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Biomedical subjects

N Fournet

Publications and source records attributed to N Fournet.

13 recordsLinked to original sources

Development and evaluation of tuberculosis screening scores in Brazilian prisons.

BACKGROUND: Tuberculosis (TB) is highly endemic in Rio de Janeiro State prisons. In addition to TB screening at entry and passive case detection, active case identification may be warranted. OBJECTIVES: To develop and evaluate performances of scores aimed at identifying "tuberculosis suspects" in order to target TB screening among inmates. METHODS: Systematic chest X-ray screening was carried out in two prisons (n=1910). TB was diagnosed among individuals with X-ray abnormalities by sputum microscopic examination and culture or, if bacteriological results were negative, by response to TB treatment. Using this strategy as a reference, the clinical score proposed in WHO guidelines "TB Control in Prisons" was evaluated. Using the same variables in a logistic regression comparing TB and non-TB cases, another score was developed and evaluated. Finally, a 'new score', based on socio-demographic and clinical variables was developed and evaluated. RESULTS: When applied to our study population (prevalence of active TB: 4.6%), these scores missed many TB cases (sensitivities: 56%, 72%, 74%, respectively). Among the "TB suspects", the probability of finding TB cases was low (positive predictive value: 10%). The scores had high negative predictive values (>97%); specificities (75%, 60%, 67%) were low. Performances were similarly poor for smear-negative and smear-positive cases. CONCLUSION: The scores investigated performed poorly and would be unhelpful to target TB screening. Therefore, systematic X-ray screening may be considered, at least during the initial stages of the reinforced TB programme, in order to reduce the impressive burden of TB.

Adult↗

Working memory functioning in medicated Parkinson's disease patients and the effect of withdrawal of dopaminergic medication.

Cognitive impairments in Parkinson's disease (PD) could be explained by a central executive (CE) deficit in A. D. Baddeley's (1986) working memory model. To test this hypothesis, verbal, spatial, and double span tasks were given to 12 medicated PD patients and control participants, with varying recall delays. The double span task was assigned to explore the coordinating and integrating function of the CE, and lengthening the recall delay was expected to implicate more attentional resources. PD patients had lower spans relative to controls in all tasks. However, the more specific implication of the CE was difficult to prove. One reason could be that PD patients were on dopaminergic treatment when tested. To control this effect, 12 PD patients on and off medication were studied in a second experiment using the same tasks. PD patients off medication had lower spans only in the double task; this result underlines the role of dopamine on working memory processes.

Adult↗

The phonological loop in medicated patients with Parkinson's disease: presence of phonological similarity and word length effects.

OBJECTIVE: To test the verbal subsystem of Baddeley's working memory model (the phonological loop) in patients with Parkinson's disease. METHODS: Fifteen patients with idiopathic Parkinson's disease and 15 controls were tested with a span paradigm to assess the effects reflecting the functioning of the phonological loop: the phonological similarity effect (in verbal and visual presentation), and the word length effect (in visual presentation). RESULTS AND CONCLUSIONS: The patients did not show any dysfunction of the phonological loop, reflected by the presence of phonological similarity and word length effects, but had lower spans than controls. The implications of these results for the working memory model are discussed.

Aged↗

Working memory in medicated patients with Parkinson's disease: the central executive seems to work.

OBJECTIVE: To determine whether a deficit of the central executive can explain the attentional deficits of patients with Parkinson's disease. METHODS: Fifteen patients with idiopathic Parkinson's disease and 15 controls were given a dual task paradigm minimising motor demands and combining verbal, visual, or spatial span with two conditions of articulatory suppression. RESULTS: Although the spans were systematically lower in medicated parkinsonian patients than in controls, suggesting a decrease of central processing resources, there was no direct evidence for a deficit of the central executive. CONCLUSIONS: A deficit of the central executive either is not an inevitable feature of the disease, or is dependent on the nature of task (visuomotor v cognitive), or is corrected by dopaminergic medication.

Aged↗

Transforming growth factor-beta inhibits ovarian 17 alpha-hydroxylase activity by a direct noncompetitive mechanism.

Transforming growth factor-beta1 (TGF-beta1) inhibits theca-interstitial cell (TIC) androgen biosynthesis while enhancing progesterone production without altering P45017 alpha protein content. The purpose of the present study was to define the mechanism of TGF-beta 1 inhibition of ovarian androgen production by determining the effects of TGF-beta 1 on steroidogenic enzyme messenger RNA (mRNA) expression and 17 alpha-hydroxylase activity in TIC in vitro. TIC isolated from hypophysectomized immature rat ovaries by Percoll gradient centrifugation were cultured with and without LH and TGF-beta 1 up to 6 days. At various times, cytoplasmic mRNA was extracted from the TIC, and P450scc, 3 beta-HSD and P450(17 alpha) mRNA were measured by specific assays, using RT-PCR. Treatment with TGF-beta 1 alone (0.1-100 ng/ml) had no effect on mRNA expression at 2 days but increased P450scc and 3 beta-HDS mRNA at 4 days. TGF-beta did not alter the LH stimulation of P450scc and 3 beta-HSD mRNA up to 6 days but caused a modest (2.5-fold) increase in P450 (17 alpha) mRNA at 2 days. Specificity studies with inhibin-A (30 ng/ml), activin-A (100 ng/ml), and MIS (300 ng/ml) demonstrated that the effects of TGF-beta 1 were unique within this family of peptides. We next examined the effect of TGF-beta 1 on 17 alpha-hydroxylase activity. Kinetic analysis revealed that the 17 alpha-hydroxylase enzyme has an apparent Michaelis-Menten constant of 3.42 mumol/liter and maximum velocity of 0.23 pmol/min x mg protein. TGF-beta 1 inhibited 17 alpha-hydroxylase activity by a noncompetitive mechanism with an apparent inhibin constant (Ki) of 46.4 pM. The results of our studies demonstrate that TGF-beta 1 directly inhibits TIC androgen production by a noncompetitive mechanism. This novel mechanism may be important in preventing excessive androgen production in developing ovarian follicles without preventing differentiation of the TIC.

Aldehyde-Lyases↗

Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone "add-back" therapy.

OBJECTIVE: To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist (GnRH-a) for prolonged therapy of symptomatic endometriosis. DESIGN: Prospective randomized open label study. SETTING: Tertiary care university-affiliated reproductive medicine program. PATIENTS: Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis. INTERVENTIONS: All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks. Group I patients (n = 10) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9) received only supplemental 10 mg norethindrone daily. Group III volunteers (n = 18) were untreated and followed for bone density changes. MAIN OUTCOME MEASURES: Disease extent at follow-up laparoscopy; pain, vasomotor, and vaginal symptom scores; bone mineral density (serial dual-energy roentgenogram absorptiometry scans); serum estrogens, lipids, and glucose and insulin response to glucose challenge. RESULTS: Painful symptoms and extent of endometriosis were reduced in both treatment groups. Despite maintenance of a chronically hypoestrogenic state for 48 weeks, no changes in bone density over time or in comparison to group III untreated controls were noted. Similarly, no evidence of significant vasomotor symptoms were reported in either treatment group. However, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II. CONCLUSIONS: The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis. Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved.

Adult↗

Effects of sodium etidronate in combination with low-dose norethindrone in patients administered a long-acting GnRH agonist: a preliminary report.

OBJECTIVE: To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone. METHODS: Eleven patients enrolled in this randomized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks. Six patients (group I) self-administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles. This regimen was supplemented by norethindrone 2.5 mg/day orally. Five patients (group II) self-administered norethindrone 10 mg/day orally. Two sets of controls were used. Group III consisted of ten previously reported patients who received the same GnRH agonist only. Group IV comprised 12 regularly cycling untreated controls. Bone mineral density, vasomotor symptoms, circulating estrogens, and lipids were assessed serially. RESULTS: The significant vasomotor instability (P < .01) and bone mineral density loss (-4.8 +/- 0.9%; P < .05) experienced by patients in group III was prevented in those in groups I and II despite maintenance of a persistent hypoestrogenic state. Bone density changes in groups I and II were similar to those in untreated controls (group IV). Persistent decreases in high-density lipoprotein (HDL) cholesterol (P = .005) and increases in the low-density lipoprotein-to-HDL ratio (P < .05) were noted only in group II patients receiving supplemental high-dose norethindrone. CONCLUSION: These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone.

Bone Density↗

Ovulation induction in women age 40 and older: the importance of basal follicle-stimulating hormone level and chronological age.

OBJECTIVES: To determine pregnancy and livebirth rates for women age 40 and older undergoing ovulation induction and to assess the impact of basal follicle-stimulating hormone (FSH) on outcome in these patients. DESIGN: Prospective, observational. SETTING: Fertility service of university medical center. PATIENTS: Infertile couples in whom the female partner was age 40 or older referred for ovulation induction therapy. INTERVENTION: Assessment of basal hormonal status; ovulation induction. MAIN OUTCOME MEASURES: Clinical pregnancy rate (PR), livebirth rate. RESULTS: Analysis of 402 cycles in 85 women age 40 and older demonstrated a clinical PR of 3.5% per cycle (95% confidence interval [CI] 1.7% to 5.3%). The livebirth rate was 1.2% per cycle (95% CI 0.1% to 2.3%). Women with a basal FSH < 25 IU/L and age < 44 years had a clinical PR of 5.2% per cycle (95% CI 2.5% to 7.9%) compared with 0.0% per cycle (95% CI 0.0% to 2.1%) in cases in which either basal FSH was > or = 25 IU/L or age was > or = 44 (P < 0.005). The prognostic importance of basal FSH and chronological age was confirmed by multivariate logistic regression analysis. The predictive value of the resulting regression equation was high (R2 = 0.94; P < 0.01). CONCLUSIONS: Pregnancy and livebirth rates are generally low during ovulation induction in women age 40 and older. In combination, basal FSH and chronological age are accurate predictors of PR, in these couples and can define a subset of patients with a more favorable prognosis. The spontaneous abortion rate in women who do conceive is high, substantially lowering the livebirth rate.

Adult↗

Internal jugular vein thrombosis after ovulation induction with gonadotropins.

An unusual case of ovarian hyperstimulation syndrome complicated by internal jugular vein and mediastinal thrombosis is presented. Hemoconcentration and perhaps immobilization appear to be the most probable causative factors. The patient was successfully treated with heparin anticoagulation. An uneventful twin pregnancy resulted from the stimulation cycle.

Adult↗

Selective localization of calcium-binding protein in human brainstem, cerebellum and spinal cord.

The 28,000-Da vitamin D-dependent calcium-binding protein, CaBP, which is induced by one hormonally active form of vitamin D3, 1,25-dihydroxyvitamin D3, was localized by immunocytochemistry in the human brainstem, cerebellum and cervical segment of the spinal cord. Positive structures (neurons and their processes) were restricted to some well-defined motor and sensory pathways. In motor regions, the highest density of immunoreactive sites was found in the Purkinje cell layer of the cerebellar cortex, and CaBP-positive neurons were also found in the reticular formation and the inferior olivary nucleus. In sensory pathways, positive neurons were mainly localized in structures associated with protopathic thermalgesia (pain and temperature), as well as in the solitary nucleus and parabrachial nucleus of the taste pathway.

Aged↗

Changes of ovarian hormonal function with aging.

Striking changes of ovarian function occur with aging. These changes begin subtly with reductions of fecundability being observed after age 25. The transition from reproductive to postreproductive life is characterized by menstrual irregularity including anovulation, or short luteal phases. The most prominent hormonal changes at the menopause are drastic reductions of estradiol and progesterone secretion by the ovary, reflecting the cessation of folliculogenesis and ovulation. Elevations of gonadotropins and reduction of inhibin levels also reflect the loss of folliculogenesis and ovulation. There are accompanying decreases of ovarian androgen secretion; however, the postmenopausal gonad directly secretes more testosterone after, than before, the menopause.

Aging↗