[Procedure used to follow-up a cohort of IVF children. Interests and limits of tools performed to longitudinal follow up for a monocentric cohort]. / Procédure de suivi d'une cohorte d'enfants FIV. Intérêts et limites de l'outil développé pour un suivi longitudinal et monocentrique.

BACKGROUND: Follow-up of in vitro fertilization (IVF) children is recommended by the French health authorities. Follow-up procedures were set-up in a medically assisted reproduction unit at the Saint-Joseph Hospital in Marseille. The objective was to ensure effective follow-up. In this context, it is important to determinate weather the designated tools are appropriate for evaluating the desired developmental outcomes. This study was designed to describe the surveillance tool and to demonstrate its usefulness and limitations. METHODS: The procedure was initiated in 2004. All existing data for every livebirth child were collected, including data concerning all IVF attempts, medical reports of pregnancy, and child health records. Parents were asked to complete questionnaires and provide their child's personal health records since birth. The quality of the data was evaluated using prenatal and postnatal analysis. The longitudinal anthropometric data of the health records were used to describe the percentiles of weights and heights from birth to 6 years in this population at age-specific reference intervals. RESULTS: The follow-up concerned 2081 children born since 1995 with a response rate of 68,9%. A brief descriptive analysis was performed for the cohort and for a group of 1053 children aged five years and older, 225 representative personal health records were used to estimate quintiles for anthropometric data. CONCLUSION: The procedure adopted for the follow-up of in vitro fertilization children meets the established qualitative health requirements. This method provides many benefits with no risk for the children. Data collection from personal health records enabled an exploitation of growth data by including the calculation of anthropometric percentiles in this IVF population. This report presents the first set of IVF child growth standards used as health indicator and health trend measurement.

[Adrenoleukomyeloneuropathy. A familial case]. / Adrénoleucomyéloneuropathie. Un cas familial.

Adrenomyeloneuropathy (AMN) was diagnosed in a 24 year old man. He had had acute periods of adrenal insufficiency since early infancy and had melanoderma, moderate mental deterioration, psychic disorders and, from 16 years of age, a spastic paraplegia. Confirmation diagnosis was obtained by the existence in the family of two definite cases (a brother and second cousin) and one probable case (a maternal uncle) of an adrenoleukodystrophy (ALD), by the demonstration of a peripheral neuropathy with characteristic lamellar inclusions in a sural nerve biopsy and by raised plasma very long chain fatty acids level. Multinodal study of evoked potentials showed anomalies due to changes in supraspinal central nervous system. Adrenoleukomyeloneuropathy or ALMN (the association within the same family of cases of AMN and ALD being possible as confirmed by the present case) is recessive and X - linked. It belongs to the peroxisomial diseases. No therapy has been proven effective on the neurological disease.

[The anterior pituitary endocrine function in Parkinson's disease]. / La fonction endocrine anté-hypophysaire dans la maladie de Parkinson.

Dopamine exerts an inhibitory or stimulant action on some of the hormones produced by the anterior pituitary gland. The dopamine content of the hypothalamus is considerably reduced in patients with Parkinson's disease. We have tested the anterior pituitary endocrine function in such patients to evaluate the repercussions on this function of the dopaminergic deficiency: the secretion of pituitary stimulins was found to be unaltered both at baseline level and after pharmacological stimulation.

[Adrenal tumors of fortuitous discovery. 13 cases]. / Tumeurs surrénaliennes de découverte fortuite. Treize observations.

An adrenal mass without any clinical or biological symptom was accidentally discovered in thirteen patients. All patients underwent surgical exploration. After surgery, pathological studies showed lesions of corticosuprarenaloma (5 considered benign, 1 malignant and 1 uncertain) myelolipoma (2 cases), adrenal cyst, ganglioneuroma, haemangioma and lymphangioma (1 case each). Since no reliable preoperative investigations are yet available to assess the nature of adrenal masses, and since these may be due to benign or malignant endocrine tumours, their surgical removal is indicated.

Gender-specific elimination of continuous-infusional 5-fluorouracil in patients with gastrointestinal malignancies: results from a prospective population pharmacokinetic study.

BACKGROUND: This study was initiated to assess the quantitative impact of patient anthropometrics and dihydropyrimidine dehydrogenase (DPYD) mutations on the pharmacokinetics (PK) of 5-fluorouracil (5FU) and to explore limited sampling strategies of 5FU. PATIENTS AND METHODS: We included 32 patients with gastrointestinal malignancies, receiving 46-h continuous-infusional 5FU and performed PK-sampling at baseline, 15, 30, 45 min, 1 and 2 h after the start of infusion and at the end of infusion, for 2 subsequent cycles. Plasma concentrations of 5FU, 5-fluorodihydrouracil (5FUH2), uracil (U) and 5,6-dihydrouracil (UH2) were determined using LC-MS/MS and submitted to population PK analysis using nonlinear mixed-effects modeling. Broad genotyping of DPYD was performed, and the potential impact of the DPYD genotype on the elimination of 5FU was assessed. Limited sampling strategies were evaluated for their accuracy to predict steady-state concentrations of 5FU (CSS(5FU)), using data simulations based on the final PK-model. RESULTS: The area-under-the concentration-time curve of 5FU (AUC(5FU)) was found to be <20 mg h/L in 33 occasions (58 %), between 20 and 30 mg h/L in 17 occasions (30 %) and >30 mg h/L in 7 occasions (12 %). Men had a 26 % higher elimination of 5FU and a 18 % higher apparent elimination of 5FUH2. Accordingly, women had a higher AUC(5FU) compared to men (22 vs. 18 mg h/L, p = 0.04). No DPYD risk variants were found, and the DPYD variants detected (c.496A>G, c.1601G>A, c.1627A>G) were not significantly associated with the elimination of 5FU. Individual baseline UH(2)/U ratio was significantly associated with AUC(5FU) (R = -0.49, p < 0.001). Limited sampling strategies with time-points <3 h after the start of infusion were not adequate to predict CSS(5FU). Female gender was the only predictor of nausea/emesis in the multivariate model. CONCLUSIONS: Gender-specific elimination of 5FU is supported by the present data and may partly explain the gender-specific association between DPYD risk variants and 5FU-specific toxicity.

Osteogenic protein-1 promotes the formation of tissue-engineered cartilage using the alginate-recovered-chondrocyte method.

OBJECTIVE: This study examined the effects of a growth factor, recombinant human osteogenic protein-1 (rhOP-1), on the formation of tissue-engineered cartilaginous tissue by adult bovine articular chondrocytes using the alginate-recovered-chondrocyte (ARC) method. DESIGN: To ascertain if rhOP-1 enhances the formation of the cell-associated matrix (CM) and the characteristics of CM formation, bovine articular chondrocytes were first cultured for up to 14 days in alginate beads in medium supplemented with serum, with or without rhOP-1. Then, the recovered chondrocytes and their associated CM were resuspended in medium, with or without OP-1, seeded onto culture inserts, and incubated for an additional 14 days. The fabricated ARC tissues were subjected to biochemical and histological analyses. RESULTS: The addition of rhOP-1 to the medium in the alginate bead culture step resulted in an increased accumulation of both proteoglycan (PG) and collagen, with a ratio of PG to collagen that was higher than that found in native adult cartilage. The addition of rhOP-1 in the second step had a similar stimulatory effect during 14 days of culture. Histological examination of the tissue formed under all conditions revealed a cartilage-like matrix, stained strongly by toluidine blue. The thickness of the tissues obtained from culture conditions that included the addition of rhOP-1 was four times greater than that of the tissues cultured without rhOP-1. CONCLUSIONS: Using the ARC method, rhOP-1 enhanced the formation of matrix and generated a voluminous tissue-engineered cartilaginous construct. These characteristics may be beneficial in generating constructs that can cover large defects.

Influence of vasodilators used in the therapy of heart failure on platelet aggregation.

Of the vasodilators used at present in the treatment of heart failure, only nitroprusside and phentolamine inhibit platelet aggregation at therapeutic dose levels. The other vasodilators studied, viz. nitroglycerin, isosorbide dinitrate, hydrallazine, dihydrallazine and prazosin, only inhibit platelet aggregation at relatively high concentrations, well above those reached in vivo. The exact nature of the platelet receptor, stimulation and blockade of which respectively initiate and inhibit aggregation, is not yet know, but it would appear to resemble the presynaptic alpha-receptors of other tissues.

Effect of sulphinpyrazone (Anturan) on uric acid excretion and plasma uric acid concentration in healthy volunteers.

Investigations in six healthy volunteers given single oral doses of sulphinpyrazone (Anturan) showed that the drug had a potent uricosuric effect, even if the concentration of uric acid in the plasma was normal. In the dose range tested of 50 to 800 mg the increase in uric acid excretion was dose-related. It reached a maximum within 2 h and was still detectable 6--8 h after the drug was taken. There was a corresponding dose-related reduction in the plasma concentration of uric acid, which reached its lowest level after 8--10 h. The administration of 300 mg twice daily for four days to a further five healthy volunteers reduced plasma uric acid from 5.06 to 1.8 mg%. The findings indicate that, even if plasma uric acid levels are unknown, it would be advisable to avoid the risk of formation of urinary calculi by administering sulphinpyrazone in gradually increasing doses, ensuring adequate fluid intake and alkalinizing the urine during the first few days of treatment.

Inhibition of adrenaline-induced platelet aggregation by the orally administered alpha-adrenergic receptor blocker phentolamine (Regitine).

In eight healthy volunteers pretreatment with phentolamine 40 mg p o inhibited platelet aggregation (1st and 2nd phases) induced by low concentrations of adrenaline (2, 1 and 0.5 muM) in plasma from blood sampled 30 min after administration of the compound. The lower the concentration of adrenaline use, the greater was the degree of inhibition elicited. These results are indicative of competitive inhibition of the action of adrenaline on the platelet membrane by phentolamine. Four to six hours after administration of the compound, the aggregation characteristics had reverted to normal. It is concluded that the increased tendency toward platelet aggregation associated with elevated blood levels of catecholamines can be prevented by therapeutic doses of phentolamine.

Contouring by electronic speckle pattern interferometry employing dual beam illumination.

In this paper we extend and study the method for generating contours of diffuse objects employing a dual beam illumination coupled with electronic speckle pattern interferometry. The sensitivity and the orientation of the contour planes are analyzed. A novel method for tilting the planes of contours and experimental results incorporating phase shifting and fringe analysis are also presented. The theoretical and the experimental results show good agreement.

The influence of acetysalicylic acid on changes in platelet function due to physical exertion.

The influence of acetylsalicylic acid (ASA) on alterations of the platelets resulting from physical exertion was studied in 10 healthy volunteers. Before and 2 h after the administration of placebo or 1 g ASA, venous blood samples were taken for platelet counts, thrombelastography (TEG) and tests of ADP- and epinephrine-induced platelet aggregation. The blood in which the 2-h values were determined was sampled at the highest work-load during sub-maximum exercise on a bicycle ergometer (5 min each at 50, 100 and 150 watts). ASA had no effect on the alterations of the platelets due to physical effort: the increase in the first phase of epinephrine-induced aggregation, the elevation of the platelet count and the hypercoagulability demonstrable by TEG still persisted after the administration of ASA. Some effects were noted, however, that are also observed after the administration of ASA at rest: the second phase of epinephrine-induced aggregation was suppressed and disaggregation after induction with ADP was accelerated.

Validity of the Wu-Hoak method for the quantitative determination of platelet aggregation in vivo.

Quantitative determinations of platelet aggregation were made by a modified version of the Wu-Hoak-method in venous blood samples from ten healthy volunteers. It was demonstrated that the extent to which aggregates are formed depends on the rate of flow in the needle and on other methodical influences as well as on the platelet count. Accordingly, no definite conclusions concerning aggregation conditions in vivo can be drawn from the results obtained with venous blood samples.

Quantitative changes in platelet aggregation due to physiological and pathological factors and medication.

Quantitative measurements of platelet aggregation in samples of venous blood were made in altogether 66 healthy volunteers by a modified version of the method of Wu and Hoak. The formation of aggregates was found to be unaffected or at the most barely affected by such factors as sex, age, smoking, fatty food, physical exertion and medication with isoprenaline or ovulation inhibitors. No difference in the number of aggregates formed was noted between 12 control patients and 16 patients with myocardial infarcts or 14 with other conditions predisposing to arterial thrombosis. Anticoagulant therapy had no effect on aggregation. It is suspected that aggregation in vitro due to methodological factors may obscure any quantitative alterations in the formation of aggregation present in vivo.

Del1: a new protein in the superficial layer of articular cartilage.

Articular cartilage contains four distinct zones, extending from the surface to the subchondral bone. Freshly isolated chondrocytes from the superficial zone of articular cartilage retain a collagenase-P-resistant cell-associated matrix. In the studies described here, the protein Del1 was identified as a component of the cell-associated matrix of superficial zone chondrocytes from adult bovine articular cartilage. Very little Del1 was associated with freshly isolated deep zone chondrocytes. Western blot analysis of articular cartilage cell and tissue extracts using polyclonal antibodies specific for Del1 showed Del1 was present in an insoluble cell-associated fraction. Extracts of the superficial zone of articular cartilage were found to be enriched in Del1 compared to the deeper layers of the tissue. Immunohistochemical staining of full-thickness articular cartilage with anti-Del1 antibodies also showed an enrichment of Del1 in the superficial zone. These observations are the first to describe the protein Del1 in a nonendothelial, nonfetal tissue.

Double-blind co-operative trial to compare trimethoprim-sulfalene and co-trimoxazole in the treatment of lower respiratory tract infections.

Two fixed trimethoprim-sulfonamide combinations were compared in a clinical trial for their effectiveness and safety in the treatment of patients with acute lower respiratory tract infections (pneumonia, bronchopenumonia, purulent tracheobronchitis, ect.). 46 in-patients were randomly allocated to Kelfiprim (trimethoprim 250 mg + sulfalene (sulfamethopyrazine) 200 mg) or to co-trimoxazole (trimethoprim 320 mg + sulfamethoxazole 1600 mg) and were treated for 1-2 weeks under double-blind conditions. Assessment of effectiveness was based on daily follow-up of subjective and objective signs and symptoms, on changes in X-ray picture, and on microbiological and laboratory findings. Response to therapy was excellent or good in 86% of patients receiving Kelfiprim and in 79% of those given cotrimoxazole. Transient side-effects were observed in three patients under Kelfiprim (two allergic reactions and one G.I. complaint) and in one under co-trimoxazole (altered kidney function).

The true metabolisable energy content of canola oilcake meal and full-fat canola seed for ostriches (Struthio camelus).

1. The true metabolisable energy (TME) of canola oilcake and full-fat canola seed was determined for ostriches to broaden our knowledge of canola as a potential protein and energy source for ostriches. 2. Both test materials were diluted with a basal diet, fed to ostriches and TME-values estimated by multiple regression analysis. 3. The TME values for canola oilcake meal and full-fat canola seed for ostriches were respectively 13.76 MJ kg(-1) and 22.5 MJ kg(-1). 4. The TME values obtained for these 2 important protein sources will assist in the more accurate formulation of diets for ostriches.