[Ulcerated plaques and papules limited to one leg].
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Biomedical subjects
Publications and source records attributed to J Freise.
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OBJECTIVE: Molecular biology techniques such as polymerase chain reaction (PCR) and ligase chain reaction (LCR) are routinely used in research for detection of C trachomatis DNA in synovial samples, and these methods are now in use in some clinical laboratories. This study aimed at determining the method best suited to molecular diagnosis of C trachomatis by examining four standard DNA preparation methods using chlamydia spiked synovial tissue and chlamydia infected monocytes. METHODS: Synovial tissue from a chlamydia negative patient with rheumatoid arthritis was spiked with defined numbers of C trachomatis elementary bodies (EB). Purified human peripheral monocytes from normal donors were infected with the organism at a multiplicity of infection 1:1 in vitro and harvested after four days. DNA was prepared from all samples by four methods: (1) QIAmp tissue kit; (2) homogenisation in 65 degrees C phenol; (3) incubation at 97 degrees C; (4) proteinase K digestion at 97 degrees C. DNA from methods 1 and 2 was subjected to PCR using two different primer sets, each targeting the C trachomatis omp1 gene. LCR was done on DNA prepared by each method. RESULTS: In synovial tissue samples spiked with EB, and in monocytes persistently infected with the organism, preparation of template using the QIAmp tissue kit (method 1) and the hot phenol extraction technique (method 2) allowed sensitive detection of C trachomatis DNA. These methods also produced template from both sample types for LCR. DNA prepared by heat denaturation (method 3) allowed only low sensitivity chlamydia detection in LCR and did not work at all for PCR. Proteinase K digestion plus heat denaturation (method 4) gave template that did not allow amplification in either PCR or LCR assays. CONCLUSIONS: The sensitivity of detection for C trachomatis DNA in synovial tissue by PCR and LCR depends strongly on the method used for preparation of the amplification template. LCR targeting the multicopy chlamydial plasmid and two nested PCR assay systems targeting the single copy omp1 gene showed roughly equivalent sensitivity. Importantly, template preparation method and the specific PCR primer system used for screening must be optimised in relation to one another for highest sensitivity.
223 patients with non-ulcer dyspepsia (dysmotility type dyspepsia or essential/idiopathic dyspepsia, also in combination with irritable bowel syndrome) were included in a prospective, randomised, reference- and double-blind controlled multicentre trial to compare two different preparations of a fixed combination of peppermint oil and caraway oil. The aim of the trial was to evaluate the equivalence of the efficacy and tolerability of these two preparations. The test formulation consisted of the drug combination in an enteric coated capsule containing 90 mg peppermint oil and 50 mg caraway oil, while an enteric soluble formulation containing 36 mg peppermint oil and 20 mg caraway oil was used as the reference. The main target item defined was the "difference in pain intensity between the beginning and the end of therapy", measured by the patient on a visual analogue scale (0 = no pain, 10 = extremely strong pain). In 213 patients (n = 108 on the test preparation, n = 105 on the reference preparation) with mean pain intensity baseline measurements of 6.1 points in the test preparation group and 5.9 points in the reference group a statistically significant decline in pain intensity was observed in the two groups (-3.6 resP. -3.3 points; p < 0.001; two-sided one-sample t-test). Equivalent efficacy of both preparations was demonstrated (p < 0.001; one-sided t-test for equivalence). With respect to concomitant variables, the results in both groups were also similar. Regarding "pain frequency", the efficacy of the test preparation was significantly better (p = 0.04; two-sided t-test for difference). Both preparations were well tolerated. Despite the higher dose, the adverse event "eructation with peppermint taste" was less frequent in the group treated with the test formulation, due to the enteric coated capsule preparation.
Fifty nine patients with Helicobacter pylori positive duodenal ulcers that failed to heal after a six week course of treatment with H2 blockers were randomly assigned to one of the following three regimens: (i) bismuth subsalicylate, 600 mg three times daily (n = 19), (ii) ranitidine, 300 mg at night (n = 20), (iii) bismuth subsalicylate plus ranitidine (n = 20). Cumulative ulcer healing rates after four and eight weeks respectively were as follows: bismuth subsalicylate 74% (14/19) and 95% (18/19), ranitidine 40% (8/20) and 65% (13/20), bismuth subsalicylate plus ranitidine 80% (16/20) and 95% (19/20). Bismuth subsalicylate treatment was better than ranitidine at both four and at eight weeks (p less than 0.05). The clearance rates for H pylori after four weeks were: bismuth subsubsalicylate 58%, ranitidine 0%, bismuth subsalicylate plus ranitidine 55%. After stopping bismuth therapy bacterial recrudescence frequently occurred. After bismuth treatment 86% (19/22) of ulcers had healed if H pylori had been cleared, whereas only 65% (11/17) had healed if H pylori persisted (NS). This study shows that bismuth subsalicylate is more effective in the treatment of resistant duodenal ulcers than standard dose ranitidine. It may be that suppression of H pylori by bismuth subsalicylate promotes ulcer healing.
The relation between intragastric acidity and duodenal ulcer activity was studied prospectively in 21 patients with endoscopically proved duodenal ulcers. The 24 hour intragastric acidity was measured on four separate occasions by continuous recording using combined glass electrodes: (a) in the presence of an ulcer crater without treatment; (b) during active ulceration being treated with ranitidine; (c) during early healing after a six week course of ranitidine; (d) during late healing six months after acute ulceration. Intragastric acidity was also monitored in 20 healthy subjects. At all stages of ulcer activity and during all predefined time periods, duodenal ulcer patients had significantly higher gastric acidity than healthy control subjects. Duodenal ulcer patients showed a similar circadian pattern of intragastric acidity during exacerbation of ulcer disease and in remission during the early and late ulcer healing periods. These results argue against a direct relation between the activity of duodenal ulcer disease and gastric acidity. It is concluded that the chronic recurrent course of duodenal ulcer disease does not result from a fluctuation in intragastric acidity.
Severe chronic pancreatitis can be easily diagnosed by means of pancreatic function tests and/or imaging procedures, whereas the mild form of the disease or its early stages are more difficult to detect and are often only retrospectively diagnosed. The reliability of imaging procedures depends mainly on the experience of the investigator, whereas the reliability of the pancreatic function tests depends on the patient's compliance. Further diagnostic procedures should be performed in accordance with the mayor symptom. If weight loss, diarrhea and/or steatorrhea dominate, indirect pancreatic function tests are required. Normal results of these tests usually exclude a pancreatogenic origin. If epigastric complaints dominate, ERCP should be performed prior to the indirect pancreatic function tests. If all findings are normal and all other upper abdominal diseases ruled out, but--due to persisting symptoms--chronic pancreatitis is still suspected, a direct function test should be performed to confirm or refute the tentative diagnosis. Chronic pancreatitis may--in its early stage--only involve the small pancreatitic ducts, not visible on ERCP examination, and indirect pancreatic function tests may show falsely normal test results.
Two-hundred and ten consecutive patients undergoing routine gastroscopy were additionally investigated for evidence of Campylobacter pylori (C.p.). 106 patients were positive in one or more tests: 99.1% using a rapid urease detecting test (CLO-test), 80.2% histology, 78.3% cytology and 60% culture. We found no difference between the CLO-test results from biopsies taken from different parts of the stomach in individual patients. C.p. was found in 100% of patients with significant chronic antral gastritis, 67.7% with gastric ulcers, 65% with duodenal ulcers and in 12.1% of normal individuals. The C.p. infection was apparently eliminated in 50% of cases treated with bismuth subsalicylate (BSS) for four weeks. The combination of BSS with amoxicillin, tinidazole or an H2-receptor antagonist offered no advantage over BSS alone. Treatment with BSS led to improvement in symptoms and histological findings including healing of ulcers in patients with or without persistent C.p. infection. The recurrence of C.p. infection after apparently successful treatment was, however, 75% in 4 weeks. In conclusion, C.p. infection correlates strongly with the presence of chronic gastritis, and significantly with gastric and duodenal ulceration. The best diagnostic approach is the combination of a rapid urease detecting test and histology. C.p. infection is of long duration and difficult to eliminate. The most effective treatment for C.p. infection remains BSS as single agent.
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The prevalence of Campylobacter pylori in gastric mucosa was investigated prospectively (by histology, cytology, bacterial culture and urease rapid-test) in 302 patients of a routine gastroenterological endoscopy programme. According to the histopathological findings the following prevalence of C. pylori was established: 3 of 35 normals (9%); 116 of 167 with antral gastritis (69%), 28 of 40 with gastric ulcers (70%); 26 of 33 with duodenal ulcers (79%); 5 of 27 with other conditions (19%). The activity degree of the gastritis correlated closely with the presence of C. pylori. In a prospective open trial 110 patients with antral gastritis or gastroduodenal ulcer were treated according to the following schedule: (a) bismuth subsalicylate, 1800 mg/d for four weeks (35 patients); (b) amoxycillin 2250 mg/d for two weeks (6); (c) ranitidine 300 mg/d for four weeks (26); (d) bismuth plus amoxycillin (20); (e) bismuth plus ranitidine (23). Immediately after the end of treatment and four weeks later the elimination rates were: (a) bismuth 51% (18) and 23% (8), respectively; (b) amoxycillin 50% (3) and 17% (1); (c) ranitidine 0% (0); (d) bismuth plus amoxycillin 60% (12) and 25% (5); (e) bismuth plus ranitidine 43% (10) and 17% (4). These data indicate that treatment with bismuth plus amoxycillin will achieve a negative bacterial result in about half the patients. But frequently as early as four weeks later C. pylori can again be demonstrated, so that the long-term elimination rate is only 15-30%.
Gabexate mesilate (FOY, ethyl-p-(6-guanidino-hexanoyl-oxy)-benzoate-methansulfonate), camostate (N,N-dimethyl-carb-amoylmethyl-4-(guanidinobenzoyloxy)-phenyl-acet ate) methansulfonate and aprotinine (Trasylol) were tested for possible inhibition of phospholipase A2. Gabexate mesilate at a concentration of 5 x 10(-4) mol/l and camostate at a concentration of 10(-3) mol/l caused a 50% reduction in enzyme activity. There was almost no inhibition by aprotinine at clinical doses; 40 million KIU/l were necessary to reduce phospholipase A2 activity by 20%. From the therapeutic dose (4,000 mg/day per i.v. infusion) and the half-life of gabexate mesilate in blood circulation (1 min) it can be calculated that the in vitro concentration of gabexate mesilate is only 10(-6) to 10(-7) mol/l. Under these conditions gabexate mesilate cannot diminish the in vivo enzyme activity of phospholipase A2.
The therapeutic effect of combined chemoembolization with lipiodol, epirubicin and cisplatin in 22 patients with nonresectable tumours, predominantly in livers with cirrhotic transformation, was analysed. Lipiodol was demonstrated in tumour tissue on average three months, maximally six months, after injection. Repeat embolization was done, if possible, after storage had subsided. There were only minor side effects. Quality of life suffered only from the, though delayed, continuing cancer growth. Survival rate was 73% after six months, 54% after one year.
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Sucralfate is an agent commonly used in the therapy of gastrointestinal ulcers. It binds itself to proteins in the ulcer crater. A selective labeling with pure 99mTc-pertechnetate is possible. For an unequivocal ulcer localization or exclusion, images have to be taken in the upright and supine positions. Encouragement of gastric emptying is useful. Images should be taken at least twice, the last one 4 h after ingestion. The method might be used when endoscopy is difficult, incomplete or contraindicated, and for follow-up during therapy. We recommend it also in the search for the cause of intermittent bleeding.
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We investigated the effect of a new synthetic protease- and phospholipase A2-inhibitor gabexate mesilate (FOY) in a multicenter (6 hospitals in Hannover and vicinity) double-blind study on the clinical course of acute pancreatitis. 50 patients were randomized into two subgroups. One group was treated with 3 X 300 mgs of gabexate mesilate per day for 9 days as a continuous intravenous infusion, the control group received placebo. There was no difference in these two groups regarding age and sex, but there was a discrepancy concerning the severity (stage I-IV) of the acute pancreatitis at the onset of treatment. More of the patients in the gabexate mesilate-group had severe disease on admission to hospital. Of the 7 patients (14%) who died, 5 were in the gabexate mesilate-group whereas only 2 were in the placebo group. This difference in the mortality rate is not significant. There was, however, a significant difference at the 5% level between the verum-group and the control group concerning the decline in alpha-amylase activity in serum and the number of complications. The difference was greatest in alcohol induced acute pancreatitis. A non-parametric test showed a significant reduction in hospitalisation time in the gabexate mesilate-group. Due to the small number of patients and the inhomogeneous clinical course of the acute pancreatitis a definite conclusion concerning the effect of gabexate mesilate on the clinical course of acute pancreatitis is not possible. Further studies with a much greater number of patients and more homogeneous groups with respect to the severity of the acute pancreatitis at the onset of the therapy with gabexate mesilate or placebo are necessary.
Four family members covering three generations presented with chronic calcifying pancreatitis. A tumor at the pancreas head was detected intraoperatively in a fifth elderly member of the family. Two of the four cases of chronic pancreatitis were diagnosed in childhood and one in adolescence. The fourth patient had typical symptoms during adolescence but the disease was not recognized at that time. Hereditary chronic pancreatitis has an autosomal-dominant inheritance with incomplete penetrance. The pathogenesis is not known. The course of the disease differed between the family members. Duodenal stenosis with gastrointestinal bleeding was observed, but also a more mild development with recurrent pain and long complaint-free intervals. The occurrence of complications and pain appears to decrease with increasing age. The extent of calcification, widening of the duct, exocrine and endocrine pancreatic insufficiency varies. The question of conservative or operative therapy depends on the course of the disease. A Whipple operation was vitally necessary in one child at the age of six. A pancreo-jejunostomy had to be introduced in a further member of the family at the age of 20 years due to an occlusion of the duct. Two patients receive only conservative treatment.