Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients’ survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter ...duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40g per day initially, with CS tapering over 12 months) or the mild regimen (10–30g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P=0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the mild regimen was observed in patients with moderate BP, with an almost twofold decrease in the risk of death or life-threatening adverse events relative to the standard regimen (hazard ratio=0.54; 95% confidence interval, 0.30–0.97; P=0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients’ outcome.
Moderate to severe ichthyosis is known to have a significant impact on quality of life. A French national survey was performed to describe in more detail how ichthyosis impacts the patients' lives. A ...questionnaire specifically dedicated to ichthyosis was distributed to patients followed in hospital expert centres or members of the French association of patients. A total of 241 questionnaires were completed and returned (response ratio: 29% for children and 71% for adults). A negative impact of ichthyosis was obvious in terms of domestic life (skin care, housework, clothing, etc.), educational/professional lives (rejections by other children, workplace discrimination, absenteeism, etc) and for leisures/sports activities. The patient's economical resources were also heavily impacted by ichthyosis with important out-of-pocket expenses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We previously proposed a set of 4 clinical criteria for the diagnosis of bullous pemphigoid (BP) that consisted of age greater than 70 years, absence of atrophic scars, absence of mucosal involvement ...and absence of predominant bullous lesions on the neck and head. These results have been challenged because direct immunoelectron microscopy (IEM), which was used as the standard diagnostic criterion in our initial study, does not identify the different antigens of the basement membrane zone.
To reassess the validity of these clinical criteria for the diagnosis of BP using immunoblot analysis of patient sera as the main diagnostic criterion, in order to precisely identify the antigens recognized by patient sera.
One hundred and eighty-nine sera from patients with various subepidermal autoimmune blistering diseases (AIBDs) were tested by immunoblotting using dermal and epidermal extracts. IEM was used as a complementary diagnostic procedure in a few patients whose serum recognized BPAG2 exclusively or was negative in immunoblotting.
142 patients (75%) had at least 3 of the 4 clinical diagnostic criteria. Sera from patients who lacked the set of BP clinical criteria were more frequently immunoblot negative (34%) than sera from patients who had the criteria (18%; p = 0.025). BPAG1 was more frequently recognized by sera from patients with the set of BP clinical criteria (78%) than by sera from patients without the criteria (45%; p = 5.10(-4)). In contrast, BPAG2 was recognized by a great number of sera from patients who lacked the criteria of BP (71%), which was in accordance with the presence of numerous patients with cicatricial pemphigoid in this group. Among patients with various subepidermal AIBDs, the diagnosis of BP could be made with a sensitivity of 86%, a specificity of 90% and an excellent prognostic positive value over 95%, if 3 of these clinical criteria were present.
These results confirm the interest of this set of clinical criteria for the rapid diagnosis of BP.
The complex arrangement of the extracellular matrix (ECM) produced by cells during tissue growth, healing and remodelling is fundamental to tissue function. In connective tissues, it is still unclear ...how both cells and the ECM become and remain organized over length scales much larger than the distance between neighbouring cells. While cytoskeletal forces are essential for assembly and organization of the early ECM, how these processes lead to a highly organized ECM in tissues such as osteoid is not clear. To clarify the role of cellular tension for the development of these ordered fibril architectures, we used an in vitro model system, where pre-osteoblastic cells produced ECM-rich tissue inside channels with millimetre-sized triangular cross sections in ceramic scaffolds. Our results suggest a mechanical handshake between actively contracting cells and ECM fibrils: the build-up of a long-range organization of cells and the ECM enables a gradual conversion of cell-generated tension to pre-straining the ECM fibrils, which reduces the work cells have to generate to keep mature tissue under tension.
Background and aims: Basaloid follicular hamartoma is a rare disorder regarded as a developmental malformation. It may be solitary or generalized, linear or regionalized, and is sometimes associated ...with myasthenia gravis or alopecia. We compared immunohistochemical staining patterns of selected markers in order to differentiate this hamartoma from fibroepithelioma of Pinkus, a basal cell carcinoma variant it can be confused with.
Methods: The expression of three immunohistochemical markers – CD‐34, Ki‐67, bcl‐2 – was studied in a basaloid follicular hamartoma and in a fibroepithelioma of Pinkus. Two basal cell carcinomas, a nodular and a fibrosing type, and a trichoepithelioma were included as controls.
Results: Basaloid follicular hamartoma shows a low proliferation index and an at least focally circumferential expression of CD‐34 around the epithelial strands. This compares to the findings in trichoepithelioma. In contrast, fibroepithelial tumor of Pinkus and two other basal cell carcinoma subtypes display a high proliferative index and an absence of CD‐34 expression around the epithelium. These findings support the non‐neoplastic nature of basaloid follicular hamartoma.
Work conditions increase the prevalence of chronically low back pain (CLBP) in labourers (LW) as well as in sedentary workers (SW). Previous studies showed that functional restoration program (FRP) ...improved the condition of patients with CLBP. Here we evaluated the differential value of FRP in LW and SW groups, with respect to spinal and abdominal muscle functions, functional capacity and autonomy, and professional reintegration.
Between 2012 and 2015, 89 patients (aged 18 to 65) with CLBP, included in the FRP, completed the program. There were 45 LW and 44 SW. Judgment criteria were physical (Sorensen test, for spinal muscles, and Shirado-Ito test, for abdominal muscles), functional (Quebec score), and socio-professional (number of sick leave days in 6 months), before and after completing the FRP.
Both groups, LW and SW, improved their functional capacities (Quebec score: 29.194 after, vs. 40.622 before the program, P=0.0022, in LW; 26. 33% after the FRP, vs. 37.6% before the program, P=0.0008, in SW), and the number of sick leave days dramatically decreased after the FRP (19.23 days after, vs. 58.08 days before, P=0.0121, in LW; mean 0.41 days after vs. 26.53 days before, P=0.0018, in SW). Sorensen test improved in both groups (119.18 after vs. 76.65 before, P=0.0192, in LW; 119.10 after FRP vs. 65.08 before, P=0.0011, in SW). Shirado-Ito Test also improved: 340.13 vs. 91.81, in LW and 128.73 vs. 65.08, P=0.0338, in SW.
FRP improved the condition of patients with CLBP in all analysed criteria, both in LW and in SW. However the repartition of improvement between LW and SW was different, particularly in physical criteria (LW improved more their abdominal muscles, and SW improved more their spinal muscles). These results suggest that isokinetic studies are needed to specifically adapt the FRP to the work conditions…
We have examined the subcellular localization of the neu protein by immunohistochemistry and immuno-electron microscopy, associated with immunoblotting of normal and neoplastic tissues with 2 ...monoclonal antibodies (MAbs). Immunoelectron microscopy clearly reveals that neu protein resides only on the lateral plasma membrane of the simple epithelium of the breast and on the plasma membrane of malignant breast cells. It is also found on the membranes of the microvilli and the apical vacuoles of the cells of the proximal convoluted tubule of the kidney. In the cytoplasm, the only immunoreactivity detected with both antibodies was on the membrane of the mitochondrial cristae of normal and malignant cells. Immunoblotting reveals that the molecular weight of the membrane protein is 185 and 155 kDa for the mitochondrial protein. The cell membrane staining pattern can be revealed by light microscopic immunohistochemistry only in malignant cells and is therefore specific for malignancy. The membrane expression in normal cells cannot be visualized in this way. The mitochondrial reactivity appears as a cytoplasmic granular staining when examined under the light microscope. Similar cytoplasmic staining has been described previously in other studies with other antibodies against the neu protein and has lead to speculation about its function in normal and malignant cells. However, it is demonstrated in this study that it is not the known neu-oncogene product.
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