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Biomedical subjects

P Drouin

Publications and source records attributed to P Drouin.

At least 91 records · Page 5Linked to original sources

Increased erythrocyte aggregation in insulin-dependent diabetes mellitus and its relationship to plasma factors: a multivariate analysis.

Red blood cell aggregation in vitro (kinetics and shear resistance) was studied in 13 healthy controls and 13 type I (insulin-dependent) diabetic patients free of severe degenerative complications who were matched for age, sex, and body mass index. Measurements were performed with a device that analyzes the laser light backscattered by a blood suspension. Both the velocity of rouleau formation and the cohesion of the rouleau network were significantly increased in diabetic patients. Plasma viscosity and whole-blood viscosity measured at low shear rate (0.95 s-1) were also significantly elevated in the diabetic group. Multivariate analyses of the whole population sample and the diabetic patients confirmed the influence of plasma proteins on the kinetics of aggregation. Fibrinogen levels, which were close to normal, affected mainly the shear resistance of the aggregates. Triglyceride and apolipoprotein (apo) B levels and indexes of metabolic control or protein glycation (fasting blood glucose and fructosamine) also appeared to influence markedly both the kinetics of rouleau formation and the cohesion of the rouleau networks. These rheological abnormalities occurred in diabetic patients before the appearance of any severe degenerative complications. We suggest that these rheological abnormalities are linked to plasma or erythrocyte factors, and are not due to angiopathy.

Adult↗

Improved visual evoked potential latencies in poorly controlled diabetic patients after short-term strict metabolic control.

OBJECTIVE: To determine whether short-term strict control of blood glucose can improve abnormal visual evoked potentials (VEPs) in poorly controlled diabetic patients with no overt diabetic complications. RESEARCH DESIGN AND METHODS: VEPs (P100 wave latencies) were recorded in 12 poorly controlled diabetic patients (7 with insulin-dependent diabetes mellitus and 5 with non-insulin-dependent diabetes mellitus) before and after at least 3 days of near normoglycemia obtained by continuous subcutaneous insulin infusion (CSII). Exclusion criteria were overt diabetic neuropathy or retinopathy. The control subjects were 12 healthy subjects matched for age and sex. Fifty-two other subjects formed a reference control population. The intra-individual coefficient of variation for P100 latency was < 3%. RESULTS: The P100 latencies were longer in diabetic patients than in control subjects (means of both eyes +/- SD: 116.8 +/- 10.1 vs. 106.2 +/- 4.5 ms, P < 0.01), and 4 of the 12 diabetic patients had abnormal VEPs. After 3 days of close blood glucose control (mean blood glucose profile fell from 13.7 +/- 2.2 mmol/l to 6.8 +/- 1.2 mmol/l, P < 0.01), the mean P100 latencies were significantly shorter (112.5 +/- 7.6 ms, P < 0.01) but were still significantly longer than control values. The longer the initial P100 latency, the greater the decrease after CSII. There was no correlation between the fall in blood glucose and improvement in VEPs. CONCLUSIONS: Short-term blood glucose normalization is associated with improved P100 wave latency in uncomplicated diabetic patients. These data suggest that abnormal VEPs are partly reversible and include functional disturbances related to glucose metabolism.

Adult↗

Self-monitoring of blood glucose and insulin dose alteration in type 1 diabetes mellitus.

The purpose of this study was to evaluate the relationship between proper use of self-monitoring of blood glucose (SMBG) including knowledge and application of specific algorithms and metabolic control in a group of randomly selected insulin-dependent diabetic patients. We studied 80 patients responding to the following criteria: intensive conventional insulin therapy and SMBG for at least 6 months using a reflectance meter, and previous 5-day hospital education period. The practical knowledge of the guidelines was evaluated by a questionnaire simulating 8 metabolic situations. A computer analysis of the SMBG data for the 3 months preceding the study allowed us to evaluate patient compliance with SMBG (number of blood glucose determinations) and patients' application of the guidelines (percentage of insulin doses modified according to the guidelines). Fifty-nine patients (79%) were compliant with SMBG and had better metabolic control than the non-compliers (HbA1c: 6.7 +/- 1.1% vs. 7.5 +/- 1.9, P < 0.05). Twenty-eight out of the 59 compliant subjects had good knowledge of the guidelines but without patent improvement of glycemic control. Seventeen of these 28 correctly used the algorithms to modify insulin dosage; their HbA1c levels were lower than those of the 11 patients who did not use the algorithms (6.1 +/- 0.9 vs. 7.1 +/- 0.9%, P < 0.05). The percentage of insulin dose modification consistent with the guidelines and the level of HbA1c was negatively correlated in the good-knowledge group. The conclusion is that good metabolic control is linked not only with the degree of knowledge but also with the application of this knowledge.

Adolescent↗

[Medical treatment of diabetic arteriopathy].

Medical care of arteriopathy of leg in a diabetic patient involves control of diabetes combined with a series of non specific measures applicable to all atheromatous arteriopathies. Allowance must be made for the often silent nature of the arterial lesion, explicable by the associated peripheral neuropathy and the site of the lesions, generally more distal or staged than in non diabetics. A stable blood sugar level must be obtained to provoke improvement in hemorrheologic parameters and to slow the atheromatous process. A dietary regimen is associated with oral hypoglycemic agents or insulin therapy, the latter systematically for trophic disorders, administered as multiple injections or by insulin pump until complete healing is obtained. Insulin therapy normalizes abnormal blood lipid levels secondary to an uncontrolled diabetes. Other vascular risk factors (primary hyperlipoproteinemia, hypertension, smoking) must be allowed for. Of major importance in these patients at risk are foot hygiene, prevention of local trauma and correction of plantar anomalies. Aggravating factors in patients with arteritis are diabetic neuropathy and foot deformities. Regular walking is encouraged. Drug therapy (oral or injectable vasoactive agents, platelet antiaggregants, prostacyclin, normal blood volume restoration) depends on the severity of the arteriopathy and any complications. Analgesics are often required in advanced stages. Local therapy and sometimes antibiotics are necessary for trophic disorders. The frequent asymptomatic character up to the stage of gangrene should not, because of the diabetic diathesis, induce a wait and see attitude, and revascularization by angioplasty or shunt operation should be envisaged. A frequent complication of sugar diabetes, arteriopathy of the leg should be diagnosed early before it is revealed by a gangrenous lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗

[Insulin in type 2 diabetes. Why, when, how?].

Non insulin-dependent diabetes is often associated with obesity and always with some degree of insulin resistance. First choice treatment consists of appropriate and sometimes hypocaloric diet and oral hypoglycemic agents. Using insulin becomes mandatory in patients with associated pathology or at risk of metabolic imbalance. Insulin administration must be discussed in each individual case when it aims at a long-term improvement of blood glucose control, taking into account the lack of consensus on this point and the potential drawbacks of insulin therapy, notably weight increase and risk of hypoglycaemia.

Diabetes Mellitus, Type 2↗

A multicenter comparison of the effects of simvastatin and fenofibrate therapy in severe primary hypercholesterolemia, with particular emphasis on lipoproteins defined by their apolipoprotein composition.

This multicenter, double-blind, randomized study was designed to compare the effects of simvastatin (20 mg/d and 40 mg/d) and fenofibrate (400 mg/d) on plasma lipids, lipoproteins, apolipoproteins (apo), and lipoprotein particles defined by their apo composition (Lp A-I, Lp A-II:A-I, Lp E:B, Lp C-III:B) in primary hypercholesterolemia. After 6 and 10 weeks of therapy, both drugs lowered plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and apo B. The effect on LDL and apo B was significantly more pronounced for simvastatin (P = .01). Simvastatin increased Lp A-I, but did not change Lp A-II:A-I, while fenofibrate decreased Lp A-I and increased Lp A-II:A-I. Lp E:B and Lp C-III:B were decreased with both drugs, but fenofibrate was significantly more effective in reducing these particles than simvastatin. This study demonstrates that both drugs have beneficial effects on the parameters positively or negatively correlated with the atherosclerotic risk, with simvastatin being more effective in reducing some of them. These results suggest that the drugs led to different structural modifications of the lipoproteins, which would not be revealed by examination of lipoprotein density classes. These differences are probably related to the different mechanisms of action of the agents.

Adolescent↗

Pathogenicity and preliminary antigenic characterization of six infectious bursal disease virus strains isolated in France from acute outbreaks.

Six isolates originating from acute outbreaks of infectious bursal disease recently reported in broiler and pullet flocks in France were studied with respect to their pathogenicity and their antigenic relatedness to the Faragher 52/70 reference strain. Although the mortality experimentally induced in susceptible chickens by the field strains was sometimes four times higher than that which followed the inoculation of the reference strain (16 to 48% versus 12%), neither mortality nor morbidity were observed in chickens previously vaccinated with a commercial live vaccine and then challenged under the same conditions. Agar gel precipitation tests demonstrated the existence of common antigens in the different strains, and high cross-neutralization indices measured in embryonated specific pathogen free eggs showed them all to belong to serotype I. These data are discussed with reference to previous European and North-American studies on the antigenic status of infectious bursal disease virus.

Acute Disease↗

Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS: Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS: The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION: Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies.

Adult↗

Apolipoprotein A-I-containing particles and reverse cholesterol transport in IDDM.

Lipoprotein particles containing apoA-I but not apoA-II are, among high-density lipoproteins, effective protectors against atherosclerosis that act by promoting the efflux of cellular cholesterol and the reverse cholesterol transport process. Because previous studies showed that in vitro nonenzymatic glycosylation of HDL impairs HDL receptor-mediated cholesterol efflux, we isolated Lp A-I from two poorly controlled insulin-dependent diabetic patients and compared the chemical composition and ability to promote cholesterol efflux with the same particles purified from two matched nondiabetic control subjects. No differences in lipid composition or in the ability to promote cholesterol efflux from cultured adipose cells were noted between the two types of Lp A-I preparations. However, when we separated Lp A-I from diabetic subjects by degree of glycosylation, the specifically glycosylated subfractions were about 50% less effective in producing cholesterol efflux than the nonglycosylated particles.

Adult↗

Lipoprotein particle analysis comparing simvastatin and fenofibrate.

This study compares the effects of fenofibrate and simvastatin in primary hypercholesterolemia, with particular regard to lipoprotein particles, as defined by their apolipoprotein composition: LpAI, LpAII: AI, LpE:B, LpCIII:B. This was a double-blind study in which patients were randomized to 2 groups, one receiving simvastatin 20 mg once daily and the other receiving fenofibrate 200 mg b.i.d., if their total cholesterol and their LDL cholesterol remained above 7.60 mmol/l (300 mg/dl) and 4.95 mmol/l (195 mg/dl) after a 4-week placebo period. Simvastatin dosage was doubled at the end of 6 weeks of therapy if the LDL-cholesterol level remained above 3.55 mmol/l (140 mg/dl). Analyses were done after 6 and 10 weeks of therapy. Apolipoprotein AI was increased significantly only at week 10 with fenofibrate (+7.4%). Simvastatin had a more pronounced effect than fenofibrate on apolipoprotein B. There was a significant difference between drugs at weeks 6 and 10. No change was observed in the LpAII:AI level with simvastatin, whereas fenofibrate increased these particles quite significantly (+13.9 and +22.3%). The drugs had opposite effects on LpAI (+2.5 and +5.6% with simvastatin; -12.8 and -15.1% with fenofibrate). LP E:B (-33.0 and -40.8% with simvastatin; -53.8 and -52.2% with fenofibrate) and LpCIII:B (-23.8 and -31.8% with simvastatin; -35.1 and -43.5% with fenofibrate) were decreased by both drugs, but fenofibrate was significantly more effective in reducing these particles than simvastatin at week 6. This study suggests that both drugs led to different structural modifications of the lipoproteins, which would not be revealed by total apolipoprotein analysis. These differences are probably related to the mechanisms of action of these drugs.

Adolescent↗

Hemobiological activity of gliclazide in diabetes mellitus.

The hemovascular abnormalities encountered in diabetes include platelet alterations, shifts in prostaglandin metabolism and disorders of fibrinolysis. Diabetes is thus associated with increased platelet adhesiveness, increased platelet aggregation with hypersensitivity to proaggregants, increased plasma levels of beta-thromboglobulin and platelet factor 4 as an expression of platelet hyperactivity, increased levels of thromboxane A2 (TXA2) and prostacyclin (PGI2), and reduced levels of tissue plasminogen activator (t-PA). It is not clear which, if any, of these abnormalities are generated by chronic hyperglycemia and can be corrected by adequate glycemic control. Studies with gliclazide have demonstrated that it exerts hemovascular effects which can be valuable to patients. Thus, treatment with gliclazide leads to a decrease in platelet adhesiveness and aggregability. This treatment also reduces thromboxane levels and increases TPA levels. The mechanisms of action of gliclazide are not fully known but it has been demonstrated that its antiplatelet action is independent of its hypoglycemic activity and is not accompanied by clinical abnormalities of blood clotting. The mechanism of direct action on platelet activity may be mediated by inhibition of activated glycogen synthetase, activation of adenylate cyclase, modulation of arachidonic acid release from platelet membranes, stimulation of PGI2 production, and inhibition of the proaggregant action of TXA2. Thus, gliclazide not only has a hypoglycemic action but also improves hemovascular parameters in type 2 diabetes when used at normal therapeutic doses.

Blood Platelets↗

[The efficacy and tolerance of simvastatin and fenofibrate in primary hypercholesterolemia].

The effects of simvastatin and fenofibrate on blood lipids and the side-effects of these two drugs were compared in a double-blind trial involving 184 adults with primary hypercholesterolemia (total cholesterol levels: 3.87 +/- 1.02 g/l in the simvastatin group, 3.78 +/- 0.79 g/l in the fenofibrate group; N.S.). During a 10-week period, the patients received either fenofibrate 200 mg twice daily or simvastatin 20 mg once daily with doubling of the dosage at week 6 if the LDL-cholesterol level remained above 1.40 g/l. Simvastatin significantly (P less than 0.01) reduced total cholesterol by -29.9 percent, LDL-cholesterol by -35.4 percent, apoprotein B by -27.3 percent and triglycerides by -16.7 percent. Fenofibrate significantly (P less than 0.01) reduced total cholesterol by -19.2 percent, LDL-cholesterol by -22.3 percent apoprotein B by 13.9 percent and triglycerides by 28.9 percent. Reduction of the first 3 parameters was significantly (P less than 0.01) greater with simvastatin and reduction of triglycerides significantly greater with fenofibrate. Apoprotein A1 levels were increased by fenofibrate (+ 7.4 percent) but not by simvastatin. Side-effects occurred with a frequency of 6 percent under simvastatin and 9 percent under fenofibrate.

Adolescent↗

An insertion deletion polymorphism in the signal peptide of the human apolipoprotein B gene.

In this communication we report the genetic properties of an insertion/deletion polymorphism in the signal peptide of the human apolipoprotein B (apo b) gene. There are two alleles of the apo B signal peptide; one codes for a peptide 27 amino acids in length and the other a peptide only 24 amino acids in length. Using the polymerase chain reaction the difference of nine nucleotides between the two alleles is readily detectable after electrophoresis of the amplification products. The relative frequencies of the Ins and Del alleles are 0.655 and 0.345, respectively. The apo B signal peptide genotypes are transmitted in a manner consistent with an autosomal codominant mode of inheritance with two alleles.

Alleles↗

Rheological properties and membrane fluidity of red blood cells and platelets in primary hyperlipoproteinemia.

Lipid fluidity of the erythrocyte membrane and intact platelets was examined in 32 male patients affected by types IIA, IIB and IV primary hyperlipoproteinemia and 15 control subjects. Lipid fluidity was determined by fluorescence polarization using two probes: DPH and TMA-DPH which are localized in different lipid areas of the cell membrane. Classical haemorheological tests were also performed including plasma viscosity, whole blood viscosity and erythrocyte aggregation. As compared to a control group, plasma viscosity and whole blood viscosity at low shear rate was significantly increased in types IIB and IV, but not in type IIA patients. In contrast, the increase in erythrocyte aggregation was significant in all HLP types. Concerning lipid fluidity, the results recorded with red cells and platelets were not significantly different for type IIA HLP compared to the control group. In contrast, erythrocyte membranes from patients with types IIB and IV HLP had a significantly higher level of fluidity in lipid regions characterized by TMA-DPH. Using DPH as a fluorescent probe, identical results were only noted in type IIB patients. Regarding intact platelets of IIB and IV patients, an increase in lipid fluidity was noted for two fluorescent probes. These findings suggest that HLP associated erythrocyte and platelet fluidity alterations are not related to hypercholesterolemia but to the triglyceride level.

Adult↗

Vaginal intraepithelial neoplasia.

This study comprised the largest number (76) of cases of vaginal intraepithelial neoplasia (VaIN) so far reported. Women diagnosed with VaIN were older (mean age 50.2 years) than those diagnosed with cervical intraepithelial neoplasia (CIN). Many of the women had previously undergone (71.2%). In the majority of cases, the diagnosis was made after cytologic testing. In 92.4% of the cases, the lesions affected the upper third of the vagina. Grades of VaIN were distributed as follows: grade 1 52.6%, grade 2 191.%, grade 3 28.9%, with a 15-year interval between VaIN 1 and 2 as a group and VaIN 3 as another group. The cases of VaIN were divided into five groups: VaIN de novo; VaIN + CIN; VaIN postradiotherapy; VaIN + CIN + VIN; and incidental finding of VaIN on the surgical specimen. The therapeutic modalities were heterogeneous; CO2 laser therapy was used most frequently (54.2%). Failures are attributed mainly to the multifocal character of the lesions (particularly with human papilloma virus infection) or their localization in the vaginal angles. Overall, the number of cases, the duration of follow-up (39.2 months), and the unsatisfactory results with CO2 laser therapy have led us to propose a therapeutic decision tree where in which 5-fluorouracil plays a major role, CO2 laser and surgical therapeutic modalities having limited and precise indications.

Adult↗

Safety, tolerability, and efficacy of simvastatin and fenofibrate--a multicenter study. Simvastatin-Fenofibrate Study Group.

Five centers participated in a double-blind, randomized, active-drug controlled study. The selected patients had a diagnosis of primary hypercholesterolemia (phenotype IIa or IIb, total cholesterol [TC] greater than 300 mg/dl, low-density lipoprotein [LDL] cholesterol greater than 195 mg/dl, triglycerides [TG] less than 350 mg/dl). Throughout the study the patients observed a lipid-lowering diet (American Heart Association). After a baseline placebo period (4 weeks), the patients were randomly assigned to simvastatin 20 mg q.p.m. or fenofibrate 200 mg b.i.d. If after 6 weeks of treatment the LDL cholesterol level remained over 140 mg/dl the dose of simvastatin was doubled. The total duration of treatment was 10 weeks. One hundred eighty-four patients completed the study; age ranged from 17 to 72 years (mean 46; 129 men, 55 women). Seventy-nine patients had ischemic heart diseases. Simvastatin significantly reduces TC, LDL, and apolipoprotein (apo) B (30%, 35%, and 27%, respectively). These effects are larger than those of fenofibrate (19%, 22%, and 14%, respectively). Fenofibrate decreased very-low-density lipoprotein and TG, and increased high-density lipoprotein and apo A1, to a larger extent than simvastatin. However, the difference reached statistical significance only for TG (29% versus 17%). Both drugs were well tolerated. Clinical adverse experiences occurred with a low frequency, and few of these were considered drug related (6 and 8% in the simvastatin and fenofibrate groups, respectively). Only two patients had serious laboratory adverse experiences considered drug related or possibly drug related (one in each treatment group with increased SGPT, gamma-GT, and/or creatine phosphokinase).

Adolescent↗