[Whole body hyperthermia in pain therapy. A controlled trial on patients with fibromyalgia]. / Ganzkörperhyperthermie in der Schmerztherapie. Eine kontrollierte Studie an Patienten mit Fibromyalgiesyndrom.

BACKGROUND: The aim of this study was to evaluate whether mild water-filtered near infrared whole body hyperthermia in patients with fibromyalgia produces a benefit when applied as an addition to a standard multimodal rehabilitation. PATIENTS AND METHODS: In this study 67 patients at a German rehabilitation clinic were included and allocated to 3 study groups: the 2 intervention groups received additional mild water-filtered near infrared whole body hyperthermia once or twice a week over 3 weeks and the control group received only standard multimodal rehabilitation. Main outcome measure was pain intensity measured at baseline, discharge from the rehabilitation clinic and 6 months after discharge. RESULTS: Additional mild water-filtered near infrared whole body hyperthermia once a week proved to be significantly better than the second hyperthermia group and the control group with respect to pain reduction and affective sense of pain. Furthermore, hyperthermia once a week tended to result in better outcome regarding fibromyalgia-related quality of life and depression. CONCLUSION: There is evidence that mild water-filtered near infrared whole body hyperthermia is a reasonable complement to multimodal rehabilitation in the treatment of fibromyalgia.

Metagenomic sequencing at the epicenter of the Nigeria 2018 Lassa fever outbreak.

The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.

Interaction of antioxidants with depth-dependent fluorescence quenchers and energy transfer probes in lipid bilayers.

Three fluorescent, lipophilic, heterocyclic antioxidants were incorporated into lipid bilayers and exposed to depth-dependent nitroxyl fatty acid quenchers. The Stern-Volmer plots curved upward at low quencher concentrations. Quantitative analysis of the results showed that this behavior is consistent with complex formation between quencher and fluorescent antioxidant, where the complex is 2-3 times more fluorescent than the parent fluorophore. At higher quencher concentrations, both free antioxidant and 'bright complex' are quenched dynamically, albeit quenching of the latter is less efficient. The complex probably results from ionic, hydrogen bond and pi-pi interactions. Formation of such a 'bright complex' is also observable in a homogeneous solution of the reactants in cyclohexane. Additional evidence for the complexation of these antioxidants with fatty acids in lipid bilayers is provided by the fact that energy transfer from the antioxidants to anthroyloxy fatty acids occurs at surface concentrations where radiative energy transfer between free molecules should be not be efficient. For directly probing the relative depths of these fluorophores in lipid bilayers we used the aqueous quenchers acrylamide and iodide. They showed that in terms of increasing depth in the bilayer, the order was U-78, 517f < U-78,518e < U-75,412e. Our results, in toto, demonstrate that the Lazaroid antioxidants are incorporated into the lipid bilayer where they occupy strictly defined positions and orientations. Complexation with fatty acyl chains should be mechanistically relevant, since it may enhance antioxidant activity by hindering free radical chain propagation.

[Perthes disease--choice of therapy with reference to psychosocial aspects]. / Morbus Perthes--Wahl der Therapieform unter Berücksichtigung psychosozialer Aspekte.

Within the scape of a comparative long-term study between conservative and operative therapy of Perthes'-disease the effort was made to estimate the dimension of the psychic and social detraction in addiction to the method of treatment by a detailed inquiry of 116 patients as well as of their accompanying parents. This happened because of the opinion, that not only the formal result should decide on the choice of therapy, but also in a justifiable dimension the way of treatment should be orientated on patients. The analysis of the anamnestic particulars showed, that also under psycho-social aspects the immediate surgical procedure has the advantage over conservative methods of treatment at Perthes' disease.

[Roentgenologic stages of Perthes disease]. / Röntgenologischer Stadienverlauf der Perthesschen Erkrankung.

Not only for giving the diagnosis "Perthes' disease" but also with regard to prognostic statements the knowledge of the radiological stages of Perthes' disease is essential. The present treatise demonstrates the radiological course of Perthes' disease, how it results from the evaluation of the courses of illness of 116 patients, which were treated in the period from 1965 to 1980 at the Orthopedic University Hospital Hamburg-Eppendorf because of a genuine Perthes' disease. The following schema turned out to be appropriate to the assessment: I. Initial stage, I a Early period, I b Late period. II. Florid stage, II a Sclerosing period, II b Fragmental period, II c Osteolytic period. III. Stage of regeneration. IV. Final stage.

[Sonographic assessment of typical lesions in shoulder dislocation]. / Sonographische Beurteilung typischer Läsionen bei der Schulterluxation.

The traumatic dislocation of the shoulder joint is the most often joint luxation. The involved patients are often sporting and between the age of 20 to 40 years. The therapeutic and prognostic point of interest is to recognize and reconstruct injured structures. Among the soft tissue injuries the Bankart lesions, among the osseous injuries the Hill-Sachs defect are numeric well to the fore. Hitherto existing diagnostic methods for these injuries are either invasive or with X-rays. Its is demonstrated, that dynamic ultrasonography examination of the shoulder joint can visualize besides the rotator cuff abnormalities of the labrum glenoidale and the caput humeri outline.

[Effect of various criteria on the course and therapy result in Perthes disease]. / Einfluss verschiedener Kriterien auf Verlauf und Therapieergebnis des Morbus Perthes.

The present treatise gives an account of the courses of illness as well as of the results of a follow-up examination of 116 patients, which have been treated in the period from 1965 to 1980 at the Orthopedic University Hospital Hamburg-Eppendorf because of a genuine Perthes' disease. Sufficient documented courses are going back to the year 1952. In the centre of interest is the question about the influence of the method of treatment, of the patients' age at the time of giving the diagnosis as well as of the radiological stage of illness at the moment of giving the diagnosis on the course and on the therapeutic result of Perthes' disease. Clinical parameters have been subdivided in the classifications of Renckhoff (1975) as well as of Howorth and Ferguson (1934). The assessment of the radiological results took place according to the classifications of Sundt (1949) as well as of Bauer und Jünger (1977). 4 therapeutic groups, 7 stage of disease and 5 age groups have been differentiated. According to the results of this long-term study at the moment the immediate intertrochanteric varus osteotomy, independent of the radiological stage of disease and of the patient's age, is being looked upon as the best method of treatment for Perthes' disease.

[Methods of surface measurements in idiopathic scoliosis]. / Oberflächenvermessungsmethoden bei der idiopathischen Skoliose.

The radiologic evaluation of scoliotic spines is a well established, exact method. In long follow-up histories these patients aquire a remarcable radiation exposure. Measurement of additional clinical parameters intends since decades to minimize this exposure. Documentation of surface deformities follows the presumption of a correlation between these and the radiologic angles. The analysis of 714 completely documented untreated idiopathic scoliotic curves showed a good overall correlation between surface deformity and Cobb angle, but single measurements varied too widely to make the used surface documentation a real alternative to x-rays. Treated scoliosis patients pose additional problems in the evaluation, a any treatment - brace and operation - further diminish the correlation. Obviously the usual clinical surface evaluation can only document the cosmetic appearance. Regular radiologic follow-up stays inevitable especially in treated scoliotic patients.

Probing the structure-function relationship of nerve growth factor.

We compared the receptor binding, antigenicity, biological activation, and cell-mediated proteolytic degradation properties of mouse nerve growth factor (mNGF) and human NGF (hNGF). The affinity of hNGF toward human NGF-receptor is greater than that of mNGF, but the affinity of mNGF toward rat NGF-receptor is greater than that of hNGF. Thus, the specificity of the interaction between NGF and its receptor resides both on the NGF and on its receptor. Using a group of anti-NGF monoclonal antibodies that competitively inhibit the binding of NGF to receptor, sites differing between mNGF and hNGF were detected. Together, these results indicate that the sites on hNGF and mNGF, responsible for binding to NGF-receptor, are similar but not identical. In comparing the relative abilities of mNGF and hNGF to stimulate a biological response in PC12 cells, we observed that mNGF was better at stimulating neurite outgrowth than was hNGF, consistent with the differences observed for receptor binding affinity. However, the ED50 for biological activation is approximately 100-fold lower than the Kd for receptor occupancy, and, thus, the dose-response curve is not consistent with a simple activation proportional to receptor occupancy. The data are consistent with a model requiring a low-level threshold occupancy of NGF-receptor (Kd = 10(-9) M) in order to stimulate full biological activity. Finally, we observed the degradation of NGF by PC12 cells. We found that the NGF molecule is significantly degraded via a receptor-mediated uptake mechanism. Together, the data provide insight into regions of the NGF molecule involved in contacts with the receptor leading to formation of the NGF:NGF-receptor complex. Additionally, they establish the link between occupancy of receptor and biological activation and the requirement for receptor-mediated uptake in order to degrade NGF proteolytically in cultured PC12 cells.

An experimental method for the determination of enzyme-competitive inhibitor dissociation constants from displacement curves: application to human renin using fluorescence energy transfer to a synthetic dansylated inhibitor peptide.

We developed a facile procedure for the determination of enzyme-competitive inhibitor dissociation constants over a wide range of potencies at any ratios of enzyme, labeled ligand, and inhibitor. The assay uses displacement curves and a fluorescent-labeled ligand to allow experimental determination of dissociation constants (Kd's) of inhibitors of human renin, a highly specific enzyme, for which numerous high affinity (up to 100 pM) inhibitors have been synthesized. The procedure involves binding a dansylated competitive inhibitor, U80215, followed by its displacement by an unlabeled inhibitor of renin. Binding of U80215 is monitored by fluorescent energy transfer from the renin tryptophans to the dansyl moiety; displacement of U80215 by an unlabeled inhibitor is monitored by a reversal of this process. The procedures may be used to determine the potencies of unlabeled inhibitors up to 100 pM affinities and to determine kinetic binding constants. The concepts described should also be useful in other protein/ligand systems.

Single-step purification and biological activity of human nerve growth factor produced from insect cells.

Human nerve growth factor (NGF) was cloned and engineered for expression in a baculovirus-infected Spodoptera frugiperda (SF-9) insect cell system. Culture supernatants contained 2-3 mg/L of recombinant human NGF. The human NGF produced by this system was purified to apparent homogeneity with a single-step affinity chromatography procedure using a high-affinity monoclonal antibody originally raised against murine NGF. The purification procedure yielded 1-2 mg of pure, human NGF per liter of culture supernatant; i.e., approximately 60% recovery of the human NGF originally released into the culture medium. Although the gene transfected into the SF-9 cells coded for pro-NGF, the NGF recovered after purification was greater than 95% fully processed, mature protein. The KD for the affinity of the pure, recombinant human NGF for NGF receptor in PC12 membranes is 0.20 +/- 0.05 nM. Activation of neurite outgrowth in PC12 cells occurs with ED50 values of 85 +/- 20 pM and 9.6 +/- 1.5 pM for a 3-day primary response and a 1-day secondary response, respectively. The pure, recombinant human NGF also stimulates a significant increase in dopamine content of PC12 cells with an ED50 of 5.8 +/- 2.7 pM. These binding and biological activation properties are consistent with values observed using murine NGF purified from submaxillary glands.