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Biomedical subjects

L Schmidts

Publications and source records attributed to L Schmidts.

6 recordsLinked to original sources

Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor.

Fibrosis and cirrhosis of the liver are often the result of chronic liver damage by a variety of different agents. Pathological accumulation of collagen, disruption of the lobular structure, and impaired hepatocellular function frequently lead to systemic involvement and fatal complications. Drugs inhibiting collagen hydroxylation and accumulation are expected to improve this situation, making prolyl 4-hydroxylase (P4H), the key enzyme of intracellular collagen processing, a rational target for pharmacological intervention. S 4682, a novel inhibitor of purified P4H (Ki = 155 nmol/L), reduced hydroxyproline (Hyp) synthesis in chicken embryo calvaria (IC50 = 8.2 micromol/L) and in cultured hepatic stellate cells (HSC) (IC50 = 39 micromol/L). S 4682 inhibited hepatic collagen hydroxylation in vivo after metabolic labeling with [14C]proline. In the CCl4 model of chronic hepatic injury, characterized by histologically and biochemically evident fibrosis and highly elevated levels of serum procollagen type III N-peptide, S 4682 reduced hepatic collagen accumulation, decreased prevalence of ascites, and lowered serum procollagen type III N-peptide (PIIINP) levels. The hepatic Hyp content of drug-treated animals was closely correlated with serum levels of PIIINP S 4682 had no influence on Hyp content of heart, lung, and kidney.

Animals↗

Examination of explanted polyurethane pacemaker leads using the scanning electron microscope.

Since 1978, 2,365 polyurethane (PU) insulated cardiac pacing leads were implanted transvenously at our institution. To date, there have been no insulation failures in those leads. Thirty-seven PU leads were explanted, mainly for exit block, and 28 of these were investigated using the scanning electron microscope. We found a homogeneous distribution of surface changes in all lead segments in 56% of the 28 examined. These changes were more pronounced at the ligature site; severe surface cracking was noticed in 21%, with the deepest crack being 40 micron (average range of 10-15 micron). There appeared to be no time-dependency of the surface changes as indicated by regression analysis (r = 0.32, p greater than 0.05). The ultimate severity and outcome of this degradation process in the leads reported in this study will only be known in the future after longer use. We conclude that excess stress must be avoided during the implantation procedure and that careful surveillance is necessary.

Equipment Failure↗

Prolonged application of pressure in transluminal coronary angioplasty.

We investigated the morphologic structure and fluid content of atherosclerotic specimens of fresh human postmortem artery segments before and after application of a pressure of 5 atmospheres simulated by a weight of 5 kg per 1 cm2. After applying pressure in nonorganized atheromata, we noticed a marked reduction in thickness while in fibrotic atheromata we observed only smaller differences in thickness. Reduction in fluid content was significantly more pronounced in nonorganized atheromatous tissue. Reduction in thickness was closely related to reduction in weight (i e, fluid content). The time of pressure application necessary to achieve the optimal result averaged 60 sec. The conclusions drawn from these experiments were incorporated into clinical application of coronary angioplasty. Prolonged balloon inflation was applied to the last 400 out of a total of 600 coronary angioplasty procedures, performed between October 1977 and October 1983. Stenoses not sufficiently responsive to balloon inflation periods of 5-10 sec were exposed to periods of 60 sec (30-120 sec). The number of "non dilatable" stenoses was 15% with the standard short pressure procedure, but only 5% with the prolonged pressure application. No serious complications related to prolonged pressure application were observed. Thus, from experimental data and clinical experience the application of longer pressure periods appears justified and beneficial.

Angioplasty, Balloon↗