Biomedical subjects

Omar Serri

Publications and source records attributed to Omar Serri.

9 recordsLinked to original sources

PubMed2006

The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy.

OBJECTIVE: In view of the association of hyperprolactinaemia with insulin resistance, we hypothesized that patients with hyperprolactinaemia may present increased cardiovascular risk markers. DESIGN: Descriptive clinical trial. METHODS: Serum glucose, insulin, insulin resistance, lipids, high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and soluble E-selectin (sELAM-1) serum levels were determined in 15 patients with hyperprolactinaemia at baseline (compared with 20 healthy subjects) and after 12 weeks of cabergoline therapy (0.5-1 mg twice per week). We also measured mononuclear cell NF-kappaB activation and TNF-alpha production in a subset of subjects. RESULTS: Serum levels of prolactin (PRL), insulin, insulin resistance (HOMA-IR) index and hsCRP were significantly higher in patients than in control subjects. Markers of mononuclear cell activation did not differ between the groups. Hyperprolactinaemia, BMI and age were predictors of hsCRP. BMI was the only predictor of HOMA-IR. Cabergoline therapy significantly reduced serum PRL, insulin, hsCRP and sELAM-1 levels. CONCLUSIONS: These data suggest that hyperprolactinaemia is associated with insulin resistance related to increased BMI and low-grade inflammation independently of BMI. Short-term cabergoline therapy can reduce the inflammatory markers.

Adult↗

PubMed2006

Canadian consensus guidelines for the diagnosis and management of acromegaly.

Acromegaly is a chronic condition associated with considerably increased morbidity and mortality if left unchecked. In December 2004, a national meeting was held to discuss the diversity in clinical practice across the country in diagnosing and treating patients with acromegaly, as well as to seek consensus on a number of management principles. The group reviewed recent guidelines and discussed issues of diagnosis, treatment, monitoring and treating comorbidities to seek a Canadian consensus on the management of this rare disorder. Consensus was that diagnosis should include clinical and biochemical findings, but is hinged on establishing GH hypersecretion with IGF-I and OGTT testing. Treatment has traditionally included surgical resection or debulking, along with adjunctive medical therapy (primarily somatostatin analogues), if necessary, to normalize GH levels. The option of primary medical therapy in managing this condition has recently emerged and can be justified for non-surgical candidates or for those in whom surgery is not expected to be curative. Overall, improved screening practices and superior epidemiological data are required, since timely diagnosis and appropriate treatment are crucial for reducing the potentially debilitating effects of this chronic, progressive disease. The current evidence also supports the need for long-term follow-up of disease activity and comorbidities in diagnosed patients. A national meeting was held to discuss the diversity in clinical practice across the country in diagnosing and treating patients with acromegaly, as well as to seek consensus on a number of management principles. After brief reviews of the most recent Canadian guidelines and the 2004 guidelines published by the American Association of Clinical Endocrinologists, the group was asked to specifically examine the issues of diagnosis, treatment, monitoring and treating comorbidities and seek a Canadian consensus on practice. This paper summarizes the working group's findings and the points of consensus that were achieved.

Acromegaly↗

PubMed2006

Canadian guidelines for the management of adult growth hormone deficiency.

PURPOSE: To develop guidelines for the management of growth hormone (GH) deficiency in Canadian adults to facilitate rational use of GH in appropriate indications. METHODS: The guidelines were developed by group of endocrinologists and an endocrine specialist nurse with an interest in neuroendocrine disorders, representing all regions of Canada and practicing in a variety of settings. A steering committee with broad expertise undertook a systematic review of the evidence relating to adult GHD and GH replacement. This evidence was reviewed by the whole group, and guidelines were developed using a consensus approach. RESULTS: The document addresses the causes and clinical characteristics of GHD in adults and reviews the evidence in support of GH replacement in this group. The authors provide recommendations for the identification of adult GHD, and guidelines for GH replacement in appropriate patients. Also, access to GH therapy across Canada is reviewed.

Adult↗

PubMed2004

Enhanced lipoprotein lipase secretion and foam cell formation by macrophages of patients with growth hormone deficiency: possible contribution to increased risk of atherogenesis?

GH deficiency is associated with increased prevalence of atherosclerosis, and recent data indicate a proatherogenic role for macrophage lipoprotein lipase (LPL) in the arterial wall. In this pilot study, we determined LPL expression and foam cell formation in monocyte-derived macrophages of 12 control subjects and nine patients with GH deficiency without GH replacement therapy. LPL mRNA levels, mass, and activity were increased in macrophages of patients with GH deficiency. In these subjects, macrophage LPL activity correlated with body mass index and fat mass. Incubation of patient macrophages with IGF-I for 24 h or differentiation of monocytes isolated from GH-deficient patients into macrophages in the presence of this growth factor decreased the amount of LPL mass. Compared with control cells, macrophages derived from GH-deficient patients took up and stored increased amounts of proatherogenic lipoproteins and were more easily converted to foam cells. In the supernatants of these cells, increased levels of free fatty acids and TNFalpha were also documented. These results demonstrate that macrophages of patients with GH deficiency secrete increased amounts of proatherogenic cytokines and are more susceptible to foam cell formation. These alterations may contribute to the increased cardiovascular risk in patients with GH deficiency.

Adult↗

PubMed2004

Long-term biochemical status and disease-related morbidity in 53 postoperative patients with acromegaly.

UNLABELLED: Assessment of postoperative disease activity of acromegaly is a major challenge. The consensus criteria for cure, which are glucose-suppressed GH less than 1 micro g/liter and normal IGF-I levels, might be discrepant, and their respective relationship to acromegaly-related morbidity is not well known. THE AIMS OF OUR STUDY WERE: firstly, to correlate plasma IGF-I with plasma glucose-suppressed GH concentrations; and secondly, to correlate each of these biochemical parameters with morbidity [impaired glucose tolerance (IGT), diabetes, and hypertension] in postoperative patients with acromegaly. Fifty-three patients with long-term follow-up (mean, 12.7 yr; range, 1-30 yr) after transsphenoidal surgery for acromegaly and 20 healthy subjects matched for age, sex, and body mass index were evaluated for plasma glucose [by 75-g oral glucose tolerance test (OGTT)], GH (by immunoradiometric assay), plasma IGF-I (by immunoradiometric assay), and blood pressure (BP) measurements. Remission was defined by a normal IGF-I. We identified 34 acromegalics in remission and 19 with active disease. There was no statistical difference between all three groups for age, sex, BMI, and for fasting and 2-h post-OGTT plasma glucose. The time elapsed since surgery was similar in both groups of acromegalics. The OGTT-GH nadir was less than 1 micro g/liter in 31 patients in remission (91.2%) and in nine patients with active disease (47.4%). Prevalence of IGT was lower in acromegalics in remission (14.7%) in comparison with patients with active disease (47.4%; P = 0.01). Plasma IGF-I and GH nadir cut-off of 0.25 microg/liter were strong predictors of abnormal glucose tolerance (odds ratio, 13.6; confidence interval, 2.5-73.7; P = 0.003). GH nadir cut-off of 1 microg/liter and basal GH of 2.5 microg/liter failed to predict abnormal glucose tolerance. There was no statistical difference for prevalence of hypertension and systolic BP values, but diastolic BP was significantly lower in patients in remission than in those with active disease (P < 0.05). Our observations indicate that the validity of the GH threshold of 1 microg/liter post OGTT might be inadequate as a criterion of biochemical remission of acromegaly and as a marker of associated comorbidities. However, normalized IGF-I concentrations and a lower GH cut-off value less than 0.25 micro g/liter are strongly associated with a lower prevalence of IGT and lower diastolic BP in long-term postoperative acromegaly.

Acromegaly↗

PubMed2003

Diagnosis and management of hyperprolactinemia.

Prolactin is a pituitary hormone that plays a pivotal role in a variety of reproductive functions. Hyperprolactinemia is a common condition that can result from a number of causes, including medication use and hypothyroidism as well as pituitary disorders. Depending on the cause and consequences of the hyperprolactinemia, selected patients require treatment. The underlying cause, sex, age and reproductive status must be considered. We describe the diagnostic approach and management of hyperprolactinemia in various clinical settings, with emphasis on newer diagnostic strategies and the role of various therapeutic options, including treatment with selective dopamine agonists.

Female↗

PubMed2003

Benefits of gliclazide in the atherosclerotic process: decrease in monocyte adhesion to endothelial cells.

Atherosclerotic cardiovascular disease is the leading cause of premature death in patients with diabetes. Atherosclerosis is a chronic immune-mediated disease, the initiation, progression, and destabilization of which is driven and regulated by inflammatory cells. One critical event in the initiation of this vascular inflammatory disease is the adhesion of leukocytes to the activated endothelium and their migration into the vessel wall. These processes are mediated by the upregulation of adhesion molecules on endothelial cells (ECs) and an increased expression in the vascular wall of chemotactic factors to leukocytes. Monocyte binding to ECs is increased in diabetes. One major determinant of this alteration could be oxidative stress. Given the free-radical scavenging activity of gliclazide, we determined the ex vivo and in vitro effects of this drug on human monocyte binding to ECs and the molecular mechanisms involved in this effect. Our results demonstrate that short-term administration of gliclazide to patients with type 2 diabetes normalizes the levels of plasma lipid peroxides and monocyte adhesion in these subjects. Gliclazide (10 microg/mL) also reduces oxidized low-density lipoprotein (oxLDL)- and advanced glycation end product (AGE)-induced monocyte adhesion to ECs in vitro. The inhibitory effect of this drug on AGE-induced monocyte adhesion involves a reduction in EC adhesion molecule expression and inhibition of nuclear factor kappaB (NF-kappaB) activation. In addition, gliclazide inhibits oxLDL-induced monocyte adhesion to cultured human aortic vascular smooth muscle cells (HASMCs) in vitro and reduces the production of monocyte chemotactic protein-1 (MCP-1) by these cells. Taken collectively, these results show that gliclazide, at concentrations in the therapeutic range, inhibits ex vivo and in vitro monocyte adhesiveness to vascular cells. By doing so, this drug could reduce monocyte recruitment into the vessel wall and thereby contribute to attenuating the sustained inflammatory process that occurs in the atherosclerotic plaque. These findings suggest that treatment of diabetic patients with this drug may prevent or retard the development of vasculopathies associated with diabetes.

Animals↗

PubMed2003

Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly.

OBJECTIVE: Acromegaly has long been associated with increased mortality but few long-term follow-up data are available in patients treated for this disease. We therefore studied a group of 103 patients who underwent transsphenoidal adenomectomy for acromegaly between 1970 and 1999 and were followed for one to 30 years. DESIGN AND PATIENTS: A retrospective chart review was performed on 103 patients living in the province of Quebec, Canada. Mortality data were obtained by hospital charts, contact with the patient's family or death certificates. Stringent biochemical criteria were used to define remission (random GH < 2.5 microg/l, or GH nadir after an oral glucose load is < 1 microg/l and IGF-I within the normal range) and patient survival in the group in remission and the group with persistent disease were compared to survival of the population of Quebec, Canada, using the probabilities of the Poisson distribution. RESULTS: There were four deaths in the perioperative period, one of which was directly related to surgery. Initial remission was obtained in 82% of microadenomas, 60% of macroadenomas and 24% of invasive adenomas. The long-term (> or = 10 years) remission rate for surgery alone was 52%. A second transsphenoidal surgery, radiation therapy and/or octreotide were used in a subset of patients with persistent disease. Long-term remission was obtained in 63% of patients. Five (mean age, 64 years) of the 57 patients in remission died; this rate did not differ significantly from the mortality rate expected in the general population (P = 0.18). Thirteen (mean age, 59.8 years) of the 34 patients with persistent disease died; this rate was significantly higher than that expected in the general population (P = 0.008). CONCLUSIONS: Our observations confirm that uncontrolled acromegaly increases mortality compared to the general population and that mortality rates similar to the general population are restored once remission is induced.

Acromegaly↗

PubMedDate not supplied

Monocyte adhesion in diabetic angiopathy: effects of free-radical scavenging.

Increased interaction of monocytes with vascular cells is linked to the development and progression of atherosclerosis in patients with diabetes. One major determinant of increased monocyte binding to vascular cells could be oxidative stress. Given the free-radical scavenging properties of gliclazide, we evaluated the ex vivo and in vitro effects of this drug on human monocyte binding to endothelial cells and smooth muscle cells (SMCs). Short-term administration of gliclazide to patients with type 2 diabetes decreases plasma lipid peroxides and lowers the enhanced adhesion of diabetic monocytes to cultured endothelial cells observed before gliclazide treatment. Gliclazide (10 microg/ml) also reduces oxidized low-density lipoprotein (oxLDL)- and advanced glycation end product (AGE)-induced monocyte adhesion to cultured endothelial cells. The suppressive effect of gliclazide on AGE-induced monocyte adhesion to endothelium involves a reduction of cell adhesion molecule mRNA and protein expression and an inhibition of NF-kappaB activation. Gliclazide also inhibits oxLDL-induced monocyte adhesion to cultured human aortic smooth muscle cells (HASMCs). Furthermore, treatment of HASMCs with gliclazide results in a marked decrease in oxLDL-induced monocyte chemoattractant protein-1 expression, both at the gene and protein levels. These results suggest that gliclazide, at concentrations in the therapeutic range (5-10 microg/ml), by its ability to decrease monocyte-vascular cell interactions could reduce monocyte accumulation in the atherosclerotic plaque and thereby contribute to attenuate the sustained inflammatory process that occurs in the vessel wall. These findings suggest that treatment of diabetic patients with gliclazide may prevent or retard the development of vascular disturbances associated with diabetes.

Aged↗