The Lesch-Nyhan syndrome

Metabolic studies in a case of Lesch-Nyhan syndrome are presented. De novo synthesis of purine was shown to be inhibited upon adenine administration. The excretion of oxypurines is elevated, however, by an increased incorporation of the administered adenine into purine bases. A side effect of adenine administration is the production of the slightly soluble and highly nephrotoxic 2,8-dioxyadenine, which can cause renal damage.     

Perioperative Strategien zur Regulierung des Sympathikotonus

Obwohl für verschiedene therapeutische Konzepte zur Verminderung der kardialen perioperativen Morbidität und Mortalität zunehmend Evidenz vorliegt, bleibt die tatsächliche Umsetzung solcher Konzepte im klinischen Alltag oft aus. Zwar ist einem großen Teil der klinisch tätigen Ärzte die wachsende Literatur bekannt; dieses Wissen wird aber nur in einem Teil der Fälle angewendet, selbst wenn allgemein akzeptierte Indikationen bestehen. Die vorliegende Übersichtsarbeit hat deshalb zum Ziel, die Gründe für die mangelnde Umsetzung aufzuzeigen und nochmals die wesentlichen Grundlagen sowie die klinische Bedeutung einzelner Strategien einschließlich des ₂-Agonismus, der -adrenergen Blockade und der Regionalanästhesien zusammenzufassen. Dies insbesondere im Hinblick auf die klinische Anwendung dieser Konzepte in einem allgemeinanästhesiologischen Umfeld. Zudem wird ein Ausblick in die auf gene profiling basierende individualisierte Pharmakotherapie der perioperativen Medizin von morgen gegeben.     

Serine proteinases of the human body louse (Pediculus humanus): sequence characterization and expression patterns

After the previous characterization of one trypsin gene (Try1) of the human body louse Pediculus humanus, genes encoding a second trypsin (Try2) and a chymotrypsin (Chy1) have been cloned using degenerate serine proteinase primers and 5- and 3-RACE, and sequenced. The deduced 259 and 267 amino acid sequences of Try2 and Chy1 show an identity of 33%–40% to trypsinogens and chymotrypsinogens of other insects. Considering previously published partial sequences, P. humanus possesses at least one Try1 gene, five variants/isoforms of Try2 and six variants/isoforms of Chy1. The genomic DNA of Try2 contains three introns and Chy1 contains five introns. Using whole mount in situ hybridization, gene expression of Try1, Try2 and Chy1 has been localized not only in the distensible anterior region of the midgut of lice but sometimes also in the area following the distensible region. The Try2 gene was always expressed at much lower levels than Try1 or Chy1. This lower expression, the constitutive expression of Try1 and Chy1 at 1, 2, 6, 12 and 24 h after feeding of adults and the regional differences have been verified in quantitative real-time PCR.     

A Snapshot of Substance Abuse Among Homeless and Runaway Youth in Denver, Colorado

We report on results of a one-day survey measuring rates of substance use and HIV risk behaviors among the homeless youth population of Denver, Colorado. On March 15, 2001, staff of Urban Peak, conducted a single-day survey of homeless and runaway youth in the Denver metropolitan region, going to locations known to be frequented by this population. All youth encountered were asked to fill out a brief survey asking about past nine month use of the following substances: alcohol, marijuana, cocaine, methamphetamine, heroin, hallucinogens, ecstasy and ketamine, and HIV risk behaviors. Chi-square analyses of the association of substance used and gender, age, living situation, and ethnicity were conducted. In addition, the use of any club drug was examined. One-hundred-eighty-six homeless or runaway youth were surveyed; 74 percent were between 16 and 25. Rates of use over the last nine months were as follows: alcohol, 69 percent; marijuana, 75 percent; methamphetamine, 18 percent; cocaine, 19 percent; heroin, 12 percent; hallucinogens, 30 percent; ecstasy, 25 percent; and ketamine, 13 percent. Eleven percent reported trading sex for drugs, money, food, or shelter; and 13 percent reported sharing needles. There were significant associations between living situation and use of marijuana, cocaine and hallucinogens. Prevalence rates of club drugs show 75 percent, 77 percent and 77 percent of homeless or runaway youth ihaving used ecstasy, ketamine and hallucinogens one to three times per month over the last nine months, respectively. Prevalence rates of substance use among homeless youth in the Denver metropolitan are similar to rates reported in other larger metropolitan areas. Routine screening for every substance needs to be part of the assessment for all homeless youth. Initial data points to a need for more research exploring protective factors among this population and to better understand the prevalence of club drug use.     

Changes in the provision of psychiatric services at a psychiatric district hospital

Changes in the provision of psychiatric services within the last decennials are probably best understood if the impact of national socialism on clinical psychiatry is regarded. Many psychiatrists took part in the "Aktion T4" the organised killing of their patients, at least they did not resist campaigns directed to killing or sterilisation patients. After WW II, a period of silence and acceptance of inhuman circumstances in the large mental state hospitals appeared, when in the sixties a new generation of psychiatrists was no longer willing to continue the traditional system of mental health care delivery. The Expert Commission on Mental Health Care reported a comprehensive agenda on reformation of service delivery in 1975, which was influential in the development of alternative structures of psychiatric services. Most mental state hospitals reduced their capacities and parallel to this process smaller units, devoted to principles of community psychiatry, associated to general hospitals were created. Overall, the number of hospital driven beds decreased at about 33 %, but in the large hospitals at two thirds within the last 25 years in Baden-Wurttemberg. This process of deinstitutionalization was accompanied by the development of structures for community care, internal reorganization and modernization, and important steps in budget development, which lead to better treatment opportunities for all kinds of psychiatric institutions. The concrete and historical reality of these circumstances and changes, and possible future directions are exemplified for the psychiatric hospital in Weinsberg.     

Prevention of in-stent restenosis via reduction of thrombo-inflammatory reactions with recombinant P-selectin glycoprotein ligand-1

The binding of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) to platelet P-selectin is central to post-angioplasty restenosis. Although intracoronary stents limit the mechanical component of restenosis, they cause marked thrombo-inflammation and neointimal proliferation leading to greater late luminal loss. We sought to demonstrate that P-selectin antagonism, using recombinant PSGL-1 (rPSGL-Ig), is effective in reducing platelet-leukocyte reactions and in-stent restenosis in double-injured porcine coronary arteries. Two weeks after initial injury by angioplasty to the coronary arteries, stents were implanted at the injury-induced lesion site, 15 min after an i.v. bolus administration of a vehicle or rPSGL-Ig (1 mg/kg). Four weeks later, adhesion of (51)Cr-platelets and (111)In-neutrophils and histomorphometric analyses were performed. In-stent residual lumen was almost 3 fold larger in rPSGL-Ig-treated arteries (3.1 +/- 0.4 mm(2)) as compared to control (1.1 +/- 0.2 mm(2)), which correspond to 64% vascular stenosis in control with no change in rPSGL-Ig animals. For a similar injury score, in-stent neointima was significantly reduced by 30 to 40% in the rPSGL-Ig group and quantitative coronary angiography showed a significant 35% reduction in late lumen loss. These effects of rPSGL-Ig were associated with a respective 70% and 53% reduction in platelet and neutrophil adhesion. In conclusion, pretreatment with rPSGL-Ig reduces thrombo-inflammatory responses, neointimal proliferation, and in-stent restenosis. P-selectin antagonism offers a promising therapy to improve clinical outcomes of coronary stenting.