Wild-type adenoviruses from groups A-F evoke unique innate immune responses, of which HAd3 and SAd23 are partially complement dependent.

Alternative human and non-human Ad serotype vectors are currently studied for gene therapy and/or vaccine applications to capitalize upon their likely ability to avoid pre-existing immunity to HAd5. However, relatively little attention has been given to the nature and scope of innate immune responses generated by alternative Ad serotypes. In this study, we characterized several innate immune responses after intravenous administration of wild-type Ad serotypes HAd31, HAd3, HAd5, HAd37, SAd23 and HAd41, representing groups A-F, respectively. Notably, biodistribution studies revealed significant differences between the serotypes, with high levels of HAd3 genomes found in the liver and lung, and HAd37 genomes found in the spleen after systemic administration. Relative to similar treatments with other Ad serotypes, HAd3 and SAd23 induced altered innate immune responses, illustrated by induction of higher levels of cellular gene transcription in several tissues, and higher plasma levels of cytokines and chemokines. We also investigated whether complement interactions have a role in HAd3- and SAd23-induced responses. We confirmed complement dependent gene transcription, plasma cytokine/chemokine responses, and liver toxicities incurred after administration of HAd3 and SAd23. This study highlights the potential benefits and/or limitations to the proposed use of alternative Ad serotypes for gene therapy or vaccine applications.

Oxegen 2004: the impact of a major music festival on the workload of a local hospital.

This prospective observational study was undertaken to assess the impact of a major music festival on the workload of a local hospital. Data were collected on all attendances at Naas General Hospital from the nearby Oxegen 2004 music festival. Patient demographics, disposition and diagnoses were recorded. Emergency department activity levels were compared before, during and after the festival. Seventy-two attendees were referred to Naas emergency department over a 3-day period, representing a 45% increase in the hospital's emergency department attendance rate. Thirty-seven of these attendees (51%) required inpatient or tertiary centre services. Thirty-four attendees (47%) were noted as having consumed alcohol and/or used illicit substances. We conclude that despite the provision of on-site medical facilities, major music events are associated with a significant increase in local health care activity and expenditure.

Sorority women's body size perceptions and their weight-related attitudes and behaviors.

Six hundred twenty-seven sorority women were surveyed to determine if sorority members constituted a subgroup of college women who may be at increased risk for disordered eating. The sorority members were administered Body Mass Index Silhouettes and the Eating Disorder Inventory. The findings indicated that these sorority women may have a greater fear of becoming fat, are more dissatisfied with their bodies, and are more weight preoccupied and concerned with dieting than are college women from previous studies. The findings also suggested that body size perceptions were distorted among both underweight and overweight women and that thin was the ideal body profile for the majority of the women. Although bulimia scores were higher for this population than for those reported in all but one of the previous studies, these differences were not significant. More research and innovative programs designed to address weight-related attitudes and behaviors among this population are called for.

Production of tumor necrosis factor alpha and interferon gamma in interleukin-2-treated melanoma patients: correlation with clinical toxicity.

Interleukin-2 (IL-2)-based immunotherapy regimens are accompanied by dose-limiting toxicity consisting of fever, tachycardia, chills and capillary leak syndrome. We hypothesized that the toxicity was caused by the induction and release of endogenous cytokines such as tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). We measured the serum levels of TNF alpha and IFN gamma in IL-2-treated melanoma patients and attempted a correlation with clinical toxicity. A total of 23 patients received either 6 x 10(6) IU or 12 x 10(6) IU Cetus IL-2/m2 by i.v. bolus daily for 5 consecutive days on weeks 1, 3 and 5. Serum TNF alpha and IFN gamma levels were measured by enzyme-linked immunosorbent assay. Clinical toxicity was scored each day by objective measurements of hypotension, tachycardia, fever and chills/rigors. Clinical toxicity and IFN gamma levels correlated nicely, peaking on the 5th day of each treatment cycle. The kinetics and magnitude of TNF alpha production, however, were not predictable and did not correlate with either IFN gamma or toxicity. Some patients had modest increases in TNF alpha production while others had markedly increased levels during the second and third treatment weeks. Remarkably, these high levels persisted during nontreatment weeks and after completion of therapy. This clinical study demonstrates novel kinetics for immunoreactive TNF alpha in IL-2 cancer patients, which do not correlate well with toxicity.

State-dependent alterations in the perception of life events in menstrual-related mood disorders.

The authors examined the reporting of daily life events by women with prospectively confirmed menstrual-related mood disorder (N = 40) and asymptomatic control subjects (N = 20). During the follicular and late luteal phases of the menstrual cycle, subjects completed a schedule of life events that monitors an individual's perception of 1) the frequency of occurrence of life events and 2) the degree of associated distress or pleasure. The patient group reported significantly more negative life events than the control group. Further, the patients with menstrual-related mood disorder showed significantly more distress associated with the same event when it occurred in the premenstrual phase than when it occurred in the post-menstrual phase.

Menstrual cycle phase-related changes in appetite in patients with premenstrual syndrome and in control subjects.

Menstrual cycle phase-dependent changes in appetite in women with premenstrual syndrome has not thus far been systematically demonstrated. In this study of 21 patients with premenstrual syndrome and 13 control subjects, there were significant increases in appetite in both groups, with a greater effect of menstrual cycle phase on appetite in the patients. Further, the premenstrual increase in appetite was highly correlated with self-ratings of mood (particularly depression) in the patients only. The authors discuss these findings with respect to endocrine influences on appetite regulation and potential implications for investigation of atypical depression.

Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects.

A variety of hypotheses have been proposed to explain the premenstrual syndromes. These hypotheses serve as rationales for an equally diverse range of proposed treatments. To investigate these hypotheses, we obtained multiple blood samples across the menstrual cycle in women with well-characterized menstrually related mood disorder and in control subjects. No diagnosis-related differences were observed in the levels or patterns of secretion of progesterone, estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone-estradiol-binding globulin, dehydroepiandrosterone sulfate, dihydrotestosterone, prolactin, or cortisol. Our data suggest that premenstrual syndrome does not represent a simple hormonal deficiency and that the cited rationales for several of the proposed treatments are of questionable merit.

TSH and prolactin responses to TRH in patients with premenstrual syndrome.

The thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH), administered during the follicular and luteal phases of the menstrual cycle, were examined in 14 women with prospectively confirmed premenstrual syndrome and in nine control subjects. There were no differences in basal or maximum increase in TSH or prolactin values between menstrual cycle phases in patients or in control subjects or between patients and control subjects in either phase. However, there was significantly greater variability in TSH response to TRH among symptomatic patients (seven of 10 patients: three with blunted and four with augmented response) than among control subjects (none of nine patients).

Intestinal adaptation. Different growth responses to disaccharides compared with monosaccharides in rat small bowel.

Midgut infusions of sucrose and other disaccharides were compared with monosaccharides for their effects on intestinal mucosal growth in rats otherwise maintained on total parenteral nutrition for 7 days. Mucosal mass progressively increased in a proportional relationship to the concentration of infused sucrose. At equal concentrations by weight, disaccharide infusions stimulated mucosal growth more than monosaccharides. Disaccharide-induced mucosal adaptation was abolished when there was no hydrolysis of the disaccharide. The results suggest that the functional work load of absorbing epithelium, including the "work of hydrolysis," plays an important role in the stimulus for intestinal adaptation.

Premenstrual mood changes. Characteristic patterns in women with and without premenstrual syndrome.

Methodologic errors have compromised previous attempts to establish the relationship between mood and menstruation in women with the premenstrual syndromes. These syndromes cannot be diagnosed by history and require confirmation with longitudinal, prospective ratings. In this paper we present the characteristic pattern of mood changes in women with and without menstrually-related mood syndrome. The theoretical and diagnostic implications of the pattern differences are discussed.

Premenstrual changes: a comparison of five populations.

Several studies have suggested that a special relationship exists between premenstrual and major affective disorders. The present report describes the incidence of reported premenstrual symptoms in women with and without prospectively confirmed premenstrual syndrome, women with bipolar or seasonal affective disorder, and controls. The inability of reported symptoms to differentiate women with and without confirmed premenstrual syndrome, as well as the reduced prevalence of reported premenstrual changes in our affective populations relative to previous reports, is discussed.

Cortisol response to dexamethasone in women with premenstrual syndrome.

There were no significant differences in post-dexamethasone cortisol between the follicular and luteal phase of the menstrual cycle in both women with premenstrual syndrome (PMS) and control subjects tested on these two occasions. Within each menstrual cycle phase, there were also no differences in post-dexamethasone cortisol between the two groups. In a second group of control subjects tested on a single occasion, post-dexamethasone cortisol values were higher when subjects were tested in the middle 2 weeks of the menstrual cycle compared with the first and last weeks of the cycle. This phenomenon, possibly due to estrogen effects, suggests that post-dexamethasone cortisol should be assessed weekly in women with PMS to determine whether they also manifest this normally observed menstrual cycle phase-related pattern, or whether it is absent, reflecting a reproductive endocrine abnormality in this patient group.

Premenstrual mood disorder and psychiatric illness.

The results of several studies suggest that a special relationship exists between premenstrual syndromes and major psychiatric disorders, particularly affective illness. These studies in general have not employed prospective criteria to diagnose premenstrual syndrome. In this paper the authors report a significant difference in the lifetime history of psychiatric illness between women with prospectively confirmed menstrually related mood disorder and those without it.

Prospective assessment of menstrually related mood disorders.

For prospective longitudinal confirmation of menstrually related mood changes, the authors selected a 100-mm visual analogue scale for twice-daily self-rating of mood. The advantages of this method are simplicity; increased compliance; ease of graphic presentation, allowing evaluation of severity and relationship to menstruation; and greater uniformity among studies of menstrually related syndromes. In a preliminary application of this measure to 20 women with self-diagnosed premenstrual syndrome, eight (40%) had a mean depression rating during the week before menstruation that was 30% higher than during the week after cessation of menstruation.