Novel variable volume injector for performing sample introduction in a miniaturised isotachophoresis device.

A microdevice design furnished with a novel sample injector, capable of delivering variable volume samples, for miniaturised isotachophoretic separations is presented. Micromachining by direct milling was used to realise two flow channel network designs on poly(methyl methacrylate) chips. Both designs comprised a wide bore sample channel interfaced, via a short connection channel, to a narrow bore separation channel. Superior injection performance was observed with a connection channel angled at 45 degrees to the separation channel compared to a device using a channel angled at 90 degrees. Automated delivery of electrolytes to the microdevice was demonstrated with both hydrostatic pumping and syringe pumps; both gave reproducible sample injection. A range of different sampling strategies were investigated. Isotachophoretic separations of model analytes (metal ions and an anionic dye) demonstrated the potential of the device. Separations of ten metal cations were achieved in under 475 s.

Prospective evaluation of novel system for jejunal feeding.

BACKGROUND: Enteral nutrition should be restored immediately after trauma, acute lesion, or surgical intervention. Nutrition through nasogastric tubes is often not feasible in patients in the posttraumatic state in medical intensive care units because of recurrent episodes of gastroesophageal reflux and subsequent aspiration due to gastric paresis. Placement of nasojejunal tubes with available techniques is unreliable. METHODS: We developed a new combined catheter system for jejunal delivery and simultaneous drainage of gastric juice (Cath-in-Cath, PreOx-RS, Germany). CONCLUSION: In this article, this new tube system is presented. The safety and excellent efficacy of the novel system for enteral nutrition therapy are reported in the first series of patients worldwide.

Effects of fluvastatin on biliary lipids in subjects with an elevated cholesterol saturation index.

OBJECTIVE: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been suggested as agents to reduce the biliary cholesterol saturation index (CSI) in duodenal bile and therefore might be supportive in primary or secondary prevention of gallstones. However, the efficiency of the therapy seems to depend on both the HMG-CoA reductase inhibitor used and the study population selected. METHODS: We therefore investigated the effect of a high-dose application of fluvastatin on biliary lipid composition in 21 subjects exhibiting mild hypercholesterolaemia and a history of current gallstones or cholecystectomy due to gallstone disease. Subjects were treated either with 40 mg fluvastatin twice per day over a 3-month period (n = 14) or with placebo (n = 7). Bile samples were aspirated during endoscopy after intravenous ceruletid stimulation before and after therapy. RESULTS: Both groups were comparable in CSI (mean +/- SD) at baseline (1.78 +/- 0.2 placebo vs. 1.97 +/- 0.4 verum). CSI significantly decreased in the verum group to 1.45 +/- 0.4 (P = 0.003) mainly due to increased phospholipid levels, whereas no difference was observed in the placebo group (1.85 +/- 0.7, n.s.). In addition, the verum group exhibited a significant reduction of hydrophobic deoxycholic acid, which has been reported to induce cholesterol crystal precipitation, and an increase of hydrophilic cholic acid. CONCLUSION: Fluvastatin might decrease the risk of cholesterol gallstone formation in patients with elevated biliary CSI during long-term treatment by reduction of biliary cholesterol saturation and percentage change in deoxycholic acid content.

Pathological pancreatic exocrine function and duct morphology in patients with cholelithiasis.

Most authors claim alcohol consumption to be the only relevant reason for chronic pancreatitis. However, gallstones might cause this disease, as they do cause acute pancreatitis. In this study 91 gallstone patients and 94 age-matched controls were investigated concerning exocrine pancreatic function (fecal elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients were evaluated for differences concerning pancreatic duct changes between patients with and without evidence of cholelithiasis. Pathological elastase 1 levels were more frequent in gallstone patients (30,8%) as compared to age-matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat intolerance were reported more often in gallstone patients. In ERCP of gallstone patients (N = 60), 77% were found to have chronic pancreatitis according to the Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic pancreatitis. In conclusion, according to these data a pathophysiological connection between gallstones and chronic pancreatitis appears to be probable.

Octreotide in the prevention of pancreatic damage induced by endoscopic sphincterotomy.

Somatostatin and the long acting analogue octreotide have been proposed as a therapeutic agent in acute pancreatitis and for the prophylaxis of pancreatic damage by ERCP and EST for their ability to reduce exocrine pancreatic secretion. However, clinical trials could not show significant beneficial effects in acute pancreatitis and ERCP. In patients undergoing EST, data remained controversial, most authors describing positive effects of prophylaxis. In this study we investigated the use of octreotide prophylaxis to reduce EST-induced pancreatic damage in a randomised, double blind trial. 94 consecutive ERCP/EST-patients were randomised to receive either octreotide 200 microgram s.c. or placebo 3 times daily, starting the night before endoscopic procedures. In 59 patients EST was performed. Blood samples were collected before and 40 min, 2 hrs, 6 hrs, 24 hrs, 48 hrs and 72 hrs after the endoscopic procedures. Samples were analysed for pancreatic serum enzymes, acute phase proteins and blood counts. A clinical pain score was investigated. Post-EST-pancreatitis (amylase > 3x upper limit and persistent abdominal pain) was diagnosed in 3 patients in the treatment group, in 4 patients in the placebo group. There were no significant differences in the time-courses of serum enzymes or acute phase proteins in-between the groups, nor in the pain-score. According to these data, prophylactic octreotide application does not prevent acute pancreatic damage induced by endoscopic sphincterotomy.

Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus.

Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 patients with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenetic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far.

Tumor M2-pyruvate kinase: a promising tumor marker in the diagnosis of gastro-intestinal cancer.

The diagnostic value of pyruvate-kinase type tumor M2 (Tumor M2-PK) has been investigated in different tumors, and showed interesting results in cases of renal cancer, pancreatic cancer, lung cancer and some cases of gastric cancer. In this study we investigated EDTA-plasma of 68 patients with gastrointestinal cancer, 22 patients with inflammatory bowel disease (IBD) and 60 healthy controls. Sensitivity of Tumor M2-PK was 70.6% for all GI-tumors, that of CA19-9 was 55.4% and that of CEA was 53.3%. In pancreatic cancer CA19-9 showed the best sensitivity. In oesophageal/gastric cancer Tumor M2-PK was most sensitive and in colorectal cancer CEA and Tumor M2-PK showed the best results. The specificity of Tumor M2-PK was 90-96, 7%. In IBD some individuals showed elevated Tumor M2-PK levels but there was no correlation to CRP or to the clinical activity score. The results indicated that Tumor M2-PK might be a valuable marker in gastrointestinal cancer.

Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.

[Spontaneous spinal epidural hematoma: good outcome after delayed treatment]. / Spontane spinale epidurale Hämatome: gute Ergebnisse auch nach verzögerter Behandlung.

Spinal epidural haematomas are rare and are often encountered after previous operations on spinal disease and in combination with anticoagulation therapy. Usually early diagnosis and surgical treatment are the most important factors for a good result and neurological recovery. In 4 cases of spinal epidural haematoma treated in our institution, we found that also after some delay of diagnosis and treatment, surgery is always worthwhile even after some days to achieve a better neurological function.

Exchange blood transfusion in severe falciparum malaria: retrospective evaluation of 61 patients treated with, compared to 63 patients treated without, exchange transfusion.

The rationale for exchange blood transfusion (ET) in severe falciparum malaria is threefold: reduction of parasitaemia, reduction of presumptive 'toxic' factors, and improvement of the rheological quality of the blood. We evaluated the records of 61 patients treated with ET to describe the present status of malaria treatment in Germany, Austria and Switzerland and to assess the efficacy of ET. Clinical data of 61 patients treated with ET were compared to data of 63 patients treated in 2 hospitals where ETs were generally not performed. We found that exchange transfusion is applied according to the clinician's subjective impression rather than strict guidelines. Logistic regression analysis adjusting for the differences in clinical parameters between patients treated with or without ET did not identify treatment as a prognostic indicator (odds ratio for relative risk of death with ET: 1.3; 95% CI: 0.4-4.9). Exchange transfusion did not significantly improve the unfavourable prognosis in cases of severe falciparum malaria. However, failure to reach statistical significance may be due to the retrospective design of the study and therefore non-systematic approach.

Nutrition and cardiovascular disease.

The association between nutrition and coronary heart disease is mainly due to the effect of nutrients on serum lipids and lipoproteins. Cholesterol intake does not play a very important role for plasma cholesterol although there is a strong interindividual difference in response. The intake of saturated fatty acids strongly negatively affects plasma low-density lipoprotein cholesterol concentration while mono- and polyunsaturated fatty acids are generally regarded as beneficial. Omega-3 fatty acids mainly decrease triglyceride concentration while omega-6 polyunsaturated fatty acids mainly affect low-density lipoprotein cholesterol. Other nutrients which affect risk for coronary heart disease are dietary fiber, calcium, magnesium, iron, antioxidants as well as vitamins. Dietary fiber decrease intake of calories and fat, while iron and antioxidants play a role in oxidative modification of low-density lipoproteins. A low intake would lead to an accelerated uptake of low-density lipoprotein into the macrophage. Yet, intervention studies have not shown conclusively the benefit of a high-dose supplementation of the antioxidants vitamin E or beta-carotene on coronary heart disease. Homocysteine plasma concentration is influenced by folate as well as vitamin B6 and B12. Whether a high-dose supplementation with these substances does not only decrease plasma concentrations of homocysteine but also positively influence the course of coronary heart disease remains to be established.

Splenectomy for suspected malignant lymphoma in two patients with loiasis.

Intrasplenic lesions can cause diagnostic difficulties because malignant diseases can be excluded only by histologic examination. We present the cases of two patients with splenic manifestations of loiasis. Both patients had visited central Africa. Several years later, intrasplenic lesions were found during routine examinations (for chest trauma and employment, respectively). Both patients underwent splenectomies because malignant lymphoma was suspected. In both cases, histologic examination of the spleen showed eosinophilic granulomata with multiple Loa loa microfilariae.

[Halofantrine in the treatment of imported malaria in nonimmune travelers]. / Halofantrin zur Behandlung der importierten Malaria bei nicht-immunen Reisenden.

The efficacy (criteria: cure rate, time to resolution of fever or absence of parasites) and safety (criteria: clinical side effects, altered laboratory parameters) of halofantrin were investigated in a multi-centre study of 96 non-immune patients (71 men, 25 women, mean age 34.3 [21-62] years) with malaria imported from regions of high resistance into Germany or Switzerland. The initial 63 patients received one-day treatment (three doses of 500 mg halofantrin), while the last 33 patients received an additional course of treatment one week later. Treatment was curative in all patients in the second group, but relapses occurred in five of the 41 patients (12.2%) with falciparum malaria who received one-day therapy. Fever resolved after a mean of 45 hours and parasites were absent after a mean of 66 hours. There were small increases in transaminase values (most probably because of the infection) in five patients, but all became normal again within a few days. Halofantrin is a safe drug and is suitable for both therapy and stand-by therapy of resistant Plasmodium infections. Treatment should be repeated after 7 days.

The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers.

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons.

Different changes of n-6 fatty acids in lipoproteins from hyperlipemic subjects after diets supplemented with n-3 fatty acids.

After diets supplemented with canned mackerel or herring, in a cross-over design, containing different amounts of long-chain n-3 fatty acids (eicosapentaenoic acid, C20:5n-3-EPA, and docosahexaenoic acid, C22(6)n-3-DHA) an increase of both EPA and DHA was confirmed in triglycerides (TG), cholesterol esters (CE) and phospholipids (PL) of very low density (VLDL) and low density lipoproteins (LDL) as well as in high density lipoproteins (HDL) from hyperlipidemic subjects. An unexpected finding was the simultaneous increase of arachidonic acid (C20:4n-6-AA) in TG and CE and its constant portion in PL of lipoproteins, whereas linoleic acid (C18:2n-6-LA) appeared lower in CE and in PL of VLDL + LDL and HDL. In general, the changes were minor after a diet supplemented with canned herring providing a lower dose of n-3 fatty acids. The results indicate dose-related changes not only of n-3 fatty acids, but also of n-6 fatty acids in serum lipids after fish diets. This different behavior of LA and AA in serum lipids might be a new aspect in the interrelations and the dietary modulation of both families of polyunsaturated fatty acids (PUFA). The accumulation of AA in neutral lipids could be linked with an elevation of prostaglandin I2, which was found apart from an increased formation of prostaglandin I3 after diets supplemented with n-3 fatty acids. The concomitant increase of prostaglandins I2 and I3 spotlights widely ignored interrelations within the eicosanoid pathway, which become evident after diets enriched with long-chain n-3 fatty acids.

[Dengue fever with hemorrhagic manifestations after a stay in Thailand]. / Denguefieber mit hämorrhagischen Manifestationen nach Thailandaufenthalt.

On returning from a 24-day long stay in Thailand a 30-year-old German woman fell ill with high fever and head and limb aches. Soon after a confluent petechial exanthem was noted, as well as conjunctival and gastrointestinal bleedings. Biochemical findings (fall in haemoglobin concentration and haematocrit, leucopenia and thrombocytopenia, rise in lactate dehydrogenase) and a rise in Dengue antibody titre to 1 : 320 (on the 13th day of illness) confirmed the diagnosis of Dengue fever with haemorrhagic manifestations. This mosquito-transmitted viral disease, while so far only rarely reported in tourists, should be considered in the differential diagnosis of fever of undetermined origin in travellers to the tropics.