[Down syndrome maternal serum screening: results' comments recommended by accredited biologists]. / Dépistage de la trisomie 21 par les marqueurs sériques maternels : justification des commentaires appliqués par les biologistes.

Down syndrome maternal serum screening is largely used in France. The aim of this article is to specify and to explain the different comments applied on the reports in order to optimize the management of the patient. These comments represent the consensus of the study group of the biologist accredited for Down syndrome maternal serum screening.

HPLC/ESI-MS(n) method for non-amino bisphosphonates: application to the detection of tiludronate in equine plasma.

Tiludronate is a non-nitrogen-containing biphosphonate drug approved in equine veterinary medicine for the treatment of navicular disease and bone sparvin in horse. Its hydrophilic properties and its strong affinity for the bone have made the control of its use quite difficult. After an initial step of method development in plasma and urine, due to a strong matrix effect and erratic detection in urine, the final method development was conducted in plasma. After addition of (3-trifluoromethylphenyl) thiomethylene biphosphonic acid as internal standard, automated sample preparation consisted of a filtration on a Nexus cartridge followed by a Solid Phase Extraction on an Oasis WAX cartridge with weak anion exchange properties. After methylation of the residue with trimethyl orthoacetate (TMOA), analysis was conducted by HPLC/ESI-MS(n) on a LTQ mass spectrometer. The method has been validated with a LOD and LOQ of respectively 1 and 2.5ng/mL. Using a weighting factor of 1/concentration(2), a linear model was suitable in the range of 2.5 up to 500ng/mL. Precision and accuracy data determined at two concentrations were satisfactory (i.e. less than 15%). Carryover would have been a problem but this has finally been fixed using the additional steps of washing during robotised SPE extraction and analysis on both the autosampler and the analytical column. The method was successfully employed for the first time to the quantification of tiludronate in plasma samples collected from horses treated with Tildren™ (Intravenous administration at the dose of 0.1mg/kg/day for 10 days).

Tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial.

REASONS FOR PERFORMING STUDY: Tiludronate regulates bone remodelling through a decrease of the resorptive process and should therefore ameliorate the remodelling processes active in osteoarthritis of the distal tarsal joints ('bone spavin') and alleviate pain associated with abnormal bone lysis. OBJECTIVE: To confirm the efficacy of tiludronate, administered as a single infusion at a dose of 1 mg/kg bwt, in the treatment of bone spavin in the horse. METHODS: A double blind placebo controlled trial on 108 clinical cases of bone spavin was undertaken. The lameness score of the lamest limb was assessed following distal tarsal analgesia of the contralateral limb and followed-up using the same procedure throughout the study. Bone spavin in the lamest limb was confirmed by distal tarsal analgesia and radiography. Horses were treated at Day 0 and reassessed 60 days later after controlled exercise. A second nonblinded treatment was given to unresponsive horses and all horses were re-examined at Day 120. Exercise levels were recorded at each examination. RESULTS: Eighty-seven horses completed the trial as per the protocol. The tiludronate horses were significantly less lame than the placebo horses (P = 0.0318). Horses treated at Day 60 with tiludronate showed further improvement in lameness at Day 120 (P = 0.0096 and P = 0.0034 for horses treated with tiludronate and placebo at Day 0, respectively). The only significant difference in radiographic findings between tiludronate and placebo was for presence of periarticular osteophytes (P = 0.006). CONCLUSIONS: Tiludronate treatment is proven to be effective in bone spavin in horses in association with a controlled exercise programme. CLINICAL RELEVANCE: Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin.

Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1.

Bioavailability and pharmacological effects of tiludronate were compared when administered as an intravenous (i.v.) bolus at a dosage of 0.1 mg/kg body weight (b.w.) once daily for 10 consecutive days (group 1, n = 6) and as a single constant rate infusion (CRI) at a total dose of 1 mg/kg b.w. (group 2, n = 6) in healthy adult horses. Tiludronate and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-1) were measured in plasma and urine. There was no statistically significant difference in area under the curve (AUC) and clearance (Cl) between the two groups. Bioavailability of the CRI was 103% (not significantly different) that of the 10 daily i.v. bolus doses. Cumulative urine tiludronate excretion could not be compared between groups because of poor sensitivity of the assay in urine. Plasma and urine CTX-1 levels were not different between groups throughout the study. However, interindividual variations were greater in group 1 than in group 2. A significant decrease in CTX-1 levels was observed in plasma after the first administration in group 1, but not in urine; while in group 2, a significant decrease in CTX-1 concentrations was observed after treatment in both plasma and urine. In conclusion, both dosage regimens of tiludronate produced similar plasma exposure and pharmacological effects in adult healthy horses.

Pharmacological effects of tiludronate in horses after long-term immobilization.

INTRODUCTION: Tiludronate, a bisphosphonate, has recently been introduced in veterinary medicine to treat orthopedic conditions in the horse. This study was designed to evaluate its effects on biochemical biomarkers of bone metabolism and on bone density and structure in an experimental model of disuse osteoporosis induced by cast application in horses. METHODS: Two groups of eight horses were immobilized during 8 weeks. The first group (P-group) received a placebo, and the second group (T-group) received tiludronate 1 mg/kg by slow IV infusion. Both treatments were administered twice, 28 days apart. Immobilization consisted of stall rest with the left forelimb packed in a fiberglass cast. It was followed by a 4-week remobilization period and an 8-week standardized training protocol. One biomarker of bone resorption, the C-telopeptides of type I collagen cross-links (CTX-1) and one biomarker of bone formation, the bone isoenzyme of alkaline phosphatase (bone ALP), were assessed. Metacarpus III (MCIII) bone mineral density (BMD) and speed of sound (SOS) were evaluated respectively by dual energy X-ray absorptiometry (DEXA) and quantitative ultrasonography (QUS). Lameness was regularly assessed during the remobilization and training periods. Group- and time-related effects were tested by analysis of variance on repeated measurements. RESULTS: A rapid, transient and significant decrease in CTX-1 concentration was seen after each treatment in the T-group only. No significant differences between groups were seen in the evolution of bone ALP activity. At the end of the experiment, the loss of MCIII BMD measured by DEXA in the immobilized limb was significantly less in the T-group than in the P-group. The MCIII SOS measured by QUS did not significantly vary within or between groups throughout the study. DISCUSSION AND CONCLUSIONS: Tiludronate was found to significantly reduce bone resorption during immobilization, as well as to prevent long-term osteopenia in the immobilized limb. Disuse osteopenia did not affect the lateral superficial cortex of MCIII.

Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo-controlled clinical trial.

REASONS FOR PERFORMING STUDY: Bisphosphonates, such as tiludronate, are used to normalise bone metabolism via inhibition of bone resorption. Areas of increased bone resorption and formation are typical lesions in a diseased navicular bone. OBJECTIVES: To determine if bone remodelling changes occurring in navicular disease may be corrected with therapies regulating bone metabolism. METHODS: We designed a double-blind, placebo-controlled clinical trial to compare 2 doses of tiludronate, 0.5 mg/kg and 1 mg/kg bwt administered via daily i.v. injections over 10 days for the treatment of navicular disease. Seventy-three horses, split into 2 subpopulations of recent and chronic cases, were enrolled to be followed-up over 6 months. Of these, 33 recent and 17 chronic cases meeting the selection criteria were maintained in the final efficacy analyses. Clinical examinations were videorecorded and reviewed blindly by an independent expert. RESULTS: Horses treated with the higher dose showed optimal improvement of lameness and return to normal level of activity 2-6 months post treatment. The more recent the onset of clinical signs at the time of treatment, the greater the efficacy. The treatment did not modify the response to extension and flexion tests. The lower dose failed to significantly improve the condition. CONCLUSIONS: Tiludronate efficacy is demonstrated in the treatment of navicular disease at the dose of 1 mg/kg bwt. POTENTIAL RELEVANCE: Our results support the clinical relevance of bone remodelling changes in the outcome of navicular disease.

[Diagnosis of phenylketonuria in a 35-year-old mother in relation to prenatal diagnosis of intrauterine growth retardation with microcephaly]. / Diagnostic de phénylcétonurie chez une mère âgée de 35 ans à l'occasion de la découverte anténatale d'un retard de croissance intra-utérin avec microcéphalie.

BACKGROUND: Some French pregnant women with phenylketonuria (PKU), born before 1978, have not been tested with the Guthrie method during the neonatal period. They have a risk of spontaneous abortion and their infants are often mentally retarded with microcephaly and/or congenital heart anomaly. CASE REPORT: A woman with a moderate mental retardation became pregnant at the age of 31 years. Her newborn had a severe intrauterine growth retardation with microcephaly and developed mental retardation. This mother became pregnant again 4 years later. Repeated fetal ultrasonography showed progressive growth retardation. Maternal blood phenylalanine concentration was 18 mg/100 mL. Therapeutic abortion at 27 weeks of gestational age showed a fetus with several abnormalities, particularly cardiovascular and cerebral. CONCLUSION: It is still possible to meet women with unrecognized atypical PKU. Fetus or infant born with unexplained growth retardation and microcephaly requires search for maternal PKU.

[Primary amenorrhea revealing congenital hydrocephalus]. / Aménorrhée primaire révélant une hydrocéphalie congénitale.

UNLABELLED: Among the various endocrine manifestations of chronic hydrocephaly, amenorrhea is not exceptional, whereas late puberty and obesity are the most frequent. The hypothalamic gonadotropic function usually returns to normal within the few months following the ventricular shunt. CASE REPORT: A 16 year-old girl, with a von Recklinghausen's disease, developed amenorrhea 2 years after the onset of puberty. X-rays of her skull showed an enlarged sella turcica and a diagnosis of hydrocephalus due to aqueductal stenosis was finally made. As her head circumference was retrospectively shown at +3 SD as early as the first month of life, the stenosis was certainly congenital, a feature known to occur in 2% of patients with von-Recklinghausen's disease. CONCLUSION: In symptomatic forms of aqueductal stenosis, the preferred surgical procedure is ventriculocisternostomy under endoscopy. Recovery of intellectual functions is often incomplete. Early diagnosis of hydrocephalus is of paramount importance; ultrasonography through anterior fontanel should be proposed to any infant with head circumference reaching +3 SD.

[Acute anemia induced by rupture of a luteal cyst, aggravated by the ingestion of antivitamin K]. / Anémie aiguë par rupture d'un kyste lutéal, aggravée par la prise d'antivitamine K.

A case of hemoperitoneum secondary to the rupture of an ovarian cyst is reported in a 14 1/2 year-old girl. The severity of the bleeding was explained by anticoagulant therapy given during the previous 3 weeks for laceration of ankle ligaments which necessitated surgery. In this age group, the differential diagnosis with a ruptured ectopic pregnancy had to be considered. The relative prevalence (10%) of complications associated with antivitamin K administration is discussed.

[Long-term results (6 to 17 years) of 372 mitral valve replacements using the Björk-Shiley prosthesis]. / Résultats lointains (six à dix-sept ans) sur 372 patients du remplacement valvulaire mitral par prothèse de Björk-Shiley.

From November 1970 to December 1981, an isolated mitral valve replacement was performed in 372 patients (166 males - 206 females), ranging in age from 2 months to 76 years (mean age 49 years). Eighty-nine patients (24%) had previously undergone one or two cardiac operations. Only one of the 24 hospital deaths (6.4%) was related to the prosthesis (early thrombosis). Three hundred and fourty-eight patients were discharged from the hospital, 35 were lost to follow-up, and 313 were observed with a mean follow-up of 8 years 8 months (ranging from 5 years 2 months to 16 years 3 months). Ninety-two patients (29.4%) died from 2 months to 16 years post-operatively. Thirteen late deaths were from extra cardiac causes. Cardiac failure and thromboembolic or haemorrhagic complications represent the main causes of late mortality, respectively 10 and 6.7%. Twenty-one deaths were related to the prosthesis (10 thrombo-embolic accidents, 7 haemorrhagic complications and prosthesis could be discussed in 11 cases of sudden deaths and in 12 cases of death of undetermined causes. Among the 34 thrombo-embolic complications and the 13 perivalvular leakages (6 of them related to infection), 23 patients required reoperation, for valve thrombosis (14 cases with 2 deaths) or perivalvular leakage (9 cases with 2 deaths). Four other cases of valve thrombosis were treated with fibrinolytic agents with 1 death. The actuarial survival rate, hospital mortality excluded, is 69% at 10 years and 55% at 15 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Incontinentia pigmenti: Xp breakpoint is not the same in a case of r(X) and in X/autosome translocations.

X-specific DNA probes were used to characterize the r(X) of a 45,X/46,X,r(X) female patient with Incontinentia pigmenti. It was found to be of maternal origin. Breakpoints were shown to be in or distal to p11.22 and between q12.2 and q13.1. When considering all known cases of Incontinentia pigmenti and X rearrangements at least four different break sites on the X have been shown.

Long-term evaluation of direct repair of traumatic isthmic aortic transection.

Direct repair of traumatic aortic isthmic transection eliminates the late complications of prosthetic graft repair. This study evaluates the long-term fate of direct aortic repair to which little attention has been paid. Among 32 patients operated upon from 1965 to 1987, 27 (84%) underwent direct repair. The tear was circumferential in 15 patients and partial in 12. Multiple traumatic lesions were present in 26 patients, including intracranial injury in 19. Partial cardiopulmonary bypass was used in 15 patients and simple aortic cross-clamping in 12. No paraplegia was observed. There were 4 deaths from associated lesions among the 14 patients operated upon for acute traumatic isthmic transection and no deaths in the others. Among the 23 survivors, 4 were lost to follow-up; the other 19 patients have excellent clinical results. Intravenous digital aortic angiography performed in 14 patients at a mean delay of 5 years 3 months showed excellent aortic reconstruction in all cases. Technically more demanding and faster than a graft interposition, direct repair is recommended as the procedure of choice in the surgical treatment of traumatic isthmic transection, particularly in young patients, the group most at risk from this lesion.

A prospective study of current diagnostic procedures for assessment of hepatic metastases in colorectal cancers.

In a prospective study of 305 patients with colorectal cancers, we assessed the diagnostic value of ultrasonography and laboratory tests. In each case laparotomy was carried out and the presence of liver metastases was established in 47 patients. The results show that the laboratory tests alone are not sufficiently accurate to detect liver metastases. Additional accuracy can be obtained by the combined use of a single liver imaging test (echography) and selected laboratory tests (C.E.A., gamma GT, Alkaline Phosphatase).

Blastogenic response of peripheral blood lymphocytes from multiparous pregnant ewes.

The immunocompetence of pregnant multiparous ewes was investigated with respect to the blastogenic response of peripheral blood lymphocytes of (PBL) to three mitogens: PHA, Con A, and PWM. The profile of PBL responses shows 1) progressive suppression at 36 and 66 days of gestation, 2) enhanced response at 97 days of gestation, which approaches the mean values observed at the premating period, and 3) a redecline of the response at 137 days of gestation to depressed values lower than observed at 36 and 66 days of gestation. The results suggest that mitogen-treated lymphocytes were depressed and that the immunodepressive factor(s), which can influence lymphocytes at the systemic level, may be involved in the maintenance of the ovine fetal semiallograft.