Differential strain and velocity generation along the right ventricular free wall in pulmonary hypertension.

BACKGROUND: In contrast to the homogeneously distributed deformation properties within the left ventricle, the right ventricular (RV) free wall (RVFW) shows a more inhomogeneous distribution. It has been demonstrated that pulmonary hypertension (PH) results in significant RVFW mechanical delay. OBJECTIVE: To assess the effect of the degree of pulmonary arterial systolic pressure on the RVFW strain gradient and on myocardial velocity generation. METHODS: Peak longitudinal strain and velocity data were collected from three different segments (basal, mid- and apical) of the RVFW in 17 normal individuals and 31 PH patients. RESULTS: A total of 144 RV wall segments were analyzed. RVFW strain values in individuals without PH were higher in the mid and apical segments than in the basal segment. In contrast, RVFW strain in PH patients was higher in basal segments and diminished toward the apex. In terms of RVFW velocities, both groups showed decremental values from basal to apical segments. Basal and mid-RVFW velocities were significantly lower in PH patients than in individuals without PH. CONCLUSIONS: PH results in significant alterations of strain and velocity generation that occurs along the RVFW. Of these abnormalities, the reduction in strain from the mid and apical RVFW segments was most predictive of PH. It is important to be aware of these differences in strain generation when studying the effect of PH on the right ventricle. Additional studies are required to determine whether these differences are due to RV remodelling.

Defining normal variables of right ventricular size and function in pulmonary hypertension: an echocardiographic study.

BACKGROUND: Right ventricular (RV) fractional area change and tricuspid annular plane systolic excursion (TAPSE) are recognised methods for assessing RV function. However, the way in which these variables are affected by varying degrees of pulmonary hypertension (PH) has not been well characterised. METHODS: RV end-systolic area (RVESA), RV end-diastolic area (RVEDA), pulmonary artery systolic pressure (PASP) and TAPSE were collected from a database of 190 patients who had been referred to the PH clinic for evaluation. RESULTS: The mean (SD) age of the study population was 56 (17) years; 82 men were included with a mean (SD) PASP of 54 (33) mm Hg (range 16-150), RVESA of 14 (9) cm(2), RVEDA of 24 (9) cm(2), RV fractional area change of 44 (18)% and TAPSE of 2.06 (0.69) cm. Receiver-operating characteristic curves identified TAPSE <2.01 cm, RV fractional area change <40.9%, RVESA >12.3 cm(2) and RVEDA >23.4 cm(2) as abnormal values with PH. Finally stratification of patients into sub-groups according to their PASP allowed means and standard deviations to be reported for each echocardiographic variable. CONCLUSION: This analysis provides a range of normal variables of RV size and function, not previously published, that can be used in routine evaluation and follow-up of patients with PH.

Effects of aging on left atrial reservoir, conduit, and booster pump function: a multi-institution acoustic quantification study.

OBJECTIVE: To assess the feasibility of measuring left atrial (LA) function with acoustic quantification (AQ) and then assess the effects of age and sex on LA reservoir, conduit, and booster pump function. PATIENTS AND SETTING: 165 subjects without cardiovascular disease, 3-79 years old, were enrolled by six tertiary hospital centres. INTERVENTIONS: Continuous LA AQ area data were acquired and signal averaged to form composite waveforms which were analysed off-line. MAIN OUTCOME MEASURES: Parameters of LA performance according to age and sex. RESULTS: Signal averaged LA waveforms were sufficiently stable and detailed to allow automated analysis in all cases. An age related increase in LA area was noted. LA reservoir function did not vary with age or sex. All parameters of LA passive and active emptying revealed a significant age dependency. Overall, the passive emptying phase accounted for 66% of total LA emptying ranging from 76% in the youngest to 44% in the oldest decade. LA contraction accounted for 34% of atrial emptying in all subjects combined with the older subjects being more dependent on atrial booster pump function. When adjusted for atrial size, there were no sex related differences in LA function. CONCLUSIONS: LA reservoir, conduit, and booster pump function can be assessed with automated analysis of signal averaged LA area waveforms. As LA performance varies with age, establishment of normal values should enhance the evaluation of pathologic states in which LA function is important.

Normal values of regional left ventricular endocardial motion: multicenter color kinesis study.

Our goal was to establish normal values for quantitative color kinesis indexes of left ventricular (LV) wall motion over a wide range of ages, which are required for objective diagnosis of regional systolic and diastolic dysfunction. Color-encoded images were obtained in 194 normal subjects (95 males, 99 females, age 2 mo to 79 yr) in four standard views. Quantitative indexes of magnitude and timing of systolic and diastolic function were studied for age- and gender-related differences. Normal limits of all ejection and filling indexes were in a narrow range (< or =25% of the mean), with no major gender-related differences. Despite invariable ejection fractions, both peak filling and ejection rates decreased with age (30 and 20%, correspondingly) with a concomitant increase in mean filling and ejection times, resulting in five- and twofold increases in the late to early filling and ejection ratios, correspondingly. Diastolic asynchrony increased with age (from 4.7 +/- 2.0 to 6.4 +/- 3.2 from the 2nd to 7th decade). The normal values of color kinesis indexes should allow objective detection of regional LV systolic and diastolic dysfunction.

Immune responses to pertussis antigens eight years after booster immunization with acellular vaccines in adults.

Pertussis-specific antibody and cell-mediated immune (CMI) responses were studied in adults 8 years after booster immunization with either a bicomponent (pertussis toxin and filamentous hemagglutinin) or a monocomponent (pertactin) acellular vaccine and in age-matched healthy controls. The levels of vaccine-induced antibodies were also compared between the serum samples collected before, 1 month, 4 years, and 8 years after immunization. Over the follow-up period, geometric mean values (GMV) of antibodies to the vaccine antigens decreased in both groups of vaccinees. However, the 8-year postimmunization GMV were 3-20 times higher than preimmunization GMV (all P values <0.01). Moreover, both antibody and CMI responses to the vaccine antigens were significantly higher in the vaccinees than in the controls (all P<0.01 for antibody; all P<0.001 for CMI responses). The results show that antibody and CMI responses induced by acellular pertussis vaccines can persist for up to 8 years after booster immunization of adults primed with whole-cell vaccine.

Local reactions and IgE antibodies to pertussis toxin after acellular diphtheria-tetanus-pertussis immunization.

Local reactions and pertussis toxin specific immunoglobulin E antibodies (PT-IgE) were investigated in healthy children following primary and booster immunization with a combined diphtheria tetanus acellular pertussis vaccine (DTPa) including pertussis toxin, filamentous haemagglutinin and pertactin. A primary series of DTPa was administered to 150 infants, and 104 of them received a booster dose of DTPa combined with inactivated polio vaccine at 2 years of age. PT-IgE was measured in serum samples from 72 children using a modified nitrocellulose RAST. Primary immunization was associated with low incidence of local reactions (1%-5%). After the booster dose 21% of children had a local reaction >/=20 mm. Local reactions after the booster dose tended to be more common in children who had experienced reaction at primary immunization. PT-IgE was detected in 18% and 86% of children following primary and booster vaccinations, respectively. Allergic and non-allergic children did not differ in PT-IgE responses. After primary immunization, elevated PT-IgE levels were found more often in children with a family history of allergy than in those without known allergy in the family. Children with local reactions had significantly higher pre- and post-booster PT-IgE levels and median post-booster pertactin IgG and diphtheria-IgG levels than children without local reactions. Conclusion Acellular pertussis immunization induces IgE antibodies to pertussis toxin, especially after booster vaccination. The higher median pre- and post-booster levels of pertussis toxin specific immunoglobulin E and post-booster levels of IgG to pertactin and diphtheria in children with local side-effects reflect a multifactorial immunological mechanism of such reactions.

Cell-mediated immune responses to antigens of Bordetella pertussis and protection against pertussis in school children.

BACKGROUND: Increasing evidence suggests that cell-mediated immunity (CMI) is involved in immune response against Bordetella pertussis. However, there are practically no studies evaluating the significance of pertussis-specific CMI in relation to protection against clinical pertussis. METHODS: An outbreak of pertussis was studied prospectively in 13-year-old pupils in a rural school. B. pertussis infection was diagnosed by culture, microagglutination and enzyme immunoassay serology with the use of pertussis toxin, filamentous hemagglutinin and pertactin as antigens. Pertussis-specific CMI responses were assessed by in vitro proliferation assay of peripheral blood mononuclear cells. RESULTS: At the initial sampling 7 of 22 children had symptoms suggestive of pertussis and 15 were asymptomatic. Of the latter 3 remained healthy, 8 were later confirmed to have had asymptomatic infection, 3 developed laboratory-confirmed pertussis and 1 developed cough without laboratory evidence of pertussis. Initial in vitro proliferations of peripheral blood mononuclear cells induced by pertussis toxin, filamentous hemagglutinin and/or pertactin were positive in all 3 healthy children, in 6 of 8 children who had asymptomatic infection, but in none of the 3 children who later developed pertussis. Although some children who remained healthy had high values of antibodies, no clear association was found between initial serum antibody values and clinical outcome. CONCLUSIONS: These preliminary data suggest that CMI may have an important role in protection against clinical pertussis but do not exclude a role for antibodies. Furthermore the results stress a multifactorial nature of the immune protection against B. pertussis.

Antibody and cell-mediated immune responses to booster immunization with a new acellular pertussis vaccine in school children.

235 healthy 10-12 years old school children were randomly immunized with either a booster dose of diphtheria-tetanus-acellular pertussis (dTap) or diphtheria-tetanus (dT) vaccine. For this booster immunization designed for school children and adults, the quantities of Bordetella pertussis antigens in the dTap vaccine had been reduced to one third of those of the Infanrix vaccine (SmithKline Beecham) commonly used for infants. IgG antibodies and cell-mediated immune (CMI) responses to pertussis toxin (PT), pertactin (PRN) and filamentous hemagglutinin (FHA) were assessed by an enzyme immunosorbent assay and in vitro proliferation of peripheral blood mononuclear cells, respectively. Before immunization, 55%, 80% and 99% of children had detectable serum IgG antibodies to PT, PRN and FHA, whereas CMI response was found in 35%, 27% and 50% of children, respectively. After immunization, a 20-30-fold increase in geometric mean level (GML) of antibodies to the pertussis antigens occurred and CMI response to PT, PRN and FHA was seen in 88%, 94% and 100% of children, respectively. Adverse reactions following the immunization were rare. The results show that booster immunization with an acellular pertussis vaccine with reduced concentrations of antigens induces both antibody and CMI responses and support further studies of this pertussis vaccine in school children.

Cytokine mRNA expression and proliferative responses induced by pertussis toxin, filamentous hemagglutinin, and pertactin of Bordetella pertussis in the peripheral blood mononuclear cells of infected and immunized schoolchildren and adults.

Pertussis infection is increasingly recognized in older children and adults, indicating the need of booster immunizations in these age groups. We investigated the induction of pertussis-specific immunity in schoolchildren and adults after booster immunization and natural infection. The expression of mRNA of gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 in the peripheral blood mononuclear cells (PBMCs) was assayed by reverse transcription-PCR. The PBMCs of 17 children immunized with one dose of an acellular vaccine containing pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) significantly proliferated in vitro after stimulation with the vaccine antigens. The PBMCs of seven infected individuals markedly proliferated in the presence of PT and FHA, but the cells of only two of these subjects responded to PRN. At least one of the antigens induced mRNA for IL-4 and/or IL-5 in the cells of 93% of tested vaccinees and patients, and FHA induced IFN-gamma mRNA in the cells of two-thirds of them. Expression of mRNA for IFN-gamma correlated with the production of the cytokine protein. Anti-FHA immunoglobulin G antibodies significantly correlated with FHA-induced proliferative responses both before and after immunization. These results show that booster immunization with acellular pertussis vaccine induces both antibody- and cell-mediated immune responses in schoolchildren. Further, booster immunization and natural infection seem to induce the expression of mRNA of T-helper 1 (Th1) and Th2 type cytokines in similar manners. This observation supports the use of acellular pertussis vaccines for booster immunizations of older children, adolescents, and adults.

Protective role of immunoglobulin G antibodies to filamentous hemagglutinin and pertactin of Bordetella pertussis in Bordetella parapertussis infection.

An outbreak of parapertussis was studied prospectively in 38 first and second grade pupils of an elementary school. Eleven (29%) children were confirmed to be culture positive for Bordetella parapertussis. Serum samples were collected from 31 children for assay of antibodies to filamentous hemagglutinin (FHA), pertactin (PRN), and pertussis toxin of Bordetella pertussis. At the first sampling, ten children were found to have a cough and 21 were asymptomatic. Of the latter, 12 remained asymptomatic and eight developed cough within 11 to 53 days (mean +/- standard deviation, 31 +/- 12 days) after sampling. One child was identified as culture positive for Bordetella pertussis and, thus, not included in the analysis of Bordetella parapertussis infection. The mean levels of IgC antibodies to FHA and PRN were significantly higher in the 12 asymptomatic children than in the eight children who later developed cough or in 20 healthy control children of the same age (for FHA, p = 0.009 and < 0.001, respectively; for PRN, p = 0.002 and 0.002, respectively). These preliminary data suggest that Bordetella parapertussis infection is more prevalent than documented, and that children with high levels of IgG antibodies to FHA and PRN can remain asymptomatic.

Detection of Bordetella pertussis by polymerase chain reaction and culture in the nasopharynx of erythromycin-treated infants with pertussis.

BACKGROUND: Pertussis is a highly contagious respiratory disease and the most serious effects occur in young infants. Recently it has been shown that rapid and highly specific PCR can be a useful diagnostic tool for detection of pertussis infection. To our knowledge there are no previous studies concerning the disappearance of Bordetella pertussis DNA from the nasopharynx during antimicrobial treatment. METHODS: We studied prospectively how rapidly live B. pertussis organisms and DNA of these bacteria disappear from the nasopharynx during erythromycin therapy in unvaccinated infants. Eighty-five nasopharyngeal swabs obtained from nine erythromycin-treated infants with pertussis on consecutive days during hospitalization were tested by PCR and culture. The PCR products were further analyzed by Southern hybridization. RESULTS: On the fourth day of treatment 56% of the samples were positive by culture and 89% by PCR, whereas after 7 days the rates were 0 and 56%, respectively. In seven of nine patients PCR remained positive for 1 to 7 days longer than culture. The follow-up study also showed the semiquantitative nature of the PCR assay. The intensity of the PCR products in agarose gel usually weakened with time during erythromycin therapy. CONCLUSIONS: The results of this study show that PCR assay can achieve the specific diagnosis of pertussis infection in a large proportion of infants even when antimicrobial treatment has killed the organisms and culture is no longer positive.

Pharmacokinetics of 2-fluorodideoxycytidine (2FddC) in patients infected with human immunodeficiency virus.

1. The aim of this study was to estimate an oral dosage regimen of 2FddC giving peak plasma drug concentrations close to the antiretroviral IC50 of 150 ng ml-1. 2. A total of 55 doses (40 intravenous infusions and 15 oral solutions) were given to 21 patients. One group (n = 6-11) received single doses of 0.01 mg kg-1 intravenously (i.v.), 0.1 mg kg-1 i.v. and 0.1 mg kg-1 orally (p.o.) in that order. The other group (n = 8-10) received single doses of 0.03 mg kg-1 i.v., 0.3 mg kg-1 i.v. and 0.3 mg kg-1 p.o. in that order. Blood and urine samples were collected up to 24 h after each dose for drug assay by h.p.l.c.-u.v. 3. The peak plasma concentrations of 2FddC were proportional to dosage across the range 0.03 to 0.3 mg kg-1. After intravenous dosing, the mean (%CV) volume of distribution was 60 (28) 1 and the mean (CV%) plasma clearance was 23 (23) 1 h-1. On average, 71% of the dose was recovered unchanged in urine and renal clearance exceeded concurrent creatinine clearance. 4. Plasma concentrations reached mean peaks of 37 and 96 ng ml-1 after oral doses of 0.1 and 0.3 mg kg-1, respectively. The mean absolute bioavailability was 50% within a 95% confidence interval of 20 to 80%. 5. The adverse events were usually mild or moderate in severity and were generally attributed to the disease rather than the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of an increased dietary intake of organic selenium on the resistance of rats to ionizing radiation, aflatoxin B1 and infection]. / Vliianie povyshennogo postupleniia organicheskogo selena s dietoi na rezistentnost' krys k vozdeistviiu ioniziruiushchego izlucheniia, aflatoksina-B1 i infektsii.

Varying concentrations of the selenium biological compound "Selena" were tested in animals subjected to the action of extremal factors simulating those that affected the population at the territories radiocontaminated as a result of the catastrophe at the Chernobyl NPS (131I and external irradiation in falling down doses). The death rate in the group of animals that were not given "Selena" comprised 30% during 6 months after irradiation, their body mass was 120 g lower as compared to the animals in the group of biological control; among the animals given 0.03 mg of selenium/day the death rate was 4 times lower.

Effect of intravenous lipid on human pancreatic secretion.

Parenteral alimentation, including intravenous fat, is sometimes used in the treatment of patients with pancreatitis, although the effect of intravenous fat on human pancreatic secretion has not been systematically studied. Intravenous fat, however, has been shown to stimulate pancreatic protein secretion in the dog. The purpose of these studies was to clarify the effect of intravenous fat on human pancreatic secretion. Pancreatic secretion was assessed by measurement of enzymes and bicarbonate in duodenal aspirate collected via a double-lumen tube from 6 healthy volunteers. Four studies were randomly conducted on different days. On day 1, graded concentrations of Intralipid (5%, 10%, and 20%) were given intravenously for 1 h each, while secretin (8.2 pmol . kg-1 . h-1) was given as a background. On day 2, the same doses of Intralipid were infused intravenously without secretin. On day 3, the same doses of Intralipid were perfused into the intestine, and, finally, on day 4, 20% Intralipid was given by intestinal infusion for 2 h while 10% Intralipid was infused intravenously during the second hour. Significant stimulation of enzyme secretion was observed only during the infusion of fat into the intestine, not after intravenous infusion at any concentration. Pancreatic enzyme secretion, stimulated by intraintestinal fat, was not significantly modified by simultaneous intravenous lipid infusion. We conclude that since intravenous fat does not stimulate pancreatic secretion, its use in conditions where pancreatic stimulation is undesirable appears safe.