Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma: a cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance? A study of 136 cases

Patients with skin nodules characterized by the infiltrate of pleomorphic small/medium T lymphocytes are currently classified as "primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma" (SMPTCL) or as T-cell pseudolymphoma. The distinction is often arbitrary, and patients with similar clinicopathologic features have been included in both groups. We studied 136 patients (male:female = 1:1; median age: 53 years, age range: 3-90 years) with cutaneous lesions that could be classified as small-/medium-sized pleomorphic T-cell lymphoma according to current diagnostic criteria. All but 3 patients presented with solitary nodules located mostly on the head and neck area (75%). Histopathologic features were characterized by nonepidermotropic, nodular, or diffuse infiltrates of small- to medium-sized pleomorphic T lymphocytes. A monoclonal rearrangement of the T-cell receptor-gamma gene was found in 60% of tested cases. Follow-up data available for 45 patients revealed that 41 of them were alive without lymphoma after a median time of 63 months (range: 1-357 months), whereas 4 were alive with cutaneous disease (range: 2-16 months). The incongruity between the indolent clinical course and the worrying histopathologic and molecular features poses difficulties in classifying these cases unambiguously as benign or malignant, and it may be better to refer to them with a descriptive term such as "cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance," rather than forcing them into one or the other category. On the other hand, irrespective of the name given to these equivocal cutaneous lymphoid proliferations, published data support a nonaggressive therapeutic strategy, particularly for patients presenting with solitary lesions.

Solitary small- to medium-sized pleomorphic T-cell nodules of undetermined significance: clinical, histopathological, immunohistochemical and molecular analysis of 26 cases

BACKGROUND: Solitary skin nodules composed of pleomorphic T lymphocytes are often the source of diagnostic problems. OBJECTIVE: To characterize the clinicopathological features, prognosis and optimal treatment modalities of patients with solitary lymphoid nodules of small- to medium-sized pleomorphic T lymphocytes. METHODS: Twenty-six patients were analysed for clinical, histopathological, immunophenotypical, molecular and follow-up data. Results: Lesions were located mainly on the head and neck (n = 16; 61.5%) or trunk (n = 8; 30.8%). Histopathology showed non-epidermotropic nodular or diffuse infiltrates of small- to medium-sized pleomorphic T lymphocytes. Monoclonality was found by PCR in 54.2% of cases (n = 13/24). After a mean follow-up of 79.7 months, a local recurrence could be observed only in 1 patient. CONCLUSIONS: Our patients have a specific cutaneous lymphoproliferative disorder characterized by reproducible clinicopathological features. The incongruity between the indolent clinical course and the worrying histopathological features poses difficulties in classifying these cases unambiguously as benign or malignant. We suggest to describe these lesions as 'solitary small- to medium-sized pleomorphic T-cell nodules of undetermined significance'. Irrespective of the name given to these equivocal cutaneous lymphoid proliferations, follow-up data support a non-aggressive therapeutic strategy.

The Role of Small and Medium-sized Centers for Territorial Development in Switzerland

This paper describes the role of small and medium-sized urban centers in Switzerland. Switzerland is a highly urbanized country where small and medium-sized urban centers play an important role in ensuring a balanced national urban system. Besides the four largest metropolitan regions （Zurich, Geneva, Basel and Bern）, small and medium-sized towns function as central places for a wider, often extensive hinterland. They provide opportunities for living and working and they connect rural and mountain regions to national and international networks. Using secondary statistics and a case study, the paper shows that small and medium-sized urban centers are home to significant concentrations of export-oriented industries. Firms in these value-adding secondary sectors are rooted in these places and benefit from strong local embeddedness while also being oriented towards global markets. Small and medium-sized urban centers also profit from their strong local identities. While these places face various challenges, they function as important pillars in creating a balanced regional development pattern. Swiss regional development policy follows the goal of polycentric spatial development and it employs various instruments that aim to ensure a balanced urban system.

Innovations in Small and Medium-Sized Family Firms

Small and medium-sized firms are a prevalent organizational form in Germany. Their importance for the German economy is indisputable. Most of them are global market leaders in their niches and are considered to be a force for innovation in the German economy. The ability to be innovative in niche markets has been identified as the antecedent of their strong, or even dominant, competitive positions in their industries. The driver of this innovation success may well be the family, which distinguishes family firms from non-family firms. Nils Kraiczy analyzes if a family influences innovation in a family firm and if this influence has only positive effects. The dissertation focuses on the impact of top management teams on innovations interacting with family firm-specific characteristics. The author shows the complexity of family influence by presenting different effects of each investigated family firm-specific characteristic on the relationship between top management team behavior and innovation.

Ready for a crisis? How supervisory boards affect the formalized crisis procedures of small and medium-sized family firms in Germany

Overcoming a crisis situation in which the socioemotional wealth (SEW) of a family is at risk can be threatened by a lack of formal crisis procedures, which can increase the probability of organizational decline. Thus, not being prepared for a crisis situation may be a critical factor in the long-term survival of family firms. From a corporate governance perspective, supervisory boards may achieve higher levels of crisis readiness. Applying the resourced-based view and SEW theory, we analyze the relationship between family ownership and formalized crisis procedures in 150 small and medium-sized German firms. Our results show that formalized crisis procedures decrease as family ownership increases. Including supervisory boards in our analysis, we find a significant moderating effect of supervisory boards on the relationship between family ownership and formalized crisis procedures. Specifically, our results suggest that family firms with supervisory boards show similar levels of formalized crisis procedures as non-family firms with supervisory boards. In contrast, family firms without supervisory boards exhibit lower levels of formalized crisis procedures compared with non-family firms without supervisory boards. We also discuss managerial implications, limitations, and future research.

Same same but different: Locational policies in small and medium-sized European cities

Globalized interurban competition is affecting cities of various sizes and locations. Small and medium-sized cities have to find ways to position themselves in global markets by formulating locational policies. This paper outlines an analytical framework of locational policies that cities adopt in order to increase their competitiveness. By comparing two European small and mediumsized cities (Lucerne and Ulm), we examine manifestations of locational policies and compare if these policies are being diverse or resemble each other. We found that strategies of both cities are sharing the intentions to be competitive, but their policy choices differ because the economic and political context is enabling or restricting certain kinds of locational policies. Furthermore, the findings point to the high explanatory power of municipal tax autonomy when studying locational policies.

Use of outdoor ranges by laying hens in different sized flocks.

In studies assessing outdoor range use of laying hens, the number of hens seen on outdoor ranges is inversely correlated to flock size. The aim of this study was to assess individual ranging behavior on a covered (veranda) and an uncovered outdoor run (free-range) in laying hen flocks varying in size. Five to ten percent of hens (aged 9–15 months) within 4 small (2–2500 hens), 4 medium (5–6000), and 4 large (≥9000) commercial flocks were fitted with radio frequency identification (RFID) tags. Antennas were placed at both sides of all popholes between the house and the veranda and the veranda and the free-range. Ranging behavior was directly monitored for approximately three weeks in combination with hourly photographs of the free-range for the distribution of hens and 6h long video recordings on two parts of the free-range during two days. Between 79 and 99% of the tagged hens were registered on the veranda at least once and between 47 and 90% were registered on the free-range at least once. There was no association between the percentage of hens registered outside the house (veranda or free-range) and flock size. However, individual hens in small and medium sized flocks visited the areas outside the house more frequently and spent more time there than hens from large flocks. Foraging behavior on the free-range was shown more frequently and for a longer duration by hens from small and medium sized flocks than by hens from large flocks. This difference in ranging behavior could account for the negative relationship between flock size and the number of hens seen outside at one point of time. In conclusion, our work describes individual birds’ use of areas outside the house within large scale commercial egg production.

Advanced nail surgery

Six techniques not yet widely known or used in the dermatologic surgery of the nails are briefly described. Small-to-medium-sized tumours of the proximal nail fold (PNF) can be excised and the defect repaired with advancement or rotation flaps. A superficial biopsy technique of the matrix for the diagnosis of longitudinal brown streaks in the nail, which allows rapid histological diagnosis of the melanocyte focus to be performed, is described here. Because the excision is very shallow and leaves the morphogenetic connective tissue of the matrix intact, the defect heals without scarring. Laterally positioned nail tumours can be excised in the manner of a wide lateral longitudinal nail biopsy. The defect repair is performed with a bipedicled flap from the lateral aspect of the distal phalanx. Malignant tumours of the nail organ often require its complete ablation. These defects can be covered by a full-thickness skin graft, reversed dermal graft, or cross-finger flap. The surgical correction of a split nail is often difficult. The cicatricial tissue of the matrix and PNF have to be excised and the re-attachment of these wounds prevented. The matrix defect has to be excised and sutured or covered with a free matrix graft taken either from the neighbouring area or from the big toe nail.

Imaging appearances of Buerger's disease complications in the upper and lower limbs

Thromboangiitis obliterans (Buerger's disease) is a rare, non-atherosclerotic, segmental, inflammatory vasculitis that most commonly involves small and medium-sized arteries, veins and nerves of the extremities and affects tobacco smokers between the ages of 25 and 45 years. The manifestations of Buerger's disease can be extremely variable and, therefore, awareness of the condition is important for both general and musculoskeletal radiologists. This paper presents the radiological appearance of the sequelae of Buerger's disease involving the upper and lower limbs.

Neuronal expression of the ubiquitin ligase Nedd4-2 in rat dorsal root ganglia: modulation in the spared nerve injury model of neuropathic pain

Neuronal hyperexcitability following peripheral nerve lesions may stem from altered activity of voltage-gated sodium channels (VGSCs), which gives rise to allodynia or hyperalgesia. In vitro, the ubiquitin ligase Nedd4-2 is a negative regulator of VGSC α-subunits (Na(v)), in particular Na(v)1.7, a key actor in nociceptor excitability. We therefore studied Nedd4-2 in rat nociceptors, its co-expression with Na(v)1.7 and Na(v)1.8, and its regulation in pathology. Adult rats were submitted to the spared nerve injury (SNI) model of neuropathic pain or injected with complete Freund's adjuvant (CFA), a model of inflammatory pain. L4 dorsal root ganglia (DRG) were analyzed in sham-operated animals, seven days after SNI and 48 h after CFA with immunofluorescence and Western blot. We observed Nedd4-2 expression in almost 50% of DRG neurons, mostly small and medium-sized. A preponderant localization is found in the non-peptidergic sub-population. Additionally, 55.7 ± 2.7% and 55.0 ± 3.6% of Nedd4-2-positive cells are co-labeled with Na(v)1.7 and Na(v)1.8 respectively. SNI significantly decreases the proportion of Nedd4-2-positive neurons from 45.9 ± 1.9% to 33.5 ± 0.7% (p<0.01) and the total Nedd4-2 protein to 44% ± 0.13% of its basal level (p<0.01, n=4 animals in each group, mean ± SEM). In contrast, no change in Nedd4-2 was found after peripheral inflammation induced by CFA. These results indicate that Nedd4-2 is present in nociceptive neurons, is downregulated after peripheral nerve injury, and might therefore contribute to the dysregulation of Na(v)s involved in the hyperexcitability associated with peripheral nerve injuries.

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

Excision of high and mid cervical spinal cord arteriovenous malformations by anterior operation

Symptomatic cervical spinal arteriovenous malformations (AVMs) located on the anterior aspect of the spinal cord are rare and surgical removal of these AVMs presents considerable challenges and risks. Surgical techniques to date have usually been by posterior approach and lateral dissection around the cord or via midline myelotomy, both approaches involving cord manipulation and retraction and in the latter, dissection through the spinal cord. We present two teenage patients with symptomatic anteriorly placed mid to high cervical spinal AVMs and associated aneurysm in which excision of the AVMs and aneurysm was performed by an anterior approach using vertebrectomy/corpectomy. The first case had a small perimedullary glomus-type AVM with an aneurysm on the anterior aspect of the cord at the C3/4 level; excision was performed using a single level vertebrectomy/corpectomy, the patient remaining neurologically intact. The second case had a medium-sized juvenile AVM with an aneurysm, both perimedullary and intramedullary, centred at the C5/6 level; excision was performed using a two-level vertebrectomy/corpectomy with no deterioration in the marked pre-operative tetraparesis, which at long-term follow up had improved and stabilised. Anterior approaches have been recently described for treatment of anteriorly placed cervical arteriovenous fistulas (AVFs) and an intramedullary haemangioblastoma, but not as yet for spinal AVMs. These are the first two reported cases of anteriorly situated cervical AVMs successfully removed surgically by an anterior approach and with good neurological outcomes.