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Biomedical subjects

R Dahan

Publications and source records attributed to R Dahan.

At least 19 recordsLinked to original sources
PubMed2002

Prospective assessment of a new polymerase chain reaction target (STEVOR) for imported Plasmodium falciparum malaria.

The diagnostic value of a polymerase chain reaction (PCR)-based method for amplifying a new target of repeated genes (STEVOR) in Plasmodium falciparum was prospectively assessed on samples from 210 febrile patients returning from areas endemic for malaria. This method is capable of detecting 0.01 parasites in one microliter of blood. Plasmodium falciparum STEVOR PCR confirmed the results of the thin- and thick-film direct examination method but identified Plasmodium falciparum in four patients in whom direct examination was inconclusive at the species level. Moreover, PCR was positive in two patients with a negative direct examination. Thus, Plasmodium falciparum STEVOR PCR had 100% sensitivity and specificity and could be used in selected parasitology laboratories when expert advice is required.

Animals↗
PubMed2002

Novel PDGFbetaR antisense encapsulated in polymeric nanospheres for the treatment of restenosis.

Nanospheres composed of the biocompatible and biodegradable polymer, poly-DL-lactide/glycolide and containing platelet-derived growth factor beta-receptor antisense (PDGFbetaR-AS) have been formulated and examined in vitro and in vivo in balloon-injured rat restenosis model. The nanospheres (approximately 300 nm) of homogenous size distribution exhibited high encapsulation efficiency (81%), and a sustained release of PDGFbetaR-AS (phosphorothioated). Cell internalization was visualized, and the inhibitory effect on SMC was observed. Partially phosphorothioated antisense sequences were found to be more specific than the fully phosphorothioated analogs. A significant antirestenotic effect of the naked AS sequence and the AS-NP (nanoparticles) was observed in the rat carotid in vivo model. The extent of mean neointimal formation 14 days after injection of AS-NP, measured as a percentage of luminal stenosis, was 32.21 +/- 4.75% in comparison to 54.89 +/- 8.84 and 53.84 +/- 5.58% in the blank-NP and SC-NP groups, respectively. It is concluded that PLGA nanospheres containing phosphorothioated oligodeoxynucleotide antisense could serve as an effective gene delivery systems for the treatment of restenosis.

Animals↗
PubMed2000

Renal nitric oxide production during the early phase of experimental diabetes mellitus.

BACKGROUND: Diabetic nephropathy (DN) is characterized by hyperfiltration and hypertrophy in experimental models of diabetes mellitus (DM). Several studies have demonstrated that the pathophysiologic and morphologic changes in DN are mediated by either an increase or decrease in renal nitric oxide (NO) production and/or activity. The goal of the present study was to determine the effects that the early diabetic state has on NO production in the kidney of rats with streptozotocin-induced DM. METHODS: Experimental DM was induced in rats with streptozotocin. Urinary NO production was measured, and levels and activity of the different NOS isoforms were determined by a combination of techniques, including immunoblotting, immunohistochemistry, diaphorase staining, and reverse transcription-polymerase chain reaction. RESULTS: During the first week of DM, urinary NO metabolites (uNO2 + NO3) were reduced as compared with controls, which were unrelated to changes in serum levels of NO. Total NO synthase (NOS) activity was reduced in the renal cortex beginning at 30 hours after the induction of DM. NADPH diaphorase staining of renal cortical slices showed reduced NOS activity in the macula densa in diabetic animals. By immunohistochemical staining with antibodies to the different isoforms of NOS, it was found that protein levels of the neuroneal NOS (nNOS) isoform was diminished in the macula densa. No changes were found in the levels of endothelial NOS (eNOS) activity and protein in the renal cortex in the early diabetic state. CONCLUSIONS: This study provides strong evidence that renal production of NO is reduced in early DM and that this reduction is associated with decreased levels of nNOS activity and protein in the macula densa.

Animals↗
PubMed1999

Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon.

AIMS: To study changes in the expression of insulin-like growth factors (IGFs) and their receptors, as well as production of the IGF-I and IGF-II polypeptides, in adenocarcinoma of the colon. METHODS: Malignant tissue obtained at operation was used. Total RNA was extracted and specific IGF-I and IGF-II and their receptor mRNAs were measured by a solution hybridisation RNase protection assay. IGF-I and IGF-II polypeptides were measured by specific immunoassays. RESULTS: All normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the polypeptide was present in small but equal amounts in normal and malignant tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in adjacent normal tissue and the concentration of the corresponding polypeptide was twice as high in the malignant tissue. IGF-I receptor expression was increased by a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4. CONCLUSIONS: This study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel.

Adenocarcinoma↗
PubMed1997

[Long-term clinical tolerance of antihypertensive treatment during the HOT study. Groupe français de l'etude HOT].

The objective of the HOT study, an international, prospective, randomised study is to determine the optimal level of the blood pressure under treatment, in linked with the lowest cardiovascular mortality and morbidity. The target diastolic blood pressure of 80, 85 and 90 mmHg was determined at the randomisation. In order to reach the target blood pressure, a strategy of treatment was determined: the 1st step was felodipine (a long acting dihydropyridine) and the next steps (if the blood pressure reduction is not enough) propose the addition of different therapeutic classes and/or the increase of each drug doses. The available data after 2 years of the patients follow-up allow us to evaluate the incidence of the reported side effects according to the target blood pressure assigned by randomisation and the number of hypertension drugs used to reach these targets. The percentage of patients with at least one side effect at 12 and 24 months of follow-up are respectively: for the target group DBP < or = 90 mmHg: 9.2% versus 6%; for the target group DBP < or = 85 mmHg: 8% versus 4.4%; for the target group DBP < or = 80 mmHg: 7.9% versus 4.9%. The overall tolerability is not influenced by the target diastolic blood pressure but depends on the number of hypertension drugs used. At 24 months, 2.8% of patients are under monotherapy; 7% under bitherapy and 9.8% under tritherapy. The incidence of the side effects decreases after the 1st year, but slower than between the third months and the first year. There is an influence of the region on the incidence of the side effects, the south European countries describing more side effects than France or the north European countries. This seems to be linked with a perception of the side effects more than with a higher rate. In conclusion, these results confirm the possibility to reach a targeted blood pressure using a predetermined strategy without increasing dramatically the incidence of the side effects.

Antihypertensive Agents↗
PubMed1997

[HOT study: quality of the blood pressure control after 2 years follow-up. Pour le Groupe français de l'étude HOT].

UNLABELLED: The objective of the HOT study, an international, prospective, randomised study was to determine the optimal level of the blood pressure under treatment, linked with the lowest cardiovascular mortality and morbidity. The target diastolic blood pressure of 80, 85 and 90 mmHg was determined at the randomisation. In order to reach the target blood pressure, a strategy of treatment was predefined: the 1st step was felodipine (a long acting dihydropyridine) and the next steps (if the blood pressure reduction was not enough) proposed the addition of different therapeutic classes and/or the increase of the doses of each drug. The blood pressure measurements were made, using the oscillometric method (automatic blood pressure measuring device, Hestia). The quality of the blood pressure control observed in the HOT study was verified after 6 months of follow-up ("Quality of the blood pressure control in the clinical practice and in the HOT study", for the French research group of the HOT study. French hypertension meeting, Paris, December 1994). The aim of this second evaluation was to see if the quality of this control was still effective in France and for all countries after 2 years of follow-up. At the inclusion, the mean diastolic blood pressure was 106 +/- 4 mmHg in France (n = 1.574) and 105 +/- 4 mmHg for all countries (n = 18.790). The results at 24 months were the following, according to the target groups: 79.9 for the < or = 80 mmHg target group; 82.1 for the < or = 85 mmHg target and 83.6 for the < or = 90 mmHg target group. The percentages of patients who reached the target blood pressure were respectively 74; 80; 89% for the 3 target groups. The number of antihypertensive treatments needed to reach this blood pressure control slightly increased in the 3 target groups between the first and the second year with a lower rate of monotherapy and a higher rate of bi and tritherapy. But in the 80 mmHg target group (the most strict), the monotherapy was used in more than half of the patients. In comparison with all countries, France had lower number of bi and tritherapies (i.e. in the 85 mmHg target group: 38.4% of bitherapy in France versus 45.6% in all countries). CONCLUSION: after 2 years of follow-up, the quality of the blood pressure control is still good. There is a trend toward a slight increase in the number of antihypertensive drugs after the first year in the 3 target groups.

Antihypertensive Agents↗
PubMed1994

A randomised clinical trial of the effect of informed consent on the analgesic activity of placebo and naproxen in cancer pain.

To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo, we conducted a prospective, randomised, single dose, placebo-controlled trial. Patients were randomly selected to receive or not information concerning the study. All patients included were then given a single dose of naproxen and placebo according to a crossover, double-blind design. Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study. Twenty-five received both treatments without any information and constituted the uninformed group. Twenty-four had a complete information about the trial; six refused to participate. The 18 others constituted the informed-consent group. Visual analogue scales of pain before and 30, 60, 120 and 180 min after the intake of naproxen and placebo were recorded. As an analgesic, naproxen was more effective than placebo in both groups of patients (p = 0.001). For naproxen as well as for placebo, the analgesic effect was better in the informed-consent group compared to the uninformed group (p = 0.012). The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients (p = 0.08). We concluded that, in contrast with parallel studies, giving information in a crossover, placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo, and decrease the perceived difference the two.

Adult↗
PubMed1992

Foscarnet induction therapy for cytomegalovirus retinitis in AIDS: comparison of twice-daily and three-times-daily regimens.

We have evaluated the effects of induction therapy with foscarnet 100 mg/kg b.i.d. via i.v. infusion in 60 AIDS patients with cytomegalovirus (CMV) retinitis and compared the findings with those in 37 such patients receiving a foscarnet induction regimen of 60 mg/kg t.i.d. via i.v. infusion. Induction therapy was given for at least 3 weeks, with the treatment period being extended in cases of slow resolution of retinitis. There was no significant difference between response rates in the two groups, with ophthalmologic response being observed in 52 (96%) of 54 evaluable b.i.d. patients and 33 (97%) of 34 evaluable t.i.d. patients over mean durations of therapy of 26 and 27 days, respectively; complete and partial responses were observed in 91 and 6%, respectively, of b.i.d. patients and 85 and 12%, respectively, of t.i.d. patients. Foscarnet was discontinued because of adverse events in 3 (3%) of 97 patients, with treatment being stopped in 2 patients because of renal insufficiency and in 1 patient because of an acute neurologic disorder. Serum creatinine concentrations increased significantly in both the b.i.d. group (from 82 to 98 mumol/L, p less than 0.01) and the t.i.d. group (from 73 to 122 mumol/L, p less than 0.001), with the difference between increases not being statistically significant. Serum creatinine concentrations greater than 200 mumol/L were observed in two b.i.d. patients and four t.i.d. patients; in four cases, concomitant medications or conditions contributed to renal impairment. Hypocalcemia of less than 1.75 mmol/L occurred in 18% of b.i.d. patients and 28% of t.i.d. patients during treatment (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide).

Gonadotropin-releasing hormone (GnRH) analogues administered for the treatment of advanced prostatic cancer induce a transient increase in plasma testosterone levels during the first week of treatment, often with a secondary rise in plasma levels of prostatic acid phosphatase and a flareup of disease. To determine whether the antiandrogen nilutamide (Anandron) blocks these effects, we carried out a multicenter, placebo-controlled study of nilutamide in men with prostatic cancer treated with the GnRH analogue buserelin. Thirty-six men with disseminated prostatic cancer and elevated plasma levels of prostatic acid phosphatase were randomly assigned to two groups. Group 1 included 17 men who received buserelin (500 micrograms daily subcutaneously) and nilutamide (300 mg daily by mouth); group 2 included 19 men treated with buserelin and placebo. Symptoms were assessed, and plasma was collected before treatment, daily for 14 days, and on days 18, 22, and 29 after the initiation of treatment. Bone pain appeared or worsened in 5 of the 17 men in group 1 and in 12 of the 19 men in group 2 (P less than 0.05). Acute urinary obstruction occurred in one man in group 2. Despite similar changes in the plasma testosterone levels in both groups, the median concentration of plasma prostatic acid phosphatase decreased almost immediately in group 1, but increased transiently, then decreased on day 14 in group 2. Median levels of prostate-specific antigen decreased immediately in group 1 and decreased on day 8 in group 2. We conclude that nilutamide can prevent the adverse consequences of the buserelin-induced transient rise in plasma testosterone levels in men with advanced prostate cancer treated with a GnRH analogue.

Acid Phosphatase↗
PubMed1988

In vitro and in vivo effects produced by the immunomodulating agent RU 41740 on human polymorphonuclear leukocytes in the elderly.

The activity of RU 41740, a glycoprotein extract from Klebsiella pneumoniae has been investigated on some polymorphonuclear (PMN) functions. Chemotaxis, random migration and oxidative metabolism (assessed by chemiluminescence, O2 consumption and O2- generation) were studied in parallel. PMN were collected from adult and aged human volunteers. Experiments were performed either in vitro or in vivo in a double blind placebo assay. In both PMN populations RU 41740 enhanced oxidative metabolism either in in vivo or in vitro experiments. However, a higher and dose-related activity was observed on PMN collected from the younger subjects whereas maximal effective concentration was reached earlier with PMN collected from aged subjects. RU 41740 did not modify random migration but inhibited chemotaxis of PMN collected from the younger population in a dose-related manner. These data corroborated previous results observed on PMN collected from various animal species and suggested an interaction of RU 41740 on PMN membrane. Moreover drug-induced macrophage and lymphocyte stimulation might also explain, at least in part, the in vivo effects described in this study. Thus RU 41740 could partly account for the protective effects exerted against bacterial and fungal infections through its activity on PMN functions.

Adult↗
PubMed1986

Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital.

To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied. The study was a single blind observer blinded trial, and patients were paired according to sex, age, and hospital environment. Randomisation assigned the first patient of each pair to the control group (without informed consent) or the group to give informed consent. Of the 56 patients, 26 refused to give informed consent, and the age and sex distribution of these differed significantly (p less than 0.02) from the 30 pairs of patients ultimately enrolled into the study. In this "biased" sample, the hypnotic activity of placebo was significantly higher in the control group (p less than 0.05). It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability.

Age Factors↗
PubMed1986

Prevention of deep vein thrombosis in elderly medical in-patients by a low molecular weight heparin: a randomized double-blind trial.

Two hundred and seventy patients over 65 years were included in a placebo-controlled randomized double-blind trial to determine whether a small dose of a low molecular weight (LMW) heparin prevents the occurrence of deep vein leg thrombosis (DVT) diagnosed by 125I fibrinogen scanning. LMW heparin (60 mg daily) significantly reduced the frequency of DVT from 9 to 3 percent (p = 0.03). Adverse drug reactions did not differ significantly between the 2 groups, except for the injection site hematomas that were more frequent in the LMW heparin group. In conclusion, LMW heparin appears of value in preventing the occurrence of DVT in an unselected elderly in-patient population.

Aged↗
PubMed1986

Clinical trials with C 1740, an immunomodulator compound proposed for prevention of acute infectious exacerbations in chronic bronchitis.

C 1740 is an immunmodulating agent of biological origin proposed for the prevention of infectious exacerbations in chronic bronchopathy. The first placebo-controlled double-blind randomized clinical trials have led to opposite conclusions regarding the utility of C 1740. The rate of infectious exacerbations in the placebo group and a large Type II error could explain the "negative clinical trials". However, two out of four "positive clinical trials" were associated with high risk of falsely positive results. The activity of C 1740 is discussed here.

Adjuvants, Immunologic↗
PubMed1986

[Hospitalization of the elderly in a department of internal medicine. Predictive elements of risk and benefit].

One hundred and thirty patients over 70 years have been examined in a prospective way, so as to determine pernicious and benefic effects of hospitalization in elderly people. Deaths appear to be more frequent in old male patients, with a high cultural level on one hand, and a "reduced" independence, on the other hand (according to the "Sandoz clinical assessment of geriatrics scale"). Benefic effects appear to be essentially dependent on primary diagnosis, and on the entourage, as well as on the previous medical care, though less important.

Aged↗