RESUMO
BACKGROUND: Infusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier. The aim of this present study was to assess the efficacy and safety of high dose MTX in patients with central nervous system (CNS) metastases of breast cancer. METHODS: Twenty-two patients with CNS metastases treated by MTX (3 g/m2) between April 2004 and October 2009 were enrolled. Clinical response rate, time to progression (TTP), overall survival (OS), and safety were assessed. RESULTS: In terms of brain metastases, 2 patients (9%) achieved a partial response, 10 patients (45%) had disease stabilization, and 10 patients (45%) had disease progression. In others metastatic sites, 7 patients (39%) achieved a disease stabilization, and 11 patients (61%) had disease progression. TTP and OS were 2.1 (95%CI 1.4-2.9) and 6.3 (95%CI 1.8-10) months, respectively. CONCLUSION: High-dose MTX demonstrated a moderate activity at 3 g/m2. Nonetheless, the favorable toxicity profile should suggest the possibility to increase the dosage and further study are planned.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Metotrexato/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/secundário , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de SobrevidaRESUMO
GOAL: To study the impact of systemic treatment in neoadjuvant strategy before surgery in prostate cancer. MATERIALS: Literature reviews with data analysis from PubMed search using the keywords "neoadjuvant", "chemotherapy", "hormonal therapy", "prostate surgery", "radical prostatectomy", but also reports from ASCO and ESMO conferences. The articles on neoadjuvant treatment before radiotherapy were excluded. RESULTS: First studies with former therapy are more than 15-years-old and with questionable methodology: lack of power to have a clear idea of the impact on survival criteria such as overall survival or relapse-free survival. However, the impact of neoadjuvant hormone therapy on the classic risk factors for relapse (positive margins, intraprostatic disease, positive lymph nodes) was demonstrated by these studies and a Cochrane meta-analysis. The association with hormone therapy seems mandatory in comparison to treatment based solely on chemotherapy and/or targeted therapy. Promising data on the use of new drugs and their combinations arise: abiraterone acetate combined with LHRH analogue showed a fast PSA decrease and higher rates of pathologic complete response. Other results are promising with hormonal blockages at various key points. CONCLUSION: Studies with 2nd generation anti-androgene agents or enzyme inhibitors seem to show very promising results. To provide answers about the effectiveness of current neoadjuvant strategy in terms of survival, other studies are needed: randomized phase III or phase II exploring predictive biomarkers. The design of such trials requires a multidisciplinary approach with urologists, oncologists, radiologists and methodologists.
Assuntos
Terapia Neoadjuvante , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Humanos , Masculino , Cuidados Pré-OperatóriosRESUMO
Acute PTH administration enhances final urine acidification in the rat. HCl was infused during 3 h in rats to determine the parathyroid and renal responses to acute metabolic acidosis. Serum immunoreactive PTH (iPTH) concentration significantly increased and nephrogenous adenosine 3H,5H-cyclic monophosphate tended to increase during HCl loading in intact and adrenalectomized (ADX) rats despite significant increments in plasma ionized calcium. Strong linear relationships existed between serum iPTH concentration and arterial bicarbonate or proton concentration (P less than 0.0001). Serum iPth concentration and NcAMP remained stable in intact time-control rats and decreased in CaCl2-infused, nonacidotic animals. Urinary acidification was markedly reduced in parathyroidectomized (PTX) as compared with intact rats during both basal and acidosis states; human PTH-(1-34) infusion in PTX rats restored in a dose-dependent manner the ability of the kidney to acidify the urine and excrete net acid. Acidosis-induced increase in urinary net acid excretion was observed in intact, PTX, and ADX, but not in ADX-thyroparathyroidectomized rats. We conclude that (a) acute metabolic acidosis enhances circulating PTH activity, and (b) PTH markedly contributes to the renal response against acute metabolic acidosis by enhancing urinary acidification.
Assuntos
Acidose/sangue , Rim/fisiopatologia , Hormônio Paratireóideo/sangue , Acidose/fisiopatologia , Adrenalectomia , Amônia/urina , Animais , Bicarbonatos/sangue , Cálcio/sangue , AMP Cíclico/metabolismo , Taxa de Filtração Glomerular , Concentração de Íons de Hidrogênio , Magnésio/sangue , Masculino , Fosfatos/urina , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Paired micropuncture experiments were carried out in plasma-replete volume-expanded rats to examine the acute effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on urinary acidification and tubular handling of bicarbonate and chloride. No effect was detected on the fractional absorption of water, total CO2, and chloride at end-proximal and early distal sites of superficial nephrons in intact animals; dDAVP, however, inhibited the fractional absorption of total CO2 in Henle's loop while stimulating that of chloride in thyroparathyroidectomized (TPTX) somatostatin-infused rats. In the distal tubule accessible to micropuncture, net total CO2 secretion was observed during hypotonic volume expansion, which reversed to net total CO2 absorption during dDAVP infusion in intact Wistar rats. Marked stimulation of urinary acidification occurred in all animals as attested by a fall in urine pH and bicarbonate excretion. Net acid excretion almost doubled in intact rats. We conclude that (a) antidiuretic hormone (ADH) inhibits fractional bicarbonate absorption in the thick ascending limb while stimulating that of chloride at least in TPTX somatostatin-infused rats, and (b) ADH stimulates proton secretion (or inhibits bicarbonate secretion) in the distal tubule and cortical collecting ducts, which leads to enhanced urinary acidification.
Assuntos
Ácidos/urina , Bicarbonatos/metabolismo , Desamino Arginina Vasopressina/farmacologia , Túbulos Renais/metabolismo , Animais , Análise Química do Sangue , Água Corporal/metabolismo , Cloretos/metabolismo , Diurese , Taxa de Filtração Glomerular , Rim/metabolismo , Masculino , Ratos , Ratos EndogâmicosRESUMO
The renal medullary thick ascending limb (MTAL) of the rat absorbs bicarbonate through luminal H+ secretion and basolateral HCO3- transport into the peritubular space. To characterize HCO3- transport, intracellular pH (pHi) was monitored by use of the pH-sensitive fluorescent probe (2',7')-bis-(carboxyethyl)-(5,6)-carboxyfluorescein in fresh suspensions of rat MTAL tubules. When cells were preincubated in HCO3-/CO2-containing solutions and then abruptly diluted into HCO3-/CO2-free media, the pHi response was an initial alkalinization due to CO2 efflux, followed by an acidification (pHi recovery). The pHi recovery required intracellular HCO3-, was inhibited by 10(-4) M diisothiocyanostilbene-2-2'-disulphonic acid (DIDS), and was not dependent on Cl- or Na+. As assessed by use of the cell membrane potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine, cell depolarization by abrupt Cl- removal from or addition of 2 mM barium into the external medium did not affect HCO3(-)-dependent pHi recovery, and the latter was not associated per se with any change in potential difference, which indicated that HCO3- transport was electroneutral. The HCO3(-)-dependent pHi recovery was inhibited by raising extracellular potassium concentration and by intracellular potassium depletion. Finally, as measured by use of a K(+)-selective extracellular electrode, a component of K+ efflux out of the cells was HCO3- dependent and DIDS sensitive. The results provide evidence for an electroneutral K+/HCO3- cotransport in rat MTAL cells.
Assuntos
Bicarbonatos/metabolismo , Medula Renal/metabolismo , Túbulos Renais/metabolismo , Potássio/metabolismo , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/farmacologia , Animais , Transporte Biológico , Cloretos/metabolismo , Técnicas In Vitro , Masculino , Ratos , Ratos EndogâmicosRESUMO
Chronic metabolic acidosis (CMA) is associated with an adaptive increase in the bicarbonate absorptive capacity of the rat medullary thick ascending limb (MTAL). To specify whether NHE-3, the apical MTAL Na/H exchanger, is involved in this adaptation, NHE-3 mRNA was quantified by a competitive RT-PCR using an internal standard which differed from the wild-type NHE-3 mRNA by an 80-bp deletion. CMA increased NHE-3 mRNA from 0.025+/-0.003 to 0.042+/-0.009 amol/ng total RNA (P < 0.005). NHE-3 transport activity was measured as the initial proton flux rate calculated from the Na-dependent cell pH recovery of Na-depleted acidified MTAL cells in the presence of 50 microM HOE694 which specifically blocks NHE-1, the basolateral MTAL NHE isoform. CMA caused a 68% increase in NHE-3 transport activity (P < 0.001). In addition, CMA was associated with a 71% increase in NHE-3 protein abundance (P < 0.05) as determined by Western blot analysis on MTAL membranes using a polyclonal antiserum directed against a cytoplasmic epitope of rat NHE-3. Thus, NHE-3 adapts to CMA in the rat MTAL via an increase in the mRNA transcript that enhances NHE-3 protein abundance and transport activity.
Assuntos
Acidose/genética , Acidose/metabolismo , Bulbo/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Cloreto de Amônio/farmacologia , Animais , Bicarbonatos/metabolismo , Transporte Biológico , Western Blotting , Células Cultivadas , Doença Crônica , Masculino , Bulbo/citologia , Reação em Cadeia da Polimerase , Bombas de Próton , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/fisiologia , Transcrição GênicaRESUMO
Preservation of honey bee (Apis mellifera L., Hymenoptera: Apidae) sperm, coupled with instrumental insemination, is an effective strategy to protect the species and their genetic diversity. Our overall objective is to develop a method of drone semen preservation; therefore, two experiments were conducted. Hypothesis 1 was that cryopreservation (-196 °C) of drone semen is more effective for long-term storage than at 16 °C. Our results show that after 1 yr of storage, frozen sperm viability was higher than at 16 °C, showing that cryopreservation is necessary to conserve semen. However, the cryoprotectant used for drone sperm freezing, dimethyl sulfoxide (DMSO), can harm the queen and reduce fertility after instrumental insemination. Hypothesis 2 was that centrifugation of cryopreserved semen to reduce DMSO prior to insemination optimize sperm quality. Our results indicate that centrifuging cryopreserved sperm to remove cryoprotectant does not affect queen survival, spermathecal sperm count, or sperm viability. Although these data do not indicate that centrifugation of frozen-thawed sperm improves queen health and fertility after instrumental insemination, we demonstrate that cryopreservation is achievable, and it is better for long-term sperm storage than above-freezing temperatures for duration of close to a year.
Assuntos
Criação de Abelhas/métodos , Abelhas/fisiologia , Preservação do Sêmen/métodos , Sêmen/fisiologia , Espermatozoides/fisiologia , Animais , Animais Domésticos , Centrifugação/métodos , Criopreservação/métodos , Crioprotetores/análise , Dimetil Sulfóxido/análise , Feminino , Longevidade , Masculino , Contagem de EspermatozoidesRESUMO
Glycogen synthase kinase-3ß (GSK3ß) is a multifunctional kinase whose inhibition is known to limit myocardial ischemia-reperfusion injury. However, the mechanism mediating this beneficial effect still remains unclear. Mitochondria and sarco/endoplasmic reticulum (SR/ER) are key players in cell death signaling. Their involvement in myocardial ischemia-reperfusion injury has gained recognition recently, but the underlying mechanisms are not yet well understood. We questioned here whether GSK3ß might have a role in the Ca(2+) transfer from SR/ER to mitochondria at reperfusion. We showed that a fraction of GSK3ß protein is localized to the SR/ER and mitochondria-associated ER membranes (MAMs) in the heart, and that GSK3ß specifically interacted with the inositol 1,4,5-trisphosphate receptors (IP3Rs) Ca(2+) channeling complex in MAMs. We demonstrated that both pharmacological and genetic inhibition of GSK3ß decreased protein interaction of IP3R with the Ca(2+) channeling complex, impaired SR/ER Ca(2+) release and reduced the histamine-stimulated Ca(2+) exchange between SR/ER and mitochondria in cardiomyocytes. During hypoxia reoxygenation, cell death is associated with an increase of GSK3ß activity and IP3R phosphorylation, which leads to enhanced transfer of Ca(2+) from SR/ER to mitochondria. Inhibition of GSK3ß at reperfusion reduced both IP3R phosphorylation and SR/ER Ca(2+) release, which consequently diminished both cytosolic and mitochondrial Ca(2+) concentrations, as well as sensitivity to apoptosis. We conclude that inhibition of GSK3ß at reperfusion diminishes Ca(2+) leak from IP3R at MAMs in the heart, which limits both cytosolic and mitochondrial Ca(2+) overload and subsequent cell death.
Assuntos
Sinalização do Cálcio , Quinase 3 da Glicogênio Sintase/fisiologia , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/enzimologia , Retículo Sarcoplasmático/metabolismo , Animais , Cálcio/metabolismo , Linhagem Celular , Glicogênio Sintase Quinase 3 beta , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/enzimologia , Miocárdio/patologia , Miócitos Cardíacos/enzimologia , Fosforilação , Processamento de Proteína Pós-TraducionalRESUMO
Several reports indicate that use of hypnotics is significantly higher in France relative to other European countries, but few reports exist concerning the cost of this high consumption of psychotropic medications. The purpose of the present study was to estimate the direct costs that may be attributed to insomnia in France. Data were derived from previously published surveys in this field. It includes the cost of sleep medications and of substances used to promote sleep, outpatient visits to physicians or to other health professionals and sleep recordings and treatment by sleep specialists. The final estimate of the total direct cost of insomnia in France in 1995 was FF 10,232,992,500 ($2,067,271,100). Public authorities have to understand that an increase in the direct costs of insomnia may be balanced by the reduction of the daytime consequences of insomnia and then by the reduction of the indirect costs of insomnia.
Assuntos
Custos de Cuidados de Saúde/estatística & dados numéricos , Distúrbios do Início e da Manutenção do Sono/economia , Adolescente , Adulto , Idoso , Efeitos Psicossociais da Doença , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Inquéritos e QuestionáriosRESUMO
The pathogenesis of excessive arginine vasopressin (AVP) release and hyponatraemia in euvolaemic intensive care unit (ICU) patients is poorly understood. Stress has frequently been proposed as a possible determinant, but its actual responsibility has not been adequately assessed. Therefore, water-load tests were prospectively performed in 11 patients admitted to the ICU for severe or potentially severe diseases, but who had no other condition which could result in excessive AVP release or impairment of renal diluting ability. Renal diluting ability was normal in 9 patients. Two patients exhibited very slight defects, which might be the consequence of subclinical haemodynamic alterations, since one had a pulmonary embolism and the other manifested a gastrointestinal haemorrhage just after the completion of the water load. Nevertheless, plasma AVP levels decreased in response to the water load in all the patients, resulting in a significant decrease in mean values. Plasma norepinephrine values were found to be elevated both before and after water loading. A highly significant correlation existed between the levels of norepinephrine and those of AVP measured before the load, but was lost after it. In addition, norepinephrine values were markedly elevated in two patients who exhibited strictly normal renal diluting abilities, and no correlation was found between plasma norepinephrine values and any parameter of renal water excretion. Our study shows that the stress of a serious illness and of admission to an ICU does not seem to interfere, by itself, with osmotic regulation of AVP secretion and renal diluting ability, and that sympathetic activation is not, under such circumstances, a predominant stimulus for AVP release.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Arginina Vasopressina/sangue , Cuidados Críticos/psicologia , Hiponatremia/sangue , Estresse Psicológico/complicações , Equilíbrio Hidroeletrolítico , Adulto , Arginina Vasopressina/biossíntese , Humanos , Hiponatremia/etiologia , Hiponatremia/fisiopatologia , Rim/fisiopatologia , Pessoa de Meia-Idade , Norepinefrina/sangue , Concentração Osmolar , Admissão do Paciente , Estudos Prospectivos , Sódio/sangue , Estresse Psicológico/sangue , Estresse Psicológico/etiologiaRESUMO
The H+ and HCO3- transporters present in the medullary thick ascending limb (MTAL) of the kidney are involved in several functions, such as transepithelial transport, defense of cell pH and cell volume. Apical H+ secretion occurs via the NHE-3 and NHE-2 isoforms of the Na+/H+ exchanger, and H(+)-ATPase. The apical Na+/H+ exchanger is responsible for most of the apical step of transepithelial HCO3- absorption and is unresponsive to cell acidification under isosmotic conditions. Basolateral HCO3- efflux mechanisms may occur via the Cl-/HCO3- exchanger and via the cotransporters K+/HCO3- (in the rat) and Na-3HCO3- (in the mouse). However, the role of each transporter in transepithelial HCO3- absorption is currently unknown. Inhibition of the basolateral Na+/H+ exchanger (NHE-1) paradoxically inhibits the apical Na+/H+ exchanger. This cross talk is independent of cell pH and may involve variations in cell volume. Arginine vasopressin (AVP) and hyperosmolality induce a differential regulation of basolateral NHE-1 and the apical Na+/H+ exchanger. They stimulate the basolateral NHE-1, and the resulting cell alkalinization probably stimulates the pHi-sensitive AE2, which restores cell volume by cellular uptake of NaCl. They also inhibit the apical Na+/H+ exchanger, which reduces net HCO3- absorption and thus may prevent interstitial fluid alkalinization. Chronic metabolic acidosis markedly increases HCO3- absorptive capacity of MTAL, by stimulating at least the synthesis of apical NHE-3 protein, as in the proximal tubule. Conversely, chronic metabolic alkalosis reduces the apical NHE-3 transport activity by decreasing the synthesis of NHE-3 protein. The paradoxical increase in HCO3- absorptive capacity of MTAL observed in the model of chronic NaHCO3-load alkalosis should be due to other factors overcoming the inhibitory effect of alkalosis on NHE-3.
Assuntos
Bicarbonatos/metabolismo , Medula Renal/metabolismo , Alça do Néfron/metabolismo , Desequilíbrio Ácido-Base/metabolismo , Animais , Humanos , Concentração de Íons de Hidrogênio , Transporte de Íons/efeitos dos fármacos , Trocadores de Sódio-Hidrogênio/fisiologiaRESUMO
The rat MTAL secretes protons into the tubular fluid and thus absorbs bicarbonate at substantial rates. Yet the cellular mechanisms of H+/HCO3- transport in the rat MTAL remain largely unsettled. We have performed intracellular pH recovery studies with use of the fluorescent probe BCECF in suspensions of rat MTAL fragments. Luminal H+ secretion occurs by two mechanisms (each responsible for 50% of the normal pHi recovery rate): (1) an electroneutral Na+/H+ antiporter that has an Na-Km of about 11 mM and is inhibited by amiloride (Ki = 2.8 x 10(-5) M); (2) a primary H+ pump that is inhibited by 10(-4) M NEM and 10(-4) M omeprazole, but not by 10(-4) M vanadate or removal of external K. These results suggest the presence of a vacuolar H(+)-ATPase rather than a H(+)-K(+)-ATPase. Basolateral HCO3 exit occurs predominantly by a Cl(-)- and Na(+)-independent electroneutral K+/HCO3- symporter, that has an HCO3-Km of about 17 mM, and is partially inhibited by 10(-4) M DIDS. Basolateral HCO3- efflux was not accompanied by variations of membrane potential monitored with the Em-sensitive fluorescent probe DIS-C3-5, and was not affected by maneuvers that depolarize the cells. It was strongly inhibited by cellular K depletion and dependent on transmembrane K gradient. We conclude that the rat MTAL should secrete protons through both Na+/H+ antiporter and H(+)-ATPase, and that basolateral HCO3- exit should occur through an electroneutral K+/HCO3- symporter.
Assuntos
Bicarbonatos/metabolismo , Proteínas de Transporte/metabolismo , Alça do Néfron/metabolismo , Transporte Biológico , Eletroquímica , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Medula Renal , ATPases Translocadoras de Prótons/metabolismo , Trocadores de Sódio-HidrogênioRESUMO
Traditional bone involvement, such as osteoitis fibrosa, has become very rare (< 1%) in primary hyperparathyroidism (PHPT); nevertheless, fractures seem more frequent than in controls, with a predilection for fractures of the distal extremity of the radius, pelvis, ribs and vertebrae, and a relative modest incidence of fractures of the upper extremity of the femur. Histo-morphometric studies have stressed a discrepancy between cortical and trabecular bone with an increase of bone remodeling. The cortical width is constantly diminished and the cortical porosity is increased whereas trabecular volume is normal and micro-architecture preserved. Bone mineral density (BMD) allows an early diagnosis of bone disease and takes a growing place in the management of patients. Since the consensus conference in 1991, the measurement of BMD has been incorporated in the surgical decision with a threshold: Z-score < -2. The demineralisation predominates on sites rich in cortical bone (1/3 proximal of the distal radius); the radius, which was the first site evaluated for technical reasons, is also the most discriminating one. Spine demineralisation is met in more severe forms and BMD measurement of the whole body is promising but requires more studies. In the absence of a radical processing, moderate forms remain stable, whereas more severe forms have a tendency to deteriorate. The evaluation of spine and femoral BMD is useful for the follow-up because the bone gain after parathyroidectomy is significant early on at these sites (rich in trabecular bone with high bone turnover), whereas the BMD of radius is relatively stable.
Assuntos
Densidade Óssea , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Hiperparatireoidismo/complicações , Humanos , Radiografia , UltrassonografiaRESUMO
Patients with suspected coronary artery disease are sometimes unable to exercise adequately (85% of age calculated maximal heart rate) to validate their ergometric stress test. Some groups suggest performing dipyridamole scintigraphy from the outset but then the information provided by exercise stress testing is lost. The aim of this study was to compare scintigraphies performed after exercise alone and after exercise combined with dipyridamole using a method of quantification. Thirteen patients with ischaemic heart disease without necrosis (coronary lesions greater than 75% luminal narrowing in: 7 right coronary, 10 left anterior descending, 3 left circumflex arteries and 1 left main coronary artery with 50% luminal narrowing) underwent exercise stress testing followed by Thallium imaging. One week later, the same exercise stress test was performed followed by an intravenous injection of dipyridamole and Thallium scintigraphy. The circumference of the radioactivity was traced and the surface of each segment calculated in three different short axis views, subdivided into 4 segments (anterior, lateral, inferior and septal walls). Any segment vascularised by a stenosed coronary artery was considered to be underperfused (105 segments). The ratios of the surfaces of underperfused/normal segments were compared using the two study protocols. Segments of the same wall in the 3 short axis views were grouped in the same myocardial zone. Thirty five myocardial zones were thus obtained: 25 zones were more underperfused after combining exercise and dipyridamole than after simple exercise stress (p = 0.014). The average increase in underperfusion after the combined exercise-dipyridamole was 12.4% compared with 5.5% after exercise alone (p = 0.03). Secondary effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doença das Coronárias/diagnóstico por imagem , Dipiridamol/administração & dosagem , Coração/diagnóstico por imagem , Eletrocardiografia , Teste de Esforço , Humanos , Computação Matemática , Cintilografia , Radioisótopos de TálioRESUMO
The goal of this paper was to summarize three studies focused on sleep/wake disorders in blind subjects. The first study was an epidemiology survey performed in 1073 blind subjects in comparison with non-blind controls. The blind had more episodes of insomnia and free running rhythms. They also took more sleeping pills and complained of more daytime somnolence. The seriousness of the sleep disorders was related to the seriousness of the blindness. In the second study, 78 blind children were compared with seeing children. They had more insomnia and more parasomnias but there was not any more free running. Finally, polysomnography was performed in 26 free running blind subjects in comparison with 26 controls. Total sleep time and sleep efficiency were lower in the blind. Sleep latency was increased and REM sleep was disturbed (longer latency and percentage decreases). There was no difference concerning slow wave sleep. Factorial analysis showed that factors such as being born blind, having ocular prosthesis, being single or having children had no influence on sleep. Working did however have an influence.
Assuntos
Cegueira/fisiopatologia , Transtornos do Sono do Ritmo Circadiano/fisiopatologia , Adolescente , Adulto , Cegueira/epidemiologia , Córtex Cerebral/fisiopatologia , Criança , Ritmo Circadiano/fisiologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Parassonias/epidemiologia , Parassonias/fisiopatologia , Polissonografia , Valores de Referência , Transtornos do Sono do Ritmo Circadiano/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Fases do Sono/fisiologiaRESUMO
Insomnia is not only a disease of sleep, it has also daily consequences: fatigue, irritability, impaired daytime functioning. These complaints are regent reported by the patients, however the objective tests assessing alertness in insomnia are usually not impaired when compared with good sleepers. We wanted to appreciate more accurately the daily consequences of insomnia, in terms of quality of life. 240 severe insomniacs (according to the DSM-IV criterias) and 391 good sleepers received a questionnaire on quality of life items. Depressed and anxious patients were excluded from this group. The questionnaire was built by a multidisciplinary group, based on insomniac's interviews. It was primarily tested in a small sample and then proposed in the entire group. Insomniac's quality of life appeared to be significantly impaired in comparison with good sleepers. They experienced more fatigue and more sleepiness during the daytime. They reported more attention disorders and memory complaints. They seemed to be more irritable and sensitive to the environment. At work they made more mistakes and had more sic leave. They also had poorer relationships with relatives and family than good sleepers.
Assuntos
Ritmo Circadiano , Qualidade de Vida , Distúrbios do Início e da Manutenção do Sono/psicologia , Adulto , Idoso , Atenção , Fadiga/psicologia , Feminino , Humanos , Humor Irritável , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicometria , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Inquéritos e QuestionáriosRESUMO
The near constancy of extracellular calcium concentration is required for the numerous physiological functions of extra- and intracellular calcium. This implies that any change in extracellular calcium concentration must be detected in order to allow the appropriate correction by the homeostatic systems. The identification and cloning of a calcium-sensing receptor (CaR), which is expressed in the plasma membrane of parathyroid cells as well as many other cell types, has been a major advance in the understanding of the mechanisms involved in the control of extracellular calcium concentration. In addition, it demonstrated that extracellular calcium concentration itself is the first informative hormone-like messenger in this system. CaR belongs to the C subfamily of seven transmembrane-spanning G protein-coupled receptors. Several inherited disorders in extracellular calcium homeostasis are due to both activating or inactivating mutations in CaR gene, strengthening the essential role of CaR in the control of calcium metabolism.
Assuntos
Cálcio/metabolismo , Erros Inatos do Metabolismo , Receptores de Superfície Celular/fisiologia , Cálcio/farmacocinética , Homeostase , Humanos , Hipercalcemia/fisiopatologia , Hiperparatireoidismo , Hipocalcemia/fisiopatologia , Glândulas Paratireoides/fisiologia , Mutação Puntual , Receptores de Detecção de Cálcio , Receptores de Superfície Celular/genéticaRESUMO
EBCT flow study offer a promising new approach to measure the renal blood flow. In vitro and in vivo studies were performed to resolve methological problems such as checking the linear relation between contras concentration and Hounsfield units or determination of the Treshold used for the mapping. First measurements of renal volumes and flow performed in patients showed expected values.
Assuntos
Circulação Renal , Tomografia Computadorizada por Raios X , Idoso , Animais , Cinerradiografia , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Hipertensão Renovascular/fisiopatologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodosRESUMO
The availability of accurate and inexpensive methods for measuring serum calcium levels has resulted in a rapid increase in the number of diagnoses of primary hyperparathyroidism, notably in its asymptomatic hypercalcemic forms. In addition, the development of a radioimmunoassay of the parathyroid hormone and, more recently, measurements of nephrogenous cyclic AMP during fasting and after calcium loading have led to the recognition of clinical variants of the disease, such as intermittent or borderline hypercalcemia and pure hypercalciuria with normal calcemia. The degree of hypercalcemia in stable primary hyperparathyroidism depends on renal tubular reabsorption of calcium rather than on bone resorption. The poor correlation observed between calcium tubular reabsorption rate and magnitude of parathyroid hormone hypersecretion suggests that as yet undetermined factors interfere with the effects of parathyroid hormone on renal tubules and probably account for the fluctuations in calcemia reported during serial determinations in patients. The sigmoid relationship between parathyroid hormone release and extracellular calcium concentrations has been analyzed from recent in vitro studies with dispersed parathyroid cells. In primary hyperplasia of the parathyroid glands hypersecretion of parathyroid hormone seems to depend principally upon the increase in tissue mass with normal sensitivity to calcium at cellular levels, whereas in adenoma the primary abnormality responsible for hypersecretion of parathyroid hormone would be an alteration in cell sensitivity to calcium, as indicated by an elevated "set point". Finally, while complicated primary hyperthyroidism requires surgery, our limited knowledge of the natural history of asymptomatic forms makes it impossible to decide which of these patients will ultimately need to be operated upon.
Assuntos
Hiperparatireoidismo/fisiopatologia , Cálcio/sangue , Humanos , Hipercalcemia/etiologia , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/terapia , Hormônio Paratireóideo/metabolismo , Estudos RetrospectivosRESUMO
Primary hyperparathyroidism was initially regarded as a rare and severe disease. In recent years, introduction of routine screening of serum calcium has contributed to a dramatic increased rate of detection of primary hyperparathyroidism in the population, and asymptomatic forms of this disease are now the rule. Surgery remains the only curative treatment. However a medical follow-up may be justified in asymptomatic patients whose serum calcium levels are only midly elevated and whose renal and bone status are close to normal. The medical follow-up is considered to be safe only with conscientious long-term monitoring. Surgery becomes mandatory if the follow-up shows worsening hypercalcemia, bone deterioration, renal impairment, calcium stone, or increased hypercalciuria.