Patients with premenstrual syndrome have a different sensitivity to a neuroactive steroid during the menstrual cycle compared to control subjects

We have evaluated the functional sensitivity to a neuroactive steroid in 12 women with and 12 women without premenstrual syndrome (PMS) at two stages of the menstrual cycle, by comparing the effects of three increasing doses of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye velocity (SEV) and self-rated sedation. Control subjects in the follicular and luteal phase showed a significant reduction in SEV after pregnanolone injections compared to vehicle. In PMS patients, pregnanolone injections induced a significant dose-related decrease in SEV compared to vehicle only in the follicular phase, not in the luteal phase. After pregnanolone injections, sedation scores increased significantly from vehicle among control subjects in the luteal phase but not among PMS patients in either cycle phase. High-severity PMS patients responded with less decrease in SEV and less increase in sedation scores following pregnanolone injections compared to low-severity patients. Control subjects increased their SEV response to pregnanolone in the luteal phase compared to the follicular phase, whereas PMS patients did not. These findings are compatible with a decreased GABAA-receptor sensitivity in brain areas controlling saccadic eye movements among PMS patients in the late luteal phase.     

A neural model of multimodal adaptive saccadic eye movement control by superior colliculus

How does the saccadic movement system select a target when visual, auditory, and planned movement commands differ? How do retinal, head-centered, and motor error coordinates interact during the selection process? Recent data on superior colliculus (SC) reveal a spreading wave of activation across buildup cells the peak activity of which covaries with the current gaze error. In contrast, the locus of peak activity remains constant at burst cells, whereas their activity level decays with residual gaze error. A neural model answers these questions and simulates burst and buildup responses in visual, overlap, memory, and gap tasks. The model also simulates data on multimodal enhancement and suppression of activity in the deeper SC layers and suggests a functional role for NMDA receptors in this region. In particular, the model suggests how auditory and planned saccadic target positions become aligned and compete with visually reactive target positions to select a movement command. For this to occur, a transformation between auditory and planned head-centered representations and a retinotopic target representation is learned. Burst cells in the model generate teaching signals to the spreading wave layer. Spreading waves are produced by corollary discharges that render planned and visually reactive targets dimensionally consistent and enable them to compete for attention to generate a movement command in motor error coordinates. The attentional selection process also helps to stabilize the map-learning process. The model functionally interprets cells in the superior colliculus, frontal eye field, parietal cortex, mesencephalic reticular formation, paramedian pontine reticular formation, and substantia nigra pars reticulata.     

Coping with anger and the premenstrual syndrome

OBJECTIVE: Investigations in recent years confirm the importance of "anger coping-behaviour" for women suffering from different diseases such as migraine, high blood pressure and coronary heart disease. The hypothesis for this investigation was that "anger-in" coping (anger-suppression) is a possible causal factor in the premenstrual syndrome. METHODS: Data analysis was undertaken on 38 patients (average age 32 years) fulfilling the inclusion criteria. The Menstrual Distress Questionnaire (MDQ) was used for measuring the intensity of premenstrual symptoms. As a result of a cluster analysis of MDQ scores, the 38 patients were divided into 3 subgroups (group 1: mild symptoms, n = 16; group 2: moderate symptoms, n = 10; groups 3: severe symptoms, n = 12). The 3 groups were compared by using different questionnaires regarding the variables anger, attitudes to menarche and menstrual bleeding, anxiety and depression. Additionally, sociodemographic data were obtained and a daily record taken for 2 days premenstrually and 5 day postmenstrually of subjective replies to a standardized protocol. RESULTS: Contrary to our expectations the results showed no significant differences for "anger coping" between the 3 subgroups. Increased daily stress (professional and familial double load) statistically significantly influenced the intensity of premenstrual symptoms. Additional significant factors were a general tendency towards somatization disorder, a negative attitude toward menarche and menstrual bleeding, as well as a tendency to depressive mood in patients with severe premenstrual symptoms. CONCLUSION: Emotional disorders (anger, anxiety) showed less influence on the premenstrual syndrome in the investigated women than daily stress and medical anamnesis.     

CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone

A disturbed hypothalamus-pituitary-adrenal gland axis and alterations at the immune system level have been observed in patients with chronic fatigue syndrome (CFS). Glucocorticoids are known to modulate T cell responses; therefore, purified CD4 T cells from CFS patients were studied to determine whether they have an altered sensitivity to dexamethasone (DEX). CD4 T cells from CFS patients produced less interferon-gamma than did cells from controls; by contrast, interleukin-4 production and cell proliferation were comparable. With CD4 T cells from CFS patients (compared with cells from controls), a 10- to 20-fold lower DEX concentration was needed to achieve 50% inhibition of interleukin-4 production and proliferation, indicating an increased sensitivity to DEX in CFS patients. Surprisingly, interferon-gamma production in patients and controls was equally sensitive to DEX. A differential sensitivity of cytokines or CD4 T cell subsets to glucocorticoids might explain an altered immunologic function in CFS patients.     

Efficacy and safety of 0.3% carbomer gel compared to placebo in patients with moderate-to-severe dry eye syndrome

PURPOSE: Carbomer gel is a water-soluble polymeric resin that has been reported to maintain the tear film in contact with the eye for an extended period. The efficacy and safety of this new artificial tear were assessed. METHODS: A multicenter, single-masked, randomized, placebo-controlled study was carried out on 123 patients with moderate-to-severe dry eyes. The placebo was a mannitol solution with benzalkonium chloride 0.008% as preservative. Patients were observed over an 8-week period, and subjective and objective changes analyzed, compared to a baseline of no therapy, after 1 to 7 days washout period from previous medication. RESULTS: All primary subjective symptoms decreased significantly in the carbomer gel-treated group compared to the placebo group (i.e., dryness, discomfort, and foreign body sensation). The carbomer gel also significantly improved the rose bengal staining score relative to placebo. When data for the primary subjective efficacy variables were stratified for disease severity, there was a statistically significant improvement from baseline by day 10 for severely affected patients and from day 42 for patients with moderate disease. Secondary subjective symptoms that improved significantly in the tear gel group compared to placebo were photophobia, erythema, tear breakup time, blurry-filmy, dry-sandy sensation, and physician impression. However, no significant improvements in the secondary subjective symptoms of tearing, itching, scaling, conjuctival discharge, palpebral conjunctival redness, bulbar conjuctival redness, conjunctival luster, relief of discomfort, ease of use, and overall acceptability were found in either group over the baseline score. In addition, neither carbomer gel nor placebo improved the baseline fluorescein staining score or the Schirmer test score. Two patients suffered local allergic reactions to the carbomer gel or its preservative, which settled on withdrawal of the medication. CONCLUSIONS: Carbomer gel was more efficacious than was placebo in improving a number of subjective and objective symptoms of moderate-to-severe dry eye syndrome. The results of this study indicate that carbomer gel was a safe as was the placebo.     

Attentional bias to brief threat-related faces revealed by saccadic eye movements.

According to theories of emotion and attention, we are predisposed to orient rapidly toward threat. However, previous examination of attentional cueing by threat showed no enhanced capture at brief durations, a finding that may be related to the sensitivity of the manual response measure used. Here we investigated the time course of orienting attention toward fearful faces in the exogenous cueing task. Cue duration (20 ms or 100 ms) and response mode (saccadic or manual) were manipulated. In the saccade mode, both enhanced attentional capture and impaired disengagement from fearful faces were evident and limited to 20 ms, suggesting that saccadic cueing effects emerge rapidly and are short lived. In the manual mode, fearful faces impacted only upon the disengagement component of attention at 100 ms, suggesting that manual cueing effects emerge over longer periods of time. Importantly, saccades could reveal threat biases at brief cue durations consistent with current theories of emotion and attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuroendocrine changes in luteal function in patients with premenstrual syndrome

The present study evaluates the luteal progesterone (P) and LH secretions in 14 patients affected by premenstrual syndrome (PMS) and in 14 asymptomatic controls through the evaluation of their episodic release. PMS was prospectively confirmed in two consecutive menstrual cycles using Moos' Menstrual Distress Questionnaire. A pulsatility study was performed during the luteal phase. Blood samples were drawn every 10 min for 12 h, beginning at 0800 h. Statistically significant pulses were detected using the Detect program, and the degree of concordance of LH and P pulses was estimated. Similar mean 12-h P levels were found in controls (mean +/- SD, 13.9 +/- 9.3 nmol/L) and patients (14.2 +/- 10.1). LH levels were also similar in the two groups. Patients showed a higher P pulse frequency (13.4 +/- 1.8 vs. 11.4 +/- 2.3; P < 0.02) and a reduced amplitude of secretory episodes (126.5 +/- 61.6% vs. 187.1 +/- 126.7%; P < 0.03) than controls. Similarly, PMS patients showed pulsatile LH release of increased frequency and reduced amplitude than controls. A significant degree of concordance between LH and P pulses was observed in both groups, with a time lag of 0-10 min; that is, P secretory episodes follow LH with a delay of 0-10 min. These findings demonstrate that despite the fact that integrated P levels in PMS patients are similar to those in control subjects, the episodic secretion of the hormone is characterized by pulses of increased frequency and reduced amplitude. This phenomenon is temporally related to LH secretion, thus reinforcing the concept of PMS as a neuroendocrine disorder.     

Inhibitory inefficiency and failures of intention activation: Age-related decline in the control of saccadic eye movements.

Young and older adults' control of saccadic eye movements was compared using an antisaccade task, which requires the inhibition of a reflexive saccade toward a peripheral onset cue followed by an intentional saccade in the opposite direction. In 2 experiments, an age-related decline was found in the suppression of reflexive eye movements, as indicated by an increased proportion of saccades toward the cue, and a longer time needed to initiate correct antisaccades. The results from Experiment 2 suggested that older adults' slower antisaccades may be explained partly in terms of increased failures to maintain the cue-action representation at a sufficient activation level. The results suggest that the notion of selective preservation with age of the ability to inhibit spatial responses does not apply to the active inhibition of prepotent spatial responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling control of eye orientation in three dimensions. I. Role of muscle pulleys in determining saccadic trajectory

This study evaluates the effects of muscle axis shifts on the performance of a vector velocity-position integrator in the CNS. Earlier models of the oculomotor plant assumed that the muscle axes remained fixed relative to the head as the eye rotated into secondary and tertiary eye positions. Under this assumption, the vector integrator model generates torsional transients as the eye moves from secondary to tertiary positions of fixation. The torsional transient represents an eye movement response to a spatial mismatch between the torque axes that remain fixed in the head and the displacement plane that changes by half the angle of the change in eye orientation. When muscle axis shifts were incorporated into the model, the torque axes were closer to the displacement plane at each eye orientation throughout the trajectory, and torsional transients were reduced dramatically. Their size and dynamics were close to reported data. It was also shown that when the muscle torque axes were rotated by 50% of the eye rotation, there was no torsional transient and Listing's law was perfectly obeyed. When muscle torque axes rotated >50%, torsional transients reversed direction compared with what occurred for muscle axis shifts of <50%. The model indicates that Listing's law is implemented by the oculomotor plant subject to a two-dimensional command signal that is confined to the pitch-yaw plane, having zero torsion. Saccades that bring the eye to orientations outside Listing's plane could easily be corrected by a roll pulse that resets the roll state of the velocity-position integrator to zero. This would be a simple implementation of the corrective controller suggested by Van Opstal and colleagues. The model further indicates that muscle axis shifts together with the torque orientation relationship for tissue surrounding the eye and Newton's laws of motion form a sufficient plant model to explain saccadic trajectories and periods of fixation when driven by a vector command confined to the pitch-yaw plane. This implies that the velocity-position integrator is probably realized as a subtractive feedback vector integrator and not as a quaternion-based integrator that implements kinematic transformations to orient the eye.     

Cat eye syndrome with hypogonadotropic hypogonadism

Epidemiological studies on the relation between selenium and human cancer have yielded strongly conflicting results. Prompted by the observation of a positive association between selenium intake and site-specific cancers, including melanoma, in a large cohort of nurses, we studied the 11-year melanoma incidence in an Italian cohort that consumed unusually high levels of inorganic selenium in tap water from 1975 to 1985. The setting was Reggio Emilia, an Italian municipality that provided a natural experiment relating to intake of high levels of inorganic selenium. We identified 2,065 individuals with high selenium exposure, who contributed a total of 20,179 person-years of follow-up, and we compared their experience with the 1,384,386 person-years of follow-up in the remaining population of Reggio Emilia. We included all cases of pathologically confirmed malignant melanoma, including intraocular melanoma, identified from the Reggio Emilia Hospital, the Bologna regional registry of hospital discharges, and the Milan National Cancer Institute. Eight cases of malignant melanoma occurred in the exposed cohort during the follow-up. Melanoma incidence was 3.9 times greater in the exposed than in the unexposed cohort (95% exact confidence limits, 1.8-7.4).     

Patients with Turner's syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation

OBJECTIVE: To evaluate whether endometrial receptivity is compromised in patients with premature ovarian failure (POF) due to Turner's syndrome who undergo oocyte donation. DESIGN: Retrospective analysis. SETTING: In vitro fertilization-ET units, anonymous oocyte donation program. PATIENTS: The study included 53 patients with POF who underwent oocyte donation. These included 7 patients with Turner's syndrome (45,X) who underwent 22 ET cycles, 15 women with Turner variants (mosaics, deletions, or isochromosomes) who underwent 36 ET cycles, and 31 other patients with POF and a normal karyotype who underwent 69 oocyte donation cycles. INTERVENTION: All patients on standby for donation were treated with E2 valerate 6 mg/d until oocytes became available; then P 100 mg/d was added. Oocyte donors were healthy women < 34 years who underwent IVF themselves. MAIN OUTCOME MEASURES: Clinical pregnancy rates (PRs), biochemical pregnancies, early abortions, and delivery rates were evaluated. RESULTS: Turner's syndrome patients had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical PR (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%), and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared with non-Turner patients. CONCLUSIONS: Patients with a complete or partial deficiency of an X chromosome have reduced PRs and an increase in early implantation failure after oocyte donation. This may indicate an inherent endometrial abnormality, possibly associated with a deficiency of X-linked genes regulating endometrial receptivity.     

Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects

Recent animal and human studies have suggested that leptin secretion is closely linked to the functions of the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, both of which are crucial in influencing the course and outcome of critical illness. Therefore, we measured basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytokine, interleukin-6, in critically ill patients with acute sepsis. Sixteen critically ill patients from the University of Leipzig Intensive Care Unit were recruited for this study. All of these patients fulfilled the standard diagnostic criteria for sepsis. Plasma leptin levels were measured in all patients and controls at 09:00. In addition, in a subgroup of eight critically ill patients and all of the nine controls plasma leptin, cortisol, ACTH and interleukin-6 concentrations were measured every 4 hours for 24 hours. Mean plasma leptin levels were three-fold higher (18.9 +/- 4.5 ng/ml) in critically ill patients than controls (3.8 +/- 1.0 ng/ml, p < 0.05). Similarly, ACTH levels were lower (7.8 +/- 3.4 pmol/l) in patients than in controls (17.1 +/- 1.5 pmol/l, p < .001), while plasma cortisol levels were increased (947.6 +/- 144 nmol/l) in patients compared to controls (361.1 +/- 29, p < 0.001). Morning plasma interleukin-6 levels were markedly elevated in all patients with sepsis (1238.0 +/- 543.1 pg/ml) versus controls (6.4 +/- 1.7, p < 0.001). The controls exhibited a nyctohemeral fluctuation in plasma leptin levels with peak levels at 23:00; in contrast, septic patients, had no nocturnal rise of leptin. In healthy controls, plasma leptin and cortisol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients, this relation was abolished. Mean leptin levels were three-fold higher in patients who survived the septic episode (25.5 +/- 6.2, n = 10) than in non-survivors (8.0 +/- 3.7, n = 6, p < 0.01). We conclude that in addition to its function as an anti-obesity factor, leptin may play a role in a severe stress state such as acute sepsis.     

Patients with stroke confined to basal ganglia have diminished response to rehabilitation efforts

Deregulation of expression of the cell cycle regulator cyclin D1 (cD1) may be responsible for rapid proliferation of squamous cell carcinoma of the head and neck (SCCHN). We have studied the expression of cD1 in 46 SCCHNs using immunohistochemistry. Before biopsy, the patients received an in vivo infusion of iododeoxyuridine (IdUrd) for cell proliferation assessment. Additionally, the level of apoptosis was estimated using in situ end labeling (ISEL). Among 33 tumors, the proportion of cD1(+) cells varied from 0.5 to 51.3% (19.9 +/- 2.2%). Thirteen tumors did not express cD1. The fraction of S-phase (IdUrd-positive) cells was 26.3 +/- 1.8% in cD1(+) versus 20.0 +/- 2.4% in cD1(-) tumors (P = 0.06). The percentages of cD1(+) cells and of S-phase cells were not correlated (P = 0.37). Apoptosis was detected by ISEL in 15 of 33 tumors studied. ISEL-positive tumors contained a significantly higher proportion of cD1(+) cells (14.9 +/- 2.6%) than cD1(-) ones (7.9 +/- 2.8%; P = 0.03). There was a positive correlation between the percentage of cD1(+) cells and the degree of ISEL (r = 0.54; P < 0.001). In noninvolved oral mucosa, cD1(+) cells were located primarily in the suprabasal layers (29.3 +/- 3.8% versus 1.2 +/- 0. 2% in the basal layer). Only 23 of 44 mucosal specimens contained cD1(+) cells. All cD1(-) samples were proliferatively active and contained IdUrd-labeled cells. The percentage of cD1(+) cells in the oral epithelium from nontumor controls (uvula samples) was significantly higher than in the SCCHN group in both basal (2.4 +/- 0.4%; P = 0.008) and suprabasal (42.7 +/- 3.3%; P = 0.005) layers. Additionally, whereas in uvuli, cD1(+) cells were distributed evenly along the epithelial lining, in SCCHN samples the regions showing cD1 expression alternated with areas in which cD1 expression was undetectable. These data indicate that cD1 expression in SCCHN varies among tumors and is not correlated with cell proliferation. In noninvolved oral mucosa, cD1 expression differs from that in truly normal epithelium obtained from nontumor patients. A correlation between cD1 expression and the extent of ISEL positivity suggests a possible involvement of cD1 expression in the apoptotic pathways.     

Can tropicamide eye drop response differentiate patients with progressive supranuclear palsy and Alzheimer's disease from healthy control subjects?

Pupillary dilation in response to dilute tropicamide eye drops has been proposed as a noninvasive diagnostic test to identify patients with Alzheimer's disease (AD). We examined 14 patients with progressive supranuclear palsy (PSP), another related neurodegenerative disorder characterized by severe widespread cholinergic deficits and known central hypersensitivity to cholinergic blockade, to determine whether they also showed a marked pupil dilation after administration of dilute tropicamide eye drops. Both PSP patients and healthy age-matched control subjects had a similar pupillary response comparable with that previously reported in AD patients. Given its lack of specificity, physicians should be very cautious in using this test for identification of patients with AD.     

Effect of isosorbide-5-mononitrate on plasma and urine levels of cyclic GMP in relation to exercise in coronary patients compared with control subjects

Nitric oxide (NO) and atrial natriuretic peptide (ANP) relax vascular smooth muscle increasing levels of cyclic guanosine 3':5' monophosphate (cGMP). Nitrovasodilators act as exogenous nitric oxide donors. The aim of this study was to ascertain the response of cGMP to exercise without medication and after the administration of 20 mg of isosorbide-5-mononitrate (IS-5-MN) in coronary patients (n = 8) and healthy control subjects (n = 9). A third group of 10 normal volunteers was studied to test plasma cGMP response to second exercise test without IS-5-MN administration. Plasma cGMP increased significantly in both patients (P < 0.02) and controls (P < 0.01) after the first ergometry. After IS-5-MN administration, plasma cGMP did not increase either before or after exercise. In normal volunteers without IS-5-MN plasma cGMP increased significantly after first (P < 0.004) and second (P < 0.0008) exercise test. In conclusion, plasma cGMP increases during exercise. Administration of IS-5-MN does not raise plasma cGMP and neither does performance of further exercise after its administration.     

Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H

We describe the clinical course, complement components, and pathological findings of 10 infants with autosomal recessive hemolytic uremic syndrome (HUS). All patients were members of one extended highly inbred Bedouin kindred. The median age of presentation was 2 weeks (range 1-20 weeks). Eight patients died, 2 patients are alive, on dialysis. Renal biopsies revealed thrombotic microangiopathy with a predominant early arteriolar involvement and subsequent development of ischemic glomerular changes. Immunofluorescence was positive for C3 in glomeruli. All patients had low complement components levels during and between relapses, and in some this was evident soon after birth and prior to the onset of symptoms. This deficiency could not be normalized by repeated plasma transfusions. Biosynthetic labelling of patients' fibroblasts demonstrated normal rates of C3 protein synthesis. Serum factor H levels were greatly decreased or absent in 4 patients tested and moderately decreased in 15 of 23 healthy unaffected siblings and patients. This defect may cause complement activation and consumption, possibly at the endothelial cell level.