Introduction

To the best of our knowledge, this is the first time triptorelin has been reported to cause benign intracranial hypertension.

Case presentation

A 43-year-old Caucasian woman who suffered from chronic menorrhagia was started on triptorelin, a gonadotrophin-releasing hormone analogue. Three days later, she developed gradually worsening headaches accompanied by bilateral visual disturbance. Examination revealed bilateral papilledema and enlarged blind spots on her visual fields. A diagnosis of benign intracranial hypertension was made and confirmed on magnetic resonance imaging.

Conclusion

We recommend that patients at high risk (women who are overweight and of reproductive age) who are using any gonadotrophin-releasing hormone analogue (for example, triptorelin) should be periodically monitored for the possible development of benign intracranial hypertension.

Europe in the Middle Ages had descended into a dark period, and none more so than in the field of medicine. The rich heritage of the pagan Greeks had largely been ignored or forgotten by medieval Europe, and instead it was the early Arabist world that embraced and developed the Hellenistic medical teachings, emerging not only as guardians of the classical learning still existent, but also as pioneers and innovators, restricted only by the development in the associated fields. The Kahhal (), or Oculist or Eye Specialist, had a privileged place in royal households, especially during the Abbasid period, in contrast to the time of Galen, whose writings referred to ophthalmologists in a rather derogatory manner. This elevated standing in the medical profession allowed Arabist scholars to cultivate remarkably erudite techniques and exceptional texts, which were used until very recently.

The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MR is cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through β-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate β-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and β-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection.

Background

Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies.

Methods

To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history.

Results

Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV.

Conclusions

Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.