Fetal alcohol exposure augments the blunting of tumor necrosis factor production in vitro resulting from in vivo priming with lipopolysaccharide in young adult male but not female rats

We previously reported altered responses of thymocytes and splenocytes to mitogen stimulation in fetal alcohol-exposed (FAE) male Sprague-Dawley rats. We also reported enhanced neuroendocrine responses to stressful stimuli in these animals. The experiments we describe herein aimed at testing whether young adult FAE rats manifest a notable dysregulation in the neuroendocrine-immune response to pathogen administration. We tested the effect of in vivo priming of the animal with a low dose of endotoxin [lipopolysaccharide (LPS), 5 micrograms/kg], considered to be suboptimal from the perspective of mounting detectable levels of circulating monokines several hours after administration, upon the production of immunoreactive tumor necrosis factor (TNF-alpha) in response to a further in vitro challenge of peripheral blood mononuclear cells with 2.5 micrograms/ml of LPS 90 min after priming. We show that the response to the LPS pathogen in vitro after priming is significantly blunted (p < 0.01) in male rats exposed prenatally to alcohol, compared with control male animals. FAE female rats and FAE ovariectomized female rats do not show significant differences in the priming response, compared with control animals. We also show that there is no correspondence between plasma corticosterone levels and TNF-alpha production after priming in any of the groups tested.     

Subscales within the dependency factor of the Depressive Experiences Questionnaire

Recent theoretical formulations differentiate two types of depressive experiences: one focused on interpersonal issues, such as loss, abandonment, and loneliness; the other focused on issues of self-esteem, such as failure, guilt, and lack of self-worth and autonomy. The Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976, 1979) assesses these two types of depression. Symptom-based measures of depression (i.e., the Beck Depression Inventory, Beck, Rush, Shaw, & Emery, 1979) have highly significant correlations with the DEQ Self-Criticism factor but only marginally significant correlations with the DEQ Dependency (or interpersonal) factor. Through the use of facet theory and Smallest Space Analysis (Guttman, 1982a), two facets were identified within the DEQ Dependency factor that appear to assess two different levels of interpersonal relatedness. One facet, labelled dependence, includes items expressing feelings of helplessness; fears and apprehensions about separation and rejection; and intense, broad-ranging concerns about possible loss unrelated to a particular relationship. The second facet, labelled relatedness, includes items that consider feelings of loss and loneliness in reaction to disruption of a relationship with a particular person. The dependence facet had significantly higher correlations with measures of depression, whereas the relatedness facet had significantly higher correlations with measures of psychological well-being, especially in women. Thus, the DEQ Dependency factor appears to contain two facets that assess interpersonal relatedness at different developmental levels and correlate differentially with measures of depression and of psychological well-being.     

Pulmonary changes as primary manifestations in Waldenstr?m macroglobulinemia]

We describe a patient with a 19-year history of lymphocytic lung infiltrations. A diagnosis of lymphocytic interstitial pneumonitis was made in 1982 after an open lung biopsy, but in 1995 a comprehensive re-evaluation led to the diagnosis of Waldenstr?m's macroglobulinaemia with primary bronchopulmonary involvement. It could also be demonstrated by polymerase chain reaction and immunological techniques that this disease had been present since before 1982. In 1995 it was still difficult to demonstrate bone marrow involvement, even with new and sensitive methods. We discuss some diagnostic problems of organ manifestations of uncommon systemic diseases. Pulmonary manifestations of Waldenstr?m's macroglobulinaemia or other diseases of the immune system should be considered in patients with atypical lung disorders.     

Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma

BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.     

Identification of yeast proteins from two-dimensional gels: working out spot cross-contamination

With the complete sequence of the yeast genome now available, efforts by many laboratories are underway to identify each of the spots on two-dimensional (2-D) gels corresponding to the most abundant yeast proteins. The high mass accuracy now attainable using matrix assisted laser desorption/ionization (MALDI)-mass spectrometry equipped with delayed extraction simplifies the process of identification, such that many spots can be unambiguously identified in a short period of time merely by using peptide mass fingerprinting and generally available database matching programs. Although it is not always possible to match spots between gels run by different laboratories, proteins generally yield the same abundant proteolytic fragments when tryptic digestions are performed. Databases containing these signature peptides not only simplify the task of reidentifying proteins from different gels, but also make it possible to identify small amounts of cross-contaminating proteins from different spots, as well as common extraneous contaminants such as human keratins. In this paper, we present data on the identification of > 20 previously unreported yeast proteins from 2-D gels. Some novel proteins were identified from randomly analyzed spots. Focusing on 14 spots in a narrow-pH-range gel, we demonstrate how organizing peak-table data and peptide match-list data into databases enables the identification of a larger percentage of the peaks.     

A systematic review of evidence for the appropriateness of neonatal screening programmes for inborn errors of metabolism

The nicotinic antagonist mecamylamine was evaluated in a randomized smoking cessation trial. Four groups of participants (n = 20 per group) received nicotine plus mecamylamine, nicotine alone, mecamylamine alone, or no drug for 4 weeks before cessation. After the quit-smoking date, all subjects received nicotine plus mecamylamine treatment for 6 weeks. Nicotine skin patches (21 mg/24 hr) and mecamylamine capsules (2.5-5.0 mg twice per day) were used. Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence; abstinence rates at the end of treatment were 47.5% with mecamylamine and 27.5% without mecamylamine. Nicotine + mecamylamine reduced ad lib smoking, smoking satisfaction, and craving more than either drug alone. Moreover, the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine. Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy.     

Basal activity of the hypothalamic-pituitary-adrenal axis in patients with the chronic fatigue syndrome (neurasthenia)

The authors report a case of biliary colic secondary to gallstones formed during a course of therapy with Ceftriaxone. Three weeks after cessation of therapy the gallstones dissolved.     

Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer. The replication-defective retroviral vector MFG was used for GM-CSF gene transfer. No dose-limiting toxicities were encountered in 16 fully evaluable patients. GM-CSF gene-transduced vaccines were equivalent in toxicity to nontransduced vaccines up to the feasible limits of autologous tumor vaccine yield. No evidence of autoimmune disease was observed. Biopsies of intradermal sites of injection with GM-CSF gene-transduced vaccines contained distinctive macrophage, dendritic cell, eosinophil, neutrophil, and T-cell infiltrates similar to those observed in preclinical models of efficacy. Histological analysis of delayed-type hypersensitivity responses in patients vaccinated with GM-CSF-transduced vaccines demonstrated an intense eosinophil infiltrate that was not observed in patients who received nontransduced vaccines. An objective partial response was observed in a patient treated with GM-CSF gene-transduced vaccine who displayed the largest delayed-type hypersensitivity conversion. No replication-competent retrovirus was detected in vaccinated patients. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous GM-CSF gene-transduced tumor vaccine for RCC patients.