Utility of ultrasound assessment in management of pregnancies with preterm prelabor rupture of membranes.

OBJECTIVES: To evaluate the utility of ultrasound markers in the management of pregnancies complicated by preterm prelabor rupture of membranes (PPROM) between 23 + 0 and 33 + 6 weeks' gestation, and to assess the ability of ultrasound markers to predict adverse neonatal outcomes. METHODS: This was a retrospective cohort study of all patients with PPROM between 23 + 0 and 33 + 6 weeks' gestation and latency period (PPROM to delivery) > 48 h, who delivered before 34 weeks' gestation at a tertiary referral center between 2005 and 2017. All patients underwent a non-stress test daily and an ultrasound scan twice a week for assessment of amniotic fluid volume, biophysical profile (BPP) and umbilical artery (UA) pulsatility index (PI). In patients with suspected fetal growth restriction, fetal middle cerebral artery (MCA)-PI was also assessed and the cerebroplacental ratio (CPR) calculated. The last ultrasound examination performed prior to delivery was analyzed. We compared the characteristics and outcomes between women who were delivered owing to clinical suspicion of chorioamnionitis and those who were not delivered for this indication. The primary objective was to evaluate the utility of ultrasound in the management of patients with PPROM. The secondary objective was to assess the diagnostic performance of ultrasound markers (BPP score < 6, oligohydramnios, UA-PI > 95th percentile, MCA-PI < 5th percentile, CPR < 5th percentile) for the prediction of composite adverse neonatal outcome, which was defined as the presence of one or more of: perinatal death, respiratory distress syndrome, periventricular leukomalacia, intraventricular hemorrhage Grade 3 or 4, necrotizing enterocolitis, hypoxic ischemic encephalopathy, neonatal sepsis or neonatal seizures. RESULTS: A total of 504 women were included in the study, comprising 120 with suspected chorioamnionitis and 384 without. Women with suspected chorioamnionitis, compared with those without, were less likely to be nulliparous (34.2% vs 45.3%; P = 0.03) and more likely to have fever (50.8% vs 2.6%; P < 0.001) and be delivered by Cesarean section (69.2% vs 42.4%; P < 0.001), mainly owing to a history of previous Cesarean section (18.3% vs 9.1%; P = 0.005) and to having non-reassuring fetal heart rate tracings (32.5% vs 14.6%; P < 0.001). No significant differences were found between the two groups with regard to the median amniotic fluid volume, overall BPP score, BPP score < 6, MCA-PI or CPR. Median UA-PI was slightly higher in the suspected-chorioamnionitis group, yet the incidence of UA-PI > 95th percentile was similar between the two groups. There was a higher incidence of composite adverse neonatal outcome in the group with suspected chorioamnionitis than in the group without (78.3% vs 64.3%, respectively; P = 0.004). However, on logistic regression analysis, none of the ultrasound markers evaluated was found to be associated with chorioamnionitis or composite adverse neonatal outcome, and they all had a poor diagnostic performance for the prediction of chorioamnionitis and composite adverse neonatal outcome. CONCLUSIONS: Commonly used ultrasound markers in pregnancies complicated by PPROM were similar between women delivered for suspected chorioamnionitis and those delivered for other indications, and performed poorly in predicting composite adverse neonatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Amniotic fluid volume at presentation with early preterm prelabor rupture of membranes and association with severe neonatal respiratory morbidity.

OBJECTIVE: Amniotic fluid volume (AFV) plays an important role in early fetal lung development, and oligohydramnios in early pregnancy is associated with pulmonary hypoplasia. The aim of this study was to evaluate the association between AFV at the time of presentation with early preterm prelabor rupture of membranes (PPROM) and severe neonatal respiratory morbidity and other adverse pregnancy outcomes. METHODS: This was a retrospective study of all women with a singleton pregnancy, admitted to a single tertiary referral center between 2004 and 2014, for expectant management of PPROM at 20 + 0 to 28 + 6 weeks' gestation. The primary exposure was AFV at presentation, classified according to sonographic maximum vertical pocket (MVP) as: normal AFV (> 2 cm), oligohydramnios (≤ 2 cm and > 1 cm) or severe oligohydramnios (≤ 1 cm). The primary outcome was a composite variable of severe respiratory morbidity, defined as either of the following: (1) need for respiratory support in the form of mechanical ventilation using an endotracheal tube for ≥ 72 h and need for surfactant; or (2) bronchopulmonary dysplasia, defined as requirement for oxygen at postmenstrual age of 36 weeks or at the time of transfer to a Level-II facility. Adjusted odds ratios (aOR) and 95% CI for the primary and secondary outcomes were calculated for each AFV-at-presentation group (using normal AFV as the reference), adjusting for gestational age (GA) at PPROM, latency period, birth weight, mode of delivery and chorioamnionitis. RESULTS: In total, 580 women were included, of whom 304 (52.4%) had normal AFV, 161 (27.8%) had oligohydramnios and 115 (19.8%) had severe oligohydramnios at presentation. The rates of severe respiratory morbidity were 16.1%, 26.7% and 45.2%, respectively. Compared with normal AFV at presentation, oligohydramnios (aOR, 3.27; 95% CI, 1.84-5.84) and severe oligohydramnios (aOR, 4.11; 95% CI, 2.26-7.56) at presentation were associated independently with severe respiratory morbidity. Other variables that were associated independently with the primary outcome were GA at PPROM (aOR, 0.54; 95% CI, 0.43-0.69), latency period (aOR, 0.94; 95% CI, 0.91-0.98) and Cesarean delivery (aOR, 2.01; 95% CI, 1.21-3.32). CONCLUSIONS: In women with early PPROM, AFV at presentation, as assessed by the MVP on ultrasound examination, is associated independently with severe neonatal respiratory morbidity. This information may be taken into consideration when counseling women with early PPROM regarding neonatal outcome and management options. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Remission in schizophrenia: the relationship to baseline symptoms and changes in symptom domains during a one-year study.

The concepts of partial recovery and remission have become increasingly important for the evaluation of the effectiveness of schizophrenia therapeutics. The relationship of baseline symptoms and changes in symptoms to remission of psychosis was evaluated. Fifty-six outpatients with residual schizophrenia completed a double-blind trial of olanzapine versus haloperidol and were then enrolled into a one-year open-label trial of olanzapine. Out of these 56 subjects, 13 (23%) met remission criteria at the beginning of the open-label treatment and were excluded. During the one-year study, 7/43 (16%) subjects met remission criteria. These subjects had significantly lower baseline ratings for tardive dyskinesia (TD) than subjects who did not achieve remission (1.8 +/- 1.5 vs. 4.2 +/- 4.6, P = 0.03). As expected, remitted subjects had significantly greater improvements in Brief Psychiatric Rating Scale total scores, positive subscale scores and scale for the Assessment of Negative Symptoms total scores. Remitted subjects also experienced a significantly greater improvement in depressive symptoms (P = 0.001), activation (P = 0.005), and Clinical Global Impressions scores (P < 0.001), as well as greater improvements in extrapyramidal symptoms (P = 0.007) and TD (P < 0.001). These results suggest that the relationship of depressive symptoms and improved side effects to the construct of remission in schizophrenia may deserve special attention. Future studies should aim to relate remission criteria to functional outcomes, cognition, and other important symptom domains.

Cardiac hemodynamics before, during and after elective cesarean section under spinal anesthesia in low-risk women.

OBJECTIVE: The aim of this study was to describe maternal central hemodynamic parameters before and during delivery as well at the early puerperium in healthy women undergoing elective cesarean section (CS) at term. STUDY DESIGN: The noninvasive Cardiac System (NICaS, NI Medical, Petah-Tikva, Israel) is a regional impedance device that measures cardiac output (CO) and its derivatives with a good correlation with the gold standard Swan-Ganz catheter. We performed a prospective longitudinal study of healthy women with a singleton pregnancy at term. Maternal hemodynamic parameters were assessed by the NICaS at six time points: a few minutes before undergoing an elective CS, immediately after receiving spinal anesthesia, immediately after delivery of the fetus and placenta, after abdominal fascia closure, and within 24 to 36 and 48 to 72 h postpartum. RESULT: Sixty-one consenting women were recruited during the study period (January 2015 to June 2015). Baseline (pre-CS) mean arterial pressure (MAP) was 87.7±7.9 mm Hg, baseline CO was 7.5±1.7 l per min and baseline total peripheral resistance (TPR) was 994±301 dyne × s per cm5. After spinal anesthesia CO significantly increased by 13%, no significant changes were observed in MAP or TPR. Immediately after delivery, a nadir for all parameters was reached: MAP and TPR were significantly reduced by 8% and 26%, respectively (comparing to pre-CS), and CO further increased by 9% (24% comparing to pre-CS). After fascia closure, partial recoveries of all parameters were observed. Twenty-four to thirty-six hours postpartum MAP returned to pre-CS values, while CO and TPR reached -9% and +11% comparing to baseline, respectively. None of the parameters differed significantly between 24 to 36 and 48 to 72 h postpartum. CONCLUSION: Significant hemodynamic changes (reduction of TPR and increase of CO) take place at the time of delivery of fetus and placenta. Knowledge of normal hemodynamic values using a reliable noninvasive technique during various stages of pregnancy and the postpartum period is feasible, and might assist clinicians in assessing the level of patient deviation from expected cardiac performance, especially in high-risk women.

The effect of placenta previa on fetal growth and pregnancy outcome, in correlation with placental pathology.

OBJECTIVE: To compare the clinical characteristics and placental histopathology between pregnancies complicated by placenta previa and controls. STUDY DESIGN: Between 2009 and 2015, cesarean deliveries (CDs) of 119 pregnancies with placenta previa were identified from which maternal outcomes, neonatal outcomes and placental pathology were reviewed. Results were compared with CDs matched for maternal age and pregnancy complications (control group, n=119). Placental lesions were classified into maternal and fetal vascular supply lesions and inflammatory response. Composite neonatal outcome was defined as one or more of early neonatal complications. Small-for-gestational age (SGA) was defined as birth weight ⩽10th percentile. RESULTS: Placentas from the previa group had higher rates of weights <10th percentile (P<0.001) and of maternal and fetal vascular supply lesions (P<0.001, for both). Higher rate of SGA (P=0.003) and worse composite neonatal outcome (P<0.001) were also observed in the previa group as compared with controls. After controlling for potential confounding bias using multivariable logistic regression models, placenta previa remained statistically significantly associated with placental maternal (adjusted odds ratio (aOR) 2.48, 95% confidence interval (CI) 1.2-4.9, P=0.009) and fetal (aOR 7.05, 95% CI 2.4-20.2, P<0.001) vascular supply lesions, SGA (aOR 10, 95% CI 2.3-44.2, P=0.002) and adverse neonatal outcome (aOR 6.87, 95% CI 2.9-11.8, P<0.001). CONCLUSIONS: More placental vascular supply lesions, higher rate of SGA and worse neonatal outcome characterized pregnancies with placenta previa in the current study. These findings may suggest that abnormal placentation is accompanied by suboptimal implantation that interferes with fetal growth.

The in vitro erythropoietin sensitivity of late erythroid progenitors subjected to opposing physiologic demands.

The in vitro sensitivity of marrow CFU(E) to erythropoietin was assessed in normal, regenerating, and plethoric marrow and correlated to the cell-cycle distribution of the cells. Although all marrow samples demonstrated a approximately 75% S-phase distribution, regenerating, but not plethoric marrow, exhibited a 5- to 10-fold greater requirement for erythropoietin in vitro. It is concluded that altered responsiveness to erythropoietin may occur independently of alterations in the CFU(E) cell cycle. Secondly, alterations in erythropoietin sensitivity occur under conditions of marrow regeneration but not polycythemic suppression.

Cell-cycle properties and proliferation kinetics of late erythroid progenitors in murine bone marrow.

The cell-cycle properties of marrow CFUE were assessed in normal regenerating cell preparations. In addition, the erythropoietin sensitivity of CFUE was correlated to the cell-cycle distribution of these cells. The results suggest a coupling of erythropoietin sensitivity to the S-phase of the CFUE cell cycle in so far as CFUE in G2/M/G1 were 2 to 10 times less sensitive to the hormone. It is concluded that the CFUE cell cycle per se is not a focus for erythropoietic regulation.

The association between umbilical cord abnormalities and the development of non-reassuring fetal heart rate leading to emergent cesarean deliveries.

OBJECTIVE: To study the contribution of umbilical cord (UC) abnormalities in emergent cesarean deliveries (ECDs) for non-reassuring fetal heart rate (NRFHR) and to explore their association with placental histopathology and neonatal outcome. STUDY DESIGN: Data from 530 ECDs for NRFHR were reviewed for the occurrence of UC abnormalities. Those included the presence of UC entanglements, the number and location of loops, true knots and short cord (<50 cm). Multiple UC entanglements were defined as ⩾ 2 UC loops. Results were compared with 530 vaginal deliveries (VD group) matched for maternal age, parity and gestational age. Additionally, we compared neonatal outcome and placental histopathology in cases of ECDs with a single vs multiple UC entanglements. Neonatal outcome consisted of low Apgar score (⩽ 7 at 5 min), cord blood pH ⩽ 7.1 and composite neonatal outcome that was defined as one or more of respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic-ischemic encephalopathy, phototherapy or death. Placental lesions were classified as: lesions related to maternal vascular supply, lesions related to fetal vascular supply (consistent with fetal thrombo-occlusive disease), and maternal and fetal inflammatory responses. RESULTS: UC entanglements, true knots and short cords were all more common in the ECD group compared with the VD group, P<0.001, P=0.002, P=0.004, respectively. The rate of one loop entanglement did not differ between the groups. The rate of multiple UC entanglements was higher in the ECD group compared with the VD group, 20.6% vs 6.4%, respectively, P<0.001. ECDs with multiple compared with single UC entanglement had higher rate of adverse neonatal outcome, P=0.031, and more placental fetal vascular lesions 19.3% vs 8.1%, P=0.027, respectively. CONCLUSION: Multiple UC entanglements, true knots and short cords were more common in ECDs for NRFHR, suggesting their role in the development of fetal placental vascular lesions and adverse neonatal outcome.

Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis.

Increased cyclic AMP-phosphodiesterase activity in peripheral blood leukocytes is associated with the immune and inflammatory hyperreactivity that characterizes atopic dermatitis. Atopic phosphodiesterase has high sensitivity to a variety of enzyme inhibitors, suggesting an increased therapeutic advantage. The objective of this study was to use in vitro assays to identify a potent phosphodiesterase inhibitor and then to investigate its effectiveness in treating atopic dermatitis. Leukocyte enzyme activity was measured by radioenzyme assay, whereas prostaglandin E2 and interleukins 10 (IL-10) and 4 (IL-4) were measured in 24-h culture supernatants of mononuclear leukocytes by immunoassays. The effect of a topical phosphodiesterase inhibitor on atopic dermatitis lesional skin was assessed by double-blind, paired comparisons of active drug and placebo ointments applied to symmetrically involved sites over a 28-d period. Using in vitro, assays, we demonstrated the ability of selective high-potency phosphodiesterase inhibitors to reduce prostaglandin E2, IL-10, and IL-4 production in atopic mononuclear leukocyte cultures. We selected the Type 4 phosphodiesterase inhibitor, CP80,633, based on its inhibitory potency, for clinical testing by topical, bilateral paired comparisons in 20 patients with atopic dermatitis and demonstrated significant reductions of all inflammatory parameters. Phosphodiesterase inhibitors modulate several pathways contributing to the exaggerated immune and inflammatory responses, which characterize atopic dermatitis. This in vivo demonstration of anti-inflammatory efficacy may provide a useful alternative to the over-reliance on corticosteroid therapy in atopic disease.

Sex hormone binding globulin: the carrier protein for d-norgestrel.

The binding of different synthetic steroids, used in hormonal contraception, to Sex Hormone Binding Globulin (SHBG) was studied by measuring their ability to displace tritiated testosterone from SHBG in a competitive protein binding system. Only 19-nortestosterone derivates had any significant ability to displace testosterone from SHBG, d-norgestrel (d-Ng) being the strongest displacer. Increasing the SHBG levels in women with previous constant plasma d-Ng levels increased these levels two- to sixfold. It is concluded that SHBG is the main carrier protein for d-Ng. The strong testosterone displacing activity of d-Ng might also explain androgenic side effects observed with d-Ng containig oral contraceptives.

Effects of sustained-release bupropion and supportive group therapy on cigarette consumption in patients with schizophrenia.

OBJECTIVE: The study examined the efficacy, tolerability, and safety of supportive group psychotherapy and adjunctive sustained-release bupropion for nicotine addiction in patients with schizophrenia. METHOD: Eight patients participated in a 14-week open-label trial. End expired breath carbon monoxide level, symptom levels, neuropsychological performance, and suppression of the P50 event-related potential were measured before and after the 14-week trial. RESULTS: Patients showed a decrease in carbon monoxide levels that was not associated with any worsening in symptom, neuropsychological, or P50 suppression measures. CONCLUSIONS: Use of sustained-release bupropion in combination with supportive group therapy may help patients with schizophrenia decrease their cigarette consumption.

Mazindol treatment of negative symptoms.

Hypodopaminergic and hyponoradrenergic pathophysiology may be a basis for primary and/or secondary negative symptoms in schizophrenia. The hypothesis that enhanced neurotransmission in these systems would be therapeutic for negative symptoms was tested by comparing mazindol and placebo in a double-blind, cross-over design trial. Outcome following mazindol supplementation was comparable to placebo supplementation (F(1,30) = 0.9; p = .57). Results for deficit and non-deficit schizophrenia subjects were similar, and were not affected by whether concurrent the antipsychotic drug treatment was clozapine, fluphenazine, or haloperidol. The efficacy hypothesis was not supported for either primary or secondary negative symptoms.

The effects of doxazosin on platelet aggregation, platelet adhesion and blood coagulation in cynomolgus monkeys.

The effect of doxazosin, a selective alpha-1 adrenergic inhibitor, on hemostasis was investigated in 9 cynomolgus monkeys. During 12 weeks of doxazosin treatment (1 mg/kg per day), serum lipids, lipoprotein cholesterols, blood coagulation, platelet aggregation and template bleeding times were measured and compared with predrug values. In addition, platelet adhesion to cultured human umbilical vein endothelial cells (HUVEC) in the presence or absence of doxazosin was evaluated. Platelet aggregation was also determined in monkeys following chronic oral exposure to aspirin (162 mg/day). Doxazosin administration was associated with significant reductions in serum total cholesterol (TC) (-16%) and low density lipoprotein cholesterol (LDL-C) (-23%), while high density lipoprotein cholesterol (HDL-C) levels increased 66%. Doxazosin did not alter any parameters of blood coagulation measured; however, bleeding times were increased significantly (33%) in doxazosin-treated animals. Although collagen-stimulated platelet aggregation was not influenced by either chronic doxazosin or aspirin treatment, the maximal extent of ADP-stimulated platelet aggregation was significantly reduced (-26% and -18%, respectively) compared with the control monkeys. Platelets from untreated control animals displayed reductions in the extent of ADP-stimulated aggregation of 13% and 23%, respectively, when incubated in vitro with 200 and 300 micrograms/ml of doxazosin. Additionally, the decrease in aggregation response of platelets obtained from doxazosin-treated monkeys was accompanied by a rapid reversal of platelet aggregation. Adhesion to HUVEC by platelets isolated from doxazosin-treated animals was significantly decreased; however, adhesion was not altered when platelets from untreated control animals were incubated with HUVEC in the presence of doxazosin. Thus, the ex vivo and in vitro studies reported in this communication suggest that doxazosin administration to nonhuman primates is associated with beneficial alterations in plasma lipids, platelet aggregation, bleeding times and platelet adhesion to endothelial cells, parameters which are thought to influence risk of cardiovascular disease in both animals and humans.

Human C1q: rapid isolation and quantitative determination by immunodiffusion.

A simple and rapid 2-step procedure for isolating C1q from human plasma at high yields (about 50%) is described. The purification involves diaminopropane precipitation followed by chromatography on IgG-Sepharose. The final product (obtained at a concentration of about 1.5 mg/ml) was electrophoretically and immunochemically pure and stable at -70 degrees C for long periods. The Mancini technique for the quantitative determination of C1q was reinvestigated and the use of gels containing high salt concentrations (1.0 M NaCl) was found to be absolutely necessary. A value of 0.076 mg/ml C1q in pooled human plasma was obtained.

Effects of prazosin on hemodynamics, hemostasis, and serum lipid and lipoprotein levels in normal and hypercholesterolemic monkeys.

The effect of prazosin on hemodynamics, hemostasis, and serum lipid and lipoprotein levels was investigated in normal and hypercholesterolemic rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys. Administration of prazosin (2 mg/kg bodyweight, orally, twice a day) for three weeks caused significant reductions in plasma cholesterol, including low- plus very low-density lipoprotein cholesterol, apolipoprotein B, and triglyceride levels. Drug therapy was associated with increased high-density lipoprotein cholesterol levels, although in one group of monkeys this rise also was associated with a reduction in apolipoprotein A1. Prazosin treatment significantly decreased mean arterial pressure in normal and hypercholesterolemic monkeys. As was expected, acute administration of phenylephrine caused mean arterial pressure to rise, with animals receiving normal- or high-cholesterol-containing diets showing similar responses. After prazosin treatment, however, a greater inhibition in the phenylephrine pressor response was observed in hypercholesterolemic monkeys compared with normal animals. Platelet aggregation in response to adenosine 5'-diphosphate, prothrombin time, and activated partial thromboplastin time were not altered by prazosin. Thus, in our nonhuman primate models of hypercholesterolemia, administration of prazosin resulted in reduction in lipid and apoprotein levels with no change in hemostasis.

Autoantibodies in patients with primary pulmonary hypertension: association with anti-Ku.

PURPOSE: Patients with primary pulmonary hypertension (PPH) frequently have Raynaud's phenomenon, serum antinuclear antibodies (ANAs), and/or pulmonary vascular lesions similar to those seen in certain connective tissue diseases, especially scleroderma. A number of relatively disease-specific autoantibodies have been described in connective tissue diseases but have not been studied in patients with PPH. Therefore, sera from PPH patients were studied for a variety of autoantibodies, seeking a possible link between this pulmonary disorder and connective tissue diseases. PATIENTS AND METHODS: Sera from 31 patients with PPH and 24 with secondary pulmonary hypertension (SPH) were studied for the following autoantibodies: anti-centromere (indirect immunofluorescence of Hep-2 cells), anti-CENP-B by immunoblotting and enzyme immunoassay (EIA) using cloned CENP-B fusion protein, anti-topoisomerase I (Scl-70), anti-Ku using immunoblotting of affinity purified antigens, anti-cardiolipin using EIA, and anti-Ro (SS-A), La (SS-B), Sm, nRNP, Jo-1, PM-Scl, and Mi-2 by counter-current immunoelectrophoresis. RESULTS: Anti-Ku antibodies were found in 23% of patients with PPH, 4% with SPH, and none of 24 normal controls (PPH versus SPH, p = 0.06: PPH versus controls, p = 0.01). Antibodies to CENP-B were found in one patient each with PPH and SPH, anti-topoisomerase I in one with SPH, and anti-Ro (SS-A) and La (SS-B) in one with PPH. Overall, 12 patients (39%) with PPH had Raynaud's phenomenon or positive ANA results, with 9 (29%) having more specific autoantibodies associated with connective tissue diseases. CONCLUSIONS: These results further suggest a link between at least a subgroup of patients with PPH and autoimmune connective tissue diseases, with anti-Ku antibodies being a possible new serologic marker.

Idiotypic analysis of human anticentromere autoantibodies.

The idiotypes (Ids) of anticentromere antibodies (ACA) have been studied using a fusion protein obtained from cloned cDNA of the major centromere antigen, CENP-B, for isolation of the autoantibodies. IgG-ACA were affinity purified from 4 patient sera and anti-Ids prepared in rabbits. Analysis revealed the existence of two distinct types of immunodominant Ids. One Id is near the antibody combining site and one is framework associated. A longterm longitudinal study of Id expression in a patient who seroconverted from ACA (-) to ACA (+) when she developed Raynaud's phenomenon showed a close correlation between Id expression and ACA titers (r = 0.94). These results may be interpreted as evidence for an autoantigen driven process in the anticentromere immune response.

Transbronchial needle aspiration: guidance with CT fluoroscopy.

BACKGROUND: Bronchoscopy with transbronchial needle aspiration (TBNA) is valuable to diagnose lesions in the mediastinum and lung, but conventional fluoroscopic guidance may be suboptimal. We describe the use of CT fluoroscopy to provide real-time, transaxial TBNA localization, thus facilitating biopsy. METHODS: Patients were selected because of prior unsuccessful bronchoscopy or anticipated difficulty owing to small size or inaccessibility of the lesion. CT fluoroscopy consists of a spiral CT scanner adapted using a rapid-reconstruction algorithm and hardware that permits real-time in-room imaging. The bronchoscope was inserted on the CT scanner, which was used to guide TBNA instruments into the target lesion. RESULTS: Of 27 patients who underwent TBNA with CT fluoroscopic assistance, 15 had mediastinal nodes, and 12 had lung nodules or focal infiltrates. Mean lesion size was 1.7 cm in the mediastinum, 2. 2 cm in the lung. A correct diagnosis was established in 10 of 12 mediastinal lesions (83%) for which follow-up was available and in 8 lung lesions (67%). Diagnoses included small cell and non-small cell lung cancer and invasive aspergillosis. False-negative results were caused by sampling errors or inability to reach the lesion as documented by CT fluoroscopy. Postprocedure CT fluoroscopy revealed no complications. CONCLUSION: CT fluoroscopy provides effective, real-time guidance for TBNA and may be particularly valuable in patients with small or less accessible mediastinal or lung lesions.

Acute lithium treatment enhances neuropeptide Y gene expression in rat hippocampus.

It has been suggested that the therapeutic action of lithium in affective disorders may be due to its inhibition of signal transduction and second messenger synthesis, in particular of the phosphoinositide (PI) pathway. Yet, previous work in neuronal cell lines indicates that lithium has an enhancing effect on gene expression mediated by protein kinase C, which is activated by the PI pathway. In this report, we have analyzed the effect of lithium on two neuropeptide encoding genes that are regulated by second messenger systems; neuropeptide Y (NPY) and proenkephalin (Enk). We find that acute treatment with lithium, resulting in serum levels that are within the therapeutic range effective in patients with mood disorders, significantly enhances basal expression of the NPY gene in rat hippocampus. In contrast, no effect on Enk expression was detected. This selective effect in a limbic structure supports the hypothesis that gene expression may be an important target of lithium's therapeutic action.

Hippocampal neuropeptide Y mRNA is reduced in a strain of learned helpless resistant rats.

The learned helpless rat is considered to be one of the better animal models of depression. A genetically inbred strain with a high vulnerability to develop helplessness (LH), as well as a highly resistant strain (NLH) have both been developed. Since the brain peptide neuropeptide Y (NPY) is involved in the regulation of a number of behaviors known to be altered in clinical depression as well as in learned helplessness, we measured the relative level of NPY mRNA in the hippocampus and cortex of control Sprague Dawley (SD), LH and NLH rats. We find that NLH rats have approximately a 30-35% decrease in basal hippocampal NPY mRNA compared with SD and LH rats. By contrast, cortical NPY mRNA and hippocampal pre-proenkephalin and somatostatin mRNA levels were not significantly different in the 3 strains. The data suggest that the regulation of NPY gene expression may be involved in the reduced vulnerability of NLH rats to develop learned helplessness.