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P Bouloux

Publications and source records attributed to P Bouloux.

At least 19 recordsLinked to original sources
PubMed2003

Sandostatin LAR (long-acting octreotide acetate) for malignant carcinoid syndrome: a 3-year experience.

BACKGROUND: Somatostatin analogues are the best therapy for controlling the symptoms of malignant carcinoid syndrome. Octreotide acetate given as subcutaneous injection up to three times daily, intramuscular Lanreotide injection given once per 1-2 weeks and monthly intramuscular Sandostatin LAR have demonstrated similar efficacy in short-term studies. AIM: To assess the long-term effect of Sandostatin LAR on the management of patients with malignant carcinoid syndrome. METHODS: This was a 3-year retrospective study. Twenty-seven patients were assessed with a median follow-up of 23 months. Thirteen patients were switched from subcutaneous octreotide and 14 patients were octreotide naive. All patients showed avid uptake on indium-111 octreotide imaging. RESULTS: Ten of the 13 patients previously on subcutaneous octreotide and 13 of the 14 patients who were octreotide naive had good symptom control on Sandostatin LAR. Over the period of follow-up, many patients showed progression of their tumour and required additional therapies. Patients expressed a preference for monthly intramuscular Sandostatin LAR as opposed to daily subcutaneous injections of octreotide. Although Sandostatin LAR was difficult to administer in certain instances, overall it was well tolerated. CONCLUSIONS: Sandostatin LAR provides good long-term symptomatic control in patients with malignant carcinoid syndrome; it is well tolerated and patients expressed improved satisfaction in their management.

Adult↗
PubMed2001

Intramuscular plasmid DNA injection can accelerate autoimmune responses.

We have investigated if the administration of plasmid vectors engineered for gene delivery into mammalian muscle induced the production of anti-double stranded (ds) DNA and anti-nuclear autoantibodies in normal and autoimmunity-prone mouse models. In normal mice, repeated injection of plasmid DNA did not trigger an anti-DNA response. The presence of eukaryotic transcription factor binding sites in plasmid vectors did not increase autoantibody formation in these animals. In contrast, repeated injection of such plasmids in autoimmunity-prone MRL/MpJ mice caused a significant increase in both anti-dsDNA and anti-nuclear antibody levels. Thus the repeated administration of bacterial plasmids containing eukaryotic promoter elements may induce immune responses with generation of antibodies cross-reacting not only with the mammalian DNA, but also with nuclear antigens. The potential for iatrogenic autoimmunity in susceptible individuals should be considered.

Animals↗
PubMed1998

New approaches to the management of hepatitis and endocrine disorders in Cooley's anemia.

Hepatitis C infection is common in patients receiving life-long blood transfusion therapy. Interferon-alpha induces long-term viral clearance in 25-30% of patients suffering from Cooley's anemia. Ribavirin, an orally active guanoside analogue together with interferon-alpha produces a sustained response in up to 40% of patients with cirrhosis, who had previously failed single agent treatment. Growth retardation in iron-overloaded patients is the result of growth hormone deficiency in up to 30% of patients. Height gain can be successfully achieved in these patients with growth hormone treatment. Pregnancy in women with Cooley's anemia is now a reality, and over 100 pregnancies have been documented. Conception may be spontaneous or the result of ovulation induction. Cardiomyopathy and diabetes require careful assessment in these patients before a decision is made to treat with gonadotrophins to induce ovulation.

Antiviral Agents↗
PubMed1994

Epinephrine sensitizes human platelets in vivo and in vitro as studied by fibrinogen binding and P-selectin expression.

Epinephrine (Epi) infusion influences platelet activation markers in vivo, but in vitro studies have mainly examined supraphysiological Epi concentrations and have yielded conflicting results. In this study whole-blood flow-cytometric measurements of platelet fibrinogen binding and P-selectin expression were used to compare enhancement of ADP (0.1 to 10 mumol/L)-induced platelet activation by Epi infusion in vivo (0.1 and 0.4 nmol.kg-1.min-1) and by Epi in vitro (10 and 50 nmol/L) in nine healthy volunteers. ADP caused concentration-dependent increases in the percentage of platelets that bound fibrinogen (from 4.4 +/- 0.9% to 69.9 +/- 4.2%) and that expressed P-selectin (from 4.5 +/- 0.5% to 44.2 +/- 3.8%). Fibrinogen and P-selectin binding indices (FgBI and PSBI; calculated from mean fluorescence intensity and percentage of positive cells) also increased from 0.18 +/- 0.03 to 11.70 +/- 1.99 for FgBI and from 0.22 +/- 0.03 to 2.34 +/- 0.29 for PSBI. Epi concentration-dependently enhanced fibrinogen binding and P-selectin expression in vitro (by approximately 30% at the midportion of the ADP curve at 10 nmol/L Epi; P < .001 for both by ANOVAs). High-dose Epi infusion enhanced FgBI similarly and increased maximal P-selectin expression by 38%. Epi (50 nmol/L in vitro) enhanced platelet activation further, whether samples were taken with or without prior Epi infusion. Total expression of glycoprotein IIb/IIIa was unaffected by Epi infusion, but glycoprotein Ib expression per platelet was reduced (P < .05). These in vivo and in vitro effects of Epi on platelet responses to agonist stimulation indicate a prothrombotic potential for sympathoadrenal activation in humans.

Adenosine Diphosphate↗
PubMed1993

Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome.

Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. Three modes of transmission, X chromosome-linked, autosomal recessive and autosomal dominant, have been described. The KAL gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization recently determined. We have searched for mutations of the KAL gene in 21 unrelated males affected by familial Kallmann syndrome. In these families, segregation of the disease was suggestive of the X-linked mode of transmission. In 2 families, large Xp22.3 deletions, both including the entire KAL gene, have been detected by Southern blot analysis. Here we report the sequence analysis of the entire coding region of the KAL gene in the 19 remaining patients. The approach consisted of sequencing each of the 14 coding exons and splice site junctions. Each exon was amplified by PCR on the genomic DNA, using oligonucleotides from the flanking intronic sequences as specific primers. Nine point mutations were identified at separate locations in four exons and one splice site, providing strong evidence for heterogeneity in mutations responsible for the X-linked Kallmann syndrome. In addition, the high frequency of unilateral renal aplasia in X-linked Kallmann patients (6 out of 11 males with identified alterations of the KAL gene) should be emphasized.

Amino Acid Sequence↗
PubMed1993

Linkage analysis of 7 polymorphic markers at chromosome 11p11.2-11q13 in 27 multiple endocrine neoplasia type 1 families.

The multiple endocrine neoplasia type 1 (MEN1) locus has been previously localized to 11q13 by combined tumour deletion mapping and linkage studies. Family linkage analysis has defined the locus order as 11 cen-PGA-(PYGM, MEN1)-(D11S97, D11S146)-INT2-11qter, and tumour deletion mapping studies have suggested that the MEN1 locus is proximal to D11S146 but distal to PYGM. In order to establish further the location of MEN1, we have utilized the seven polymorphic DNA probes: D11S288, D11S149, PGA, PYGM, D11S97, D11S146 and INT2, in linkage studies of 339 members (116 affected) from 27 MEN1 families. Linkage between MEN1 and 6 of the 7 loci was established, and the highest peak lod scores [Z(theta)] were observed with PYGM and D11S97 at Z(theta) = 13.71, theta = 0.047 and Z(theta) = 13.76, theta = 0.076 respectively. Multilocus analysis suggested the most likely locus order as: 11 pter-(D11S288, D11S149)-11 cen-PGA-PYGM-MEN1-D11S97-D11S146-INT2-1 1qter. In addition, an examination of individual recombinants indicated a centromeric location of D11S149 in relation to D11S288. Thus, the results of our study, which favoured a location of MEN1 proximal to D11S97 and distal to PYGM, have established a panel of recombinants that will facilitate further meiotic mapping studies of the MEN1 locus.

Chromosomes, Human, Pair 11↗
PubMed1993

Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism.

The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX), ichthyosis (XLI), and Kallmann syndrome (KAL). We describe the clinical symptoms of a patient with a complex syndrome compatible with all these conditions plus ocular albinism (OA1). He has a terminal Xp deletion of at least 10 Mb of DNA. Both the mother and sister of the patient are carriers of the deletion and show a number of traits seen in Turner's syndrome. The diagnosis of ocular albinism was confirmed in the patient and his mother, who shows iris translucency, patches and streaks of hypopigmentation in the fundus, and macromelanosomes in epidermal melanocytes. By comparative deletion mapping we can define a deletion interval, which locates the OA1 gene proximal to DXS143 and distal to DXS85, with the breakpoints providing valuable starting points for cloning strategies.

Abnormalities, Multiple↗
PubMed1993

Xp22.3 deletions in isolated familial Kallmann's syndrome.

Several familial cases of Kallmann's syndrome (KS) have been reported, among which the X-chromosome-linked mode of inheritance is the most frequent. The gene responsible for the X-linked KS has been localized to the terminal part of the X-chromosome short arm (Xp22.3 region), immediately proximal to the steroid sulfatase gene responsible for X-linked ichthyosis. Large deletions of this region have been previously shown in patients affected with both X-linked ichthyosis and KS. We report here the search for Xp22.3 deletions in 20 unrelated males affected with isolated X-linked KS. Only 2 deletions were found using Southern blot analysis, indicating that large deletions are uncommon in patients affected with KS alone. Both deletions were shown to include the entire KAL gene responsible for X-linked KS. The patients carrying these deletions exhibit additional clinical anomalies, which are discussed: unilateral renal aplasia, unilateral absence of vas deferens, mirror movements, and sensory neural hearing loss.

Adolescent↗
PubMed1992

X chromosome-linked Kallmann syndrome: stop mutations validate the candidate gene.

Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. This syndrome is from a defect in the embryonic migratory pathway of gonadotropin-releasing hormone synthesizing neurons and olfactory axons. A candidate gene for the X chromosome-linked form of the syndrome was recently isolated by using a positional cloning strategy based on deletion mapping in the Xp22.3 region. With the PCR, two exons of this candidate gene were amplified on the genomic DNAs from 18 unrelated patients affected with the X chromosome-linked Kallmann syndrome. Three different base transitions--all leading to a stop codon--and one single-base deletion responsible for a frameshift were identified. We thus conclude that the candidate gene is the actual KAL gene responsible for the X chromosome-linked Kallmann syndrome. Furthermore, unilateral renal aplasia in two unrelated patients carrying a stop mutation indicates that the KAL gene is itself responsible for this Kallmann syndrome-associated anomaly. The gene is, therefore, also involved in kidney organogenesis. Additional neurologic symptoms in Kallmann patients are also discussed.

Base Sequence↗
PubMed1991

High-dose naloxone modifies cardiovascular and neuroendocrine function in ambulant subjects.

To determine the role of the opioids in the control of the cardiovascular system in awake ambulatory subjects, eight healthy men were infused with a high dose of naloxone (10 mg bolus plus 7 mg/hr), or saline placebo, for 12 hr. Ambulatory monitoring of blood pressure and heart rate every 10 min indicated no differences between trials for blood pressure (p greater than 0.80), but a significant difference for the maximal heart rate response during stair climbing or 1 km walks (p less than 0.02). Plasma cortisol concentration were increased during the naloxone trials (p less than 0.05), as was total urinary epinephrine and dopamine output (p = 0.005 and less than 0.03, respectively). Plasma FSH and LH concentrations were elevated during naloxone infusion (FSH: p less than 0.02, LH: p less than 0.01), but neither exercise or mental tasks significantly altered their levels (p greater than 0.20). The cardiovascular responses during moderate mental tasks were not affected by naloxone (p greater than 0.05). These results indicate that in the normal ambulatory state the opioid system has a minor role in cardiovascular regulation, as demonstrated by the urinary catecholamines. Its role becomes more evident when considerable stress is imposed.

Adult↗
PubMed1990

Endogenous opioids modulate the cardiovascular response to mental stress.

The role of endogenous opioids in the cardiovascular response to mental stress was investigated in two controlled studies. In the first, cardiovascular, hormonal and psychological measures were made in a group of subjects before, during and after presentation of either a mental stress task or a non-stressful control task in the presence of naloxone (8 mg), an opiate antagonist, or an equal volume of saline. The study was carried out in random order and single(subject)-blind. Naloxone specifically enhanced the heart rate response to the stressful task but had no effect on blood pressure, plasma epinephrine or norepinephrine, or feelings of anxiety. Naloxone increased plasma cortisol and ACTH in both stressful and control tasks. A second, double-blind, study replicated the effect on heart rate. An endogenous opioid mechanism thus appears to inhibit the cardiovascular response to stress.

Adolescent↗
PubMed1990

The role of alpha-2-adrenoceptors in the control of ACTH secretion; interaction with the opioid system.

This study examined the effects of an alpha-2-adrenoceptor antagonist on the secretion of ACTH basally and in response to the opioid antagonist naloxone, which is known to stimulate ACTH secretion by an adrenergic mechanism. Eight normal men were given, in double-blind, random order, intravenous infusions of normal saline (placebo), idazoxan (alpha-2-adrenoceptor antagonist), naloxone and the combination of idazoxan and naloxone. Naloxone increased plasma ACTH and cortisol concentrations in comparison to placebo. Idazoxan significantly enhanced the ACTH and cortisol responses to naloxone but had no effect on plasma ACTH or cortisol concentrations when given alone. These findings suggest that during some conditions of increased ACTH secretion, inhibitory alpha-2-adrenoceptors are activated and that these receptors limit the ACTH response. This provides an explanation for some of the apparent contradictions in interpreting the data from previous studies on the effects of catecholamines on the secretion of ACTH.

Adrenergic alpha-Antagonists↗
PubMed1989

Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11.

Familial multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disorder characterized by the combined occurrence of tumors of the parathyroid glands, the pancreas, and the pituitary gland. Pancreatic tumors have previously been shown to be associated with the loss of alleles on chromosome 11; we therefore looked for similar genetic alterations in specimens of parathyroid tumors, which are the most common feature of MEN-1. We obtained parathyroid tumors and peripheral-blood leukocytes from six patients with MEN-1; 18 cloned human DNA sequences from chromosome 11 were then used to identify restriction-fragment-length polymorphisms. A loss of heterozygosity was detected in parathyroid tumors from three of the six patients with MEN-1; this finding demonstrated that allelic deletions on chromosome 11 are involved in the monoclonal development of parathyroid tumors in patients with MEN-1. In addition, studies of three affected families (with 17 affected members and 51 unaffected members) established linkage with the oncogene INT2 (peak lod score, 3.30, at 0 percent recombination); the MEN-1 gene was thus mapped to the pericentromeric region of the long arm of chromosome 11 (11q13). Our location of the MEN-1 gene at 11q13 is close to the location previously reported. We conclude that a single inherited locus on chromosome 11, band q13, causes MEN-1 and that the monoclonal development of parathyroid and pancreatic tumors in patients with MEN-1 involves similar allelic deletions on chromosome 11.

Adolescent↗