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.

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.

Physical mapping of rDNA and heterochromatin in chromosomes of 16 Coffea species: a revised view of species differentiation.

The chromosome organization among 15 wild diploid Coffea species and cultivated tetraploid C. arabica was determined by fluorochrome banding (CMA, DAPI) and double fluorescence in-situ hybridization (FISH) of 5S and 18S rDNA achieved on the same chromosome plates. Two to five chromosome pairs (plus one putative chromosome B) are marked. Overall, there are two SAT-chromosome pairs for East African species and one for the Malagasy and the West and Central African species. 18S rDNA loci are telomeric and strongly marked the SAT-chromosome pairs. Generally, only one pericentromeric 5S rDNA locus characterized East African species, while an additional minor locus co-localized with the 18S rDNA-SAT locus for the Malagasy species and West and Central African species. A combination of rDNA FISH plus CMA and DAPI banding patterns enables identification of almost all the species, even those for which the genetic or botanical status is still being discussed. C. arabica clearly appears to be an allotetraploid species, including one genome from East Africa and one from West and Central Africa. However, since the minor 5S rDNA-SAT locus present in West/Central African genomes is not detected, two evolutionary hypotheses could be put forward for C. arabica. Considering only the diploid species, global trends are obvious in rDNA signal patterns, genome size variations, and geographic distribution of the species, but there are no clear evolutionary trends. However, complex interactions between these factors and environmental growing conditions exist, which have resulted in loss and gain of rDNA loci and probably also in copy repeat number variations in each rDNA family.

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.

Evaluation of Maize Inbreds for Maize stripe virus and Maize mosaic virus Resistance: Disease Progress in Relation to Time and the Cumulative Number of Planthoppers.

ABSTRACT Five tropical maize lines were tested and compared with the susceptible control line B73 for resistance to Maize stripe virus (MStV) and Maize mosaic virus (MMV), both propagatively transmitted by the planthopper Peregrinus maidis (Homoptera: Delphacidae). Resistance to each virus was evaluated separately by artificial inoculations with planthoppers viruliferous for either one virus or the other. Disease incidence and symptom severity progression were quantified in relation to time and the cumulative number of planthoppers. Line Hi40 was found to be susceptible to MStV and highly resistant to MMV. Generally, no MMV symptoms developed on Hi40, even under intense inoculation pressure by a large number of viruliferous planthoppers. Line Rev81 showed a partial but strong resistance to MStV, which mainly reduced disease incidence. Nevertheless, this resistance to MStV was the highest ever reported and held up, even when challenged by large numbers of planthoppers. The percentage of infected plants in line Rev81 never exceeded 30 to 40% in our experiments. Moderate levels of resistance to MStV, and to a lesser extent MMV, were found in lines 37-2, A211, and Mp705. However, resistance in these lines was completely overcome using a large number of insects transmitting either of the two viruses. These results suggest that different types of resistance to MMV and MStV are available in maize lines from Caribbean and Mascarene germ plasm. The expression of virus-specific resistance identified in Hi40 and Rev81 lines was not affected by intense inoculation pressure. In contrast, the moderate resistance in 37-2, A211, and Mp705 was partially effective against both viruses but not at high inoculation pressure. These different types of resistance, when present in the same genotype, could provide protection against both viruses.

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.

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.

[Conjunctival and peri-ungual angioscopy in noninsulin-dependent diabetes mellitus. Informational value of observed anomalies]. / Angioscopies conjonctivales et péri-unguéales dans les diabètes non insulino-dépendants. Valeur informationelles des anomalies observées.

Microangiopathy is one of the most frequent and serious complications of diabetes. Its diagnosis is based on fundus of eye and fluorescein angiography findings, but several teams have emphasized the value of conjunctival angioscopy (CA) and peri-ungual capillaroscopy (PUC), describing suggestive anomalies: microectatic venous dilatation (V/A greater than 4.5), sludge on CA, "fish shoal" capillaries on PUC. Up to the present, however, the diagnostic value of these anomalies has not been evaluated based on data that are sensitive, specific and indicate predictive positive and negative values of a sign (Se, Sp, PPV, NPV). Anomalies of CA and PUC as a function of presence or absence of "diabetes" were studied in 114 patients with moderate hypertension, including 46 "diabetics" (33 with glucose regulation disorders and 13 non-insulin dependent diabetics). "Diabetes" was observed more predominantly in males of more advanced age and with a significantly higher global CA score (4.25 +/- 1.44 as against 2.65 +/- 1.35), and this in an increased manner as the "diabetes" was severe. Some anomalies had themselves a major orientation value with an Sp greater than 80% and an Se close to 40% (global score greater than 4; V/A greater than 4.5, microectasia, rheologic changes). For the fish shoal appearance the Sp was 73.5% and the Se 43.5%. The Sp was greater than 95% when at least 4 of the following 6 signs were present: global score greater than 4, V/A greater than 4.5, microectasia, rheologic disorders, fish shoal, gerontoxons. The more signs associated the more the Sp increased; the Se decreased from 40% for one sign to less than 10% for 4 associated signs.(ABSTRACT TRUNCATED AT 250 WORDS)

[Microcirculatory hemodynamic effects of Urapidil (Eupressyl)]. / Effets hémodynamiques microcirculatoires de l'Urapidil (Eupressyl).

A laser Doppler measurement of the microcirculatory flow rate was performed in 10 patients with moderate arterial hypertension before the delivery of a 30 mg capsule of Urapidil and 3 hours later. A significant increase in this flow rate was evidenced, thus demonstrating the arteriolar vasodilative action of Urapidil.

[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.

[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.

Base composition of Coffea AFLP sequences and their conservation within the genus.

Amplified fragment length polymorphism (AFLP) is often used for genetic mapping and diversity analysis, but very little information is currently available on their sequence characteristics. Species-specific sequences were analyzed from a single Coffea genome (Coffea pseudozanguebariae) associated with clustered or nonclustered AFLP loci of known genetic position. Compared with the expressed sequence tag (EST) sequence composition, their AT content exhibited a bimodal distribution with AT-poor sequences corresponding mainly to putative coding sequences. AT-rich sequences, apart from the EST distribution, were usually clustered on the genetic map and might correspond to noncoding sequences. Conversion of these AFLP markers into sequence-characterized amplified region (SCAR) anchor markers allowed us to assess sequence conservation within Coffea species with respect to species relatedness.

Genetic mapping of maize stripe disease resistance from the Mascarene source.

Maize stripe virus (MStV) is a potentially threatening virus disease of maize in the tropics. We mapped quantitative trait loci (QTLs) controlling resistance to MStV in a maize population of 157 F(2:3) families derived from the cross between two maize lines, Rev81 (tropical resistant) and B73 (temperate susceptible). Resistance was evaluated under artificial inoculations in replicated screenhouse trials across different seasons in Réunion Island, France. Composite interval mapping was employed for QTL detection with a linkage map of 143 microsatellite markers. Heritability estimates across seasons were 0.96 and 0.90 for incidence and severity, respectively, demonstrating a high genotypic variability and a good control of the environment. Three regions on chromosomes 2L, 3 and 5, with major effects, and another region on chromosome 2S, with minor effects, provided resistance to MStV in Rev81. In individual seasons, the chr2L QTL explained 60-65% of the phenotypic variation for disease incidence and 21-42% for severity. The chr3 QTL, mainly associated with incidence and located near centromere, explained 42-57% of the phenotypic variation, whereas the chr5 QTL, mainly associated with severity, explained 26-53%. Overall, these QTLs explained 68-73% of the phenotypic variance for incidence and 50-59% for severity. The major QTLs on chr2 and 3 showed additive gene action and were found to be stable over time and across seasons. They also were found to be included in genomic regions with important clusters of resistance genes to diseases and pests. The major QTL on chr5 appeared to be partially dominant in favour of resistance. It was stable over time but showed highly significant QTL x season interactions. Possible implications of these QTLs in different mechanisms of resistance against the virus or the insect vector are discussed. The prospects for transferring these QTLs in susceptible maize cultivars and combining them with other resistances to virus diseases by conventional or marker-assisted breeding are promising.

[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.

First controlled progenies checked by isozymic markers in cultivated yams Dioscorea cayenensis-rotundata.

As tested progeny have never been obtained, breeding studies on African yams (Dioscorea cayenensisrotundata) are scarce. We report here the first progenies checked by isoenzyme markers. This was made possible by the choice of well-known genitors [one male (cv Zrezrou) and three females (cvs 'Sopéré', 'Dahomey' and 'C 20')] and special hybridization conditions. Six enzymatic systems [esterase (EST), isocitrate dehydrogenase (ICD), malate dehydrogenase (MDH), 6-phosphogluconate dehydrogenase (6PGD), shikimate dehydrogenase (SDH), and phosphoglucoisomerase (PGI)] were used to check the progenies and detect outbreeding. Despite the small number of progeny, it was possible to provide information on the genetics of the isoenzymatic systems.

[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.