Evaluation of the treatment costs and duration of topical treatments for multiple actinic keratosis based on the area of the cancerization field and not on the number of lesions.

BACKGROUND: The cost of topical treatments for actinic keratosis (AK) has historically been evaluated in relation to the number of lesions requiring treatment or simply by the price of a single tube/sachet of the drug used. OBJECTIVE: To demonstrate a new method of costing topical treatments in AK, which takes into account the actual cancerization area treated. METHODS: In order to evaluate the actual cost of each treatment, the official approval status of the drug was used to estimate the amount of cream needed per one cm2 . This value was then applied to the hypothetical cancerization area sizes to demonstrate the impact of the size treated on the actual cost of treatment. The price considered was the ex-factory price in Italy. RESULTS: Areas which could be treated with a single tube/sachet of Metvix® , Picato® , Aldara® , Solaraze® and Zyclara® were 200, 25, 25, 33.3 and 200 cm2 , respectively. For the treatment of smaller areas (<100 cm2 ), treatment with Metvix® was the most costly topical option in Italy. However, for the treatment of cancerization areas larger than 100 cm2 , Metvix® was the least expensive treatment option. Treatment with Metvix® was least long, requiring a single day of treatment for an area of up to 200 cm2 , compared with up to 224 days of treatment with Aldara® for the treatment of a similar size. CONCLUSION: Changing treatment costing strategy in the management of multiple AKs towards costing per cancerization area instead of costing per lesion is a much more accurate representation of the 'real world cost' for AK.

Performance of a biomass adapted to oncological ward wastewater vs. biomass from municipal WWTP on the removal of pharmaceutical molecules.

The performance of a biomass adapted to Oncological Ward Wastewater (OWW) in a membrane bioreactor (MBR) was compared with that of a municipal WWTP, on the removal of pharmaceutical molecules and more specifically on their overall resistance and purifying ability in the presence of pharmaceutical cocktails. Sorption and biotransformation mechanisms on two antineoplastics, one antibiotic and a painkiller were evaluated. Sludge acclimated to OWW allowed for a 34% increase in the removal rate and in the minimum inhibition concentration. The percentage of the amounts of specific pharmaceutical compounds removed by biotransformation or by sorption were measured. These results are positive, as they show that the observed removal of pharmaceutical molecules by biomass acclimated to OWW can mostly be attributed to developed biotransformation, unlike the biomass from the municipal WWTP for which sorption is sometimes the only removal mechanism. The biotransformation kinetic and the solid-water distribution coefficients in this study show good agreement with literature data, even for much higher pharmaceutical concentrations in OWW.

Satisfactory long-term MRI after autologous chondrocyte implantation at the knee.

PURPOSE: Autologous chondrocyte implantation (ACI) to address isolated condylar lesions is supposed to limit degenerative deterioration in neutrally aligned knees. Here, we report long-term results of the first-generation ACI technique with periosteal flap. METHODS: Twelve patients, 29 years old on average, were included on the basis of pre-operative MRI selection of lesions >2 cm2. Cartilage carrots were harvested arthroscopically, then cultured and finally re-implanted within a mean time interval of 12 weeks. Ten-year MRI results were analysed according to a semi-quantitative scale, along with functional assessment based on International Knee Documentation Committee score, Lysholm et al. score and the Tegner et al. activity scale. RESULTS: One patient secondarily required valgus tibial osteotomy with mosaic plasty. Another incurred graft hypertrophy that necessitated arthroscopic peeling. MRI showed that cartilage repair filled more than 50% of the initial defect in 9 patients. Standard radiographs revealed slight narrowing of the joint line. Overall, functional scores improved durably by 50%, although activity level decreased substantially. CONCLUSION: ACI contained degenerative changes within moderate stages while maintaining durable functional improvement. However, in the absence of controls, it was difficult to differentiate between these findings and the spontaneous evolution of non-treated lesions. LEVEL OF EVIDENCE: Case series, Level IV.

A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation.

We describe a large multigenerational multiple endocrine neoplasia Type 1 (MEN1) family with clinical expression suggestive of anticipation. In the second and third generations, two deceased obligate gene carriers died at the ages of 85 and 76 without the history of MEN1, whereas two other living gene carriers above the age of 65 have had no clinical evidence of MEN1 to date. In the fourth generation, eight members were affected, with four having severe MEN1-related and atypical malignancies: a case of metastatic endocrine pancreatic tumor, two cases of metastatic thymic carcinoids, and a case of spinal ependymoma. In the fifth generation, all five patients were below the age of 22 when the disease was detected. MEN1 was confirmed in the family by linkage analysis using MEN1-linked microsatellite markers and by identification of a nonsense mutation in the MEN1/menin gene. Alleotyping showed loss of heterozygosity (LOH) involving the wild-type alleles in seven tumors in the family including the ependymoma, which is the first MEN1-related case that shows genetic abnormality in chromosome 11q13, suggesting that MEN1 gene might be involved in the tumorigenesis of a subset of ependymomas. In relation to clinical anticipation, repeated expansion studies were carried out but failed to detect any expansion. We conclude that this is a unique MEN1 family and that an unknown genetic mechanism might be contributing to the anticipation phenomenon. We demonstrate in this family that all gene carriers, including the very young members, will need close and careful follow-up.

[Clinical and genetic study of a familial case of multiple endocrine neoplasia type 1 (MEN 1). From value of multidisciplinary collaboration]. / Etude clinique et génétique d'une famille prédisposée à la néoplasie endocrinienne multiple de type 1 (NEM 1). De l'intérêt d'une collaboration multidisciplinaire.

Multiple Endocrine Neoplasia type 1 (MEN 1) is an autosomal dominant familial syndrome characterized by involvement of several endocrine glands, including parathyroid, pancreatic islet cells, anterior pituitary and diffuse neuroendocrine tissues (carcinoids). The gene causing this syndrome has been localized to chromosome 11 but was not cloned up-to-date. Pre-clinical diagnosis in predisposed MEN 1 families was based on the use of genetic linkage analysis with polymorphic DNA probes flanking the disease locus. The set-up collaborative multi-disciplinar medical and surgical network facilitates further clinical and genetic studies on MEN 1 families. Semiological course of the disease is complex and the main objective in clinical follow-up of patients and related is to limit the probability of misdiagnosis. The present report describe the clinical and genetic analysis in a MEN 1 family and the difficulties related to diagnose the disease. An interesting observation on two cases of hyperprolactinemia by two individuals further excluded by genetic analysis assess the potential risk of bias in genetic linkage studies in non-well documented families. Concerted analysis of genetic and bio-clinical data permitted the evaluation of each patient and to exclude the risk of MEN 1 in all children tested. This example demonstrates the need of a complete clinical information previously to genetic analysis and a multi-disciplinar and collaborative approach in follow-up of patients in each family.

Multiple endocrine neoplasia type 1 in France: clinical and genetic studies.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by the involvement of several endocrine glands, including the parathyroid glands, the pancreatic islet cells, the anterior pituitary gland and other neuroendocrine tissues. In order to build up a French MEN1 register, a collaborative network was developed through the 'Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1' or GENEM 1. A 2-year follow-up in 40 medical and surgical units allowed the identification of more than 150 individual patients and 45 MEN1 families, and defined the major clinical features of the disease in our series. Multiple endocrine neoplasia type 1 is inherited as an autosomal dominant trait. The gene causing this syndrome has been localized to chromosome 11, band 11q13, and molecular genetic markers flanking the MEN1 locus are of use in identifying disease gene carriers in predisposed families. Selected data were presented in order to discuss the management of patients by combined clinical, biochemical and genetic screening. The set-up of a national register by a multi-disciplinary and collaborative medical and surgical network will facilitate further research on the clinical management of MEN1 patients and the basic physio-pathology of the disease.

[Cutaneous microvascular flow studied by laser-Doppler. A study of 100 healthy volunteers]. / Flux microcirculatoire cutané étudié par laser-doppler. Etude sur une population de 100 sujets volontaires sains.

Cutaneous capillary flow (tip of the 3rd right finger) was measured with a laser Doppler (Periflux, Perimed), in 100 healthy volunteers without any history of hypertensive or vasospatic diseases, 15 females smoke and were taking contraceptive drugs. Smokers (n = 16 M, 25 F) stopped smoking 3 hours before the study. Basal laser Doppler flux (BLDF), amplitude of vasomotion waves (AV), post-occlusive reactive hyperthermia peakflow (F Max), difference between BLDF and F Max (delta F Max), time to reach 50 percent of the initial value (t1/2 r) and total recovery (tr), t Max (peak of over-shoot) and t/2 over shoot were measured. F Max after heating stimulus (40 degrees) (f Max H), delta F Max H (difference between BLDF and F Max H) and t Max H time (mn) to reach F Max H were measured before a cold stimulus was applied. Results were expressed in arbitrary units (cvolts), BLDF showed inter-individual variation but was reproducible over months in the same subject. The basal flux was statistically different between males (352.7 +/- 21.7) and females (249.6 +/- 22.4). Spontaneous vasomotion waves and different times (in sec.) to reach the peak after three minutes of arterial occlusion could be measured with this technique. These normal range of values can allow comparison and assessment of variations in pathological conditions, mainly Raynaud's phenomenon, high blood pressure, diabetes, smokers, sickle-cell anemia. Acute pharmacological tests can be carried out with drugs showing specific action on microcirculation and spontaneous vasomotion.

[Gonadotropic pituitary adenoma and pregnancy. Value of bromocriptine]. / Grossesse chez une femme traitée pour adénome gonadotrope. Intérêt de la bromocriptine.

The authors report a case of pituitary adenoma with positive immunospecific staining for beta-FSH and serum alpha subunit. The tumour was revealed by an amenorrhoea-galactorrhoea syndrome with hyperprolactinaemia and without increase in serum gonadotrophin values. Pregnancy occurred during bromocriptine treatment which made it possible to control an hemianopsia developed in the fourth month of gestation. The adenoma was successfully removed a few months later.

Hyperthyroidism due to selective pituitary resistance to thyroid hormones in a 15-month-old boy: efficacy of D-thyroxine therapy.

A 15-month-old boy had clinical features of hyperthyroidism. In spite of elevated serum thyroid hormone levels (mean serum T4, 230 nmol/L; T3, 4.2 nmol/L), serum TSH levels ranged between 3.3-5.6 mU/L and rose to 35.4 mU/L after TRH stimulation. There was no abnormal serum thyroid hormone binding or any evidence of a pituitary tumor. The boy was treated with carbimazole for 6 months and became euthyroid. However, his thyroid size enlarged, and serum TSH rose to 45 mU/L. In an attempt to suppress TSH secretion, 3,5,3'-triiodothyroacetic acid was added to carbimazole in daily doses from 0.7-1.4 mg. This combined therapy failed to suppress TSH secretion (serum TSH, 10.2 mU/L) and led to recurrence of symptoms of hyperthyroidism. A trial using highly purified dextrothyroxine (contamination by L-T4, 0.05%) as sole therapy then was carried out. Serum TSH levels promptly declined to normal, both basally and after TRH stimulation (basal, 2.4 mU/L; peak, 13.8 mU/L). During a 24-month follow-up period, the boy remained euthyroid. Serum TSH levels remained in the normal range, as did his serum L-T4 levels (93 nmol/L). Complete remission was achieved using a 5-mg daily dose of D-T4. Temporary discontinuation of D-T4 led to prompt relapse of hyperthyroidism. Our patient's TSH hypersecretion appears to be due to selective pituitary resistance to thyroid hormones. Purified D-T4 effectively inhibited TSH secretion in this patient, without inducing significant side-effects, even when the daily dose was high. The cause of partial pituitary unresponsiveness to thyroid hormones is not known. We suggest that transport of thyroid hormones into the thyrotroph cells could be deficient in our patient.

[Inappropriate thyrotropin secretion. Part 1: tumoral (author's transl)]. / Sécrétion inappropriée de thyréostimuline. 1re partie: production tumorale.

Release of thyroxine and triiodothyronine from the thyroid gland is stimulated by the pituitary hormone thyrotropin, or thyroid-stimulating hormone (TSH). TSH secretion in turn is regulated by control mechanisms, which include a negative feedback effect of the thyroid hormones themselves and the actions of the hypothalamic peptide TRH and of several central neurotransmitters. Hyperthyroidism secondary to excessive TSH secretion is a rare entity. In most cases TSH hypersecretion results from an adenoma of the pituitary gland and may then be associated with increased prolactin or growth hormone production. It should be emphasized that most patients with pituitary adenoma have high serum levels of alpha TSH subunit and undetectable beta TSH subunit.

[Inappropriate thyrotropin secretion. Part 2: non tumoral (author's transl)]. / Sécrétion inappropriée de thyréostimuline. 2e partie: production non tumorale.

Some patients are clinically euthyroid despite high thyroid hormones levels associated with detectable but not elevated serum TSH. These patients are considered as being resistant to thyroid hormones. The resistance may be severe or partial and in most cases seems to be autosomal dominant; it affects some tissues more than others, thus giving rise to a variety of clinical symptoms. In a few patients with high TSH levels extensive studies have failed to provide evidence of pituitary tumour of resistance to thyroid hormones; the cause of TSH hypersecretion in such cases remains uncertain. Several factors (non specific serum proteins, cross-reactivity circulating antibodies) may result in falsely high T3, T4 and TSH values on radioimmune assays and must be carefully investigated in the presence of unexpectedly high serum TSH levels.

[Male pseudohermaphroditism. State and present problems (author's transl)]. / Situation et problèmes actuels du pseudohermaphrodisme masculin.

The authors describe the male phenotypic sexual development in the fetus: transformation of the undifferentiated gonad into testis under the HY antigen influence; testicular secretion of testosterone (which allows the development of the wolffian ducts derivatives) and of MIF (which inhibits the development of the mullerian duct; masculinization of the external genitalia under the influence of dihydrotestosterone. They outline the three abnormalities which may lead to a male pseudohermaphroditism: disorders of testicular differentiation, defects of testicular function and androgen insensitiveness at the target areas. They consider the diagnostic steps and the therapeutic management especially in relation to the choice of the sex and the risk of gonadoblastoma.

[Classification and metabolic relationship of plasma apoproteins (author's transl)]. / Données actuelles sur les apoprotéines.

The apoproteins are the constitutive peptides of the plasma lipoproteins. The most widely employed nomenclature is that based on the family concept of constitutive polypeptides. The apoproteins are synthetized in the liver and/or in the intestine. During the lipolysis, apoprotein transfers and/or exchanges are observed. The apoproteins play a major role in the structure of the macromolecular lipid-protein complexes, and in the activity of several enzymes involved in the lipoprotein catabolism. An expanding information on apoprotein metabolism will allow a better comprehension of the hyperlipidemia pathogenesis.

[Intrasellar chordoma (author's transl)]. / Les chordomes intra-sellaires. Principaux aspects cliniques, biologiques, radiologiques, évolutifs et histologiques. A propos de deux observations.

The authors present two cases of intrasellar chordoma and review these tumor's most important characters. This intrasellar localization seems to be very rare. Endocrinological disorders, when observed, leads only to insfufficiency and never to hypersecretion. Final diagnosis is established by histological studies. Their volume is important, so that the recurrence after surgery is common and the middle term prognosis is bad.