Clinical and pathological characteristics of melanoma: a population-based study in a French regional population.

BACKGROUND: Although incidence and mortality data are numerous, population-based studies including clinical and pathological characteristics of melanoma are rare. OBJECTIVES: To describe the characteristics of melanoma in a rural French region during 2004-2008 and to identify differences according to age, gender and geographical areas. METHODS: Pathology reports of cutaneous melanomas diagnosed in residents from the Champagne-Ardenne region during 2004-2008 were anonymously collected from pathology laboratories. Demographic, clinical and pathological data were extracted and analysed by experts, including dermatologists, pathologists and epidemiologists. RESULTS: One hundred and seventy-seven in situ melanomas were diagnosed in 177 patients (female/male ratio : 1.72). Patients with head and neck in situ melanomas were older than patients with melanomas in other locations (72 vs. 54 years; P < 0.0001). Six hundred and sixty-one invasive melanomas were diagnosed (female/male ratio : 1.26), corresponding to an annual incidence rate of 6.3/100,000. Male patients had thicker and more frequently ulcerated tumours. The location widely varied between genders, involving the trunk in 47% of male patients and the lower limb in 48% of female patients. Older patients had thicker and more advanced melanomas, with a more frequent head and neck location. Nodular, acral lentiginous and unclassified melanomas were much thicker than superficial spreading and lentigo maligna melanomas (4.37 vs. 1.33 mm, P < 0.0001). Primary melanomas of advanced stages were more frequent in one of the four districts of the study area. Overall, the mean Breslow thickness (2.02 mm) was much higher than that previously observed in other regions of north-eastern France (1.59 mm). CONCLUSIONS: Information and screening campaigns should particularly target rural areas, males, older people and focus on nodular, acrolentiginous and unclassified subtypes.

Characterization and comparison of bone marrow and peripheral blood mononuclear cells used for cellular therapy in critical leg ischaemia: towards a new cellular product.

BACKGROUND AND OBJECTIVES: Autologous transplantation of either bone marrow (BM) or peripheral blood (PB) mononuclear cells (MNC) induces therapeutic angiogenesis in patients with peripheral arterial occlusive disease. Yet, the precise nature of the cellular product obtained from BM or PB and used in these therapeutic strategies remains unclear. MATERIALS AND METHODS: We have analysed the characteristics of BM-MNC and PB-MNC collected without mobilization and implanted in patients with critical limb ischaemia in a clinical trial of cellular therapy including 16 individuals treated by BM-MNC and eight by PB-MNC. These MNCs were characterized by cell counts, viability assessment and enumeration of leucocyte subsets, CD34 stem and endothelial progenitor cells (EPCs) (CD34+/CD133+/VEGF-R2+) by flow cytometry. Mean fluorescence intensity ratios were determined for CD34, CD133 and VEGF-R2 markers. All analyses were simultaneously performed in two laboratories. RESULTS: Accuracy and reliability between both laboratories were achieved. BM-MNCs and PB-MNCs were quantitatively and qualitatively heterogeneous and quite different from each other. Stem cells and EPCs were significantly more present in BM- compared to PB-cell products, but with similar mean fluorescence intensity ratios. A weakly positive correlation was observed between CD34+ cell counts and EPCs levels, confirming the specificity of cell identification. CONCLUSION: A great variability was observed in cell product characteristics according to their origin and also between individuals. These data stress the necessity of optimal characterization of cell products especially in multicentric clinical trials.

Increased risk of colonic neoplasia in patients with sporadic duodenal adenoma.

BACKGROUND: Recent studies have shown an increased risk of colorectal neoplasia in patients with duodenal neoplasia. The aim of this retrospective case-control study was to confirm this risk. PATIENTS AND METHODS: Rate of colorectal neoplasia in 29 patients with one or more duodenal adenomas were compared with controls matched for gender and age, but without duodenal adenomas (one case to two controls). Patients with neoplasia of the ampulla, familial adenomatous polyposis or other known hereditary conditions of the digestive tract were excluded. Indications for upper and lower gastrointestinal endoscopy in controls were abdominal pain or changes in bowel habits. Controls with anemia or digestive bleeding were not included. Neoplastic lesions found at colonoscopy were classified as adenomas, advanced adenomas (size > or =10 mm, villous component, high-grade dysplasia), cancers and advanced neoplasia (cancers and advanced adenomas). Comparison between groups was by Fisher's exact test or Student's t test. Odds-ratios (OR) and 95% confidence intervals were calculated, if the difference was significant. RESULTS: Mean age of the 29 cases (seven women, 22 men) was 63.2 years and that of the 58 controls (14 women, 44 men) was 62.5 years. First-degree family history of colorectal cancer was present in four cases (13.8%) and eight controls (13.8%) (NS). Colonoscopy showed at least one adenoma in 15 cases (51.7%) and 11 controls (19%) (P=0.0027; OR 1.87, 1.0-3.49), advanced adenomas in four cases (13.8%) and three controls (5.2%) (NS), and colonic adenocarcinoma in three cases (10.3%) and no controls (0%) (P=0.03). Advanced neoplasia was present in seven cases (24.1%) and three controls (5.2%) (P=0.014; OR 2.86, 0.96-8.52). Results were not significantly modified after the exclusion of patients with a family history of colorectal cancer. CONCLUSION: Although lacking in statistical power, these results confirm that patients with sporadic duodenal adenoma are at high risk of colonic adenoma and advanced neoplasia, warranting systematic colonoscopy.

[Surgical treatment of hidradenitis suppurativa: a retrospective study of 93 cases]. / Maladie de Verneuil: étude rétrospective chez 93 malades traités chirurgicalement.

INTRODUCTION: Hidradenitis suppurativa is a chronic disease, severe forms of which may be highly invalidating. Although wide surgery is usually considered the most effective curative therapy, few medical teams in France have extensive experience of this approach. Our aim was to evaluate the clinical history and the results of surgery in all patients operated with curative intent in an experienced centre. PATIENTS AND METHODS: Medical records were reviewed for all patients operated between January 1985 and January 2007. In addition, the patients were contacted by telephone and/or letter and asked about their clinical history, the repercussions of their disease on their daily lives, postsurgical relapse and their overall satisfaction regarding surgery. Separate analyses were carried out for patients and for individual operated sites. RESULTS: Of 93 patients followed-up for between one and 205 months (mean: 30 months), 209 anatomical sites were operated with curative intent, using either limited excision (i.e. including all visible lesions without margins) or wide excision (i.e. including all lesions with a significant margin). The disease had been present for an average of 7.6 years before surgical treatment, with onset seven years earlier in women. Most patients had previously received multiple and often unsuitable medical treatments. Patients' personal and professional lives were highly affected. Surgery required hospitalization for an average duration of 6.6 days, caused complications in 21% of cases and was often perceived as trying. Relapse in the operated areas occurred in 33% of cases and this was more frequent after limited excision. Nevertheless, 74% of patients were ultimately satisfied with their surgical treatment and most regarded surgery as the only really effective therapy. DISCUSSION: Our study confirms the heavy repercussions of hidradenitis suppurativa on patients' day-life as well as the value of surgical management by experienced surgeons. CONCLUSION: Wide excision remains the mainstay of therapy in extensive forms of hidradenitis suppurativa. However, this chronic, disseminated and recurrent disease continues to be insufficiently understood and innovative medical approaches, including the development of clinical trials, are required.

Predictive value of sequential maternal anti-HPA-1a antibody concentrations for the severity of fetal alloimmune thrombocytopenia.

BACKGROUND: Fetal/neonatal alloimmune thrombocytopenia results from maternal immunization against fetal platelet alloantigens (HPAs), and the major risk is intracranial hemorrhage. The severity of thrombocytopenia increases in subsequent pregnancies, and antenatal therapy has been developed. Until now, the fetal status can only be assessed by fetal blood sampling, which carries a risk of fetal loss or premature delivery. OBJECTIVES: To develop non-invasive methods to gain information on the fetal condition. PATIENTS/METHODS: Quantification of the maternal anti-HPA-1a alloantibody concentration was performed with a standardized monoclonal antibody-specific immobilization of platelet antigens (MAIPA) procedure for 43 mothers. A correlation between this concentration and the fetal/neonatal platelet counts was studied. RESULTS: (i) Before antenatal therapy, there was a significant correlation between maternal anti-HPA-1a concentrations > or =250 AU mL(-1) and fetal thrombocytopenia (2-66 x 10(9) L(-1)) whatever the gestational age (Fisher's exact test P = 0.0021). (ii) During subsequent pregnancies, we observed a decrease of the maternal anti-HPA-1a concentration for 14/19 women. Just before delivery, all women had anti-HPA-1a concentrations <250 AU mL(-1). In four cases, there was a therapy failure and the severely thrombocytopenic babies required postnatal therapy. CONCLUSION: The maternal anti-HPA-1a concentration could provide obstetricians with clinically useful information concerning the appropriateness and the timing of invasive monitoring procedures. However, though we observed a tendency toward a decrease in maternal antibody concentration after treatment, this finding does not allow us to draw any conclusions on the effectiveness of therapy.

Evidence that mouse astrocytes may be derived from the radial glia. An immunohistochemical study of the cerebellum in the normal and reeler mouse.

Astrocytic cells of unusual aspect can be detected in the cerebellum of normal mice during the first 4 weeks of life. They are visualized with anti-GFAP (glial fibrillary acidic protein), anti-S100 and anti-vimentin immune sera. Their perikaryons, located in the white matter or in the granular layer, extend long processes which are inserted onto the pial surface. These cells may be transitional forms between the radial glial cells and some of the differentiated astroglial elements. These unusual astrocytes are more numerous and heavily stained in the reeler mutant than in the normal mouse and it is suggested that our observations signify some degree of glial immaturity in the cerebellum of the mutant.

Partial expression of monoaminergic (serotoninergic) properties by the multipotent hypothalamic cell line F7. An example of learning at the cellular level.

A serum-free medium supplemented with a glial conditioned medium, a brain extract from 8-to 10-day-old mice, hormones, and eye-derived growth factor has been devised which permitted the mouse primitive hypothalamic nerve cell line F7 to express some biochemical properties typical of monoaminergic neurons. Maximal expression was obtained when the culture conditions were applied for 2 days. Most (90-95%) cells then synthesized [(3)H]serotonin from [(4)H]5-hydroxytryptophan (but not from [(3)H]tryptophan). No synthesis was detected in the presence of carbidopa (20 ?M), therefore suggesting the involvement of l-aromatic-amino-acid decarboxylase in this process. In addition, F7 cells cultured in such serum-free medium exhibited the capacity of accumulating exogenous serotonin by an ouabain-sensitive mechanism. These data further supported that active molecules in the cell environment can induce, in a primitive cell line, some of the enzymatic activities associated with monoaminergic neurons. Since other well-defined culture conditions can promote the differentiation of the same clone into oligodendrocytes (De Vitry et al., 1983), it can be concluded that the F7 cell has the properties of an embryonic stem cell of the CNS which, depending on external signals, may switch into different alternative developmental neural pathways. We postulate that the stabilization of neuron-like properties due to repetitive cell stimulation by active signals in the environment may represent an example of learning at the cellular level.

Neuronal localization of 5-HT1A receptor mRNA and protein in rat embryonic brain stem cultures.

The aim of the present work was to study the cellular localization of 5-HT1A receptor protein and mRNA in rat embryonic brain cultures. Primary cultures of the whole brain from rat fetuses at embryonic day (ED) 12 and of the brain stem at ED 14-ED 16 were stained with specific anti-5-HT1A receptor antibodies or a 40-mer biotin-labelled deoxyoligonucleotide complementary to the 5-HT1A receptor mRNA. The use of a biotinylated probe allowed the morphology of the cells to be preserved. 5-HT1A receptor mRNA was already detected in primary cultures from the brain of ED 12 embryos whereas the receptor protein first appeared two days later, at ED 14. Both 5-HT1A receptor mRNA and protein were found within neuron-like cells (labelled with antibodies against neuron specific enolase, microtubule-associated protein 2 or aromatic L-amino acid decarboxylase) but not in glial cells (specifically labelled with antibodies against glial fibrillary acidic protein, myelin basic protein or carbonic anhydrase II). Double staining with the 5-HT1A receptor mRNA probe and anti-5-HT antibodies suggests that 5-HT1A (auto)receptors are expressed by serotoninergic neurons during early ontogenesis.

Dopamine increases the expression of tyrosine hydroxylase and aromatic amino acid decarboxylase in primary cultures of fetal neurons.

Previous studies, aimed at identifying which diffusible signals may influence the differentiation of embryonic neurons towards the monoaminergic phenotypes during brain development, have shown that serotonin itself could promote the 'serotoninergic-like properties' of hypothalamic cells from mouse embryos. We presently reinvestigated such 'autocrine/paracrine' regulatory mechanisms by exposing dissociated cell cultures from embryonic rat hypothalamus and brain stem to dopamine--or related agonists--in an attempt to influence their differentiation towards the catecholaminergic phenotype. Chronic treatment of cells by dopamine or apomorphine (a mixed D1/D2 agonist), but not selective D1 and D2 agonists, significantly increased the number of cells that expressed tyrosine hydroxylase (TH: as assessed with a specific anti-TH antiserum) and the activity of aromatic L-amino acid decarboxylase (AADC) in the cultures. Furthermore, apomorphine treatment also decreased the levels of cholecystokinin-like material in primary cultures from the brainstem (but not the hypothalamus) where both dopamine and cholecystokinin are--partly--colocalized in mesencephalic dopaminergic neurons. The maximal effects of both dopamine and apomorphine on TH expression and AADC activity occurred earlier in the brainstem (on cells from 14- to 15-day-old embryos) than in the hypothalamus (on cells from 15- to 16-day-old embryos), in line with the well established caudo-rostral maturation of the rat brain. Furthermore both the expression and the dopamine-induced modulation of AADC activity and TH immunoreactivity appeared to occur independently of each other. Present and previous data are in agreement with a possible autocrine/paracrine action of dopamine and serotonin during brain development.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular recording from hypothalamic neurosecretory cells in tissue culture (clone HT9-C7).

Electrophysiological and pharmacological studies have been performed on a clone of mouse hypothalamic neurosecretory cells synthesizing neurophysin and vasopressin (HT9-C7). These neurons possessed low resting membrane potential (RMP) and weak membrane resistance (MR). They did not exhibit spontaneous activity. Electrical stimulation or microiontophoretic application of putative neurotransmitters did not induce action potentials. Nevertheless, dopamine and gamma-aminobutyric acid appeared to exert a slight hyperpolarizing effect on RMP. Radioimmunoassays, carried out on the culture medium after electrical stimulation, did not reveal any measurable quantities of vasopressin. However, an electron microscopic analysis of the cytoplasmic processes of these cells did not reveal axonal outgrowth. It can be assumed that the weak electrophysiological and pharmacological properties of these neurons have to be related to their weak morphological differentiation. Two hypotheses might account for the absence of most characteristics of in situ magnocellular hypothalamic neurons in HT9-C7 cells: the lack of pituicytes, the target cells for the axon terminal of magnocellular neurons, and the SV40 transformation itself which may impede neuronal maturation.

Dorsally displaced distal radius fractures: comparative study of Py's and Kapandji's techniques.

INTRODUCTION: Within the framework of a regional clinical study, the radiographic results of Py's and Kapandji's fixation techniques for dorsally displaced distal radius fractures were compared. PATIENTS AND METHODS: A prospective randomised monocenter and multi-operator study (phase III clinical trial) comparing the Py's (isoelastic pinning) and Kapandji's (intrafocal pinning) techniques was conducted. Two comparable groups were established: the Py (P) and Kapandji (K) groups. The frontal radial tilt (FRT), sagittal radial tilt (SRT), radial length and ulnar variance were measured. Analysis of subjective and objective function was based on the range of motion according to six parameters, the DASH and Jakim scoring systems. The quality of anatomical restoration was assessed arthroscopically during pin removal at 6 postoperative weeks. RESULTS: Ninety-seven patients were included in the study with a follow-up period of 1 year. The preoperative FRT was 15.17° and SRT was -19.2°. At one-year follow-up, the FRT was 25.5° in the PY group and 22.6° in the K group (p=0.009), the SRT was 10.5° in the PY group and 6.7° in the K group (p=0.04). For fractures with postero-medial fragment and Gerard Marchand's fractures, the DASH score at last follow-up was 22 in the Py group, 42 and 32 respectively in the K group. The Jakim score was 71 in the PY group and 58 in the K group (p=0.03) for fractures with postero-medial fragment. There was no report of tendon rupture in our study. DISCUSSION: Besides the good results achieved with both pinning techniques in the treatment of distal radius fractures, this series also underlines the importance to adapt the type of fixation to the fracture pattern and patient. CONCLUSION: Pinning for treating dorsally displaced distal radius fractures appears a suitable option provided that the indications and the surgical technique for each method are respected. However, pinning is not suitable for all types of fractures. LEVEL OF EVIDENCE: Level II. Randomised prospective therapeutic study.

Immediate anatomic results after the endovascular treatment of unruptured intracranial aneurysms: analysis of the ATENA series.

BACKGROUND AND PURPOSE: A precise analysis of the immediate postoperative anatomic results in a large series of unruptured intracranial aneurysms treated by endovascular approach has not previously been presented. This study aimed to assess the efficacy of endovascular treatment of unruptured intracranial aneurysms in light of immediate postoperative anatomic results in a prospective, multicenter study (the Analysis of Treatment by Endovascular Approach of Nonruptured Aneurysms study; ATENA). MATERIALS AND METHODS: Postoperative anatomic results from digital subtraction angiography (DSA) were evaluated with the Montreal scale by the treating physician and by 2 anonymous, independent, experienced neuroradiologists. RESULTS: The analysis included 622 patients (449 women, 173 men; age range, 22-83 years; mean age, 51.2 +/- 11.3 years) harboring 694 aneurysms. Evaluation of the postoperative anatomic results by the 2 independent reviewers indicated total occlusions in 437 aneurysms (63.0%), neck remnants in 156 aneurysms (22.5%), and aneurysm remnants in 101 aneurysms (14.6%). Several factors favorably affected the quality of the aneurysm occlusion with treatment, including patient age (< 65 years old; P < .0001), aneurysm diameter ( 1.5; P = .0388), and endovascular technique (coiling or remodelling compared with stent placement; P = .0001). CONCLUSIONS: The endovascular treatment of unruptured aneurysms provided satisfactory postoperative occlusion rates, with a high percentage of complete occlusion or neck remnants (85.4%). Postoperative anatomic results were significantly affected by aneurysm size and neck size, but not aneurysm location.

Similar safety in centers with low and high volumes of endovascular treatments for unruptured intracranial aneurysms: evaluation of the analysis of treatment by endovascular approach of nonruptured aneurysms study.

BACKGROUND AND PURPOSE: The outcome of treatment for unruptured intracranial aneurysm by surgery or endovascular therapy appeared to be related to the volume of patients treated by the hospital. We performed an analysis in the ATENA series to determine whether the outcome of endovascular treatment was different in hospitals with low and high volumes of cases. MATERIALS AND METHODS: The ATENA series included 649 patients with 739 unruptured intracranial aneurysms. Patients were classified into 2 groups. Group A had 171 patients with 197 aneurysms in 13 centers that treated < or =20 patients; group B, 478 patients with 542 aneurysms in 14 centers that treated > or =21 patients. RESULTS: Groups A and B had similar patient populations and aneurysm characteristics. Stent placement was used in group B more frequently than in group A (9.6% versus 2.5%, P = .0016). The global rate of adverse events was not significantly different in groups A and B (16.0% and 14.4%, respectively). Thromboembolic events and intraoperative rupture were not significantly more frequent in group A than in group B. One-month mortality and morbidity rates were not significantly different in groups A (2.3% and 1.8%, respectively) and B (1.0% and 1.7%, respectively). Anatomic outcomes for groups A and B were not significantly different. CONCLUSIONS: Clinical and anatomic outcomes of endovascular treatments for unruptured intracranial aneurysms were similar in hospitals with low and high volumes of cases.

Ultrastructural and cytochemical features of SV 40 transformed hypothalamic cell lines.

A continuous cell line was previously obtained by Simian Virus (SV) 40 transformation of primary cultures of dissociated mouse fetal hypothalami. One clone from this cell line has been previously shown to possess some of the ultrastructural features, immunological properties and synthesizing capacities of magnocellular hypothalamic neurons which secrete vasopressin and neurophysins. The present paper reports on the morphological characterization of 14 other clones or subclones of the original cell line, using the following criteria: phase contrast microscopy, electron microscopy, Gomori's aldehyde fuchsin staining, cytochemical detection of beta-glucuronidase, immunochemical staining with antisera against bovine neurophysin I, bovine neurophysin II, lys-vasopressin, oxytocin, LH-RH and TRH. The results allowed the conclusion that the clones as well as the subclones can be distributed into two groups: 1) neurosecretory neurons which all possess several of the ultrastructural and cytochemical features of the neurophysin-vasopressin synthesizing clone, and 2) primitive nerve cells which are devoid of such features but display numerous bundles of filaments. In addition some clones were found to display intermediate features between groups 1 and 2. A similar diversity was observed within clones of the original strain and subclones of a neurosecretory clone. It is suggested that the primitive clones could represent precursors of the neurosecretory clones.

Myogenic cells in the rat embryonic brain stem.

The principal finding of this study is the establishment of culture conditions that permit the survival of a very limited population of muscle precursor cells from the embryonic and neonatal rat brain stem, with these cells displaying the capacity to differentiate into contractile striated fibers under these in vitro conditions. Examination of desmin and troponin T expression by immunoperoxidase analysis revealed the presence of the two muscle proteins in the mononucleated precursors and in differentiated multinucleated myotubes. In vivo, examination of sections at corresponding stages revealed the simultaneous presence of troponin T, desmin, and lectin binding sites--a property of endothelial cells--association which appears to be transitory, since it is no longer detectable in the adult brain. The presence of the choroid plexus neuroepithelium, in close vicinity with TnT+, desmin+cells located in a limited zone of the brain stem, as well as the stage of expression for these markers suggest an interaction between brain myogenic cells and the onset of the embryonic circulation. The question of the embryological origin of the brain myogenic cells is discussed.

Immunological detection of somatostatin in a primitive hypothalamic mouse cell line, precursor of a neurophysin cell lineage.

A primitive nerve cell line (F7 clone), obtained by SV 40 transformation of mouse fetal hypothalamic cells, has been previously shown to share some properties with a progenitor cell for neurophysin synthesizing neuron. This paper describes the immunological detection, at the light microscope level, of somatostatin in this cell line. A SV 40 transformed neurosecretory clone, synthesizing neurophysin and vasopressin, was used as control.

Serotonin initiates and autoamplifies its own synthesis during mouse central nervous system development.

Some cells from cultured embryonic mouse hypothalamus were found to express aromatic-L-amino acid decarboxylase (EC 4.1.1.28) activity and serotonin uptake and storage. These neuron-like cells differed from serotoninergic neurons in cultured embryonic mouse brain stem since they did not contain tryptophan hydroxylase. We studied the effect of the serotonin agonist 8-hydroxy-2-[di-(n-propyl)amino]tetralin on neuronal differentiation of hypothalamic cells from 12- to 15-day embryos. Repeated treatment of cultures with the serotonin agonist for 10 days resulted in an increased number of serotonin cells containing high levels of decarboxylase activity. Both the increase in cell numbers and the elevated decarboxylase activity could be suppressed by the addition of the serotonin antagonist metergoline to the culture medium. These data show that serotonin (or an agonist), acting on specific receptors, can initiate and amplify its own synthesis in embryonic hypothalamic neurons, as observed in the primitive hypothalamic nerve cell line F7 [De Vitry, F., Catelon, J., Dubois, M., Thibault, J., Barritault, D., Courty, J., Bourgoin, S. & Hamon, M. (1986) Neurochem. Int. 9, 43-53]. Such an autocrine-like mechanism may be active during nervous system development and may represent an example of learning at the cellular level.