An unusual manifestation of post-transplant lymphoproliferative disorder in the lip after pediatric heart transplantation.

PTLD is a serious and frequently observed complication after solid organ transplantation. We present a six-yr-old girl with a rapidly growing, solid tumor of the lip four yr after orthotopic heart transplantation, which was classified as monomorphic PTLD with the characteristics of a diffuse large B-cell lymphoma. Treatment with reduction in immunosuppression, ganciclovir, and anti B-cell monoclonal antibody (rituximab) resulted in full remission since 12 months. To the best of our knowledge, this report is the first description of PTLD in the lip in a pediatric patient after heart transplantation in the English literature.

Present risk of anthracycline or radiation-induced cardiac sequelae following therapy of malignancies in children and adolescents.

Anthracyclines are very potent drugs in the therapy of malignancies in childhood. The major dose limiting adverse effect of these drugs is the risk of dilated cardiomyopathy. We performed a retrospective study on 168 patients who were treated with anthracyclines for a malignant disease with or without chest radiation at the department of Pediatric Hematology and Oncology at the University of Duesseldorf between 2000 and 2004. During and after chemotherapy the patients were screened by echocardiography and ECG examinations prior to each administration of anthracyclines. Only four patients presented with adverse cardiac events, one of whom developed acute cardiac failure. This patient was additionally treated with chest radiation. Three of the four patients showed intermittent arrhythmias, mainly supraventricular tachycardia. One of them presented with atrial ectopic tachycardia and left ventricular dysfunction. We conclude that the frequency of cardiac sequelae after chemotherapy with anthracyclines is low under present guidelines. Detection of early cardiac sequelae may be more difficult than in the past. Only one patient with cardiac sequelae in our study group was diagnosed by regular performed examinations for cardiac sequelae of chemotherapy. We therefore need to modify our screening methods to increase the effectiveness of detection of cardiac dysfunction prior to clinical manifestation.

[Clinical analysis of musicians' focal hand dystonia. Review of 86 cases]. / Análisis clínico de la distonía focal en los músicos. Revisión de 86 casos.

INTRODUCTION: Focal hand dystonia in musicians due to its rareness and specificity. It has been insufficiently described thus remaining a largely unknown condition. OBJECTIVE: To describe the clinical characteristics of musician's focal dystonia. METHODS AND RESULTS: We analyzed 658 musicians' cases seen during the past 4 years in a medical center for performing artists. Of the musicians treated, 86 (13 %) suffered from focal dystonia, 42 % were guitarists, 21% pianists and 6% violinists. Men were more affected than women (7:1). Sufferers reported longer practice times (4.8 hours per day) and were older (33.6 years). In comparison, other pathologies were seen when musicians were younger (26.5 years) and played no more than 3.5 hours per day. CONCLUSIONS: Focal dystonia in musicians appear to be the consequence of a long history of intense and repetitive manual work while playing music added to other factors, as for example, gender.

Análisis clínico de la distonía focal en los músicos. Revisión de 86 casos / Clinical analysis of musicians' focal hand dystonia. Review of 86 cases

Introducción. La distonía focal en el músico, por su ra¬reza y especificidad, ha sido descrita insuficientemente y, por tanto, es poco conocida.Objetivo. Describir las características clínicas de la distonía focal en los músicos.Métodos y resultados. Se analizan los 658 músicos atendidos en un centro especializado en la atención de artistas escénicos durante 4 años. De éstos, 86 fueron diagnosticados de distonía focal (13 %). Como factores de riesgo para la distonía se identifican el hecho de tocar la guitarra (representa el 42 % de los casos, seguido del piano con 21 % y el violín 6 %), ser varón (proporción: 7:1) y haber acumulado una cantidad de horas de ensayo superior a la mediana (la distonía aparece en músicos de 33,6 años de edad media que tocan 4,8 h diarias, mientras que otras patologías se presentan a los 26,5 años en músicos que tocan 3,5 h al día en nuestra muestra).Conclusiones. La distonía focal en el músico parece la consecuencia de un trabajo manual repetitivo, intenso y refinado realizado durante muchos años sobre el instrumento musical a lo que se añadirían otros factores como, por ejemplo, el sexo

Introduction. Focal hand dystonia in musicians due to its rareness and specificity. It has been insufficiently described thus remaining a largely unknown condition.Objective. Io describe the clinical characteristics of musician's focal dystonia.Methods and results. We analyzed 658 musicians' cases seen during the past 4 years in a medical center for performing artists. Of the musicians treated, 86 (13 %) suffered from focal dystonia, 42 % were guitarist, 210/0 pianists and 6 % violinists. Men were more affected than women (7:1). Sufferers reported longer practice times (4.8 hours per day) and were older (33.6 years). In comparison, other pathologies were seen when musicians were younger (26.5 years) and played no more than 3.5 hours per day.Conclusions. Focal dystonia in musicians appear to be the consequence of a long history of intense and repe¬titive manual work while playing music added to other factors, as for example, gender

[Posttraumatic pain. Causes and therapeutic possibilities]. / Posttraumatische Schmerzen. Ursachen und Therapiemöglichkeiten.

Each patient has the right of a dedicated pain therapy according to the state of the art. However an efficient pain therapy is not possible without knowing the cause of pain. In most posttraumatic pain situations peripheral nociceptors are activated and normal afferences are conducted via an intact nociceptive system. In contrast, neuropathic pain pain is caused by lesions of the nervous system itself. Mechanisms of central sensibilization and involvement of the sympathetic nervous system may lead to chronification of such pain conditions. The therapeutic regime of nociceptive and neuropathic pain is demonstrated by algorithms of treatment modalities. Apart from classic non-opioid analgesics, co-analgesics and opioids have an important status in chronic pain management as well. Prescription of these substances has to follow strictly defined standards of pain therapy. Blockades with local anaesthetics as mono-therapy of chronic pain are obsolete. In posttraumatic pain, however, a certain number of adjuvant blockades or infiltrations of triggerpoints may be helpful. The exceptional place of sympathetic blockades are in diagnosis and therapy of sympathetic maintained pain (SMP).

[Pharmacist's attitudes towards opioid prescription]. / Betäubungsmittelverschreibungsordnung. Einstellung der Apotheker.

UNLABELLED: The prescription of strong opioids underlies a special legislation. The attitude of the pharmacists towards the long-term treatment with these analgesics and their opinion about the legislation is unknown in Germany and other European countries. METHODS: A questionnaire was included in the Journal "Mitteilungsblatt der Apothekerkammer Westfalen-Lippe" and send to all 2300 pharmacists of the region Westfalen-Lippe in December 1997. RESULTS: 797 (35%) questionnaires were returned. In 82.4% of the pharmacies strong opioids are kept in stock. However, 140 pharmacists do not have opioids in stock due to too many different preparations or low prescription rate. 54% of the pharmacists warn their patients about endangering by the medication. The fear of psychological addiction (48.1%) is the main argument, also in patients with regular intake of the opioids (20.1%) and related to long acting opioids (10.8%). Nevertheless, 73% of the pharmacists advocate for a liberalization and 10.7% for an abolishment of the actual prescription laws. DISCUSSION: The importance of the therapy with strong opioids is well accepted by the pharmacists. An ease of the prescription is demanded to improve the situation of the patients with chronic pain. However, the majority of the pharmacists warns the patients about this medication. Contact between prescribing doctors and pharmacists and an intensified education concerning the therapy with opioids are needed in addition to the education of the medical staff and the liberalization of the prescription laws.

Post-traumatic pain. Causes and therapeutic concepts.

Each patient has the right of a dedicated pain therapy according to the state of the art. However an efficient pain therapy is not possible without knowing the cause of pain. In most posttraumatic pain situations peripheral nociceptors are activated and normal afferences are conducted via an intact nociceptive system. In contrast, neuropathic pain pain is caused by lesions of the nervous system itself. Mechanisms of central sensibilization and involvement of the sympathetic nervous system may lead to chronification of such pain conditions. The therapeutic regime of nociceptive and neuropathic pain is demonstrated by algorithms of treatment modalities. Apart from classic non-opioid analgesics, co-analgesics and opioids have an important status in chronic pain management as well. Prescription of these substances has to follow strictly defined standards of pain therapy. Blockades with local anaesthetics as mono-therapy of chronic pain are obsolete. In posttraumatic pain, however, a certain number of adjuvant blockades or infiltrations of triggerpoints may be helpful. The exeptional place of sympathetic blockades are in diagnosis and therapy of sympathetic maintained pain (SMP).

[Are tramadol enantiomers for postoperative pain therapy better suited than the racemate? A randomized, placebo- and morphine-controlled double blind study]. / Sind Tramadol-Enantiomere für die postoperative Schmerztherapie besser geeignet als das Racemat? Eine randomisierte, Plazebo- und Morphin-kontrollierte Doppelblindstudie.

The goal of this prospective, randomised and double-blind pilot-study was to investigate the analgesic potency and the side-effects of tramadol enantiomers in clinical practice. One hundred patients recovering from orthopaedic surgery with a postoperative pain intensity of more than 50 on a visual analogue scale 0-100 mm (Table 1) were recruited for the study. They were treated in a randomised, double-blind way with a maximal dose of 150 mg i.v.(+)-,(-)-tramadol, racemate, or 15 mg i.v. morphine or saline in the placebo group (5 groups, 20 patients each). The primary criterium of efficacy was the number of responders defined as patients with a pain reduction of at least 20 on VAS after 40 min. In case of pain, responders were allowed to continue with the double-blind drug up to six hours. The non-responders were treated with morphine as the rescue analgesic. The secondary criterium was the incidence and severity of side-effects. Six patients terminated the study prematurely. One patient was excluded because of an allergic reaction to morphine, one patient could not be treated sufficiently with morphine, four were excluded because of protocol violations. There were 8 responders in the (+)-tramadol-,6 in the (-)-tramadol- and 6 in the racemate group, 16* (P < 0.05) in the morphine group, and 5 in the placebo group. Pain intensity after 40 min was reduced by 20 (p < 0.05), 17 (p < 0.05), 17 (p < 0.05), 36 (p < 0.01 vs placebo, p < 0.05 vs (+)-,(-)-tramadol, and racemate group) and 5 mm on the VAS in the (+)-, (-)-, (+/-)-tramadol-, morphine- and placebo-group, respectively. Thirty eight adverse events like nausea, vomiting, PCO2-increase, and urinary retention occurred in 20 patients, most frequently in the (+)-tramadol- and morphine group. Sedation was significantly less profound in the (-)-tramadol group 1-4 h postoperatively. There were no side-effect in the tramadol racemate group. The enantiomers were equal to the racemate in analgesic potency, but inferior by far to morphine. They showed more adverse events and, hence, can not be preferred to the racemate in postoperative pain therapy.

Experiences with the prescription of opioids: a patient questionnaire.

Forty-three German patients who had been treated with strong opioids were questioned about their experiences during therapy. The prescription of opioids was well accepted by most patients. Some, however, felt stigmatized by taking opioids. Fourteen patients (33%) were asked by their relatives, friends, or other patients about the special prescription form. Six patients (14%) had difficulties in redeeming the prescription at the pharmacy, seven patients (16%) were warned against taking the medication by the pharmacist, 21 patients observed that their general practitioner (GP) was mistrustful about the treatment, and 16 patients (37%) reported that the GP terminated the therapy. Despite the beneficial effect for the patient, opioid treatment started and supervised in a pain clinic is not always continued by the GP. In Germany, it may not be possible to administer opioid therapy outside of a specialized pain clinic. In those few cases in which an opioid therapy is successfully instituted, difficulties continue due to prejudices, insufficient education, and complicated prescription laws.

Long-term treatment of cancer pain with transdermal fentanyl.

The long-term therapy of 51 patients using transdermal fentanyl was evaluated. The transdermal therapy was performed for 158 days (range, 15-855 days). The need for increasing dosages of transdermal fentanyl was caused by the progression of the underlying cancer disease (mean initial dose, 69.5 micrograms fentanyl/hr; mean final dose, 167.7 micrograms fentanyl/hr). The transdermal system was changed every third day. Application intervals had to be shortened in 23.5% of the patients. Pain reduction was good throughout the study. Severe side effects did not occur. Constipation and the need for laxatives occurred less frequently than with previously administered oral morphine. Skin tolerance of the transdermal system was good. The treatment of cancer pain with transdermal fentanyl can be performed as a long-term therapy and result in good pain relief. Considering its specific pharmacokinetic properties, it is an alternative medication on step III of the World Health Organization's guidelines for cancer pain management.

[Indications and limits of nerve block techniques]. / Indikation und Grenzen von Blockadetechniken.

Repetitive nerve blocks as a monotherapeutic treatment are loosing importance in the therapy of chronic pain. Such invasive methods for pain reduction are just one strategy in the interdisciplinary and multimodal planning of pain therapy. They are mostly used in special indications, e.g. reflex sympathetic dystrophy neurolysis in S3-S5 localized cancer pain. Premises for an invasive pain therapy are the patient's knowledge and agreement concerning this method. Furthermore, it is necessary for the physician to know the typical complications of the invasive treatment and to be able to manage them. It is recommended to document the pain course.

Long-term effects of nerve blocks in chronic pain.

Regional blockade techniques have been of crucial importance for decades in chronic pain therapy, but in recent years some developments have made a new definition of the status of invasive procedures necessary. The realization of chronic pain as a multifactorial process led to the establishment of an interdisciplinary approach to pain therapy, leaving blockades as only one step in a multimodal therapy. The mainstay of local anaesthetic blocks now is diagnostic and prognostic, but correct interpretation of the results is limited by different factors, and controlled studies on the diagnostic value of local anaesthetic blockade are lacking. In cancer pain, invasive procedures are necessary in only a few cases. Some neuroablative techniques can offer long-term pain reduction. In non-cancer pain, neurodestructive procedures should be reserved for some special indications (e.g. lumbar sympathetic neurolytic blocks in ischaemic diseases). In a great number of chronic pain conditions the sympathetic nervous system is involved or even has a central status. In the acute stage of these diseases sympathetic blockades can be the therapy of choice. There is no disease in which different invasive procedures are performed so frequently and so uncritically as in chronic low back pain. Up to now, however, all controlled studies of invasive procedures only demonstrated short-term effects and failed to prove long-term efficacy. Therefore any invasive technique should only be performed in well-selected patients over a defined period and with a limited number of blockades.

[A survey of physicians' knowledge about pain therapy with strong opioid analgesics]. / Befragung schmerztherapeutisch interessierter Arzte zur Verschreibung starker Opioidanalgetika.

INTRODUCTION: The WHO analgesic ladder, including the use of strong opioid analgesics for the treatment of cancer pain, is widely accepted. However, the use of opioids for the treatment of non-cancer pain is still controversial. This study investigates doctors' medical knowledge about basic aspects of pain management. Additionally, we determined whether the deficiencies in the treatment of patients suffering from pain are based on the rigorous national narcotic control system in Germany. METHODS: We investigated the juridical and technical knowledge of physicians specializing in pain therapy by a questionnaire. During a postgraduate course the knowledge about pain therapy according to the WHO analgesic ladder and the beliefs concerning the narcotic regulations in Germany were evaluated. The survey participants were asked to rate their attitudes on a 10-point analogue scale (1=disagreement, 10=full agreement). The participants were also asked to indicate occupational criteria such as specialty, clinical practice area, and postgraduate years of practice. Descriptive statistics for the mean values were used. RESULTS: One hundred and forty-three questionnaires were completed. The majority of participants worked at departments of anaesthesiology. Some 51.1% of the participants had no specific multiple-copy prescriptions for opioid analgesics. Only 72% of the physicians knew from which governmental institution they could order multiple-copy prescriptions. In general, more doctors would prescribe opioids by the use of normal forms. The controlled substance laws were seen as an impediment by the majority of participants, without relevant differences as to their years of practice. The regulations were regarded as ineffective protection against illegal use of opioids. Treatment of pain with strong opioid analgesics was seen as beneficial for the patients. The use of strong opioids for long-term treatment was recommended, and psychological addiction was regarded as non-existent. CONCLUSION: Therapy with strong opioids is accepted practice, but significant deficits of legal and technical knowledge uphold the undertreatment of patients suffering from cancer and non-cancer pain. Patients with a legitimate need for pain relief by strong opioids are the unintended victims of tight narcotic regulations and deficits in medical education. An ease of regulatory conditions is mandatory to reduce the reluctance for prescribing opioids. On the other hand intensified continuous medical education is mandatory to reduce the undertreatment of patients with severe pain conditions.

[Opioids and driving ability]. / Opioide und Fahrtüchtigkeit.

INTRODUCTION: Clinical observations of patients under oral opioid treatment suggest that the initially appearing central side effects such as sedation, dizziness or drowsiness decrease after a few weeks of treatment. However, it is still unclear whether long-term treatment with opioids impairs complex psychomotor functions such as driving a car. METHODS: Twenty patients on stable dosages of oral opioids were examined using a driving simulator. The patients were regular car drivers and not older than 70 years. Additionally, every patient had to complete a questionnaire for mental condition and vigilance and the "d II" letter cancellation task. Control groups tested in the same way were: patients before an elective operation after taking benzodiazepines for sedation, volunteers after alcohol consumption (0.80 per thousand ), physicians on call with less than 4 h of sleep and healthy volunteers without any medication. RESULTS: Some of the patients treated with opioids reacted as fast as medication-free volunteers. There were no significant differences between the reaction times of older patients (>50 years) receiving opioids in comparison to the group of older healthy volunteers. The same result was obtained in the letter cancellation task. No differences could be seen between medication-free volunteers and patients receiving opioids with regard to tasks of visual or motor control skills. The volunteers under influence of alcohol and the patients under benzodiazepines had a considerable decrease in performance. CONCLUSIONS: Long-term therapy with opioids does not inevitably impair complex skills, but the decision to permit driving a car can only be made in the individual case. PRACTICAL RECOMMENDATIONS: At the beginning of therapy with opioids the physician has to fulfil his duty to inform the patient of any possible dangers of treatment. From the medical point of view, driving must be prohibited until a stable opioid dosage is reached. Any changes in dosage (increase, reduction), change of the opioid and poor general condition independent of the opioid therapy must result in prohibition of car driving. Continuous control of the therapy with documentation is a duty of the physician. The written documentation should include the patients' physical and mental condition, side effects and the therapeutic result. From the medical point of view, driving can be possible when dosage treatment and general condition remain stable. In any case, the doctor has to remind the patient of the responsibility of critical self-examination. In doubt, special performance investigation should be taken into consideration.

Structure-activity studies for a novel series of N-(arylethyl)-N-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamine s possessing dual 5-HT uptake inhibiting and alpha2-antagonistic activities.

In search of an alpha2-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the alpha2-receptor (K(i) = 6.71 nM) and the 5-HT uptake site (20.6 nM). A series of tertiary amine analogs of 3 were synthesized and assayed for their affinity at both the alpha2-receptor and the 5-HT uptake site. The structure-activity relationship reveals that a variety of structural modifications to the arylethyl fragment are possible with retention of this dual activity. On the tetralin portion, 5-OMe substitution and the (R) stereochemistry at C-1 are optimal with alternate substitutions producing compounds retaining high affinity for the alpha2-receptor but lacking affinity for the 5-HT uptake site. Data for several rigidified 5-O-alkyl analogs suggests that the favored orientation of the oxygen lone pairs may be away from the 6-position of the tetralin.

Antibody immobilization using heterobifunctional crosslinkers.

Covalent attachment of functional proteins to a solid support is important for biosensors. One method employs thiol-terminal silanes and heterobifunctional crosslinkers such as N-succinimidyl 4-maleimidobutyrate (GMBS) to immobilize proteins through amino groups onto glass, silica, silicon or platinum surfaces. In this report, several heterobifunctional crosslinkers are compared to GMBS for their ability to immobilize active antibodies onto glass cover slips at a high density. Antibodies were immobilized at densities of 74-220 ng/cm2 with high levels of specific antigen binding. Carbohydrate-reactive crosslinkers were also compared to GMBS using a fiber optic biosensor to detect fluorescently-labeled antigen. At the concentrations tested, the antibodies immobilized with carbohydrate-reactive crosslinkers bound more antigen than GMBS immobilized antibodies as indicated by the fluorescence signal.

[Anesthesia and intensive care management of severely burned children of Jehovah's Witnesses]. / Anästhesiologisches und intensivmedizinisches Management bei schwer brandverletzten Kindern der Zeugen Jehovas.

A 3.5-year-old girl suffered from a thermal injury affecting 37% of the body surface area. The parents, being Jehovah's witnesses, refused permission for their child to receive blood transfusions. As the haemoglobin level was only 7.5% and a necrectomy was planned, the patient was likely to need blood transfusions. Indications for transfusion were defined as clinical signs of hypoxia and/or cardiovascular instability. A judicial declaration was proposed. Hb decreased during the therapy. To stimulate the erythropoiesis erythropoietin and iron were administered. During the clinical course the anaemia worsened. First, a conservative treatment with polyvidoniodine ointment for tanning was started, to avoid an operation during the acute phase after the injury, as in this case it was thought a blood transfusion would definitely be necessary. On the 19th day after the injury a necrectomy of 10% of the body surface was necessary because of fever and leucocytosis not responding to antibiotics. The most likely cause of the symptoms was an infection of the burned area. Hb was 4.6 g/dl%. General anaesthesia was performed with midazolam, ketamine and vecuronium and mechanical ventilation. No blood transfusion was required during the operation. Vital signs were stable during the preoperative period, during anaesthesia and following the operation. There were no signs of tissue hypoxia. Peripheral oxygen saturation ranged between 98% and 100%, lactate and arterial blood gas samples were normal, and the child was awake and cooperative before and after anaesthesia. The lowest Hb was 3.3 g/dl on the 22th day after injury (3rd postoperative day). In this phase the patient was still playing and riding a tricycle. On the 45th day after injury the child was discharged home with Hb of 10.9 g/dl and reticulocytosis of 33%.