction and esophageal dysmotility in systemic sclerosis.

OBJECTIVE: The primary event in the pathogenesis of gastrointestinal involvement in systemic sclerosis (SSc) has been hypothesized to be an early neural lesion. We investigated the association of autonomic nervous dysfunction and esophageal involvement in SSc. METHODS: Thirty-six consecutive patients with SSc were investigated by esophageal manometry and autonomic nervous function tests for cardiovascular and pupillary autonomic dysfunction. RESULTS: In 27 of 36 patients, esophageal manometry showed esophageal dysfunction. Twelve patients had either pupillary (n = 6) or cardiovascular (n = 5) dysfunction or both (n = 1). All patients with autonomic dysfunction had esophageal dysfunction. Patients with autonomic dysfunction had significantly reduced mean distal esophageal contraction amplitudes compared to patients without autonomic nervous dysfunction (p < 0.05). The association of autonomic dysfunction and esophageal dysfunction was significant (p = 0.02). CONCLUSION: Our results support the concept of a role for neurogenic defects in the development of esophageal dysfunction in SSc.

Adolescent↗

[After-care of colorectal carcinoma: what has efficacy?].

The efficacy of standardized follow-up examinations after surgery for colorectal carcinoma has been repeatedly questioned. Although many studies have assessed the value of different diagnostic tools none of these procedures proved to have a predictive value high enough to accurately predict the recurrence of disease and to justify its regular use in these patients. Even a combined diagnostic approach provided a benefit only for a minority of these patients (3.5 to 4.5%). Considering the physical and psychological strain imposed by this approach risk-adapted follow-up schemes are urgently needed. Prognostic parameters indicating the individual risk for disease recurrence can be deduced from increasing CEA values as well as from classification and grading of the primary tumor. Colonoscopy is an effective procedure for early detection of intraluminal relapse or metachronous tumors with potential impact on survival of the patient. An abdominal ultrasound study appears to be the method of choice for detection of metastasis of the liver due to its high sensitivity and low invasiveness. Other imaging procedures are not indicated in routine follow-up for colorectal carcinoma. It remains to be demonstrated whether molecular biology or new scintigraphic techniques will be helpful in follow-up examinations of patients with colorectal carcinomas.

Aftercare↗

Anorectal function in systemic sclerosis: correlation with esophageal dysfunction?

PURPOSE: This study was designed to compare esophageal and anorectal function parameters in patients with systemic sclerosis and to define the role of anorectal manometry in the diagnosis of gastrointestinal involvement of systemic sclerosis. PATIENTS AND METHODS: Twenty-six consecutive patients (22 females) with systemic sclerosis originally referred for assessment of esophageal function were evaluated by esophageal and anorectal manometry. Anorectal function parameters were compared between patients with normal and those with disturbed esophageal function. RESULTS: A total of 17 of 26 patients (65 percent) had severe esophageal dysfunction with aperistalsis of the lower two-thirds of the esophagus, whereas 9 patients (35 percent) had normal esophageal manometry. Only three patients (11.5 percent) suffered from occasional fecal incontinence. Anorectal function parameters (resting pressure, maximum squeeze pressure, perception threshold) were not significantly different between patients with normal and those with disturbed esophageal motility. Rectoanal inhibitory reflex was excitable in nearly 90 percent of patients. CONCLUSION: In an unselected group of patients with systemic sclerosis, fecal incontinence and abnormal anorectal function are rather rare findings. Anorectal manometry cannot differentiate between patients with and without gastrointestinal involvement of systemic sclerosis.

Adolescent↗

Esophageal manometry in systemic sclerosis: screening procedure or confined to symptomatic patients?

The predictive value of esophagus-related symptoms for the diagnosis of esophageal dysmotility induced by systemic sclerosis (SSc) was prospectively evaluated in 50 consecutive patients with SSc. Patients were classified as symptomatic when either dysphagia or repeated episodes of heartburn were present. All patients underwent esophageal manometry; SSc-induced esophageal dysfunction was diagnosed when there was aperistalsis or marked hypocontractility of the distal two-thirds of the esophageal body. Twenty-nine patients (58%) had a history of esophagus-related symptoms, while 21 patients (42%) were asymptomatic. Compared to esophageal manometry, esophagus-related symptoms had a sensitivity of 64%, a specificity of 52%, a negative predictive value of 50% and a positive predictive value of 62% for the diagnosis of SSc-induced esophageal dysfunction. In conclusion, the association of esophagus-related symptoms and esophageal motility pattern is poor. As clinical management strategies depend on proof of esophageal dysfunction, screening examinations are mandatory in all patients with SSc.

Adult↗

Spontaneous rupture of liver in a patient with Ehlers Danlos disease type IV.

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue disease caused by mutations in the type III collagen gene resulting in extreme tissue fragility. Affected individuals are at risk of dramatic and often fatal complications, mostly spontaneous arterial, uterine, or colonic ruptures. Phenotypic expression of EDS type IV is variable and clinical signs are generally quite subtle, thus making a prompt diagnosis difficult. The case of a 33-year-old woman is described who presented with a wide range of clinical features and sequelae that eventually led to the diagnosis of EDS type IV. She presented with spontaneous liver rupture, renal infarction, and pneumothorax, all representing rare complications of EDS type IV. Prior history revealed a uterine rupture in advanced pregnancy associated with ischemic necrosis of the descending and sigmoid colon. EDS type IV should be suspected in young individuals who present with such unusual complications. Early diagnosis is essential if severe or even lethal complications are to be avoided in the diagnostic and therapeutic management of such patients.

Adult↗

Influence of a haematoporphyrin derivative on the protoporphyrin IX synthesis and photodynamic effect after 5-aminolaevulinic acid sensitization in human colon carcinoma cells.

Haematoporphyrin derivatives (HPDs) are potent sensitizers in photodynamic therapy (PDT), associated with prolonged skin photosensitivity. 5-Aminolaevulinic acid (5-ALA), a natural precusor of haem, is converted intracellularly into the photosensitive agent protoporphyrin IX (PPIX), causing direct cytotoxicity after laser light irradiation but limited skin photosensitivity over 1-2 days and higher tumour selectivity. Unfortunately, the use of 5-ALA in PDT has been shown to cause only superficial tissue necrosis. Therefore, a combination of HPD and 5-ALA could be of great clinical value in the treatment of tumours if a synergistic effect of both sensitizers on tumour cell necrosis with less skin photosensitivity could be demonstrated. Human colon adenocarcinoma cells (HT-29) were cultured with either HPD or 5-ALA alone, simultaneously for 24 h with 5-ALA and HPD or in succession with 5-ALA (18 h) followed by HPD (6 h at different concentrations. Intracellular PPIX concentrations were determined by high-performance thin-layer chromatography. Furthermore, PDT was performed with an incoherent light source (lambda = 580-740 nm) using a light dose of 30 J cm(-2) and an output power of 40 mW cm(-2). The intracellular PPIX concentration correlated well with 5-ALA drug dose and incubation time and was highest after single 5-ALA sensitization. In the presence of HPD, either simultaneously or sequentially, PPIX decreased significantly. The PDT effect after simultaneous incubation with both sensitizers for 24 h was not superior to incubation with HPD alone. If 5-ALA incubation (18 h) was followed by HPD (6 h) cytotoxicity after PDT was higher than with either single drug. 5-ALA (80 microg ml(-1)) led to a decrease in tumour cell viability by 40%. A similar effect could be observed when 5-ALA and HPD were sequentially combined allowing for a reduction of the 5-ALA dose from 80 microg ml(-1) in the absence of HPD to 60 microg ml(-1) and 5 microg ml(-1) together with 0.5 microg ml(-1) and 2 microg ml(-1) HPD respectively. We speculate that the enhanced PDT effect after the combined administration of 5-ALA and HPD to cultures of colon carcinoma cells should be even more impressive in the tumour in vivo, since HPD primarily targets the tumour microvasculature and secondarily tumour cells.

Aminolevulinic Acid↗

Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging.

Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this complication of advanced liver disease still remains unclear. Magnetic resonance spectroscopy was used to assess prospectively cerebral metabolism in 51 patients with histologically proven cirrhosis (Child-Pugh classes A, B, and C, 18, 18, and 15, respectively) and 36 healthy volunteers. According to the results of psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and no encephalopathy were found in 14, 21, and 16 patients, respectively. Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter voxel were reduced significantly (P < .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16). In addition, patients showed a significant reduction (P = .024) in white matter choline/creatine ratio (.77 +/- .27) compared with controls (.92 +/- .25), and glutamine/glutamate level was elevated in cirrhotic patients compared with controls (gray matter, P < .0001; white matter, P = .036). Changes in cerebral myoinositol and glutamine/glutamate levels correlated significantly with the severity of hepatic encephalopathy (P < .0001). However, these metabolic alterations were also detected in patients without hepatic encephalopathy (normal psychometric test results). N-acetyl aspartate/creatine ratios did not differ between patients and controls. Magnetic resonance imaging detected bright basal ganglia in 37 patients, which correlated significantly with portal-systemic shunting and elevation of glutamine/glutamate, but not with the degree of hepatic encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed that alterations of cerebral metabolism are common in patients with cirrhosis, even without evidence of clinical or subclinical hepatic encephalopathy.

Adult↗

In situ detection of lipid peroxidation by-products in chronic liver diseases.

Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. The deleterious consequences of this mechanism are related in part to the formation of reactive aldehydic products that bind to intra- or extracellular molecules to form adducts. Specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, allowed us to investigate in situ, with an immunohistochemical procedure, the occurrence of lipid peroxidation in a panel of different chronic liver diseases. Intracellular HNE and MDA adducts were detected respectively in 24 of 39 cases (62%) and in 12 of 34 cases investigated (35%). They were localized mainly in the cytoplasm of hepatocytes, with the strongest staining observed in hemochromatosis, Wilson's disease, and in areas of acute alcoholic hepatitis in cases of alcoholic liver diseases. A peculiar pattern of immunostaining was observed in primary biliary cirrhosis where biliary cells of destroyed but also intact bile ducts strongly expressed HNE adducts. The liver extracellular matrix also displayed MDA adducts (30 of 34 cases, 88%) and HNE adducts (23 of 39 cases, 59%). While HNE adducts were specifically localized on large bundles of collagen fibers, MDA adducts were detected in a thin reticular network and in sinusoidal cells around portal tracts or fibrous septa. In conclusion, lipid peroxidation by-products are detectable in chronic liver diseases. Immunohistochemical results suggest that this mechanism is implicated very early in the pathogenesis of some of these diseases.

Adolescent↗

Enhanced effectiveness of photodynamic therapy with laser light fractionation in patients with esophageal cancer.

BACKGROUND AND STUDY AIMS: The fractionated application of laser light has been shown to enhance the effect of photodynamic therapy (PDT) on normal rat colon after photosensitization with 5-aminolevulinic acid. In a pilot study, we examined whether this modified laser treatment can also enhance the effect of PDT in patients with esophageal cancer after sensitization with hematoporphyrins. PATIENTS AND METHODS: Six patients (four cases of early esophageal carcinoma and two cases of advanced esophageal carcinoma, one of the latter patients having tumor overgrowth on a metal stent) were treated in nine sessions. In four sessions, laser energy was fractionated to enhance the PDT effect using a hematoporphyrin polyester. Irradiation was carried out 48 hours after sensitization. The total laser energy of 150 J/cm2 was applied either continuously or in fractions, with a single break of five minutes after 75 J/cm2. RESULTS: Among the three patients who underwent continuous laser light irradiation, one patient experienced a complete remission of two of three superficial esophageal cancers. The patient with tumor overgrowth on an implanted metal stent showed a partial response, with improvement of dysphagia without destruction of the stent, while in another patient with advanced esophageal cancer, the dysphagia did not improve after continuous laser treatment. Fractionated laser therapy led to complete remission in all three patients with early cancers, one of whom had failed to respond to previous treatment with continuous PDT. A partial remission was obtained in a fourth patient with a uT2 cancer who had also shown no remission after continuous PDT treatment. However, after fractionated laser therapy, three mild esophageal stenoses occurred, in comparison with none after continuous PDT. CONCLUSIONS: Light fractionation during PDT improved the effectiveness of the treatment in a small number of patients, and increased side effects such as the occurrence of mild esophageal stenosis. This modified treatment can be a promising approach in the effort to reduce the dose of hematoporphyrins or other sensitizers required, and to avoid prolonged skin sensitization or local stenosis.

Aged↗

Post-ERP pancreatitis as a model for cytokine induced acute phase response in acute pancreatitis.

BACKGROUND/AIMS: By contrast with animal models, in most cases it is not possible to examine the systemic response in patients in the first hours after onset of acute pancreatitis. The aim was to determine whether endoscopic retrograde cholangiopancreaticography (ERP)-induced pancreatitis can be used as a human model for the study of cytokine release and acute phase response in the first hours of the disease. PATIENTS AND METHODS: Seventy consecutive patients undergoing ERP for different reasons were prospectively evaluated by sampling blood before and 0, 1, 4, 12, 24, and 48 hours after ERP and, in patients who developed an acute post-ERP pancreatitis, daily until C reactive protein (CRP) was within normal range. A post-ERP pancreatitis was defined as a three-fold increase of amylase or lipase and at least two of the clinical symptoms: abdominal pain, nausea, vomiting, and peritonism during 24 hours after ERP. RESULTS: Nine out of 70 patients developed an acute pancreatitis. Cytokines and other biochemical variables were measured in those nine and in 34 patients out of the 61 not developing pancreatitis. In the nine patients amylase and lipase increased within the first hour after ERP with maximum values between four and 12 hours. Interleukin-6 increased to maximal concentrations after 24-48 hours and the highest CRP concentrations were found 72 hours after ERP. Tumour necrosis factor did not change. CONCLUSION: Post-ERP pancreatitis is an ideal model in which to examine the initial cytokine and acute phase response in the first hours after the initiation of the disease.

Acute Disease↗

In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features.

AIMS: To assess the occurrence of lipid peroxidation in chronic hepatitis C and to evaluate its relation to pathological features and liver iron concentrations. METHODS: Liver biopsy samples of 43 patients with untreated chronic hepatitis C were studied by immunohistochemistry using specific antibodies directed against two major aldehyde metabolites of lipid peroxidation, malondialdehyde (MDA), and 4-hydroxynonenal (HNE). RESULTS: MDA and HNE adducts (aldehydes covalently linked to another molecule) were detected in the liver samples in 77% and 30% of cases, respectively. MDA adducts were detected both in the extracellular matrix and sinusoidal cells localised in areas of periportal and lobular necrosis. HNE adducts appeared in the cytoplasm of only a few hepatocytes. Comparison of the semiquantitative assessment of adducts (MDA and HNE indexes) with the grading and the staging of chronic hepatitis showed that the MDA index was correlated with fibrosis score (p < 0.001) and the grade of activity (p < 0.01). There was also a tendency to correlation with liver iron concentration (p = 0.09). No correlation was observed between the HNE index and pathological features or liver iron concentration. CONCLUSION: Lipid peroxidation products are detectable in the liver of chronic hepatitis C patients. The presence of MDA adducts in areas of active fibrogenesis and the correlation between the MDA index and fibrosis score suggest a role for lipid peroxidation in liver fibrosis.

Adult↗

Gastrointestinal manifestations of progressive systemic sclerosis.

Management of patients with progressive systemic sclerosis requires a thorough gastroenterological examination and a profound knowledge of possible gastrointestinal manifestations of the disease. The esophagus is the gastrointestinal segment most often involved. Smooth muscle atrophy leads to a loss of esophageal peristalsis, a defect of the lower esophageal sphincter, and gastric hypomotility, thus predisposing to severe reflux esophagitis. A rational diagnostic approach includes standard manometry and endoscopy. The prevention of strictures is the main aim of therapeutic efforts that may consist of lifestyle changes, prokinetic drugs, long-term application of proton pump inhibitors, and, if inevitable, surgical intervention. Involvement of the small intestine and colon is less common but may lead to life-threatening complications like chronic pseudoobstruction or pneumatosis cystoides intestinalis. The main therapeutic options consist of antibiotics for bacterial overgrowth and nutritional supplementation. Recently, a preliminary study with octreotide yielded promising results. Anorectal dysfunction can lead to fecal incontinence or rectal prolapse.

Digestive System↗

[Acute hemolytic crisis as the initial manifestation of Wilson disease].

A 25-year-old woman who had delivered a normal child after a normal pregnancy four months ago, was suffering from a common cold. The latter was treated by tetracyclines. A few days later she developed an acute severe hemolysis. Moreover she had signs of hepatic failure which was characterized by a considerably reduced synthetic capacity of the liver but low serum aminotransferase levels and a proximal renal tubular disorder. With a negative Coombs test an autoimmune hemolytic anemia was unlikely. Therefore diagnostic procedures were directed at the cause of the liver injury. An increased urinary excretion of copper, strongly elevated levels of liver tissue copper and the detection of a Kayser-Fleischer ring by slit-lamp examination proved the diagnosis of Wilson's disease-presenting clinically only as severe hemolysis. Ceruloplasmin concentration in serum was in low normal range and not diagnostic.

Acute Disease↗

[Endosonographic demonstration of extrapancreatic and extraintestinal gastrinoma].

HISTORY AND CLINICAL FINDINGS: No cause had been found for chronic diarrhoea in a 57-year-old man. Up to 15 watery stools daily had been without relation to food intake and without blood admixture. But muscular cramps had developed, especially in the legs. The patient had a history of recurrent peptic ulcers for which a selective proximal vagotomy had been performed 13 years ago. Physical examination was unremarkable. INVESTIGATIONS: Alkaline phosphatase activity (182 U/l) and C-reactive protein (9.3 mg/l) were slightly raised; serum iron was 42 micrograms/dl, while all other routine laboratory tests, including protein electrophoresis, blood picture and differential count were within normal limits. Gastroscopy revealed ulcerative duodenitis, gastritis with erosions and numerous ulcers and reflux oesophagitis, grade III-IV. Endosonography showed enlarged gastric mucosal relief as sign of foveolar hyperplasia and a ca. 4 x 3 cm tumour next to the duodenal bulb. Gastrin level was 7537 pg/ml (normal < 150 pg/ml). Computed tomography and somatostatin receptor scintigraphy confirmed the site and size of the gastrinoma. TREATMENT AND COURSE: Treatment with omeprazole (40 mg three times daily) slightly improved the symptoms. The tumour was excised a week after diagnosis. The patient has been symptom-free since then. CONCLUSION: Chronic diarrhoea of unknown aetiology can be caused by an endocrine tumour; endosonography can often provide information on the diagnosis and location of such a tumour.

Chronic Disease↗

[CT-guided percutaneous endoscopic gastrostomy: a successful method if transillumination is not possible].

BACKGROUND AND OBJECTIVE: If transillumination is not possible, percutaneous endoscopic gastrostomy (PEG) is contraindicated. In these cases the stomach had so far to be punctured directly during radiological monitoring. A new method is described which combines endoscopy and computed tomography (CT) for performing a percutaneous endoscopic gastrostomy. PATIENTS AND METHODS: Among 189 patients who were to have the procedure there were eleven (nine men, two women) in whom transillumination was not possible. After endoscopic insufflation of air PEG was done under CT guidance, using the common pull-through technique. RESULTS: The combined method was successful in ten of the eleven patients without complication. In one patient with hepatomegaly and interposition of the transverse colon PEG was not possible even with CT guidance. CONCLUSIONS: The combined endoscopic-radiological method is practicable and safe in cases in which transillumination is not possible. There are several advantages compared with direct puncturing: The common pull-through technique can be used; radiological exposure is low and other clinically relevant findings may be revealed by the endoscopy.

Adult↗

[Asymptomatic choledochal cyst].

HISTORY AND FINDINGS: A 45-year-old woman sustained an ankle fracture in an accident. At examination she was found to have marked pallor of skin and mucosae. There was no hint for melaena or haematemesis. INVESTIGATIONS: Biochemical tests showed marked iron deficiency anaemia (haemoglobin 7.5 g/dl) and raised serum bilirubin and C-reactive protein levels (1.94 mg/dl and 85.2 mg/l, respectively). Abdominal sonography revealed a cystic space-occupying mass (8 x 4.5 cm) projecting onto the gallbladder, interpreted as a choledochal cyst of unknown origins without bleeding. After treatment of the ankle fracture an endoscopic retrograde cholangiopancreatography was performed. This showed a large cyst of the choledochal duct into which the cystic and choledochal ducts entered, without evidence of tumour or haematoma. There was also a 1 cm prepapillary common choledochal and Wirsung duct. TREATMENT AND COURSE: With these findings, the diagnosis of a congenital choledochal cyst (type Ia of Todani) could be made. After healing of the ankle fracture the cyst was removed and a Roux Y-anastomosis created. The cystic tissue was benign. At follow-up 6 months later the patient was symptom-free and no longer anaemic. CONCLUSIONS: Congenital choledochal cysts are very rare in Europeans. The symptom-free course with anaemia and no manifestation until adulthood is also very unusual.

Anastomosis, Roux-en-Y↗