Detection of invasion-related chromosomal changes in highly and weakly invasive melanoma cell clones by a modified comparative genomic hybridization approach

Invasion is a key step in the systemic spread of tumour cells. The aim of this study was to investigate whether specific chromosomal aberrations in melanoma occur during acquisition of a strongly invasive phenotype. We previously selected highly and weakly invasive cell clones from the human melanoma cell line Mel Im. Both cell clones retained a stable phenotype over more than 40 passages, revealing a five-fold difference in their invasive potential in vitro. Direct comparative genomic hybridization (CGH) (modified CGH) of the two cell clones was used as a powerful tool to screen for different chromosomal aberrations in both clones. Standard CGH and fluorescence in situ hybridization (FISH) was performed to verify the results of this improved technique. In general, the CGH pattern showed a high degree of identity consistent with the fact that the cell lines represent subclones of the same cell line. However, a few defined changes between the two cell clones were observed, including loss of 1q21-qter, 4q, 11p14-pter, 19q and 20p in the highly invasive cell clone. Two of the regions (1q and 11p) have already been suggested to be involved in melanoma progression, whereas changes in the others have not been detected before. In summary, our direct CGH approach proved to be suitable for fast and direct comparison of two cell types and allowed the identification of two known and three novel chromosomal changes involved in the acquisition of a strongly invasive melanoma cell phenotype.     

The gatekeeper model is inefficient for the delivery of dermatologic services

BACKGROUND: Gatekeeper-paradigm managed care systems may discourage the use of dermatologists in the management of skin conditions by limiting direct access. This may limit the quality of care patients with skin disorders receive and may be an inefficient use of medical resources. OBJECTIVE: The purpose of this study was to determine the likelihood that patients with dermatologic conditions who see a primary care provider will be referred to a dermatologist. METHODS: Data on the disposition of outpatient visits to primary care physicians for one and only one dermatologic diagnosis were obtained from the 1990-1994 National Ambulatory Medical Care Survey. These data were used in an econometric model to estimate the likelihood of referral to a dermatologist for an episode of care. RESULTS: Of all visits for a single dermatologic diagnosis, 39% were to primary care physicians. The disposition of referral was more common for these dermatology-related visits than for all office visits to primary care physicians (5.8% vs 4.5%, P < .001). The most frequent diagnoses associated with referral were common dermatologic problems, not rare disorders. The number of visits per episode of care was highly dependent on the assumptions of the analysis, resulting in estimate ranges for referral rates per episode between 6.8% and 18.5% for pediatricians, 8.2% and 23% for family and general practitioners, and 16.6% and 46.5% for internists. CONCLUSION: The relative difficulty for primary care providers of managing skin problems is reflected by their frequent need to refer patients with common skin problems and by the greater likelihood of referral for skin disorders than for other medical conditions. The high rates of referral per episode of care supports the cost-effectiveness of direct access to dermatologists.     

Histologische und audiometrische Studie über den alternsbedingten Struktur- und Funktionswandel des Innenohres

Zusammenfassung Die altersbedingte, schon vom 2. und 3. Dezennium an nachweisbare, mit zunehmendem Alter fortschreitende Hörverschlechterung wird beschrieben und kritisch auf die unvermeidliche Subjektivität bei der Festlegung dessen, was als altersbedingtes Normalgehör zu gelten hat, hingewiesen. Es ist notwendig, die ggf. krankheitsbedingten von den lediglich altersbedingten Hörstörungen abzugrenzen. Bei überschwelligen Messungen an über 100 Personen mit altersgemäßem Schwellengehör ergibt die Intensitätsunterschiedsschwellenbestimmung nachLüscher u.Zwislocki in der überwiegenden Mehrzahl normale bzw. vergrößerte Werte und die Geräuschaudiometrie denLangenbeckschen Gangliontyp mit ausgeprägter pathologischer Verdeckbarkeit. Im Sprachaudiogramm nahmen im höheren Alter die Kurventypen zu, bei denen eine stärkere Erhöhung der Intensität mit Zunahme des Diskriminationsverlustes einhergeht (R-Typ). Deutlicher tritt diese Erscheinung bei der Sprachprüfung im Geräusch hervor. Das Fehlen eines Recruitments im Tonaudiogramm macht wahrscheinlich, daß pathologische Verdeckbarkeit und zentrale Faktoren die Ursache sind. — Bei der histologischen Untersuchung der Felsenbeine von 100 Personen aller Altersgruppen, die zur Hälfte ein nachweislich normales Gehör vor dem Tode hatten, zeigt sich als einziger Befund, der regelmäßig nachweisbar und bei quantitativer Bestimmung sich als progredient erweist, der also dem Verhalten des Tongehörs voll entspricht, ein Schwund der Zellen im Ganglion spirale, vornehmlich in der basalen Windung. Andere Veränderungen amCorti-Organ, an Stria, Basilarmembran usw. sind ohne Regelmäßigkeit hinsichtlich Lokalisation und Altersverteilung, so daß sie als teils postmortalartifiziell, teils krankheitsbedingt-akzidentell, aber nicht altersbedingt angesprochen werden. Ausführungen zur morphologischen, cytochemischen, funktionellen und phylogenetischen Sonderstellung des Spiralganglions ergänzen die Darlegung der Befunde und kennzeichnen den altersbedingten Ganglienzellenschwund des Innenohres als einen Prozeß von hohem allgemeinem Interesse für die Erforschung der Gesetzmäßigkeit des Alterns.Mit 2 Textabbildungen     

Pituitary response to bolus and continuous intravenous infusion of luteinizing hormone-releasing factor in normal women and women with polycystic ovarian syndrome.

Plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured in response to luteinizing hormone-releasing factor (LRF), given as a 100 microgram intravenous bolus and/or as a 4 hour infusion of 0.2 microgram per minute to 27 normal menstruating women and 15 women with the polycystic ovarian syndrome (PCOS). In PCOS, LH response to bolus LRF was significantly greater than those of normal women at days 1 to 4 and 8 to 10 of the cycle, whereas FSH responses were similar in all women studied. Continuous LRF infusion resulted in a biphasic LH release pattern. In normal women, the early phase was low until days 12 to 14 of the normal cycle, whereas the second phase rose progressively from the early follicular to the periovulatory period. In PCOS, the early phase was relatively large and qualitatively resembled the normal periovulatory pattern. The increased pituitary LH response to LRF in PCOS is associated with a relatively large early releasable LH pool and a low FSH response.     

Physikalische Urtikaria

The different types of physical urticaria are triggered by mechanical and thermal stimuli, as well as electromagnetic waves. Localized forms restricted to the skin and mucous membranes are most common, but generalized urticaria with variable extracutaneous manifestations can also occur. Physical urticaria is usually sporadic but may rarely have a familial form; it is often associated with chronic urticaria. In most instances, the short time interval between the physical stimulus and reaction points to a causal relationship, but in delayed types the exact diagnosis may be missed without provocation tests. The clinical implication of physical urticaria is demonstrated by investigations showing a greater degree of disability in affected patients as compared to other types of urticaria. There is still an incomplete understanding of the crucial pathophysiological aspects; most likely inflammatory reactions involving leukocytes, endothelial cells and nerves stimulated by various mediators play an important role in this form of urticaria.     

Infection with Mansonella perstans Nematodes in Buruli Ulcer Patients,Ghana

During August 2010–December 2012, we conducted a study of patients in Ghana who had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co-infected with Mansonella perstans nematodes; 13% of controls also had M. perstans infection. M. perstans co-infection should be considered in the diagnosis and treatment of Buruli ulcer.     

Depression by morphine-6-glucuronide of nociceptive activity in rat thalamus neurons: comparison with morphine

To assess the contribution of the active metabolite of morphine, morphine-6-glucuronide (M6G), to the analgesic effect of systemically administered morphine, experiments were carried out on rats under urethane anesthesia in which nociceptive activity was evoked by electrical stimulation of afferent C fibers in the sural nerve and recorded from single neurons in the ventrobasal complex of the thalamus. Intravenous (i.v.) injections of morphine completely blocked the activity at doses of 500 and 1000 μg/kg, the ED,, being 44 μg/kg. M6G administered by i.v. injection reduced the evoked nociceptive activity only by about 40% at 80 and 160 μg/kg, the ED₅₀ being 6 μg/kg. After intrathecal (i.t.) injection, morphine produced maximum depression of 55% of the control activity at 20 μg the ED₅₀ is 18 μg. M6G injected i.t. produced maximum depression of 40% at doses ranging from 0.2 to 10 μg. The ED₅₀ of M6G i.t. is below 0.2 μg. The effects of morphine and M6G were reversed by naloxone (200 μg/kg i.v.). The results show that M6G is more potent than morphine, regardless of the route of administration, while morphine is more effective when injected i.v. Due to the low efficacy of M6G, it seems unlikely that this glucuronide contributes substantially to the analgesic effect of morphine when renal function is normal. The results also make evident that the maximum effect of morphine results from an action at spinal and supraspinal sites.     

Pharmacokinetics of tetrachloroethylene in steady stage conditions

Pharmacokinetic behaviour of tetrachloroethylene (clearance, pool, elimination kinetics, metabolic capacity) was studied by intravenous and inhalative long term administration. Concentrations of tetrachloroethylene in blood can be calculated from the concentration in the external air, as to be predicted for a substance, practically not metabolizable and eliminated totally by exhalation. The advantages of steady state techniques and their applicability to problems of industrial pharmacology are discussed.     

Ultrasound versus digitally directed prostatic needle biopsy

During an 8-month period 55 patients with suspected but unproved prostatic carcinoma were entered randomly into a study designed to evaluate the effectiveness of ultrasound-directed transperineal needle biopsy of the prostate. Each patient was biopsied with and without ultrasound assistance; the method used first was determined randomly. Of the 15 patients diagnosed as having adenocarcinoma only 9 were proved by conventional transperineal biopsy, whereas ultrasound-guided biopsy was accurate in all 15 patients (p less than 0.005). Transrectal ultrasound guidance significantly improves the yield of transperineal needle biopsy when it is performed for suspected malignancy.