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M Ruppert

Publications and source records attributed to M Ruppert.

35 records · Page 2Linked to original sources

[Potassium citrate versus potassium chloride in essential hypertension. Effects on hemodynamic, hormonal and metabolic parameters].

A study was conducted on 25 patients (18 men, seven women; mean age 48 [24-70] years) with essential hypertension (EH) to see whether an increase in potassium supply influences blood pressure as well as metabolic and hormonal parameters, and whether the anion administered together with potassium affects the results. In a randomized, cross-over trial sequence the patients daily received 120 mmol potassium chloride, 120 mmol potassium citrate or a placebo, each for 8 weeks. Between each of the three periods there was a "wash-out" phase of 4 weeks each. After 8 weeks of potassium citrate intake the systolic and diastolic pressures were reduced significantly, by a mean of 6.2/3.8 mm Hg (P < 0.05). But after potassium chloride there was only a small, not significant, reduction. Metabolic and hormonal parameters (fasting glucose concentration, glucose tolerance test, lipid electrophoresis; plasma renin activity, plasma concentration of aldosterone, noradrenaline and insulin) were not significantly changed.--These findings suggest that an increased supply of potassium has a favourable haemodynamic effect, but this varies markedly between different potassium salts. An increase in potassium supply should thus be considered as an additional measure in the treatment of EH. As long as renal function is normal no unfavourable metabolic effect need be feared.

Adult↗

Age is a major determinant of the divergent blood pressure responses to varying salt intake in essential hypertension.

Blood pressure responses to 1 week of low (20 mmol sodium/day) and high (300 mmol sodium/day) salt intake were investigated in a double-blind, randomized study in 46 white, nonobese subjects with essential hypertension (13 women, 33 men; mean age 45.3 +/- 2.2 years, age range 25 to 80 years). The individuals were classified as salt-sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high salt intake, as salt-resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counter-regulators" when mean arterial blood pressure fell by at least 5 mm Hg during the high salt diet. Mean arterial blood pressure of all subjects taken together increased from 101.9 +/- 1.4 mm Hg during salt restriction to 103.7 +/- 1.5 mm Hg (P < .05) during salt loading. Eleven subjects (23.9%) were classified as salt-sensitive, 27 (58.7%) as salt-resistant, and 8 (17.4%) as counter-regulators. Multiple regression analysis revealed that age, but not baseline blood pressure, sex, body mass index, or family history of hypertension contributed significantly to the change in blood pressure following the diets. Ten of the 11 salt-sensitive subjects were older than the median age of 45 years. In salt-sensitive, as compared to salt-resistant, hypertensive subjects, creatinine clearance was lower and plasma renin activity was suppressed at baseline as well as during low and high salt intake. In contrast, plasma concentrations of norepinephrine and atrial natriuretic peptide were elevated in salt-sensitive subjects. These differences between the groups appeared, at least partially, to be age-related.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The L1 adhesion molecule is a cellular ligand for VLA-5.

The L1 adhesion molecule is a member of the immunoglobulin superfamily shared by neural and immune cells. In the nervous system L1 can mediate cell binding by a homophilic mechanism. To analyze its function on leukocytes we studied whether L1 could interact with integrins. Here we demonstrate that VLA-5, an RGD-specific fibronectin receptor on a wide variety of cell types, can bind to murine L1. Mouse ESb-MP cells expressing VLA-5 and L1 could be induced to aggregate in the presence of specific mAbs to CD24 (heat-stable antigen), a highly and heterogeneously glycosylated glycophosphatidylinositol-linked differentiation antigen of hematopoietic and neural cells. The aggregation was blocked by both mAbs to L1 and VLA-5, respectively. Aggregation was blocked also by a synthetic RGD-containing peptide derived from the Ig-domain VI of the L1 protein. ESb-MP subclones with low L1 expression could not aggregate. In heterotypic binding assays mouse bone marrow cells could adhere in an L1-dependent fashion to platelets that expressed VLA-5. Also purified L1 coated to polystyrene beads could bind to platelets. The binding of L1-beads was again inhibited by mAbs to L1 and VLA-5, by soluble L1 and the L1-RGD peptide in a dose-dependent manner. Thymocytes or human Nalm-6 tumor cells expressing VLA-5 could adhere to affinity-purified L1 and to the L1-derived RGD-containing peptide coated to glass slides. The adhesion was strongly enhanced in the presence of Mn(2+)-ions and blocked by mAbs to VLA-5. We also demonstrate a direct L1-VLA-5 protein interaction. Our results suggest a novel binding pathway, in which the VLA-5 integrin binds to L1 on adjacent cells. Given its rapid downregulation on lymphocytes after induction of cell proliferation, L1 may be important in integrin-mediated and activation-regulated cell-cell interactions.

Amino Acid Sequence↗

Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin.

P-selectin is a Ca(2+)-dependent lectin that participates in leukocyte adhesion to vascular endothelium and platelets. Myeloid cells and a subset of T lymphocytes express carbohydrate ligands at the cell surface. Previously, we suggested that heat stable antigen (HSA/mouse CD24), an extensively glycosylated cell surface molecule on many mouse cells, is a ligand for P-selectin. Here we show that HSA mediates the binding of monocytic cells and neutrophils to P-selectin. The monocytic cell lines ESb-MP and J774, peritoneal exudate cells, and bone marrow neutrophils could bind to lipopolysaccharide-activated bend3 endothelioma cells under rotation-induced shear forces and this binding was inhibited by mAb to P-selectin and HSA. Blocking was weak at room temperature but more efficient at 4 degrees C when integrin-mediated binding was decreased. Also the adhesion of neutrophils to stimulated platelets expressing P-selectin was blocked by HSA- and P-selectin-specific mAb. Latex beads coated with purified HSA from myeloid cells bound to activated endothelioma cells or platelets, and the binding was similarly blocked by mAb to P-selectin and HSA respectively. The HSA-coated beads were stained with P-selectin-IgG, very weakly with L-selectin-IgG but not with E-selectin-IgG. The staining was dependent on divalent cations and treatment with endoglycosidase F or neuraminidase indicated that sialylated N-linked glycans were recognized. The presence of these glycans was confirmed by biosynthetic labeling studies. Our data suggest that HSA, in addition to the recently identified 160 kDa glycoprotein ligand on mouse neutrophils, belongs to a group of monospecific P-selectin ligands on myeloid cells.

Animals↗

The lymphocyte Na+/H+ antiport: activation in primary hypertension and during chronic NaCl-loading.

Increased activity of the Na+/H+ antiport may be a major abnormality in essential hypertension. The activity of this transport system was investigated in lymphocytes from 13 patients with untreated essential hypertension (Ht) and 13 normotensive control subjects (Nt) on an ad libitum (130-170 mmol d-1) NaCl intake. Furthermore, the effects of different states of NaCl balance on lymphocyte Na+/H+ antiport were evaluated in two groups of Nt volunteers receiving 20 vs. 300 mmol d-1 (n = 8) and 85 vs. 200 mmol d-1 (n = 14) of NaCl for 1 week each and in seven Ht patients (20 vs. 300 mmol NaCl d-1 for 1 week each). Additionally, during the 20 and 300 mmol/d NaCl intake red blood cell membrane transport was studied in eight subjects. For the determination of lymphocyte antiport activity, cells were loaded with the cytosolic pH (pHi) indicator bis-carboxyethyl carboxyfluorescein (BCECF-AM) and acidified by addition of different amounts of Na(+)-propionate (5-40 mM). Initial pHi-recovery was taken as the activity of the antiport system and plotted against pHi-values after acidification. Non-linear regression analysis yielded higher 'apparent' maximal transport rates in Ht than Nt (Nt: 2.00 +/- 0.22; Ht: (3.81 +/- 0.59) x 10(-3) s-1; P < 0.025). In contrast, baseline pHi-values and pHi-values at half-maximal activity (pK) were identical in Nt and Ht. In normotensive control subjects on an NaCl intake of 20, 85, 200 and 300 mmol d-1 for 7 d, 'apparent' maximal transport rates averaged 2.75 +/- 0.20, 2.89 +/- 0.17, 2.81 +/- 0.18 and (3.62 +/- 0.25) x 10(-3) s-1, respectively. Thus, antiport activity was significantly (P < 0.05) stimulated on the 300 mmol d-1 intake as compared to the three other NaCl intakes. The extreme intakes of NaCl (20 vs. 300 mmol d-1) in normotensive volunteers did not affect the erythrocyte Na+/K+ pump, Na+/K+ cotransport and Na+/Li+ countertransport. Our study supports the concept that a group of patients with primary hypertension exhibit an activated Na+/H+ antiport. Furthermore, our data demonstrate that a chronic high intake of NaCl is associated with an increase in lymphocyte antiport activity towards the high values observed in primary hypertension.

Adult↗

Effects of severe and moderate salt restriction on serum lipids in nonobese normotensive adults.

The effects of severe and moderate sodium restriction on blood pressure and serum lipids were studied in nonobese normotensive adults. Subjects (n = 163) were given a low (20 mmol Na/d) and high (300 mmol Na/d) salt diet for 1 week each in random order. Of these subjects, 25 were selected to participate in a second study with moderate salt restriction (85 mmol na/d) or "normal" sodium diet (200 mmol Na/d) given for 4 weeks each in random order. After severe salt restriction, 19% of the 163 subjects had a significant decrease in blood pressure (salt-sensitive), 15% showed a significant rise (counter-regulator), and 66% exhibited no change (salt-resistant). Severe sodium restriction increased serum total and low density lipoprotein (LDL) cholesterol and triglycerides. After correction for hematocrit, the changes in blood lipids remained significant in the counter regulators only. After moderate salt restriction, serum lipid concentrations and blood pressure did not change.

Adult↗

Neurohormonal and metabolic effects of severe and moderate salt restriction in non-obese normotensive adults.

OBJECTIVE: The effects of severe and moderate sodium restriction on blood pressure, neurohormonal activity and serum lipids were studied in non-obese normotensive adults. METHODS: In the first part of the study, 163 subjects were randomly assigned to a diet of 20 or 300 mmol/day sodium for 1 week each. In the second part, 25 subjects were given a diet of 85 or 200 mmol/day sodium for 4 weeks each in random order. RESULTS: After severe salt restriction 19% of the subjects had a significant decline (salt-sensitive group), 15% showed a significant rise (counter-regulator group) and 66% exhibited no change in blood pressure (salt-resistant group). Severe sodium restriction increased plasma renin activity and noradrenaline concentration, as well as serum total and low-density lipoprotein-cholesterol and triglycerides. After correction for haematocrit, only the changes in total and low-density lipoprotein-cholesterol remained significant. The rise in plasma renin activity during salt restriction was steeper in the counter-regulator group than in the other groups, whereas the changes in plasma noradrenaline concentrations were similar in all groups. During moderate salt restriction, plasma renin activity and noradrenaline concentration were significantly increased, but serum lipid concentrations and blood pressure did not change. CONCLUSION: In non-obese normotensive adults, severe and moderate salt restriction stimulates neurohormonal activity. In contrast to severe salt restriction, a moderate reduction in dietary salt intake does not influence blood lipids in normotensive subjects.

Adult↗

Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects.

Blood pressure responses to 1 week of low-salt (20 mmol sodium/d) and high-salt (300 mmol sodium/d) intake were investigated in a single-blind randomized study in 163 white, nonobese normotensive subjects (65 women and 98 men; mean age, 38 +/- 1.2 years). The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake, as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counterregulator" when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet. Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible. Thirty subjects (18.4%) were classified as salt sensitive, 108 (66.3%) as salt resistant, and 25 (15.3%) as counterregulators. Multiple regression analysis revealed that age, body weight, and family history of hypertension contributed significantly to the change in blood pressure after the diets. Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension. An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension. Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects. The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects. Plasma norepinephrine concentrations were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Bullous poikilodermatitic amyloidosis of the skin with junctional bulla development in IgG light chain plasmacytoma of the lambda type. Histology, immunohistology and electron microscopy].

A 75-year-old patient presented with bullae, poilokilodermatic skin and nail dystrophy as signs of systemic amyloidosis 1 year before an IgG myeloma of the lambda type was diagnosed. The skin lesions appeared at mechanically irritated locations on the trunk and at the tensor sites of the extremities. Histology showed a subepidermal blister and necrotic keratinocytes in the epidermis. There were amyloid deposits in the papillary dermis perivascular, and in the deep dermis around eccrine glands and in arrectores pilorum muscles. Polyclonal antibodies allowed classification of the deposits as amyloid composed of lambda light-chain immunoglobulins. Electron microscopy revealed globoid deposits of non-branching filaments typical of amyloid. The blister was formed at the level of the lamina lucida, with the lamina densa at the base of the bottom of the bulla. So far, junctional blister formation in bullous amyloidosis of the skin has been described only once. Our case is the second report of this blister type, and to our knowledge the first published report of a junctional blister in myeloma-associated systemic amyloidosis.

Actin Cytoskeleton↗

Membrane transport, sodium balance, and blood pressure regulation.

Essential hypertension is characterized by polygenic inheritance and quantitative and/or qualitative abnormalities of membrane transport systems may function as intermediate phaenotypes. The present review attempts to evaluate the importance of sodium transport systems such as the sodium pump, cotransport and countertransport as aetiological or pathogenetic factors involved in primary hypertension. Furthermore, the relative importance of NaCl balance as an exogenous factor modifying these transport systems is reviewed. Controversial results exist with respect to the activity of the sodium pump and cotransport both as a function of blood pressure and NaCl balance. In contrast, accumulating evidence suggests that the activity of the counter-transport system is increased in essential hypertension and that this may be observed even before the elevation of blood pressure can be documented. In own studies performed in normotensive volunteers on a low (20 mmol/day) and high (320 mmol/day) NaCl intake, lymphocyte antiport activity was significantly higher during chronic NaCl loading. Therefore, alterations of the Na+/H+ antiport system may represent an intermediate phaenotype of gene(s) involved in the genesis of primary hypertension. Preliminary evidence suggests that NaCl balance may be an exogenous modulator of this system.

Animals↗

Short-term dietary sodium restriction increases serum lipids and insulin in salt-sensitive and salt-resistant normotensive adults.

Evidence suggests that dietary salt reduction similar to diuretic therapy may adversely affect lipid and glucose metabolism. We studied 147 non-obese normotensive subjects (60 females and 87 males) aged 19-78 years who entered a single-blind crossover trial and were randomly assigned to a low salt diet of 20 mmol or a high salt diet of 300 mmol sodium per day, for 7 days each. Sodium restriction lowered mean arterial blood pressure (MAP) by a mean of 7.5 mmHg in 17% (salt-sensitive), had no hemodynamic effect in 67% (salt-resistant) and raised MAP by a mean of 6 mmHg in 16% of the subjects (reverse reactors). With dietary salt restriction serum total- and LDL-cholesterol as well as serum insulin and uric acid concentrations increased significantly in all three groups. The largest increases in total (10%) and LDL- (12%) cholesterol occurred in the reverse reactors. Salt-sensitives had significant higher lipoprotein(a) values than the other two groups. Salt-restriction had no significant effect on this parameter. Plasma renin activity, as well as plasma aldosterone and noradrenaline concentrations rose in all three groups during the low salt diet, the largest increases being observed in the reverse reactors. Short-term sodium restriction in normotensive adults has unfavourable effects on lipid and glucose metabolism, especially in subjects who do not derive hemodynamic benefit. Further studies are necessary to examine the effects of more moderate salt reduction for longer periods on the risk factor profile for cardiovascular disease before a low salt diet can be regarded as a safe public health measure for the general population.

Adult↗

Glycosyltransferase activities and the differentiation of human promyelocytic (HL60) cells by retinoic acid and a phorbol ester.

The activities of five glycosyltransferases were measured following the induction of HL60 cells to differentiate to mature myeloid forms or to macrophages by the addition of retinoic acid or a phorbol ester, respectively. Gal-T-II, Fuc-T-I and (NeuAc-T-I) are all increased and Fuc-T-II decreased in activity upon treatment with RA. Gal-T-I and Fuc-T-II are decreased and Gal-T-II increased in activity upon with TPA treatment. The increases in enzyme activities with RA are measurable as early as 1 day but while Fuc-T-I and NeuAc-T-I are fully elevated at 2 days, Gal-T-II shows a biphasic rise with initial elevation by day 2 and a further rise at days 3 to 5. The rises in Gal-T-II are due to increases in the enzyme form present in uninduced cells.

Cell Differentiation↗

[Physostigmine reversal of central anticholinergic syndrome induced by midazolam/fentanyl, benzoctamine/buprenorphine and etomidate/carticaine or by atropine/promethazine/pethidine for premedication? (author's transl)].

Five cases of post narcotic delirium, somnolence or coma are interpreted as central anticholinergic syndromes as they were reversed by physostigmine. There is to date no information whether the drug combinations midazolam/fentanyl, benzoctamine/buprenorphine and etomidate/carticaine may act as central anticholinergic agents.

Adult↗

What have we learnt after two years working with the da Vinci robot system in digestive surgery?

Robotic- assisted surgery has been introduced recently in order to overcome some of the difficulties surgeons encounter during advanced laparoscopic surgery. Due to the 3D vision equipment, higher number of degrees of freedom in manipulating instruments and better ergonomics it is hoped that by using robot techniques the indications of minimally invasive surgery in the field of digestive surgery can be broadened or that difficult procedures will be easier to perform. Since the introduction of the system in our hospital now almost two years ago 70 procedures have been performed with the aid of the da Vinci system covering the whole spectrum of GI surgery. Conversion took place in 2.5% and peroperative morbidity related to the use of robotic techniques was 10%. Although we had the subjective feeling that the procedures were indeed easier to perform and more relaxing for the surgeon, some major problems still exist as the complete lack of tactile feedback and the cost effectiveness of these procedures. Before robotics can be introduced in the every day clinical practice of the surgeon, its true benefit still needs to be established. This can only be done by well randomised prospective studies comparing one technique with the other.

Digestive System Surgical Procedures↗

Intestinal necrosis in a patient with rheumatoid arthritis receiving anti-TNF treatment.

Vasculitis leading to intestinal necrosis is a rare complication of rheumatoid arthritis. The introduction of anti-TNF treatment for methotrexate-resistant cases improved disease-control substantially in these often more aggresive forms of rheumatoid arthritis. As far as we know only two cases of severe vasculitis following anti-TNF treatment have been reported. We describe a 45-year old female patient with severe rheumatoid arthritis, who presented with an epileptic insult, renal failure and a quickly deteriorating general condition due to intestinal vasculitis, while she had been receiving anti-TNF treatment for 6 months.

Antibodies, Monoclonal↗