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Biomedical subjects

H Fuchs

Publications and source records attributed to H Fuchs.

At least 37 records · Page 2Linked to original sources
PubMed1996

Laparoscopic repair of recurrent inguinal hernias.

BACKGROUND: Repair of recurrent inguinal hernias is associated with recurrence rates as high as 30% and complication rates higher than for primary hernias. PATIENTS AND METHODS: In a prospective study, results were evaluated after laparoscopic transabdominal preperitoneal hernia repair in 192 patients with 200 recurrent inguinal hernias. A total of 132 hernia repairs followed one previous repair, 41 followed two repairs, 17 followed three repairs, 6 followed four, 3 followed five, and 1 followed six previous repairs. The surgical technique is described. RESULTS: Follow-up ranged from 9 to 31 months (mean 18.4). Twelve patients (6%) had groin seromas or hematomas; 3 (1.5%) had transient thigh numbness. One patient (0.5%) underwent laparoscopy a second time because of a large hematoma. In 1 patient (0.5%), a staple on the n. cutaneus femoris lateralis was removed laparoscopically. Patients described postoperative pain as being much less severe compared with their previous operation. Of the total group, 76% of patients were able to return to work within 2 weeks of surgery. One recurrence (0.5%) occurred after 6 months because of too small a prosthetic mesh. CONCLUSIONS: This laparoscopic technique can be applied to recurrent hernias, even in difficult cases, with low morbidity rates. Recurrence rates as low as for laparoscopic repair of primary hernias can be expected.

Adult↗
PubMed1996

Antiphospholipid syndrome associated with seizures.

Antiphospholipid antibodies have been associated with thrombosis, fetal wasting, and thrombocytopenia. We discuss a case of antiphospholipid syndrome with the rarely recognized presentation of generalized tonic-clonic seizure during pregnancy. This case emphasizes the need for evaluation of possible hypercoagulable states in young adults with cerebrovascular events or newly diagnosed seizures.

Adult↗
PubMed1996

Borrelia burgdorferi induces secretion of pro-urokinase-type plasminogen activator by human monocytes.

Borrelia burgdorferi is transmitted by infected ticks and causes Lyme disease. To infect distant organ sites, B. burgdorferi spirochetes must disseminate from the site of the tick bite. During dissemination from the dermal tissue, they breach tissue barriers, probably by proteolysis. The previous findings that spirochetes bind serum-derived plasminogen and that plasmin favors spirochetal invasiveness and infectivity suggested a role for plasmin in the pathogenicity of B. burgdorferi. Binding of plasminogen to spirochetes and activation into plasmin is favored in a microenvironment that is rich in plasminogen and plasminogen activators. Plasminogen is abundant in plasma and interstitial fluids, and it is increased in inflammatory exudates. Since B. burgdorferi does not express endogenous plasminogen activators, the conversion of spirochete-bound plasminogen depends on host-derived plasminogen activators. In this report, we show that both intact B. burgdorferi organisms and its recombinant outer surface lipoprotein A induce human monocytes to express and secrete urokinase-type plasminogen activator in its zymogen form (pro-uPA). Moreover, we demonstrate that the presence of B. burgdorferi accelerates the interaction between (pro-)uPA and plasmin(ogen), leading to spirochete-bound plasmin. In a pro-uPA-serum mixture, spirochete-bound plasmin activity is generated. Taken together, the data suggest that B. burgdorferi may induce pro-uPA in a monocyte-containing inflammatory site and that the spirochetal surface provides an appropriate milieu for subsequent interactions between (pro-)uPA and plasmin(ogen), which result in spirochete-bound plasmin even in the presence of inhibitors for plasminogen activators and plasmin.

Borrelia burgdorferi Group↗
PubMed1996

[The possibility of preventing non-insulin dependent diabetes].

High and rapid growing up incidence of non-insulin-dependent diabetes mellitus (NIDDM) leading to severe chronic complications and significant reduction of life expectancy, as well as a huge rise of direct and indirect costs connected with the disease oblige to search for methods of its prevention. Scientific basis of the prevention grounded on a knowledge of genetic and environmental pathogenetic factors as well as natural history of NIDDM does exist. The article discussed shortly the strategy of prevention based on attempts of life style (diet, physical exercise) and pharmacological interventions. Actually, primary prevention of NIDDM seems to be hypothesis requiring further testing, but the possibility and necessity of secondary and tertiary prevention is incontroversible.

Diabetes Mellitus, Type 2↗
PubMed1995

Direct calibration ELISA: a rapid method for the simplified determination of association constants of unlabeled biological molecules.

We present a novel method for the rapid determination of association constants. The method is based on the direct calibration of an enzyme-linked immunosorbent assay (dcELISA) and does not require any external calibration. It combines kinetic and equilibrium binding experiments and can be performed on a single microtiter plate. The absorbance data are evaluated by several linearized plots without the need for sophisticated computations. The dcELISA has been used to analyze the binding of a monoclonal antibody, OKT9, to its cognate antigen, the human transferrin receptor, and yielded an association constant of Ka = 2.2 x 10(9) l/mol and a complex formation rate constant of kc = 2.7 x 10(-4) s-1. A 26% larger association constant was obtained with a radioimmunoassay (RIA)-based Scatchard analysis using 125I-labeled OKT9. By quantifying the binding of the same iodinated antibody with the dcELISA we were able to verify that the iodination modifies the binding properties of the antibody. The dcELISA thus appears to be superior to all methods requiring covalent modifications. In principle, the direct calibration method can also be combined with all other solid phase assays. It should thus expand their scope in quantifying the binding properties of biologically important molecules.

Animals↗
PubMed1995

Functional reconstitution of the human placental transferrin receptor into phospholipid bilayers leads to long tubular structures proceeding from the vesicle surface.

We have reconstituted the human placental transferrin receptor (hTfR) into phospholipid vesicles using either dialysis, dilution, or gel filtration. Several different detergents and phospholipids and a variety of lipid-to-protein weight ratios were tested. Preformed vesicles as well as detergent-solubilized phospholipids were used. Reconstituted mixtures were fractionated by sucrose density gradient centrifugation and screened for ferritransferrin binding activity, and peak fractions were analyzed by electron microscopy. The efficiency of reconstitution was strongly influenced by the choice of the phospholipids used and the reconstitution method. Best results were obtained when hTfR was dissolved with octylpolyoxyethylene, mixed with detergent-solubilized soy bean lecithin, and reconstituted by slow dialysis. The data show that hTfR capable of binding ferritransferrin was reconstituted into vesicles with an irregular surface and many protrusions. In addition the reconstitution of hTfR resulted in the formation of tubular structures proceeding from the vesicle surface, which may serve as an in vitro model for future studies on the relevance of self-assembly processes for cellular endocytosis.

Centrifugation, Density Gradient↗
PubMed1995

Cyclophosphamide in combination with sargramostim for treatment of recurrent medulloblastoma.

Thirteen patients with recurrent medulloblastoma were treated with cyclophosphamide in association with Sargramostim. Cyclophosphamide was given at doses ranging between 1.0-2.5 g/m2 daily for two doses. Sargramostim was given at a fixed dose of 250 micrograms/m2 subcutaneously twice a day beginning 24 hours after the second cyclophosphamide dose and continuing through the leukocyte nadir until the ANC was more than 1,000 cells/microliters for two consecutive days. A total of 33 courses were given with toxicity consisting of grade 4 neutropenia in all courses and grade 3-4 thrombocytopenia in 10 of 13 patients. There were no deaths related to infection or bleeding. Four patients were taken off study because of prolonged myelosuppression. Three of these patients were at the 2.5 g/m2 level, and of these three, two developed lung toxicity (grades 2 and 4, respectively). One patient developed an allergic reaction following the first injection of Sargramostim and was also taken off study. Of 10 evaluable patients, there were 9 PR and 1 SD. We conclude that cyclophosphamide at a dose of 2.0 g/m2/day x 2 days q 4 weeks in association with Sargramostim demonstrates marked activity with acceptable toxicity in patients with recurrent medulloblastoma.

Adolescent↗
PubMed1995

Schistosoma mansoni and S. haematobium: miracidial host-finding behaviour is stimulated by macromolecules.

The miracidia of Schistosoma mansoni and S. haematobium approach their host snails by increasing their rate of change of direction (RCD) in increasing gradients of snail-conditioned water (SCW), and they perform a turnback response in decreasing gradients. After contact with the host "repeated investigation" is the typical host-specific response. Both species show no significant directed chemotactical orientation towards their snail hosts. All three host-finding responses (increased RCD, turnback response, and "repeated investigation") seem to be stimulated in both species by a similar component of SCW, a macromolecular glycoconjugate with a molecular weight > 30,000. The saccharide chains seem to be O-glycosidically linked via serine and N-acetylgalactosamine. The glycoconjugate is sensitive to lysozyme which may suggest that muramic acid as a gastropod-specific component is involved in the recognition process. Small molecular components of SCW, as well as magnesium chloride offered as pure chemical, may cause a moderate increase in the RCD. Therefore a minor contribution of these components to the host-finding response of schistosome miracidia cannot be excluded. That schistosome miracidia respond to complex macromolecules as host cues may indicate an adaptation to avoid interference of the host-finding with ubiquitous small molecular mud components and it might enable the miracidia to achieve a high degree of host-specificity in their host-finding.

Animals↗
PubMed1995

"Cardioplegia on the contractile apparatus level": evaluation of a new concept for myocardial preservation in perfused pig hearts.

UNLABELLED: The concept of a reversible desensitization of the myocardial contractile apparatus for calcium by 2,3 Butanedione Monoxime (BDM) as a method to improve the myocardium's tolerance to cold ischemia was evaluated in normal pig hearts (n = 14). The results were compared to those obtained after application of Bretschneider's HTK cardioplegic solution. METHODS: Series I) After BDM treatment (concentrations: 0-30 mmol/L) the isometric force output and the intracellular calcium transients (measured using the FURA-2 ratio method) of electrically driven (1 Hz) isolated left-ventricular muscle strips excised from beating pig hearts (n = 14) were recorded simultaneously in order to analyse the mode of action of BDM; Series II) The cardioprotective effects of BDM (30 mmol/L) and Bretschneider's cardioplegic solution (HTK) were compared in a large-animal model: after "in situ perfusion" of pig hearts with either 2000 ml ice-cold BDM solution (30 mmol/L) (n = 7) or 2000 ml HTK (n = 7) the hearts were explanted and stored at 4 degrees C in the same solutions for up to 42 h. The contractile properties of muscle fibres, excised after storage periods of 8, 24, and 42 h from these hearts were analyzed in terms of isometric force development and isotonic shortening. 280 muscle fibres from 14 pigs were used for measurements. RESULTS: Series I) In pig myocardium a dose-dependent reduction of isometric force development was found after BDM application. The shape and the amplitude of the intracellular calcium transient were also affected by BDM. At 30 mmol/L BDM no force development could be elicited despite the presence of an intracellular calcium transient (amplitude < 70% of the control). Series II) Shortening, calcium transient, and force of left-ventricular muscle strips of pig myocardium excised after storage periods for up to 42 h showed complete recovery when BDM was applied. In contrast HTK perfusion allowed complete recovery of these parameters when the storage period did not exceed 6 hours. CONCLUSION: Under the given experimental conditions reversible desensitization of the contractile apparatus for calcium results in a considerable prolongation of the tolerance to cold ischemia in explanted pig hearts. The present study shows that the protective effects of BDM are not only present when isolate muscle fibres were stored (and the extracellular space is large) but also after storage of complete hearts in a solution in a solution containing BDM. Thus BDM may become a useful agent to enlarge the storage period of donor hearts in heart transplatation considerably.

Animals↗
PubMed1995

Transferrin-binding protein complex is the receptor for transferrin uptake in Trypanosoma brucei.

In Trypanosoma brucei, the products of two genes, ESAG 6 and ESAG 7, located upstream of the variant surface glycoprotein gene in a polycistronic expression site form a glycosylphosphatidylinositol-anchored transferrin-binding protein (TFBP) complex. It is shown by gel filtration and membrane-binding experiments that the TFBP complex is heterodimeric and binds one molecule of transferrin with high affinity (2,300 binding sites per cell; KD = 2.1 nM for the dominant expression site from T. brucei strain 427 and KD = 131 nM for ES1.3A of the EATRO 1125 stock). The ternary transferrin-TFBP complexes with iron-loaded or iron-free ligand are stable between pH 5 and 8. Cellular transferrin uptake can be inhibited by 90% with Fab fragments from anti-TFBP antibodies. After uptake, the TFBP complex and its ligand are routed to lysosomes where transferrin is proteolytically degraded. While the degradation products are released from the cells, iron remains cell associated and the TFBP complex is probably recycled to the membrane of the flagellar pocket, the only site for exo- and endocytosis in this organism. It is concluded that the TFBP complex serves as the receptor for the uptake of transferrin in T. brucei by a mechanism distinct from that in mammalian cells.

Animals↗
PubMed1995

Intravenous immune globulin in the treatment of patients with systemic lupus erythematosus and end-stage renal disease.

Intravenous immune globulin (IVIg) has been advocated as efficacious therapy for a variety of disorders including idiopathic thrombocytopenic purpura and Kawasaki disease. Several reports have also documented the effectiveness of IVIg in systemic lupus erythematosus (SLE). Two patients with symptomatic SLE and ESRD were treated with IVIg. Both patients tolerated IVIg administration well and demonstrated clinical and serologic improvement. Both individuals also experienced a transient decline in serum albumin concentration with IVIg treatment. The mechanisms by which IVIg might have effected improvement in these patients are varied and are likely related to the immunomodulatory actions of IVIg. The reversible change in albumin concentration seen in these individuals may be secondary to abrupt alterations in oncotic homeostasis. Despite this unusual effect, the documented improvement in these patients suggests that IVIg therapy may be of benefit in patients with active SLE and ESRD. Further studies are warranted to examine the mechanisms by which IVIg may exert its therapeutic effect.

Adult↗
PubMed1995

MRI of papillary meningiomas in children.

We report two cases of papillary meningioma in children. The MRI appearance of this special type of meningioma is described for the first time. Both lesions were dura based and associated with cystic components. We review the literature pertaining to this type of meningioma and discuss the differential diagnosis of the MRI appearance. Because this is a malignant type of meningioma, early diagnosis and surgical intervention are important in the management of patients.

Child, Preschool↗
PubMed1995

[Elevated plasma prekallikrein level in patients with diabetes].

The contact activation of intrinsic pathway in the coagulation system accompanied by plasma kallikrein-induced kinin generation is thought to be involved in the pathogenesis of diabetic retinopathy. Plasma prekallikrein (PPK), a proenzyme of plasma kallikrein, is a single-chain glycoprotein synthesized mainly in the liver. The aim of our study was to evaluate plasma prekallikrein level in diabetic patients and to examine the relationship between PPK and the metabolic control of diabetes and development of retinopathy. In 53 diabetic patients and 33 healthy subjects as controls the following parameters have been assessed: plasma prekallikrein, serum fructosamine, glycated haemoglobin HbA1c, prothrombin time, partial thromboplastin time and antithrombin III (AT III). Compared to the control group, PPK level was significantly higher in diabetics, especially in patients with proliferative retinopathy. The significant positive correlations have been found between PPK and HbA1c in diabetic patients and between PPK and serum fructosamine concentration but only in diabetics without retinopathy. No differences in prothrombin time and AT III have been observed between diabetics and healthy subjects. A suggestion is presented on increase of plasma prekallikrein level in diabetics due to hyperglycaemia-stimulated glycoprotein over-synthesis in the liver, what would confirm the role of kallikrein-kinin system in the pathogenesis of microangiopathy.

Adult↗
PubMed1994

The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor.

The spirochete Borrelia burgdorferi is the causative agent of Lyme borreliosis (Lyme disease) and is transmitted to mammalian hosts by tick vectors. In humans, the bacteria induce a complex disease, which involves the skin, joints, heart, and nervous system. However, the pathogenic principles of this multisystem illness are far from being understood. To disseminate from the site of the tick bite and invade multiple organ sites, spirochetes have to penetrate normal tissue barriers, such as vascular basement membranes and other organized extracellular matrices. Substantial evidence from other invasive bacterial infections suggest that spirochetes may use endogenous or host-derived enzymes--in particular, proteinases--for this purpose. Here we show that B. burgdorferi binds human plasmin(ogen)--mainly via its outer cell surface lipoprotein A. Binding of plasminogen to spirochetal receptor leads to an accelerated formation of active plasmin in the presence of host-derived plasminogen activator. The cell-surface-associated plasmin cannot be regulated by the serum inhibitor alpha 2-antiplasmin and degrades high-molecular-weight glycoproteins, such as fibronectin. It is suggested that the acquisition of host-derived proteinase plasmin(ogen) contributes to the pathogenicity of B. burgdorferi.

Antigens, Surface↗