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Biomedical subjects

L Alexandre

Publications and source records attributed to L Alexandre.

At least 19 recordsLinked to original sources

Selegiline enhances erectile activity induced by dopamine injection in the paraventricular nucleus of the hypothalamus in anesthetized rats.

Apomorphine delivered in the paraventricular nucleus of the hypothalamus (PVN) induces penile erection in rats, suggesting a role of dopaminergic projection to the PVN in the control of penile erection. We assessed whether the selective inhibitor of monoamine oxidase B, selegiline, could enhance the erectile activity induced by dopamine delivery in the PVN. Intracavernous and blood pressure (ICP and BP) were monitored in anesthetized rats to quantify ICP rises (number and percentage of ICP maximum/mean BP (ICPmax/BP x 100)) elicited by 10 micro g dopamine injection in the PVN after saline or 3 mg/kg i.v. selegiline (8 rats per group). The number of ICP rises (mean+/-s.d.: 4.5+/-2.9 vs 1.4+/-1.9; P=0.017) and their ICPmax/BP x 100 (49+/-8% vs 34+/-9%; P=0.015) were significantly greater upon dopamine injection in the PVN than upon vehicle. Compared to saline i.v., 3 mg/kg selegiline pretreatment significantly increased the number of ICP rises induced by dopamine injection in the PVN (9.4+/-2.6 vs 4.5+/-2.9; P<0.001), without affecting their amplitude. This suggests that drugs potentiating dopaminergic responses in the central nervous system might enhance proerectile commands of supraspinal origin.

Animals↗

Electron microscopic immunocytochemical detection of PSD-95, PSD-93, SAP-102, and SAP-97 at postsynaptic, presynaptic, and nonsynaptic sites of adult and neonatal rat visual cortex.

Membrane-associated guanylate kinases (MAGUKs) assemble protein complexes at sites of cell-cell contact. At excitatory synapses in brain, MAGUKs localize to the postsynaptic density (PSD) and interact with N-methyl-D-aspartate (NMDA) glutamate receptors and downstream signaling proteins. However, NMDA receptors are not restricted to the PSDs, as electron microscopic immunocytochemical (EM-ICC) results indicate that NMDA receptors also occur at nonsynaptic portions of dendrites, perhaps functioning as reserves for rapid insertion into synaptic membranes in response to appropriate synaptic activity. NMDA receptors also occur in axons, at least in part to support glutamate-dependent enhancement of transmitter release. In this study, a systematic EM-ICC survey was performed to determine whether the distributions of four neuronal MAGUKs-PSD-95, PSD-93, SAP-102, and SAP-97-resemble that of NMDA receptors. Quantitative analysis revealed that the density of PSD-95 over thick PSDs of asymmetric axo-spinous synaptic junctions is 2-3-fold the level in the immediately adjacent cytoplasm of spines and terminals, while symmetric synapses show no association with PSD-95. Similarly, all four MAGUKs occur over PSDs of spines. However, we also detected MAGUK immunoreactivity, albeit more diffusely, along presynaptic membranes and in the cytoplasm of axons and dendritic shafts. In fact, the overall distribution of PSD-95 within the neuropil is equally prevalent along plasma membranes (including synaptic portions) as in the cytoplasm, away from plasma membranes. These results suggest that MAGUKs have dual roles: to maintain receptors at synapses and to regulate shuttling of receptors between nonsynaptic and synaptic sites.

Adaptor Proteins, Signal Transducing↗

Spinal proerectile effect of apomorphine in the anesthetized rat.

Considering the presence of dopaminergic receptors in the lumbosacral spinal cord, we tested whether apomorphine could exert a proerectile effect by acting at the spinal level. Intracavernous (ICP) and blood pressures (BP) were measured in anesthetized rats. ICP rises were quantified (duration, percentage of ICPmaximum/meanBP (ICPmax/BPx100), area under ICP curve (AUC/BP) and sum of AUC/BP after intravenous (i.v.) and intrathecal (i.t.) injections of apomorphine alone or in presence of i.t. oxytocin (10 ng). Both 10 and 30 microg i.v. apomorphine dosings elicited erectile events evidenced by ICP rises. Upon the 30 microg i.v. injection, duration of ICP rises were increased from 25+/-10 to 69+/-18 s (P<0.001), ICPmax/BPx100 from 21+/-3 to 50+/-14% (P=0.001), AUC/BP from 3+/-1 to 14+/-6 s (P=0.002) and sum of AUC/BP from 5+/-7 to 34+/-35 s (P=0.021). Upon 30 microg i.t. injections of apomorphine at the lumbosacral level, the number of ICP rises was increased from 0.2+/-0.4 to 3.0+/-1.5, ICPmax/BPx100 from 16+/-9 to 43+/-12 and sum of AUC/BP from 1+/-3 to 31+/-15 s compared to vehicle injection (P<0.05 for all parameters). Injection of 30 microg i.v. or i.t. apomorphine non-significantly enhanced the number and amplitude of the ICP rises induced by 10 ng i.t. oxytocin. However, the enhancement of the amplitude of the ICP rises elicited by i.t. oxytocin was more pronounced with i.t. apomorphine than with i.v. apomorphine. These results suggest the existence of a spinal site of action for apomorphine which may (1) participate to generation of erection and (2) exerts a facilitator effect on erection of supraspinal origin.

Animals↗

Vaginal physiological changes in a model of sexual arousal in anesthetized rats.

The understanding of the pathophysiology of female sexual dysfunction suffers from the lack of a convenient model for the study of female genital sexual response. In this study, systemic arterial blood pressure (BP) as well as partial oxygen tension, temperature, and blood engorgement of the vagina [using laser-Doppler flowmetry in arbitrary units (AU)] were measured in anesthetized, ovariectomized (1 wk before the start of the experiment) female rats. Vaginal sexual arousal was replicated by electrical stimulation of the pelvic nerve (PNS). PNS induced reproducible increases in the different vaginal parameters (from baseline value, respectively: 16 +/- 10 to 30 +/- 12 mmHg; 34.9 +/- 0.6 to 36 +/- 0.6 degrees C; 450 +/- 196 to 1,500 +/- 360 AU; P < 0.05, paired t-test) and BP (90 +/- 7 to 123 +/- 13 mmHg, P < 0.05, paired t-test). Vaginal vascular resistance was significantly decreased during PNS (from 0.23 +/- 0.15 to 0.08 +/- 0.02 mmHg/AU). Vaginal wall tension was also measured with a force transducer. PNS induced an increase in vaginal wall tension (1.0 +/- 0.2 g), followed by a decrease under the prestimulation value. Intravenous atropine sulfate (1 mg/kg) injection abolished the increase in vaginal wall tension without significantly affecting vaginal vascular resistance. Intravenous vercuronium bromide (2 mg/kg) injection abolished the decrease in vaginal wall tension. Concomitant electrical stimulation of the paravertebral sympathetic chain inhibited vaginal response induced by PNS. Electrical stimulation of the medial preoptic area of the hypothalamus induced a response qualitatively equivalent to PNS with a significant decrease of vaginal vascular resistance. These data support that vaginal contractions involve both smooth and striated muscles and indicate that neural control of vaginal sexual arousal have great similarities in male and female rats.

Anesthesia↗

Morphological features of the human umbilical vein in normal, sickle cell trait, and sickle cell disease pregnancies.

Pathological changes often occur in the placenta of women with sickle cell disease (SCD). These alterations are caused by sickling of erythrocytes and vasoocclusion in the placental circulation, leading to regional hypoxia. However, the morphological status of the umbilical cord, which is in close physical association with the placenta, is not documented under such conditions. To explore this, the umbilical vein structure in healthy, sickle cell trait (the heterozygous state), and SCD pregnancies was studied using scanning (SEM) and transmission electron microscopy (TEM). Interestingly, the sickle cell trait umbilical vein architecture was morphologically similar to that in control veins, whereas numerous alterations were seen in the SCD umbilical vein wall. In SEM, the SCD umbilical vein endothelial cells showed atypical morphologies. TEM analysis of the tunica media showed (1) smooth muscle cell proliferation and increase in the thickness of the basement membrane underlying the cells; (2) areas of necrosis; (3) reduplication of the inner elastic lamina. Such features were often seen in sickle patients vasculature at autopsy. Our findings could have importance because tissue hypoxemia is an integral part of vasoocclusion. We conclude that the SCD umbilical vein may be an additional tool for studying vasoocclusion in sickle cell disease.

Adult↗

Efficiency of prenatal counselling for sickle cell disease in Guadeloupe.

As in most caribbean countries, Sickle Cell Disease (SCD) is a major public health problem in Guadeloupe. A prenatal counselling program was developed, at an early stage of pregnancy, for at-risk couples. Over a 6 year period, 144 couples at-risk of having a child with homozygous sickle cell (SS: n = 103) or sickle cell C disease (SC: n = 41) were seen for prenatal counselling. Among those belonging to the SS risk group, 64 (62%) underwent prenatal diagnosis (PND), which allowed identification of 27 SS fetuses, with an induced abortion rate of 70%. Among those of the SC risk group, 14 (34%) accepted PND and the diagnosis of SC was made in 5 cases with an induced abortion rate of 60%. Factors, appeared to play a role in seeking PND and induced abortion, were the type of risk (SS or SC), multiparity, existence of affected child in the family and gestational age at the time of counselling. Our experience reveals that, an early prospective identification of at-risk couples combined with education to increase the awareness of the problem at the individual and population level need to be achieved to further improve the efficiency of our prevention program.

Abortion, Induced↗

[Cadaver donor nephrectomy. Surgical technique in the context of multi-organ donation].

95% of renal transplantations performed in France use cadaver donor kidneys. Two donor nephrectomy techniques are proposed: a beating heart technique and an arrested heart technique. In the very great majority of cases (80%), donor nephrectomy can be performed during multi-organ removal, performed according to bioethical regulations: unrelated, anonymity between donor and recipient, security, traceability and evaluation. The urologist has a role to play at each step of organ donation, in which he is the main protagonist. The first steps are performed in close collaboration with the intensive care unit which established the diagnosis of brain death of the potential donor. The following steps, guided by the French transplant establishment, are the urologist's responsibility: He is responsible for abdominal exploration looking for a tumour or any other abnormality. A strictly aseptic technique is essential to prevent contamination of the organ. He is responsible for removing kidneys in such a way as to ensure the shortest possible warm ischaemia time, the best storage solution, and the best preservation of their anatomical structure. He must be familiar with the outcome of transplants in order to adapt his technique to the results of transplants.

Brain Death↗

[Double kidney-total pancreas transplantation with bladder reimplantation. 25 cases].

Twenty five double kidney-pancreas transplantations were performed according to the total pancreas transplantation technique with drainage of exocrine secretions into the bladder via a vesicoduodenostomy. 72% of kidney-pancreas grafts were functional at one year and 59% were functional at four years. The authors observed a slightly higher rejection rate (0.56 versus 0.34) and a higher incidence of urinary tract infection (60% versus 35%) following double pancreas and renal transplantation than after isolated renal transplantation. Complications were rare: two venous thromboses and two cases of urethritis requiring of rediversion of the duodenum into the intestine. These good results, comparable to those reported in the international registry, reflect the value of the pancreatic and renal transplantation technique using a total pancreas drained into the bladder. It would probably be preferable to transplant patients earlier, when chronic renal failure secondary to insulin-dependent diabetes induces end-stage renal failure and the need for haemodialysis.

Adolescent↗

Insertion of a double pigtail ureteral stent for the prevention of urological complications in renal transplantation: a prospective randomized study.

PURPOSE: Urologists successfully use ureteral stents to protect the ureterovesical anastomosis in nontransplant patients. MATERIALS AND METHODS: We determined the value of ureteral stents in transplant patients. The frequency of urological complications (leaks, obstructions and urinary tract infections) was compared in a prospective randomized series of 194 kidney transplantations (97 with and 97 without a double pigtail ureteral stent). RESULTS: In the stent group 1 patient had a urinary leak and 35 had urinary tract infections (including 2 cases of Corynebacterium cystitis). In the no stent group 6 patients had urinary leaks, 4 had obstructions and 32 had urinary tract infections. The 1-year patient and graft survival rates were similar in both groups, and renal function at 1 year was also similar (229 versus 208 mumol./l. creatinine in the stent and no stent groups, respectively). A small number of stent related complications occurred (2 stent breakages and 1 stent migration). No stones formed in any case. CONCLUSIONS: Ureteral stent insertion significantly decreases the rate of vesicoureteral leakage and obstruction in renal transplantation.

Adult↗

[Impact of weight difference between donor and recipient on the function of the transplanted kidney].

OBJECTIVE: The objective of this retrospective study was to determine whether the difference between the donor's weight (wd) and the recipient's dry weight (wr) could influence the function of renal transplants. METHODS: Between 1987 and 1994, 185 patients with a mean age of 43.3 years +/- 12 were transplanted with a locally harvested cadaver kidney, corresponding to 120 men (42.2 years +/- 1.4) and 65 women (45 years +/- 12.8). The weight variation between donors and recipients (wd - wr) was 0.06 for men and 0.22 for women. The serum creatinine of recipients at 1 year was 147 mumol +/- 41.7. We used analysis of variance for univariate statistical analysis and multiple linear regression for multivariate analysis. RESULTS: On univariate analysis, the serum creatinine at 1 and 2 years was significantly higher (p < 0.02 and p < 0.035 respectively) when the donor's weight was 10% lower than the recipient's weight. Multivariate analysis, taking into account the donor's age and sex and the recipient's serum creatinine, confirmed the influence of the donor-recipient weight difference on serum creatinine at 2 years (p0.03), but also the role of the donor's age at 1 and 2 years (p < 0.0001 and p < 0.0004, respectively). CONCLUSION: In our study, the donor-recipient weight difference was a factor influencing the recipient's serum creatinine at 2 years. The donor's age also influences the recipient's serum creatinine, 1 and 2 years after renal transplantation.

Adolescent↗

[Coxiella burnetii endocarditis on a mechanical valvular prosthesis. Apropos of 2 cases].

The authors report two cases of prosthetic valve endocarditis due to Coxiella burnetii. The histories were chronic and complex suggesting an auto-immune disease: prolonged recurrent fever despite antibiotic therapy with a biological inflammatory syndrome whilst blood cultures remained negative. The first patient presented with prosthetic valve dehiscence and acute glomerulonephritis. The second patient had coagulation defects with prosthetic valve thrombosis, mesenteric adenopathy and congestive cardiac failure without prosthetic valve dysfunction. In suspected endocarditis with negative blood cultures, serological tests should be extended to intracellular pathogens difficult to identify and justifying specific and prolonged bactericidal therapy (fluoroquinolones, cyclines, rifampincine). Long-term serological surveillance is essential even when the outcome could have led to the termination of antibiotic therapy. Usually, antibiotic therapy provides a bacteriological cure, but treatment has to be continued for at least 3 years, and, in some patients, all their lives. Valve replacement is reserved for haemodynamic complications of the pathology which determine the ultimate prognosis.

Adult↗

[Cancer of the kidney, prognostic value of nuclear grading for the early diagnosis of metastasis].

OBJECTIVES: Since immunotherapy or surgery can sometimes lead to remission of metastatic renal cell carcinoma, it is important to recognize factors predicting metastasis. We therefore evaluated the usefulness of nuclear grading in predicting metastasis of renal cell carcinoma. METHODS: We retrospectively reviewed 95 patients (69 males, 26 females; mean age 63.9 years) who successively underwent surgical exeresis of a renal cell carcinoma. The TNM classification was established on the basis of preoperative work-up (thoraco-abdominal computed tomography, bone scintigraphy) and pathology examination of the surgical specimen. Nuclear grading was performed by a pathologist who was unaware of the histology results. Outcome was evaluated on the basis of physical examination and computed tomography results 6 months after surgery. RESULTS: There were 34 cases of clear cell carcinoma, 10 granulosus tumours, 2 oncocyte tumours and 16 renal cell carcinomas of undetermined type. Mean tumour diameter was 70.3 +/- 37.8 cm. Tumour classification gave (< 5 cm, n = 23; > 5 cm, n = 26; local invasion, n = 28; invasion of neighbouring organs, n = 2). Metastases had been identified in 11 patients before surgery. Nuclear grading according to the Führman scale gave F1 (n = 3), F2 (n = 28), F3 (n = 34) and F4 (n = 24). Tumour size and the TNM classification were correlated with the observed nuclear grading scores. Within one year of surgery, metastasis was observed in 6 patients whose Führman grades were F3 (n = 1) and F4 (n = 5). Metastasis occurred in 26% of the patients with a Führman grade 4. CONCLUSION: Nuclear grading can be used to identify patients who should be closely followed after surgical removal of renal cell carcinoma in order to improve early diagnose of metastasis.

Adenocarcinoma↗

[Cytopuncture: an alternative to pelviscopy in the diagnosis of lymphatic metastases of urologic pelvic tumors].

119 patients with prostatic or vesical tumours without metastases were studied by lymphography-aspiration cytology to detect lymph node metastases. 12% of aspiration cytologies were uninterpretable, corresponding to N-patients. 12% of the 105 interpretable cases were positive. Some of the patients with negative biopsies were treated nonsurgically. 28 bladder tumours were treated intravesically. 11 prostatic cancers were treated by radiotherapy and 63 patients underwent surgical resection. These 63 patients had an interpretable aspiration cytology and surgical control. Aspiration cytology was falsely negative in 7 cases: 4 microscopic metastases and 3 macroscopic metastases. The sensitivity of aspiration cytology after lymphography is 66% and its specificity is 100%. The positive predictive value is 100% and the negative predictive value is 92.3%. These 7 false-negative results included 3 macroscopic metastases already identified on CT scan and 4 micrometastases in which surgical resection was legitimate.

Adenocarcinoma↗