Characterization of a new extracellular hydrolase from Thermobifida fusca degrading aliphatic-aromatic copolyesters.

The paper describes the purification, biochemical characterization, sequence determination, and classification of a novel thermophilic hydrolase from Thermobifida fusca (TfH) which is highly active in hydrolyzing aliphatic-aromatic copolyesters. The secretion of the extracellular enzyme is induced by the presence of aliphatic-aromatic copolyesters but also by adding several other esters to the medium. The hydrophobic enzyme could be purified applying a combination of (NH(4))SO(4)-precipitation, cation-exchange chromatography, and hydrophobic interaction chromatography. The 28 kDa enzyme exhibits a temperature maximum of activity between 65 and 70 degrees C and a pH maximum between pH 6 and 7 depending on the ion strength of the solution. According to the amino sequence determination, the enzyme consists of 261 amino acids and was classified as a serine hydrolase showing high sequence similarity to a triacylglycerol lipase from Streptomyces albus G and triacylglycerol-aclyhydrolase from Streptomyces sp. M11. The comparison with other lipases and esterases revealed the TfH exhibits a catalytic behavior between a lipase and an esterase. Such enzymes often are named as cutinases. However, the results obtained here show, that classifying enzymes as cutinases seems to be generally questionable.

Safe and cost effective use of alteplase for the clearance of occluded central venous access devices.

PURPOSE: To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs). MATERIALS AND METHODS: Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. However, the practicality of using alteplase as the thrombolytic of choice for this indication remained conjectural. To make this approach economically feasible, alteplase was diluted to 1 mg/mL and 2.5-mL aliquots were stored at -20 degrees C until use. A need to confirm that the cryopreserving and thawing of the reconstituted solution did not compromise the safety and efficacy reported from prior trials was recognized. A quality assessment initiative was undertaken to concurrently monitor the safety and efficacy of this approach. Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). Data, including efficacy, adverse reactions, dwell time, and catheter type, were collected over a 5-month period. RESULTS: One hundred twenty-one patients accounting for 168 attempted clearances were assessable for safety and efficacy. One hundred thirty-six (81%) of the 168 catheter clearance attempts resulted in successful catheter clearance (95% confidence interval, 74% to 86%). No adverse events were reported. CONCLUSION: Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.

Biodegradation of aliphatic-aromatic copolyesters: evaluation of the final biodegradability and ecotoxicological impact of degradation intermediates.

The biological degradation behaviour of the aliphatic-aromatic copolyester Ecoflex was investigated with regard to the degree of degradation and the intermediates formed during the degradation process. The individual thermophilic strain Thermomonospora fusca, isolated from compost material, was used for the degradation experiments in a defined synthetic medium at 55 degrees C. After 22 days of degradation more than 99.9% of the polymer had depolymerized and with regard to the degradation of the diacid and diol components of Ecoflex only the monomers of the copolyesters (1,4-butanediol, terephthalate and adipate) could be detected by gas chromatography/mass spectroscopy (GC-MS) measurements in the medium. In interrupted degradation experiments predominantly the monoesters of adipic acid and terephthalic acid with 1,4-butanediol were observed in addition to the monomers. In toxicological tests with Daphnia magna and Photobacterium phosphoreum no significant toxicological effect was observed, neither for the monomeric intermediates nor for the oligomeric intermediates. From a risk assessment it can be concluded that there is no indication for an environmental risk when aliphatic-aromatic copolyesters of the Ecoflex-type are introduced into composting processes.

Biodegradation of polyesters containing aromatic constituents.

Polymers, which undergo a controlled biological degradation by micro-organisms came to remarkable interest during the last years. Composting for instance could so be established as an alternative waste management system for parts of the plastic waste. Within this group of innovative polymer, polyesters play a predominant role, due to their potentially hydrolyzable ester bonds. While aromatic polyesters such as poly(ethylene terephthalate) exhibit excellent material properties but proved to be almost resistant to microbial attack, many aliphatic polyesters turned out to be biodegradable but lack in properties, which are important for application. To combine good material properties with biodegradability, aliphatic-aromatic copolyesters have been developed as biodegradable polymers for many years. This article reviews the attempts to combine aromatic and aliphatic structures in biodegradable plastics and work, which has been done to evaluate the degradation behaviour and environmental safety of biodegradable polyesters, containing aromatic constituents.

Degradation of natural and synthetic polyesters under anaerobic conditions.

Often, degradability under anaerobic conditions is desirable for plastics claimed to be biodegradable, e.g. in anaerobic biowaste treatment plants, landfills and in natural anaerobic sediments. The biodegradation of the natural polyesters poly(beta-hydroxybutyrate) (PHB), poly(beta-hydroxybutyrate-co-11.6%-beta-hydroxyvalerate) (PHBV) and the synthetic polyester poly(epsilon-caprolactone) (PCL) was studied in two anaerobic sludges and individual polyester degrading anaerobic strains were isolated, characterized and used for degradation experiments under controlled laboratory conditions. Incubation of PHB and PHBV films in two anaerobic sludges exhibited significant degradation in a time scale of 6-10 weeks monitored by weight loss and biogas formation. In contrast to aerobic conditions, PHB was degraded anaerobically more rapidly than the copolyester PHBV, when tested with either mixed cultures or a single strained isolate. PCL tends to degrade slower than the natural polyesters PHB and PHBV. Four PHB and PCL degrading isolates were taxonomically identified and are obviously new species belonging to the genus Clostridium group I. The depolymerizing enzyme systems of PHB and PCL degrading isolates are supposed to be different. Using one isolated strain in an optimized laboratory degradation test with PHB powder, the degradation time was drastically reduced compared to the degradation in sludges (2 days vs. 6-10 weeks).

Determination of the aerobic biodegradability of polymeric material in aquatic batch tests.

Results of an international ring-test of two laboratory methods are presented for investigating the biodegradability of organic polymeric test materials in aquatic test systems based on respirometry and the evolution of carbon dioxide. These methods are developed further from the well-known standardized biodegradation tests ISO 9408 (1999) and ISO 9439 (1999), which have been successfully used for many years. The most important improvements are the extension of the test period up to six months, the increase of the buffer capacity and nutrient supply of the inorganic medium, an optimization of the inoculation, and optionally, the possibility of a carbon balance. A ring test, organized by the International Biodeterioration Research Group (IBRG), was run using a poly(,-caprolactone)-starch blend and an aliphatic-aromatic co-polyester as test materials and a microcrystalline cellulose powder as a reference material. The test results and the experience gained by the participants showed that the methods are suitable and practicable. The test methods have been meanwhile established as standards ISO 14851 (1999) and ISO 14852 (1999).

A brief review of antifungal therapy for deep fungal infection.

With the continuing increase in clinically important fungal disease, especially seen in the neutropenic patient, the need for new and improved systemic antifungal agents marches on. A pharmacy and therapeutics committee may select an antifungal agent based on these criteria: spectrum of action, pharmacokinetic profile, toxicity, potential for resistance, and cost. A number of agents are now available for treating deep fungal infections, including amphotericin B in conventional and liposomalformulations, and the triazoles itraconazole (Sporanox) and fluconazole (Diflucan). It is important to note that there is lack of agreement in practice over what constitutes ideal therapy. The lipidformulations of amphotericin B and the improved oral solution and new intravenous formulation of itraconazole are recent additions to therapeutic options that are already having a significant influence on drug selection and treatment practices.

Biodegradation of aliphatic-aromatic copolyesters by Thermomonospora fusca and other thermophilic compost isolates.

Random aliphatic-aromatic copolyesters synthesized from 1,4-butanediol, adipic acid, and terephthalic acid (BTA) have excellent thermal and mechanical properties and are biodegradable by mixed cultures (e.g., in compost). Over 20 BTA-degrading strains were isolated by using compost as a microbial source. Among these microorganisms, thermophilic actinomycetes obviously play an outstanding role and appear to dominate the initial degradation step. Two actinomycete strains exhibited about 20-fold higher BTA degradation rates than usually observed in a common compost test. These isolates were identified as Thermomonospora fusca strains. They appeared to be particularly suitable for establishment of rapid degradation tests and were used in comparative studies on the biodegradation of various polyesters.

[Reliability of ultrasound pregnancy screening]. / Die Verlässlichkeit des sonographischen Schwangerschaftsscreenings.

This study investigates the reliability of ultrasonographic screenings for detecting fetal malformations in pregnancy. The data from 1505 screening examinations of pregnant women who underwent routine checks at the Department of Obstetrics of the University of Vienna, were compared with the anomalies diagnosed in the newborn of the same collective. Fetal malformations were diagnosed in 28 screening cases. The statistical distribution of these anomalies is shown for the different organ systems. In 5 newborn malformations were found, which had not been diagnosed sonographically. Another 23 newborn had minor malformations in regions that are not included in the routine screening ultrasound. The results show a high accuracy of the sonographic screening examination, with the exception of the median facial region and the large vessels of the base of the heart. The fact that not all of the cardiac malformations were diagnosed prompts the performance of an extended sonographic inspection of the fetal heart within the framework of routine screening.

Preventing medication errors in cancer chemotherapy.

Recommendations for preventing medication errors in cancer chemotherapy are made. Before a health care provider is granted privileges to prescribe, dispense, or administer antineoplastic agents, he or she should undergo a tailored educational program and possibly testing or certification. Appropriate reference materials should be developed. Each institution should develop a dose-verification process with as many independent checks as possible. A detailed checklist covering prescribing, transcribing, dispensing, and administration should be used. Oral orders are not acceptable. All doses should be calculated independently by the physician, the pharmacist, and the nurse. Dosage limits should be established and a review process set up for doses that exceed the limits. These limits should be entered into pharmacy computer systems, listed on preprinted order forms, stated on the product packaging, placed in strategic locations in the institution, and communicated to employees. The prescribing vocabulary must be standardized. Acronyms, abbreviations, and brand names must be avoided and steps taken to avoid other sources of confusion in the written orders, such as trailing zeros. Preprinted antineoplastic drug order forms containing checklists can help avoid errors. Manufacturers should be encouraged to avoid or eliminate ambiguities in drug names and dosing information. Patients must be educated about all aspects of their cancer chemotherapy, as patients represent a last line of defense against errors. An interdisciplinary team at each practice site should review every medication error reported. Pharmacists should be involved at all sites where antineoplastic agents are dispensed. Although it may not be possible to eliminate all medication errors in cancer chemotherapy, the risk can be minimized through specific steps. Because of their training and experience, pharmacists should take the lead in this effort.

Homeotic duplication of the pelvic body segment in regenerating tadpole tails induced by retinoic acid.

Homeosis, the ectopic formation of a body part, is one of the key phenomena that prompted the identification of the essential selector genes controlling body organization. Shared elements of such homeotic genes exist in all studied animal classes, but homeotic transformations of the same order of magnitude as in insects, such as the duplication of the thorax in Drosophila mutants, have not been described in vertebrates. Here we investigate the capacity of retinoic acid to modify tail regeneration in amphibians. We show that retinoic acid causes the formation of an additional body segment in regenerating tails of Rana temporaria tadpoles. A second pelvic section, including vertebral elements, pelvic girdle elements and limb buds, forms at the mid-tail level. This is the first report of a homeotic duplication of a whole body segment in vertebrate axial regeneration.

A pharmacy intervention program: recognizing pharmacy's contribution to improving patient care.

An on-line pharmacy intervention program developed to document and evaluate pharmacist's contribution to patient care is described. Over a 1-year period, the number and types of interventions and their impact on patient care were collated and reviewed by a clinical coordinator. Two thousand four hundred ninety-nine interventions were recorded. The most common types of interventions were order clarification/change (18%), pharmacokinetic consult (16%), chart review (13%), restricted drug follow-up (8%), discharge medication screen (7%), initiate drug therapy (6%), drug information (5%), discontinued drug (4%), and therapeutic alternative (4%). There were 3459 impact codes assigned to these interventions. Forty-one percent decreased toxicity, 35% increased efficacy, 17% decreased cost, 16% avoided allergy or drug interaction, 8% improved compliance, and 22% were classified as other. Our analysis found that pharmacy interventions elevated the standard of care and prevented major organ damage and potentially life-threatening events. This program shows that pharmacists play a significant role in improving patient outcomes.

Prenatal observation of umbilical cord abnormalities: a triple knot and torsion of the umbilical cord.

Umbilical cord abnormalities can be observed with ultrasonography. Two cases are described where a triple knot and torsion of the umbilical cord are observed. These cases allow the elucidation of the mechanics of formation of a triknot and torsion abnormality.

Karen Horney's "resigned person" heralds DSM-III-R's borderline personality disorder.

It is shown here that what Karen Horney called the resignation solution to the problem of basic anxiety leads to psychopathology very similar to DSM-III-R's borderline personality disorder (BPD). Both the "resigned person" and the borderline personality show instability of self-image, social relationships, and mood, and live out the associated deficits with similar styles. While not specifically using the term "splitting", Horney showed how alternating expansive and self-effacing trends can coexist in the resigned person, and how these oscillations in self-other-world constitution influence the resigned person's behavior in a way similar to borderline splitting. Horney's descriptive and psychodynamic analysis of the resignation phenomenon elaborates and gives additional credibility to DSM-III-R's BPD as a diagnostic category.

Jet-ski injury: a case history.

A case history is presented which involves a patient who sustained severe vaginal lacerations as a result of falling backwards off of a jet-ski. The surgical repair of the lacerations and postoperative course is discussed. An extensive search of the literature has failed to reveal any published reports of a similar injury.

Is there a neural basis for borderline splitting?

It is proposed here that borderline splitting and borderline pathology may have a neural basis. For the infant who splits its emotional and cognitive constitution of its mother during separation-individuation, the "good mother"--"bad mother" engram may be lateralized in the brain in a different way than for an infant who does not use this defense. The infant may be developmentally vulnerable to the effects of splitting during separation-individuation (18 to 36 months) because interhemispheric communication necessary for mental unity is not possible at this time, since neurons connecting left and right hemispheres are not totally myelinated and because the infant has not yet fully acquired language, a prerequisite for an integrated psychological reality. Two separate, unintegrated--and alternating--mental systems may come into being. Later, as myelination is completed, the infant's split emotional and cognitive constitutions of mother and of self may create a neural "template" for splitting all further experience and behavior through the two separate, alternating mental systems. The possibility that emotional trauma occurring later than separation-individuation, and involving other issues, may be the occasion for splitting is considered, as well as the possibility that a congenital abnormality in brain structure or function may be a primary factor in borderline pathology. Ways to test the hypothesis that borderline splitting has a neural basis are suggested.