Merkel cell carcinoma of the gingival mucosa in a black young adult

Merkel cell carcinoma (MCC) is a rare and aggressive primary neuroendocrine neoplasm of the skin with a poor prognosis. It occurs mainly in the skin of white elderly patients. Its occurrence in intraoral mucosal sites is rare. We report a rare case of MCC that arose in the gingival mucosa of young black adult.     

Implementation of an in‐house quantitative real‐time polymerase chain reaction method for Hepatitis B virus quantification in West African countries

Hepatitis B virus (HBV) is a major cause of chronic liver disease worldwide. HBV infection is diagnosed by serological tests, while real‐time polymerase chain reaction (qRT‐PCR) assays are used to quantify viral load, which is a crucial parameter to determine viral replication and to monitor antiviral treatments. However, measuring viral load in resource‐limited countries remains nonsystematic, due to the high cost of commercial kits. Here, we describe the development, validation and implementation of a low‐cost, in‐house qRT‐PCR assay to monitor HBV viral load in chronic carriers enrolled in the PROLIFICA programme in the Gambia and Senegal. Over 1500 HBsAg‐positive patients, including 210 chronically infected HBV patients, who were given antiviral treatment (tenofovir), were monitored by qRT‐PCR using the SYBR Green‐ and HBV‐specific primers. Twenty‐four tenofovir‐treated patients were followed up and their viral load was tested every 3 months over the 12‐month experimental time course. Compared to commercial assays, our in‐house assay was shown to be (i) highly reliable, with good intra‐ and interassay reproducibility over a wide range (45–4.5 × 10⁸ copies mL^?1), (ii) very similar in the viral loads detected (R² = .90), (iii) highly sensitive, as it detected loads as low as 30 copies mL^?1 (~5 IU mL^?1), (iv) cheaper (2‐ to 3‐fold), (v) easier to implement and (vi) more rapid. Based on our experience, we recommend this assay as a reliable alternative to commercial assays, for monitoring HBV viraemia in resource‐limited, highly endemic countries to reduce the cost and technical obstacles associated with commercial kits.     

Implementing family‐focused HIV care and treatment: the first 2 years’ experience of the mother‐to‐child transmission ‐plus program in Abidjan,Côte d’Ivoire

Objectives To describe a family‐focused approach to HIV care and treatment and report on the first 2 years experience of implementing the mother‐to‐child transmission (MTCT)‐plus program in Abidjan, Côte d’Ivoire. Program The MTCT‐plus initiative aims to enrol HIV‐infected pregnant and postpartum women in comprehensive HIV care and treatment for themselves and their families. Main outcomes Between August 2003 and August 2005, 605 HIV‐infected pregnant or postpartum women and 582 HIV‐exposed infants enrolled. Of their 568 male partners reported alive, 52% were aware of their wife’s HIV status and 30% were tested for HIV; 53% of these tested partners were found to be HIV‐infected and 78% enrolled into the program. Overall only 10% of the women enrolled together with their infected partner. On the other hand, the program involved half of the seronegative men who came for voluntary counselling and testing (VCT) in the care of their families. Of 1624 children <15 years reported alive by their mothers (excluding the last newborn infants of the most recent pregnancy systematically screened for HIV), only 10.8% were brought in for HIV testing, of whom 12.3% were found to be HIV‐infected. Lessons learned and challenges The family‐focused model of HIV care pays attention to the needs of families and household members. The program was successful in enrolling HIV women, their partners and infants in continuous follow‐up. However engaging partners and family members of newly enrolled women into care involves numerous challenges such as disclosure of HIV status by women to their partners and family members. Further efforts are required to understand barriers for families accessing HIV services as strategies to improve partner involvement and provide access to care for other children in the households are needed in this West African urban setting.     

CEA,CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC)

Background We previously reported that CEA kinetics are a marker of progressive disease (PD) in metastatic colorectal cancer (mCRC). This study was specifically designed to confirm CEA kinetics for predicting PD and to evaluate CA19-9, cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) kinetics.Methods Patients starting a chemotherapy (CT) with pre-treatment CEA > 5 ng/mL and/or CA19.9 > 30 UI/mL were prospectively included. Samples were collected from baseline to cycle 4 for CEA and CA19-9 and at baseline and the sixth week for other markers. CEA kinetics were calculated from the first to the third or fourth CT cycle.Results A total of 192 mCRC patients were included. CEA kinetics based on the previously identified >0.05 threshold was significantly associated with PD (p < 0.0001). By dichotomising by the median value, cfDNA, ctDNA and CA19-9 were associated with PD, PFS and OS in multivariate analysis. A circulating scoring system (CSS) combining CEA kinetics and baseline CA19-9 and cfDNA values classified patients based on high (n = 58) and low risk (n = 113) of PD and was independently associated with PD (ORa = 4.6, p < 0.0001), PFS (HRa = 2.07, p < 0.0001) and OS (HRa = 2.55, p < 0.0001).Conclusions CEA kinetics alone or combined with baseline CA19-9 and cfDNA are clinically relevant for predicting outcomes in mCRC.Trial registration number {"type":"clinical-trial","attrs":{"text":"NCT01212510","term_id":"NCT01212510"}}NCT01212510.Subject terms: Colon cancer, Genetic markers     

Transglutaminase‐1 gene mutations in autosomal recessive congenital ichthyosis: Summary of mutations (including 23 novel) and modeling of TGase‐1

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of rare cornification diseases. Germline mutations in TGM1 are the most common cause of ARCI in the United States. TGM1 encodes for the TGase‐1 enzyme that functions in the formation of the cornified cell envelope. Structurally defective or attenuated cornified cell envelop have been shown in epidermal scales and appendages of ARCI patients with TGM1 mutations. We review the clinical manifestations as well as the molecular genetics of ARCI. In addition, we characterized 115 TGM1 mutations reported in 234 patients from diverse racial and ethnic backgrounds (Caucasion Americans, Norwegians, Swedish, Finnish, German, Swiss, French, Italian, Dutch, Portuguese, Hispanics, Iranian, Tunisian, Moroccan, Egyptian, Afghani, Hungarian, African Americans, Korean, Japanese and South African). We report 23 novel mutations: 71 (62%) missense; 20 (17%) nonsense; 9 (8%) deletion; 8 (7%) splice‐site, and 7 (6%) insertion. The c.877‐2A>G was the most commonly reported TGM1 mutation accounting for 34% (147 of 435) of all TGM1 mutant alleles reported to date. It had been shown that this mutation is common among North American and Norwegian patients due to a founder effect. Thirty‐one percent (36 of 115) of all mutations and 41% (29 of 71) of missense mutations occurred in arginine residues in TGase‐1. Forty‐nine percent (35 of 71) of missense mutations were within CpG dinucleotides, and 74% (26/35) of these mutations were C>T or G>A transitions. We constructed a model of human TGase‐1 and showed that all mutated arginines that reside in the two beta‐barrel domains and two (R142 and R143) in the beta‐sandwich are located at domain interfaces. In conclusion, this study expands the TGM1 mutation spectrum and summarizes the current knowledge of TGM1 mutations. The high frequency of mutated arginine codons in TGM1 may be due to the deamination of 5′ methylated CpG dinucleotides. Hum Mutat 0, 1–12, 2009. © 2009 Wiley‐Liss, Inc.     

5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats

Background and purpose

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT_1A receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT_1A receptors.

Experimental approach

Male Wistar rats received i.p. injections of vehicle or CBD (1, 10 or 20 mg kg⁻¹) and 30 min later were submitted to 60 min of restraint where their cardiovascular responses were recorded. The protocol of the second experiment was similar to the first one except that animals received i.p. injections of the 5-HT_1A receptor antagonist WAY100635 (0.1 mg kg⁻¹) before CBD treatment and exposure to restraint. 24 h later they were also tested in the elevated plus-maze (EPM), an animal model of anxiety.

Key results

Exposure to RS increased blood pressure and heart rate and induced an anxiogenic response in the EPM 24 h later. These effects were attenuated by CBD. WAY100635 by itself did not change the cardiovascular and anxiogenic response to RS, but blocked the effects of CBD.

Conclusion and implications

The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT_1A receptor-mediated neurotransmission.