Clinical rubella reinfection during pregnancy in a previously vaccinated woman.

We report a documented case of clinically apparent rubella reinfection during pregnancy with rubelliform rash and fever followed by lymphodenopathy at the 18th week of gestation, in a previously vaccinated woman with haemagglutination inhibition (HI) antibody titre of 1:32. The serological tests results (including neutralizing antibodies) demonstrated a significant rise in her rubella specific IgG level with strongly positive IgM reactivity. In addition, rubella-specific IgG antibody avidity testing displayed high avidity index (53-88%) typical of rubella reinfection. Umbilical cord blood, drawn by sonographic-guided cordocentesis at 24 weeks' gestation, was found to be negative for rubella-specific IgM antibody. The pregnancy was continued to term, and a healthy infant was born.

Placental transfer of maternal rubella antibodies to full-term and preterm infants.

Premature infants are vulnerable to infections, partly because of the low transplacental transfer of maternal antibodies. The present study investigated the placental transfer of maternal rubella-specific antibodies to full-term and preterm infants. The study group consisted of 133 healthy, native Israeli mothers and their 159 newborns. Of these, 69 were full-term infants (gestational age > 37 weeks) of 69 mothers, and 90 were preterm infants (gestational age < 35 weeks) of 64 mothers. Antibody titers against rubella were measured in maternal and umbilical cord blood samples by hemagglutination inhibition and microneutralization techniques. There was no significant difference in the level of protection and in geometrical mean titers by hemagglutination between the full-term and preterm groups. Conversely, significant differences in geometric mean titers of neutralizing antibodies were found between full-term and preterm infants, e.g., 65.9 and 39.8, respectively (P < 0.001). Very low birth weight preterm infants are at greater risk of rubella infection during the first year of life, due to the diminished transfer of neutralizing maternal antibodies. Therefore, earlier vaccination of this group may be beneficial.

Subclinical rubella reinfection during pregnancy followed by transmission of virus to the fetus.

We report a documented case of rubella reinfection during pregnancy in a previously vaccinated woman with residual antibody titre to rubella of 15 IU/ml. The reinfection occurred following an exposure to rubella virus (contact with 6-year-old daughter with clinical rubella) between the 7th and 10th week of pregnancy which resulted in transmission of the virus to the fetus. Umbilical cord blood drawn by cordocentesis was found to be strongly positive for rubella IgM antibody. After termination of the pregnancy rubella virus was isolated in cell culture from fetal tissues.

Rubella in pregnancy in Israel: 15 years of follow-up and remaining problems.

Despite extensive vaccination programs introduced in Israel since 1973, rubella virus continues to pose a threat to pregnant women. Screening for antibodies from women of childbearing age between 1980 and 1994 showed a decrease in seronegativity from 15.4% to 7% between the years 1980 and 1988, followed by an increase to 9.6% in 1991-92 due in part to the large wave of immigration from the former USSR, and a decrease back to 6.9% in 1993-94. The morbidity fluctuated, with peaks in 1983, 1987 and 1991, yielding a total of 219 cases in the target population of women of childbearing age. Additional problems encountered were reinfections, vaccine failures, and false positive results in screening. During the study period we confirmed 35 cases of reinfections in pregnancy, 19 of which resulted in delivery of healthy babies. In two of four cases of abortion following reinfection that we could follow, the fetus was infected. Immunization of 15-month-old babies introduced in 1989 and the new policy of two-dose vaccination introduced in 1995 are expected to further reduce the spread of rubella virus in the coming years.

Detection of rubella-specific IgM antibodies by the staphylococcal absorption method (SAM).

The use of SAM for the detection of rubella-specific IgM was evaluated in the sera of 318 rubella convalescents, 79 vaccinees and 53 infants with congenital rubella syndrome (CRS). The method employed was based on the use of crude inactivated suspension of Staphylococcus aureus strain Cowan I in the hemagglutination inhibition (HI) test and 1-h incubation of antigen and antibody. Among convalescents, 99% were found positive when tested within 30 days, and 84.6% were positive within 90 days following onset of clinical symptoms. Infants with CRS were 50 to 55% positive at the age of 0 to 6 months and 23% at the age of 7 to 11 months. Overnight incubation of antigen and antibody increased the proportion of positive results, particularly among sera of rubella vaccinees. No false-positives were detected among 1,035 healthy controls; nor in 40 patients following cytomegalovirus or Epstein-Barr virus infection, nor in 22 sera containing rheumatoid factor (RF). Comparison of SAM with a commercial enzyme-linked immunosorbent assay (ELISA) kit based on antibody capture showed 84% correlation between the two methods. Discrepancies were observed mainly in low-IgM.antibody-containing sera.

Perfusion of lung periphery: effects of local exposures to ozone and pressure.

Following ozone (O3) exposure, airways reactivity increases. We investigated the possibility that exposure to O3 causes a decrease in pulmonary perfusion, and that this decrease is associated with the increase in reactivity. Perfusion was measured with radiolabeled microspheres. A wedged bronchoscope was used to isolate sublobar segments in the middle and lower lobes of anesthetized dogs. Isolated segments were exposed to either O3 or an elevated alveolar pressure. Although increased alveolar pressure decreased microsphere density, exposure to 1 ppm O3 did not. Collateral system resistance rose significantly following exposure to O3 and to high pressure. These studies do not support the hypothesis that pulmonary perfusion is decreased following O3 exposure and is associated with subsequent increases in reactivity.

Interstitial fibrosis and collateral ventilation.

Interstitial fibrosis may increase resistance to collateral flow (Rcoll) because of decreased lung volume and destruction of collateral channels or it may decrease Rcoll because of emphysematous changes around fibrotic regions. In addition, if interstitial fibrosis involves a small region of lung periphery, interdependence from surrounding unaffected lung should produce relatively large changes in volume of the fibrotic region during lung inflation. We studied the effects of interstitial fibrosis on collateral airflow by measuring Rcoll at functional residual capacity (FRC) in nine mongrel dogs before and 28 days after the local instillation of bleomycin into selected lung segments. In six of these dogs Rcoll was also measured at a higher lung volume (transpulmonary pressure = 12 cmH2O above FRC pressure). Rcoll increased in fibrotic lung segments following local treatment with bleomycin. With lung inflation (high transpulmonary pressure) Rcoll fell a similar proportion in fibrotic and nonfibrotic lung regions. These observations suggest that collateral resistance increases in fibrotic segments because lung volume decreases or because collateral pathways are involved directly in the fibrotic process. Compensatory increases in collateral communications do not occur. In addition, pulmonary interdependence does not cause disproportionate increases in volume and decreases in Rcoll of the fibrotic region during lung inflation.

Bronchial blood flow affects recovery from constriction in dog lung periphery.

We investigated the effect of eliminating the bronchial circulation on recovery time from intravenous histamine challenge in canine lung periphery. Results from animals with intact bronchial circulations were compared with a second group in which the left lower lobe was isolated in situ. The pulmonary artery to this lobe was perfused and a bronchoscope was wedged in a small airway, which provided an index of resistance to airflow through the collateral system. The lobe was challenged with intravenous histamine, and the time constant of recovery (tau) from bronchoconstriction was measured. With or without pulmonary blood flow, elimination of the bronchial circulation increased tau 44.4 and 48.5%, respectively. This increase was similar to that found by stopping pulmonary blood flow alone (56.5%). Histamine challenges were also performed in sympathectomized or vagotomized animals with intact bronchial circulations. Neither of these conditions increased tau. We conclude that blood flow through the bronchial circulation affects the recovery time from intravenous histamine challenge in the lung periphery to a degree similar to that of the pulmonary circulation.

Pulmonary blood flow affects recovery from constriction in dog lung periphery.

The influence of blood flow through the pulmonary circulation on the time course of recovery of the lung periphery from challenge with three bronchoconstrictive agents was studied in dogs. The rate of perfusion of the left lower lobe was varied between 0 and 300 ml/min. A fiber-optic bronchoscope (OD = 5.5 mm) was wedged in a small airway in the same lobe, and resistance to airflow through the collateral system was continuously monitored. The lung was challenged with histamine aerosol for 1 min, or with intravenous boluses of histamine, acetylcholine, or methacholine. The time constant (tau) of recovery from each of the challenges was measured under the various pulmonary blood flow conditions. The mean tau of the recoveries from histamine was inversely related to the rate of blood flow. However, pulmonary blood flow had no effect on recovery from challenge with acetylcholine or methacholine, two agents metabolized by cholinesterase in lung tissue. From this study we conclude that recovery of the lung periphery from histamine is perfusion dependent, whereas recovery from acetylcholine or methacholine is perfusion independent. This suggests that the rate of blood flow through the pulmonary circulation could play an important role in recovery of the peripheral airways from certain mediators of bronchoconstriction.

Dry air-induced constriction in lung periphery: a canine model of exercise-induced asthma.

We studied the effects of the flow of dry air on collateral tone in the lung periphery. A bronchoscope was wedged in sublobar segments of anesthetized dogs, and measurements of collateral resistance (Rcs) were recorded before and after flow was increased from 200 to 2,000 ml/min for a 5-min period. Five minutes after exposure was completed, Rcs increased by an average of 117 +/- 25.2% (SE) over control. Maximum Rcs occurred 5 min after the challenge was concluded and required 48 +/- 10.5 min to return to base line. When flow rate was held constant and exposure period varied, Rcs increased with increased stimulus duration. With exposure times held constant, the response of the collateral system was positively associated with changes in stimulus strength (flow rate). No refractory period was observed with repetitive challenges. Finally, when dry air (delivered at 22 degrees C) and conditioned air (i.e., delivered at 28 degrees C; relative humidity = 80%) challenges were alternated in the same wedged segment, dry air produced a mean increase in Rcs of 93.2%, whereas challenge with warm moist air increased Rcs only 33.5%. Regardless of which challenge was presented first, dry air consistently produced a greater constrictor response. This response is similar to that observed in cold air- and exercise-induced asthma and indicates that the lung periphery in dogs, like larger airways in asthmatic subjects, has the potential to increase tone when exposed to dry air. Peripheral airways in dogs thus constitute a model that can be used for the investigation of exercise-induced asthma.

Effects of changes in abdominal pressure on left ventricular performance and regional blood flow.

Many clinical conditions are associated with an increase in abdominal pressure. While the effects on venous return have been studied in the past, little attention has been given to the effect of abdominal pressure on left-sided hemodynamic events. The effects of acute changes in abdominal pressure (Pab) on left ventricular (LV) hemodynamics and outflow distribution were evaluated in ten open-chest dogs, which had undergone right heart bypass to eliminate the influence of changes in Pab on systemic venous return. Pressures were measured in the left atrium (Pla), aorta (Pao), and stomach (Pab). Electromagnetic flow probes were positioned around the ascending aorta (Qaa), descending aorta (Qda) and the innominate or subclavian artery (Qin) to reflect total cardiac output and the respective regional caudad and cephalad blood flows. Compressing the abdomen to increase acutely Pab (9.2 +/- 0.6 torr) also significantly increased Pao (7.8 +/- 1.2 torr), Pla (1.7 +/- 0.4 torr), and Qin (15.2 +/- 4.5%), while Qaa (-9.5 +/- 2.0%) and Qda (-26.3 +/- 7.0%) significantly decreased. Opposite findings were obtained immediately after release of abdominal compression. Thus, an acute increase in Pab with a constant pulmonary artery inflow increased the afterload imposed on the left ventricle and redistributed LV output, with a reduction in flow to the abdomen. Part of the fall in Qaa and increase in Pla could be attributed to passive elevation of the diaphragm by the increase in Pab, i.e., heart-lung-diaphragm interdependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Tonic beta-sympathetic activity in the lung periphery in anesthetized dogs.

The present study was undertaken to determine whether beta-adrenoceptors could be physiologically detected in the lung periphery and whether they were under tonic stimulation in the resting state in anesthetized dogs. A fiberoptic bronchoscope was wedged in a sublobar segment of lung in anesthetized male mongrel dogs for measurement of resistance through the collateral system (Rcs). beta-Agents were delivered locally as aerosols through the bronchoscope, and the response was evaluated by changes in Rcs. Distilled water alone produced a mean increase of 8.5 +/- 2.43% (SE) in Rcs at 2 min in six dogs, whereas dl-isoproterenol produced a mean decrease of 8.9 +/- 2.10% (P less than 0.03), thus demonstrating the presence of submaximally stimulated beta-receptors. To test whether the beta-receptors were under tonic stimulation, we compared the effect of aerosolized d- and dl-propranolol in 5 dogs. d-Propranolol that lacks significant beta-blocking activity and dl-propranolol both produced large transient increases in Rcs. However, with d-propranolol, Rcs had returned to base line at 15 min, whereas with dl-propranolol Rcs remained elevated at a mean of 20% above base line for greater than 2 h (P less than 0.01). Local timolol aerosol also produced a sustained increase in Rcs. After pretreatment with reserpine or after bilateral adrenalectomy, both d- and dl-propranolol still produced large transient increases in Rcs, but dl-propranolol no longer produced a sustained increase. Neither isoproterenol nor atropine affected Rcs in the presence of dl-propranolol, nor did pretreatment with atropine affect the response of Rcs to dl-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of lung inflation on lung blood volume and pulmonary venous flow.

Phasic changes in lung blood volume (LBV) during the respiratory cycle may play an important role in the genesis of the respiratory wave in arterial pressure, or pulsus paradoxus. To better understand the effects of lung inflation on LBV, we studied the effect of changes in transpulmonary pressure (delta Ptp) on pulmonary venous flow (Qv) in eight isolated canine lungs with constant inflow. Inflation when the zone 2 condition was predominant resulted in transient decreases in Qv associated with increases in LBV. In contrast, inflation when the zone 3 condition was predominant resulted in transient increases in Qv associated with decreases in LBV. These findings are consistent with a model of the pulmonary vasculature that consists of alveolar and extra-alveolar vessels. Blood may be expelled from alveolar vessels but is retained in extra-alveolar vessels with each inflation. The net effect on LBV and thus on Qv is dependent on the zone conditions that predominate during inflation, with alveolar or extra-alveolar effects being greater when the zone 3 or zone 2 conditions predominate, respectively. Lung inflation may therefore result in either transiently augmented or diminished Qv. Phasic changes in left ventricular preload may therefore depend on the zone conditions of the lungs during the respiratory cycle. This may be an important modulator of respiratory variations in cardiac output and blood pressure.

Subclinical rubella in pregnancy--occurrence and outcome.

Between the years 1972 and 1979, 40,589 pregnant women were tested for rubella antibodies following suspected illness or exposure, using hemagglutination-inhibition (HI), complement fixation and staphylococcal absorption for determination of specific immunoglobulin M (IgM). Recent primary infection was confirmed by antibody rise in paired sera and/or the presence of specific IgM. Reinfection was differentiated from primary asymptomatic rubella by absence of specific IgM. Determination of neutralizing antibodies was also useful in confirming reinfections. Clinical rubella was confirmed in 1,448 patients (3.6%). In 154 cases asymptomatic rubella infection was detected; 98 had primary infection and 56 experienced reinfection. In a selected group of 2,200 women exposed to confirmed rubella, 6.8% had clinical rubella, 3.8% asymptomatic infection, and in 7.1% the results were doubtful. Reinfection was detected in 12.4% of 265 women with initially low HI titers. The prospective follow-up on pregnancy outcome was available in 87 women with asymptomatic infection. Seven cases of congenital rubella were detected in the group of primary infections, while all 25 children born following reinfection were healthy.

Local vagal responses in the lung periphery.

In previous work we studied responses to ozone (O3) in the lung periphery of anesthetized male mongrel dogs. O3 (0.1 ppm) delivered locally to the lung periphery through a bronchoscope wedged in a segmental airway increased collateral resistance (Rcs) 31.5 +/- 5%. Bilateral cervical vagotomy or pretreatment with atropine aerosol prevented these responses to O3. In the present study we asked two questions. First, is the vagus necessary for responses to 0.1 ppm O3 because it maintains base-line tone? Second, are physiological responses to O3 administered through a bronchoscope localized to the challenged region? To answer the first question, we increased base-line Rcs (38.4 +/- 11.8%) by administering an acetylcholinesterase inhibitor, neostigmine (aerosol), through the bronchoscope. Following neostigmine, O3 exposure increased Rcs (55.8 +/- 18.4%) only if the vagi were intact. To answer the second question, we introduced two bronchoscopes simultaneously into different regions of the lung. When O3 was delivered through one bronchoscope, responses were detected only in the exposed region. However, when the whole left lung was exposed to O3, the responses were also detected in the right lung, but only when the vagi were intact. We conclude that the lung has the capacity to respond to localized oxidant insult with vagally mediated responses limited to the region that is challenged. However, when a larger area is exposed, vagally mediated responses become generalized and affect both lungs.

Maintenance of muscarinic tone after vagotomy in the lung periphery.

We developed a method for maintaining muscarinic tone in a small region of the lung periphery after vagotomy. A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs and was used to deliver aerosols of distilled water (0.1 ml), neostigmine (0.022 mg), atropine (0.1 mg), and histamine (1.5 X 10(-4) mg). Measurements of resistance through the collateral system (Rcs) were used to monitor responses to these agents. Rcs increased 37.0 +/- 5.0% (mean +/- SE) after the administration of neostigmine and remained elevated for at least 50 min. The administration of neostigmine in vagotomized animals or in those where the obstructed lung segment was pretreated with atropine resulted in a small increase in Rcs that lasted only 2 min. When bilateral vagotomy was performed 10 min after neostigmine administration Rcs remained elevated for at least another 80 min. However, Rcs returned to baseline when atropine was administered 20 min after vagotomy, but increased when histamine was administered 50 min after atropine. We conclude that after neostigmine administration, parasympathetic tone, dependent on mediators released from the vagus nerve, can be maintained in the lung periphery after vagotomy.

A re-evaluation of the hemodynamic consequences of intermittent positive pressure ventilation.

The hemodynamic effects of intermittent positive pressure ventilation (IPPV) have generally been considered straightforward, being dominated by the inspiratory reduction in systemic venous return. Paradoxically, there is considerable debate regarding the effects of PEEP. We have studied both right ventricular (RV) and left ventricular (LV) performance during a single IPPV respiratory cycle in dogs with intact circulatory systems or the right heart bypassed in open and closed chest conditions. We have found that the "reverse pulsus paradoxus" during inspiration reflects both transmission of the increased intrathoracic pressure to the thoracic aorta and an increase in LV stroke volume (SV). This inspiratory increase in LVSV has been found to be influenced by, but not dependent on: (a) respiratory variations in RVSV; (b) variations in functional residual capacity or tidal volume altering pulmonary venous return and the degree of physical compression of the heart by the lungs; (c) an inspiratory decrease in RV volume, increasing LV diastolic compliance and, thus, probably improving pulmonary venous return; (d) a decreased transmural aortic diastole pressure reflecting an effective decrease in LV afterload produced by both the general increase in intrathoracic pressure and the direct compression of the heart; and (e) variations in the pulmonary vascular volume as indicated by changes in the transmural LV end-diastolic pressure. An understanding of IPPV during a single respiratory cycle facilitates an appreciation of the steady state hemodynamic effects of IPPV with or without PEEP. Our results imply that measurements made only at end-expiration, ignoring inspiratory events, may have serious limitations. Furthermore, they suggest that IPPV with PEEP should be evaluated as a form of LV assist in LV failure.

Susceptibility to rubella and borderline immunity.

Immunity to rubella in women of childbearing age has been determined by hemagglutination inhibition (HI) and/or hemolysis in gel (HIG) methods. Susceptibility was defined as absence of antibody at a dilution of 1:16 in HI and a hemolysis zone of less than 7 mm in HIG tests. In screening 30,330 women during the years 1980-81, 13.7% were found seronegative. Among 439 women immunized with RA-27/3 vaccine, 92% showed seroconversion, when tested by HI greater than or equal to 2 months following vaccination. Paired sera from 35 vaccines who remained seronegative were tested by two additional methods: sensitizing antibody (SA) and enzyme-linked immunosorbent assay (ELISA). Ten women were confirmed as vaccine failures by these two methods. The remaining women presented the following results: 19 had borderline and stable titers in their paired sera and 6 showed seroconversion, by SA and ELISA. These results indicate that both SA and ELISA are more sensitive than the HI and HIG tests for evaluation of rubella immunity and response to vaccination.