Intrinsic Connectivity Networks in post-traumatic stress disorder during sub- and supraliminal processing of threat-related stimuli.

OBJECTIVE: To investigate the functional connectivity of large-scale intrinsic connectivity networks (ICNs) in post-traumatic stress disorder (PTSD) during subliminal and supraliminal presentation of threat-related stimuli. METHOD: Group independent component analysis was utilized to study functional connectivity within the ICNs most correlated with the Default-mode Network (DMN), Salience Network (SN), and Central Executive Network (CEN) in PTSD participants (n = 26) as compared to healthy controls (n = 20) during sub- and supraliminal processing of threat-related stimuli. RESULTS: Comparing patients with PTSD with healthy participants, prefrontal and anterior cingulate cortex involved in top-down regulation showed increased integration during subliminal threat processing within the CEN and SN and during supraliminal threat processing within the DMN. The right amygdala showed increased connectivity with the DMN during subliminal processing in PTSD as compared to controls. Brain regions associated with self-awareness and consciousness exhibited decreased connectivity during subliminal threat processing in PTSD as compared to controls: the claustrum within the SN and the precuneus within the DMN. CONCLUSION: Key nodes of the ICNs showed altered functional connectivity in PTSD as compared to controls, and differential results characterized sub- and supraliminal processing of threat-related stimuli. These findings enhance our understanding of ICNs underlying PTSD at different levels of conscious threat perception.

Neural correlates of self-reflection in post-traumatic stress disorder.

OBJECTIVE: Disturbances in self-referential processing (SRP) are increasingly recognized in post-traumatic stress disorder (PTSD). In healthy adults, SRP tasks engage the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) brain regions that have shown altered function in PTSD. We hypothesized that individuals with PTSD would differ from controls in functional activation of the MPFC and PCC during SRP. METHOD: We compared neural activation in healthy controls (n = 15) and participants with PTSD (n = 20) during a SRP task, using fMRI at 4.0T. RESULTS: Controls made faster responses to the self-relevance of personal characteristics than to the accuracy of general facts, whereas response times did not differ between these conditions in PTSD. Controls also demonstrated greater MPFC (dorsal and ventral) and PCC response when considering the self-relevance of personal characteristics in comparison with the accuracy of general facts. Individuals with PTSD demonstrated less MPFC response than did healthy controls for the contrast of self-relevance of personal characteristics relative to general facts. CONCLUSIONS: These results implicate MPFC in SRP disturbances associated with PTSD. These findings are relevant to current proposals for including symptoms of negative self-referential cognition and identity-existential disturbance as diagnostically relevant to PTSD.

Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation.

OBJECTIVE: The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD. METHOD: Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength. RESULTS: PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects. CONCLUSIONS: The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.

Insulin stimulates transepithelial sodium transport by activation of a protein phosphatase that increases Na-K ATPase activity in endometrial epithelial cells.

The objective of this study was to investigate the effects of insulin and insulin-like growth factor I on transepithelial Na(+) transport across porcine glandular endometrial epithelial cells grown in primary culture. Insulin and insulin-like growth factor I acutely stimulated Na(+) transport two- to threefold by increasing Na(+)-K(+) ATPase transport activity and basolateral membrane K(+) conductance without increasing the apical membrane amiloride-sensitive Na(+) conductance. Long-term exposure to insulin for 4 d resulted in enhanced Na(+) absorption with a further increase in Na(+)-K(+) ATPase transport activity and an increase in apical membrane amiloride-sensitive Na(+) conductance. The effect of insulin on the Na(+)-K(+) ATPase was the result of an increase in V(max) for extracellular K(+) and intracellular Na(+), and an increase in affinity of the pump for Na(+). Immunohistochemical localization along with Western blot analysis of cultured porcine endometrial epithelial cells revealed the presence of alpha-1 and alpha-2 isoforms, but not the alpha-3 isoform of Na(+)-K(+) ATPase, which did not change in the presence of insulin. Insulin-stimulated Na(+) transport was inhibited by hydroxy-2-naphthalenylmethylphosphonic acid tris-acetoxymethyl ester [HNMPA-(AM)(3)], a specific inhibitor of insulin receptor tyrosine kinase activity, suggesting that the regulation of Na(+) transport by insulin involves receptor autophosphorylation. Pretreatment with wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase as well as okadaic acid and calyculin A, inhibitors of protein phosphatase activity, also blocked the insulin-stimulated increase in short circuit and pump currents, suggesting that activation of phosphatidylinositol 3-kinase and subsequent stimulation of a protein phosphatase mediates the action of insulin on Na(+)-K(+) ATPase activation.

A short echo proton magnetic resonance spectroscopy study of the left mesial-temporal lobe in first-onset schizophrenic patients.

BACKGROUND: Past 1H magnetic resonance spectroscopy (MRS) studies of the temporal lobe in schizophrenic patients have shown decreased levels of N-acetylaspartate (NAA) suggesting reduced neuronal density in this region. However, the measured volumes have been large and included contributions from mostly white matter. METHODS: Short echo 1H MRS was used to measure levels of NAA and other metabolites (i.e., glutamate and glutamine) from a 6 cm3 volume in the left mesial-temporal lobe of 11 first-episode schizophrenic patients and 11 healthy control subjects of comparable age, gender, handedness, education, and parental education levels. Spectra were quantified without operator interaction using automated software developed in our laboratory. Metabolite levels were normalized to the internal water concentration of each volume studied. Images were also obtained to determine temporal lobe gray and white matter volumes. RESULTS: No significant differences were found between levels of NAA or other metabolites, or gray and white matter volumes, in first-episode schizophrenic patients and comparison subjects. CONCLUSIONS: Since the volume studied was small compared to previous studies and contained mostly gray matter, this result suggests consequential NAA decreases may be restricted to regions of white matter.

A short echo 1H spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive-compulsive disorder and comparison subjects.

OBJECTIVE: It is likely that the corpus striatum is involved in obsessive-compulsive disorder (OCD). Prior studies have inconsistently found alterations in caudate volumes in patients with OCD. This study was undertaken in the hope that N-acetylaspartate and volumetric measures together would elucidate the presence and nature of corpus striatum volumetric abnormalities in OCD. METHOD: Thirteen patients meeting the DSM-IV criteria for OCD, who had been medication free for a minimum of 6 weeks, and 13 psychiatrically normal matched comparison subjects participated in the study. Short echo 1H magnetic resonance spectroscopy (1H-MRS) was used to measure levels of N-acetylaspartate and several other cerebral metabolites from a 4.5-cm3 volume in the left corpus striatum of all 26 subjects. Metabolite levels were estimated by fitting the time domain spectroscopy data with a noninteractive computer program. Volumes of the left and right head of the caudate nucleus in each subject were determined by semiautomatic segmentation of the volumetric images. RESULTS: N-Acetylaspartate levels from the left corpus striatum were significantly lower in the patients with OCD than in the comparison subjects. There were no differences in either left or right caudate volume between the two groups. CONCLUSIONS: Despite the lack of differences in caudate volumes between the OCD patients and the comparison subjects, the lower level of N-acetylaspartate in the left corpus striatum of the patients suggests reduced neuronal density in this region. Inconsistent volumetric findings among prior studies may reflect a poorer sensitivity of magnetic resonance imaging morphometry for detecting neuronal loss compared with 1H-MRS measurement of N-acetylaspartate.

Development and evaluation of an ELISA to measure antibody responses to both the nucleocapsid and spike proteins of canine coronavirus.

A rapid and reproducible enzyme linked immunosorbent assay (ELISA) was developed for detection of canine coronavirus (CCV) specific antibodies directed to both the nucleocapsid (NC) and the spike (S) proteins. The coating antigen, a methanol-treated, S-protein enriched preparation, was produced by subjecting infected cells to Triton X-114 detergent followed by phase separation. The sensitivity of this assay was determined by following the course of infection in dogs experimentally infected with CCV. The specificity of the antibody response was determined by Western blot analysis and supported the increased magnitude of the ELISA response and the presence of serum neutralizing (SN) antibody. Due to the sensitivity and specificity of the IgG response detected by this assay it can be used to determine both virus exposure and vaccine efficacy.

Canine parvovirus vaccine elicits protection from the inflammatory and clinical consequences of the disease.

Inflammatory changes following infection are central to the clinical manifestation of disease. However, information regarding such changes in animal disease is limited. In canine parvovirus infected puppies we measured the levels of acute phase proteins and changes in leukocyte phenotypes and cell trafficking by flow cytometry. These parameters correlated with conventional assessment of clinical disease in a vaccine efficacy study. Seropositive (CPV-2) 6-week-old puppies given three doses of a CPV-2 containing vaccine developed significant antibody titers and remained healthy after experimental infection with CPV-2b. Unvaccinated controls developed clinical signs and shed virus. Importantly, acute phase proteins became elevated, and lymphopenia, neutropenia and modulation of neutrophil-CD4 were detected in controls but not in vaccinates.

Magnetic resonance imaging volumetric and phosphorus 31 magnetic resonance spectroscopy measurements in schizophrenia.

The purpose of this study was to examine the relationship between phosphorus magnetic resonance spectroscopy (31P MRS) parameters and left prefrontal volumes in both patients with schizophrenia and healthy subjects. 31P MRS parameters and magnetic resonance imaging (MRI) volumetric data were collected in the left prefrontal region in 10 patients with schizophrenia and 10 healthy subjects of comparable age, handedness, sex, educational level, and parental educational level. No correlations were found between any MRS parameter and grey matter volumes in the combined subjects. Phosphomonoester (PME) and grey matter volumes, however, were both correlated negatively with age. PMEs were found to be decreased, and calculated intracellular magnesium ([Mg2+]intra) was found to be increased in the patients with schizophrenia compared with healthy subjects after adjusting for left prefrontal grey and white matter, total brain volume, and age. These findings suggest that cortical grey and white manner volumes are not directly related to PME and [Mg2+]intra abnormalities in schizophrenia patients.

The effect of sodium meclofenamate in premenstrual asthma: a controlled clinical trial.

We speculated that changes in endogenous prostaglandin synthesis might be responsible for the syndrome of premenstrual asthma (worsening of asthma in relation to menstruation). To test our hypothesis, we compared the effects of sodium meclofenamate, a prostaglandin synthesis inhibitor, and placebo on premenstrual asthma in a 4-month, double-blind, crossover study of 17 women with asthma. Day-by-day evaluation revealed that peak expiratory flow reached a nadir during menstruation on both meclofenamate and placebo therapy and varied inversely with menstrual symptoms and asthma symptoms. Meclofenamate therapy resulted in significant improvement in peak expiratory flow during the early premenstrual period but had no treatment effect on the exacerbation of asthma during the late premenstrual period and early menstruation. The overall improvement in pulmonary function caused by meclofenamate therapy was correlated with the treatment effect on menstrual symptoms. Meclofenamate caused a small, nonsignificant decrease in use of theophylline and oral beta-agonist agents, whereas corticosteroid use increased slightly but not significantly. This study demonstrates the temporal relationship between menstrual symptoms and asthma. The study also demonstrates that inhibition of prostaglandin synthesis does not prevent exacerbation of asthma in relation to menstruation.

Serum 13-14-diOH-15-keto-prostaglandin F2 alpha and airway response to meclofenamate and metaproterenol in relation to the menstrual cycle.

In order to evaluate whether adverse reactions to a nonsteroidal antiinflammatory agent (NSAIA) were related to variations in prostaglandin levels during the menstrual cycle, we measured 13-14-diOH-15-keto-prostaglandin F2 alpha in serum and the effect on airways of a single dose of 100 mg oral meclofenamate and 1.5 mg inhaled metaproterenol during the early (follicular phase) and late (luteal phase) menstrual cycle. Among 24 women with premenstrual asthma (PMA), four women with regular asthma (REA), and four healthy women, the 13-14-diOH-15-keto-PGF2 alpha averaged 140.9 +/- 68.4 pg/0.1 ml during the follicular phase but only 14.4 +/- 2.2 pg/0.1 ml during the luteal phase (p less than 0.0001). Acute asthma reactions to the meclofenamate occurred during the follicular phase in six women with PMA but were never observed during the luteal phase (p = 0.016). These reactions occurred preferentially in patients on corticosteroids (p = 0.004). Conversely, one patient with PMA had 18% improvement in FEV1 with meclofenamate during the luteal phase. A placebo-controlled, double-blind evaluation of the healthy women and the women with REA revealed a trend toward improvement in FEV1 during the luteal phase (0.15 less than p less than 0.10) but no change during the follicular phase. The effect of metaproterenol did not vary with the menstrual cycle, and there was no interaction between the effects of meclofenamate and those of metaproterenol. It appears that meclofenamate causes adverse effects on pulmonary function in asthmatic women primarily during the follicular phase of the menstrual cycle. This effect is associated with corticosteroid treatment and may be related to monthly variation in serum 13-14-diOH-15-keto-PGF2 alpha.

Incontinence in the female patient.

Incontinence, the distressing accompaniment of old age and the frequent annoyance of young women, should be adequately diagnosed and treated. Although th physiology of bladder function is not completely understood, and urologists and gynecologists continue to change their opinions about just which bladder deformities or what changes in pressure profiles are important, enough is known to help the patient. The woman who is afraid to leave home and has sexual inhibitions and personal difficulties because of her "leaking bladder" can be helped to a fuller life. The family physician can distinguish between stress incontinence and detrusor instability. Adequate treatment of detrusor instability and proper referral of patients with stress incontinence are within the purview of the family physician. This paper describes diagnostic procedures easily performed in the office, preventive measures from childhood through the postmenopausal periods, and the options and effectiveness of treatment.