Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant.

The standard therapy against hepatitis C virus (HCV) recurrence postliver transplantation includes interferon (IFN)α and ribavirin. IFNL4 ss469415590 polymorphism has been reported as a novel predictor of the response to IFN therapy for chronic HCV infection. We examined the impact of IFNL4 polymorphism on the responsiveness to IFN therapy after liver transplantation. Tissue specimens were collected from 80 HCV-infected recipients and 78 liver donors, and their IFNL4 ss469415590 genotype, hepatic IFNL4 and interferon-stimulated genes' mRNA expression levels were examined. The association of the polymorphism and expression levels in terms of the IFN therapy response to HCV recurrence was analysed. Most individuals who had rs8099917 risk alleles also had ss469415590 risk alleles (R(2) = 0.9). Sustained virological response (SVR) rates were higher in both liver graft recipients and transplants with ss469415590 TT/TT alleles than in those with the risk ΔG allele (P = 0.003 and P = 0.005, respectively). In recipients with ss469415590 TT/TT, IFNL4 TT mRNA levels showed no significant differences between livers of patients who responded to therapy and those who did not (P = 0.4). In recipients with the risk ΔG allele, IFNL4 ΔG mRNA expression levels were significantly lower in SVR patients than in non-SVR patients (P = 0.02). Hepatic interferon stimulable genes and IFNL4 mRNA expression were correlated. Our findings suggest that analysing the ss469415590 genotype and IFNL4 ΔG expression provides a novel prediction strategy for the possible response to IFN therapy after liver transplantation.

The Evidence-practice Gap in Minimal Intervention Dentistry: An International Comparison Between Dentists in Japan and Brazil.

OBJECTIVES: This study was designed to: 1) evaluate and compare the evidence-practice gap (EPG) in minimal intervention dentistry (MID) in Japan and Brazil by measuring concordance between dentists' clinical practice and published evidence; and 2) identify dentists' factors associated with the EPG in both countries. METHODS: We performed a cross-sectional study using a web-delivered questionnaire among 136 Japanese and 110 Brazilian dentists. The questionnaire consisted of three questions concerning "restoration diagnosis and treatment," "deep caries diagnosis and treatment," and "caries risk assessment" regarding MID. A chi-square test was used to analyze differences in concordance among clinical practice and evidence from the literature between Japanese and Brazilian dentists. Logistic regression analyses were performed to analyze dentists' factors associated with overall concordance for all three questions. RESULTS: Overall concordance was significantly higher in Brazil (55%) than in Japan (38%) (p<0.01). Concerning how evidence was obtained, textbooks, nonacademic journals, and seminars and workshops were used as information sources more frequently by Japanese than Brazilian dentists (p<0.001), whereas scientific journal articles in English were used more frequently by Brazilian dentists (p<0.001). On logistic regression analysis, overall concordance was higher for Japanese dentists who frequently obtained evidence from scientific journal articles in English (p<0.05), whereas Brazilian dentists who frequently obtained evidence from the Internet were associated with lower overall concordance (p<0.05). CONCLUSIONS: Because overall concordance was significantly higher in Brazil than in Japan, Japan may have a greater EPG in MID practice. Specific characteristics of Japanese and Brazilian dentists showed significant associations with overall concordance.

Causes of the Evidence-practice Gap and Its Association with the Effects of Minimal Intervention Dentistry Education to Clinicians.

OBJECTIVES: To identify causes of the evidence-practice gap (EPG) in dentistry in Japan and analyze whether these causes are associated with: (a) improvement of EPG in minimal intervention dentistry (MID) following an educational intervention and (b) specific dentist characteristics. METHODS: We conducted a mixed-methods questionnaire survey among 197 Japanese dentists that integrated both quantitative and qualitative data. Causative factors for the EPG identified in the quantitative survey were clarified by qualitative analysis. We measured the EPG in a baseline survey using an EPG measurement tool based on MID. To examine how feedback using the latest scientific evidence affected change in the EPG, we measured the EPG again immediately after feedback was provided to participating dentists. RESULTS: Qualitative analysis classified all dentists into one of four "EPG cause" groups, namely "evidence-", "dentist-", "patient-", and "health insurance system-related" causes. Quantitative analysis confirmed that improvement in the EPG following the feedback intervention was indeed associated with group classification. The highest concordance was found for the "evidence-related" group while the lowest concordance was in the "dentist-related" group (p=0.004). Concordance improved after evidence feedback in all groups but was lowest in the "dentist-related" group. More dentists reported practice busyness in the "dentist-related" group. CONCLUSIONS: In this study, we identified four groups of causes of EPG among Japanese dentists. The degree of concordance between evidence and clinical practice was the lowest in the "dentist-related" group, and the results of this study are expected to provide useful information for the development of intervention methods for closing the EPG in the future.

Activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth: a case report and a review of the literature.

A 47-year-old woman was diagnosed with extragenital mullerian adenosarcoma with sarcomatous overgrowth. One month after her initial surgery, the patient developed pelvic recurrence, which was completely excised by surgery. However, one month later, the patient developed further recurrences in her pelvis and upper abdomen. A clinical complete response was achieved with three cycles of liposomal doxorubicin and is currently clinically free of disease. So far, including the present case, 23 cases of extragenital mulleian adenosarcoma have been reported in the English literature. Because of the rarity of the reported cases, there are no treatment guidelines based on a good level of evidence. In the current report, through a literature review, we provide information on the activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth.

Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain.

Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.There are only a few examples of nanocarriers that can transport bioactive substances across the blood-brain barrier. Here the authors show that by rapid glycaemic increase the accumulation of a glucosylated nanocarrier in the brain can be controlled.

Intrathecal chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated into hybrid liposomes for meningeal gliomatosis: an experimental study.

1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), one of the chloroethyl nitrosoureas, is effective against malignant glioma. To develop its use in intrathecal chemotherapy, we encapsulated BCNU in hybrid liposomes composed of dimyristoylphosphatidylcholine and micellar surfactants (Tween 20) and dissolved it in artificial cerebrospinal fluid (lipo-BCNU). We then studied the toxicity of hybrid liposomes and cellular proliferation inhibition of lipo-BCNU in vitro. We found that 3 mM hybrid liposomes did not affect the viability of human endothelial cells and that lipo-BCNU inhibited the proliferation of human glioma cell lines U-105MG, U-251MG, and U-373MG, and rat glioma cell lines C6 and 9L in a concentration-dependent fashion. Wistar rats that were administered lipo-BCNU intracisternally showed no weight loss, neurological symptoms, or histological changes of the brain and spinal cord. A Wistar rat model of meningeal gliomatosis was established by intracisternal inoculation of 0.1 ml cell suspension containing 1 x 10(6) or 5 x 10(6) viable C6 glioma cells. Two days after inoculation, lipo-BCNU (BCNU, 2.5 mg/kg) was administered intracisternally. When 1 x 10(6) glioma cells were inoculated (experiments 1 and 2), the median survival times were 24.5 and 26 days in the control groups and 32 and 45 days in the lipo-BCNU-treated groups. respectively. When 5 x 10(6) glioma cells were inoculated (experiments 3-6), the median survival times were 17-29.5 days in the control groups and 23-44 days in the treated groups, respectively. Significantly prolonged survival was obtained in three of six experimental groups. After the administration of 1 ml lipo-BCNU (BCNU, 4.67 mM) or 1 ml BCNU solubilized with 5% dextrose/water (BCNU, 4.67 mM) into the cisterna magna of dogs, the cisterna magna cerebrospinal fluid was sampled, and the BCNU concentrations were assayed by high-performance liquid chromatography. The half-life of the lipo-BCNU was longer than that of BCNU solubilized with 5% dextrose/water. These results suggest that the intrathecal administration of lipo-BCNU may be possible for the treatment of meningeal gliomatosis.

Mechanism of the immunosuppressive effect in vivo of novel immunosuppressive drug beta-SQAG9, which inhibits the response of the CD62L+ T-cell subset.

INTRODUCTION: We synthesized sulfo-glycolipid, beta-SQAG9 (designate square beta-SQAG9 liposome, because it efficiently forms a liposome structure) that possessed immunosuppressive effects such as inhibition of T-cell responses in human allogeneic MLR and skin allograft survival in rats, and bound to CD62L (L-selectin) in vitro. In this study, we further investigated the immunosuppressive mechanism in vivo by beta-SQAG9 liposome in a skin-allografted rat model. METHODS: ACI rats (RT1(a)) were grafted skin of LEW rats (RT1(1)) treated with PBS or beta-SQAG9 liposome IV once a day for 7 days. Subsequently, we investigated the population of T cells and CD62L(+) T-cell subset in the spleen, axillary lymph nodes (ALNs), and peripheral blood of skin-allografted rats by two-color flow cytometry. RESULTS: Five of 11 (45.5%) rats that were treated with 50 mg/kg beta-SQAG9 liposome showed graft survival and another showed moderate rejection in graft. The CD62L(+) T-cell subset population in ALNs of beta-SQAG9 liposome-treated rats decreased in a dose-dependent manner. No significant difference in the T-cell population was observed between the beta-SQAG9 and control groups. These data suggest that beta-SQAG9 could bind to the CD62L(+) T-cell subset in vivo as well as in vitro and affect T-cell migration, which might lead to T-cell tolerance in vivo.

The first grid for the oral and maxillofacial region and its application for speech analysis.

OBJECTIVES: Introduction of a new grid-based method for analyzing speech functions which takes into account the related information of patients' data and the oral air flow with pronouncing analyzed by computational fluid dynamics. METHODS: An on-line speech analyzer was developed for clinical use utilizing GridPort2.3.1 based on globus2.4.2, comprising several computational tools such as unified data storage, semantic data analysis, computational fluid dynamics analysis and three-dimensional visualization of calculated results from different hardware sources with various types of operation systems. RESULTS: The power transportation layer between dental clinics and computational and storage resources could be provided by using a WWW-based portal. The backend data management system could be constructed using a storage resource broker (SRB) and extensible mark up language (XML). CONCLUSIONS: The new method allows the construction of a data warehouse through this grid-based speech function analysis in order to extract the principal factors related to speech disorders.

Modulatory effect of 4 beta-phorbol 12-myristate 13-acetate (PMA) on carbachol-induced Ca2+ mobilization in rat parotid acinar cells.

Treatment of rat parotid acinar cells with 4 beta-phorbol 12-myristate 13-acetate (PMA) significantly inhibited an increase in cytosolic free Ca2+ concentration ([Ca2+]i) induced by carbachol (CCh), a muscarinic agonist. The CCh-induced increase in [Ca2+]i was also inhibited by another active phorbol ester, 4 beta-phorbol 12,13-dibutyrate, but not by 4 alpha-phorbol 12,13-didecanoate, which does not activate protein kinase C. The treatment with PMA had no effect on increases in [Ca2+]i evoked by ionomycin and thapsigargin, which do not stimulate phosphoinositide hydrolysis. In contrast, an increase in [Ca2+]i induced by NaF, a direct activator of GTP-binding proteins, was delayed in the presence of PMA. The formation of inositol phosphates in response to CCh was suppressed significantly by PMA treatment. In radioligand binding assays, PMA did not directly interfere with the specific binding of [3H]quinuclidinyl benzilate ([3H]QNB), a muscarinic antagonist, to plasma membranes. Furthermore, the [3H]QNB binding to plasma membranes prepared from the PMA-pretreated cells was not different from that to the control membranes. These results indicate that PMA attenuated the CCh-induced increase in [Ca2+]i through inhibition of phosphoinositide hydrolysis. Activation of protein kinase C may play a role in negative-feedback control of the muscarinic pathway in rat parotid acinar cells.

Growth hormone-releasing hormone (GHRH)-GH-somatic growth and luteinizing hormone (LH)RH-LH-ovarian axes in adult female transgenic mice expressing human GH gene.

We have examined alterations in the hypothalamo-pituitary GH-somatic growth axis and the hypothalamo-pituitary LH-ovarian axis in a line of transgenic ICR mice expressing human GH (hGH) under the influence of the whey acid protein promoter. Transgenic female mice weighed twice as much as control females and were infertile. The size of the anterior pituitary (AP) was 1/3 that of the controls. In transgenic mice, acinar cells in the mammary and mandibular glands displayed hGH-immunoreactivity, and plasma hGH was detected by radioimmunoassay. In the medial basal hypothalamus (MBH) of transgenic females, the immunoreactive-GHRH level was decreased (P<0.01). There was a corresponding reduction in the number of GHRH-immunoreactive neurons in the arcuate nucleus (ARC) and in the immunostaining of GHRH nerve terminals in the median eminence. The level of somatostatin (SRIH) in the MBH was increased (P<0.05), and SRIH-immunoreactive neurons in the periventricular nucleus (PeV) were increased in size and number in transgenic mice. The MBH level of LHRH in transgenic animals was greater (P<0.01) than in controls, although there was no apparent difference in the number of LHRH-immunoreactive neurons or in LHRH level in the preoptic area. There are fewer SRIH- and LHRH-immunoreactive neurons in the ARC in transgenic mice. Cells in the AP for GH, PRL, and LH were fewer in transgenic mice. The ovary suffered disturbance of follicular development and of corpora lutea formation. These results demonstrate that chronic overproduction of hGH may profoundly affect the organization of the GHRH/SRIH-GH-somatic growth axis and the LHRH-LH-ovarian axis due to reduction of GHRH-, SRIH- and LHRH-neurons in the ARC and increase of SRIH-neurons in the PeV.

Effects of Triton WR-1339 on lipoprotein lipolytic activity and lipid content of rat liver lysosomes.

The characteristics of lipoprotein lipolytic activity in lysosomes after the administration of Triton WR-1339 were studied, and the observed decrease in the density of the particles is discussed. The light mitochondrial fraction prepared from rat liver according to the method of De Duve et al. (Biochem. J. (1955) 60, 604) was used as a crude lysosomal fraction, in which acid phosphatase and lipoprotein lipase activities were concentrated. The lipoprotein lipolytic activity of lysosomes had a pH optimum of 4.0. The activity was strongly inhibited by Triton WR-1339 in vitro at low concentrations, while the acid lipase activity was almost unaffected, though relatively high concentration of the detergent significantly inhibited the latter activity. When Triton WR-1339 administered to rats (150 mg/100 g body weight), the activities of both the lipoprotein lipase and acid lipase of lysosomes from the treated rats decreased to one-third of those of control rats. Low-density and high-density lysosomes were partially purified from the light mitochondrial fraction from Triton WR-1339-treated and silver colloid-treated rats, respectively, by sucrose density gradient centrifugation. The low-density lysosomes (d = 1.00-1.13) from Triton WR-1339 administered rats had approximately 4 and 3 times higher contents of triglyceride and cholesterol, respectively, than the high-density lysosomes (d greater than 1.30) from silver colloid-treated rats. In view of these results and the fact that the density of Triton WR-1339 is quite high (at least d = 1.20), the decrease in density of hepatic lysosomes upon Triton WR-1339 administration cannot be due simply to incorporation of the detergent, and may rather be a result of incorporation and accumulation of some lipid(s) (possibly as lipoprotein) into lysosomes together with Triton WR-1339.

Occlusal disharmony affects plasma corticosterone and hypothalamic noradrenaline release in rats.

Few neuro-endocrinological studies have examined the relationship between occlusal disharmony and stress. To determine the effect of occlusal disharmony on the central nervous system, we measured plasma corticosterone and extracellular noradrenaline in the vicinity of the hypothalamic paraventricular nucleus in rats both with and without incisal caps. After the caps were set, plasma corticosterone and extracellular noradrenaline levels gradually increased, reaching a peak at 8.5 and 6.5 hours, respectively, after which they decreased. Furthermore, plasma corticosterone and extracellular noradrenaline levels increased in a circadian fashion around the onset of the dark phase in rats without caps, but not in rats with caps. These results suggest that occlusal disharmony causes chronic stress in the rat.

Root resorption related to hypofunctional periodontium in experimental tooth movement.

Orthodontic movement of non-occluding teeth may result in undesirable apical root resorption. These teeth present with a histologically altered periodontium and are considered to be hypofunctional. The purpose of this study was to compare the amount of root resorption associated with a normal and a hypofunctional periodontium in rats during experimental tooth movement caused by heavy continuous force. The mandibular first molar was induced into a non-occluding condition in the hypofunctional periodontium group. Mesial orthodontic force was applied by means of 50-gram-force closed-coil springs for 15 days in both groups. The active root-resorption lacunae from histological sections, identified by tartrate-resistant acid phosphatase, were measured in terms of length, depth, and area. The results showed that the amount of root resorption was significantly greater in teeth with a hypofunctional periodontium than in those with a normal periodontium (p < 0.05). These results suggest that orthodontic movement of non-occluding teeth should be performed with caution.

Early treatment of subarachnoid hemorrhage after preventing rerupture of an aneurysm.

Twelve patients with Hunt and Hess neurological Grades III to V underwent thrombosis of aneurysms using cellulose acetate polymer within 23 hours of aneurysm rupture. On computerized tomography (CT), nine of these patients had difuse or localized thick subarachnoid blood clots, two had diffuse thin clots and one had intraventricular clots. Immediately after thrombosis, all patients were administered tissue plasminogen activator (TPA) through spinal or ventricular catheters. The pressure of the lumbar cerebrospinal fluid was maintained at 100 to 150 mm H2O. The TPA was given as multiple injections of 2 mg on Day 0 and 1 to 2 mg on the following 1 to 2 days. In two patients the second injection of TPA was not given because of severe brain damage resulting from the initial subarachnoid hemorrhage. Ten patients showed complete clearance of the cisternal clot on CT within 72 hours after thrombosis. Seven partially thrombosed aneurysms and five multiple aneurysms were clipped during delayed surgery. Only one patient experienced mild vasospasm as shown on the follow-up angiogram. Eight patients improved clinically and had a good recovery, two had severe disability, and two died. Urgent thrombosis of a ruptured aneurysm followed by immediate postthrombotic administration of TPA may be a safe and reasonable means of preventing vasospasm and improving patient outcome.

In situ hybridization for matrix metalloproteinase-1 and cathepsin K in rat root-resorbing tissue induced by tooth movement.

The movement of teeth during orthodontic treatment occasionally induces undesirable root resorption. Although high collagenolytic activity has been detected in resorbing tissue of deciduous teeth, the cellular origin of collagenolytic enzymes in root-resorbing tissue caused by tooth movement has not been identified. Here, rats were subject to 7 days of experimental tooth movement to induce root resorption. In situ hybridization with digoxigenin-labelled RNA probes was performed on sections of the maxillary bone to detect the mRNAs that encode matrix metalloproteinase-1 (MMP-1) and cathepsin K in root-resorbing tissue. MMP-1 mRNA was detected in fibroblastic cells, cementoblasts and osteoblasts, but not in odontoclasts nor osteoclasts. Moreover, MMP-1 mRNA was highly expressed in some cementocytes located near odontoclasts and in many osteocytes. In contrast, cathepsin K mRNA was expressed only in odontoclasts and osteoclasts. These results suggest that MMP-1 and cathepsin K are important in root resorption during tooth movement in a mode similar to bone resorption.

[Specific inhibitory effect of hybrid liposomes on the growth of hybridoma cells in vitro].

Remarkably high inhibitory effects of the hybrid liposomes composed of L-alpha-dimyristoyl-phosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (C14(EO)n, n = 6-8 and C12(EO)n, n = 8-12)) on the growth of human lymphoma-human B-lymphocyte hybridoma (HF) cells in vitro were obtained. The hybrid liposomes composed of 90 mol% DMPC/10 mol% C14(EO)n (n = 6-8) or C12(EO)n (n = 8-12) were more fluid as compared with 90 mol% DMPC/10 mol% C14(EO)4 or C12(EO)n (n = 4, 23) hybrid liposomes on the basis of fluorescence polarization measurements. These results suggest that the inhibitory effects of the hybrid liposomes on the growth of HF cells should be related to the membrane fluidity. No toxicity to normal rats in vivo was observed in the experiment using 90 mol% DMPC/10 mol% C14(EO)7 or 90 mol% DMPC/10 mol% C12(EO)12 hybrid liposomes.

[Specific inhibitory effects of hybrid liposomes on the growth of various tumor cells].

The inhibitory effects of hybrid liposomes composed of lipids having a variety of head groups (zwitterionic L-alpha-dimyristoylphosphatidylcholine (DMPC), anionic L-alpha-dimyristoylphosphatidylglycerol (DMPG), and cationic 1,2-dimyristoyl-3-trimethylammonium propane (DMTAP)) and polyoxyethylene (10) dodecyl ether (C12(EO)10) on the growth of tumor cells (human lung carcinoma (RERF-LC-OK), human hepatoma (Hep-G2), human stomach tumor (GT3TKB)) in vitro were examined. The hybrid liposomes of DMPC/10 mol% C12(EO)10 and DMPG/10 mol% C12(EO)10 were fairly more effective for inhibiting the growth of all tumor cells employed in this study as compared with liposomes (DMPC and DMPG) or micelles (C12(EO)10). Especially, it is attractive that the highly specific inhibitory effect of the hybrid liposomes of DMPG/10 mol% C12(EO)10 without any antitumor drugs on the growth of RERF-LC-OK and GT3TKB was obtained for the first time.

Structural organization and fine distribution of lymphatic vessels in periodontal tissues of the rat and monkey: a histochemical study.

The structural organization and fine distribution of lymphatic vessels in the periodontal tissues (gingiva, periodontium and alveolar process) were examined by light and electron microscopy using an enzyme-histochemical method. Whole mount preparations of periodontal membranes peeled from the teeth and cryostat sections of normal or decalcified tissues treated with EDTA were double-stained using 5'-nucleotidase (5'-Nase)-alkaline phosphatase (ALPase) and examined by light microscopy. This staining procedure allowed the lymphatic vessels in the periodontal tissue to be differentiated from blood vessels. Well-developed 5'-Nase-positive lymphatics were observed in the gingiva and periodontium. The histochemical aspects of 5'-Nase activity in lymphatic vessels are discussed in detail, with special reference to the supply of Mg++ ions. A network of 5'-Nase-positive lymphatics was observed in whole mount preparations of the periodontal membrane for the first time. This network was also observed in the tissue sections. More 5'-Nase-positive lymphatics were seen in the root area of the periodontium than in the cervical area. 5'-Nase-positive lymphatics in residual tissue blocks remaining after cryostat sectioning and in whole mount preparations were highlighted with good contrast and resolution on backscattered electron images produced by scanning electron microscopy. Dense granular precipitations resulting from the 5'-Nase reaction were observed on the luminal surface of the lymphatic endothelial cells as well as on the basal side but were absent in the blood vessels.

[Midecamycin acetate-susceptibility of clinical isolates from dental and oral surgical infections].

To investigate the clinical and bacteriological usefulness of orally administered midecamycin acetate (MOM), the susceptibility of clinical isolates to MOM, Mb-12 (the main metabolite of MOM), josamycin (JM), ampicillin (ABPC) and cephalexin (CEX) was determined. The results are summarized as follows. Antibacterial activities of MOM against aerobic Gram-positive cocci, B. catarrhalis, and anaerobic bacteria were inferior to those of JM by 2-fold, but superior to those of CEX. Activities of MOM against S. aureus, Bacteroides spp., Fusobacterium spp., Veillonella spp. were superior to those of ABPC and CEX. Since serum and tissue concentrations of Mb-12 after 200 mg administration in humans have been reported to be 1-2 micrograms/ml, it can be presumed that the causative bacteria would be eradicated by a usual dosage of MOM used in the present study. From these considerations, it is speculated that MOM may be successfully used in the treatment of dental and oral surgical infections.

[Therapeutic effect of a mineralocorticoid in patients with hyponatremia of central origin].

Patients with hyponatremia of central origin were treated with a mineralocorticoid, and the therapeutic effect assessed. The subjects of this study were 14 patients (5 with subarachnoid hemorrhage, 2 with hypertensive intracerebral hemorrhage and 7 with head injury) who developed hyponatremia as a complication during their hospital stay for treatment of their intracranial lesions between March 1993 and April 1994. Hyponatremia of central origin was defined as serum Na+ levels below 135 mEq/l for at least two consecutive days with no other discernible etiology. The mineralocorticoid used was fludrocortisone acetate, and as a rule administration was started the day after the onset of hyponatremia. The mean interval until the onset of hyponatremia was 7.5 days, and the mean minimum serum sodium level was 125.7 mEq/l. The dose of fludrocortisone was 0.3 congruent to 0.6 mg/day, the mean period of administration 5.8 days, and route was via a stomach tube in 3 cases and by mouth in 11 cases. The therapeutic effect was good (improvement within 5 days) in 11 cases and fair (improvement in 5 to 8 days) in 3 cases. None of the patients manifested side effects. All of the patients had lower urinary sodium excretion than before administration, with the mean rate of decrease of 66.9%. Mineralocorticoids, which suppress natriuresis, are safe and effective in the treatment of hyponatremia of central origin. It appears that mineralocorticoid therapy may be aggressively tried in severe cases in which NaCl loading is ineffective.