Prenatal diagnosis of 30 fetuses at risk for fragile X syndrome

The results of 30 prenatal diagnoses for fragile X syndrome are reported. Amniotic fluid cells were examined in 1 case, fetal blood in 4, and chorionic villi samples in the others. Of the 5 fetuses analyzed by cytogenetic methods, 1 had showed 4% of fraXq27.3 expression sites and the pregnancy was terminated. For 1 diagnosis, linkage analysis was used: the female fetus turned out to be normal. In 24 fetuses, the direct analysis of the mutation by StB12.3 probe was performed: 6 female and 3 male fetuses were found to carry a full mutation and 1 female fetus was found to carry a premutation. In 3 cases, the diagnoses were verified on fetal blood samples. Several tissues of 2 aborted male fetuses were analyzed for the fragile X mutation. The results are reported and discussed. © 1996 Wiley-Liss, Inc.     

Spanish Society of Medical Oncology consensus for the use of haematopoietic colony-stimulating factors in cancer patients

Neutropenia is a common complication of cancer chemotherapy. Colony-stimulating factors (CSF) may be used to avoid neutropenia-associated complications. The Spanish Society of Medical Oncology (SEOM) recently constituted a working group to review the main issues concerning the use of CSF and carried out a consensus process about the use of CSF in cancer patients, held in Madrid on 26 May 2006. The group concluded the following recommendations: prophylactic use of CSF is recommended when a rate of febrile neutropenia (FN) higher than 20% is expected without the use of CSF or when additional risk factors for neutropenia exist; therapeutic use of CSF is recommended in order to treat FN episodes but not to treat afebrile neutropenic episodes. In addition, the use of CSF is considered effective when used to mobilise stem cells before high-dose chemotherapy and when used for chemotherapy schedule optimisation in dose-dense and in dose-intense regimens. Supported by an unrestricted educational grant from MSD Oncology     

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer

Purpose

To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC).

Methods

Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m² of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal.

Results

Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032).

Conclusion

This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.     

Detection of the high risk pyrethroid resistant Varroa destructor mites in apiaries of the Warmia-Mazury province in Poland

BACKGROUND: The aim of our current study was to investigate the possible occurence of pyrethroid (taufluvalinate) resistant Varroa mites infestations in 24 randomly chosen apiaries of Warmia-Mazury province of northeast Poland. METHODS: The methodology used for the analysis of resistant Varroa strains strictly followed the protocol described by Milani. RESULTS: We identified 3 apiaries that were infested with high risk pyrethroid resistance mites and a further 9 apiaries that were free from this resitance. The brood samples collected from the remaining apiaries did not contain sufficient numbers of parasites to enable us to properly perform the assay. CONCLUSIONS: Our finding that 25% of the tested brood samples showed a high risk of fully pyrethroid resistant Varroa mite contamination indicates that resistant Varroa may become wide spread in apiaries in Poland. Interestingly these high risk resistant mites were found in honeybee colonies with low levels of Varroa infestation, with an average rate of 2.16%. We also discuss the role of amitraz (amidine) in the phenomenon of Varroa resistance to pyrethroids.     

Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a novel sequence as first-line treatment of patients with small-cell lung cancer

PURPOSE: To evaluate the efficacy and tolerability of paclitaxel, carboplatin and etoposide when administered in combination to previously-untreated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients (n=95) with limited-stage disease (LSD; n=45) or extensive-stage disease (ESD; n=50) from 14 Spanish hospitals were entered into the study. Etoposide was administered 80 mg/m(2)/day intravenous (i.v.) on days 1, 2 and 3, paclitaxel 175 mg/m(2) i.v. on day 3 and carboplatin area-under-the-concentration-time-curve=6; i.v. on day 3, of a 3-week cycle, and repeated for up to 6 cycles. RESULTS: The overall response (OR) rate was 74% (n=70; 32 complete, 38 partial). Although the OR in LSD and ESD patients was similar (73 vs 74%, respectively), the percentage complete response was significantly higher among the former (49 vs 20%). The main toxicities were grade 3-4 neutropenia and febrile neutropenia (62 and 18%, respectively) and there were 3 toxic deaths. Other toxicities were rare or easily manageable. Disease-free survival and overall survival rates at 1 year were 53 and 70% in LSD and 18 and 39% in ESD patients, respectively. CONCLUSION: The results indicate that the combination of paclitaxel, etoposide and carboplatin has an anti-tumour activity in SCLC that is comparable to other combination regimens, and is well tolerated.     

Selective deficiency of IgG and IgA as a first stage defect in B cell differentiation

Summary A case of selective deficiency of IgG and IgA, in a 13-year old girl, is described. Immunologic investigations, showing an almost complete absence of IgG- and IgA-bearing lymphocytes and significant amounts of IgD and IgM positive cells, suggest the possibility of a block in the shift from IgM to IgG synthesis at the B lymphocyte level.

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Zusammenfassung Bei einem 13jährigen Mädchen, das seit früher Kindheit an gehäuften Infekten litt, wurde ein selektives Fehlen von Ig-G und Ig-A festgestellt. Zusätzlich waren eine Reihe neurologischer Ausfälle vorhanden. Ig-M im Serum war normal. Ig-G und Ig-A-tragende Lymphozyten fehlten fast vollständig, während Ig-D und Ig-M-positive Lymphozyten vorhanden waren. Diese Befunde könnten durch eine Blockierung des Übergangs von der Ig-M-zur Ig-G-Synthese auf der entsprechenden Reifungsstufe der B-Lymphozyten erklärt werden.

     

5-HT3 receptor antagonists for prevention of late acute-onset emesis

OBJECTIVE: To review the currently available literature on the efficacy of the 5-HT(3) receptor antagonists in the prevention of late acute-onset chemotherapy-induced nausea and vomiting (12-24 h after cytotoxic treatment). DATA SOURCES:Primary articles were identified by PubMed search (performed in March 2004) and through secondary sources. Search terms included granisetron, ondansetron, tropisetron, dolasetron, acute, chemotherapy, nausea, and vomiting (a further search was performed for palonosetron in March 2004). STUDY SELECTION AND DATA EXTRACTION: All studies that performed regular assessments (every 2-6 h) of antiemetic control over the first 24 hours with 5-HT(3) receptor antagonists were evaluated. DATA SYNTHESIS: Current guidelines recommend the use of 5-HT(3) receptor antagonists for the control of chemotherapy-induced nausea and vomiting but do not differentiate between the available agents. However, there is variability in the pharmacokinetic and pharmacodynamic profiles of these agents, and this has implications for dosing regimen, safety, efficacy, and potential drug-drug interactions. Cytotoxic agents vary in the time profile of their emetic effect; this must be considered when choosing an appropriate 5-HT(3) receptor antagonist. The optimal agent should be simple to administer and provide safe and effective antiemetic protection over the whole 24-hour period. CONCLUSIONS: The differences between the 5-HT(3) receptor antagonists have important consequences for their dosing and efficacy in the control of late acute-onset chemotherapy-induced nausea and vomiting.