Severe ciguatera poisoning in Madagascar: A case report

In a single outbreak on the East coast of Madagascar, more than 500 people, 98 of whom died, were poisoned by the flesh of a shark, Carcharhinus amboinensis. From clinical symptoms it can be concluded that this poisoning is due to ciguatera toxins. It is the first case of a severe outbreak caused by a shark, and it is the first case with a mortality rate of 20%.     

Identification of 50- and 23-/25-kDa HeLa cell membrane glycoproteins involved in poliovirus infection: occurrence of poliovirus specific binding sites on susceptible and nonsusceptible cells.

Glycoproteins in the range 50 and 23/25 kDa were identified as poliovirus specific binding sites on HeLa cells with the monoclonal antibody mAb 122. mAb 122 is characterized by its partial inhibiting effect on poliovirus reproduction and adsorption when prebound to HeLa cells. The binding sites are endocytosed in native cells and specific for poliovirus as mAb 122 did not interfere with the adsorption of human rhinovirus type 14 (HRV 14). The poliovirus binding sites are present also on nonprimate so called nonsusceptible cells, e.g., mouse L-cells, as could be shown with sensitive ELISA based binding assays and performance of binding studies with fixed cells at 37 degrees.     

Safety and efficacy of interferon retreatment in children with chronic hepatitis B

More than 50% of children with chronic hepatitis B do not respond to treatment with alpha-interferon. Since these patients continue to display high viral replication and progressive liver disease, retreatment should be considered. To date it has not been well evaluated whether a second course of treatment could increase the response rate. In two alpha-interferon retreatment trials in adult patients the response rate, defined by seroconversion from HBeAg to anti-HBe, ranged between 11% and 44%. One beta-interferon retreatment study in children reported a seroconversion rate of 32%. Regrettably, none of the studies included a control group observing the `spontaneous' seroconversion rate after a first interferon cycle. Thus, a nonrandomized alpha-interferon retreatment study in children including control patients was performed. Alpha-interferon for retreatment was administered 3 times a week for 16–24 weeks in 15 children (5–16 years) at least 6 months after ceasing the first cycle. Four children received 5 MU/m² of a natural alpha-interferon and 11 children 9 MU/m² recombinant alpha-interferon 2b. Follow up was 18–47 months after initial treatment. In parallel, a control group of 19 un-retreated children with comparable clinical and demographic data was followed for 12–39 months. HBeAg seroconversion was observed in 5 (33%) of the retreated children and in 5 (26%) of the control patients during follow up. The difference is not significant. In the initially nonresponding children, those with high ALT levels before the first treatment showed late HBeAg seroconversion more frequently than those with low ALT levels (P = 0.017) irrespective of retreatment. The ALT level before retreatment was not a predictor for response. Conclusions A second cycle of alpha-interferon during the 3 years following the first treatment in nonresponding children with chronic hepatitis B can be safely performed but did not increase HBeAg/anti-HBe seroconversion compared with the spontaneous seroconversion rate of patients without retreatment. Received: 29 July 1997 / Accepted in revised form: 23 October 1997     

Multicentre study for diagnostic evaluation of an assay for simultaneous detection of antibodies to HIV-1, HIV-2 and HIV-1 subtype 0 (HIV-0)

Summary The aim of the study was to evaluate a new ELISA for detection of HIV-1, HIV-2 and HIV-1 subtype 0 (HIV-0) antibodies. The assay format is based on the antigen sandwich principle. To enable specific detection of HIV-0 antibodies, in addition to HIV-1 and HIV-2 antigens HIV-0 antigen is used for coating the solid phase and for the conjugate. The results show that all 12 HIV-0 samples tested were detected with a high degree of reactivity, as were all the 1,144 anti-HIV-1 and 424 anti-HIV-2 positive samples. The capacity of the test to enable early detection of seroconversions is equivalent to that of other sandwich ELISAs. The specificity of the assay was determined to be 99.89/99.94% (initial/after retest) using 58,366 samples, which is superior to the other ELISAs used for comparison. Even with difficult samples (i.e. samples of African origin, samples known to cause false-positive reactivity in different ELISAs, or samples containing potential interference factors) there were very few false-positive reactions. Therefore, the new assay is well suited for screening blood donations as well as for evaluating samples from patients of different geographic origin.

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Multizenterstudie zur Bewertung eines Testsystems für den gleichzeitigen Nachweis von Antikörpern gegen HIV-1, HIV-2 und HIV-1 Subtyp 0 (HIV-0)

Zusammenfassung Ziel der Studie war die Bewertung eines neuen ELISA zum Nachweis von Antikörpern gegen HIV-1, HIV-2 und dem HIV-1 Subtyp 0 (HIV-0). Der Test beruht auf dem Antigen-Sandwich-Prinzip. Für den spezifischen Nachweis von Antikörpern gegen HIV-0 wird HIV-0-Antigen zusammen mit HIV-1 und HIV-2-Antigen zur Beschichtung der festen Phase und für das Konjugat verwandt. Die Ergebnisse zeigten, daß alle 12 getesteten HIV-0-Proben mit hoher Reaktivität nachweisbar waren sowie alle 1 144 anti-HIV-1- und 424 anti-HIV-2-positiven Proben. Die Fähigkeit des Testsystems zum frühen Nachweis einer Serokonversion entspricht derjenigen anderer Sandwich-ELISAs. Die Spezifität des Tests wurde an 58 366 Proben mit 99,89/99,94% (initial/Wiederholungstestung) ermittelt und liegt über derjenigen von anderen zum Vergleich herangezogenen ELISAs. Auch bei schwierigen Proben (zum Beispiel Proben aus Afrika, Proben, bei denen falsch-positive Reaktivität in verschiedenen ELISAs beobachtet worden war oder Proben, die mögliche Interferenzfaktoren enthalten) fanden sich nur sehr wenige falsch positive Reaktionen. Der neue Test eignet sich daher gut für das Screening von Blutspenden und für die Beurteilung von Proben von Patienten unterschiedlicher geographischer Herkunft.

     

Anaphylactic shock depends on endothelial Gq/G11

Anaphylactic shock is a severe allergic reaction involving multiple organs including the bronchial and cardiovascular system. Most anaphylactic mediators, like platelet-activating factor (PAF), histamine, and others, act through G protein–coupled receptors, which are linked to the heterotrimeric G proteins G_q/G₁₁, G₁₂/G₁₃, and G_i. The role of downstream signaling pathways activated by anaphylactic mediators in defined organs during anaphylactic reactions is largely unknown. Using genetic mouse models that allow for the conditional abrogation of G_q/G₁₁- and G₁₂/G₁₃-mediated signaling pathways by inducible Cre/loxP-mediated mutagenesis in endothelial cells (ECs), we show that G_q/G₁₁-mediated signaling in ECs is required for the opening of the endothelial barrier and the stimulation of nitric oxide formation by various inflammatory mediators as well as by local anaphylaxis. The systemic effects of anaphylactic mediators like histamine and PAF, but not of bacterial lipopolysaccharide (LPS), are blunted in mice with endothelial Gα_q/Gα₁₁ deficiency. Mice with endothelium-specific Gα_q/Gα₁₁ deficiency, but not with Gα₁₂/Gα₁₃ deficiency, are protected against the fatal consequences of passive and active systemic anaphylaxis. This identifies endothelial G_q/G₁₁-mediated signaling as a critical mediator of fatal systemic anaphylaxis and, hence, as a potential new target to prevent or treat anaphylactic reactions.     

Distribution of lymphocyte surface antigens in healthy neonates

Using flow cytometric analysis we investigated the distribution of major lymphocyte surface antigens in newborn infants. A total of 221 newborns entered the study, of whom 53 fullfilled our criteria of healthy mature neonates. Percentages of immunofluorescent-positive cells were as follows (median and range from 25th to 75th percentiles given): for CD1 3.8%; 2.3%–5.8%. CD2 60.9%; 52.4%–66.8%. CD3 57.5%; 50.5%–63.3%. TcRaß 57.7%; 48.1%–60.0%. CD4 36.3%; 28.0%–42.6%. CD8 23.0%; 20.0%–27.4%. CD11a 56.3%; 46.3%–68.5%. CD19 12.1%; 8.6%–14.8%. CD20 10.9%; 8.4%–12.9%. CD25 2.6%; 2.1%–4.5%. CDw52 61.0%; 51.2%–76.1%. CD71 5.2%; 3.1%–9.3%. While the ranges for the percentage of immunofluorescent-positive cells were rather small, there was a wide variation in the absolute numbers of marker immunofluorescent-positive cells.     

Granulocyte function in premature infants before the 34th week of pregnancy and in mature newborn infants]

BACKGROUND: Preterm and term neonates have an increased risk to develop severe bacterial infections. Impairment of neutrophil function may be responsible for this increased risk. Other diseases related to prematurity like retinopathia of prematurity (ROP) or broncho-pulmonary dysplasia (BPD) on the other hand may be due to poorly controlled O2-radical production. PATIENTS AND METHODS: Blood samples of 112 premature (34 weeks of gestation and older) and term neonates were analysed. Blood samples of 23 healthy adults (18 to 50 years old) served as controls. O2-radical production and phagocytosis of neutrophils were determined by flow cytometry, using a commercial test system. RESULTS: Under the experimental conditions applied, the capacity to produce O2-radicals following vigorous stimulation (E. coli) is comparable between neutrophils of preterm/term neonates and healthy adults. However, unstimulated or weakly stimulated (fMLP) neutrophils of preterm and term neonates show a statistically higher O2-radical production as neutrophils of the control group. The production of oxygen radicals increases during the first 10 days of the life. The capability of neutrophils to phagocytose E. coli is significantly lower in newborns (preterm and term) compared to the adult controls. CONCLUSIONS: The values reported here for phagocytosis and O2-radical production utilizing a commercially available test system may serve as "preliminary normal values" for neonates. No differences were found between the groups of neonates with and without infection. Impaired neutrophil-phagocytosis possibly contributes to the increased risk of preterm and term neonates to acquire bacterial infections. The increased spontaneous O2-radical production, on the other hand, may play a role for the development of so called "free radical diseases" such as ROP or BPD. However, our results cannot add further proof to this hypothesis.     

Lymphadenitis colli due to non-tuberculous mycobacteria (NTM): a case-series and review of the literature

OBJECTIVE: Lymphadenitis colli due to NTM should always be considered in children with cervical Lymphadenitis. For Germany there is a lack of data concerning the incidence, the epidemiology, the diversity and frequency of the different bacteria, the diagnosis, the clinical manifestation and the medical treatment. METHODS: By means of a questionnaire, which was retrospective for 1985 to 1994 and was sent to 277 children's hospitals in Germany, we collected data on Lymphadenitis colli in Germany. In our study we also incorporated cases from the "National Laboratory for Mycobacteria" in Borstel as well as six cases from our hospital in Mainz. Therefore our data includes both clinical (28) and laboratory (30) cases. Additionally we screened the literature on "Lymphadenitis colli in children due to NTM". RESULTS: A total of 51 cases of Lymphadenitis due to NTM could be identified. The illness occurs typically in young children up to six years of age. The most frequent cause were species of the Mycobacterium avium-intracellulare-scrofulaceum complex. Except for the local diagnosis of a cervical Lymphadenitis other clinical symptoms are missing, just as specific laboratory parameters with a subacute or chronic course. The tuberculin skin test can be false positive. The diagnosis is confirmed by biopsy and histology as well as through microbiological tests. CONCLUSIONS: The best treatment is complete surgical excision, whereas the importance of additional or exclusive treatment with Clarithromycin, Rifabutin and other antibiotics could not be clarified completely. But in patients with AIDS Rifabutin and other drugs could perhaps be useful, even for prophylaxis. Also if complete excision is impossible, treatment with certain drugs (Clarithromycin or Azithromycin in combination with Rifampicin) will be recommended. It still remains in question if NTM infections in children are really increasing.     

Griscelli syndrome: a case report

BACKGROUND: Griscelli syndrome is a rare disorder with poor prognosis. It is characterized by silver-grey hair or strands of silver-grey hair in childhood, and variable cellular immunodeficiency. The course of the untreated disease is fatal. Recurrent episodes of fever and lymphohistocytic infiltration of organs lead to hepatosplenomegaly, lymphadenopathy, pancytopenia, and progressive neurological impairment. Prognosis on morbidity and lethality depends on an early diagnosis. PATIENT: The girl we report on suffers from Griscelli syndrome. She developed normally and only her grey strands of hair, grey eyebrows, and eyelids were conspicuous. With the age of 4 years, she presented with a first episode of illness. RESULTS: Cytostatic treatment seemed to ameliorate the course of the disease although further accelerated phases could not be prevented. The only therapeutic option is a bone marrow transplantation, which we conferred upon our patient. CONCLUSION: The finding of grey hairs in childhood should alert clinicians to consider Griscelli syndrome since an early diagnosis is life and health saving.