Nummular keratopathy in a patient with Hyper-IgD Syndrome

<p>Abstract</p> <p>Purpose</p> <p>To report a case of recurrent nummular keratitis in a pediatric patient with Hyperimmunoglobulinemia D syndrome.</p> <p>Methods</p> <p>A retrospective chart review.</p> <p>Results</p> <p>A 14-year-old boy with Hyperimmunoglobulinemia D syndrome (HIDS) presented with photophobia and ocular irritation concomitant with disease exacerbation. He was found on exam to have significant nummular keratitis, which responded to a short course of topical steroids. Despite acute response to local immunosuppression, the patient had several recurrent attacks and eventually developed a large corneal scar and decreased vision. After initiation of infliximab therapy his ocular sequelae improved dramatically and his vision returned to 20/20.</p> <p>Conclusion</p> <p>One possible form of end-organ damage associated with HIDS is vision threatening nummular keratopathy.</p

Engineering a Diverse Ligase Toolbox for Peptide Segment Condensation

The substrate profile of peptiligase, a stable enzyme designed for peptide ligation in aqueous environments, was mapped using six different peptide libraries. The most discriminating substrate binding pocket proved to be the first nucleophile binding subsite (S1), which is crucial for the peptide ligation yield. Two important amino acids shaping the S1 pocket are M213 and L208. A site-saturation library of the M213 position yielded two variants with a significantly broadened substrate profile, i.e., M213G and M213P. Next, examination of two libraries with M213G+L208X and M213P+L208X (with X being any proteinogenic amino acid) resulted in a toolbox of enzymes which can accommodate any proteinogenic amino acid in the S1 pocket, except proline. The applicability of a particular enzyme variant in chemoenzymatic peptide synthesis was demonstrated by coupling at the gram scale of two peptide segments to yield exenatide, a 39-mer therapeutic peptide used in the treatment of diabetes type II. The overall yield of 43% is at least 2-fold higher than yields reported for conventional syntheses of exenatide by full solid-phase peptide synthesis; large-scale production costs are expected to be significantly reduced if the enzymatic coupling process is employed to manufacture this peptide.</p

Safe use of medication in patients with cirrhosis:pharmacokinetic and pharmacodynamic considerations

Contains fulltext : 218240.pdf (Publisher’s version ) (Open Access)Introduction: The global burden of cirrhosis is rising, and clinicians increasingly face the challenge of safely prescribing medicines for complications of hepatic disease and comorbidities. Prescribing in patients with cirrhosis is complicated by alterations that can occur in the pharmacology of medicines.Areas covered: This paper provides an overview of current knowledge on the pharmacokinetics and pharmacodynamics of medicines in patients with cirrhosis. We describe the pathophysiological changes that occur and their consequences on pharmacokinetic parameters. We explain that the influence of cirrhosis on the pharmacokinetics depends on several drug and patient characteristics. Patients with cirrhosis also have an increased susceptibility to some toxicological effects of medicines, such as renal impairment and hematological toxicity, which we describe in detail. In addition, we discuss approaches to apply this knowledge in practice and improve safe medication use in patients with cirrhosis.Expert opinion: Tailored pharmacotherapy is needed to ensure safe and appropriate use of medicines in patients with cirrhosis. Clinicians are supported by freely available recommendations on safe drug use in cirrhosis published on a website. In addition, a regular evaluation of medication use in patients with cirrhosis could resolve and prevent medication-related problems

Everolimus and long acting octreotide as a volume reducing treatment of polycystic livers (ELATE): study protocol for a randomized controlled trial

Contains fulltext : 97893.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Polycystic liver disease (PLD) is defined as having more than 20 liver cysts and can present as a severe and disabling condition. Most symptoms are caused by the mass effect of the liver size and include abdominal pain and distension. The somatostatin analogues octreotide and lanreotide have proven to reduce polycystic liver volume. mTOR inhibitors such as everolimus inhibit cell proliferation and might thereby reduce growth of liver cysts. This trial aims to assess the benefit of combination therapy of everolimus and octreotide compared to octreotide monotherapy. In this study we present the structure of the trial and the characteristics of the included patients. METHODS/DESIGN: This is a randomized open-label clinical trial comparing the effect of 12 months of everolimus and octreotide to octreotide monotherapy in PLD patients. Primary outcome is change in liver volume determined by CT-volumetry. Secondary outcomes are changes in abdominal symptoms and quality of life. Moreover, safety and tolerability of the drugs will be assessed. DISCUSSION: This trial will compare the relative efficacy of combination therapy with octreotide and everolimus to octreotide monotherapy. Since they apply to different pathways of cystogenesis we expect that combining octreotide and everolimus will result in a cumulative reduction of polycystic liver volume. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01157858

Field evaluation of six Gros Michel banana accessions (Musa spp., AAA group) for agronomic performance, resistance to Fusarium wilt race 1 and yellow Sigatoka

Three Gros Michel mutants (‘IBP 5-B’, ‘IBP 5–61’ and ‘IBP 12’) from the Cuban Instituto de Biotecnología de las Plantas, two semi-dwarf Gros Michel varieties (‘Highgate’ and ‘Cocos’) and a Thai accession (‘Hom Thong Mokho’) were evaluated in Australia over a five year period. They were screened for their resistance to Fusarium wilt Race 1 (FocR1) caused by the pathogen Fusarium oxysporum f.sp. cubense, as well as resistance to yellow Sigatoka (Pseudocercospora musae Zimm [teleomorph Mycosphaerella musicola Leach]). They were also grown for a plant and ratoon crop in the tropics (17°S) and a plant crop in the subtropics (28°S) with no disease pressure to record their agronomic characteristics. They were compared with Australian industry standards, ‘Williams’ (AAA, Cavendish subgroup) and ‘Lady Finger’ (AAB, Pome subgroup). In the subtropics the Gros Michel mutants and semi-dwarf accessions were sensitive to cold and very susceptible to FocR1 and yellow Sigatoka while their agronomic performance in the tropics was good, with ‘Highgate’ having the best bunch weight on a shorter, more manageable plant. Of the six accessions evaluated, ‘Hom Thong Mokho’ showed the highest level of resistance to FocR1 although it had poor cold tolerance, as did the other Gros Michel selections, and consequently had low productivity compared to ‘Williams’ and even ‘Lady Finger’. However in the warmer, more humid tropics ‘Hom Thong Mokho's performance was much better and it was less susceptible to yellow Sigatoka than the other Gros Michel selections. Subsequent genetic analysis by Christelová et al. (2011) has revealed that although ‘Hom Thong Mokho’ is marketed as a Gros Michel variety in Asia, it is closer to the Rio subgroup (AAA) of dessert bananas

An International Consensus List of Potentially Clinically Significant Drug-Drug Interactions in Older People.

Objectives We aimed to establish an explicit list of potentially clinically significant drug-drug interactions (DDIs) in people aged ≥65 years. Design A preliminary list of potentially clinically significant DDIs was compiled, based on 154 DDIs identified from literature review. Subsequently, a 2-round online Delphi survey was undertaken with a multidisciplinary expert panel. A consensus meeting and a final round were conducted to validate the final DDI list and the scope of information provided. Setting and Participants Twenty nine experts, including geriatricians and clinical pharmacists from 8 European countries. Measures For each DDI, in the first 2 rounds, experts were asked to score the severity of potential harm on a 5-point Likert-type scale. DDIs were directly included on the final list if the median score was 4 (major) or 5 (catastrophic). DDIs with a median score of 3 (moderate) were discussed at a consensus meeting and included if ≥75% of participants voted for inclusion in the final round. Results Consensus was achieved on 66 potentially clinically significant DDIs (28 had a median score of 4/5 and 48 of 3 in the Delphi survey). Most concerned cardiovascular, antithrombotic, and central nervous system drugs. The final list includes information on the mechanism of interaction, harm, and management. Treatment modification is recommended for three-quarters of DDIs. Conclusion and Implications We validated a list of potentially clinically significant DDIs in older people, which can be used in clinical practice and education to support identification and management of DDIs or to assess prevalence in epidemiologic and intervention studies.pre-print896 K

Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

Contains fulltext : 109282.pdf (publisher's version ) (Open Access)BACKGROUND: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD). The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial. METHODS/DESIGN: This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, alpha1-microglobulin, KIM-1, H-FABP, MCP-1) and serum (fibroblast growth factor 23) biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed. DISCUSSION: We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response. TRIAL REGISTRATION NUMBER: Clinical trials.gov NCT01354405