Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.     

Decreasing the level of translation initiation factor 4E with antisense rna causes reversal of ras-mediated transformation and tumorigenesis of cloned rat embryo fibroblasts

Transformation of cloned rat embryo fibroblasts (CREF) with the T24-ras oncogene results in loss of contact inhibition, growth in soft agar and tumor formation in nude mice. Previously we showed that in such cells (CREF T24), the phosphorylation rate of protein synthesis initiation factor 4E (elF-4E) is increased, correlating with an increase in the general rate of protein synthesis. In the present study, we have expressed antisense RNA complementary to elF-4E mRNA in CREF T24 cells using a stably integrated vector. Cells expressing antisense RNA (CREF T24/AS) contained 30-50% of the normal level of elF-4E and exhibited many of the properties of untransformed cells. CREF T24 had a spindle-shaped, refractile appearance, whereas CREF T24/AS grew in ordered, parallel patterns and exhibited contact inhibition similar to untransformed CREF. The rates of growth and protein synthesis in CREF T24/AS were decreased compared to CREF T24 but were not as low as in CREF. The efficiency of growth in soft agar was 11-fold lower for CREF T24/AS compared with CREF T24. The latency period for tumor formation in nude mice was increased from 8 days for CREF T24 to 17-27 days for CREF T24/AS and various clonal lines derived from them. Cell lines established from these CREF T24/AS-derived tumors were shown to have partially regained the elF-4E levels characteristic of CREF T24. These results demonstrate that many of the phenotypic alterations associated with ras-induced malignant transformation can be reversed by a moderate reduction of the translational initiation capacity and therefore may be mediated through a translational mechanism.     

Pharmacology of calcium-induced long-term potentiation in rat hippocampal slices

A transient increase (10 min) in extracellular calcium concentration (4 mM) causes a long-lasting (greater than 2 hr) enhancement of population spike responses evoked by radiatum fibers to CA1 pyramidal neurons in rat hippocampal slices. This phenomenon is similar to tetanic long-term potentiation (LTP), and is also related to memory processes. The influence of various drugs was investigated on calcium-induced LTP. The NMDA antagonist 2 amino-5-phosphonopentanoic acid (AP5; 100 microM) was able to prevent the calcium-induced LTP, while atropine sulphate (10 microM), propranolol hydrochloride (10 microM) and verapamil hydrochloride (100 microM) were ineffective. The results suggest an involvement of the NMDA receptor in the development of calcium-induced LTP.     

How do genes exert their role? Period 3 gene variants and possible influences on mood disorder phenotypes

The action of multiple liability genes is responsible for complex phenotypes at the same time, a single gene, could control several phenotypic features. This is the case of human period 3 gene (hper3), mainly involved in the setting of the biologic clock. Some variants of this gene, besides being associated with the Delayed Sleep Phase Syndrome, showed a key role in determining evening preference rather than morning one. According to this rationale, we hypothesized that this gene could influence circadian mood fluctuations, in mood disorders. Our study demonstrated that rare genetic variants of hper3 are significantly associated to a number of mood disorders features, such as age of onset, response to SSRIs treatment, circadian mood oscillations and characteristics of temperament. These preliminary results could shed further light on the involvement of circadian genes in various aspects of physiological and psychopathological mechanisms of the brain.     

Enumeration of S-phase cells in normal rat liver by immunohistochemistry using bromodeoxyuridine-antibromodeoxyuridine system

The visualization of incorporation sites of the thymidine analog bromodeoxyuridine (BrdU) into DNA, detected by immunocytochemistry, has been proposed as an index of the percentage of S-phase cells in a variety of tissues and as an easy, less expensive alternative to autoradiography. This technique has not yet been applied to the study of physiological cell renewal in the normal liver. In the present study, results obtained with this method in the liver of normal young adult rats is reported. BrdU was administered in vivo and subsequent incorporation was detected by the PAP technique using monoclonal anti-BrdU antibodies. The nuclei exhibiting a positive reaction within the liver were few and accounted for about 0.45% of all hepatocytes. Positive cells were located preferentially in zone 1, which contained 82.7% of the labeled cells. Zone 2 contained 15.4%, while only 1.9% of the labeled cells were found in zone 3. Positive-staining Kupffer cell nuclei were rare (about 0.5% of all Kupffer cells) and were distributed randomly in the hepatic lobule. These findings provide quantitative data about hepatocyte renewal in the normal liver in the absence of a growth stimulus. The simplicity and the reproducibility of this technique suggests that further application of this method in situations assessing hepatic regeneration are indicated.     

Six cases of travel-associated legionnaires' disease in Ischia involving four countries

Summary The detection of travel-associated legionellosis can be extremely difficult; hence, an extensive case investigation is recommended in pneumonia-striken travellers and tourists, who are particularly at risk of acquiring the disease. On the Island of Ischia (Isola d'Ischia, Naples, Italy) a total of six cases of Legionnaires' disease occurred from 1986 to 1990. All patients (one man and two women from Germany, one Austrian woman, one Swiss man, and one Italian woman) had taken thermal baths and stayed in local hotels; they all experienced severe pneumonia, and three of them died. These cases were associated with hotels, and the hot-water supply was presumed to have transmitted the infection. Remedial procedures were applied to the hot-water plumbing of the hotels according to the WHO recommendations and were proved to be effective. The occurrences described in this paper stress the importance of rapid and accurate reporting of diagnosed cases to the country where the infection was probably acquired, in order to ensure early detection of endemic foci and emerging clusters of legionellosis.

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Sechs Fälle von reiseassoziierter Legionärskrankheit in Ischia unter Beteiligung von vier Ländern

Zusammenfassung Der Nachweis reiseassoziierter Legionärskrankheit gestaltet sich häufig schwierig. Eine Überwachung von Touristen und Reisenden, die ein erhöhtes Legionellose-Risiko haben, ist daher zu empfehlen. Zwischen 1986 und 1990 traten auf der Insel Ischia (Neapel, Italien) insgesamt sechs Fälle von Legionärskrankheit auf. Alle Patienten (ein Mann und zwei Frauen aus Deutschland, eine Österreicherin, ein Schweizer und eine Italienerin), die in Hotels auf der Insel wohnten, hatten Thermalbäder besucht. Sie erkrankten an schweren Pneumonien, wobei drei Todesfälle auftraten. Die Ansteckungsquelle konnte mit Hotels in Verbindung gebracht werden, wobei die Übertragung der Infektion über die Warmwasserleitungsnetze als gesichert anzunehmen war. Desinfektionsmaßnahmen in den betreffenden Hotels, die nach den Empfehlungen der WHO ausgeführt wurden, erwiesen sich als wirksam. Das genannte Infektionsgeschehen weist auf die Notwendigkeit hin, Fälle von Legionärskrankheit so rasch wie möglich dem Ursprungsland unter Angabe der vermuteten Infektionsquelle zu melden, um sicherzustellen, daß eine Früherkennung endemischer Herde bzw. assoziierter Legionellosen bekannt gemacht wird.

     

Neuropsychological correlates of subclinical paroxysmal EEG activity in children with epilepsy. 2: Quantitative aspects

Altered cognitive functioning has often been reported in patients with epilepsy. In our study we looked for quantitative correlation between the recurrence of Subclinical Spike-and-Wave Discharges (SSWD) during EEG recording, the scores on the intelligence test (WISC) and the electro-clinical characteristics of 29 epileptic children with subclinical discharges of generalized spike-and-wave complexes. In our sample we found a below-normal mean IQ, with greater impairment on performance than on verbal tasks. No clear quantitative correlation was found between the weighted scores on the various subtests and the "time density" of the spike-and-wave complexes. These findings suggest that the SSWD interfere with cognitive development (mainly with visuo-spatial and sensorimotor coordination abilities) and selectively impair some of the functions involved in the cognitive processes.     

Pharmacokinetics and tolerance of a new penem antibiotic,FCE 22101, in healthy volunteers after a single intravenous dose

Summary The clinical tolerance and pharmacokinetics of FCE 22101 (sodium (5R, 6S)-6-[(1R)-hydroxyethyl]-2-carbamoyloxymethyl-2-penem-3-carboxylate), a new penem antibiotic, have been studied after giving a single i.v. dose of 4 mg·kg^–1 to ten healthy male volunteers. The pharmacokinetics was estimated according to a two-compartment open model. The peak plasma concentration (C_max) was 15.5 (1.08) µg·ml^–1, mean (SEM). FCE 22101 was rapidly cleared from the systemic circulation [ =44.2 (4.2) min; CL=7.21 (0.47) ml·kg^–1·min^–1]. The mean apparent volume of distribution at steady-state was 246 (16.9) ml·kg^–1. The mean residence time relative to the 10 min infusion was 39.4 (1.5)min. Urinary recovery of FCE 22101 showed wide inter-subject variation, ranging from 10.2 to 53.6% of the dose. No subject complained of adverse effects.     

Juvenile Idiopathic Arthritis

Overexpression of cytokines in inflamed joints plays an important role in joint inflammation and in damage to articular tissue. Biological agents aimed at specifically antagonising tumour necrosis factor (TNF) are effective in the treatment of adult rheumatoid arthritis. A recent trial of etanercept, a genetically engineered fusion protein consisting of the Fc domain of human IgG1 and the TNF receptor p75, has demonstrated that this agent is also well tolerated and effective in patients with juvenile idiopathic arthritis (JIA). Etanercept offers a promising new alternative for patients with JIA who have persistently active arthritis despite treatment with methotrexate. Further studies are needed to clarify whether etanercept is equally effective in the various onset types of JIA (oligoarthritis, polyarthritis and systemic arthritis), whether it can modify disease progression and whether it can be administered safely for long periods of time to children.