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Biomedical subjects

Michael Schmidt

Publications and source records attributed to Michael Schmidt.

47 records · Page 3Linked to original sources

Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients.

Analysis of data of 6931 patients with cutaneous melanoma seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians-University of Munich between 1977 and 1998 identified 36 patients in whom cutaneous melanomas developed during childhood or adolescence (age <18 years). Clinical courses of all patients and histopathologic characteristics of the lesions were reviewed. Seventeen patients were boys and 19 patients were girls. The median ages of the boys and girls were 15 and 16 years, respectively (range, 2-17 years). Thirty-one patients presented with nonmetastatic primary melanomas and 5 patients presented with metastatic melanoma. Forty-seven percent of the primary lesions were associated with a nevus (22% with congenital nevi and 25% with acquired nevi). Tumor thickness ranged from 0.24 to 7.0 mm, with a median of 1.29 mm (mean, 1.67 mm). All patients with primary melanomas received surgical therapy; patients with metastatic disease received chemotherapy, radiation therapy, or both. Relative 5-year survival was 87.5% for the group of patients younger than 18 years. Similar to experience in adult patients, survival strongly correlated with tumor thickness and clinical stage at the time of diagnosis. The data emphasize that a high index of suspicion for cutaneous melanoma is needed by clinicians assessing melanocytic lesions in children and adolescents for early diagnosis. Reduction of the melanoma mortality rate in children and adolescents will be achieved through identification of patients at increased risk.

Adolescent↗

Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size.

Gene therapy vectors based on adeno-associated viruses (AAVs) show promise for the treatment of retinal degenerative diseases. In prior work, subretinal injections of AAV2, AAV5, and AAV2 pseudotyped with AAV5 capsids (AAV2/5) showed variable retinal pigmented epithelium (RPE) and photoreceptor cell transduction, while AAV2/1 predominantly transduced the RPE. To more thoroughly compare the efficiencies of gene transfer of AAV2, AAV3, AAV5, and AAV6, we quantified, using stereological methods, the kinetics and efficiency of AAV transduction to mouse photoreceptor cells. We observed persistent photoreceptor and RPE transduction by AAV5 and AAV2 up to 31 weeks and found that AAV5 transduced a greater volume than AAV2. AAV5 containing full-length or half-length genomes and AAV2/5 transduced comparable numbers of photoreceptor cells with similar rates of onset of expression. Compared to AAV2, AAV5 transduced significantly greater numbers of photoreceptor cells at 5 and 15 weeks after surgery (greater than 1,000 times and up to 400 times more, respectively). Also, there were 30 times more genome copies in eyes injected with AAV2/5 than in eyes injected with AAV2. Comparing AAVs with half-length genomes, AAV5 transduced only four times more photoreceptor cells than AAV2 at 5 weeks and nearly equivalent numbers at 15 weeks. The enhancement of transduction was seen at the DNA level, with 50 times more viral genome copies in retinas injected with AAV having short genomes than in retinas injected with AAV containing full-length ones. Subretinal injection of AAV2/6 showed only RPE transduction at 5 and 15 weeks, while AAV2/3 did not transduce retinal cells. We conclude that varying genome length and AAV capsids may allow for improved expression and/or gene transfer to specific cell types in the retina.

Animals↗

Adeno-associated virus type 2 Rep78 inhibition of PKA and PRKX: fine mapping and analysis of mechanism.

Hormones and neurotransmitters utilize cyclic AMP (cAMP) as a second messenger in signal transduction pathways to regulate cell growth and division, differentiation, gene expression, and metabolism. Adeno-associated virus type 2 (AAV-2) nonstructural protein Rep78 inhibits members of the cAMP signal transduction pathway, the protein kinases PKA and PRKX. We mapped the kinase binding and inhibition domain of Rep78 for PRKX to amino acids (aa) 526 to 561 and that for PKA to aa 526 to 621. These polypeptides were as potent as full-length Rep78 in kinase inhibition, which suggests that the kinase-inhibitory domain is entirely contained in these Rep peptides. Steady-state kinetic analysis of Rep78-mediated inhibition of PKA and PRKX showed that Rep78 appears to increase the K(m) value of the peptide kinase substrate, while the maximal velocity of the reaction was unaffected. This indicates that Rep78 acts as a competitive inhibitor with respect to the peptide kinase substrate. We detected homology between a cellular pseudosubstrate inhibitor of PKA, the protein kinase inhibitor PKI, and the PRKX and PKA inhibition domains of Rep78. Due to this homology and the competitive inhibition mechanism of Rep78, we propose that Rep78 inhibits PKA and PRKX kinase activity by pseudosubstrate inhibition.

Amino Acid Sequence↗

[Introduction of the DRG system in Germany: problems and perspectives from the point of view of the German Hospital Federation].

The medical self-governing bodies at state level have been legally commissioned to develop a DRG-based reimbursement system in Germany till January 1, 2003, the general political and economic conditions being outlined in a DRG law regulating the introduction of a DRG-based case payment system (Fallpauschalengesetz). From the point of view of the German Hospital Federation, though, caution is advised as many of these general conditions cannot easily be implemented into the reality of German hospital practice. For example, the time frame set for introducing DRGs in Germany seems to be near record levels and is bound to cause qualitative cutbacks on the introduction of the new DRG system meant to improve the quality of care. Current hospital planning will be turned inside out. Also, the interfaces between the hospital sector on the one hand and other areas of care on the other will be put to a real test of endurance.

Diagnosis-Related Groups↗

Beryllium Chelation by Dicarboxylic Acids in Aqueous Solution.

Maleic and phthalic acids are found to react with Be(OH)(2), generated in situ from BeSO(4)(aq) and Ba(OH)(2)(aq), in aqueous solution at pH 3.0 or 4.4, respectively (25 degrees C), to give solutions containing the complexes (H(2)O)(2)Be[(OOCCH)(2)] (1) and (H(2)O)(2)Be[(OOC)(2)C(6)H(4)] (3). The products can be isolated in high yield and identified by microanalytical data. With 2 equiv of the dicarboxylic acids and the pH adjusted to 5.5 and 5.9, respectively, by addition of ammonia, the bis-chelate complexes [(NH(4))(+)](2){[Be[(OOCCH)(2)](2)}(2)(-) (2) and [(NH(4))(+)](2){Be[(OOC)(2)C(6)H(4)](2)}(2)(-) (4) are obtained, which can also be isolated. The compounds show distinct (9)Be, (1)H, and (13)C resonances in their NMR spectra in aqueous solutions. Layering of an aqueous solution of compound 4 with acetone at ambient temperature leads to the precipitation of single crystals suitable for an X-ray structure determination. This salt (5) was found to contain the bis-chelated dianion {Be[(OOC)(2)C(6)H(4)](2)}(2)(-) with the beryllium atom in the spiro center of two seven-membered rings and an overall geometry approaching closely C(2) symmetry. These anions are associated with two crystallographically independent but structurally similar counterions [MeC(O)CH(2)CMe(2)NH(3)](+), which are the product of a condensation reaction of the ammonium cation with the acetone solvent. In the crystal the ammonium hydrogen atoms of the cations form N-H.O hydrogen bonds with the oxo functions of the dianion.

Journal Article↗

Fluoro[eta(3)-hydrotris(3-R-5-methylpyrazol-1-yl)borato]zinc(II): The First TpZnF Complexes, Convenient Precursors to Zinc Hydride Complexes(,).

Fluoro[eta(3)-tris(3-R-5-methylpyrazol-1-yl)hydroborato]zinc(II) complexes, Tp(R,Me)ZnF (with R = p-Tol, t-Bu), have been prepared by metathesis of Tp(p-)()(Tol,Me)ZnOAc with KF in MeOH/THF and by reaction of KTp(t-)()(Bu,Me) with Zn(ClO(4))(2) and KF in MeOH. The molecular structure of Tp(p-)()(Tol,Me)ZnF has been determined by X-ray crystallography. Crystal data: a = 11.8719(12), c = 37.051(3) Å; trigonal, space group R3c (No. 161); Z = 6. The complex contains tetrahedrally coordinated Zn(II). The tolyl rings deviate by 21 degrees from coplanarity with the pyrazolyl plane. The reaction of Tp(p-)()(Tol,Me)ZnF with py.BF(3) leads to the tetrafluoroborate salt [Tp(p-)()(Tol,Me)Zn(py)](+)BF(4)(-). The analogous reaction with Et(2)O.BF(3) probably gives a solvent complex [Tp(p-)()(Tol,Me)Zn(Et(2)O)](+)BF(4)(-) that however could not be isolated. Triethylsilane reacts with Tp(p-)()(Tol,Me)ZnF to yield the zinc hydride Tp(p-)()(Tol,Me)ZnH. Trimethylsilyl derivatives Me(3)Si-X (X = Cl, Br, I, NCO, OAc) similarly give Tp(p-)()(Tol,Me)ZnX, whereas bis(trimethylsilyl) malonate yields the bridged complex Tp(p-)()(Tol,Me)Zn-O-C(O)-CH(2)-C(O)-O-ZnTp(p-)()(Tol,Me).

Journal Article↗

Hepatocellular ultrastructure after ischemia/reperfusion injury in human orthotopic liver transplantation.

The number of patients requiring organ transplants still outpaces the number of available transplantable organs. During the process of orthotopic liver transplantation (OLTx), donor organs undergo significant stress resulting from ischemia and reperfusion. Healthy organs respond to this stressful environment with compensatory mechanisms that ideally allow for complete recovery. However, "marginal" organs do not compensate as well. Hepatic steatosis typically renders an organ nontransplantable; a liver with 30% or more fat has a 25% chance of primary nonfunction (PNF) or graft failure after a technically sound operation. In this study, we report on the significant markers of cellular ultrastructural change in steatotic livers. These include glycogen content, mitochondrial swelling, and hepatocellular blebbing. The data disclosed here argue that further investigation of these factors in marginal organs subjected to I/R may better facilitate our understanding of PNF.

Analysis of Variance↗

Xenon washout during in-vitro extracorporeal circulation using different oxygenators.

BACKGROUND: Xenon anesthesia is known to have no adverse influence on myocardial contractility and cardiocirculatory function even in cardiac compromised patients. To make use of this advantages for cardiac surgery patients undergoing extracorporeal circulation (ECC) it must be known if oxygenators are diffusible for xenon in order to avoid losses of the very expensive noble gas. METHODS: Xenon saturated blood was recirculated in an in-vitro ECC. In 8 experiments four common oxygenators were investigated using continuous mass spectrometry at the exhaust port to measure xenon concentrations in the exspired gas. RESULTS: Xenon concentrations at the exhaust port of the oxygenator increased during filling the oxygenator with blood. Peak level was detected within one minute after onset of ECC. No xenon could be measured two minutes after onset of ECC. CONCLUSIONS: Using common oxygenators xenon is eliminated during ECC and lost into the atmosphere. To maintain anesthesia during ECC continuous xenon application would be necessary to compensate these losses. Due to its high price it would be too expensive to continue xenon anesthesia during ECC. Therefore it is not practicable to use the today's oxygenators and ECC equipment in xenon anesthesia.

Anesthesia↗

Prehospital cardiac arrest in a paramedic first-responder system using the Utstein style.

OBJECTIVES: To describe the characteristics of patients found to have cardiac arrest and to evaluate the characteristics predictive of survival after cardiac arrest in a paramedic first-responder model. METHODS: All patients who suffered out-of-hospital cardiac arrest in the city of Reading, Ohio, from January 1998 to December 2003 were recorded in the Utstein style. The number and incidence rate of witnessed arrests, initial rhythms, rate of bystander cardiopulmonary resuscitation (CPR), and 30-day mortality rate were retrospectively collected. Demographics, time to hospital, and response times were evaluated as predictors of survival. RESULTS: Of those patients initially found to be in cardiac arrest, 14.3% were discharged alive. Witnessed arrests were more likely to result in live discharge of the patient. Whether bystander CPR was performed was not found to affect survival, nor was initial rhythm, although no patients initially found in asystole were discharged alive. No demographic characteristics or response times were predictive of survival. CONCLUSION: The rates of survival in this paramedic first-response system are favorable compared with basic emergency medical technician first-response systems. Further study using direct comparison methodology is warranted to confirm these findings.

Aged↗