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Biomedical subjects

R Gallego

Publications and source records attributed to R Gallego.

At least 19 recordsLinked to original sources
PubMed2006

Steroids and bone density in patients with functioning kidney allografts.

INTRODUCTION: Osteopenia and osteoporosis after renal transplantation have been associated with factors related to the cause of end-stage renal disease, as well as to clinical events and therapeutic factors in the posttransplant period. We studied the prevalence of low bone density (LBD) according to WHO criteria. METHODS: A cross-sectional study was performed in a cohort of 106 patients (54 men and 52 women) with functioning renal allografts, who underwent bone densitometry (DEXA) of the lumbar spine and femoral neck. Patients were grouped according to DEXA into those with normal bone density (NBD) or LBD. We studied clinical, analytical, and therapeutic variables. RESULTS: Thirtysix patients (34%) had NBD and 70 patients (66%) LBD. Weight was the only parameter showing a significant difference (P = .034), namely, among NBD it was 80.44+/-15.13 versus LBD 73.94 +/- 14.54 kg, respectively. Creatinine clearance (CCr) tended to be lower among patients with LBD 59.62 +/- 22.73 versus 69.59 +/- 28.15 mL/min in patients with NBD (P = .052). PTHi levels were higher in patients with LBD (149.39 +/- 110.75) than those with NBD (110.94 +/- 82.61) (P = .069). In the multivariate analysis the important determinants were weight Exp(ss) = 0.967 [CI = 0.939 to 0.996] (P = .036); CCr Exp(ss) = 0.982 [CI = 0.965 to 1.000] (P = .055); and PTHi levels Exp(ss) = 1.003 [CI = 0.932 to 0.994] (P = .059). CONCLUSIONS: Osteopenia and osteoporosis are frequent among kidney transplant patients (66%), with a similar distribution between the lumbar spine and femoral neck. Excess weight and possibly better renal function may be protective factors. The cumulative steroid dose showed a significant effect on bone density. As expected, secondary hyperparathyroidism in patients with renal impairment seemed to be a risk factor for LBD.

Absorptiometry, Photon↗
PubMed2006

Crossmodal audio-visual interactions in the primary visual cortex of the visually deprived cat: a physiological and anatomical study.

Blind individuals often demonstrate enhanced non-visual perceptual abilities. Neuroimaging and transcranial magnetic stimulation experiments have suggested that computations carried out in the occipital cortex may underlie these enhanced somatosensory or auditory performances. Thus, cortical areas that are dedicated to the analysis of the visual scene may, in the blind, acquire the capacity to participate in other sensory processing. However, the neural substrate that underlies this transfer of function is not fully characterized. Here we studied the synaptic and anatomical basis of this phenomenon in cats that were visually deprived by dark rearing, either early visually deprived after birth (EVD), or late visually deprived after the end of the critical period (LVD); data were compared with those obtained in normally reared cats (controls). The presence of synaptic and spike responses to auditory stimulation was examined by means of intracellular recordings in area 17 and the border between areas 17 and 18. While none of the cells recorded in control and LVD cats showed responses to sound, 14% of the cells recorded in EVD cats showed both subthreshold synaptic responses and suprathreshold spike responses to auditory stimuli. Synaptic responses were of small amplitude, but well time-locked to the stimuli and had an average latency of 30+/-12ms. In an attempt to identify the origin of the inputs carrying auditory information to the visual cortex, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected in the visual cortex and retrograde labeling examined in the cortex and thalamus. No significant retrograde labeling was found in auditory cortical areas. However, the proportion of neurons projecting from supragranular layers of the posteromedial and posterolateral parts of the lateral suprasylvian region to V1 was higher than that in control cats. Retrograde labeling in the lateral geniculate nucleus showed no difference in the total number of neurons between control and visually deprived cats, but there was a higher proportion of labeling in C-laminae in deprived cats. Labeled cells were not found in the medial geniculate nucleus, a thalamic relay for auditory information, in either control or visually deprived cats. Finally, immunohistochemistry of the visual cortex of deprived cats revealed a striking decrease in pavalbumin- and calretinin-positive neurons, the functional implications of which we discuss.

Acoustic Stimulation↗
PubMed2006

HER-2 status determination in breast carcinomas. A practical approach.

Accurate evaluation of HER-2 status is crucial in the selection of breast carcinoma patients for trastuzumab (Herceptin) treatment. Various laboratory methods have been used for this purpose. The aim of the present work was to analyse the results obtained in the routine practice by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in determination of HER-2 status. Five hundred and three cases of breast invasive ductal carcinoma were selected to analyse the HER-2 overexpression by immunohistochemistry (HercepTest, Dako). HercepTest 2+ equivocal cases (60) were studied by FISH (PathVysion, Vysis) to determine HER-2 gene amplification. HER-2 overexpression determined by Herceptest was shown in 97/503 cases (19%). FISH performed on equivocal cases demonstrated HER-2 amplification in 11/60 tumours (18%). IHC and FISH together showed HER-2 overexpression/gene amplification in 21% of breast invasive carcinomas. Immunohistochemical determination of HER-2 status represents an easy and standardized method that (in contrast to FISH) can be performed in all pathology laboratories without need of any special microscope and enabling to check the morphologic features of the cells analysed. However, in order to assure the reliability of the results, standardization of fixation protocols, automation of the immunohistochemical procedure, and training of pathologists in the interpretation of the results (scoring criteria) should be a priority. Equivocal HercepTest cases must be analysed by FISH preferably in a reference laboratory.

Antibodies, Monoclonal↗
PubMed2005

Evaluation of risperidone in the treatment of behavioral and psychological symptoms and sleep disturbances associated with dementia.

BACKGROUND: Dementia is associated with progressive cognitive impairment and behavioral and psychological symptoms. Sleep-wake cycle disturbances are common in patients with dementia. This study evaluated the efficacy and safety of risperidone in the treatment of the behavioral and psychological symptoms of dementia (BPSD) and associated sleep-wake cycle disturbances. METHODS: In this open-label, 12-week, observational, prospective study, the effects of risperidone were assessed using the Neuropsychiatric Inventory (NPI) total and subscale scores. Sleep-wake cycle disturbances were rated by patients/caregivers using a newly developed sleep behavior questionnaire that included assessment of sleep duration, quality, awakenings, and effects on daily activities. Tolerability assessments included the Udvalg for Kliniske Undersogelser (UKU) subscale for extrapyramidal symptoms (EPS) and the recording of adverse events. RESULTS: A total of 338 patients entered the study, with 321 patients completing. Following 12 weeks of risperidone treatment (mean dose 1.49 mg/day at end-point), the mean NPI score was reduced to 10.6 from a baseline score of 28.7. Compared with baseline, patients/caregivers reported significant improvements following 12 weeks of risperidone in total sleep hours at night (5.5 vs. 7.1 hours), hours awake in bed at night (2.3 vs. 1.2 hours), insomnia (40.1% vs. 8.4%), and other sleep-related variables. Six patients reported a total of 10 adverse events, including somnolence (n = 3) and sialorrhea (n = 2). Scores on the UKU subscale of EPS improved significantly (mean 4.0 at baseline vs. 1.7 at week 12). CONCLUSIONS: Risperidone is effective and well tolerated in the treatment of BPSD and associated sleep disturbances.

Aged↗
PubMed2005

Regulation of peroxisome proliferator activated receptor-gamma in rat pituitary.

Peroxisome proliferator activated-receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and, in addition to its relation with obesity and insulin sensitivity, it has recently been localized in human and mice pituitary, indicating a functional significance of PPARgamma in adenopituitary tumours. In the present study, we localized the PPARgamma mRNA and protein in different cell types of rat pituitary. Moreover, using the real-time polymerase chain reaction, we assessed the mRNA expression of PPARgamma in different physiological and pathological settings known to be associated with alterations in anterior pituitary cell proliferation and/or function. Our experiments have shown that PPARgamma mRNA levels were repressed by oestrogen through an oestrogen receptor-alpha effect. However, PPARgamma protein levels were only modified in males but not in females. On the other hand, PPARgamma mRNA expression was increased in dwarf rats in comparison with Lewis rats. Finally, nutritional, thyroid status or pregnancy did not change PPARgamma expression. Taken together, we provide new data regarding the regulation of pituitary PPARgamma mRNA by hormonal and metabolic status.

Animals↗
PubMed2005

Cellular distribution of growth hormone-releasing hormone receptor in human reproductive system and breast and prostate cancers.

Growth hormone releasing hormone receptor (GHRH-R) mRNA and protein was first localized to the anterior pituitary gland, consequent with the action of its ligand on GH synthesis and release. Subsequent studies found GHRH-R also expressed in the hypothalamus and in systemic tissues including those of the reproductive system. In the present work, we studied the distribution of GHRH-R in human reproductive system of males and females by immunohistochemical method. GHRH-R immunostaining was localized in male reproductive system: Leydig cells, Sertoli and basal germ cells of the seminiferous tubules and prostate secretory cells. GHRH-R immunostaining was also demonstrated in the ovary: oocytes, follicular cells, granulosa, thecal and corpus luteum cells. Endometrial glands, placenta and normal mammary glands also showed GHRH-R immunostaining. Our results demonstrate the localization of GHRH-R in the reproductive system, which may mediate the direct action of GHRH in these tissues. Moreover, GHRH-R was demonstrated in prostate and breast carcinomas, opening a variety of possibilities for the use of GHRH antagonists in the treatment of prostatic and mammary tumors.

Adenocarcinoma↗
PubMed2005

Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome.

Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH-IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.

Carcinoma, Papillary↗
PubMed2004

The endogenous growth hormone secretagogue (ghrelin) is synthesized and secreted by chondrocytes.

Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHS-R), is a recently isolated hormone, prevalently expressed in stomach but also in other tissues such as hypothalamus and placenta. This novel acylated peptide acts at a central level to stimulate GH secretion and, notably, to regulate food intake. However, the existence of further, as yet unknown, effects or presence of ghrelin in peripheral tissues cannot be ruled out. In this report, we provide clear evidence for the expression of ghrelin peptide and mRNA in human, mouse, and rat chondrocytes. Immunoreactive ghrelin was identified by immunohistochemistry in rat cartilage, being localized prevalently in proliferative and maturative zone of the epiphyseal growth plate, and in mouse and human chondrocytic cell lines. Moreover, ghrelin mRNA was detected by RT-PCR and confirmed by Southern analysis in rat cartilage as well as in mouse and human chondrocytes cell lines. Ghrelin mRNA expression has been studied in rat along early life development showing a stable profile of expression throughout. Although ghrelin expression in chondrocytes suggests the presence of an unexpected autocrine/paracrine pathway, we failed to identify the functional GH secretagogue receptor type 1A by RT-PCR. On the other hand, binding analysis with 125I ghrelin suggests the presence of specific receptors different from the 1A isotype. Scatchard analysis revealed the presence of two receptors with respectively high and low affinity. Finally, ghrelin, in vitro, was able to significantly stimulate cAMP production and inhibits chondrocytes metabolic activity both in human and murine chondrocytes. In addition, ghrelin is able to actively decrease both spontaneous or insulin-induced long chain fatty acid uptake in human and mouse chondrocytes. This study is the first to provide evidence for the presence of this novel peptide in chondrocytes and suggests novel potential roles for this newly recognized component of the GH axis in cartilage metabolism.

Animals↗
PubMed2003

Serotonin upregulates the activity of phagocytosis through 5-HT1A receptors.

1 In this study, we investigated whether serotonin could regulate the in vitro activity of phagocytosis through 5-hydroxytryptamine or serotonin (5-HT(1A)) receptors. 2 Mouse peritoneal macrophages were cultured with serotonin and the activity of phagocytosis was assessed by the uptake of zymosan and latex particles added to the culture media. Specific binding of [(3)H]8-OH-DPAT and immunohistochemistry using an affinity-purified anti-5-HT(1A)-receptor antibody were assayed in the macrophages. In addition, we took advantage of the availability of pharmacological inhibitors of nuclear factor-kappaB (NF-kappaB) to explore its role in the regulation of the 5-HT(1A) receptor. 3 Serotonin increased the in vitro activity of phagocytosis in a dose-dependent manner. The 5-HT(1A) receptor agonist (+/-)-8-hydroxy-2-(di-n-propyl-amino)-tetralin (R(+)-8-OH-DPAT) reproduced these effects. Serotonin- or R(+)-8-OH-DPAT-induced increases in phagocytosis were blocked by the 5-HT(1A) receptor antagonist WAY100635 and the NF-kappaB inhibitor pyrrolidinedithiocarbamate. Moreover, mouse peritoneal macrophages expressed specific binding sites for [(3)H]8-OH-DPAT when cultivated in the presence of zymosan or latex beads. Immunohistochemistry confirmed the expression of the 5-HT(1A) receptor protein in the macrophages. 4 These results show that serotonin can upregulate the activity of peritoneal macrophages through 5-HT(1A) receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

MOC-31/Ep-CAM immunoreactivity in Merkel cells and Merkel cell carcinomas.

AIMS: To evaluate the monoclonal antibody MOC-31 in Merkel cell carcinomas and normal Merkel cells. Merkel cell carcinoma is a rare and aggressive tumour that occurs mainly in elderly individuals. The histological diagnosis of Merkel cell carcinoma can be difficult because it looks similar to other small blue cell tumours, particularly skin metastases of small-cell lung carcinomas. This antibody recognizes the epithelial cell adhesion molecule (Ep-CAM), that has been assigned to the small cell lung cancer cluster 2 of antibodies. To the best of our knowledge, immunostaining for MOC-31/Ep-CAM has not been previously described in Merkel cells or Merkel cell carcinomas. METHODS AND RESULTS: Thirty-one cases of Merkel cell carcinoma and three samples of normal human fingertip were selected to analyse the expression of MOC-31/Ep-CAM by immunohistochemistry. A high number of Merkel cell carcinomas (21/31, 67.7%) showed intense and readily interpretable positivity. Immunostaining was diffuse or focal and always localized to the plasma membrane. Normal Merkel cells of human fingertip also showed plasma membrane immunoreactivity for MOC-31/Ep-CAM. CONCLUSION: The demonstration of positivity for MOC-31/Ep-CAM in Merkel cell carcinomas precludes the use of this immunohistochemical marker to distinguish between tumours and skin metastases of small-cell lung carcinoma.

Adult↗
PubMed2003

European Union diabetes indicators: fact or fiction?

Diabetes mellitus is one of the major causes of morbidity and mortality in EU/EFTA countries. Monitoring risk factors for diabetes and its complications will offer the possibility to evaluate the development in time as well as the influence of possible interventions. In this investigation a list with core and secondary indicators is proposed. Availability of these indicators and their data sources is discussed. An important variability of data sources is used in EU/EFTA countries, interfering with the comparability of the outcome. Further harmonisation as well as continuous evaluation of data sources will be necessary to provide reliable tools to monitor diabetes mellitus and its outcome on a routine basis.

Comorbidity↗
PubMed2001

Transition from oscillatory to excitable regime in a system forced at three times its natural frequency.

The effect of a temporal modulation at three times the critical frequency on a Hopf bifurcation is studied in the framework of amplitude equations. We consider a complex Ginzburg-Landau equation with an extra quadratic term, resulting from the strong coupling between the external field and the unstable modes. We show that, by increasing the intensity of the forcing, one passes from an oscillatory regime to an excitable one with three equivalent frequency-locked states. In the oscillatory regime, topological defects are one-armed phase spirals, while in the excitable regime they correspond to three-armed excitable amplitude spirals. Analytical results show that the transition between these two regimes occurs at a critical value of the forcing intensity. The transition between phase and amplitude spirals is confirmed by numerical analysis and it might be observed in periodically forced reaction-diffusion systems.

Journal Article↗
PubMed2001

Localization of growth hormone receptors in rat and human thyroid cells.

Growth hormone (GH) exerts its multiple actions by binding to a specific receptor (GHR) widely distributed in the organism. It is well established that, in acromegaly, the thyroid gland is larger than normal and that GH increases triiodothyronin concentrations and decreases those of tetraiodothyronin (thyroxine). The aim of the present study was to analyze the presence of GHR and its mRNA in rat and human thyroid gland by Western blot, in situ hybridization techniques, and immunohistochemistry. A band of the expected size for GHR was shown in rat and human thyroid by Western blot. GHR immunoreactivity was found in virtually all follicles. The signal was mainly localized in the cytoplasm, although a nuclear positivity was also found. In situ hybridization techniques demonstrated the presence of GHR messenger RNA in the thyroid gland (cytoplasm of the follicular cells). These results provide direct morphological evidence that GHR is localized in the thyroid gland of mammals and opens up the possibility that GH regulates thyroid cell function directly or via local autocrine or paracrine production of insulin-like growth factor I.

Animals↗
PubMed2001

Computerising a guideline for the management of diabetes.

This paper reports an experience of computerising a clinical guideline for the management of non-insulin-dependent diabetes mellitus (NIDDM). The guideline, designed by the European NIDDM Policy Group is being used in a National Programme for Diabetes supported by the Portuguese Ministry of Health, who is keen to supporting its widespread use by general practitioners, namely in computerised form. The paper presents the main characteristics of the prototype that was implemented within the European project Prestige, and was developed according to the Prestige Protocol Model. The model is briefly described, together with the generic architecture that supports it. Then the main design decisions of the prototype are explained, regarding the modelling of a general practitioner workflow during a typical consultation and the user interface, two key issues for obtaining acceptance from the users. The limitations of the system are discussed and a number of directions are outlined in order to circumvent such limitations, and broaden the scope of applicability of the system.

Diabetes Mellitus, Type 2↗