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Biomedical subjects

I Hervás

Publications and source records attributed to I Hervás.

15 recordsLinked to original sources

Is there a correlation between brain naturietic peptide levels and echocardiographic and hemodynamic parameters in heart transplant patients?

BACKGROUND: Brain naturietic peptide (BNP) elevations have been reported in heart transplant patients both at baseline and during rejection. An association between BNP levels and certain echocardiographic and hemodynamic abnormalities has also been found in nontransplanted heart disease patients. We sought to determine whether BNP values were correlated with echocardiographic and hemodynamic parameters among a large cohort of heart transplant patients. MATERIALS AND METHODS: We studied 71 consecutive heart transplant patients, excluding combined grafts, retransplants, and pediatric cases. We performed 488 BNP determinations during catheterization and within 48 hours of echocardiography. Hemodynamic parameters included mean pulmonary artery pressure, right ventricular systolic and diastolic pressures. Doppler echocardiography parameters were wall thickness, ventricular mass, left and right ventricular end-diastolic and end-systolic diameters, isovolumic relaxation time, and mitral flow deceleration time. RESULTS: We observed significant correlations between BNP values and left ventricular size, ventricular mass, and a restrictive filling pattern. BNP levels were also significantly correlated with right ventricular size, mean pulmonary artery pressure, and right ventricular diastolic and end-diastolic pressures. CONCLUSIONS: In heart transplant patients, BNP levels positively correlated with ventricular diameters and a restrictive filling pattern. An increase in right ventricle and pulmonary artery pressures was associated with elevated BNP values.

Biomarkers↗

[Bone scintigraphy and somatostatin receptor scintigraphy in pediatric patients with bone involvement in Langerhans cell histiocytosis].

Langerhans cell histiocytosis (LCH) is a granulomatous disease which can involve multiples sites of the body. Diagnostic imaging is of utmost importance in the management of these patients. Up to now radiographic skeletal survey and bone scintigraphy (BS) have been used to assess bone involvement (both with low specificity). Magnetic resonance imaging (MRI) and CT have been used to assess visceral involvement but with the limitation that they cannot give information about the functional status. Recently somatostatin receptor scintigraphy (SSRS) has been proposed to detect active lesions and to monitor response to treatment. The aim of this study is to assess bone and somatostatin receptor scintigraphy in the detection of bone involvement in LCH in children. Twenty scintigraphies (12 SSRS and 8 BS) were performed in seven patients (3 girls and 4 boys) aged at diagnosis: 18 month-12 years (mean age 6 years). The findings obtained in the scintigraphies were compared with clinical evolution and other imaging techniques. Bone scintigraphy detected all the LCH bone lesions, and discovered one unknown lesion. SSRS scintigraphy visualised the active lesions in 3 patients (clinical and other imaging techniques were also positive). SSRS was negative in one patient classified as disease free and another in clinical remission. SSRS detected 2 new unknown bone lesions, but could not detect LCH bone lesions confirmed in other imaging techniques in 2 patients. Somatostatin receptor and Bone scintigraphy can be used to detect active LCH bone lesions in children and can help to monitor response to treatment. Further studies with more patients are needed to confirm the diagnostic usefulness of these techniques.

Biomarkers↗

Radioimmunometric assay of B-type natriuretic peptide (BNP) in heart transplantation: correlation between BNP determinations and biopsy grading of rejection.

The aim of this study was to determine whether elevated brain natriuretic peptide (BNP) levels after heart transplantation are correlated with the severity of rejection by using endomyocardial biopsy (EMB) and echocardiographic parameters indicative of ventricular function of the transplanted heart. This was an observational study of 80 orthotopic heart transplant recipients (11 women and 69 men; mean age 53+/-11 years). BNP determinations were performed within 48 h of endomyocardial biopsy. The echocardiographic study and BNP determination were also performed in a group of healthy volunteers. We found significantly higher BNP mean levels in heart transplant patients than in healthy volunteers (volunteers, 16.7+/-16.2 pg.ml-1; transplant, 213.4+/-268.6 pg.ml-1; P<0.001). Transplant recipients with rejection grades 2, 3 and 4 on EMB had significantly higher BNP levels than those with rejection grades 0 and 1 (higher rejection grade, 162.5+/-168.4 pg.ml-1; lower rejection grade, 292+/-361.8 pg.ml-1; P<0.01). BNP values of patients with good left ventricular function (LVF) were significantly lower than in patients with mildly and moderately impaired LVF and patients with severely impaired LVF (good function, 199.76+/-233.6 pg.ml-1; mildly/moderately impaired LVF, 937+/-644.5 pg.ml-1; severely impaired LVF, 1038+/-491.2 pg.ml-1; P<0.001). It is concluded that BNP plasma levels are elevated in heart transplant patients compared to the normal population. The distribution of BNP levels in heart transplanted patients show a wide range. BNP elevation is greater in patients with higher rejection grades on EMB and greater impairment of left ventricular function.

Adolescent↗

Hodgkin's disease. Prognostic value of Gallium-67 scintigraphy.

AIM: The aim of this study is to assess the clinical impact of gallium-67 scintigraphy, before and after treatment, in patients with Hodgkin's disease, and to compare the overall survival between the patients whose gallium studies after treatment were negative and those whose studies remained positive. METHODS: We have studied 75 patients (40 women, 35 men) with Hodgkin's disease. All the patients underwent (67)Ga scintigraphy at the moment of the diagnosis (basal study) and in the case that basal study was positive (abnormal hyper-uptake focus) we performed follow-up studies after the treatment. We have calculated the overall survival among patients whose studies after treatment were negative (1(st) group) and those whose studies remained positive (2(nd) group) and between patients whose studies were negative at diagnosis (3(rd) group). RESULTS: Gallium scintigraphy was positive at diagnosis in 47 patients (62.6%). In 39 of them we were able to perform the follow-up study after treatment. The follow-up study was negative in 31 patients while in 8 patients the gallium scintigraphy remained positive. The overall survival was significantly higher (p<0.001) in the 1(st) group compared with the 2(nd) group. The overall survival was higher in the 1(st) group compared with the 3(rd) but statistic significance level was not reached. CONCLUSION: Our data suggest that: 1) in Hodgkin's disease (67)Ga scintigraphy is useful to establish the diagnosis of complete remission; 2) if the gallium scan remains positive after treatment, the prognosis of patients is worse than the prognosis of patients with a negative scan.

Adolescent↗

Desensitization of 5-HT(1A) autoreceptors by a low chronic fluoxetine dose effect of the concurrent administration of WAY-100635.

Using microdialysis, receptor autoradiography and in situ hybridization, we examined the effects of fluoxetine alone or with WAY-100635 on: (a) extracellular 5-HT in frontal cortex; and (b) density and sensitivity of 5-HT(1A) autoreceptors in rat brain. WAY-100635 (0.3 mg/kg, s.c.) doubled the increase in extracellular 5-HT produced by fluoxetine (3 mg/kg, i.p.) in frontal cortex. Two-week minipump treatments with these daily doses significantly raised extracellular 5-HT to 275 +/- 33% (fluoxetine) and 245 +/- 10% (fluoxetine plus WAY-100635) of controls. Fluoxetine 3 mg/kg.day desensitized dorsal raphe 5-HT(1A) autoreceptors, an effect prevented by the concurrent WAY-100635 administration. However, WAY-100635 (alone or with fluoxetine) did not change 5-HT(1A) autoreceptor sensitivity. The density of 5-HT(1A) receptors and its encoding mRNA, was unaffected by these treatments. These results suggest that prolonged blockade of 5-HT(1A) receptors in vivo prevents the autoreceptor desensitization induced by fluoxetine but does not result in receptor sensitization.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Microvascularized fibular graft for mandibular reconstruction: detection of viability by bone scintigraphy and SPECT.

Bone allografts are often used in reconstructive mandibular surgery, generally after extensive oncologic resection, post-traumatic pseudoarthrosis, or osteomyelitis. Vascularized fibular bone grafts have advantages compared with other bone grafts in the restoration of the contour and function of defective mandibles. Bone scintigraphy is often used to assess bone revascularization, because positive uptake of Tc-99m hydroxy methylene diphosphonate (HDP) reflects patent anastomoses and viability of the grafted bone. Mandibular reconstruction with a free fibular flap was performed in 11 patients. Bone scintigraphy and SPECT were applied in the follow-up of eight patients. The grafts were assessed semi-quantitatively using a six-grade scoring system based on a comparison of tracer uptake in the graft and in the calvarium. Complications were observed in one graft. Planar scintigrams showed a tracer uptake greater than grade 5 in grafts with an uncomplicated course. SPECT was performed in addition to planar imaging in two patients who had greater graft uptake. A lack of tracer uptake was observed in the failed graft. Bone scintigraphy performed within the first week after the mandibular reconstruction is a useful tool to monitor the viability and early complications of microvascularized fibular grafts and plays an important role in the decision-making process during repeated surgical exploration. SPECT is more sensitive than planar imaging for assessing graft viability.

Adult↗

Is the depth correction using the geometric mean really necessary in a 99Tcm-DMSA scan in the paediatric population?

Determination of the left to right dimercaptosuccinic acid (DMSA) uptake ratio is theoretically one of the easiest quantitative procedures in nuclear medicine. The quantification can be performed on the posterior view, with or without the lateral view for correction of kidney depth. The geometric mean can also be determined using both the anterior and the posterior views. The aim of this study was to evaluate the occurrence of remarkable differences in the results from quantification of the relative renal function using the geometric mean and those obtained using the posterior counts only. Moreover, we evaluated to what extent the patient age influenced these differences. We reviewed 328 99Tcm-DMSA scans. The difference between the relative renal function obtained using the posterior view and that obtained using the geometric mean was calculated and analysed statistically. For the purpose of evaluating the value of performing the geometric mean calculation in patients of different ages, patients were divided into four age groups (group I, < or =2 years; group II, 3-9 years; group III, 10-18 years; group IV, >18 years). Using the Student's t test, no statistical differences were found in the relative renal function obtained by the two methods (posterior projection and geometric mean) in groups I (t = 0.01, P = 0.992) and II (t = 1.43, P = 0.155), which consisted of patients younger than 10 years (77% of the patients). In groups III and IV statistical differences were found (t = 2.27, P = 0.028 and t = 2.170, P = 0.038), respectively. We conclude that for children under 10 years it is unnecessary to perform depth correction using the geometric mean except in rare cases of major malformations and position anomalies.

Adolescent↗

Role of uptake inhibition and autoreceptor activation in the control of 5-HT release in the frontal cortex and dorsal hippocampus of the rat.

1. Using brain microdialysis, we compared the relative role of 5-hydroxytryptamine (5-HT; serotonin) blockade and somatodendritic 5-HT(1A) and/or terminal 5-HT(1B) autoreceptor activation in the control of 5-HT output. 2. Fluoxetine (10 mg kg(-1) i.p.) doubled the 5-HT output in frontal cortex and dorsal hippocampus. The 5-HT(1A) receptor antagonist WAY 100635, (0.3 mg kg(-1) s.c.) potentiated the effect of fluoxetine only in frontal cortex (to approximately 500 % of baseline). 3. Methiothepin (10 mg kg(-1) s.c.) further enhanced the 5-HT rise induced by fluoxetine+WAY 100635, to 835+/-179% in frontal cortex and 456+/-24% in dorsal hippocampus. Locally applied, methiothepin potentiated the fluoxetine-induced 5-HT rise more in the former area. 4. The selective 5-HT(1B) receptor antagonist SB-224289 (4 mg kg(-1) i.p.) enhanced the effect of fluoxetine (10 mg kg(-1) i.p.) in both areas. As with methiothepin, SB-224289 (4 mg kg(-1) i.p.) further enhanced the 5-HT increase produced by fluoxetine+WAY 100635 more in frontal cortex (613+/-134%) than in dorsal hippocampus (353+/-59%). 5. Locally applied, fluoxetine (10 - 300 microM; EC(50)=28 - 29 microM) and citalopram (1 - 30 microM; EC(50)=1.0 - 1.4 microM) increased the 5-HT output two to three times more in frontal cortex than in dorsal hippocampus. These data suggest that the comparable 5-HT increase produced by systemic fluoxetine in frontal cortex and dorsal hippocampus results from a greater effect of reuptake blockade in frontal cortex that is offset by a greater autoreceptor-mediated inhibition of 5-HT release. As a result, 5-HT autoreceptor antagonists preferentially potentiate the effect of fluoxetine in frontal cortex.

Animals↗

Postsynaptic 5-HT1A receptors control 5-HT release in the rat medial prefrontal cortex.

5-HTt1A receptor agonists reduce the neuronal release of 5-hydroxytryptamine (5-HT) by activation of raphe 5-HT1A autoreceptors. Using in vivo microdialysis in unanesthetized rats, we show that the local application of the selective 5-HT1A receptor agonist 8-OH-DPAT decreased the 5-HT output to approximately 50% of controls in medial prefrontal cortex (mPFC) but not in dorsal hippocampus. The decrease in 5-HT output was counteracted by the concurrent application of the selective 5-HT1A receptor antagonist WAY-100635. This agent also reversed the decrease in 5-HT output elicited by the novel 5-HT1A receptor agonist BAY x 3702 (30 microM) in mPFC and dorsal raphe nucleus. These results indicate that postsynaptic 5-HT1A receptors in mPFC also participate in the control of serotonergic activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. Role of 5-HT autoreceptors.

Using microdialysis, we examined the effects of the antidepressant drug fluoxetine on 5-hydroxytryptamine (5-HT) output in rat brain. Fluoxetine (1, 3 and 10 mg/kg i.p.) dose dependently increased 5-HT output in the dorsal and median raphe nuclei and four forebrain areas. Maximal elevations were noted in the raphe nuclei. At 1 and 3 mg/kg, fluoxetine elicited minor or no increases of 5-HT output in the forebrain. When citalopram was present in the perfusion fluid, fluoxetine (10 mg/kg) reduced 5-HT output, an effect reversed by the administration of the selective 5-HT1A receptor antagonist ¿N-[2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl]-N-(2-pyridyl) cyclohexane carboxamide.3HCl¿ (WAY 100635). This reduction was more marked in the frontal cortex than in the dorsal hippocampus. Consistent with this, WAY 100635 potentiated the effect of 3 and 10 mg/kg fluoxetine more in the frontal cortex than in the dorsal hippocampus. The administration of a combination of WAY 100635 (0.3 mg/kg s.c.) and the 5-HT1B/1D receptor antagonist ¿N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl),[1,1-biphenyl]-4-carboxiamide¿ (GR 127935; 5 mg/kg s.c.) potentiated the effect of 3 mg/kg fluoxetine to an extent similar to that of WAY 100635 alone in both areas. These results suggest that somatodendritic 5-HT1A receptors offset the effect of fluoxetine in the frontal cortex but not (or to a lesser extent) in the dorsal hippocampus. GR 127935 may have a partial antagonistic action at terminal 5-HT autoreceptors in vivo.

Analysis of Variance↗

In vivo control of 5-hydroxytryptamine release by terminal autoreceptors in rat brain areas differentially innervated by the dorsal and median raphe nuclei.

Selective serotonin reuptake inhibitors (SSRIs) reduce the 5-HT release in vivo. This effect is due to the activation of somatodendritic 5-HT1A receptors and it displays a regional pattern comparable to that of selective 5-HT1A agonists, i.e., preferentially in forebrain areas innervated by the dorsal raphe nucleus (DRN). However, despite a comparatively lower 5-HT1A-mediated inhibition of 5-HT release and a greater density of serotonergic uptake sites in hippocampus, the net elevation produced by the systemic administration of SSRIs is similar in various forebrain areas, regardless of the origin of serotonergic fibres. As terminal autoreceptors may also limit the SSRI-induced elevations of 5-HT in the extracellular brain space, we reasoned that a differential control of 5-HT release by terminal autoreceptors in DRN- and median raphe-innervated areas might be accountable. To examine this possibility, we have conducted a regional microdialysis study in the DRN, MRN and four forebrain regions preferentially innervated either by the DRN (frontal cortex, striatum) or the median raphe nucleus (MRN; dorsal and ventral hippocampus) using freely moving rats. Dialysis probes were perfused with 1 microM of the SSRI citalopram to augment the endogenous tone on terminal 5-HT autoreceptors. The non-selective 5-HT1 antagonist methiothepin (10 and 100 microM, dissolved in the dialysis fluid) increased extracellular 5-HT in frontal cortex and dorsal hippocampus in a concentration-dependent manner. The 5-HT(1B/1D) antagonist GR 127935 was ineffective at 10 microM and tended to reduce 5-HT in dorsal hippocampus at 100 microM. The local infusion of 100 microM methiothepin significantly elevated the extracellular 5-HT concentration to 142-173% of baseline (mean values of 260 min post-administration) in the DRN, MRN, frontal cortex, striatum and hippocampus (dorsal and ventral). Comparable elevations were noted in the four forebrain regions examined. As observed in frontal cortex and dorsal hippocampus, the perfusion of 10 microM GR 127935 did not elevate 5-HT in DRN. MRN, striatum or ventral hippocampus. Because the stimulated 5-HT release in the DRN has been suggested to be under control of 5-HT(1B/1D) receptors, we examined the possible contribution of these receptor subtypes to the effects of methiothepin in the DRN. The perfusion of sumatriptan (0.01-10 microM) or GR 127935 (0.01-10 microM) did not significantly modify the 5-HT concentration in dialysates from the DRN. Thus, the present data suggest that the comparable effects of SSRIs in DRN- and MRN-innervated forebrain regions are not explained by a preferential attenuation of 5-HT release by terminal 5-HT1B autoreceptors in hippocampus, an area with a low inhibitory influence of somatodendritic 5-HT1A receptors. Methiothepin-sensitive autoreceptors (possibly 5-HT1B) appear to play an important role not only in the projection areas but also with respect to the control of 5-HT release in the DRN and MRN. In addition, our findings indicate that GR 127935 is not an effective antagonist of the actions of 5-HT at rat terminal autoreceptors.

Animals↗

The 5-HT1A antagonist WAY-100635 selectively potentiates the presynaptic effects of serotonergic antidepressants in rat brain.

The increases in extracellular serotonin (5-hydroxytryptamine; 5-HT) produced by some antidepressent drugs in forebrain are attenuated by the activation of somatodendritic 5-HT1A autoreceptors by the excess 5-HT induced by these agents in the midbrain raphe. Using microdialysis, we have examined the effects of the selective 5-HT1A antagonist WAY-100635 in rats pretreated with the selective 5-HT reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, the tricyclic antidepressants clomipramine and desipramine and the monoamine oxidase inhibitor phenelzine. WAY-100635 markedly potentiated the increases in 5-HT produced by the SSRIs, clomipramine and phenelzine but it did not alter that produced by desipramine. These results indicate that the effects of serotonergic antidepressant drugs (but not those of desipramine, which mainly blocks noradrenaline reuptake) can be potentiated by 5-HT1A autoreceptor blockade.

Animals↗