Lymphomatoid papulosis types D and E: a multicentre series of the French Cutaneous Lymphomas Study Group.

BACKGROUND: Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. AIM: To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. METHODS: The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. RESULTS: After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. CONCLUSION: LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

T-cell papulosis associated with B-cell malignancy: a distinctive clinicopathologic entity.

BACKGROUND: A distinctive eruption referred to as 'insect bite-like reaction' or 'eosinophilic dermatosis of haematological malignancy' has been described during the course of haematological B-cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. METHODS: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo-vesicles and/or nodules were included. Clinical, histopathological, immunohistochemical and molecular data were reviewed. RESULTS: No significant insect bite history or seasonal predominance was recorded. Patients had pruritic papules (81%), papulo-vesicles (43%) and nodules (38%), often predominated in the head and neck region (84%), without complete remission periods in most cases (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%). Histological and immunohistochemical review showed a dense dermal lymphocytic infiltrate predominantly composed of T lymphocytes (100%), with frequent eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic) pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides; clusters of tumour B cells were identified in 47% of cases using appropriate phenotyping markers. In 10/14 cases (71.4%) tested for B-cell IgH gene rearrangement, a B-cell clone was identified in skin lesions (identical to the blood clone in nine cases), whereas no T-cell clone was present. CONCLUSION: We propose the denomination 'T-cell papulosis associated with B-cell malignancy' (TCP-BCM) for this distinctive eruption. Although resulting in various histopathological pictures, it can be easily recognized by clinicians and may be identified by informed pathologists relying on some key features. An extravasation of tumour B cells with skin-homing properties associated with a secondary, predominant, T-cell immune reaction could explain the clinicopathologic aspect and the prolonged regressive and recurrent course of the disease.

Vorinostat and Mithramycin A in combination therapy as an interesting strategy for the treatment of Sézary T lymphoma: a transcriptomic approach.

SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and Drug Administration (FDA) for treating advanced refractory cutaneous T cell lymphomas. As SAHA alters the expression of many genes under control of the Sp1 transcription factor, we examined the effect of its association with the FDA-approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive inhibitor of Sp1 binding to DNA. Sézary syndrome (SS) cells, expanded ex vivo from peripheral blood mononuclear cells of 4 patients, were tested for their sensitivity to the drugs regarding cytotoxicity and differential responsive gene expression. Multivariate statistical methods were used to identify genes whose expression is altered by SAHA, MTR, and the synergist effect of the two drugs. MTR, like SAHA, induced the apoptosis of SS cells, while the two drugs in combination showed clear synergy or potentiation. Expression data stressed a likely important role of additive or synergistic epigenetic modifications in the combined effect of the two drugs, while direct inhibition of Sp1-dependent transcription seemed to have only limited impact. Ontological analysis of modified gene expression suggested that the two drugs, either independently or synergistically, counteracted many intertwined pro-survival pathways deregulated in SS cells, resistance of these tumors to intrinsic and extrinsic apoptosis, abnormal adhesion migration, and invasive properties, as well as immunosuppressive behavior. Our findings provide preliminary clues on the individual and combined effects of SAHA and MTR in SS cells and highlight a potential therapeutic interest of this novel pair of drugs for treatment of SS patients.

[Papular mycosis fungoides]. / Mycosis fongoïde papuleux.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. A new form of incipient MF has recently been described: papular MF. Herein, we report a case and propose a literature review. PATIENTS AND METHODS: A 63-year-old man presented with erythematous and non-pruritic papular lesions of the trunk. The general examination was unremarkable. A skin biopsy showed moderately dense epidermotropic lymphocytic infiltration consistent with MF. Screening for CD30 was negative. Treatment with an extremely potent corticosteroid (clobetasol, one application per day) seemed effective, with almost complete disappearance of the lesions. DISCUSSION: Many clinical variants of the initial stages of MF have been described, one of the most recent of which is papular mycosis fungoides (PMF), of which 10 cases are reported in the literature. PMF begins clinically with an erythematous, non-pruritic and chronic papular rash that is not associated with the classic erythematous-squamous lesions of incipient MF. There appears to be no predominance of gender, and the age of onset ranges from 31 to 63 years. Histological examination of the PMF lesions revealed an epidermotropic subepidermal infiltrate composed predominantly of CD4+T-cells. The prognosis appeared good with the treatments conventionally used for incipient MF. PMF is likened to a form of incipient MF with a good prognosis. Associated classic MF lesions comprising erythematous-squamous plaques have been described as the condition progresses. Differential diagnoses include pilotropic MF, pityriasis lichenoides chronica, pityriasis lichenoides varioliformis acuta, and especially type B lymphomatoid papulosis, the histopathological findings of which may be close to PMF. CONCLUSION: Papular MF would appear to be a papular variant of incipient MF with a good prognosis. However, it is necessary to obtain clinical and disease progression data for a greater number of patients in order to better characterize this entity.

[Cutaneous events during anti-TNF alpha therapy: a prospective observational study of 41 cases]. / Evénements cutanéomuqueux au cours des traitements par anti-TNF alpha : étude observationnelle prospective de 41 cas.

BACKGROUND: The cutaneous adverse effects of TNFalpha inhibitors and their potential implication in the onset of associated dermatoses remain poorly understood. PURPOSE: To describe the different clinical dermatological situations seen in patients treated with TNFalpha inhibitors. PATIENTS AND METHODS: We conducted a prospective, observational study of patients followed at the Dermatology Department of the CHU Nord university teaching hospital of Marseilles. All patients, referred by various departments, were treated with TNFalpha inhibitors and presented cutaneous events. RESULTS: Forty-one patients were included in the study. Various cutaneous manifestations were observed, including: 15 psoriatic rashes, six skin infections, three eczema rashes, three cases of lupic syndrome, two anaphylactic reactions to infusion and two cutaneous drug reactions. An original case of parapsoriasis was observed. Cutaneous tumors are rarely described. DISCUSSION: This study confirms the multiple clinical dermatological situations observed in patients treated with TNFalpha inhibitors and illustrates the need for good coordination between dermatologists and other specialists in order to ensure optimal management of this population.

Endovascular treatment of descending aortic dissection (type B): short- and medium-term results.

BACKGROUND: Optimal treatment of type B dissections is open to debate. The use of endoprostheses is an option that requires evaluation. AIM: To report our experience with endoprostheses in type B aortic dissections. METHODS: We report our short- and medium-term results with covered prostheses for the treatment of acute (n=7) and chronic (n=28) type B aortic dissections. The criteria used to indicate treatment were the same as those usually used for surgery: acute complications or dilated aneurysm. Cover of the main intimal tear was obtained in all cases with an improvement in symptoms in patients with acute dissections. RESULTS: Early mortality was 14.3% (five patients), linked in three cases to the occurrence of a retrograde dissection of the ascending aorta. No neurological complications were observed. Four patients required an additional endovascular and/or surgical procedure. On early control scans, complete thrombosis of the false lumen at the thoracic level was observed in 40% of cases, partial thrombosis in 42.8% and an absence of thrombosis in 11.4%. After a mean follow-up of 20.8 months, one patient died of a pneumopathy. No secondary aneurysm expansion was noted at the thoracic stage whereas three patients presented with dilation of the abdominal aorta. CONCLUSION: The results of treatment of type B dissections with covered endoprostheses are encouraging. However, the morbimortality associated with treatment and the uncertainty of long-term results do not allow the use of this therapeutic option outside the criteria usually recognized to indicate surgery.

Bullet embolization from the left brachiocephalic vein to the right ventricle.

We present a rare case of bullet embolism from the left brachiocephalic vein to the right ventricle, following a chest gunshot wound, in a 56-year-old soldier. The bullet was accidentally discovered on a systematic chest X-ray. The bullet was very close to the tricuspid subvalvular apparatus and was about to come out from the ventricle. We removed it under cardiopulmonary bypass.

Long-term survival of heart transplant recipients with lung cancer: the role of chest computed tomography screening.

OBJECTIVE: We sought to evaluate the screening modality and outcome of lung cancer occurring in heart transplant recipients (HTR) during a 21-year period. METHODS: We conducted a retrospective review to investigate the incidence, risk factors, screening modality, treatment, and outcomes in HTR with lung cancer. We compared them with a case-matched HTR control group. RESULTS: Out of 829 recipients of heart transplants, 19 cases of bronchogenic carcinoma were found either by routine chest X-ray (n = 10), chest computed tomographic (CT) scanning (n = 4), or by assessment of clinical symptoms (n = 5). The mean time from transplantation to bronchogenic carcinoma diagnosis was 68.8 +/- 42.4 months. A history of smoking was the only risk factor in HTR with bronchogenic carcinoma compared to their case-matched HTR control group ( P < 0.05). Of 18 patients with non-small cell lung cancer (NSCLC), 13 underwent surgery and 5 with advanced cancer underwent chemotherapy and/or radiotherapy. NSCLC was diagnosed by chest X-ray (n = 10), and 6 of these patients died after an average of 43.7 +/- 62.2 months following cancer detection. NSCLC was also diagnosed on the basis of clinical symptoms (n = 4), and 2 of these patients died after a mean follow-up of 9 +/- 4.2 months after cancer diagnosis. All 4 patients in whom cancer was detected by CT scan were alive at an average of 53.5 +/- 36.7 months following cancer detection. The survival rates did not differ between the study and control groups ( P = 0.5). CONCLUSIONS: Optimal outcomes of treatment for primary lung cancer after heart transplantation seem to be related to early detection. A high proportion of deaths from NSCLC may be prevented by chest CT scan screening.

Quantitative videomicroscopic analysis of the sociologic behavior of non-invasive and invasive tumor cell lines.

To analyze the spatial distribution of tumor cell lines with different invasive properties, we used time-lapse videomicroscopic recordings associated with software programs we have developed for quantification. We observed that non-invasive tumor cells rapidly formed small clusters which aggregated to form larger clusters, whereas highly invasive tumor cells remained isolated and did not form clusters. An attraction index computed from a cellular automaton model was used to quantify the degree of attraction-repulsion between cells. The results suggest that the cluster formation by noninvasive cells is not related to a global attraction model and that the random (dispersed) distribution of invasive cells is not related to cell repulsion. According to these results, we can conclude that random cell movement combined with the intrinsic properties of cells explains the phenomenon of cluster formation.

[Prognostic factors of coronary artery bypass surgery]. / Facteurs pronostiques de la chirurgie coronaire.

During these 10 last years, even though patients had a more and more severe condition, the results of coronary artery bypass surgery have continuously improved. According to Society of Thoracic Surgeons data, the operative risk increased by 1/3 (2.6% in 1990 vs. 3.4% in 1999), whereas the per-operative mortality was reduced by 1/4 (3.9% in 1990 vs. 3% in 1999), and is currently stabilized around 2.5-3%. The incidence of complications is a non-negligible marker. The complications observed are mostly neurological (2%), renal (4%), myocardial (4%), infectious (0.5 to 2%), and respiratory (10%). Their occurrence is related to the presence of preoperative risk factors: age (>60 years), sex (female), EF <50%, diabetes, severe obesity, lung disease, renal failure, recent myocardial infarction, redo and/or emergency surgery... The detection and peri-operative control of these factors permit a reduction of complications incidence and limit the length of stay; a better management of per-operative blood glucose in diabetic patients reduced significantly the morbidity. These factors are used in different scores, such as the Euroscore, which seems to be the best predictor of mortality. Patients stratification according to their risk profile permits to inform the patient and his/her family regarding the operative risk and take peri-operative therapeutic decisions, in order to reduce the morbidity and mortality during coronary artery bypass surgery.

Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.

Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta(2)-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta(2)-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, -1.8%; P < 0.01) and quality (-8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.

Results after orthotopic heart transplantation accepting donor hearts >50 years: experience at La Pitie Salpetriere, Paris.

INTRODUCTION: We sought to examine the results of orthotopic heart transplantation accepting hearts from donors >50 years of age with special regard to the usefulness of peripheral extracorporeal membrane oxygenation for posttransplant graft dysfunction. PATIENTS: Between January 2000 and December 2004, a total of 247 patients underwent orthotopic heart transplantation. In 143 patients (58%) the heart donor was <50 years (group I, mean age of donor hearts 36 +/- 11 years; range, 8-49 years). In 104 recipients (42%) the heart donor was >50 years (group II, mean age of donor hearts 56 +/- 15 years; range, 50-67 years). Pretransplant characteristics of the two groups showed no significant differences. RESULTS: The in-hospital mortality was slightly increased in group II (24% vs 20% in group I, NS) and the 5-year survival rate significantly increased in group I (75% vs 63% in group II). Freedom from transplant vasculopathy after 3 years was similar in both groups (86% in group I vs 87% in group II). A total of 25 patients (17%) in group I and 27 patients (26%) in group II developed graft dysfunction. Eleven patients in group I and 10 patients in group II were treated using peripheral extracorporeal membrane oxygenation, whereas 3 of the 11 patients in group I and 5 of the 10 patients in group II were discharged following a complete recovery. Two patients in group I and 4 patients in group II were survivors beyond year. CONCLUSION: In our experience it was possible to increase the cardiac donor pool by accepting allografts from donors >50 years of age in selected cases. The incidence of transplant vasculopathy was not increased, whereas in-hospital mortality was slightly higher. In our limited cohort, patients with older donor hearts was developed graft dysfunction profited from primary extracorporeal membrane oxygenation implantation, an indication that should be examined further without delay.

Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture.

INTRODUCTION: Animal studies suggest that bone remodeling is under beta-adrenergic control via the sympathetic nervous system. beta blockers have been suggested to stimulate bone formation and/or inhibit bone resorption in animals as well as to reduce the risk of fracture in humans. The purpose of this study was to examine if these agents can have a preventive or therapeutic effect in osteoporosis. MATERIALS AND METHODS: We have studied the association of beta blockers use with BMD, bone geometry, microarchitecture and fractures rates in postmenopausal women referred for bone density testing. From a total sample of 944 women, we identified 158 women who were taking beta blockers and 341 age-matched women as controls. Bone geometry was investigated at the femoral neck on DXA images. Microarchitecture was evaluated by the H mean fractal parameter at the calcaneus. RESULTS: The odds ratio for fracture (at all sites) in the beta blocker users was 0.56 (95% CI, 0.30-0.99). beta blocker use was associated with a higher BMD at the femoral neck (+4.2%, p<0.05) and L1-L4 (+3.2%, p<0.05). Proximal femur scans revealed significantly higher cortical width (+3.6%, p<0.05) at the femoral neck under beta blockers. Femoral shaft measurement did not significantly differ under beta blockers. Medication use and lifestyle factors indicated no association between beta blockers and smoking, alcohol use, physical activity, corticosteroids and estrogen therapies. The H mean parameter was significantly higher in the beta blockers group (0.619+/-0.029 vs. 0.607+/-0.023 in controls, p<0.05), suggesting a better trabecular microarchitectural organization. CONCLUSION: Our data suggest that the association of current use of beta blockers with low fracture risk is mediated, at least in part, by effects on BMD, cortical bone geometry and trabecular bone microarchitecture.

Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells.

The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na(+) absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na(+), Mg(2+), P, S and Cl(-)) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR(inh)-172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF.

[Pseudo-aneurysms of the ascending aorta in patients previously operated for acute aortic dissection]. / Pseudo-anévrismes de l'aorte ascendante chez les patients déjà opérés d'une dissection aortique aiguë. Diagnostic, traitement.

Pseudo-aneurysms of the ascending aorta are a rare but serious complication of surgery for acute dissection of the aorta. The diagnostic methods and surgical technique have changed in recent years. The authors report their experience over a period of 20 years. From January 1981 to December 2001, 21 patients underwent reoperation for pseudo-aneurysms of the ascending aorta. The average age was 54.2 +/- 3 years. Diagnosis is no longer based on aortography but on transthoracic or oesophageal multiplane echocardiography, thoracic spiral computed tomography or magnetic resonance imaging. Four patients presented with a recent history of severe pulmonary oedema. The risk associated with reopening the sternum is avoided by current operative techniques. The authors have chosen anterograde perfusion of the cervical arteries by direct canulation for cerebral protection. The operative mortality at one month is high (30%). All patients who had pulmonary oedema or cardiogenic shock in the immediate preoperative period died. There were no neurological complications. Twelve patients survived and one has to undergo a further operation for recurrence of the pseudo-aneurysm. The authors conclude that patients operated for dissection of the aorta must be followed up. It is important to resect as much as possible of the pathological aorta during the initial operation to avoid the risk of pseudo-aneurysm formation, at least in the proximal segment of the ascending aorta.

[Long term survival with the Bentall button operation in 150 patients]. / Suivi à long terme de l'opération de Bentall avec collerettes sur 150 patients.

Between May 1980 and May 2000, 150 patients (123 males and 27 females) underwent surgery with the same surgeon for ascending aortic replacement with a valvular conduit and coronary reimplantation with the aid of a collar of aortic wall (button technique). The average age was 50 +/- 16 years. Within this population, 114 patients had isolated annulo-ectasial disease, 36 had Marfan syndrome and 20 had dissection (5 acute and 15 chronic). A carbon fibre valve with 2 leaflets was implanted in 124 patients, a mono-leaflet valve in 20 and 6 others required a heterograft due to their age or a contra-indication to anticoagulation. The associated procedures were: 12 arch replacements, 5 myocardial revascularisations, 4 mitral replacements, 1 tricuspid plasty, 1 inter-atrial communication closure. In 30 patients (20%) there was a cardiovascular surgical re-intervention. The operative and first month mortality amounted to one sudden death on the 19th day, ie 0.6%. Three patients were lost to follow up. The average survival was 7.87 +/- 5.37 years (minimum 1, maximum 20 years). The actuarial survival was 85% at 10 years and 60% at 20 years. These figures are much higher than those reported in our previous statistics from 1994 when the percentage of survivors at 12 years was only 61%. In the group of patients undergoing surgery before 60 years of age, the survival at 14 years was 94% and 81% at 20 years. Only four late re-interventions were attributable to the Bentall procedure, of which 2 were left coronary ostium stenoses. The rate of thrombosis and embolism was 0.42 per 100 patient-years and the rate of haemorrhagic accidents was identical, including minor accidents. This considerable improvement in long-term prognosis is explicable by the adoption of a single operative technique, considered to be the best, with the best myocardial protection thanks to coronary retro-perfusion and cold or hot cardioplegia, and also without doubt with the best medical survival.

Gap junction communication between cells aggregated on a cellulose-coated polystyrene: influence of connexin 43 phosphorylation.

The appropriate functioning of tissues and organ systems depends on intercellular communication such as gap junctions formed by connexin (Cx) protein channels between adjacent cells. We have previously shown that Swiss 3T3 cells aggregated on hydrophilic cellulose substratum Cuprophan (CU) establish short linear gap junctions composed of Cx 43 in cell surface plaques. This phenomenon seems to depend on the high intracellular cyclic AMP (cAMP) concentration triggered by attachment of the cells to CU. We have now used a cellulose-coated polystyrene inducing the same cell behaviour to analyse the gap junction communication between aggregated cells. The transfer of the dye Lucifer Yellow (LY) between cells showed that cells aggregated on cellulose substratum rapidly (within 90 min) establish functional gap junctions. Inhibitors of cAMP protein kinase (PKI) or protein kinase C (GF109203X) both inhibited the diffusion of LY between neighbouring cells. Western blot analysis showed that this change in permeability was correlated with a decrease in Cx 43 phosphorylation. Thus, cellulose substrata seem to induce cell-cell communication through Cx 43 phosphorylation modulated by PKA and PKC. To understand the mechanisms by which a substratum regulates gap junctional communication is critically important for the emerging fields of tissue engineering and biohybrid devices.