Post-conference session: Experience with patient self-management of oral anticoagulation

Long-term oral anticoagulation requires careful patient monitoring in order to optimize results and to limit hemorrhagic or thromboembolic complications of treatment. For this reason, any improvement in anticoagulant control and management can be expected to have far-reaching consequences in extending longevity and decreasing complications in anticoagulated patients after heart valve surgery. Because one attractive means of improving anticoagulant management is to give patients a share of the responsibility, a program was designed to encourage patients to take an active role in monitoring their own prothrombin time (PT) and managing their own oral anticoagulation. During the period from August 1986 to February 1992, 600 patients requiring long-term anticoagulation, mainly after heart valve replacement, were trained to measure their own PT at the Cardiac Rehabilitation Center (Herz-Krauslauf-Klinik, Bad Berleburg, Germany) and to manage their own therapy: 216 patients could be followed with regard to their self-determined prothrombin times. The results were within the target range in 83.1% of the PT determinations (n=12,306 measurements) taken by the patients themselves. Neither major bleeding nor thromboembolic complications were observed in 205 patient-years of self-monitoring of PT and self-management of oral anticoagulation.     

Antimykotische Wirkstoffe, 20. Mitt.: Bioisostere 6-Arylpyrimidin-Derivate

Antimycotic Agents, XX Bioisosteric 6-Arylpyrimidine Derivatives Condensation of N-(2-hydroxyethyl)-N-methylguanidine-sulfate ( 1 ) with the β-diketones 4a - e bearing 1-aryl substituents leads to the bioisosteric 2-[(2-hydroxyethyl)-methylamino]-6-arylpyrimidines 5a - e . Compounds 5a - c exhibit significant antimycotic in vivo and in vitro activities.     

Lack of Nonshivering Thermogenesis in Infants Anesthetized with Fentanyl and Propofol

Background: Sweating, vasoconstriction, and shivering have been observed during general anesthesia. Among these, vasoconstriction is especially important because-once triggered-it minimizes further hypothermia. Surprisingly, the core-temperature plateau associated with vasoconstriction appears to preserve core temperature better in infants and children than adults. This observation suggests that vasoconstriction in anesthetized infants may be accompanied by hypermetabolism. Consistent with this theory, unanesthetized infants rely on nonshivering thermogenesis to double heat production when vasoconstriction alone is insufficient. Accordingly, the authors tested the hypothesis that intraoperative core hypothermia triggers nonshivering thermogenesis in infants.

Methods: With Ethics Committee approval and written parental consent, the authors studied six infants undergoing abdominal surgery. All were aged 1 day to 9 months and weighed 2.4-9 kg. Anesthesia was maintained with propofol and fentanyl. The infants were mechanically ventilated and allowed to cool passively until core (distal esophageal) temperatures reached 34-34.5 degrees Celsius. Oxygen consumption-the authors' index of metabolic rate- was recorded throughout cooling. Because nonshivering thermogenesis triples circulating norepinephrine concentrations, arterial blood was analyzed for plasma catecholamines at [nearly equal] 0.5 degrees Celsius intervals. Thermoregulatory vasoconstriction was evaluated using forearm - fingertip, skin-surface gradients, with gradients exceeding 4 degrees Celsius, indicating intense vasoconstriction. The patients were subsequently rapidly rewarmed to 37 degrees Celsius. Regression analysis was used to correlate changes in oxygen consumption and plasma catecholamine concentrations with core temperature.

Results: All patients were vasoconstricted by the time core temperature reached 36 degrees Celsius. Further reduction in core temperature to 34-34.5 degrees Celsius did not increase oxygen consumption. Instead, oxygen consumption decreased linearly. Hypothermia also failed to increase plasma catecholamine concentrations.     

Primitive neuroectodermal tumors after prophylactic central nervous system irradiation in children. Association with an activated K-ras gene.

Three patients had supratentorial malignant brain tumors 7 to 9 years after prophylactic central nervous system (CNS) treatment for acute lymphocytic leukemia or malignant T-cell lymphoma. Therapy was administered at the age of 3 to 8 years and included cranial irradiation (total dose, 1800 to 2400 cGy) and intrathecal methotrexate. The brain tumors had histologic and immunohistochemical features of primitive neuroectodermal tumors (PNET), including neuroblastic rosettes, rhythmic arrangement of tumor cells, and immunohistochemical expression of glial, and in one patient neuronal, marker proteins. Using polymerase chain reaction-mediated DNA amplification from paraffin-embedded tissues and subsequent DNA sequence analysis, an activating point mutation was detected in the K-ras protooncogene in one tumor. This mutation was a G to A transition in position 2 of codon 12, substituting aspartate (GAT) for glycine (GGT). This type of mutation has not been observed before in human brain tumors, but it is frequent in radiation-induced murine lymphomas. These observations suggest that PNET can be induced after completion of the embryonal and fetal development of the human CNS. Oncogene-activating point mutations may represent a pathogenetic mechanism involved in the genesis of radiation-induced brain tumors.     

Mumpsimpfstoffe: Virologische Grundlagen

Zusammenfassung Nur attenuierte Lebendimpfstoffe haben sich bisher für die Prävention der Mumpsvirusinfektion als wirksam erwiesen. Die verschiedenen Impfstämme unterscheiden sich im. Grad ihrer Attenuierung, die schwer steuerbar ist. Der Grat zwischen Restvirulenz und Überattenuierung ist schmal. Wenig attenuierte Impfstämme zeigten zwar eine höhere Immunogenität, aber auch häufiger Impfkomplikationen. Heute werden nur noch relativ stark abgeschwächte Impfstämme verwendet, die zwar kaum je zu einer impfassoziierten Erkrankung führen, deren Immunogenität aber geringer sein dürfte als ursprünglich angenommen.

---

Summary The prevention of mumps virus infection reties on the application of live, attenuated mumps virus vaccines. The process of attenuation from a wildtype mumps isolate to a safe vaccine has been empirical. A lower degree of attenuation results in solid immunity but carries an increased risk of post-vaccination meningitis due to the vaccine strain. Currently used vaccine strains are highly attenuated and essentially free of vaccine strain induced disease. However, their immunogenicity may be lower than previously reported.

---

Résumé La prévention des oreillons est effectuée grâce aux vaccins contenant des virus ourliens vivants atténués. La différence entre un virus ourlien sauvage et un atténué est très petite. Un virus légèrement atténué engendre une forte immunité mais augmente le risque de développer des méningites postvaccinales. Actuellement on utilise des souches fortement atténuées qui ne font que très peu de complications mais dont l'immunogénicité semble plus faible que prévue.

     

Biphasic Shocks Compared with Monophasic Damped Sine Wave Shocks for Direct Ventricular Defibrillation during Open Heart Surgery

Background: Biphasic waveform shocks are more effective than monophasic shocks for transchest ventricular defibrillation, atrial cardioversion, and defibrillation with implantable defibrillators but have not been studied for open chest, intraoperative defibrillation. This prospective, blinded, randomized clinical study compares biphasic and monophasic shock effectiveness and establishes intraoperative energy dose-response curves.

Methods: Patients undergoing cardiothoracic surgery with bypass cardioplegia were randomly assigned to the monophasic or biphasic shock group. Ventricular fibrillation occurring after aortic clamp removal was treated with escalating energies of 2, 5, 7, 10, and 20 J until defibrillation occurred. If ventricular fibrillation persisted, a 20-J crossover shock of the other waveform was used.

Results: Cumulative defibrillation success at 5 J, the primary end point of the study, was higher in the biphasic group than in the monophasic group (25 of 50 vs. 9 of 41 defibrillated;P = 0.011). In addition, the biphasic group required lower threshold energy (6.8 vs. 11.0 J;P = 0.003), less cumulative energy (12.6 vs. 23.4 J;P = 0.002), and fewer shocks (2.5 vs. 3.5;P = 0.002). Crossover-shock effectiveness did not differ between groups. Dose-response curves show biphasic shocks to have higher cumulative success rates at all energies tested.     

Spectral analysis of prespeech sounds (spontaneous cries) in infants with unilateral cleft lip and palate (UCLP): a pilot study.

OBJECTIVE: The objectives of the present study were: (1) to analyze the cry features of infants with cleft lip and palate (UCLP) by means of spectral analysis, (2) to describe changes of the acoustic parameters from birth until 9 months of age, and (3) to compare these data with existing cry data of infants without cleft (control group). DESIGN: The study was designed on a interdisciplinary, prospective, and longitudinal basis. SETTING: Interdisciplinary study: (1) Institute of Anthropology at the Humboldt-University, Berlin; (2) Heidelberg University Hospital: Interdisciplinary Cleft Palate and Craniofacial Center. PATIENTS AND METHOD: The cry parameters of five patients with complete unilateral cleft lip, alveolar ridge, and hard and soft palate were analyzed from birth to 9 months of age. The patients were treated with the same protocol. At the age of 24 months, sensomotor development was assessed using the KIPHARD test. Perceptual judgment of speech, performed after 36 months of life, included nasal resonance, nasal emission of air, articulation disorders, and speech intelligibility. MAIN OUTCOME MEASURE: The cry parameters of fundamental frequency (F(0)), pitch period perturbation quotient (PPQ), and cry duration (Tsam) were analyzed. RESULTS: Contrary to the expectation that laryngeal parameters are not affected by vocal tract malformations, differences of cry parameters were found between the patients with UCLP and the non-cleft group. Particularly, the F(0) and its short-time variability (PPQ) were affected. CONCLUSIONS: The preliminary results of this study showed that F(0) and PPQ of spontaneous cries are influenced in patients with UCLP, and a cry analysis might become a noninvasive tool for early detection of an at-risk status for neuromuscular development and prediction of an at-risk status for later speech and language acquisition in infants with cleft lip and palate. Future research strategies are outlined.