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Biomedical subjects

M Walter

Publications and source records attributed to M Walter.

At least 91 records · Page 5Linked to original sources
PubMed1998

Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I.

Plasmas of patients with Tangier disease (TD) lack lipid-rich alpha-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free prebeta-HDL. By contrast to normal plasma, TD plasma does not convert prebeta-HDL into alpha-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of prebeta-HDL into alpha-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37 degrees C but not at 4 degrees C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40-50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40-50% and 30-35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of prebeta-HDL into alpha-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.

Adult↗
PubMed1998

[Palliative surgical therapy].

Advanced malignancies may cause distress, torture, and pain. According to these circumstances palliative treatment using surgical or interventional techniques can be essential. In every single case it has to be assessed, by which means in consideration of patients' strain the outcome may be improved. A close cooperation of all involved disciplines should be the basis of the therapeutic decisions.

Female↗
PubMed1997

Phosphatidylcholine-specific phospholipase C regulates thapsigargin-induced calcium influx in human lymphocytes.

The involvement of phosphatidylcholine-specific phospholipase C (PC-PLC) and D (PC-PLD) in the regulation of the thapsigargin-induced Ca2+ increase was investigated. Pretreatment of human lymphocytes with the PC-PLC inhibitors D609 or U73122 enhanced the thapsigargin-induced Ca2+ influx. By contrast, no effect was observed in the presence of phospholipase D inhibitor butanol. Addition of exogenous PC-PLC but not PC-PLD to lymphocytes prestimulated with thapsigargin led to a decrease of intracellular Ca2+. In addition, thapsigargin was shown to release diacylglycerol (DAG) from cellular phosphatidylcholine pools. The thapsigargin-induced DAG formation was inhibited by U73122 and D609 but not by butanol. Moreover, no formation of the PC-PLD activity marker phosphatidylbutanol was detected. Thapsigargin-induced DAG formation was dependent on the Ca2+ entry, as it was abolished in the absence of extracellular Ca2+ or in the presence of Ni2+. Further investigations demonstrated that the inhibition of the cellular DAG target, protein kinase C (PKC), enhanced thapsigargin-induced Ca2+ increase, whereas direct PKC activation had an inhibitory effect. Taken together, our results reveal the involvement of PC-PLC in the regulation of the thapsigargin-induced Ca2+ increase and point to the existence of a physiologic feedback mechanism activated by Ca2+ influx and acting via consecutive activation of PC-PLC and PKC to limit the rise of intracellular Ca2+.

Bridged-Ring Compounds↗
PubMed1997

Diverse effects of pH on the inhibition of human chymase by serpins.

Inhibition of human chymase by the serpins alpha1-antichymotrypsin (ACT) and alpha1-proteinase inhibitor (PI) at pH 8.0 produces a complex stable to dissociation by SDS/dithiothreitol and a second product, hydrolyzed/inactivated serpin. The first product is the presumed trapped acyl-enzyme complex typical of serpin inhibition, and the second is the result of a concurrent substrate-like reaction. As a result of the hydrolytic reaction, stoichiometries of inhibition (SI) appear greater than 1; values of 4 and 6.0 are observed for the chymase-ACT and -PI reactions. In this study the effect of pH on the inhibition rate constant (kinh) and the SI of each reaction were evaluated to better define the rate-limiting steps of the inhibitory and hydrolytic reaction pathways associated with chymase inhibition. Reactions were evaluated over a pH range to correlate kinh and SI with the ionizations (pK values of 7 and 9) that typically regulate serine protease catalytic activity. The results show that the effects of pH on SI and kinh differ for each inhibitor. On reducing the pH from 8.0 to 5.5, the chymase-ACT reaction exhibited a decrease in SI (to about 1) and little change in kinh, whereas the chymase-PI reaction revealed an increase in SI and a marked decrease in kinh. On increasing the pH from 8.0 to 10.0, the chymase-ACT reaction exhibited little change in SI and a marked decrease in kinh, whereas the chymase-PI reaction revealed a decrease in SI and a marked increase in kinh. Chymase catalytic properties determined for a peptide substrate were atypical over the high pH range exhibiting increases for kcat/Km and kcat and decreases for Km. This behavior suggests the presence of a high pH enzyme form with enhanced hydrolytic activity. From these results and others involving analyses of ACT/PI reactive loop chimeras and ACT point variants exhibiting a range of SI values, we suggest that the diverse pH effects on kinh and SI are caused largely by a difference in the abilities of ACT and PI to interact with low (catalytically inactive) and high (catalytically enhanced) pH forms of chymase. The constancy of kinh for the chymase-ACT reaction over the low pH range suggests that the rate-limiting step for inhibition is pH insensitive and not reflective of diminished chymase hydrolytic activity. Low pH did not appear to affect the rate of SDS-stable complex formation as complex accumulation, assessed qualitatively by SDS-PAGE, correlated with the loss of chymase enzymatic activity.

Catalysis↗
PubMed1997

Low-density lipoproteins inhibit the Na+/H+ antiport in human platelets. A novel mechanism enhancing platelet activity in hypercholesterolemia.

BACKGROUND: LDL have been reported to augment platelet activation, and increased platelet reactivity has been observed in familial hypercholesterolemia. However, the underlying mechanisms of this putatively atherogenic effect is unknown. Because intracellular pH (pHi) may play an important role in platelet function, we examined the influence of LDL on pHi and Na+/H+ antiport activity in human platelets and compared it with the effect of [3-methylsulfonyl-4-piperidinobenzoyl] guanidine hydrochloride (HOE 694), a selective Na+/H+ antiport inhibitor. METHODS AND RESULTS: Using a fluorescent dye technique, we demonstrated that incubation of platelets with physiological concentrations of LDL or with HOE 694 decreased pHi. In addition, both LDL and HOE 694 inhibited the Na+/H+ antiport in platelets treated with sodium propionate or thrombin. The inhibitory effect of LDL was observed both in normal and in glycoprotein (GP)IIb/IIIa-as well as in GPIIIb (CD36)-deficient platelets and was not influenced by the covalent modification of apolipoprotein B lysine residues, suggesting that specific LDL binding sites were not involved. Thrombin-induced phosphoinositide breakdown, diacylglycerol formation, and Ca2+ mobilization, as well as platelet aggregation and granule secretion, were potentiated by both LDL and HOE 694. pHi and Na+/H+ antiport activity were significantly reduced in platelets from patients with familial hypercholesterolemia. Both parameters were normalized after normalization of LDL levels by apheresis treatment. CONCLUSIONS: LDL inhibits the Na+/H+ antiport most likely via receptor-independent mechanisms, thereby augmenting platelet reactivity. This novel mechanisms explains increased platelet reactivity in patients with familial hypercholesterolemia and may contribute to the atherogenic potential of LDL.

Adult↗
PubMed1997

Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Subarachnoid haemorrhage is commonly associated with natriuresis and hyponatraemia. One possible explanation for these features is a defect in the central regulation of renal sodium reabsorption with increased secretion of a natriuretic factor. We investigated whether excess sodium secretion in patients with subarachnoid haemorrhage is related to increased secretion of natriuretic peptides or to the presence of digoxin-like immunoreactive substances. METHODS: We measured the plasma concentrations of digoxin-like immunoreactive substances (by a fluorescence polarisation immunoassay) and natriuretic peptides, aldosterone, renin, and antidiuretic hormone (by radioimmunoassay) in ten patients with aneurysmal subarachnoid haemorrhage, ten patients undergoing elective craniotomy for cerebral tumours, and 40 healthy controls of similar age and sex distribution. Samples were collected before surgery, 1 h, 4 h, and 12 h after surgery, then daily until 7 days postoperatively in the two groups of patients. FINDINGS: All patients with subarachnoid haemorrhage, but none of the tumour patients, showed increased urine output and urinary excretion of sodium (p = 0.018 for comparison of means of curves to 7 days). The patients with subarachnoid haemorrhage had much higher plasma concentrations of brain natriuretic peptide (BNP) than controls, on admission (mean 15.1 [SE 3.8] vs 1.6 [1.0] pmol/L, p < 0.001) and throughout the study period, accompanied by lower than normal aldosterone concentrations and normal plasma concentrations of atrial and C-type natriuretic peptides (ANP, CNP). The patients with tumours had similar plasma concentrations of ANP, BNP, and CNP to the controls. We did not detect digoxin-like immunoreactive substances in either group of patients. INTERPRETATION: Salt-wasting of central origin may induce hyponatraemia in patients with aneurysmal subarachnoid haemorrhage, possibly as a result of increased secretion of BNP with subsequent suppression of aldosterone synthesis.

Brain Neoplasms↗
PubMed1997

Palliative iodized talc pleurodesis with instillation via tube thoracostomy.

Pleural effusions are a severe complication of advanced malignant disease. Palliative treatment strategies should be simple and effective. We investigated iodized talc pleurodesis through tube thoracostomy for this purpose. A total of 43 patients received a suspension of 5 g talc with 3 g thymol iodine via chest tube. The procedure was well tolerated without major complications in all cases. Unfortunately, 4 patients died of disease within the 1st month after treatment, so that only 39 patients were evaluable for treatment outcome. Follow-up ranged from 1 to 14 months. The success rate after 3 months was 92.5%. In conclusion, iodized talc pleurodesis is an excellent tool in the palliative management of malignant pleural effusions. Administration via chest tube is sufficient for treatment success.

Adult↗
PubMed1997

[Hans von Haberer--the beginnings of reconstructive carotid surgery].

Hans von Haberer (1875-1958) gained wide experience in the reconstructive surgery of vascular aneurysms at the universities of Innsbruck, Graz, Düsseldorf and Cologne. In this period he operated on 421 vascular aneurysms--including 30 carotid aneurysms--mainly by means of direct circular vascular suture. In 1914 von Haberer described the first repair of a carotid aneurysm. Therefore he is the pioneer of reconstructive carotid surgery. Based on detailed clinical and operation reports on approximately 16,000 cases, written by Hans von Haberer between 1904 and 1949, and on the contemporary literature, we describe his experience in vascular surgery.

Carotid Artery Diseases↗
PubMed1997

[Gasless video-endoscopic implantation of aortobifemoral vascular prostheses via extraperitoneal approach in the animal experiment].

The gasless videoendoscopic implantation of GELSOFT aortobifemoral vascular prostheses times 6 x 6 mm in diameter using an extraperitoneal approach was tested in ten porcine experimental models at the Surgical Department of the University of Cologne, Germany. Gasless videoendoscopic surgery is performed with a laparolift-laparofan system. Aortobifemoral GELSOFT prostheses were successfully implanted in nine of ten animals, whereby one animal died during preparations for surgery of massive coronary infarctions. Average surgical durations using the extraperitoneal approach were 270 min. Dissection of the infrarenal aorta until occlusion took 45 min, average aortic occlusion 75 min, and iliacofemoral occlusion 45 min for the left side and 75 min for the right side. After successful videoendoscopic implantation of aortobifemoral GELSOFT prostheses all nine animals underwent laparotomy and resection of the aortobifemoral prosthetic segment. The quality of the endoscopically sutured aortic end-to-side anastomoses was examined in vitro under artificial circulation of glycerol/Ringer's lactate solution for evaluation of possible leakage and bursting pressures and then compared to conventionally sutured end-to-side anastomoses of 6-h-old porcine abdominal aorta and GELSOFT prostheses 6 mm in diameter. The maximum bursting pressure of all endoscopically sutured anastomoses was 480 mmHg mean pressure: the minimum was 140 mmHg mean pressure. The minimum leakage per minute was less than 10 ml/min for systolic pressure values between 120 and 350 mmHg. All endoscopically sutured aortic end-to-side anastomoses were comparable to conventionally sutured anastomoses concerning in vitro evaluation of bursting pressure and leakage per minute.

Anastomosis, Surgical↗
PubMed1997

Hans von Haberer: a forgotten pioneer in vascular surgery.

After carrying out the first free vein graft transplantation on an aneurysm of the axillary vein by Lexer in 1907, many attempts were made to reconstruct arterial injuries with direct vascular suture technique or vein graft transplants during the Balkan War (1912) and the First World War (1914-1918). Hans von Haberer gained wide experience in the reconstructive surgery of traumatic aneurysms at the Department of Surgery at the University of Innsbruck. During this period, he operated on a total of 201 vascular aneurysms, mainly using a direct circular vascular suture technique. In 1914, von Haberer described the first reconstruction of a carotid aneurysm. First experiences with vein bypasses were made, but not pursued in the following years.

Aneurysm↗
PubMed1997

Pediatric aerodigestive foreign body injuries are complications related to timeliness of diagnosis.

Foreign body (FB) injury from aspiration or ingestion is a common pediatric health problem. Diagnosis relies on clinical judgment plus medical history, physical examination, and radiographic evaluation. A multi-institutional review of 1269 FB events revealed that 85% were correctly diagnosed following a single physician encounter. However, 15% of the children had an elusive diagnosis (>1 week), despite previous evaluation. Delays in diagnosis were seven times more likely to occur in aspirations than in ingestions. Secondary injuries (e.g., pneumonia and atelectasis) occurred in 13% of airway FBs but in only 1.7% of esophageal FBs. Plain radiographs were used in 82% of children, and special studies (e.g., fluoroscopy) in only 7%. We conclude that diagnosis of FB injury in children is frequently achieved at the initial evaluation but that continued surveillance by follow-up visits to health care facilities from parents and other caretakers is important, to reduce pulmonary injuries.

Adolescent↗
PubMed1997

Enhancing endogenous effects of natriuretic peptides: inhibitors of neutral endopeptidase (EC.3.4.24.11) and phosphodiesterase.

Because diuretic drugs remain the main treatment for disorders of sodium and water metabolism, the quest for improved diuretic and natriuretic agents continues in the hope of achieving fewer side effects and a more rational basis in pathophysiology. One aim has been to enhance endogenous diuretic and natriuretic activity by selective manipulation of atrial natriuretic peptide and related compounds. The first approach has been to inhibit degradation of these peptides using inhibitors of their main catabolic enzyme, neutral endopeptidase, and to offset any antagonistic effect of the renin-angiotensin system by combination with an angiotensin-converting enzyme inhibitor. The second and more recent approach has been to inhibit breakdown of the second messenger of atrial natriuretic peptide, cGMP, using phosphodiesterase inhibitors. As yet, neutral endopeptidase inhibition has not advanced successfully beyond animal experimentation and phosphodiesterase inhibition is still in its infancy. Both strategies suffer from the problem that, on the one hand, neutral endopeptidase metabolizes a variety of bioactive peptides, including endothelin, and it is not possible to develop inhibitors that will be selective for a given peptide; whereas, on the other hand, there are several phosphodiesterase isoforms metabolizing cGMP and cAMP, both second messengers for many different bioactive compounds, and selective inhibitors are still under development.

Animals↗
PubMed1997

Allergenicity of alpha-caseins from cow, sheep, and goat.

The allergic potential of alpha-caseins from bovine, ovine, and goat's milk sharing more than 85% identical amino acids was compared. Caseins were purified by anion-exchange chromatography and used for a specific IgE and IgG ELISA with diluted human sera. Sera were from 17 children with immediate-type allergy to cow's milk, from 59 children with atopy but without food allergy, and from 27 healthy children without atopy disease. The sera of cow's milk-allergic children showed a significantly higher IgE and IgG binding to alpha-caseins from all three species than the sera of the other groups. All groups showed an increased antibody binding to bovine alpha-casein compared to the sheep and goat proteins, but the differences were significant only in the groups of atopic children and of healthy controls. Furthermore, inhibition of the IgE binding to bovine alpha-casein with alpha-casein from cow, goat, and sheep revealed that the alpha-casein from these species are highly cross-reactive; on the basis of the small differences in their primary structure. In conclusion, the milk of goat and sheep harbor an allergic potential and is not suitable for the nutrition of milk-allergic patients.

Animals↗
PubMed1997

Gasless videoendoscopic implantation of aortobifemoral vascular prostheses via a transperitoneal approach--an animal experiment.

BACKGROUND: Standard approach for aortobifemoral vascular approach prostheses is the transperitoneal approach, following median laparotomy and bilateral inguinal incision. The goal of this animal experiment was the development of a new minimal-invasive surgical technique utilizing a less-traumatic approach for aortobifemoral bypass. METHODS: The gasless videoendoscopic implantation of 6 x 6 mm diameter aortobifemoral-bifurcation prostheses in transperitoneal approach was tested at the Surgical Department of the University of Cologne in 10 domestic pigs. Gasless videoendoscopic surgery is performed with a laparolift-laparfan-system. After videoendoscopic implantation of aortobifemoral prostheses, all 9 animals underwent laparotomy and resection of the aortobifemoral prosthetic segment. The quality of the endoscopically sutured aortic end-to-side anastomoses was examined under artificial in-vitro circulation of glycerol/ringer-lactate solution for evaluation of possible leakage and bursting pressures. Moreover, the anastomoses were compared to conventionally sutured end-to-side anastomoses of six-hour old porcine abdominal aortas and 6 mm diameter prostheses. The maximum bursting pressure of all endoscopically sutured anastomoses averaged 450 mmHg, whereby the minimum bursting pressure amounted to 100 mmHg mean pressure. RESULTS: Aortobifemoral prostheses were successfully implanted in 9 out of 10 animals, one animal dying during preparation for the surgery, succumbing to massive coronary infarctions. Surgical durations for the transperitoneal approach averaged four hours, whereby surgical durations were reduced with increasing experience to a minimum of 3 hours 30 minutes. Dissection of the infrarenal aorta until occlusion required 35 minutes. Average aortic occlusion duration amounted to 1 hour; iliacofemoral occlusion duration amounted to 1 hour for each side. The leakage per minute at the beginning achieved a maximum of 80 ml/min and systolic pressure values of 350 mmHg in consideration of all flow levels, 60 ml/min for systolic pressure values of 200 mmHg and 20 ml/min for systolic pressure values of 120 mmHg. The minimum level leakage per minute was less than 10 ml/min for systolic pressure values between 120-350 mmHg. CONCLUSION: Gasless videoendoscopic implantation of aortobifemoral vascular prostheses in transperitoneal approach is practicable in animal experiments. All endoscopically sutured aortic endo-side anastomoses were comparable to conventionally sutured anastomoses in in-vitro evaluation of bursting pressure and leakage per minute.

Animals↗