Superior physical and mental health of healthy volunteers before and five years after mobilized stem cell donation.

BACKGROUND: Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being "warm glow", hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally. METHODS: We enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire. RESULTS: Baseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time. CONCLUSIONS: HSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk-benefit assessment of volunteer HSPC donation. Trial registration National Clinical Trial NCT01766934.

[Differential indications of opioids in pain therapy]. / Differenzialindikation von Opioiden in der Schmerztherapie.

Due to their strong analgesic potency opioids are highly effective in the therapy of acute and particularly cancer-induced chronic pain; however, the individual opioids differ considerably with respect to their pharmacokinetic and physicochemical properties and may therefore not be equally applicable for every patient. Caution should be taken especially in patients with impaired organ function. Furthermore, the metabolism of opioids leads to active or inactive metabolites. This process can be substantially influenced by genetic polymorphisms or drug interactions. Knowledge of all these factors for individual opioids, which influence the efficacy and side effects, is therefore crucial. In this review the pharmacology, clinical applications, metabolism and genetic factors of the most important opioids used for pain management are discussed.

[Disseminated nocardiosis : Diagnostic challenge]. / Disseminierte Nocardiose : Diagnostische Herausforderung.

Nocardiosis is a rarely found bacterial infection in Europe which can particularly affect immunocompromized patients. Localized infections of the dermis and lungs, as well as disseminated infections can be observed. Suspicion of nocardiosis should be reported to the microbiological laboratory so that goal-directed molecular genetic techniques and extended cultivation can be implemented for identification of the causative agent. A multitude of antibiotics can be used for successful therapy but the duration of therapy must be extended over 6-12 months. The mortality of disseminated infections ranges between 15-85% depending on the underlying immune status of the patient. The polymorphic appearance of nocardiosis is described based on the case of an intensive care patient.

Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from soil to plants.

Within the scope of a joint project to study soil-to-plant carryover of polyfluorinated compounds (PFCs), five cultivated plants (spring wheat, oats, potatoes, maize, and perennial ryegrass) were sown or planted in Mitscherlich pots. Six variants per species were used, each with a different concentration level of PFOA and PFOS (from 0.25 to 50 mg/kg as aqueous solution) to detect possible concentration dependence in the transfer of these two PFCs from soil to plant. PFOA and PFOS were detected by liquid chromatography-tandem mass spectrometry after appropriate sample preparation (partial drying, mincing, homogenizing, extraction). Since PFOA and PFOS presently represent the most widely studied PFCs, they are classified as "leading compounds." The results show that concentrations of PFOA/PFOS in the plants vary greatly, depending on the concentrations applied to the soil. PFOA values were higher than PFOS values in all plants except potatoes, in which these differences could be quite substantial. From the results presented here it can be seen that uptake and storage are much more intensive in the vegetative portion of the plant than relocation in the storage organs. This is particularly evident from the the comparison of concentrations found in the grain and ear and those in the straw or rest of the plant in spring wheat, oats, and maize. Transfer from "soil to crops" provides a possible explanation for the presence of PFCs in foodstuffs and in human body fluids such as blood, plasma, serum, or breast milk. The aim of the present study was to determine whether a statistically significant, concentration-dependent carryover of PFOA and PFOS in crop plants can take place, which would provide a potential entrance point for these substances into the food chain.

[Peridural anaesthesia with ropivacaine for a patient with Friedrich's ataxia. Caesarean section after dorsal stabilisation of the spinal column (Th5-L1)]. / Periduralanästhesie mit Ropivacain bei Friedreich-Ataxie. Sectio bei einer Patientin nach dorsaler Stabilisierung der Wirbelsäule (Th5-L1).

Friedreich's ataxia (FA) is a hereditary disease, which leads to degenerative changes in the spinal cord and cerebellum (incidence 1:50,000). These changes are caused by a defect in the gene that encodes a mitochondrial gene called frataxin and causes muscle weakness, scoliosis, cardiomyopathy and impaired glucose tolerance. Therefore, these patients require special care during anaesthesia. We report the case of a 25-year-old primigravida with a history of FA and dorsal stabilisation of the vertebral column, who was admitted to our hospital for elective caesarean section. Due to increased sensitivity to muscle relaxants, peridural anaesthesia with 8 ml 0.75% ropivacaine and 10 microg sufentanil was used in this case. The perioperative neurological consultation revealed no undue exacerbation of symptoms.

Bilateral primary adrenal non-Hodgkin's lymphoma - a case report and review of the literature.

Primary adrenal non-Hodgkin's lymphoma (PAL) is a rare neoplastic disease. Clinical symptoms are often related to the presence of lymphoma or adrenal insufficieny. Diagnostic strategies include endocrine evaluation, imaging studies and histopathological examination. In case of suspicious PAL, percutaneous CT or US-guided needle biopsy is recommended to rapidly establish diagnosis before starting chemotherapy. We report about an 84-year-old male who presented with significant weight loss and chronic lumbar pain. Abdominal CT scans revealed bilateral masses highly suggestive of malignancy. After open bilateral adrenalectomy with abdominal lymphadenectomy, histological examination showed bilateral PAL. Five months after surgery, the patient died due to progressive tumor disease.

[Daptomycin for the treatment of gram-positive infections after cardiac surgery]. / Daptomycin zur Behandlung grampositiver Infektionen nach herzchirurgischen Eingriffen.

BACKGROUND AND METHOD: Surgical infection remains a main cause of death after heart surgery, despite advances in pharmacological therapy. Daptomycin is a cyclic lipopeptide antibiotic, useful in gram-positive organisms resistant to standard treatment, including vancomycin. The aim of this study was to describe the use of daptomycin regarding efficacy, efficiency and safety in patients with gram-positive infections after heart surgery using a retrospective analysis on 49 adult patients. CONCLUSION: Daptomycin shows excellent in vitro and in vivo activity against gram-positive organisms, such as Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, especially MRSA. Daptomycin is also effective against increasing vancomycin-resistant or vancomycin-intermediate S. aureus.

Stress doses of hydrocortisone reduce systemic inflammatory response in patients undergoing cardiac surgery without cardiopulmonary bypass.

BACKGROUND: Systemic inflammatory response occurs after cardiac surgery (CS) and leads to a worse outcome in many cases. Stress doses of hydrocortisone have been successfully used to reduce SIRS and to improve outcome of patients after CS with cardiopulmonary bypass grafting (on-pump CABG), but the effect of hydrocortisone on patients undergoing CS without cardiopulmonary bypass grafting (off-pump CABG) is unclear. Therefore, we evaluated the effect of stress doses of hydrocortisone in this group of patients. METHODS: A total of 305 patients undergoing off-pump CABG were enrolled in a prospective randomized trial according to the study protocol. The patients either received stress doses of hydrocortisone or placebo. We measured various laboratory and clinical variables characterizing the patients' outcomes. RESULTS: The two study groups did not differ with regard to demographic data. Patients receiving hydrocortisone had an increased Higgins score and a decreased ejection fraction. Furthermore, patients from the hydrocortisone group had significantly lower levels of IL-6 (275 [162/677] pg/mL vs. 450 [320/660] pg/mL, P=0.001) and a shorter stay in the ICU (1 [1/3] day vs. 2 [2/3] days, P=0.04). Both groups did not differ in regard to catecholamine support, duration of mechanical ventilation, incidence of postoperative atrial fibrillation, blood loss, and mortality rate. CONCLUSION: We conclude that intravenous stress doses of hydrocortisone lead to a reduction of systemic inflammation and to a potential improvement in the early outcome of patients undergoing off-pump CABG.

Malignant melanoma of the anal region.

Malignant melanoma (MM) of the anal region is an uncommon disease. In many cases, the disease is undetected or mistaken for a benign polyp or haemorrhoids until it reaches an advanced state. Owing to delayed diagnosis and early metastases, the prognosis is often poor. In contrast to melanomas of the skin, a history of sun exposure does not seem to have an impact in development of MM in this region. Anorectal melanomas (AM) are most common in the rectum, followed by the anal canal and anal verge. Ras mutations, especially in codon 61 of the N-ras oncogene, are common in CM and rare in melanomas of the vulva and anorectum. The diagnosis of an AM is usually made using a biopsy. Histopathological examinations show spindle-shaped and pleomorphic cells. Adjuvant immunohistological markers are the calcium-binding protein S-100, the melanoma antigen HMB-45, the melanoma-expressed protein Melan A, and microphthalmia-associated transcription factor (MiTF). To date, there are few published guidelines for the correct management of AM, and surgery remains the mainstay of treatment. We report on a 39-year old man who presented with a 5-week history of recurrent prolapse of an anal tumour. The tumour was histologically confirmed to be malignant melanoma.

Plasma resistin levels in patients with type 1 and type 2 diabetes mellitus and in healthy controls.

Resistin is a recently discovered hormone that is exclusively expressed in adipose tissue. Its expression in rodents was reported to be elevated or suppressed in genetic and diet-induced obesity, respectively. Resistin treatment impaired glucose tolerance and insulin action. Immunoneutralization of resistin improved insulin sensitivity, while thiazolidinedione treatment reduced resistin expression. Therefore, resistin could play a critical role in the development of obesity and type 2 diabetes. In this study were determined resistin plasma levels in humans suffering from type 1 and type 2 diabetes and in healthy controls. Plasma levels of resistin in healthy controls were 38.78 ng/ml. They were not statistically different in individuals with a broad BMI range. Resistin plasma levels in type 2 diabetes were 38.7 ng/ml, and 39.4 ng/ml in type 1 diabetes. Thiazolidinedione treatment did not influence resistin plasma levels. We conclude from our data: 1. resistin can be detected in human plasma, 2. plasma resistin levels are not different in type 1 and type 2 diabetes.

Problem-solving as a function of age, sex and the role appropriateness of the problem content.

The purpose of this study was to investigate problem-solving ability as a function of age, sex and problem content by using 20 problems chosen from the problem-solving literature. The problems were administered without time limits to 8 males and 8 females in each of three age groups: 20--30, 40--50, 60--70. Analysis revealed that only age influenced performance with the middle-age group scoring significantly higher than the other groups. Analysis of the time required by each age group to solve the problems showed the young group required significantly less time than the other groups. Finally, the young group was seen to make more errors of commission while the older group made more errors of omission.

Transcription elongation factor S-II is not required for transcription-coupled repair in yeast.

Two different subpathways play a role in removal of UV-induced cyclobutane pyrimidine dimers (CPDs) by nucleotide excision repair (NER). The relatively slow global genome repair subpathway operates on all CPDs irrespective of their position in the DNA, whereas the transcription-coupled repair subpathway is responsible for the rapid removal of CPDs from transcribed strands. In Saccharomyces cerevisiae, the RAD26 gene is implicated in transcription-coupled repair. However, transcription-coupled repair is not completely absent in rad26 mutants, and therefore other gene products are possibly involved in this subpathway. Based on in vitro experiments with purified components, the transcription elongation factor S-II appeared to be a candidate for a function in transcription-coupled repair. To investigate a possible role of S-II in transcription-coupled repair in vivo in yeast, S-II null mutations were introduced into various genetic backgrounds differing in NER capacity. UV sensitivity was not altered by disruption of the S-II gene in a RAD+ (NER proficient) strain, or in rad26 (impaired in efficient transcription-coupled repair), rad7 (lacking global genome repair), or rad7 rad26 (lacking global genome repair, but having residual transcription-coupled repair capacity) mutants. Moreover, S-II did not influence the repair rate on the transcribed strand of the RPB2 gene, either in repair-proficient or in rad7 rad26 backgrounds. Hence, transcription-coupled repair is fully functional in yeast cells lacking the gene encoding S-II. Furthermore, S-II is not required for the Rad26-independent residual transcription-coupled repair in vivo.

HLA antigens in cases of giant cell arteritis.

HLA tissue-type antigen determination for A-, B- and C-antigens in 88 patients suffering from giant cell arteritis of the temporal artery showed no significant deviations as compared to a control material of 3164 blood donors. A weak indication of association with antigen HLA-B8 appeared to be of interest due to a corresponding indication in previous investigation. The patients were a mixed hospital material, consisting of cases of clinical temporal arteritis and patients with polymyalgia rheumatica. There was an overrepresentation of women (77%). Familial occurrence was demonstrated sporadically (3 pairs of siblings).