Asthmatic child without asthma

Two boys aged 13 and 7 years, displayed chronic coughing, dyspnoea on exertion, anorexia, weight loss, and fatigue. At first a diagnosis of asthma was made. However, a correct interpretation of anamnestic and clinical features, laboratory findings and radiographic results led to the diagnosis of 'pigeon breeder's disease' in both cases. Both patients recovered after drug treatment and avoidance of re-exposure to pigeon antigen.     

Photosensitized production of hydrogen by hydrogenase in reversed micelles

Hydrogenase (hydrogen:ferricytochrome c₃ oxidoreductase, EC 1.12.2.1) from Desulfovibrio vulgaris was encapsulated in reversed micelles with cetyltrimethylammonium bromide as surfactant and a chloroform/octane mixture as solvent. Reducing equivalents for hydrogenase-catalyzed hydrogen production were provided by vectorial photosensitized electron transfer from a donor (thiophenol) in the organic phase through a surfactant-Ru²⁺ sensitizer located in the interphase to methyl viologen concentrated in the aqueous core of the reversed micelle. The results show that reversed micelles provide a microenvironment that (i) stabilizes hydrogenase against inactivation and (ii) allows an efficient vectorial photosensitized electron and proton flow from the organic phase to hydrogenase in the aqueous phase.     

Patients’ and Psychologists’ Preferences for Feedback Reports on Expected Mental Health Treatment Outcomes: A Discrete-Choice Experiment

In recent years, there has been an increasing focus on routine outcome monitoring (ROM) to provide feedback on patient progress during mental health treatment, with some systems also predicting the expected treatment outcome. The aim of this study was to elicit patients’ and psychologists’ preferences regarding how ROM system-generated feedback reports should display predicted treatment outcomes. In a discrete-choice experiment, participants were asked 12–13 times to choose between two ways of displaying an expected treatment outcome. The choices varied in four different attributes: representation, outcome, predictors, and advice. A conditional logistic regression was used to estimate participants’ preferences. A total of 104 participants (68 patients and 36 psychologists) completed the questionnaire. Participants preferred feedback reports on expected treatment outcome that included: (a) both text and images, (b) a continuous outcome or an outcome that is expressed in terms of a probability, (c) specific predictors, and (d) specific advice. For both patients and psychologists, specific predictors appeared to be most important, specific advice was second most important, a continuous outcome or a probability was third most important, and feedback that includes both text and images was fourth in importance. The ranking in importance of both the attributes and the attribute levels was identical for patients and psychologists. This suggests that, as long as the report is understandable to the patient, psychologists and patients can use the same ROM feedback report, eliminating the need for ROM administrators to develop different versions.

     

SMAD2 Mutations Are Associated with Arterial Aneurysms and Dissections

We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF‐β signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF‐β signaling pathway exhibit arterial aneurysms and dissections as key features     

Estimating Renal Survival Using the ANCA-Associated GN Classification

A histopathological classification system for ANCA-associated vasculitis was recently published, but whether this system predicts renal outcome requires validation. Here, we analyzed data from 164 consecutive patients with biopsy-proven renal involvement of ANCA-associated vasculitis. The ANCA-associated GN (AGN) classification categorizes patients as having focal, mixed, crescentic, or sclerotic GN. Five-year renal survival rates by categories of the AGN classification scheme were 91% for focal, 69% for mixed, and 64% for crescentic (log-rank P<0.0001). Only one patient was classified as sclerotic. Furthermore, the percentage of normal glomeruli found on biopsy estimated renal survival with the same precision as did the AGN classification scheme. Patients classified as crescentic or mixed, however, had worse survival when the percentage of normal glomeruli was <25%. In conclusion, the AGN classification for renal biopsy specimens is a practical and informative scheme with which to categorize patients with ANCA-associated vasculitis, but adding the percentage of normal glomeruli to the system seems to improve its predictive value.Necrotizing crescentic GN is a common feature in ANCA-associated vasculitis (AAV).¹ Histologically, renal lesions in AAV are characterized by cellular crescents, fibrinoid necrosis, and interstitial inflammation. Recently, an international vasculitis working group proposed a histopathologic classification of GN in patients with AAV to assess its predictive value for renal survival.²To validate the ANCA-associated GN classification system (AGN classification), we scored all AAV renal biopsy specimens from patients with AAV who participated in the Limburg Renal Registry, a prospective renal biopsy study on glomerular diseases.^3,4 The database was searched for patients with pauci-immune necrotizing crescentic GN.⁵Two hundred twenty-one consecutive patients who underwent renal biopsy between January 1, 1979, and August 31, 2011, in the province of Limburg, The Netherlands, were identified as having pauci-immune necrotizing crescentic GN. Eight of these patients were excluded for concomitant renal disease (six with diabetic nephropathy and two with thin glomerular basement membrane nephropathy). Forty-nine patients were excluded because <10 glomeruli were found in the renal biopsy specimen.²Thus, 164 patients with a mean age ± SD of 61.0±14.6 years were included (113 men and 52 women) with a mean follow-up of 8.5 years (range, 1 day–33 years). Eighty-three patients were positive for proteinase-3 ANCA and 81 were positive for myeloperoxidase (MPO) ANCA. Mean baseline serum creatinine was 349.7 ± 242.6 µmol/L, and median baseline proteinuria was 1.3 g per 24 hours (range, 0–11).Before 2000, patients received corticosteroids in combination with oral cyclophosphamide. Since 2000, all patients have been treated according to the European League Against Rheumatism (EULAR) guidelines:⁵ induction therapy with steroids and oral cyclophosphamide, 2 mg/kg per day, over 3–6 months and maintenance therapy with azathioprine and low-dose corticosteroids.⁶ Since 2009, induction therapy consisted of corticosteroids with intravenous cyclophosphamide at a dose of 15 mg/kg per cycle over three to six pulses with 2-week intervals, or with oral cyclophosphamide.⁷ Patients with a serum creatinine >500 μmol/L or alveolar lung hemorrhage at the time of renal biopsy were considered to have severe or life-threatening vasculitis and received 1000 mg of prednisolone per day for 3 days or plasma exchange in addition to the standard treatment as described above.⁵Eighty-one (49.4%) biopsy specimens were classified as focal, 43 (26.2%) as crescentic, and 39 (23.8%) as mixed. Only one biopsy specimen was classified as sclerotic (i.e., >50% sclerotic glomeruli). Baseline characteristics (at the time of renal biopsy) are presented in

A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

Physical beauty: only skin deep?

Personal appearance and physical beauty are becoming increasingly important in our societies and, as a consequence, enter into the realm of medicine and health care. Adequate and just health care policies call for an understanding of this trend. The core question to be addressed concerns the very idea of beauty. In the following, a conceptual clarification is given in terms of beauty's meaning, value and function (i.e. beauty that is used instrumentally, and beauty that is attained). Furthermore, some relevant distinctions are drawn between physical and artistic beauty, and physical beauty in a human sense. The core idea for this is formed by a Kantian notion of the beauty concept. It is argued that beauty judgements should be understood as relative to persons and their contexts. Physical beauty should be taken seriously when it is understood in this deeper sense of being related to the shaping of a person's identity.     

Cryopreservation of ovarian tissue; now is the time for ethical considerations

The development of ovarian tissue cryopreservation will expand the range of clinical applications in reproductive medicine. This emerging technology may have beneficial opportunities for patients, particularly in oncology, as well as for the process of oocyte donation. However, it will also lead to new moral problems requiring critical reflection concerning the criteria for tissue banking and future clinical applications. Because cryopreservation of ovarian tissue nowadays is the focus of experimental research, technology assessment is currently appropriate, anticipating introduction into clinical practice. Specific guidelines, developed by the medical profession in cooperation with ethicists and lawyers can contribute to prudent clinical use.     

Starting a crossover kidney transplantation program in the Netherlands: ethical and psychological considerations

On April 15th, 2003, the first crossover kidney transplantation took place in The Netherlands. In September of the same year, a national database was established to facilitate kidney exchange between two donor-recipient couples. During 2004, kidneys from living donors will be exchanged between the seven university medical centers in The Netherlands. One of the conditions for successfully implementing this program was the need to address the ethical and psychologic implications involved. In this article we will discuss the ethical and psychologic considerations that are accompanying the practical preparations for the first Dutch crossover transplantation program. We identified five topics of interest: the influence of "donation by strangers" on the motivation and willingness of donor-patient couples, the issue of anonymity, the loss of the possibility of "medical excuses" for unwilling donors, the view that crossover is a first step to commercial organ trade, and the interference with existing organ donation programs. We concluded that whether viewed separately or in combination, these issues do not impede the efficient organization of a crossover program or raise worrying ethical issues.