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Biomedical subjects

J Lefebvre

Publications and source records attributed to J Lefebvre.

At least 37 records · Page 2Linked to original sources
PubMed2000

A comparative review of the efficacy of antihypertensive agents on 24 h ambulatory blood pressure.

BACKGROUND: Ambulatory blood pressure (ABP) monitoring has contributed significantly to the diagnosis, prognosis and treatment of hypertension. However, most of the published reviews have not focused on the 24 h efficacy of conventional and new antihypertensive agents as measured by ABP monitoring. OBJECTIVES: To discuss the importance of 24 h blood pressure control, and to review the antihypertensive efficacy of conventional antihypertensive agents and of angiotensin II type I receptor (AT1R) blockers as assessed by ABP monitoring. PATIENTS AND METHODS: The 24 h antihypertensive efficacy of the different classes of agents was reviewed based on clinical, randomized, double-blind trials published in peer review journals. These trials were mainly performed in the authors' research unit but were performed in other centres as well. RESULTS AND CONCLUSIONS: Most antihypertensive agents provided 24 h ABP control. However, in the authors' experience, hydrochlorothiazide, some angiotensin converting enzyme inhibitors and low dosages of the calcium antagonist diltiazem did not permit satisfactory blood pressure reduction as assessed by ABP monitoring in truly hypertensive patients. AT1R blockers and especially those of the new generation characterized by tight and long lasting AT1-receptor binding produced adequate 24 h ABP control and continued effectiveness during the high risk early morning hours.

Adrenergic beta-Antagonists↗
PubMed2000

[Human pancreatic stem cell and diabetes cell therapy].

Cell therapy offers today important perspectives for the treatment of type 1 diabetes. The current utilization of primary human islets of Langerhans nevertheless forbids all hope of developing this treatment on a large scale. The recent description of the persistence of stem cells capable of proliferating and differentiating in the adult pancreas offers an attractive alternative for the production in vitro of homologous insulin-secreting cells. We first reproduced in vitro from human islet preparations the proliferation of ductal epithelial structures and their progressive organization. Thereafter, we focused on the description of a reproducible source of human ductal cells by the transdifferentiation of exocrine preparations. More recently we described in these exocrine derived ductal cells the the expression the of insulin promoter factor-1 (IPF-1/otherwise known as PDX-1), a transcription factor essential for the differentiation of ductal cells into endocrine cells during both development and pancreatic regeneration. If the proliferation and differentiation of these cells is confirmed, this approach could lead to the description of an abundant source of human pancreatic stem cells for the production ex vivo of human insulin secreting cells and may even allow autologous cell therapy, in the absence of immunosuppression.

Cell Culture Techniques↗
PubMed1999

[Relationship between corticotropin and arginine vasopressin in endocrine diseases].

VASOPRESSIN: The action of vasopressin (AVP) is not limited to regulating water excretion but also plays an essential role in regulating the corticotropic axis during stress. PHYSIOLOGY: Vasopressin is synthesized in the hypothalamus and stored in the posterior pituitary. It acts on 3 types of receptors (RV). RV1a are vascular receptors mediating the vasoconstrictor and glycogenolytic effects of the hormone. Anterior pituitary RV1b or V3 mediate stimulating effects on the corticotropic axis. Renal RV2 regulate water and urea excretion. Hypothetical extrarenal RV2 would be responsible for the vasodilator and procoagulant effects of the hormone. MODIFICATIONS IN ENDOCRINE DISEASES: Pituitary or adrenal hypocorticism syndromes include hyponatremia with secondary plasma hypoosmolality and reduced glomerular filtration due to the direct effect of glucocorticoids and also the effect of vasopressinism. Certain endogenous hypercorticisms appear to be related to an overexpression of RV: in ACTH-independent Cushingís syndrome, adrenal overexpression of eutopic RV1a, and in ACTH-dependent Cushingís syndrome, pituitary overexpression of eutopic RV1b or ectopic RV2. In addition, inappropriate secretion of antidiuretic hormone is frequent after transphenoidal surgery, particularly for corticotropic adenomas. DYNAMIC TESTS: The physiological response of ACTH and also AVP to corticotropin releasing hormone (CRH) in the petrous sinus, the unusual responses of certain corticotropic tumors to dDAVP, or certain forms of ACTH-independent hypercortisolism to lysine vasopressin (LVP) suggest excessive or ectopic expression of RV in corticotropic or adrenal cells: tumorgenesis of these cells could also depend, at least partially, on AVP.

Adrenocorticotropic Hormone↗
PubMed1999

Transient pseudo-hypoaldosteronism following resection of the ileum: normal level of lymphocytic aldosterone receptors outside the acute phase.

Pseudo-hypoaldosteronism (PHA) is due to mineralocorticoid resistance and manifests as hyponatremia and hyperkalemia with increased plasma aldosterone levels. It may be familial or secondary to abnormal renal sodium handling. We report the case of a 54-year-old woman with multifocal cancer of the colon, who developed PHA after subtotal colectomy, ileal resection and jejunostomy. She was treated with 6 g of salt daily to prevent dehydration, which she stopped herself because of reduced fecal losses. One month later she was admitted with signs of acute adrenal failure, i.e. fatigue, severe nausea, blood pressure of 80/60 mmHg, extracellular dehydration, hyponatremia (118 mmol/l); hyperkalemia (7.6 mmol/l), increased blood urea nitrogen (BUN) (200 mg/dl) and creatininemia (2.5 mg/dl), and decreased plasma bicarbonates level (HCO3-: 16 mmol/l; N: 27-30). However, the plasma cortisol was high (66 microg/100 ml at 10:00 h; N: 8-15) and the ACTH was normal (13 pg/ml, N: 10-60); there was a marked increase in plasma renin activity (>37 ng/ml/h; N supine <3), active renin (869 pg/ml; N supine: 1.120), aldosterone (>2000 pg/ml; N supine <150) and plasma AVP (20 pmol/l; N: 0.5-2.5). The plasma ANH level was 38 pmol/l (N supine: 5-25). A urinary steroidogram resulted in highly elevated tetrahydrocortisol (THF: 13.3 mg/24h; N: 1.4+/-0.8) with no increase in tetrahydrocortisone (THE: 3.16 mg/24h; N: 2.7+/-2.0) excretion, and with low THE/THF (0.24; N: 1.87+/-0.36) and alpha THF/THF (0.35; N: 0.92+/-0.42) ratios. The number of mineralocorticoid receptors in mononuclear leukocytes was in the lower normal range for age, while the number of glucocorticoid receptors was reduced. Small-bowel resection in ileostomized patients causes excessive fecal sodium losses and results in chronic sodium depletion with contraction of the plasma volume and severe secondary hyperaldosteronism. Nevertheless, this hyperaldosteronism may be associated with hyponatremia and hyperkalemia suggesting PHA related to the major importance of the colon for the absorption of sodium. In conclusion, this case report emphasizes 1) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation; 2) the major increase in AVP and the small increase in ANH; 3) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios; 4) the normal number of lymphocytic mineralocorticoid receptors outside the acute episode.

Colectomy↗
PubMed1999

Changes in serum amylase, lipase and leukocyte elastase during diabetic ketoacidosis and poorly controlled diabetes.

Diabetic ketoacidosis (DKA) is frequently associated with pancreatic enzyme abnormalities. In order to determine the main factors that lead to this increase, serum total amylase (TA), pancreatic amylase (PA), lipase (L) and leukocyte elastase (LE), an early predictor of acute pancreatitis, were measured in four groups of patients on admission. Group 1 consisted of 52 patients with DKA (age: 41.9 +/- 19.2 years; blood glucose (Glc): 27.4 +/- 11.5 mmol/L; pH: 7.20 +/- 0.16; plasma bicarbonate: 10.5 +/- 6.2 mmol/L; blood urea nitrogen (BUN): 0.60 +/- 0.44 g/L; HbA(1C): 12.5% +/- 2.8%). Group 2 consisted of 90 patients with poorly controlled non-ketotic diabetes (age: 53.4 +/- 16.0; Glc: 14.3 +/- 0.6; HCO(3)(-): 26.6 +/- 3.2; BUN: 0.38 +/- 0.20; HbA(1C): 11.3 +/- 2.1). Group 3 consisted of 22 patients with well-controlled diabetes (age: 53.7 +/- 12.8; Glc: 10. 1 +/- 5.2; HCO(3)(-): 27.4 +/- 3.8; BUN: 0.36 +/- 0.19; HbA(1C): 6.8 +/- 0.8). Group 4 (controls) comprised 27 non-diabetic patients (age: 46.0 +/- 15.0; Glc: 4.9 +/- 0.5; HCO(3)(-): 28.4 +/- 2.5; BUN: 0.30 +/- 0.16; HbA(1C): 5.2 +/- 0.7) (means +/- SD). Increased enzyme activities were more frequent in group 1 (TA: 30.7; PA: 27.0; L: 36.5; LE: 73%) than in groups 2 (TA: 8.9; PA: 7.1; L: 8.9; LE: 45. 5%), 3 (TA: 13.6; PA: 9.0; L: 18.1; LE: 31.8%) and 4 (TA: 7.0; PA: 3. 0; L: 0.0; LE: 29.6%). Mean serum enzyme activities were significantly different in the 4 groups (ANOVA, P < 0.01) and were higher in group 1 than in groups 2, 3 and 4 (Student's t-test; group 1 vs 2 or 3 or 4: P < 0.001). In groups 1 + 2 + 3 + 4 (all patients), the four enzymes correlated with one another and also with Glc, BUN and HCO(3)(-) (P < 0.001). In group 1, TA correlated negatively with HCO(3)(-) (P < 0.001) and pH (P < 0.05); PA and L correlated positively with Glc and BUN (P < 0.01) and negatively with HCO(3)(-) (respectively, p < 0.01 and 0.05). PA correlated positively with pH (P < 0.01); LE correlated with Glc (P < 0.05) and BUN (P < 0.01). In conclusion, this study suggests that the serum levels of pancreatic enzymes increase with the degree of diabetic disequilibrium, and mainly correlate with metabolic factors such as hyperglycaemia, dehydration and acidosis. Increased pancreatic enzyme activities in patients with DKA, even in combination with abdominal pain, should not be diagnosed as acute pancreatitis; this could be important, particularly for younger clinicians.

Adult↗
PubMed1999

Chronotherapeutics: are there meaningful differences among antihypertensive drugs?

In the past decade, many publications have dealt with the possible relationship between biological rhythms and the incidence of cardiovascular events. A high proportion of treated hypertensive patients have cardiovascular complications, and chronotherapy, which permits the use of drugs that are maximally effective at different points in the circadian cycle, may be an interesting and valuable approach to decreasing morbidity and mortality in these patients. This article summarizes current knowledge on the new science of chronopharmacology, as demonstrated in several clinical studies that have used conventional agents administered at various points in the circadian cycle as well as new chronotherapeutic agents, such as controlled onset extended release (COER)-verapamil. In addition, emphasis is given to a rigorous evaluation of antihypertensive agents in terms of efficacy and duration of effect to obtain adequate and sustained lowering of blood pressure over the 24-hour period.

Antihypertensive Agents↗
PubMed1999

Structural investigation of beta-lactoglobulin gelation in ethanol/water solutions.

The aggregation and gelation properties of beta-lactoglobulin (BLG), a globular protein from milk, was studied in hydro-ethanolic solutions (50/50% (v/v)) at room temperature. The phase state diagrams as a function of pH and ethanol concentration showed that a gel structure appeared after a period ranging from 1 min to 1 week depending on the physico-chemical conditions. The aggregation kinetics, studied by infrared spectroscopy and dynamical rheological measurements, highly depended upon the pH; the process being the fastest at pH 7. Alcohol-induced aggregation of BLG was characterized by the formation of intermolecular hydrogen bonded beta-sheet structures. Small angle neutron scattering indicated that the aggregates structures in the final gels were similar at pH 7, 8 and 9. Through the data obtained at the molecular and macroscopic levels, it can be concluded that the kinetics of gelation were pH dependent while the spatial arrangements of the aggregates were similar in the final structures. The heterogeneous structures formed in hydro-ethanolic gels could be analysed in terms of a phase separation, the syneresis being the final visible state.

Ethanol↗
PubMed1999

Human pancreatic islet quality control: easy assessment of metabolic functions.

We describe simplified and rapid methods to assess islet function with the aim to develop better protocols for islet isolation and to determine islet characteristics before transplantation. These methods are also useful in the assessment of the potentially beneficial or deleterious effects of compounds added to the culture media in stimulation experiments. To this end, we took advantage of the multiscreen assay system produced by Millipore SA. This 96-well unit allowed the free-floating culture of islets on filter membranes, the rapid vacuuming and collection of conditioned media or reaction buffer and thus successive testing of the same number of islets, possibly at different culture times. We estimated islet viability by determination of the metabolic activity of cells, normal function of islets by their ability to metabolize glucose and to synthesize and secrete insulin and of nitrite release, a reflection of nitric oxide (NO) status of cells, which may be involved in a signaling pathway during glucose-stimulated insulin secretion or in cytokine inducible pathway. Assays may be performed either on selected islets or on aliquots of semi-purified preparations designated for grafting, allowing thus the rapid estimation of graft function of the entire preparation. This herein described system may be also extended to many other functional tests.

Automation↗
PubMed1999

Second generation of the automated Cobas Amplicor HCV assay improves sensitivity of hepatitis C virus RNA detection and yields results that are more clinically relevant.

The first and second generations of the Cobas Amplicor HCV assay were compared among patients at risk of hepatitis C virus (HCV) infection. The second-generation test was found to be of greater sensitivity and of good specificity among clinical specimens containing HCV RNA of different genotypes. Finally, this new test is shown to predict the outcome of interferon therapy better.

Hepacivirus↗
PubMed1999

Aldosterone-producing adenoma without hypertension: a report of two cases.

Normotensive primary hyperaldosteronism is exceedingly rare. We report two new cases of this syndrome in two middle-aged women, one of Asian origin. The presenting signs were tetany in one case and an adrenal mass in the other. Neither patient had hypertension, despite repeated measurements with a manual armlet. A typical biological profile of primary hyperaldosteronism was demonstrated in both patients, including hypokalemia with inappropriate kaliuresis, elevated resting plasma aldosterone, and undetectable plasma renin activity. The circadian rhythm of blood pressure was studied by ambulatory monitoring pre- and post-operatively. It confirmed the lack of hypertension, but the circadian rhythm of blood pressure was lost before surgery in one patient. Surgical removal of the histologically typical aldosterone-producing adenomas normalized the kalemia. The main finding in these two patients was spontaneously low blood pressure in the post-operative period. This suggests that excess aldosterone induced relative hypertension in these patients whose blood pressure was spontaneously very low. Genetic screening for dexamethasone-sensitive hyperaldosteronism was negative in both patients.

Adenoma↗
PubMed1999

[Nephrogenic diabetes insipidus].

Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by polyuro-polydipsic syndrome (> 30 ml/kg/day in adult) related to an inability to concentrate the urine secondary to resistance to the antidiuretic action of vasopressin (AVP) or to its V2 agonist, dDAVP. NDI may be congenital or acquired. Congenital NDI, familial in most cases, are related in 90% of cases to mutations of the gene coding for V2 receptor of AVP (X-linked recessive disease), and in 10% of cases, to mutations of the gene encoding for aquaporin 2 (autosomic recessive disease). This water channel is expressed at the apical membrane of principal cells of collecting ducts and mediates water transport across the apical plasma membrane of these cells. It is regulated by AVP in two ways. First, AVP has a short term effect in triggering translocation of aquaporin-2-containing intracytoplasmic vesicles to the apical membrane. Second, AVP has a long term effect in increasing the expression of aquaporin-2 in collecting duct. Acquired NDI are iatrogenic (lithium), or related to electrolytic (hypokalemia) or renal abnormalities. The mechanism of these acquired NDI is a decrease of aquaporin 2 abundance in the renal collecting duct.

Aquaporin 2↗
PubMed1998

Urinary cortisol metabolites in the assessment of peripheral thyroid hormone action: overt and subclinical hypothyroidism.

UNLABELLED: Biological assessment of peripheral thyroid hormone action may be important in subclinical hypothyroidism, where decision-making is often difficult. The impairment of urinary cortisol metabolites in overt hypothyroidism reflects an acquired 11 beta hydroxysteroid dehydrogenase (11 beta OHSD) deficiency, and is assessed in terms of a reduction in the tetrahydrocortisone (THE)/tetrahydrocortisol (THF) ratio or THE/THE + alpha THF ratio; the alpha THF/THF ratio reflects 5 beta reductase activity. The aim of this study was to determine if urinary cortisol metabolite ratios are a good index of peripheral thyroid hormone action in subclinical hypothyroidism. MATERIALS AND METHODS: the THE/THF, THE/THF + alpha THF and alpha THF/THF ratios were measured in 24 h urine samples from 3 groups of subjects: 1) 18 euthyroid subjects; 2) 25 patients with elevated serum TSH and low FT4 levels (overt hypothyroidism); and 3) 25 patients with increased serum TSH and normal FT4 levels (subclinical hypothyroidism. RESULTS: 7/25 overtly and 5/25 subclinically hypothyroid patients had a THE/THF + alpha THF ratio below the mean control value -2 SD, while respectively 20/25 and 11/25 patients had a THE/THF ratio below the mean control value -2 SD. The mean THE/THF + alpha THF, THE/THF and alpha THF/THF ratios were significantly different among the 3 groups (ANOVA) and were lower in the overtly hypothyroid group than in the other two groups (Fisher's test); daily urine sodium output was also significantly different between the three groups and lower in the overtly and subclinically hypothyroid groups than in the control group (Fisher's test). FT3 and FT4 both correlated with THE/THF + alpha THF in the overtly hypothyroid patients (r = 0.43; p < 0.05 and r = 0.40; p < 0.05, respectively). In the subclinically hypothyroid patients, TSH correlated with THE/THF + alpha THF (r = 0.44; p < 0.05) and THE/THF (r = 0.43; p < 0.05). FT3, FT4 and TSH levels correlated with THE/THF + alpha THF (p < 0.001), THE/THF (p < 0.001), alpha THF/THF (p < 0.001) and daily natriuresis (p < 0.05) in the whole population (patients + controls). In conclusion, urinary cortisol metabolites, although impaired in overt hypothyroidism, are not an accurate index of peripheral thyroid hormone deficiency in subclinical hypothyroidism. We also identified an increase in the alpha THF/THF ratio in overt hypothyroidism, which may be related to 5 beta reductase disturbances.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Factors related to utilization of services for mental health reasons in Montreal, Canada.

This study examines factors related to the utilization of services for mental health reasons by Montreal residents. Data were drawn from telephone interviews. A random sample of 893 respondents completed a questionnaire on service utilization and the Diagnostic Interview Schedule Self Administered to assess DSM-III-R psychiatric disorders. Results indicate that 12.8% of the population had used such services in the past year. Medical doctors and psychiatrists, whose services are free of charge under universal health coverage, were consulted, respectively, by 4.1% and 2.0% of respondents. Psychologists, whose services are not free, were seen by 3.4% of respondents. In all, 42.0% of respondents who presented a current diagnosis used services in the past year. The highest proportion of users (48.0%) was found among respondents who presented both current and lifetime diagnoses and among respondents with comorbidity. The choice of caregiver was related also to pattern of disorders: respondents with current and comorbid disorders tended to consult general practitioners, while respondents with lifetime disorders or with lifetime and current disorders favoured specialized care. In line with other studies, self-perception of mental health, gender and marital status were related to utilization; unlike other studies, attitudes and age were not. It is argued that particularities found in this study stem not only from methodological considerations, but also from the configuration of the mental health system in Quebec, where the greater availability of psychologists may facilitate service utilization.

Adolescent↗
PubMed1998

Intraoperative insulin measurement during surgical management of insulinomas.

Intraoperative hormonal measurements have been used successfully to guide the surgical treatment of various endocrine diseases. In this study, we report the results of intraoperative insulin measurement (IIM) in patients with organic hypoglycemia. IIMs were performed during 52 operations in 51 patients. Hyperinsulinism was secondary to a sporadic insulinoma (M = 40), a type I multiple endocrine neoplasia (MEN-I) (M = 8), an insulin-secreting carcinoma (M = 1), or pancreatic nesidioblastosis (M = 2). The insulin was measured with a radioimmunologic assay in blood samples simultaneously drawn from a peripheral vein and the portal vein at the beginning of the operation (T1) and 20 minutes after tumor removal (T2). Normoglycemia was achieved after surgery in 50 cases (96%). Systemic and portal insulin levels were normal at T1 in eight patients, precluding any further interpretation of the test. Completeness of surgery was confirmed by normalization of both systemic and portal insulin levels at T2 in 36 patients. In seven cases the systemic or portal insulin levels (or both) remained elevated at T2 despite a favorable outcome after surgery. Failure of the surgical procedure was predicted in two patients by the persistence of high levels of insulin at T2. In patients with initially elevated serum insulin levels, the positive predictive value and the specificity of intraoperative insulin measurement for completeness of surgery were both 100%. The sensitivity was 84%, the negative predictive value 22%, and the accuracy of the test 84%. We concluded that IIM is a simple, highly reliable tool for predicting the completeness of surgery in patients with organic hypoglycemia. IIM appears to be a valuable addendum to the surgical armamentarium against insulinoma especially for patients with atypical causes, such as MEN, insulin-secreting carcinoma, or pancreatic nesidioblastosis.

Adolescent↗
PubMed1998

Effects of pH and salt environment on the association of beta-lactoglobulin revealed by intrinsic fluorescence studies.

The effects of pH, ionic strength and heat on the structure of beta-lactoglobulin (beta-lg) have been investigated by studying the intrinsic tryptophan fluorescence of the protein. Between pH 2 and 9, for sodium chloride concentrations varying from 0.0 to 0.2 M, the position of the fluorescence emission maximum at 20 degrees C remained constant at 328 nm, suggesting that the hydrophobic environment of the fluorophores remained unchanged. The fluorescence intensity increased significantly at pH 2, 7 and 9 on reducing the NaCl concentration of the solutions. The most likely explanation for this, supported by recent light scattering data, is that the presence of NaCl is necessary for beta-lg to dimerize. At the higher NaCl concentrations it was found that dimerization accompanied a reduction in fluorescence intensity. Thus, dissociation appears to reduce the self-quenching of tryptophan residues that occurs within the dimer. The fluorescence of solutions heated below the denaturation temperature reflected the state of association of the protein molecules. Above the denaturation temperature and associated with protein aggregation, an irreversible increase in intrinsic tryptophan fluorescence was observed. We also report what we believe to be the first front-face fluorescence measurements on globular protein gels, showing effects of pH and NaCl concentration.

Animals↗