The epidemiology of Clostridium difficile in Scotland

The objective of this study was to characterise the epidemiology of Clostridium difficile in Scotland by determining the distribution of PCR ribotypes and antimicrobial susceptibility in 1613 isolates collected from all healthboard areas of Scotland in the period November 2007-December 2009. Three PCR ribotypes predominated amongst the Scottish isolates of C. difficile; ribotype 106 (29.4%), ribotype 001 (22%) and ribotype 027 (12.6%) followed by the less prevalent ribotypes including 002, 015, 014, 078, 005, 023 and 020. The distribution of ribotypes varied between healthboard areas. Ribotype 106 or 001 was the predominant ribotype in 10 healthboard areas, while ribotype 027 was the predominant type in two neighbouring areas. Antimicrobial susceptibility testing of C. difficile isolates showed high frequencies of resistance to moxifloxacin, levofloxacin, erythromycin and cefotaxime in the epidemic C. difficile ribotypes 001, 027 and 106 compared to other less common ribotypes. Furthermore, reduced susceptibility to metronidazole was found only in the epidemic strains. These findings are compatible with the hypothesis that fluoroquinolones, macrolides and cephalosporins may play a role in the spread of C. difficile in Scotland (while the role of metronidazole needs further investigations), and highlights the role of antimicrobial stewardship in preventing and controlling C. difficile infection (CDI).     

Detection of genetic hypopituitarism in an adult population of idiopathic pituitary insufficiency patients with growth hormone deficiency

Idiopathic pituitary insufficiency (IPI) is diagnosed in 10% of all hypopituitary patients. There are several known and unknown aetiologies within the IPI group. The aim of this study was to investigate an adult IPI population for genetic cause according a screening schedule. From files of 373 GH deficient (GHD) patients on GH replacement 50 cases with IPI were identified. Of the 39 patients that approved to the study, 25 patients were selected for genetic investigation according to phenotype and 14 patients were not further tested, as sporadic isolated GHD (n = 9) and GHD with diabetes insipidus (n = 5) have low probability for a known genetic cause. Genotyping of all coding exons of HESX1, LHX4, PROP1, POU1F1 and GH1 genes were performed according to a diagnostic algorithm based on clinical, hormonal and neuroradiological phenotype. Among the 25 patients, an overall rate of 8% of mutations was found, and a 50% rate in familial cases. Among two sibling pairs, one pair that presented with complete anterior pituitary insufficiency, had a compound heterozygous PROP1 gene mutation (codons 117 and 120: exon 3 p Phe 117 Ile (c349 T>A) and p Arg 120 Cys (c358 C>T)) with a phenotype of very late onset ACTH-insufficiency. In the other sibling pair and in the sporadic cases no mutation was identified. This study suggests that currently known genetic causes are rare in sporadic adult IPI patients, and that systematic genetic screening is not needed in adult-onset sporadic cases of IPI. Conversely, familial cases are highly suspect for genetic causes.     

Proneurotrophin-3 may induce Sortilin-dependent death in inner ear neurons

Contrast adaptation is a basic property of visual information processing. However, important questions about contrast adaptation in the lateral geniculate nucleus (LGN) remain. For example, it is unclear whether the different information channels have the same or distinct contrast adaptation properties and mechanisms. It has been recognized that the visual system is not a one-way ascending pathway, but also contains descending feedback projections. Although studies have explored the role of this feedback system, it is unclear whether corticothalamic feedback contributes to adaptation in the LGN. To investigate these questions, we studied contrast adaptation of LGN neurons in anesthetized and paralysed cats by measuring electrophysiological responses to visual test stimuli before and after adaptation induced by prolonged visual stimulation. After adaptation, contrast response functions were usually shifted towards higher contrasts, indicating decreased contrast gain, and the maximum response decreased. Also, contrast adaptation effects were stronger in Y-cells than in X-cells. Furthermore, adaptation effects were still observed in the LGN when the corticothalamic feedback was inactivated. Changes in the contrast gain of Y-cells were diminished in the absence of feedback, while contrast gain was largely unchanged in X-cells. Our observations confirm that contrast adaptation occurs in LGN neurons and furthermore demonstrate that Y-cells show stronger adaptation effects than X-cells. These results also provide an example of how corticothalamic feedback modulates contrast information processing distinctly in different information channels.     

Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: Observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts

Objective

To determine whether cigarette smoking influences the response to treatment in patients with early rheumatoid arthritis (RA).

Methods

We retrieved clinical information about patients entering the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) early RA cohort from 1996 to 2006 (n = 1,998) who were also in the Swedish Rheumatology Register (until 2007). Overall, 1,430 of the 1,621 registered patients were followed up from the time of inclusion in the EIRA cohort. Of these, 873 started methotrexate (MTX) monotherapy at inclusion, and 535 later started treatment with a tumor necrosis factor (TNF) inhibitor as the first biologic agent. The primary outcome was a good response according to the European League Against Rheumatism criteria at the 3‐month visit. The influence of cigarette smoking (current or past) on the response to therapy was evaluated by logistic regression, with never smokers as the referent group.

Results

Compared with never smokers, current smokers were less likely to achieve a good response at 3 months following the start of MTX (27% versus 36%; P = 0.05) and at 3 months following the start of TNF inhibitors (29% versus 43%; P = 0.03). In multivariate analyses in which clinical, serologic, and genetic factors were considered, the inverse associations between current smoking and good response remained (adjusted odds ratio [OR] for MTX response 0.60 [95% CI 0.39–0.94]; adjusted OR for TNF inhibitor response 0.52 [95% CI 0.29–0.96]). The lower likelihood of a good response remained at later followup visits. Evaluating remission or joint counts yielded similar findings. Past smoking did not affect the chance of response to MTX or TNF inhibitors. Evaluating the overall cohort, which reflects all treatments used, current smoking was similarly associated with a lower chance of a good response (adjusted ORs for the 3‐month, 6‐month, 1‐year, and 5‐year visits 0.61, 0.65, 0.78, 0.66, and 0.61, respectively).

Conclusion

Among patients with early RA, current cigarette smokers are less likely to respond to MTX and TNF inhibitors.

     

Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease

Progressive renal failure often complicates Fabry disease, the pathogenesis of which is not well understood. To further explore this we applied unbiased stereological quantitative methods to electron microscopic changes of Fabry nephropathy and the relationship between parameters of glomerular structure and renal function in 14 young Fabry patients (median age 12 years). Renal biopsies were obtained shortly before enzyme replacement therapy from these patients and from nine normal living kidney donors as controls. Podocyte globotriaosylceramide (GL-3) inclusion volume density increased progressively with age; however, there were no significant relationships between age and endothelial or mesangial inclusion volume densities. Foot process width, greater in male Fabry patients, also progressively increased with age compared with the controls, and correlated directly with proteinuria. In comparison to the biopsies of the controls, endothelial fenestration was reduced in Fabry patients. Thus, our study found relationships between quantitative parameters of glomerular structure in Fabry nephropathy and age, as well as urinary protein excretion. Hence, podocyte injury may play a pivotal role in the development and progression of Fabry nephropathy.     

Aortic valve replacement in a patient with severe nickel allergy

Nickel allergy can raise clinical problems in patients undergoing cardiac surgery who require sternal closure with stainless steel wire. We describe the case of a 51-year-old woman with severe nickel allergy who underwent aortic valve replacement with a nickel-free ON-X prosthesis and sternal closure by Fiberwire # 2 suture without complications. Considering its biocompatibility and its mechanical characteristics including optimal strength and knot resistance, this suture might be a viable alternative in patients in which the use of stainless steel wire is contraindicated.     

The Biliopancreatic Diversion with a Duodenal Switch (BPDDS): How Is It Optimally Performed?

Background  

The biliopancreatic diversion with duodenal switch can be performed by different combinations of restriction and malabsorption. The aim of this study was to evaluate weight loss and potential side effects for two variants of the procedure.     

PulseCath(R) as a right ventricular assist device

The PulseCath(?) is a pulsatile pump that offers a circulatory support up to 3?l/min. The PulseCath(?) is indicated for patients who require a higher degree of support than that offered by the intra-aortic balloon pump. We describe the first two cases of the use of the PulseCath(?) as a temporary support for the right ventricle after insertion through the pulmonary artery trunk. Two patients developed an acute right ventricular failure with severe hemodynamic instability after cardiac surgery. The PulseCath(?) was chosen to assist the right ventricle. An immediate improvement of hemodynamic parameters was observed in both cases. In the first patient an irreversible metabolic unbalance, already present prior to PulseCath(?) insertion, led to multi-organ failure and eventually to death. In the second case the early utilization of PulseCath(?) led to a complete recovery of the right ventricle and the patient was discharged in good clinical condition. Besides the technical feasibility, this report would suggest that a correct timing is the key to success for the PulseCath(?) as a right ventricular assist device.