Altered plasma glutathione levels in bipolar disorder indicates higher oxidative stress; a possible risk factor for illness onset despite normal brain-derived neurotrophic factor (BDNF) levels.

BACKGROUND: Oxidative stress and neurotrophic factors have been implicated in the pathophysiology of bipolar disorder. Our objective was to determine whether plasma glutathione or brain-derived neurotrophic factor (BDNF) levels were abnormal in bipolar disorder and therefore useful as possible biomarkers. METHOD: Blood samples were collected from subsyndromal, medicated bipolar I patients (n = 50), recruited from OXTEXT, University of Oxford, and from 50 matched healthy controls. Total and oxidized glutathione levels were measured using an enzymatic recycling method and used to calculate reduced, percentage oxidized, ratio of reduced:oxidized and redox state. BDNF was measured using an enzyme-linked immunoassay. Self-monitored mood scores for the bipolar group were available (Quick Inventory of Depressive Symptomatology and the Altman Self-Rating Mania Scale) over an 8-week period. RESULTS: Compared with controls, bipolar patients had significantly lower levels of total glutathione and it was more oxidized. BDNF levels were not different. Age of illness onset but not current mood state correlated with total glutathione levels and its oxidation status, so that lower levels of total and reduced glutathione were associated with later onset of disease, not length of illness. CONCLUSIONS: Plasma glutathione levels and redox state detect oxidative stress even in subsyndromal patients with normal BDNF. It may relate to the onset and development of bipolar disorder. Plasma glutathione appears to be a suitable biomarker for detecting underlying oxidative stress and for evaluating the efficacy of antioxidant intervention studies.

Surveyor v: television pictures.

Surveyor V landed in a small crater, 8.5 meters wide and 12.5 meters long, which was probably formed by drainage of surficial fragmental debris into a subsurface fissure. The lunar surface debris layer is exposed in the walls of this crater. At depths below about 10 centimeters, the debris appears to be composed mainly of shock-compressed aggregates, ranging from a few millimeters up to 3 centimeters in diameter, set in a matrix of less-coherent finer particles. Rocky chips and fragments larger than a millimeter are dispersed as a subordinate constituent of the debris.

Predictors of mortality among women with AIDS in Illinois, USA.

Population-based surveillance data can help guide research priorities and plan programmes to prevent death among women with AIDS. We describe the predictors of mortality among women diagnosed with AIDS in Illinois, USA. Using the HIV/AIDS Reporting System), we identified 1944 adult women who were diagnosed with AIDS during January 1999-December 2004. The proportion of women who died within one year of diagnosis of AIDS declined from 97% in 1999 to 12% in 2005. Multivariate analysis indicated that age >or=45 years, intravenous drug use, diagnosis of clinical AIDS and hospitalization at the time of AIDS diagnosis were significant predictors of death among women with AIDS. The number of women who died soon after diagnosis with AIDS declined substantially. Nevertheless, prevention programmes designed to improve survival among women with AIDS should emphasize early diagnosis and referral for care in an effort to prevent first diagnosis with clinical AIDS during hospitalization.

Combined spinal/caudal catheter anesthesia: extending the boundaries of regional anesthesia for complex pediatric urological surgery.

BACKGROUND: Spinal anesthesia (SA) is an established anesthetic technique for short outpatient pediatric urological cases. To avoid general anesthesia (GA) and expand regional anesthetics to longer and more complex pediatric surgeries, the authors began a program using a combined spinal/caudal catheter (SCC) technique. STUDY DESIGN: The authors retrospectively reviewed the charts of all patients scheduled for surgery under SCC between December 2016 and April 2018 and recorded age, gender, diagnosis, procedure, conversion to GA/airway intervention, operative time, neuraxial and intravenous medications administered, complications, and outcomes. The SCC technique typically involved an initial intrathecal injection of 0.5% isobaric bupivacaine followed by placement of a caudal epidural catheter. At the discretion of the anesthesiologist, patients received 0.5 mg per kilogram of oral midazolam approximately 30 min prior to entering the operating room. One hour after the intrathecal injection, 3% chloroprocaine was administered via the caudal catheter to prolong the duration of surgical block. Intra-operative management included either continuous infusion or bolus dosing of dexmedetomidine, as needed, for patient comfort and to optimize surgical conditions. Prior to removal of caudal catheter in the post-anesthesia care unit, a supplemental bolus dose of local anesthesia was given through the catheter to provide prolonged post-operative analgesia. RESULTS: Overall, 23 children underwent attempted SCC. SA was unsuccessful in three patients, and surgery was performed under GA. The remaining 20 children all had successful SCC placement. There were 11 girls and nine boys, with a mean age of 16.5 months (3.3-43.8). Surgeries performed under SCC included seven ureteral reimplantations, two ureterocele excisions/reimplantations, two megaureter repairs, four first-stage hypospadias repairs, one distal hypospadias repair, one second-stage hypospadias repair, two feminizing genitoplasties, and one open pyeloplasty. Average length of surgery was 109 min (range 63-172 min). Pre-operative midazolam was given in 13/20 (65%). All SCC patients were spontaneously breathing room air during the operation, and there were no airway interventions. Only one SCC patient received opioids intra-operatively. There were no intra-operative or perioperative complications. DISCUSSION: This pilot study shows that the technique of SCC allows one to do more complex urologic surgery under regional anesthesia than what would be possible under pure SA alone. The main limitations of the study include the relatively small number of patients and the small median length of the operative procedures. As a proof of concept, however, this does show that complex genital surgery bladder level procedures such as ureteral reimplantation can be performed under regional anesthesia. CONCLUSION: SCC allows for more complex surgeries to be performed exclusively under regional anesthesia, thus obviating the need for airway intervention, minimizing or eliminating the use of opioids, and thus avoiding known and potential risks associated with GA. The latter is of particular importance given current concerns regarding hypothetical neurocognitive effects of GA on children aged below 3 years.

Benefits of spinal anesthesia for urologic surgery in the youngest of patients.

INTRODUCTION: Increasing concerns regarding potential negative effects of early use of inhalational and intravenous anesthetics on neurocognitive development have led to a growing interest in alternative forms of anesthesia in infants. The study institution's outcomes with spinal anesthesia (SA) for urologic surgery in infants aged less than 90 days are reported and their outcomes with a matched cohort of patients who underwent general anesthesia (GA) are compared. METHODS: This is a retrospective single-center analysis. Patients aged less than 90 days who underwent SA for four urologic surgeries (inguinal hernia repair, scrotal exploration, posterior urethral valve ablation, and ureterocele puncture) were identified from the study institution's SA database. An age- and procedure-matched control cohort was identified from a list of patients who underwent the aforementioned four procedures under GA since 2013. Outcomes of interest included success rate of SA, complications from spinal placement, narcotic use, need for supplemental medications and oxygen, and length of hospital stay. RESULTS: Forty patients were identified; 20 in the SA and 20 in the GA group. Mean patient age was 54 (standard deviation, 35) days. There were no significant differences between the groups in age, gender, weight, history of prematurity, or presence of comorbidities. Eighty percent of SA patients had successful SA; reasons for conversion to GA included failure of spinal needle placement (75%) and agitation during operative procedure (25%). Ninety-six percent of patients who received GA (primarily or converted) had an endotracheal tube (ETT) placed. No patient in the SA group had a complication from spinal needle placement. Patients in the SA group were less likely to receive narcotics during the operative procedure (P = 0.001) and also had a lower mean morphine equivalent dose/kilogram (P = 0.002). Patients in the SA group were also less likely to receive any supplemental medications during the operative procedure (P = 0.001), particularly intravenous corticosteroids (P < 0.001). There were no significant differences in the length of hospital stay. CONCLUSIONS: The use of SA has clear advantages for this medically vulnerable population. For the majority of patients, it obviates the need for ETT placement and airway management and avoids the potential negative effects of GA on neurocognitive development. It also decreases the use of narcotics and other supplemental medications. In scenarios in which the benefit of surgery must be weighed against the risk of GA, such as neonatal torsion, SA may allow a paradigm shift in the timing of surgery.

Heterogeneity of human factor V deficiency. Evidence for the existence of antigen-positive variants.

Functional human Factor V has been purified using a rapid immunoaffinity method. Following barium citrate adsorption of plasma, Factor V was precipitated with polyethylene glycol at a concentration between 5 and 14%. The resulting preparation was applied to a column containing an immobilized immunoadsorbent consisting of an IgG fraction containing a naturally occurring human monoclonal (IgG(4)lambda) antibody with inhibitory activity against human Factor V. The solid phase immunoglobulin quantitatively bound Factor V from human plasma. The bound Factor V was effectively eluted with a Tris buffer pH 7.2 containing 1.2 M NaCl and 1 M alpha-methyl-D-mannoside. The isolated native Factor V with high specific activity (92 U/mg) showed a single band (M(r), 350,000) on both reduced and nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Factor V was purified 5,100-fold over plasma with an overall yield of 77%. The purified Factor V when subjected to thrombin activation exhibited an 18-fold increase in coagulant activity. The isolated Factor V neutralized the inhibitory activities of the monoclonal antibody that was used to purify it, as well as the rabbit antibodies produced by immunizing the animals with the purified Factor V. Immunoelectrophoresis of purified Factor V against the polyclonal rabbit antiserum resulted in a single precipitin arc of identical mobility to the Factor V in normal human plasma. Analysis by double immunodiffusion showed a line of identity between plasma and purified Factor V and crossed immunoelectrophoresis showed a single species in normal plasma.A competitive enzyme-linked immunosorbent assay using the rabbit antibody against Factor V was applied to quantify Factor V antigen level in human plasma. Reconstitution of congenitally deficient or immunodepleted plasma with normal plasma or purified Factor V gave parallel dose-response curves. In 14 normal plasma the coagulant activity was 0.98+/-0.02 U/ml (mean+/-SEM) and antigen concentration was 11.1+/-0.4 mug/ml. A pool of 14 patients with congenital Factor V deficiency were studied. 10 patients had Factor V antigen ranging from 1.0 to 2.4 mug/ml with corresponding coagulant activities (0-0.17 U/ml) indicating a low concentration of normal Factor V, presumably due to decreased synthesis or increased degradation. When these patient plasmas and the normal plasmas were analyzed together an excellent correlation (r = 0.97, P < 0.01) was obtained. However, four patients with coagulant activity (0-0.08 U/ml) had Factor V antigen concentrations ranging from 4.4 to 6.1 mug/ml, indicating the presence of a reduced concentration of abnormal Factor V protein. The presence of patients with antigen similar in concentration to coagulant activity and antigen in excess of Factor V activity indicates the heterogeneity of congenital Factor V deficiency.

Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats.

Plasma concentrations of LH, FSH, prolactin and progesterone were measured during the oestrous cycle in obese (fa/fa) and non obese (Fa/?) Zucker rats. In obese rats the mid-afternoon surge of LH during prooestrus was reduced compared with that in non-obese rats (P less than 0.05), and the maximum concentrations of FSH and prolactin declined more slowly during oestrus. Progesterone concentrations were higher during most of the oestrous cycle in obese rats. Oestradiol and progestin receptors were measured in the hypothalamus of female Zucker rats. Lower concentrations of oestradiol receptors were found in the preoptic area of obese rats (P less than 0.05). Concentrations of oestradiol receptors in the medial basal hypothalamus were also lower in obese rats, though the difference was not statistically significant. Concentrations of progestin receptors were similar in both phenotypes in the preoptic area and media basal hypothalamus. It seems likely that the abnormalities in reproductive hormones and oestradiol receptors contribute to the infertility of obese female Zucker rats. The underlying mechanism has still to be determined.

Reduced tissue androgen receptors in the congenitally obese male Zucker rat.

Androgen receptor (AR) concentrations were measured in the prostates and livers of the infertile congenitally obese male Zucker rat and their fertile non-obese litter-mates. In obese rats AR concentrations were significantly lower in both the liver (p less than 0.001) and the prostates (p less than 0.01) of the obese rats compared with the non-obese rats, despite similar plasma testosterone concentrations in both phenotypes. These findings suggest that a potential cause for the infertility observed in the obese Zucker rat is a reduced sensitivity of target tissues to circulating androgens.

Plasma oestradiol-17 beta and testosterone concentrations as possible causes of the infertility of congenitally obese Zucker rats.

The plasma oestradiol-17 beta concentrations of obese and non-obese female Zucker rats have been measured in three phases of the oestrous cycle. The oestradiol concentrations of both phenotypes were similar, and changed normally with the oestrous cycle. The weights of the uteri also changed normally with the cycle. Plasma androgen concentrations in male Zucker rats have also been measured: the mean concentration was slightly but significantly lower in obese rats, and androgen-sensitive tissues were slightly reduced in weight. The oestradiol-17 beta concentrations in males of both phenotypes were similar. It seems unlikely that deficient plasma concentrations of gonadal hormones cause the infertility of obese rats of either sex.

The effects of ovarian hormones on regulation of energy balance in Zucker rats.

Congenitally obese Zucker rats showed greater food intake, less running in activity wheels and greater body weight and fat content than the normal phenotype. Their food intake, running and body weight did not change significantly with the phase of the oestrous cycle. Ovariectomy had no effect on these variables or on body composition. Oestradiol replacement had little effect. Zucker rats of normal weight, however, showed a normal pattern of responses to the oestrous cycle, ovariectomy and oestradiol administration. The central regulation of energy balance and body weight appear to be insensitive to oestrogens in the obese Zucker rat.

The presence of beta-adrenoceptors in rat endometrium is dependent on circulating oestrogen.

It has been proposed that the change in sensitivity of the uterus to catecholamines during the oestrous cycle may result from changes in beta-adrenoceptor density in the myometrium. In the present work we applied the technique of light-microscopic autoradiography using the radioligand [125I]iodocyanopindolol to study the density and distribution of beta-adrenoceptors in the rat uterus during the normal oestrous cycle, following ovariectomy, and after ovariectomy with oestradiol replacement. We found that beta-adrenoceptor density in the endometrium, but not the myometrium, varied during the oestrous cycle, being highest during pro-oestrous. The endometrium of the ovariectomized rats was devoid of any beta-adrenoceptors, whilst that of the oestradiol-treated rats was very intensely labelled. Following ovariectomy there was an increase in beta-adrenoceptor density in the myometrium, but this was not observed in the animals given oestradiol replacement. It appears that both the presence and density of beta-adrenoceptors in rat endometrium is dependent on circulating oestrogens.

Multiple mechanisms of heterologous beta-adrenoceptor regulation in rat uterus.

The inhibitory effects of catecholamines on rat myometrium mediated by beta-adrenoceptors are modulated by ovarian steroids. Previously reported findings of radioligand binding studies on myometrial membranes have demonstrated changes in the numbers of beta-adrenergic binding sites following ovarian steroid treatment. However, these changes were not accompanied by parallel functional changes. In the present study, we have investigated possible mechanisms of heterologous beta-adrenoceptor regulation by ovarian steroids. Binding studies were performed on myometrial membrane and cytosolic preparations from rats which had been ovariectomized and subsequently received no hormonal treatment or had been treated with oestradiol, progesterone or combined oestradiol and progesterone. The beta-adrenergic antagonist [125I]iodocyanopindolol and the unlabelled competing agonist, isoprenaline, were used in the present studies. Hormonal treatment had no effect on the concentration of beta-adrenergic binding sites in the myometrium (i.e. the number of membrane-bound and cytosolic binding sites per mg protein). However, significant changes were found in the total number of binding sites; these were associated with the hormone-induced tissue hypertrophy. In myometrium from ovariectomized-alone rats, approximately 50% of beta-adrenergic binding sites were present in the cytosolic fraction. Oestradiol treatment, either on its own or in combination with progesterone, resulted in the translocation of binding sites to the cell membrane. However, in the absence of progesterone only 33% of the membrane-bound binding sites bound the beta-adrenergic agonist, isoprenaline, with a high affinity, suggesting that the majority of these membrane-bound binding sites represented non-functional beta-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential expression of renal adenosine A(1) receptors induced by acute renal failure.

The distribution of renal adenosine A(1) receptors was investigated in rats with glycerol- or mercuric chloride (HgCl(2))-induced acute renal failure. Receptors were localised by autoradiography using [(3)H]8-cyclopentyl-1,3-dipropylxanthine ([(3)H]DPCPX), a selective A(1) adenosine receptor antagonist. In saline-injected control animals, significant labelling with [(3)H]DPCPX was detected in glomeruli, the inner stripe of outer medulla, and the inner medulla. Sixteen hours following induction of glycerol-induced acute renal failure (ARF), a 34% increase in labelling in glomeruli was noted compared to saline-injected controls, and by 48 hr, glomerular labelling had increased by 200%. In addition, 48 hr following glycerol injection, significant labelling was now detected in the cortical labyrinth and medullary rays whilst, in the inner medulla, labelling had decreased by 34%. By contrast to glycerol-induced ARF, the only significant change noted 48 hr following induction of HgCl(2)-induced ARF was a 39% decrease in labelling in the inner medulla. It is concluded that glycerol-induced ARF results in differential expression of renal adenosine A(1) receptors with increased expression in the cortex and reduced expression in the inner medulla. Increased density of A(1) receptors in glomeruli may account, at least in part, for the increased renal vasoconstrictor response to adenosine and depressed glomerular filtration rate noted previously in this type of acute renal failure.

The effect of instituting an elective labor epidural program on the operative delivery rate.

OBJECTIVE: To evaluate labor outcome as well as maternal and neonatal morbidity before and after the initiation of elective labor epidural capability. METHODS: On October 1, 1993, a sudden change in military requirements mandated provision of elective labor epidural capability at our institution. Before this time, epidural provision had been primarily in response to urgent obstetrician requests. Pre-labor and labor characteristics and outcomes were reviewed for the year before this policy change (group 1, n = 373) and for the year after it (group 2, n = 421) in a population of nulliparous patients delivering singleton, vertex fetuses at 36-42 weeks' gestational age. In addition, the group of patients receiving labor epidurals before their ready availability (group 1E, n = 49) was compared with the group receiving them after ready availability (group 2E, n = 247). RESULTS: Maternal labor characteristics showed a slight (10 minutes on average) prolongation of the second stage of labor in group 2. The incidence of diagnosed chorioamnionitis was higher in group 2. Patients receiving epidurals in each time frame were analyzed to identify epidural-related findings, as opposed to findings associated with intrinsically more problematic labors. Epidural-related factors included the slightly prolonged second stage of labor, increased use of oxytocin, and a higher incidence of diagnosed chorioamnionitis. CONCLUSION: Our study demonstrated no increase in the rate of operative deliveries in a population that suddenly received access to on-request labor epidurals. We believe this option should be offered to parturients without making them feel that they must choose between comfort and safety.