Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy.

Long-acting beta adrenergic agonists, such as clenbuterol accumulate in the liver, but not meat of treated farm animals, and result in epidemic poisonings in consumers. We describe an outbreak of poisoning in 15 people, following the consumption of meat. Clinical symptoms (distal tremors, palpitations, headache, tachipnoea-dyspnoea, and also moderate hyperglycaemia, hypokalemia and leucocytosis) were seen in nine hospitalised patients, starting about 0.5-3 h after poisoning, and disappearing within 3-5 days later. Clenbuterol was found in the urine of all the symptomatic patients, at higher levels than pharmacokinetic computing (mean level 28 ng/ml, 36 h after ingestion), based on the levels found in the meat (1140-1480 ng/g edible tissue). Thus, epidemic poisoning can be produced following the consumption of contaminated meat. The need for a better definition of pharmaco- and toxico-kinetics, not only for drugs ingested as parent drug, but also when ingested as residues with animal tissues, is recommended.

Prognostic value of 24-hour blood pressure in pregnancy.

CONTEXT: Elevated blood pressure (BP) measured at the physician's office may reflect true hypertension or white coat hypertension (WCH). The prognostic value of WCH among pregnant women is unknown. OBJECTIVE: To assess the prognostic value of WCH in pregnancy. DESIGN: Prospective cohort study conducted between September 1994 and October 1997. SETTING: Community hospital. PATIENTS: Women without preexisting hypertension and not treated with antihypertensive drugs aid with high (n = 148) or normal (n = 106) office BP (high office BP was defined as > or =140 mm Hg systolic and/or > or =90 mm Hg diastolic) matched for gestational age during their third trimester of pregnancy. All women underwent 24-hour noninvasive BP monitoring, and women without hypertension on 24-hour monitoring (125/74 mm Hg or less for average 24-hour BP) with office hypertension were classified as having WCH. Women were followed up through the end of pregnancy. MAIN OUTCOME MEASURES: Duration of pregnancy, gestational hypertension, preeclampsia or eclampsia, cesarean delivery, placental and neonatal weight, and length of maternal and neonatal hospital stays for those with and without elevated office BP. RESULTS: After application of exclusion criteria, data for 7 women were removed from the analysis. For the remaining subjects, in the group with elevated BP, prevalence of WCH was 29.2% (42/144). Duration of pregnancy was similar in the normotensive and WCH groups (39.6 vs 39.8 weeks; P = .50), but shorter (38.3 weeks; P<.001) in the true hypertension group. Incidence of preeclampsia was similar in the normotensive and WCH groups (5.8% vs 7.1 %; P = .86) but higher in the true hypertension group (61.7%; P<.001). Frequency of cesarean delivery was lower in the normotensive (12.4%) than in the WCH (45.2%; P = .008) and true hypertension (41.1 %; P = .009) groups. Neonatal weight was lower (P<.001) in the true hypertension (mean, 2911 g) than in the normotensive (3336 g) and WCH groups (3435 g), which did not differ (P = .68). The duration of neonatal hospital stay did not differ between the normotensive and the WCH group (5.3 vs 6.9 days; P = .13) but was longer in the true hypertension group (12.3 days; P<.001). CONCLUSIONS: In women with elevated BP during their third trimester of pregnancy, 24-hour BP was superior to office BP (distinguishing true hypertension from WCH) for prediction of the outcome of pregnancy. Outcomes in the normotensive and WCH group were comparable, but the increased incidence of cesarean delivery in the WCH group may reflect decision-making processes influenced by office BP.

Twenty four-hour ambulatory blood pressure monitoring in women with pre-eclampsia.

The aim of our study was to evaluate by means of ambulatory 24 h monitoring the diurnal systolic (SBP) and diastolic (DBP) blood pressure profiles in a group (n = 18) of gravid patients with pre-eclampsia compared with a group (n = 17) of healthy control subjects matched for age and week of gestation to assess whether: (i) ambulatory BP is also raised in pre-eclampsia; (ii) the increase of BP, if present, occurs to the same extent during both daytime and night; and (iii) a blunted BP pattern is consistently present in pre-eclampsia. BP was recorded at intervals of 15 min for 25 h using a TM2420 non-invasive pressurometer. The presence of a circadian rhythm of BP was assessed by cosinor analysis. SBP was higher in women with pre-eclampsia (24 h average 115 +/- 11 vs. 136 +/- 12, P = 6 x 10(-6); daytime 117 +/- 12 vs. 139 +/- 13, P = 6 x 10(-6); night 110 +/- 11 vs. 129 +/- 14, P = 5 x 10(-5) as well as DBP (24 h average 67 +/- 5 vs. 86 +/- 6, P = 8 x 10(-12); daytime 69 +/- 6 vs. 89 +/- 5, P = 2 x 10(-11); night 62 +/- 4 vs. 80 +/- 8, P = 5 x 10(-10).(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol-specific impairment of T-lymphocyte activation is caused by a transitory block in signal-transduction pathways.

BACKGROUND: Immune system derangement is characteristic of alcoholic liver cirrhosis. However, in vitro studies have never clarified the alcohol-induced T-lymphocyte dysfunction. The aim of this study was to examine any discrete phenotypical and functional abnormalities and possible impairment in transmembrane signal-transduction pathways that, if present on lymphocytes of patients with alcoholic cirrhosis, would also be reproducible after in vitro ethanol exposure of normal T cells. METHODS: Lymphocytes from 25 patients were analyzed for their in vitro proliferative functions, intracellular Ca2+ fluxes, and inositol 1,4,5-triphosphate (IP3) generation. The same procedures were applied to normal T cells exposed in vitro to ethanol. RESULTS: Lymphocytes failed to respond to anti-CD3 and anti-CD2 after in vitro stimulation, with decreased intracellular Ca2+ mobilization and IP3 generation but showed normal proliferative response to phytohemagglutinin. In vitro ethanol incubation of normal T lymphocytes resulted in rearrangement of the membrane CD45 antigen, favoring the expression of high-molecular-weight isoforms, and showed a poor blastogenic response to anti-CD3 and anti-CD2 with a decrease in intracellular Ca2+ mobilization and IP3 production. After a 6-month period of ethanol withdrawal, some patients had normalization of phenotypic and functional alterations. CONCLUSIONS: The T-lymphocyte response to specific polyclonal activators may be severely impaired in alcohol abusers. However, it seems reversible after a period of controlled ethanol withdrawal.

IgG subclass deficiency and sinopulmonary bacterial infections in patients with alcoholic liver disease.

Abnormalities in IgG subclass distribution were sought in serum samples and bronchoalveolar lavage fluid from 15 patients with alcoholic liver disease to explain their increased susceptibility to bacterial respiratory infections. Serum IgG4 deficiency alone or in association with low IgG2 levels was revealed in approximately 30% of patients with alcoholic liver disease. This fact prompted us to further investigate the immunoglobulin concentrations in broncho-alveolar lavage fluid, paying special attention to the distribution of IgA and IgG subclasses. IgA levels were found to be normal or slightly elevated. However, there were substantial defects in total IgG and IgG1 concentrations, often associated with reduced IgG2 and IgG4 levels, in approximately 70% of patients with alcoholic liver disease, which proved to be closely correlated with the number and type (pneumonia) of bacterial respiratory infections. A prospective study of intravenous immunoglobulin substitutive therapy involving two patients with recurrent pneumonia and very low serum IgG2 values demonstrated a reduction in the number of respiratory infectious episodes as well as an increase in both serum and, to a lesser extent, bronchoalveolar lavage fluid IgG1 and IgG2 levels. We identified immune defects that may represent an important pathogenetic mechanism that, when considered together with the alcohol-related suppression of alveolar macrophage and ciliary functions and the inhibition of leukocyte migration into the lungs, should help clarify the complex relationships between alcohol and immune defense.

T-lymphocyte activation pathways in alcoholic liver disease.

Immune system derangement in cirrhotic patients with evidence of malnutrition is a well-recognized characteristic of chronic alcohol abuse. However, in vitro studies on cellular immune function performed with lectin mitogens have produced conflicting results. The recent development of more accurate immunological techniques for studying lymphocyte transformation, that use monoclonal antibodies directed against surface structures (CD3 and CD2) involved in antigen recognition, as well in adhesion functions, prompted us to study discrete in vitro T-cell hypo-responsiveness in a series of alcoholic liver disease (ALD) patients with no evidence of malnutrition or hepatic cirrhosis. The results indicated that the CD2 pathway is markedly defective in ALD T lymphocytes, accompanied by reduced interleukin-2 (IL-2) receptor expression upon in vitro activation. This defect cannot be reversed by the addition of recombinant IL-2 (rIL-2) or rIL-1. Faulty intracellular signal transduction by protein kinase C (PKC) and defective intracellular Ca2+ mobilization may be responsible for the CD2 pathway impairment. The addition of small amounts of phorbol 12-myristate, 13-acetate, but not Ca2+ ionophore A23187, is able to overcome the defect, thereby suggesting a direct PKC involvement. The hypothesis of a direct ethanol effect on transmembrane signal transduction systems is suggested by the demonstration of an expansion of circulating virgin (naive) T cells (CD3+/UCHL1-low) that binds tyrosine phosphatase (CD45RA antigen) on their surface.

Immunoregulatory T cells in alcoholic liver disease: phenotypical dissection of circulating Leu3+/T4+ inducer T-lymphocytes.

Alcoholic liver disease (ALD) patients had normal absolute lymphocyte counts, increased percentage of Leu3+/T4+ cells (p less than 0.001) and raised T4/T8 ratio (p less than 0.01). Double-colour immunofluorescence analysis using isotype-specific goat anti-mouse immunoglobulins, fluorescein or rhodamine-conjugated, demonstrated that the rise in inducer (Leu3+/T4+) T-cells was almost entirely represented by an expanded population of T4+TQ1- and 5/9+ true helper lymphocytes. T4+ cells also expressed IL2 receptors, as detected by the anti-Tac monoclonal antibody (range 1-18%). On the other hand, the percentage of Leu3+/T4+ cells which bind the K562 cell-line or co-express NK markers on their surface, such as Leu7 (HNK-1), was within the normal range in the majority of ALD patients. Functional studies on patients' cultured total or B-enriched lymphocytes in a pokeweed-mitogen-driven B-cell differentiation assay showed an enhanced plasma cell generation even in unstimulated cultures. Co-culture experiments with normal enriched-B lymphocytes demonstrated that both irradiated and non-irradiated patient T cells led to an increased plasma cell generation. These findings indicate that helper T cells and B cells are all simultaneously activated in vivo, and that the suppressor T lymphocyte function is normal in ALD.

Immunological studies in patients with alcoholic liver disease: evidence for the in vivo activation of helper T cells and of the monocyte-macrophage system.

Immunologic parameters were evaluated in 22 patients with alcoholic liver disease (ALD). Patients with ALD had increased levels of circulating immune complexes (CIC) and serum immunoglobulins, particularly IgA. The classical complement pathway was preferentially activated in CIC-positive patients. There was no increase in total lymphocyte or total T lymphocyte counts, but a significant rise in both the helper/inducer population (OKT4) and helper/suppressor cell ratio (T4/T8) was noted. The presence of interleukin-2 receptors and HLA-DC/DS and HLA-DR antigens suggested in vivo activation of ALD patients' T cells. The rate of differentiation of B cells to plasma cells was high in both pokeweed mitogen-stimulated and unstimulated cultures of ALD patients' B cells, whereas plasma cell generation doubled when patient T lymphocytes were added to enriched normal B cells. The above data support a role for activated helper (T4+) T cells in the immune response initiated by alcoholic hepatitis. Serum angiotensin-converting enzyme levels and lysozyme levels were increased in ALD patients, and cultured adherent mononuclear cells from ALD patients secreted more lysozyme in vitro than normal cells, suggesting the presence of an activated monocyte-macrophage system in ALD.