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Biomedical subjects

H Schramm

Publications and source records attributed to H Schramm.

At least 37 records · Page 2Linked to original sources

[Is there a chronic appendicitis in childhood? Analysis of pediatric surgical patients from 1993-1997].

The right lower quadrant abdominal pain and the "chronic" appendicitis in childhood and adolescence are frequently connected with a lot of different diagnostical problems for the treating physician. Since the introduction of diagnostical laparoscopy and laparoscopical appendectomy in our hospital the rate of appendectomy has been increased to 35% in case of the histological diagnosis of "chronic" appendicitis. A special problem in childhood and adolescence is the request of the parents for clarification of chronic recurrent pain in their children and therefore the demand of laparoscopy and not seldom appendectomy. After appendectomy with the pathological-histological findings of "chronic" appendicitis children are in 83% without any abdominal pain. Therefore the question arises whether there exists a "chronic" appendicitis in childhood justifying surgery in these cases. Although the rate of complications and conversions (3.8%) in diagnostical laparoscopy and laparoscopical appendectomy is quite low the indication should only be made after careful examination considering differential diagnostical problems. In our hospital 56.5% of the children with the histological diagnosis of "chronic" appendicitis suffered retrospectively on other diseases, that had been caused the symptoms of appendicitis. Before operation the patients should be informed on the complications in detail.

Adolescent↗

Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen)

OBJECTIVE: To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases. METHODS: Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only. RESULTS: The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients. CONCLUSION: According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was therefore terminated.

Adult↗

[Interim analysis of a prospective, randomized multi-center study by the "Liver Metastases" Study Group: adjuvant intra-arterial chemotherapy after curative liver resection of colorectal metastases].

Recurrence after resection of colorectal liver metastases occurs after 9-12 months in up to 80% of patients. Half of the relapses is isolated to the liver. An intraarterial chemotherapy with 5-FU and folinic acid was compared to only resection. Main objective of the trial was survival. Within 14 days after resection followed the 6-month therapy with 5-FU 1000 mg/m2 continuously over 5d/28d and Folinic Acid 200 mg/m2 over 15 minutes 5d/28d. The first interim-analysis with 226 randomised patients showed in the intention-to-treat-analysis a median survival of 34.5 months (m.) with therapy versus 40.8 months (p = 0.1519 with a negative trend. (95%-Confidence interval for hazard ratio: [0.5; 1.15]) and time to progression of 14.2 m. with therapy versus 13.7 m. Severe toxicities (WHO grade III/IV) occurred in 25.6% of cycles and 62.9% of patients. Mainly registered were stomatitis (57.6%) and nausea (55.4%). The recruitment of patients for study was terminated, because in best case the risk to die could be lowered only by 15% and therefore clinical relevant prolongation of survival is not to achieve with this type of adjuvant therapy.

Adult↗

[Preoperative diagnosis in laparoscopic cholecystectomy: is intravenous cholangiography currently still justified?].

Laparocopic cholecystectomy requires essentially the safe exclusion of choledocholithias. The aim of this study was to compare the intravenous cholangiography and ERCP in addition to a basic program (case history, laboratory results ultrasound) with references to the diagnostic ability and therapeutic consequences in patients with choledocholithiasis. The results show, that the intravenous cholangiography not provides extra important informations after the case history, ultrasound and laboratory findings and therefore its general use is not justified. Instead of the intravenous cholangiography the preoperative ERCP should be performed generously if choledocholithiasis is suspected, especially because the ERCP offers the possibility to extract the stone.

Cholangiography↗

[Therapy of acute cholecystitis from the surgical viewpoint].

The over notion, "acute gallbladder" includes the acute cholecystitis, also the gallbladder dropsy, the persistent colicky pain of the impaction, the complications of acute cholecystitis like the cholecystoempyema an necrotising the calculous impaction inflammation. In the last cases an emergency operation ist necessary. The acute cholecystitis and also the acute gallbladder dropsy have to be operated in an unit of time of 72 hours. By this patients the capability of operation and narcosis is a prerequisite. The late operation also the interval operation are united with greater operative technical difficulties an the danger of intraoperative complications. The indication for the cholecystostomy ist rare. Is an anaesthesia not possible a surgical stomy in local anaesthesia or a percutaneous transhepatic puncture drainage with sonography and CT-control ist possible. There are scarcely contra-indications for the laparoscopy.

Acute Disease↗

[Changes in indications in laparoscopic appendectomy?].

Acute appendicitis requires timely surgery. Still history and physical exam essentially lead us to the diagnosis. The definite histological-pathological finding of acute inflammation postoperatively confirms the diagnosis. Other findings especially chronic or chronic-recurrent inflammation should rise doubt. Therefore other criteria are needed to evaluate the quality of diagnosis for instance the nearly equal male to female relation of 1:1 in all appendectomies as well as in each decade. Today the principles of a strict indication for appendectomy becomes more loose because of the use of laparoscopy as we have shown in or own investigations. The valid standard have to be kept up, on the other hand we must reconsider the indication for surgery under the diagnosis "chronic or chronic-recurrent appendicitis".

Adolescent↗

[Intra-arterial (5-FU/FA and FUDR) versus systemic chemotherapy (5-FU/FA) of non-resectable colorectal liver metastases].

The relative efficacy of HAI FUDR, HAI 5-FU/FA, and i.v. 5-FU/FA chemotherapy for the treatment of unresectable colorectal liver metastases was compared in a prospective randomized clinical trial. The response rate after HAI treatment was significantly higher as compared to i.v. treatment with no statistical benefit regarding survival and time to progression. HAI FUDR treatment was inferior as compared to HAI or i.v. 5-FU/FA. i.v. 5-FU/FA-therapy is therefore the method of choice outside clinical trials.

Adult↗

Chemotherapeutic activity of levofloxacin (HR 355, DR-3355) against systemic and localized infections in laboratory animals.

Ofloxacin, its optical isomers levofloxacin (HR 355, DR-3355) and D-ofloxacin (DR-3354) and ciprofloxacin were administered orally to mice and rats which had systemic and localized infections. Both levofloxacin and ciprofloxacin were equally effective in treating systemic murine infections caused by staphylococci. Enterobacteriaceae or Pseudomonas aeruginosa with ED50s ranging from 0.18 to 15.8 mg/kg and 0.42 to 16.3 mg/kg respectively and both these agents were twice as effective as ofloxacin which had an ED50 0.41 to 39.7 mg/kg. In contrast, D-ofloxacin was either inactive or exhibited only modest chemotherapeutic activity against the staphylococci and the Gram-negative organisms tested. When given to mice to treat staphylococcal abscesses and lung infections due to Klebsiella pneumoniae DT-S levofloxacin was up to four times more effective and produced a more pronounced bactericidal effect against the pathogens in vivo than the reference compounds. Despite possessing a similar, if not lesser, in-vitro activity against the infecting pathogens, levofloxacin was more effective than ofloxacin and ciprofloxacin in rats with localized infections caused by Enterobacteriaceae and P. aeruginosa.

Abscess↗

[The importance of puncture cytology in diagnosis of benign and malignant breast changes].

In 500 mamma needle biopsies that were cytologically examined we found a precision of 87.4%, with 2.6% false negative, and 6.2% false positive results. In 19 cases a cytological diagnosis was not possible resulting in a sensitivity of 0.94 and a specificity of 0.86. False positive findings were due to misinterpretations of the cytological pictures, as were also false negative findings. In the latter cases sampling mistakes could also be the reason. Cytological diagnostic should only be made using triple diagnostic technique since the methods are complementary to each other in respect to their diagnostic security. Practical experience in the puncturing technique as well as an experienced cytologist are prerequisites using this method successfully as a diagnostic tool.

Biopsy, Needle↗

[Prevention of arterial and venous vascular diseases, especially the correlation between risk factors and arteriosclerosis].

In a epidemiological study 3840 clerks of state of North Rhein Westfalia were investigated concerning the frequency of atherosklerotic leasions of the carotid and femoral arteries in duplex scanning. 17% of all investigated showed independency to age, sex and risk factors alterations of the vessel walls. Men had twice as much plaques as women and male subjects with multiple risk factors had four times more plaques than those without.

Adult↗

Modulation of selenium-dependent glutathione peroxidase by perfluorodecanoic acid in rats: effect of dietary selenium.

Forty-eight male Sprague-Dawley rats fed a diet containing 0.4, 0.2 or 1.0 mg of selenium (Se)/kg of diet were injected with a single dose (35 mg/kg) of perfluorodecanoic acid (PFDA) in corn oil and killed 2 wk later. Control animals were pair-fed and treated with an equal volume of vehicle. PFDA treatment significantly increased Se-dependent glutathione peroxidase (Se-GSHPx) activity in liver cytosol of rats fed the 0.04 mg of Se/kg of diet but not in rats fed the other diets. The increase in liver cytosolic Se-GSHPx activity in rats fed 0.04 mg of Se/kg of diet paralleled increases in Se content and serum Se-GSHPx activity. Determination of Se-GSHPx by an enzyme-linked immunosorbent assay showed that PFDA caused a decrease in Se-GSHPx protein in rats fed 0.2 or 1.0 mg of Se/kg of diet but not in rats fed 0.04 mg of Se/kg of diet. Further analysis revealed that the ratio of Se-GSHPx activity to antibody-reactive protein was increased by PFDA in all three groups. The in vitro addition of PFDA directly to the assay mixture for Se-GSHPx activity did not produce any effect. Reduced glutathione was significantly increased by PFDA treatment in all three groups. These data show that PFDA affects the Se content, Se-GSHPx activity and Se-GSHPx protein in rat liver and that the effect is dependent on the dietary/hepatic Se level.

Animals↗

The distribution, induction and isoenzyme profile of glutathione S-transferase and glutathione peroxidase in isolated rat liver parenchymal, Kupffer and endothelial cells.

The distribution and inducibility of cytosolic glutathione S-transferase (EC 2.5.1.18) and glutathione peroxidase (EC 1.11.1.19) activities in rat liver parenchymal, Kupffer and endothelial cells were studied. In untreated rats glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene and 4-hydroxynon-2-trans-enal as substrates was 1.7-2.2-fold higher in parenchymal cells than in Kupffer and endothelial cells, whereas total, selenium-dependent and non-selenium-dependent glutathione peroxidase activities were similar in all three cell types. Glutathione S-transferase isoenzymes in parenchymal and non-parenchymal cells isolated from untreated rats were separated by chromatofocusing in an f.p.l.c. system: all glutathione S-transferase isoenzymes observed in the sinusoidal lining cells were also detected in the parenchymal cells, whereas Kupffer and endothelial cells lacked several glutathione S-transferase isoenzymes present in parenchymal cells. At 5 days after administration of Arocolor 1254 glutathione S-transferase activity was only enhanced in parenchymal cells; furthermore, selenium-dependent glutathione peroxidase activity decreased in parenchymal and non-parenchymal cells. At 13 days after a single injection of Aroclor 1254 a strong induction of glutathione S-transferase had taken place in all three cell types, whereas selenium-dependent glutathione peroxidase activity remained unchanged (endothelial cells) or was depressed (parenchymal and Kupffer cells). Hence these results clearly establish that glutathione S-transferase and glutathione peroxidase are differentially regulated in rat liver parenchymal as well as non-parenchymal cells. The presence of glutathione peroxidase and several glutathione S-transferase isoenzymes capable of detoxifying a variety of compounds in Kupffer and endothelial cells might be crucial to protect the liver from damage by potentially hepatotoxic substances.

Animals↗

Perfluorodecanoic acid decreases the enzyme activity and the amount of glutathione S-transferases proteins and mRNAs in vivo.

The effects of the anti-wetting agent perfluoro-n-decanoic acid (PFDA) on various glutathione S-transferase (GST) enzyme activities were studied in vitro and in vivo. In addition the effects of PFDA treatment on the amount of some glutathione S-transferase subunits and their corresponding translatable mRNA were studied in vivo. PFDA like some other peroxisome proliferators was a non-competitive inhibitor of several GST enzyme activities in vitro. In vivo PFDA reduced the enzyme activity towards substrates which are indicative for the Ya, Yb1 and Yb2 subunits of GSTs to a larger extent than the enzyme activity towards the substrate indicative for the Yc subunit. Whereas the reduction of GST enzyme activities by other peroxisome proliferators was shown to be caused by an inhibition of the relevant enzymes in vivo, PFDA was found to decrease the GST enzyme activities at least in part by lowering the amount of the various GST subunits in vivo due to a lowered concentration of translatable mRNA coding for these enzymes. In addition PFDA abolished the inducibility of GST mRNAs by phenobarbital. Thus PFDA might be an interesting tool for mechanistic studies of the control of GST expression in the liver.

Animals↗

A time-course investigation of vitamin A levels and drug metabolizing enzyme activities in rats following a single treatment with prototypic polychlorinated biphenyls and DDT.

Xenobiotics previously characterized as selective inducers of drug-metabolizing enzymes were chosen to probe possible relationships between enzyme induction and vitamin A metabolism. Liver, kidney and serum retinol and retinyl palmitate levels were investigated in male Sprague--Dawley rats receiving a single i.p. injection of the polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl (300 mumol/kg) or 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (DDT) (150 mumol/kg). While 2,2',5,5'-tetrachlorobiphenyl, a weak or non-inducer, and 2,2',4,4',5,5'-hexaclorobiphenyl and DDT, phenobarbital-type inducers of cytochrome P-450, led to no reduction in total vitamin A content of liver or kidney during the 7 day time-course, administration of 3,3',4,4'-tetrachlorobiphenyl, a toxic PCB and a potent 3-methylcholanthrene-type inducer of cytochrome P-450, resulted in progressively lowered liver vitamin A levels (to 40% of control values by day 7). During this time, kidney total vitamin A content increased 3-fold. The increase in kidney vitamin A (due primarily to increased retinol content) was only equal to 1/40 of total vitamin A which had disappeared from the liver. Although 3,3',4,4'-tetrachlorobiphenyl specifically induced certain drug-metabolizing enzyme activities, e.g. aryl hydrocarbon hydroxylase and UDP-glucuronosyltransferase (toward 4-nitrophenol), no highly significant correlations were found among the vitamin A levels and drug-metabolizing enzyme activities in the liver (aminopyrine N-demethylase, aryl hydrocarbon hydroxylase, aldrin epoxidase, microsomal epoxide hydrolase, UDP-glucuronosyltransferase toward 4-nitrophenol, glutathione transferase toward 1-chloro-2,4-dinitrobenzene and cytochrome P-450 content) as determined by multiple linear regression analysis.

Animals↗

The gerontological decline of the renin-aldosterone system: a chronobiological approach extended to essential hypertension.

The circadian (about 24-hr) oscillating function of the renin-angiotensin-aldosterone system (RAAS) was investigated as a function of age in clinically healthy participants and in essential hypertensive patients. A peculiar age-related decline in the RAAS circadian mesor (rhythm-adjusted mean) and amplitude (variability from mesor) was found in the essential hypertensive patients. This finding suggests a nonphysiologic evolution in the tonic (24-hr mean level) as well as phasic (oscillating amplitude) circadian activity of the RAAS with increasing age. A relative hyperreninemic aldosteronism characterized the aged essential hypertensive patients.

Adolescent↗