ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19.

BACKGROUND: COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration. OBJECTIVE: To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality. METHODS: A retrospective, single-centre study of 558 hospital inpatients with confirmed COVID-19 admitted from 1 March to 30 April 2020, followed up until 24 May 2020. AKI and macrovascular thrombosis were primary end-points, and in-hospital mortality was a secondary end-point. RESULTS: AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, and 200 (35.9%) died. Overlap propensity score-weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified end-points. On exploratory analysis, severe chronic kidney disease (CKD) increases odds of macrovascular thrombi (OR: 8.237, 95% CI: 1.689-40.181, P = 0.009). The risk of AKI increased with advancing age (OR: 1.028, 95% CI: 1.011-1.044, P = 0.001) and diabetes (OR: 1.675, 95% CI: 1.065-2.633, P = 0.025). Immunosuppression was associated with lower risk of AKI (OR: 0.160, 95% CI: 0.029-0.886, P = 0.036). Advancing age, dependence on care, male gender and eGFR < 60 mL min-1 /1.73 m2 increased odds of in-hospital mortality. CONCLUSION: We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.

Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs.

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.

Hypertonicity, but not hypothermia, elicits substance P release from rat C-fiber neurons in primary culture.

Isocapnic dry gas hyperventilation provokes hyperpnea-induced bronchoconstriction in guinea pigs by releasing tachykinins from airway sensory C-fiber neurons. It is unknown whether dry gas hyperpnea directly stimulates C-fibers to release tachykinins, or whether this physical stimulus initiates a mediator cascade that indirectly stimulates C-fiber tachykinin release. We tested the hypotheses that mucosal hypothermia and/or hyperosmolarity--physical consequences of airway heat and water loss imposed by dry gas hyperpnea--can directly stimulate C-fiber tachykinin release. Neurons isolated from neonatal rat dorsal root ganglia were maintained in primary culture for 1 wk. Cells were then exposed for 30 min at 37 degrees C to graded concentrations of NaCl, mannitol, sucrose, or glycerol (0-600 mOsm) added to isotonic medium, or to isotonic medium at 25 degrees C without or with 462 mOsm mannitol added. Fractional release of substance P (SP) was calculated from supernatant and intracellular SP contents following exposure. Hyperosmolar solutions containing excess NaCl, mannitol, or sucrose all increased fractional SP release equivalently, in an osmolarity-dependent fashion. In marked contrast, hypothermia had no effect on fractional SP release under isotonic or hypertonic conditions. Thus, hyperosmolarity, but not hypothermia, can directly stimulate tachykinin release from cultured rat sensory C-fibers. The lack of effect of glycerol, a solute which quickly crosses cell membranes, suggests that neuronal volume change represents the physical stimulus transduced by C-fibers during hyperosmolar exposure.

Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension.

Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway leading to prostacyclin (PGI2) production. Patients with severe pulmonary hypertension have a PGIS deficiency of their precapillary vessels, but the importance of this deficiency for lung vascular remodeling remains unclear. We hypothesized that selective pulmonary overexpression of PGIS may prevent the development of pulmonary hypertension. To study this hypothesis, transgenic mice were created with selective pulmonary PGIS overexpression using a construct of the 3.7-kb human surfactant protein-C (SP-C) promoter and the rat PGIS cDNA. Transgenic mice (Tg+) and nontransgenic littermates (Tg-) were subjected to a simulated altitude of 17,000 ft for 5 weeks, and right ventricular systolic pressure (RVSP) was measured. Histology was performed on the lungs. The Tg+ mice produced 2-fold more pulmonary 6-keto prostaglandin F1alpha (PGF1alpha) levels than did Tg- mice. After exposure to chronic hypobaric hypoxia, Tg+ mice have lower RVSP than do Tg- mice. Histologic examination of the lungs revealed nearly normal arteriolar vessels in the Tg+ mice in comparison with vessel wall hypertrophy in the Tg- mice. These studies demonstrate that Tg+ mice were protected from the development of pulmonary hypertension after exposure to chronic hypobaric hypoxia. We conclude that PGIS plays a major role in modifying the pulmonary vascular response to chronic hypoxia. This has important implications for the pathogenesis and treatment of severe pulmonary hypertension.

Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis.

Primary pulmonary hypertension (PPH) is a disease of unknown etiology characterized by lumen-obliterating endothelial cell proliferation and vascular smooth muscle hypertrophy of the small precapillary pulmonary arteries. Because the vascular lesions are homogeneously distributed throughout the entire lung, we propose that a tissue fragment of the lung is representative of the whole lung. RNA extracted from the fragments is likely to provide meaningful information regarding the changes in gene expression pattern in PPH when compared with structurally normal lung tissue. We hypothesize that the lung tissue gene expression pattern of patients with PPH has a characteristic profile when compared with the gene expression pattern of structurally normal lungs and that this characteristic gene expression profile provides new insights into the pathobiology of PPH. Using oligonucleotide microarray technology, we characterized the expression pattern in the lung tissue obtained from 6 patients with primary pulmonary hypertension (PPH)-including 2 patients with the familial form of PPH (FPPH)-and from 6 patients with histologically normal lungs. For the data analysis, gene clusters were generated and the gene expression pattern differences between PPH and normal lung tissue and between PPH and FPPH lung tissue were compared. All PPH lung tissue samples showed a decreased expression of genes encoding several kinases and phosphatases, whereas several oncogenes and genes coding for ion channel proteins were upregulated in their expression. Importantly, we could distinguish by pattern comparison between sporadic PPH and FPPH, because alterations in the expression of transforming growth factor-beta receptor III, bone morphogenic protein 2, mitogen-activated protein kinase kinase 5, RACK 1, apolipoprotein C-III, and the gene encoding the laminin receptor 1 were only found in the samples from patients with sporadic PPH, but not in FPPH samples. We conclude that the microarray gene expression technique is a new and useful molecular tool that provides novel information pertinent to a better characterization and understanding of the pathobiology of the distinct clinical phenotypes of pulmonary hypertension.

Detection of salivary immunoglobulin A antibodies to HIV-1 in infants and children.

Secretory immunoglobulin A (slgA) antibodies of non-maternal origin are present in newborns and slgA to HIV-1 antigens has been detected in infected adults. In this study we investigated the presence of HIV-1-specific IgA in saliva from 41 children (aged 1 day-46 months) born to women at risk for HIV-1 infection. Saliva samples were assayed for HIV-1 antibodies with IgA-specific Western blot. The samples from 10 out of 11 children with subsequently proven infection, including one aged 6 months, demonstrated IgA antibodies to HIV-1 envelope antigens. Samples from infants under 15 months, who were born to infected mothers and subsequently shown to be uninfected, were slgA negative. Of the 12 children with continued indeterminate HIV-1 status, eight showed neither slgA nor serologic evidence of infection and four showed slgA antibodies. HIV-1-specific slgA was detectable before the age of 15 months and may prove to be valuable in the diagnosis of HIV-1 infection in infants.

Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV. Perinatal AIDS Collaborative Transmission Studies.

OBJECTIVES: To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine. DESIGN: Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities. METHODS: The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics. RESULTS: The overall transmission risk was 18% [95% confidence interval (CI), 16-21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6-2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4-2.2), maternal CD4+ lymphocyte count < 500 x 10(6) cells/l (RR, 1.7; 95% CI, 1.3-2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3-2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4-0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors. CONCLUSIONS: Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

Hormonal control of pubertal spermatogenesis.

The spermatogenic process of normal rats at 20, 32, and 44 days of age was characterized. Variations in numbers of degenerating and abnormal cells were noted during the cycle in most age groups, indicating a stage-related vulnerability of these cells. The most advanced cell types that were seen at a particular age were frequently abnormal or degenerating. When the numbers of viable cells available to degenerate were considered, the degeneration rate in normal pubertal animals was about 15, 10, and 2 times greater in 20-, 32-, and 44-day-old animals, respectively, than in 75-day-old animals. In 32-day-old rats, neither hypophysectomy nor hypophysectomy and subsequent hormone supplementation resulted in an alteration in the qualitative pattern of germ cell degeneration during the spermatogenic cycle compared with that in the normal animal; however, the treatments did alter the quantitative response of cellular degeneration. Three days posthypophysectomy there was a marked increase in the numbers of total degenerating germ cells. FSH (60 micrograms) given twice daily (as were all hormones) reduced the numbers of degenerating cells significantly, as did LH (13 micrograms). Low dose LH (0.3 micrograms), representing the approximate contaminating dose of LH in the 60-micrograms FSH preparation, and low dose FSH (30 micrograms) did not elicit a response significantly different from that to hypophysectomy alone. LH (13 micrograms) plus FSH (60 micrograms) reduced the levels of degenerating cells such that there was no significant difference from levels in intact 32-day-old rats. The data indicated, for the cell types studied, a lack of specificity of various hormones or hormone combinations in the survival of specific germ cell types. It emphasizes the importance of FSH in pubertal spermatogenesis as well as the synergistic actions of LH and FSH.

Maternal and neonatal characteristics associated with HIV infection in infants of seropositive women.

In this prospective study of infants born to human immunodeficiency virus (HIV) seropositive mothers, neonatal and maternal characteristics of infected and noninfected infants were compared to determine the factors that may be associated with or contribute to vertical transmission of HIV. Of 134 infants entered as newborns in the study, 31 have definite serological and/or clinical evidence of infection and 103 are considered noninfected (transmission rate, 23.1%). Significantly more of the infected infants had birth weights below 2,500 g (48.4% versus 22.3%), and more infected infants were found to be small for gestational age (16.2% versus 5.8%). A greater number of infected infants experienced two or more problems in the neonatal period than noninfected infants (51.6% versus 24.2%). The incidence of confirmed and suspected bacterial infections was also significantly increased in the infected group. Multiple logistic regression analysis indicated low birth weight had the strongest association with vertical transmission of HIV. There was no significant difference between the two groups in mean maternal age at first pregnancy, mother's marital status, education, type of family, or past history of type of substances abused. Mothers who transmitted HIV to their infants had a trend towards a higher frequency of clinical chorioamnionitis (16.1% versus 5.8%), reported sexually transmitted diseases during pregnancy (45.2% versus 22.3%), and continued illicit drug use (67.7% versus 49.0%). In this group of infants, low birth weight, poor intrauterine growth, neonatal infections and possibly maternal chorioamnionitis, STDs during pregnancy, and continued drug use are associated with vertical transmission of HIV.

High prevalence of genital tract papillomavirus infection in female adolescents.

To investigate clinical condyloma, abnormal cervical cytologic findings, and evidence of human papillomavirus infections, 89 adolescent girls were examined. Cellular DNAs extracted from exfoliated cervical cells were examined for human papillomavirus genomic sequences by Southern transfer hybridization using 32P-labeled human papillomavirus DNA probes. Human papillomavirus sequences were detected in 12 (13%) young women, abnormal cytologic specimens in 21 (24%), and vulvar condylomas in 12 (13%). The human papillomavirus types identified included HPV-6/11 (four instances), which is known to be associated with benign lesions, and HPV-16, -18, and -31 (eight instances) which are considered to have oncogenic potential. Two young women were infected with both HPV-16 and -31. Human papillomavirus sequences were found in 48% of the young women with abnormal cytologic findings and in 3% of patients with normal cytologic findings (P less than .0001). Condylomatous changes in the cervical smear were associated with the presence of HPV-6/11 and mild dysplasia with the presence of HPV-16, -18, and -31. The presence of vulvar condylomas correlated with condylomatous changes in the cervical smear and with the recovery of HPV-6/11 from the cervical epithelium. The results indicate that the prevalence of human papillomavirus infections in this population is high and that a majority of the infections are with viruses associated with lower genital tract malignancies.

Role of eicosanoids in hyperpnea-induced airway responses in guinea pigs.

Guinea pigs mechanically hyperventilated with dry gas exhibit hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH). Tachykinins released from airway C-fiber neurons are the central mediators of guinea pig HIB but play only a contributory role in HIBVH. Recent studies suggest that eicosanoid mediators can provoke bronchoconstriction and bronchovascular hyperpermeability, are released by dry gas hyperpnea, and can themselves elicit or modulate tachykinin release. We therefore hypothesized that eicosanoids may participate in HIB and/or HIBVH. To test these hypotheses, we analyzed respiratory system resistance changes and Evans blue-labeled albumin extravasation into the airways of 60 tracheostomized and mechanically ventilated guinea pigs. Animals were subjected to 10 min of isocapnic dry gas hyperpnea or to quiet breathing of humidified gas and received as pretreatment either piroxicam, a cyclooxygenase (CO) inhibitor; A-63162, a 5-lipoxygenase (5-LO) inhibitor; BW-755c, a combined CO and 5-LO inhibitor; ICI-198,615, a leukotriene D4 receptor antagonist; or no drug. HIB was substantially (50-80%) reduced by each of the four eicosanoid-modulating drugs. In contrast, HIBVH was reduced only by BW-755c, and this effect occurred only within the extrapulmonary airways (42% reduction). These data indicate that both CO and 5-LO products, including leukotriene D4, participate in the pathogenesis of HIB but that, like tachykinins, they play only a small contributory role in HIBVH. Together with our previous demonstration that sensory neuropeptide release is critical for the occurrence of HIB, we conclude that the roles of eicosanoids and tachykinins in guinea pig HIB are interdependent.

Time course of bronchoconstriction induced by dry gas hyperpnea in guinea pigs.

We examined the effects of hyperpnea duration and abrupt changes in inspired gas heat and water content on the magnitude and time course of hyperpnea-induced bronchoconstriction (HIB) in anesthetized mechanically ventilated male Hartley guinea pigs. In 12 animals subjected to 5, 10, and 15 min (random order) of dry gas isocapnic hyperpnea [tidal volume (VT) 4-6 ml, 150 breaths/min) followed by quiet breathing of humidified air (VT 2-3 ml, 60 breaths/min), severe bronchoconstriction developed only after the cessation of hyperpnea; the magnitude of respiratory system resistance (Rrs) increased with the duration of dry gas hyperpnea [peak Rrs 1.0 +/- 0.2, 1.8 +/- 0.3, and 2.3 +/- 0.3 (SE) cmH2O.ml-1.s, respectively]. Seven other guinea pigs received, in random order, 10 min of warm humidified gas hyperpnea, 10 min of room temperature dry gas hyperpnea, and 5 min of dry gas hyperpnea immediately followed by 5 min of warm humidified gas hyperpnea. After each hyperpnea period, the animal was returned to quiet breathing of humidified gas. Rrs rose appreciably after the 10 min of dry and 5 min of dry-5 min of humidified hyperpnea challenges (peak Rrs 1.3 +/- 0.2 and 0.7 +/- 0.2 cmH2O.ml-1.s, respectively) but not after 10 min of humidified hyperpnea (0.2 +/- 0.04 cmH2O.ml-1.s). An additional five animals received 10 min of room temperature dry gas hyperpnea followed by quiet breathing of warm humidified air and 10 min of room temperature dry gas hyperpnea followed by 30 min of warm humidified gas hyperpnea in random order.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind randomized study comparing amoxicillin and erythromycin for the treatment of Chlamydia trachomatis in pregnancy.

OBJECTIVE: To compare the efficacy and patient tolerance of amoxicillin to that of erythromycin in the treatment of lower genital tract chlamydia infections during pregnancy. METHODS: A double-blind, randomized study was conducted comparing oral amoxicillin 500 mg three times daily versus oral erythromycin 500 mg four times daily for 7 days. One hundred forty-three women with positive cervical cultures for chlamydia at less than 36 weeks' gestation were enrolled. A test-of-cure culture was obtained 4 weeks after entry into the study and side effects were assessed. Success of the regimen was defined as completing the course of medication and having a negative test-of-cure culture. RESULTS: Thirty of the 65 women in the erythromycin group (46.1%) developed symptoms while taking the medication and 15 of them were unable to continue treatment (23.1%). In contrast, five of the 65 women (7.7%) in the amoxicillin group became symptomatic, with only one of these patients intolerant of the side effects (1.5%) (P < .001). Of the 50 patients in the erythromycin group who were able to complete their course of medication, only three had a positive test of cure (6.0%). In comparison, nine of the 64 patients (14.1%) taking amoxicillin who completed their course had positive cultures at test of cure. This difference was not statistically significant (P = .14). Forty-seven of the 65 patients (72.3%) in the erythromycin group successfully completed their regimen, compared to 55 of the 65 women (84.6%) in the amoxicillin group. This difference was not statistically significant. CONCLUSIONS: These findings suggest that amoxicillin is a reasonable alternative for the treatment of chlamydia in pregnant patients intolerant to erythromycin. The incidence of side effects and intolerance to therapy for amoxicillin are less than those for erythromycin.

Second trimester abortion using prostaglandin E2 suppositories with or without intracervical Laminaria japonica: a randomized study.

OBJECTIVE: To compare the abortifacient efficacy of vaginal prostaglandin (PG) E2 suppositories with and without pretreatment with intracervical PGE2 gel and Laminaria japonica. METHODS: One hundred seventy-five women between 16 and 20 weeks' gestation requesting abortion were divided randomly into three groups. Forty-one received PGE2 vaginal suppositories alone to induce abortion, 72 had Laminaria placed 24 hours before vaginal PGE2, and 62 were given intracervical 0.5 mg PGE2 gel plus Laminaria 24 hours before vaginal PGE2. Maternal demographic characteristics, induction to delivery time, number of suppositories required, and complications were analyzed. RESULTS: The mean maternal age, gravidity, parity, race, and gestational age were similar among groups. Ninety-five percent of all women delivered within 24 hours. The induction to delivery time was significantly longer in the PGE2-only women (mean +/- standard deviation 689+/-319 minutes) compared with that of those receiving PGE2 plus Laminaria (487+/-321 minutes) and PGE2 plus Laminaria plus gel (547 +/-374 minutes, P = .01). There was a statistically significant difference in the number of suppositories needed to complete the abortion process. The PGE2-only group required more suppositories (median three, range 1-8) compared with PGE2 plus Laminaria (median 3, range 1-3) and PGE2 plus Laminaria plus gel (median 2.5, range 1-9; P = .001). Patients in the PGE2 plus Laminaria plus gel group reported more pain associated with placement (median pain score 4, range 0-10) compared with PGE2 plus Laminaria (median 2, range 0-9; P = .003). There was a lower incidence of febrile episodes in the PGE2-only group (29%) compared with PGE2 plus Laminaria (68%) and PGE2 plus Laminaria plus gel (54%, P = .002). CONCLUSION: Placement of Laminaria japonica 24 hours before PGE2 vaginal suppository-induced abortion resulted in a significantly shorter induction-to-delivery time, and pretreatment with Laminaria japonica decreased the number of suppositories required to complete abortion. Pretreatment with intracervical PGE2 gel increased pain associated with Laminaria placement and did not improve the efficacy of the procedure.

Interactions of human immunodeficiency virus infection and pregnancy.

OBJECTIVE: To assess the influence of human immunodeficiency virus (HIV) infection on pregnancy outcome and the effect of pregnancy on the short-term course of HIV infection. METHODS: Pregnant women with identified risk factors for HIV infection but without AIDS were tested serologically for HIV antibodies. Seropositive women were compared to seronegative patients with similar risk factors and demographic characteristics at enrollment, at delivery, and 6-8 weeks postpartum. One hundred one seropositive and 97 seronegative subjects were evaluated for symptoms or physical manifestations of HIV infection; evidence of immune dysfunction; historical, physical, or laboratory evidence of related infections; and maternal and neonatal outcome. Both groups were compared to the entire obstetric population delivering at the University of Maryland Hospital during 1 year. RESULTS: There was a significant reduction in reported risk behaviors in both groups during pregnancy as compared to the period before pregnancy (P < .001). The majority of women in both groups were asymptomatic, but seropositive women were more likely to have a history or physical evidence of condylomata (13 versus 4%; P < .05) and higher temperatures on admission to the labor suite (98.6 +/- 1.0 versus 98.3 +/- 0.8F; P = .02). Seropositive women were not at greater risk for antepartum medical complications. Only one woman developed an AIDS-defining opportunistic infection. Although hematologic indices in seropositive women were abnormal, these did not progress over the course of pregnancy. At delivery, seropositive women were more likely to receive antibiotics (25 versus 10%; P = .006) and less likely to have an episiotomy (25 versus 40%; P = .03), but obstetric outcome was unaffected. Neonatal status was independent of antibody status. CONCLUSION: Our findings support a growing body of evidence that pregnancy has no discernible effect on the early progression of HIV disease in asymptomatic women, and infection does not influence perinatal outcome.

Role of tachykinins in hyperpnea-induced bronchovascular hyperpermeability in guinea pigs.

Isocapnic dry gas hyperpnea causes bronchoconstriction in guinea pigs that is mediated by release of tachykinins from airway sensory nerves. Exogenous neuropeptides can induce microvascular leak. Therefore we tested whether dry gas hyperpnea also elicits bronchovascular hyperpermeability by measuring Evans blue-labeled albumin extravasation along the airways of mechanically ventilated guinea pigs. We found that 1) room temperature dry gas hyperpnea increased Evans blue extravasation in extrapulmonary and intrapulmonary airways as a specific consequence of local airway heat/water losses, 2) capsaicin pretreatment ablated the bronchoconstrictor response to dry gas hyperpnea and reduced bronchovascular leak only in intrapulmonary airways, 3) phosphoramidon given to capsaicin-pretreated animals partially restored dry gas hyperpnea-induced bronchoconstriction and increased the vascular hyperpermeability response to hyperpnea in intrapulmonary airways, and 4) propranolol administration had no important effects on any of these airway responses. We conclude that dry gas hyperpnea causes bronchovascular hyperpermeability in guinea pigs. Tachykinins have a dominant role in this response in the intrapulmonary airways, although another mechanism may also contribute to the microvascular leak in the extrapulmonary airways.

Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pigs.

Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of stimulation. We tested whether dry gas HIB is also increased in newborn guinea pigs (NGPs). We quantified HIB as the fractional increase of respiratory system resistance (Rrs) over baseline (BL) in five 4- to 7-day-old NGPs after 10 min of hyperpnea, as well as changes in Rrs elicited by intravenous methacholine or capsaicin, and compared these responses with those of AGPs. During hyperpnea, analogous stimuli were delivered by mechanically imposing hyperpnea at 3.0, 4.5, and 6.0 times quiet eucapnic minute ventilation (VE). In AGPs, hyperpnea caused significant bronchoconstriction that increased with VE; peak fractional increase of Rrs was 7.6 +/- 2.0 times BL. In contrast, hyperpnea caused insignificant bronchoconstriction in NGPs (1.4 +/- 0.2 times BL after the largest VE; P < 0.05 vs. AGP). Responses elicited by methacholine (10(-10)-10(-7) mol/kg) or capsaicin (0.01-10.0 microgram/kg) were similar in NGPs and AGPs. In AGPs, hyperpnea suppressed HIB until posthyperpnea. To determine whether the reduced HIB of NGPs was caused by enhanced suppression, NGPs and AGPs were administered acetylcholine (10(-10)-10(-7) mol/kg i.v.) during BL eucapnic ventilation and during eucapnic hyperpnea with warm humidified gas. Responses to acetylcholine were suppressed in AGPs and NGPs to a similar degree. We conclude that HIB is markedly diminished shortly after birth in guinea pigs and that it increases substantially during maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of airway narrowing during hyperpnea-induced bronchoconstriction in guinea pigs.

Increasing minute ventilation of dry gas shifts the principal burden of respiratory heat and water losses from more proximal airway to airways farther into the lung. If these local thermal transfers determine the local stimulus for bronchoconstriction, then increasing minute ventilation of dry gas might also extend the zone of airway narrowing farther into the lung during hyperpnea-induced bronchoconstriction (HIB). We tested this hypothesis by comparing tantalum bronchograms in tracheostomized guinea pigs before and during bronchoconstriction induced by dry gas hyperpnea, intravenous methacholine, and intravenous capsaicin. In eight animals subjected to 5 min of dry gas isocapnic hyperpnea [tidal volume (VT) = 2-5 ml, 150 breaths/min], there was little change in the diameter of the trachea or the main stem bronchi up to 0.75 cm past the main carina (zone 1). In contrast, bronchi from 0.75 to 1.50 cm past the main carina (zone 2) narrowed progressively at all minute ventilations greater than or equal to 300 ml/min (VT = 2 ml). More distal bronchi (1.50-3.10 cm past the main carina; zone 3) did not narrow significantly until minute ventilation was raised to 450 ml/min (VT = 3 ml). The estimated VT during hyperpnea needed to elicit a 50% reduction in airway diameter was significantly higher in zone 3 bronchi [4.3 +/- 0.8 (SD) ml] than in zone 2 bronchi (3.5 +/- 1.1 ml, P less than 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

Toxoplasmosis and parvovirus B19.

Pregnant women might well improve their chances for a successful pregnancy outcome by following the advice of W. C. Fields: avoid contact with small children and animals whenever possible. Failing widespread acceptance of this philosophy, management of T. gondii and parvovirus B19 infections continues to be a challenge for the foreseeable future.

Ovarian pregnancy diagnosed after a failed midtrimester therapeutic abortion. A case report.

Ovarian pregnancy is a rare phenomenon. Its presentation often is difficult to distinguish from that of tubal ectopic pregnancy and hemorrhagic ovarian cyst. A patient had an ovarian pregnancy diagnosed following failed midtrimester therapeutic abortion in a suspected bicornuate uterus. Despite vaginal prostaglandin suppositories and intraamniotic instillation of urea and prostaglandin, neither the abortion process nor rupture of the ovarian pregnancy ensued. This is the first reported case of this most unusual presentation of ovarian pregnancy.