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Biomedical subjects

L Favre

Publications and source records attributed to L Favre.

At least 19 recordsLinked to original sources

[Pneumonology. Ultrasound-guided transbronchial needle aspiration].

After discovering a lung cancer without extrathoracic metastases, the preoperative mediastinal check-up is of great importance to determine the patients operability. The 78% specificity of activity measuring FDG in a PET examination is clearly insufficient to avoid a biopsy of the incriminated lymph nodes. The investigation of a suspected malignant adenopathy justifies a complete examination by mediastinoscopy or-tomy, which are considered gold standards. The transbronchial fine needle aspiration guided by ultrasound (EBUS-TBNA) constitutes the recent evolution of TBNA, method known for 20 years now but underused. Depending on the operators skill, this new procedure needs a learning curve before being able to replace mediastinoscopy.

Biopsy, Needle↗

Role of Fas ligand expression in promoting escape from immune rejection in a spontaneous tumor model.

Tumors escape immune-mediated rejection by a variety of mechanisms during tumor progression. The elucidation of these mechanisms in vivo suffers from a lack of suitable models of spontaneous tumor formation escaping active specific immunotherapy (ASI). In a rat neu transgenic (rNeu-TG) mouse model of spontaneous breast tumor formation, we showed that rNeu-TG mice developed late escape tumors despite the presence of a persistent rNeu-specific immune response after ASI. Cell suspensions derived from these escape tumors grew in vaccinated tumor-free mice, whereas injected spontaneous tumor cells were rejected. Escape tumors retained rNeu or MHC class I expression but significantly upregulated Fas (CD95, Apo-1) ligand. We further demonstrated that Fas-L on escape tumor cells correlated with apoptosis of infiltrating T lymphocytes. Thus, our results provide evidence that spontaneous breast tumors upregulate Fas-L expression after vaccination that may promote tumor escape in vivo after ASI.

3T3 Cells↗

Targeting HER-2/neu for active-specific immunotherapy in a mouse model of spontaneous breast cancer.

The identification of tumor-associated antigens has led to increased interest in vaccination strategies to treat and/or prevent cancer. This study examined the feasibility of active-specific immunotherapy against the breast-tumor antigen HER-2/neu using a HER-2/neu transgenic (rNeu-TG) mouse model. rNeu-TG mice develop spontaneous breast tumors after pregnancy, indicating that they fail to mount an effective immune response against rNeu. Allogeneic fibroblasts expressing HER-2/neu were used as a cell-based vaccine. Vaccination induced a rNeu-specific anti-tumor immune response that prevented tumor formation of transplanted breast-tumor cells, and also protected mice from spontaneous tumor formation. Both T-cell-mediated and humoral immune responses were detectable in vaccinated mice. Vaccination also protected tumor-bearing mice from a challenge with cell suspensions isolated from spontaneous tumors, indicating that rNeu-TG mice are not tolerant to rNeu, even after spontaneous tumor formation. However, established spontaneous tumors themselves were never affected. This observation correlated with T-cell infiltrations in the injected but not in the established spontaneous tumor. Thus, allogeneic fibroblasts are efficient vaccine vectors to prime a specific immune response against an over-expressed tumor antigen. Moreover, our results suggest striking differences in the immunological requirements for the rejection of an established vs. a transplanted tumor.

3T3 Cells↗

Female-biased dispersal in the monogamous mammal Crocidura russula: evidence from field data and microsatellite patterns.

We investigated dispersal patterns in the monogamous Crocidura russula, based both on direct field observations (mark-recapture data) and on genetic analyses (microsatellite loci). Natal dispersal was found to be low. Most juveniles settled within their natal territory or one immediately adjacent. Migration rate was estimated to two individuals per year and per population. The correlation between genetic and geographical distances over a 16 km transect implies that migration occurs over short ranges. Natal dispersal was restricted to first-litter juveniles weaned in early May; this result suggests a direct dependence of dispersal on reproductive opportunities. Natal dispersal was highly female biased, a pattern unusual among mammals. Its association with monogamy provides support for the resource-competition model of dispersal. Our results demonstrate that a state-biased dispersal can be directly inferred from microsatellite genotype distributions, which opens new perspectives for empirical studies in this area.

Animals↗

Origin and evolution of homologous repeated sequences in the mitochondrial DNA control region of shrews.

The complete mitochondrial DNA (mtDNA) control region was amplified and directly sequenced in two species of shrew, Crocidura russula and Sorex araneus (Insectivora, Mammalia). The general organization is similar to that found in other mammals: a central conserved region surrounded by two more variable domains. However, we have found in shrews the simultaneous presence of arrays of tandem repeats in potential locations where repeats tend to occur separately in other mammalian species. These locations correspond to regions which are associated with a possible interruption of the replication processes, either at the end of the three-stranded D-loop structure or toward the end of the heavy-strand replication. In the left domain the repeated sequences (R1 repeats) are 78 bp long, whereas in the right domain the repeats are 12 bp long in C. russula and 14 bp long in S. araneus (R2 repeats). Variation in the copy number of these repeated sequences results in mtDNA control region length differences. Southern blot analysis indicates that level of heteroplasmy (more than one mtDNA form within an individual) differs between species. A comparative study of the R2 repeats in 12 additional species representing three shrew subfamilies provides useful indications for the understanding of the origin and the evolution of these homologous tandemly repeated sequences. An asymmetry in the distribution of variants within the arrays, as well as the constant occurrence of shorter repeated sequences flanking only one side of the R2 arrays, could be related to asymmetry in the replication of each strand of the mtDNA molecule. The pattern of sequence and length variation within and between species, together with the capability of the arrays to form stable secondary structures, suggests that the dominant mechanism involved in the evolution of these arrays in unidirectional replication slippage.

Animals↗

Twenty-four hour blood pressure and heart rate profiles of diabetic patients with abnormal cardiovascular reflexes.

Twenty-four hour ambulatory blood pressure and heart rate profiles of 24 patients with diabetes were monitored in order to assess the effect of autonomic neuropathy on 24-h haemodynamic profiles. Eighteen patients had abnormal cardiovascular reflexes. Mean arterial pressure rose at night in six of the patients with autonomic neuropathy and fell by less than or equal to 5 mmHg in seven. In the remaining five patients with autonomic neuropathy and in the six diabetic patients with normal cardiovascular reflexes, the fall in nocturnal mean arterial pressure was comparable to that of 11 non-diabetic patients with essential hypertension. Median 24-h mean arterial pressure was similar in all four groups of diabetic patients. Prevalence of autonomic symptoms was not related to the change in blood pressure in those with autonomic neuropathy. Twenty-seven months after monitoring, three fatal and five severe non-fatal cardiovascular or renal events had occurred in four of the six patients with a rise in nocturnal blood pressure, compared with one non-fatal event in those with a small fall and no severe events in those with a pronounced fall (p = 0.02). Blood pressure rises at night in certain diabetic patients with abnormal cardiovascular reflexes and the nocturnal rise appears to be associated with a poor prognosis.

Adult↗

Interaction of oxindanac and frusemide in man.

Oxindanac, a moderately active cyclo-oxygenase inhibitor in vitro, is a new antiinflammatory agent under clinical investigation. Its effects on frusemide-induced natriuresis have now been studied. Eight male volunteers receiving frusemide 40 mg b.d. were also given either oxindanac 300 mg b.d. or placebo in two consecutive periods separated by a treatment-free period, according to a randomized cross-over study design. Urinary prostaglandin excretion (PGF2 alpha) fell by 75% after 3 days on oxindanac. Frusemide-induced renin activity reached 66% of the control value in the presence of oxindanac. However, the natriuresis induced by frusemide did not differ significantly whether oxindanac or placebo was administered, despite the inhibitory action of the former on prostaglandin synthesis in vivo.

Adult↗

Effect of calcium-channel blockade on the aldosterone response to sodium depletion and potassium loading in man.

Angiotensin II (Ang II) and potassium (K+) increase aldosterone (Aldo) production in vitro via Ca2+-dependent mechanisms. To determine the effects of Ca2+ antagonism in vivo, we examined the influence of nifedipine on the Aldo response to Na+ depletion and K+ loading in 11 healthy subjects. On the fifth day of a low-Na+/high-K+ diet (10 mmol Na+/100 mmol K+) the subjects were randomly given either nifedipine 30 mg po or placebo, and on the sixth day they received the alternative drug. KCl in 5% glucose was infused on days 5 and 6 from 10:00 to 12:00 AM (0.6 mmol/kg over 2 hours). Dexamethasone was given to suppress adrenal corticotrophic hormone. Plasma renin activity (PRA) and plasma Aldo were determined every 20 minutes. Nifedipine induced a rise in heart rate at 60 minutes but did not change blood pressure. During KCl/glucose infusions, plasma glucose increased significantly, but plasma K+ remained stable. PRA, but not baseline plasma Aldo, was stimulated by nifedipine. KCl provoked a significant and similar Aldo rise (P less than .01) under placebo and nifedipine. Baseline Aldo/PRA ratio was reduced under nifedipine when compared to placebo (P less than .01), whereas during KCl infusions this ratio was similarly elevated under placebo and nifedipine. We conclude that acute inhibition of slow Ca2+ channels does not interfere with K+-induced Aldo secretion in man, suggesting that adaptive mechanisms operate in vivo.

Adult↗

[Nyctohemeral arterial pressure profile and heart rate in autonomic diabetic neuropathy].

Autonomic failure reduces the physiological nocturnal decline of blood pressure (BP) and heart rate (HR). To assess the effect on circadian hemodynamic rhythms of sympathetic (s) and parasympathetic (ps) impairment in diabetic autonomic neuropathy (DAN), we measured BP automatically every 15 min and HR continuously for 24 hour in 11 diabetic patients. They were divided into 3 groups according to the results of cardiovascular reflex tests: a) DAN s + ps, b) DAN ps, c) no DAN. Nine of the patients were hypertensive. Eleven non-diabetic hypertensives served as controls. The disturbance of the circadian BP profile was related to the severity of the DAN, nocturnal BP tending to rise in group a, to fall in group b, and falling markedly in group c and in the control group. FC fell to a similar extent in all the groups. We conclude that the circadian BP profile is more affected by DAN than the FC profile, and that study of the circadian BP profile could reveal the presence of predominantly nocturnal hypertension.

Adult↗

Influence of nifedipine and enalapril on osmoregulation of vasopressin.

To determine whether calcium fluxes and angiotensin II influence osmoregulation of vasopressin (AVP) secretion, the effects of the calcium antagonist nifedipine and of the converting enzyme inhibitor enalapril on the AVP response to an osmotic load were compared to those of a placebo in seven normal female subjects. Plasma and urinary AVP were measured before and during a 3-h infusion of 2.5% hypertonic saline. Nifedipine (10 mg orally 2 h before and 10 mg at the start of the infusion) increased heart rate but did not change blood pressure. The changes in free water clearance and in urinary AVP induced by hypertonic saline under nifedipine were greater than in the control test, but the slope and the intercept of the regression line of plasma AVP upon plasma osmolality were not significantly different. Enalapril (10 mg 3 h before the infusion) did not change heart rate or blood pressure. Free water clearance and urinary AVP did not differ from the control test, but the slope of the regression line was less steep. These slight modifications of the response to an osmotic load suggest that calcium fluxes and angiotensin II only exert a limited influence on AVP osmoregulation in normal females.

Angiotensin-Converting Enzyme Inhibitors↗

[Endocrine arterial hypertension 1985].

Recent progress in the diagnostic work-up of secondary forms of arterial hypertension caused by mineralocorticoids or catecholamines excess is briefly reviewed.

Adrenal Gland Neoplasms↗

[Nyctohemeral blood pressure profiling by automatic measurement in ambulatory hypertensive patients. Treatment with acebutolol].

Variations in night and day blood pressure were evaluated in 11 patients with essential hypertension. The instrument used (Pressurometer II) automatically records blood pressure every 15 minutes for a mean period of 22 hours and ECG tracings continuously. The mean values of arterial pressure and heart rate were significantly higher during day time than at night, revealing a relative "hypotension" and "bradycardia" during sleep. The cardioselective beta-blocker acebutolol induced a significant fall in diurnal and nocturnal blood pressure, thus uniformly lowering the 24-hour profile.

Acebutolol↗

Adrenocortical responsiveness after discontinuous corticosteroid therapy.

Plasma cortisol levels and the response of the adrenal gland to 0.25 mg ACTH administration were measured in 12 patients receiving 15 mg or more of a short-acting steroid (fluocortolone or prednisone) on three out of four days, in 10 patients on daily steroid treatment (15 mg prednisone or more per day), and in 9 normal subjects. The basal plasma cortisol level of the first group was between that of patients on daily prednisone treatment and that of normal subjects. The adrenal function in patients on the three out of four day treatment schedule appeared to be slightly diminished, yet still within the accepted limits for adrenals capable of responding adequately to stress. The adrenal function proved insufficient in all patients on daily steroids. The three out of four day steroid regimen thus offers a solution with many advantages over continuous steroid treatment for patients refractory to the alternate-day schedule.

Adolescent↗