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Biomedical subjects

A Bennet

Publications and source records attributed to A Bennet.

At least 19 recordsLinked to original sources
PubMed2007

Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors.

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is rare and generally presents as a sporadic disease. We describe a familial case of AIMAH with in vivo and in vitro demonstration of aberrant 5-HT4 and vasopressin adrenal receptors. Two sisters presented with clinical and biological features of mild Cushing's syndrome with bilateral macronodular adrenal enlargement on computerized tomography (CT)-scan evaluation. In vivo pharmacological tests showed a significant increase in plasma cortisol after terlipressin and metoclopramide administration. Unilateral adrenalectomy was performed in one of these patients. Reverse transcriptase-PCR analysis of the hyperplastic tissue revealed expression of 5-HT4 receptor isoforms (a), (b), (c), (i), and (n), and of vasopressin receptors, V1 and V2. Their father and brother were overweight, had easy bruisability and presented with biological features of subclinical Cushing's syndrome. CT scan showed moderate adrenal enlargement. In vivo pharmacological screening tests for the detection of adrenal aberrant receptors in the brother were negative. Finally, three out of the two sisters' children were evaluated. They had neither clinical nor biological features of Cushing's syndrome. Their adrenal glands were normal on CT-scan evaluation. In vivo evaluation for the detection of aberrant adrenocortical receptors performed in one of these subjects was negative. In conclusion, this study shows that (i) familial AIMAH could be an autosomal dominantly inherited disorder; (ii) aberrant 5-HT4 serotonin and vasopressin receptors can be expressed in familial AIMAH; and (iii) phenotypic expression of familial AIMAH could be varied in a same family and more pronounced in female than in male patients.

Adrenal Glands↗
PubMed2006

Persistent and moderate hypercalcemia related to an ovarian clear cell adenocarcinoma: Pre- and postoperative parathyroid hormone related-peptide and 1,25-dihydroxyvitamin D3 levels.

OBJECTIVE: To evaluate the role of PTH-related peptide (PTH-rP) and 1,25-dihyhydroxyvitamin D3 in a case of hypercalcemia related to an ovarian adenocarcinoma. DESIGN: We report a case of humoral hypercalcemia in a patient aged 74 yr with a clear cell adenocarcinoma of the right ovary at an early stage of its development (stage T1aN0M0) revealed by moderate and persistent hypercalcemia (variable level between 2.7 and 3.2 mmol/l without any treatment) over six months. METHODS: PTH-rP and 1,25-dihydroxyvitamin D3 were measured in blood samples taken before and after hysterectomy and bilateral salpingooophorectomy and in blood samples taken intraoperatively from the right ovarian vein and a peripheral vein. RESULTS: High levels of plasma PTH-rP and 1,25-dihydroxyvitamin D3 concomitant with high serum calcium and low PTH levels were found before surgery, which was followed by normalisation of all parameters studied. A concentration gradient was found regarding plasma PTHrP (right ovarian vein 60.4 pmol/l, peripheral vein 4.5 pmol/l), not 1,25-dihydroxyvitamin D3. CONCLUSION: 1) moderate and persistent hypercalcemia can be observed at an early stage of an ovarian carcinoma; 2) the gradient of PTH-rP concentration between the samples taken from the right ovarian vein and a peripheral vein provides evidence for a direct secretion of PTH-rP by the ovarian tumor; 3) the increased 1,25-dihydroxyvitamin D3 level is not related to a direct ovarian production, but is a consequence of PTH-rP secretion.

Adenocarcinoma, Clear Cell↗
PubMed2005

An unusual form of Riedel's thyroiditis: a case report and review of the literature.

We report the case of a 36-year old woman with a history of long-term fever associated with a biologic inflammatory syndrome that was not corrected by several courses of corticosteroid treatment. The only remarkable result during previous investigations was the presence of a positive Epstein-Barr virus (EBV) serology. Clinical examination revealed an heterogenous thyroid with a nodule on the right lobe. Serum thyrotropin (TSH) concentration was normal. The levels of antiperoxidase antibodies and thyrocalcitonin were normal. Ultrasound examination of the neck showed a 3-cm hypoechogenous nodule in the right lobe of the thyroid. A total thyroidectomy was performed. Histopathologic findings led to the diagnosis of Riedel's thyroiditis. We observed a dramatic improvement after surgery with absence of fever and normalization of inflammatory parameters. The role of EBV infection in the process of this unusual form of Riedel's thyroiditis is discussed.

Adult↗
PubMed2004

Normal pregnancy in a woman with nesidioblastosis treated with somatostatin analog octreotide.

OBJECTIVE: We report the case of a 36-yr-old woman with nesidioblastosis treated throughout pregnancy with high doses of octreotide. We studied the course of blood glucose, foetal growth and development. METHODS: Blood samples were obtained every month throughout pregnancy and taken at birth from the umbilical cord. Sonography was performed repeatedly to monitor foetal growth. RESULTS: The daily dose of octreotide was adapted to blood glucose levels: a dose of 1000 microg was infused during the first part of pregnancy, then it was decreased step by step during the last trimester of gestation. An elective cesarean section was performed at 32 weeks of gestation. High octreotide concentrations were obtained during the first part of gestation (range 2888-5021 pg/ml). During the third trimester of pregnancy blood glucose increased despite high insulin levels attesting physiological insulin-resistance. Plasma levels of placental GH and IGF-1 levels were similar to those observed in a normal pregnancy. Despite the presence of octreotide in the umbilical cord, TSH, free T4, PRL and pituitary GH concentrations were normal at birth. The female newborn (weight 3520 g, length 52 cm) had no malformation, and presented with normal postnatal development. CONCLUSION: Our study demonstrates that: 1) octreotide treatment can be effective in controlling endogenous hyperinsulinism during pregnancy; 2) octreotide does not affect physiological changes during pregnancy such as insulin-resistance or placental GH level; 3) exposure of the foetus to octreotide throughout pregnancy does not induce any malformation and does not affect foetal development.

Adult↗
PubMed2004

Pituitary apoplexy and idiopathic thrombocytopenic purpura: a new case and review of the literature.

Pituitary apoplexy can occur as a complication of idiopathic thrombocytopenic purpura. We report here a new case of such association. A male patient aged 59 years, complaining of decreased libido for one year, was referred to the emergency department for purpura and severe thrombocytopenia (4000 platelets/mm3). 24 hours after the cutaneous rash the patient presented with clinical symptoms of bilateral cavernous sinus compression comprising ptosis, bilateral ophtalmoplegia and right supraorbital hypoesthesia. Cranial CT scan showed an enlarged sella and a pituitary mass with signs of intrapituitary haemorrhage. Hormonal evaluation showed hyperprolactinemia (50 ng/mL) and hypopituitarism, and the patient needed substitution with hydrocortisone and levothyroxine. Immunoglobulins and corticosteroids were given to the patient to treat thrombocytopenia, then worsening of neurological and ophtalmological symptoms led to pituitary surgery. Histopathological examination found necrotical pituitary tissue. Immunostaining with an anti-prolactin antibody was positive in several groups of cells. Neurological symptoms subsided and thrombocytopenia was corrected by treatment. In conclusion, we report a case of pituitary apoplexy due to severe thrombocytopenia occurring as a complication of a preexisting macroprolactinoma.

Adrenal Cortex Hormones↗
PubMed2003

Serotonin transporter availability correlates with alcohol intake in non-human primates.

A low level of alcohol intoxication upon initial exposure and impulsive aggressiveness predispose humans to alcoholism. In non-human primates, central serotonin transporter availability and turnover rate were associated with aggressive behavior and a low response to initial alcohol exposure. We assessed the respective effects of these factors on alcohol intake in a free choice paradigm. Serotonin transporter availability in the raphe area, the origin of central serotonergic projections, was measured with single-photon emission computed tomography and the radioligand [(123)I]beta-CIT in 11 rhesus monkeys with low and high central serotonin turnover. The amount of alcohol intake in the 3-month observation period was positively correlated with serotonin transporter availability (R=0.76, P=0.006), but not with aggressiveness (R=0.19, P=0.6) or alcohol response upon first exposure (R=-0.48, P=0.2). In a linear multiple regression analysis with serotonin transporter availability, alcohol response, and aggressiveness as independent variables, 82% of the variance of alcohol intake was explained and serotonin transporter availability emerged as the only statistically significant factor (beta=7.81, P=0.006). These observations indicate that there may be a direct relationship between serotonin transporter availability and alcohol intake after controlling for aggression and alcohol response on first exposure.

Aggression↗
PubMed2002

Intraoperative testosterone assay for virilizing ovarian tumor topographic assessment: report of a Leydig cell tumor of the ovary in a premenopausal woman with an adrenal incidentaloma.

Ovarian virilizing tumors are rare and can lead to assessment difficulties because of their small size. A 41-yr-old female was referred for evaluation of hirsutism that had increased within the previous 3 yr. Menstrual cycle length was normal. Plasma testosterone was 3.9 ng/ml (normal range, 0.2-0.8 ng/ml), was not suppressible by 2 mg dexamethasone (4.3 ng/ml), and was increased (6.3 ng/ml) after three daily injections of hCG (5000 IU). Abdominal computed tomography scan showed an adrenal nodule (13 x 6 mm) that remained unchanged after 3 months. Ultrasound examination of the pelvis was normal. Ovarian and adrenal venous catheterization did not yield additional information. Topographic assessment was made by intraoperative measurement of testosterone in the samples taken from each ovarian vein (competitive chemiluminescent immunoassay ADVIA Centaur; right ovarian vein, 105 ng/ml; left ovarian vein, 5 ng/ml; peripheral blood, 7 ng/ml). Right annexectomy resulted in normalization of testosterone levels (0.22 ng/ml). Histopathological examination found a Leydig cell tumor of hilar type (1.5 cm). This observation illustrates the usefulness of intraoperative measurement of testosterone by a rapid automated technique for topographic assessment of ovarian virilizing tumor in premenopausal women.

Adult↗
PubMed2002

[Hirsutism and hypertrichosis in adults: investigations and treatment].

Hypertrichosis, characterized by increased hair growth located in non-androgen-dependent areas, does not justify the monitoring of hormone levels, conversely to hirsutism, with increased hair growth in androgen-dependent areas of the female genitals. Adult hypertrichosis is iatrogenic (minoxidil, ciclosporine, diazoxide or glucocorticosteroids), of metabolic origin (porphyria), nutritional (anorexia) or paraneoplastic (hypertrichosis lanuoginosa). Metabolic or general assessment can help clinical diagnosis. In non-iatrogenic hirsutism the following must be eliminated: 1) a virilizing tumor (ovarian, adrenal) when confronted with rapid progression or recent hirsutism, plasma testosterone (T)>1.5ng/ml and/or (adrenal tumor) DHEA-sulfate (DHEAS)>700 microgram/dl and associated with hypertension; 2) when confronted with characteristic signs of hirsutism, Cushing's syndrome (post-dexamethasone cortisol), hyperprolactinemia (pooled PRL), or acromegalia (IGF1). Measurement of 17-OH-progesterone at 8 am on the 4th day of the cycle detects the late manifestation homozygous forms of a 21-hydroxylase (21OHD) block. The more frequent forms are: 1) ovarian polymicrocystic or hirsutism-anovulation syndromes without other causes (LH/FSH, T, hyperinsulinemia, sonography); 2) functional adrenal hyperandrogenia (increased DHEAS without organic cause); 3) idiopathic hirsutism. Treatment can be local (discoloration, depilation, diathermo-coagulation, laser). Treatment of hirsutism of organic origin is etiologic. The inhibitory effects of glucocorticosteroids are mediated by 21OHD. The most effective treatments are anti-androgenic: cyproterone acetate, progesterone-like and anti-gonadotropic (contraceptive) agents; and the only product in France officially indicated in hirsutism , spironolactone (anti-mineralocorticosteroid); and flutamide, pure anti-androgen (probably hepatoxic). Finasteride (type II 5 alpha-reductase inhibitor) appears less effective. Estrogen-progestagen-like agents can be associated with anti-androgens. We should also mention the GnRH-agonists, and finally, dietetics and metformine (in cases of insulin-resistance).

Adult↗
PubMed2001

Primary hyperparathyroidism and cutaneous T-cell lymphoma: fortuitous association?

This is the third report of an association between T-cell cutaneous lymphoma (mycosis fungoides) and primary hyperparathyroidism (adenoma). Some studies support the concept that hyperparathyroidism may have promotional activity for the development of certain malignant tumors. A high risk for successive or concurrent neoplasms has been reported in patients with parathyroid adenomas. Primary hyperparathyroidism in a neoplastic context may be underreported. Patients with tumor-associated hypercalcemia should be evaluated for the possibility of primary hyperparathyroidism.

Humans↗
PubMed2000

Calcium affinity of regulatory sites in skeletal troponin-C is attenuated by N-cap mutations of helix C.

Site-directed mutagenesis was used to make amino acid substitutions at position 54 of skeletal troponin C, testing a relationship between the stability of helix C and calcium ion affinity at regulatory sites in the protein. Normally, threonine at position 54 is the first helical residue, or N-cap, of the C helix; where helices C and D, and the loop between, comprise binding site II. Mutations were made in the context of a previously described phenylalanine 29--> tryptophan (F29W) variant (Trigo-Gonzalez et al., Biochemistry 31, 7009-7015 (1992)), which allows binding events to be monitored through changes in the intrinsic fluorescence of the protein. N-Cap substitutions at position 54 were shown to attenuate the calcium affinity of regulatory sites in the N-terminal domain. Calcium affinities diminished according to the series T54 T54S > T54A > T54V > T54G with dissociation constants of 1.36 x 10(-6), 1.36 x 10(-6), 2.09 x 10(-6), 2.28 x 10(-6), and 4.24 x 10(-6) M, respectively. The steady state binding of calcium to proteins in the mutant series was seen to be monophasic and cooperative. Calcium off-rates were measured by stopped flow fluorescence and in every instance two transitions were observed. The rate constant of the first transition, corresponding to approximately 99% of the change in fluorescence, was between 900+/-20 and 1470+/-100 s(-1), whereas the rate constant of the second transitions was between 94+/-9 and 130+/-23 s(-1). The significance of two transitions remains unclear, though both rate constants occur on a time scale consistent with the regulation of contraction.

Animals↗
PubMed1999

Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with a novel mutation in the DAX-1 gene.

We have studied a 20-yr-old male patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism (HH) due to a C to A transversion at nucleotide 825 in the DAX-1 gene, resulting in a stop codon at position 197. The same mutation was detected in his affected first cousin (adrenal hypoplasia congenita and HH) and in a heterozygous state in their carrier mothers. The patient had had acute adrenal insufficiency at the age of 2 yr and 6 months, bilateral cryptorchidism corrected surgically at the age of 12 yr, and failure of spontaneous puberty. Plasma testostereone (T) was undetectable (<0.30 nmol/L), gonadotropin levels were low (LH, <0.4 IU/L; FSH, 1.5 IU/L) and not stimulated after i.v. injection of 100 microg GnRH. The endogenous LH secretory pattern was apulsatile, whereas free alpha-subunit (FAS) levels depicted erratic pulses, suggesting an incomplete deficiency of hypothalamic GnRH secretion. During i.v. pulsatile GnRH administration (10 microg/pulse every 90 min for 40 h), each GnRH pulse induced a LH response of low amplitude (0.54 +/- 0.05 UI/L), whereas mean LH (0.45 +/- 0.01 IU/L) and FAS (63 +/- 8 mU/L) levels remained low. Amplitude of LH peaks (0.83 +/- 0.09 IU/L), mean LH (0.53 +/- 0.02 IU/L), and FAS (161 +/- 18 mU/L) levels increased (P < 0.01), whereas the T concentration remained low (0.75 nmol/L) when the pulsatile GnRH regimen was raised to 20 microg/pulse for a 40-h period, suggesting a partial pituitary resistance to GnRH. Thereafter, plasma T levels remained in prepubertal value after three daily im injections of 5000 IU hCG (3.6 nmol/L) and after 1-yr treatment with weekly i.m. injections of 1500 IU hCG (1.2 nmol/L), implying Leydig cell resistance to hCG. The patient had a growth spurt, bone maturation, progression of genital and pubic hair stages, and normalization of plasma T level (15.8 nmol/L) after a 12-month treatment with twice weekly injections of hCG and human menopausal gonadotropin (75 IU International Reference Preparation 2) preparations, suggesting that, in presence of FSH, a Sertoli cell-secreted factor stimulated Leydig cell production of T. In conclusion, we report a novel mutation in the DAX-1 gene in patients with AHC and HH. Our results suggest that the hypogonadism is due to a combined hypothalamic-pituitary-gonadal defect and imply that the DAX-1 gene may play a critical role in human testicular function.

Base Sequence↗
PubMed1999

Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration.

We have studied a kindred with three siblings with isolated hypogonadotropic hypogonadism caused by compound heterozygote mutations in the GnRH receptor gene. The disorder was transmitted as an autosomal recessive trait. The R262Q mutation in intracellular loop 3 of the receptor was associated with a mutation in the third transmembrane domain of the receptor, A129D, that has never been described before. This A129D mutation results in a complete loss of function, indicated by the lack of inositol triphosphate (TP3) 3 production by transfected Chinese hamster ovary (CHO) cells after GnRH stimulation. The two brothers had microphallus and bilateral cryptorchidism and were referred for lack of puberty, whereas their sister had primary amenorrhea and a complete lack of puberty. Their basal gonadotropin concentrations were below the reference range, and their endogenous LH secretory patterns were abnormal, with a low-normal frequency of small pulses or no apparent LH pulse. Pulsatile GnRH administration (10 microg/pulse every 90 min for 40 h) resulted in increased mean LH without any significant changes in testosterone levels in the two brothers, whereas the LH secretory profile of their sister remained apulsatile. Larger pulses of exogenous GnRH (20 microg every 90 min for 24 h) caused the sister to produce recognizable low amplitude LH pulses. The concentrations of free alpha-subunit significantly increased in all patients during the pulsatile GnRH administration. Thus, these hypogonadal patients are partially resistant to pulsatile GnRH administration, suggesting that they should be treated with gonadotropins to induce spermatogenesis or ovulation rather than with pulsatile GnRH.

Adolescent↗
PubMed1998

Vulnerability factors in the anxiety disorders.

Groups of non-clinical individuals scoring high and low on a measure of trait anxiety were compared to a group of people with a history of clinical anxiety on measures of locus of control of behaviour and reported parental rearing practices (group size = 30 in each group). The Parental Bonding Instrument (Parker, Tulping & Brown, 1979) was used to assess parental overprotection and care. A scale relating to parental sensitization was also used in this study. It was hypothesized that the high-trait anxiety group would produce similar results to the anxiety-disorder group on locus of control and parental overprotection, and similar results to the low-trait anxiety group on parental care and parental sensitization. The hypotheses were, in most cases, supported and a relationship between trait anxiety and parental overprotection was suggested. The results also suggested that parental sensitization may be particular to anxiety disorders.

Adolescent↗
PubMed1996

[Aldosterone precursors and hypertension with hypokalemia and adrenal module non caused by primary hyperaldosteronism].

The purpose of the study was to evaluate the interest of aldosterone precursors assays in arterial hypertension with hypokaliemia and adrenal nodules non due to aldosterone. Seven hypertensive patients, 3 men and 4 women, aged 59.5 +/- 10.1 years were included in the study. After drug withdrawal, kaliemia was 3.1 +/- 0.3 mmol/l (2.7-3.6), active renin 2.9 +/- 1.4 ng/l, plasma aldosterone (aldo) 108 +/- 49.4 pg/ml, cortisol 13 +/- 3.1 micrograms/100 ml, and [S] 0.47 +/- 0.5 micrograms/100 ml. Adrenal CT scan showed an adenoma in 3 patients (30.5 +/- 5 mm) and an unilateral nodular hyperplasia in 4 patients. In all patients, the plasma levels (RIA, chomatographic step) of the following steroids in the mineralocorticoid (MC) pathway were determined: DOC, 18 OH-DOC, B, 18 OH-B and aldosterone. Two from 7 (28%) exerted aldosterone precursors excess, 1 with DOC-producing adenoma (DOC-PA) (table), and 1 with a partial 11 beta hydroxylase deficiency (DOC: 211 pg/ml; S: 1 mu/100 ml). Aldosterone/DOC + 18 OH-DOC ratio proposed as a malignancy index was decreased in the patient with DOC-PA (8.1). No dysfunction in the MC pathway was identified in the 5 other patients. [table: see text] The study suggests the relevance of aldosterone precursors assays in low renin hypertension non due to aldosterone and in incidentally discovered adrenal masses.

Adenoma↗
PubMed1995

[Use of a gonadoliberin agonist with or without gonadoliberin pulses for ovulation induction in ovarian dystrophies].

OBJECTIVES: Determine whether ovulation in dystrophic ovaries treated with GnRH agonist followed by GnRH pulses is due to the GnRH pulse or is patient-dependent. SITE. Endocrinology department, CHU Purpan, Toulouse, France. METHODS: Fifteen infertile patients, age range 22 to 35 years, with ovarian dystrophy were given GnRH agonist (Decapeptyl, 3.75 mg IM on day 3 of the cycle). In 5 patients, an IV pulse of GnRH was then given (6 micrograms/90 min). STATISTICAL ANALYSIS: Mann-Whitney U test, corrected chi 2 test. RESULTS: Ovulation was achieved in 8/15 cases (3/5 with and 5/10 without pulsatile GnRH p = NS) and 3 pregnancies (without pulsatile GnRH). Before treatment LH was higher in patients who had an ovulation. CONCLUSION: Ovulation can be achieved after GnRH agonist treatment in patients with dystrophic ovaries, with or without pulsatile GnRH, particularly if the initial LH levels are high.

Adult↗