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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
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↗
PubMed1998

Coxsackie B virus infection and beta cell autoantibodies in newly diagnosed IDDM adult patients.

BACKGROUND: Environmental agents such as viruses have been identified as potentially important determinants of insulin-dependent diabetes mellitus (IDDM). Enterovirus infections, Coxsackievirus B especially, could be linked to the beta cell damaging process and to the onset of clinical IDDM. OBJECTIVES: Enteroviral (EV) infection and beta cell autoimmunity were studied in adult patients at the onset of IDDM. STUDY DESIGN: A total of 14 newly diagnosed-IDDM patients with ketosis or ketoacidosis were compared to, anteriorly diagnosed IDDM patients with metabolic decompensation, non-IDDM patients with metabolic decompensation and healthy adults. EV infection was studied by genomic RNA detection in whole blood using a RT-PCR assay. In order to assess the level of beta cell autoantibodies at the time of the initial metabolic decompensation, serum specimens from IDDM patients were tested for GAD65 antibodies and islet cell antibodies (ICAs). RESULTS: Coxsackie B3 or B4 virus genome was detected and genotyped in five of 14 (35.7) newly diagnosed IDDM patients and in one of 12 (8%) patients in the course of IDDM. By contrast, none of the 12 non-IDDM patients and none of the 15 healthy adults was positive for enterovirus RNA detection in whole blood. Positive GAD65 antibodies and ICAs assays were not significantly correlated to a positive EV-RNA detection. CONCLUSION: The present study demonstrates that Coxsackie B virus RNA sequences can be detected in the peripheral blood from adult patients at the onset or in the course of IDDM and suggests that a Coxsackie B virus infection could initiate or accelerate beta cell autoimmune damaging process.

Adult↗
PubMed1998

Essential hypertension: first reason for persistent hypertension after unilateral adrenalectomy for primary aldosteronism?

BACKGROUND: Despite cure of primary aldosteronism by surgical resection, hypertension persists postoperatively in 30% to 50% of patients. The aim of this study was to determine factors influencing long-term outcome of blood pressure after unilateral adrenalectomy for primary aldosteronism. METHODS: Records of 100 patients who underwent unilateral adrenalectomy for primary aldosteronism from 1970 through 1997 were reviewed. Patients were distributed in 2 groups according to whether blood pressure was normal (criteria of World Health Organization). Clinical, biochemical, and pathologic data were compared. RESULTS: All patients were biochemically cured. Blood pressure was normal in 56 patients and improved in 44 (mean follow-up, 69 and 59 months). Persistent hypertension correlated with age, known duration and seriousness of preoperative hypertension, family history of hypertension, no preoperative response to spironolactone, and contralateral adrenal hypertrophy. Gender, surgical approach, and pathologic findings were not predictive factors of blood pressure outcome. The prevalence of hypertension was almost the same in these postoperative patients as the prevalence of essential hypertension in a random population of the same age. CONCLUSIONS: Early unilateral adrenalectomy allows cure or improvement of hypertension in all patients with primary aldosteronism induced by unilateral excessive source of aldosterone secretion regardless of the pathologic findings. Persistent hypertension suggests that coexisting essential hypertension is present.

Adolescent↗
PubMed1998

Noninvasive imaging of insulinomas and gastrinomas with endoscopic ultrasonography and somatostatin receptor scintigraphy.

BACKGROUND: Classic morphological techniques are of limited value for imaging endocrine duodenopancreatic tumors, and invasive procedures such as intraarterial stimulation are often used. Two noninvasive procedures, endoscopic ultrasonography (EUS) and somatostatin receptor scintigraphy (SRS), were recently described with promising results. METHODS: In this study we correlated the results of preoperative EUS (n = 34) and SRS (n = 30) with operative findings in patients with histologically proven insulinoma (n = 20) or gastrinoma (n = 21). RESULTS: The sensitivity and positive predictive value (PPV) of EUS were respectively 77% and 94% for pancreatic tumors (insulinomas and gastrinomas), 40% and 100% for duodenal gastrinomas, and 58% and 78% for metastatic lymph nodes. The sensitivity and PPV of SRS for insulinoma were 60% and 100%, respectively. In patients with gastrinoma, the sensitivity and PPV of SRS were respectively 25% and 100% for pancreatic gastrinomas, 72% and 100% for duodenal gastrinomas or periduodenal metastatic lymph nodes, and 67% and 80% for liver metastasis. In patients with multiple endocrine neoplasia, neither one of the two techniques detected all tumors. Overall sensitivity of combined EUS and SRS was 89% for insulinoma (n = 9) and 93% for gastrinoma (n = 14). CONCLUSIONS: EUS and SRS for gastrinomas and insulinomas should be considered as the initial preoperative imaging procedures and may render invasive procedures unnecessary for most patients.

Adolescent↗
PubMed1998

Comparative effects of felodipine ER, amlodipine and nifedipine GITS on 24 h blood pressure control and trough to peak ratios in mild to moderate ambulatory hypertension: a forced titration study.

OBJECTIVE: To evaluate the 24 h antihypertensive efficacy and duration of action of felodipine extended release (ER) in comparison with two other long acting dihydropyridine calcium antagonists, amlodipine and nifedipine gastrointestinal therapeutic system (GITS), in patients with mild to moderate essential hypertension substantiated by ambulatory blood pressure (BP) monitoring. DESIGN: Randomized, forced titration, parallel group study. Clinic BP was measured at every patient's visit, and 24 h ambulatory BP was monitored at baseline and at the end of each dose-titration period. SETTING: Single centre: hypertension research unit in Quebec City, Quebec. PATIENTS: There were 89 patients enrolled into the study. Eighty-four eligible patients were randomized, and 83 completed the study and were included in the final efficacy analysis. INTERVENTIONS: Following a two-to four-week washout period (baseline), patients were randomly allocated to receive felodipine ER 5 mg, amlodipine 5 mg or nifedipine GITS 30 mg for four weeks (low dose). All study patients had their daily dose doubled to felodipine ER 10 mg, amlodipine 10 mg or nifedipine GITS 60 mg for a further four weeks (high dose). MAIN RESULTS: Significant (P < 0.001) and similar changes from baseline in clinic BP were observed in all treatment groups for low and high doses. Ambulatory BP profiles showed comparable blood pressure reductions with felodipine ER and amlodipine, and a trend towards a lesser reduction with nifedipine GITS during 24 h, daytime and night-time periods. BP loads were similarly reduced with the three treatments. Trough to peak ratios (T:Ps) were calculated from 24 h ambulatory BP curves according to two different approaches: for diastolic and systolic BP, respectively, the global approach produced T:Ps of 0.49 and 0.50 with felodipine ER 5 mg; 0.50 and 0.34 with felodipine ER 10 mg; 0.70 and 0.60 with amlodipine 5 mg; 0.88 and 0.82 with amlodipine 10 mg; 0.65 and 0.55 with nifedipine GITS 30 mg; 0.68 and 0.53 with nifedipine GITS 60 mg. T:Ps in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg; 0.23 and 0.31 with felodipine ER 10 mg; 0.22 and 0.31 with amlodipine 5 mg; 0.45 and 0.58 with amlodipine 10 mg; 0.27 and 0.31 with nifedipine GITS 30 mg; and 0.24 and 0.40 with nifedipine GITS 60 mg. CONCLUSION: There was no evidence in this study of a difference among felodipine ER, amlodipine and nifedipine GITS in lowering ambulatory or clinic BP. Treatment based on ambulatory BP may be preferable to treatment guided by T:Ps because ambulatory BP is firmly established as a predictor of cardiovascular risk. Furthermore, there is no consensus on how to calculate T:Ps, and different methods of calculation may give divergent results.

Adult↗
PubMed1997

Detection of coxsackie B virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus.

Enteroviruses may be linked to insulin-dependent diabetes mellitus (IDDM). The prevalence of enteroviral (EV) infection at onset of adult IDDM was investigated by detection of specific EV sequences in peripheral blood using a reverse transcription and a seminested polymerase chain reaction (seminested RT-PCR). EDTA-treated whole blood samples taken from 12 newly diagnosed IDDM patients with ketosis or ketoacidosis were examined. The comparison groups were 12 adult patients suffering from metabolic decompensation in the course of IDDM, 12 adult patients with decompensated non-IDDM, and 15 healthy adults without any presumed EV infection or metabolic disease. EV genome was detected in five of 12 (42%) newly diagnosed IDDM patients and in one of 12 (8%) patients in the course of IDDM. By contrast, none of the 12 non-IDDM patients and none of the 15 healthy adults had EV sequences in whole blood. Subsequent sequencing of the EV PCR products from the six positive patients showed a significant homology with Coxsackie B3 or B4 viruses, and some common patterns were observed among the sequences. The present study demonstrates that Coxsackie B virus RNA sequences can be detected in peripheral blood from patients at the onset or in the course of IDDM and provides evidence for a role for enteroviruses in adult type I diabetes.

Adult↗