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Biomedical subjects

R Schmitz

Publications and source records attributed to R Schmitz.

At least 19 recordsLinked to original sources
PubMed2000

Pancreatic beta-cell K(ATP) channel activity and membrane-binding studies with nateglinide: A comparison with sulfonylureas and repaglinide.

Nateglinide (A-4166) is an amino acid derivative with insulinotrophic action in clinical development for treatment of type 2 diabetes. The aim of this study was to determine whether nateglinide's interaction at the K(ATP) channel/sulfonylurea receptor underlies its more rapid onset and shorter duration of action in animal models. Binding studies were carried out with membranes prepared from RIN-m5F cells and HEK-293 cells expressing recombinant human sulfonylurea receptor 1 (SUR1). The relative order for displacement of [(3)H]glibenclamide in competitive binding experiments with RIN-m5F cell membranes was glibenclamide > glimepiride > repaglinide > glipizide > nateglinide > L-nateglinide > tolbutamide. The results with HEK-293/recombinant human SUR1 cells were similar with the exception that glipizide was more potent than repaglinide. Neither nateglinide nor repaglinide had any effect on the dissociation kinetics for [(3)H]glibenclamide, consistent with both compounds competitively binding to the glibenclamide-binding site on SUR1. Finally, the inability to measure [(3)H]nateglinide binding suggests that nateglinide dissociates rapidly from SUR1. Direct interaction of nateglinide with K(ATP) channels in rat pancreatic beta-cells was investigated with the patch-clamp method. The relative potency for inhibition of the K(ATP) channel was repaglinide > glibenclamide > nateglinide. Kinetics of the inhibitory effect on K(ATP) current showed that the onset of inhibition by nateglinide was comparable to glibenclamide but more rapid than that of repaglinide. The time for reversal of channel inhibition by nateglinide was also faster than with glibenclamide and repaglinide. These results suggest that the unique characteristics of nateglinide are largely the result of its interaction at the K(ATP) channel.

ATP-Binding Cassette Transporters↗
PubMed1999

[Long-term results after tension-free inguinal hernia repair].

A total of 186 consecutive patients underwent open tension-free inguinal hernia repair, either on one or both sides. Overall, 220 hernias were repaired under local anesthesia conditions after intraoperatively classifying the size of the hernia. The follow-up investigation took place as planned in 165 hernias. The mean follow-up time was 15.5 months, with a range from 6.6 to 30. 8 months, and the follow-up rate was 75.0 %. During this first follow-up it was especially interesting to read the patients, self-assessment concerning their physical restrictions during the first month after the operation. Furthermore, we were interested in learning about the objective and subjective operation-linked consequences in the patients, inguinal region. Most patients (89.7 %) were able to do sports and drive their car; 86.1 % were able to manage their usual physical activity 4 weeks after the operation. Focusing on the operation site, patients complained about chronic unpleasant effects, such as mild pain (21.2 %), local hypoesthesia (12.1 %), weather-dependent changes in sensitivity (7.2 %), moderate pain (3.6 %), inguinal syndrome (1.8 %) and hyperesthesia (1.2 %). Persistent swelling in the parainguinal region was found in 1.8 % of the patients and only one recurrence was found (0.6 %). In the analysis we found that mild chronic pain was not related to the time period after the operation and the age or sex of the patient, but there was a correlation with the size of the hernia. Patients with small hernias significantly more often experienced chronic pain than patients with bigger hernias. These results suggest that open tension-free inguinal hernia repair according to Lichtenstein appears to be overtreatment in patients with small inguinal hernias.

Activities of Daily Living↗
PubMed1999

Complicated diverticulitis of the sigmoid: a prospective study concerning primary resection with secure primary anastomosis.

BACKGROUND: The Hartmann procedure remains the standard concerning the surgical treatment of acute complicated sigmoid diverticulitis. The aim of this study was to prove the possibility of performing a secure primary anastomosis without colostomy in patients with complicated acute diverticulitis. METHODS: From June 1988 to October 1996, 113 patients suffering from acute complicated sigmoid diverticulitis were included in this prospective study. Within 24-48 h of hospital admission, when symptoms of the illness persisted despite the use of antibiotic therapy, the patients underwent primary resection of the sigmoid. In all patients primary anastomosis was performed, using CEEA staplers, avoiding colostomy and intraoperative colon irrigation. RESULTS: During the observation period of 19 days, there was no anastomotic leakage found either by radiological methods or clinical parameters. Two patients died of early septic complications, 1 of therapy-resistant endocarditis. CONCLUSION: The results of this study demonstrate the safety of primary anastomosis after primary resection of the sigmoid under antibiotic conditions, avoiding the disadvantages associated with two-stage procedures.

Acute Disease↗
PubMed1997

Identification of phosphopeptide ligands for the Src-homology 2 (SH2) domain of Grb2 by phage display.

We report here on the identification of phosphopetide ligands which interact with the Src-homology 2 (SH2) domain of the adapter protein Grb2 by screening a random peptide library established on phage. Phage were phosphorylated in vitro at an invariant tyrosine residue by a mixture of phosphotyrosine kinases c-Src, Blk and Syk. Selection of binding motifs was carried out by interaction of the library with the recombinant SH2 domain of Grb2 expressed as a glutathione S-transferase (GST) fusion protein. Several subsequent cycles of selection led to the enrichment of phage which bound to the GST-Grb2 SH2 domain only when previously phosphorylated. Sequence analysis revealed that all of the selected phage displayed peptides with the consensus motif Y*M/ENW (Y* denotes phosphotyrosine). One of these peptides, bearing the Y*ENW motif, bound the Grb2 SH2 domain with a threefold higher affinity than the peptide motif Y*VNV derived from the natural ligand Shc. Thus, phage display can be employed to rapidly identify high affinity ligands to SH2 domains.

Adaptor Proteins, Signal Transducing↗
PubMed1997

["Tension-free technique" in open inguinal hernia repair. A prospective, randomized study of postoperative pain perception ("tension-free reconstruction" vs. Shouldice technique)].

A prospective randomized study was performed on 64 patients suffering from primary inguinal hernia. Two groups were formed, each consisting of 32 patients. The patients either underwent tension-free surgical treatment or Shouldice herniorraphy. The aim of the study was to determine if the tension-free operative technique on inguinal hernia patients reduces postoperative pain intensity by 2 days in comparison to the patients receiving Shouldice repair treatment. By using the VAS was shown that at no time was there any significant difference in the pain sensation levels between the two groups. The amount of pain tablets consumed among the patients was similar in each group. The number of complications in both groups was also comparable. During the postoperative follow-up of 6 days six patients in the tension-free surgical group and four patients in the Shouldice group developed uncomplicated hematomas on the 4th day, which were traced to the heparin medication. One patient from the Shouldice group suffered from temporary swelling of the scrotum. The advantage of open tension-free repair using extraperitoneally placed polypropylene mesh is that the technique is simple, size-adapted, and can be carried out easily and at any time under local anesthesia. With regard to the lower recurrence rate of hernia as published in the American literature, this can only be verified by randomized studies.

Adolescent↗
PubMed1997

Randomized clinical trial of conventional cholecystectomy versus minicholecystectomy.

BACKGROUND: The main argument for laparoscopic cholecystectomy in preference to open cholecystectomy appears to be based on less traumatic incisions inflicted on the abdominal wall. To investigate the effects of different incision lengths on patients following elective open cholecystectomy, a randomized clinical study was conducted. METHODS: In this study 130 patients were randomly assigned to undergo either open cholecystectomy through a transverse subcostal incision of mean length 5.8 cm, so called minicholecystectomy (65 patients), or to undergo conventional cholecystectomy through a paracostal incision of mean length 13.1 cm (65 patients). The perception of pain after operation was measured by a visual analogue scale. To register late complications the mean(s.d.) hospitalization period after operation was extended to 11.5(1.2) days in the minicholecystectomy group and 15.4(2.5) days in the conventional cholecystectomy group. RESULTS: The perceived pain and analgesic requirements were found to be similar in both groups. Twelve of 65 patients in the minicholecystectomy group and four of 65 in the conventional cholecystectomy group developed wound haematoma. CONCLUSION: On the basis of this prospective randomized study, the hypothesis that a smaller incision length on the abdominal wall could lower the level of perceived pain, and therefore decrease the postoperative analgesic intake after minicholecystectomy, could not be confirmed.

Adult↗
PubMed1997

[Extraperitoneal, "tension free" inguinal hernia repair with local anesthesia--a contribution to effectiveness and economy].

In this present randomized controlled study, two groups, each consisting of 45 patients, underwent tension-free inguinal hernia repair under general versus local anesthesia. Patients in the local anesthesia group described their pain during mobilisation by using the VAS and were found to have a significant pain level decrease from the first to the fifth postoperative day. In conclusion, it could be shown that tension-free hernia repair under local anesthesia is superior to tension-free hernia repair during general anesthesia concerning perception of pain and pain management.

Adolescent↗
PubMed1996

Catalytic specificity of phosphotyrosine kinases Blk, Lyn, c-Src and Syk as assessed by phage display.

Protein tyrosine kinases (PTKs) are implicated in cell proliferation, differentiation, and receptor-mediated signalling events. Recruitment of intracellular PTKs into the signalling complex, often localized at the inner surface of the cell membrane, involves SH2 and SH3 domains attached to the catalytic kinase domain. While the interaction of SH2 and SH3 domains with their target sequences is well documented in a number of cases, the contribution of the catalytic domain itself in conferring specificity to a given signal cascade is not fully understood. We addressed this question and employed the phage display technique to assess the substrate requirements for the highly related Src-like PTKs c-Src, Blk, Lyn and the distantly related Syk. A diverse peptide library on phage was established, and after multiple rounds of phosphorylation and selection of phage displaying phosphotyrosine-containing peptides, canonical substrate sequences for each of the PTKs were enriched. The PTKs Blk and Lyn implicated in B cell signalling were found to prefer peptide substrates of the structure I/L-Y-D/E-X-L which resemble critical features of the ITAM motifs found in, e.g. the intracellular components Ig-alpha and Ig-beta of the beta cell receptor. All Src-like PTKs had a requirement for isoleucine or leucine in the position -1 with respect to the phosphorylated tyrosine residue in position 0. While Blk and Lyn had a strong preference for a negatively charged amino acid in position +1, c-Src preferred tryptophan or glycine in this position. Syk, not belonging to the Src-like PTK family, revealed a distinct substrate requirement for aspartic acid in position -1 and glutamic acid in position +1. In general, all PTKs we have tested had a strong preference for a particular amino acid in the positions -1 and +1 adjacent to the tyrosine residue.

Amino Acid Sequence↗
PubMed1995

Estimating increases in outpatient dialysis costs resulting from scientific and technological advancement.

The Medicare program's base payment rate for outpatient dialysis services has never been adjusted for the effects of inflation, productivity changes, or scientific and technological advancement on the costs of treating patients with end-stage renal disease. In recognition of this, Congress asked the Prospective Payment Assessment Commission to annually recommend an adjustment to Medicare's base payment rate to dialysis facilities. One component of this adjustment addresses the cost-increasing effects of technological change--the scientific and technological advances (S&TA) component. The S&TA component is intended to encourage dialysis facilities to adopt technologies that, when applied appropriately, enhance the quality of patient care, even though they may also increase costs. We found the appropriate increase to the composite payment rate for Medicare outpatient dialysis services in fiscal year 1995 to vary from 0.18% to 2.18%. These estimates depend on whether one accounts for the lack of previous adjustments to the composite rate. Mathematically, the S&TA adjustment also depends on whether one considers the likelihood of missing some dialysis sessions because of illness or hospitalization. The S&TA estimates also allow for differences in the incremental costs of technological change that are based on the varying advice of experts in the dialysis industry. The major contributors to the cost of technological change in dialysis services are the use of twin-bag disconnect peritoneal dialysis systems, automated peritoneal dialysis cyclers, and the new generation of hemodialysis machines currently on the market. Factors beyond the control of dialysis facility personnel that influence the cost of patient care should be considered when payment rates are set, and those rates should be updated as market conditions change. The S&TA adjustment is one example of how the composite rate payment system for outpatient dialysis services can be modified to provide appropriate incentives for producing high-quality care efficiently.

Health Care Costs↗
PubMed1995

Generation of rabbit monoclonal antibody fragments from a combinatorial phage display library and their production in the yeast Pichia pastoris.

We have applied the combinatorial immunoglobulin library and phage display technologies to generate monoclonal rabbit single-chain Fv (scFv) antibody fragments specific for recombinant human leukemia inhibitory factor (rhLIF). The B cell immunoglobulin repertoire of an immunized rabbit was immortalized by the combinatorial cloning of the rearranged variable domains of light (VL) and heavy (VH) chains. Affinity selection of the library displaying the rabbit antibody domains on the phage surface resulted in the isolation of phage encoding scFv antibodies which specifically bind to the antigen. We utilized the methylotrophic yeast Pichia pastoris for high level secretion of soluble and functional scFv antibody fragment. More than 100 mg/L of pure and functional rabbit anti-rhLIF scFv antibody was obtained directly from the P. pastoris culture supernatant by one-step affinity chromatography.

Amino Acid Sequence↗