Biomedical subjects

G Lambert

Publications and source records attributed to G Lambert.

At least 109 records · Page 6Linked to original sources

PubMed1996

Reactions of the middle meningeal artery of the cat to neural and humoral stimulation.

The physiology and pharmacology of the middle meningeal artery was investigated in cats in order to determine whether this artery was subject to normal neural and humoral control mechanisms. Carotid and middle meningeal arterial blood flows and resistances were measured in 16 cats anaesthetized with chloralose. The cervical sympathetic nerves were stimulated electrically. Stimulation of the cervical sympathetic nerves pre-ganglionically reduced blood flow in the middle meningeal artery by producing vasoconstriction in its resistance bed. The vasoconstriction was mediated via catecholamine-containing nerves, as it was abolished by prior intravenous administration of bretylium. Intravenous injections of noradrenaline or adrenaline also produced vasoconstriction in the middle meningeal arterial bed. 5-Hydroxytryptamine (5HT), on the other hand, produced a dilatation in the middle meningeal artery. We conclude that neurally or humorally released catecholamines can provide a plausible mechanism for vasoconstriction in the middle meningeal artery. The dilator effect of 5HT contrasts with the constrictor effect of the 5HT1-like receptor agonist sumatriptan and suggests a complex 5HT receptor pharmacology for the artery.

Adrenergic Fibers↗

PubMed1996

Heterosexual behavior during pregnancy and perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the relationship between maternal heterosexual activity during pregnancy and perinatal transmission of HIV-1. DESIGN: A retrospective analysis of 175 New York City HIV-1-seropositive women enrolled during pregnancy or immediately post-partum from 1986 to 1994 in a prospective cohort study. METHODS: Frequency of heterosexual intercourse and condom use during pregnancy was determined from self-report measures. Unprotected intercourse was defined as follows: 'none', consistent condom use or abstinence; 'moderate', inconsistent condom use and fewer than 80 episodes of intercourse; and 'high', inconsistent condom use and 80 or more episodes. RESULTS: The rate of perinatal HIV-1 transmission was 9.1% (four out of 44) among women with no unprotected intercourse during pregnancy, 22.2% (20 out of 90) among those with moderate frequency, and 39.0% (16 out of 41) among those with high frequency (P < 0.01). The relative risk (RR) of perinatal transmission was higher among women with moderate [RR, 2.4; 95% confidence interval (Cl), 0.9-6.7] and high frequency of unprotected sexual intercourse (RR, 4.3; 95% Cl, 1.6-11.8) compared with women with no unprotected sexual intercourse. When potential covariates (maternal injecting drug use, CD4 lymphocyte count, AIDS, zidovudine use, pelvic inflammatory disease or sexually transmitted disease during pregnancy, delivery mode, and extreme prematurity) were included in a logistic regression model (n = 128), the rate of perinatal transmission remained significantly higher among women with any unprotected sexual intercourse during pregnancy. CONCLUSIONS: Data suggest that unprotected sexual intercourse during pregnancy influences perinatal HIV-1 transmission.

Bias↗

PubMed1996

Autoregulation in the middle meningeal artery.

In cats anesthetized with alpha-chloralose, autoregulation of blood flow (F) in the middle meningeal and common carotid arteries was assessed by bleeding and subsequently reinfusing the animals to achieve a 25% step reduction in mean arterial blood pressure (P), while maintaining the systolic blood pressure >80 mmHg. The integrity of autoregulation was assessed by calculating the gain factor Gf = 1 - [(deltaF/F)/(deltaP/P)]. Cats were examined intact, after hexamethonium (10 mg/kg), and after papaverine (6 mg/kg). Reduction of blood pressure of 25 to 60 mmHg produced equivalent drops in carotid blood flow (Gf = 0.041 +/- 0.34; mean +/- standard deviation, n = 12). There were only small changes in flow in the middle meningeal artery during this procedure (Gf = 0.91 +/- 0.29). Hexamethonium did not block autoregulation in the middle meningeal artery (Gf = 0.92 +/- 0.13, n = 4). However, papaverine almost completely abolished the ability of the artery to autoregulate (Gf = 0.10 +/- 0.16, n = 7). The results suggest that the middle meningeal artery possesses an ability similar to that of the cortical circulation to autoregulate its blood flow through intrinsic, non-neuronal mechanisms. This will have important implications for the study of disturbances of dural arterial control in migraine and other headaches.

Animals↗

PubMed1996

Prospective study of human immunodeficiency virus 1-related disease among 512 infants born to infected women in New York City. The New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the incidence of HIV-1-related clinical findings, mortality and predictors of death in a cohort of HIV-exposed infants followed from birth. METHODS: Data were collected approximately bimonthly during the first and second year of life and used in Kaplan-Meier and Cox proportional hazards survival analyses to predict time to the development of symptoms and death. RESULTS: One hundred sixteen infected and 396 uninfected infants were followed for a median of 26 months at 7 New York City hospitals from 1986 to 1995. Two or more nonspecific HIV-related symptoms, AIDS or death occurred in 83% of infected children by the first year. Fifty infected infants (43%) developed AIDS and 19 (38%) of these had Pneumocystis carinii pneumonia. Estimated median age at AIDS/death was 30 months and 64% of infected children remained alive and AIDS-free at 1 year. Estimated infant mortality among infected children was 160/1000 live births, and median survival after AIDS was 21 months; 55% of infected children survived > 12 months after diagnosis of AIDS. P. carinii pneumonia was the most common cause of death. Although birth CD4 values did not predict AIDS or death, CD4 counts as early as 6 months of age were highly correlated with both. Thirteen (68%) of 19 infants who remained AIDS-free up to 3 to 6 months of age with CD4 count < or = 1500 cells/microliters subsequently developed AIDS vs. 18 (30%) of 61 with CD4 count > 1500 (P = 0.0001). CONCLUSIONS: Most HIV-1-infected infants develop disease in the first year of life. AIDS or death can be predicted by a threshold CD4 count of 1500 cells/microliters at 3 to 6 months of age.

CD4 Lymphocyte Count↗

PubMed1996

In vitro analysis of the Na(+)-K+ ATPase activity in neonatal and adult red blood cells.

We studied the role of albuterol in inducing potassium flux mediated by Na(+)-K+ ATPase in neonatal cells under hyperkalemic conditions. Using rubidium as a tracer element, we determined net transmembrane potassium flux in neonatal and adult red blood cells (RBCs) maintained in a buffer solution containing 10 mM KCl. We demonstrated that under these hyperkalemic conditions, albuterol does not increase the net transmembrane potassium flux of the adult RBC. However, neonatal RBCs maintained in these same hyperkalemic conditions demonstrate a significant 50% increase in net transmembrane potassium flux when exposed to albuterol. We conclude the albuterol may be useful in lowering the serum potassium levels in neonates even with extreme hyperkalemia.

Adult↗

PubMed1996

Spicule formation in the New Zealand ascidian Pyura pachydermatina (Chordata, Ascidiacea).

The New Zealand solitary ascidian Pyura pachydermatina (Phylum Chordata, Subphylum Urochordata) is a sessile filter feeder in rocky wave-swept coastal areas. The body is on a long stalk; both are covered by a tough fibrous tunic. Two types of spicules are formed in vascularized areas: "antler-shaped" branched spicules of amorphous calcium carbonate in blood sinuses in the body tissues and "dogbone-shaped" knobbed calcitic spicules in the tunic blood vessels. Both types form extracellularly, contain intraspicular organic components and are covered by an organic matrix coat within an epithelium of sclerocytes. SEM and TEM analysis of the spicules and their formation is included, along with calcein incorporation data used to estimate rate of growth. A comparison with spicules of other ascidians and in selected other organisms is included, with comments on the shared features of biomineralization that these disparate groups exhibit.

Animals↗

PubMed1996

Benefit of primary prophylaxis before 18 months of age in reducing the incidence of Pneumocystis carinii pneumonia and early death in a cohort of 112 human immunodeficiency virus-infected infants. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effectiveness of primary prophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection. METHODS: We conducted a retrospective analysis of a cohort of infants followed from birth at six metropolitan hospitals and one outpatient clinic for pregnant, drug-using women in New York City. Outcomes measured were histologically confirmed PCP and/or death. The potential confounding effect of the infant's stage of illness, as determined by CD4 count, was controlled by including all CD4 determinations as time-dependant covariates in a Cox proportional hazards analysis. Cases were censored at PCP onset, death, loss to follow-up, and 18 months of age. RESULTS: One hundred twelve HIV-infected children were enrolled at birth between 1986 and 1993. Sixty of these were tracked beyond 18 months of age; of the others, 21 died before this age, 4 were considered lost to follow-up, and 27 had not reached 18 months of age at the last visit. Only 3 cases (4%) of confirmed PCP occurred among the 70 children who received primary PCP prophylaxis before 18 months of age, compared with 12 cases (28%) among 42 children not receiving PCP prophylaxis at any point before 18 months of age. The Kaplan-Meier estimated incidence of PCP in the first year among children not receiving prophylaxis was 25% (95% confidence interval [CI], 12 to 39). Using Cox methods, the unadjusted risk of PCP among infants not receiving prophylaxis, relative to those receiving it, was 4.1 (95% CI, 1.1 to 15); the relative risk was 4.4 (95% CI, 1.2 to 17) adjusting for the percentage of CD4-positive lymphocytes and 5.1 (95% CI, 1.3 to 20) adjusting for the absolute number of CD4-positive cells. Eight of 26 deaths were caused by PCP, and the likelihood of early death was significantly diminished if PCP prophylaxis was given (relative risk controlling for absolute CD4 cells, 2.57; 95% CI, 1.1 to 6.1). CONCLUSIONS: We report evidence that primary antimicrobial PCP prophylaxis is highly effective in decreasing the frequency of PCP and early death in infants with perinatal HIV infection. These findings support the revised National Pediatric HIV Resource Center and Centers for Disease Control and Prevention guidelines for PCP prophylaxis in children.

AIDS-Related Opportunistic Infections↗

PubMed1996

Measles antibody in vaccinated human immunodeficiency virus type 1-infected children.

OBJECTIVES: The goals of this study were to evaluate the proportion of previously vaccinated human immunodeficiency virus (HIV) type 1-infected children with detectable postvaccination measles antibody; to assess risk factors for vaccine failure; and to evaluate the response to reimmunization. METHODS: A total of 81 perinatally HIV-infected children receiving medical care in the Bronx, New York who had previously received measles vaccine were enrolled. The Centers for Disease Control and Prevention (CDC) HIV class, lymphocyte subsets, and measles antibody were determined upon enrollment. Additional data abstracted from medical records included dates and number of prior measles vaccinations and CDC HIV class at the time of vaccination. Measles antibody was determined by microneutralization enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at time of study was 42 months (range, 9 to 168 months). Overall, 58 (72%) subjects had detectable measles antibody (microneutralization ELISA titer > 1:5). Children studied within 1 year of vaccination were more likely to have detectable measles antibody than children evaluated more than 1 year after vaccination (83% vs 52%, P < .01). The proportion of children with detectable measles antibody was higher among children with no or moderate immunosuppression compared to those with severe immunosuppression when immune status was based on CD4%. Children vaccinated at 6 to 11 months of age appeared to have a higher proportion of detectable measles antibody than those who received a first measles vaccination after age 1. Only 1 (14%) of 7 previously vaccinated children who were seronegative or had very low titers experienced a four-fold rise in measles antibody when reimmunized. CONCLUSION: These results support current recommendations to vaccinate HIV-infected children against measles. The proportion of children with detectable measles antibody among vaccinated HIV-infected children is considerably lower than in vaccinated healthy children. HIV-infected children may respond better to measles vaccine when it is administered before the first birthday. From our limited data it appears that reimmunization of previously vaccinated HIV-infected children with moderate to severe immunosuppression does not result in an antibody recall response.

Adolescent↗

PubMed1995

Transcriptional regulation of apolipoprotein A-I expression in Hep G2 cells by phorbol ester.

The regulation of apolipoprotein A-I (apo A-I) gene expression by 12-O-tetradecanoylphorbol 13-acetate (TPA) was investigated in the human hepatoma cell line Hep G2. TPA treatment decreased apo A-I mRNA levels in a time-dependent manner, by up to 50% versus control cells within 24 h. Nuclear run-on transcription assays demonstrated a transcriptional effect of TPA. Using transfection analysis with a plasmid construct containing the -1378/+11 apo A-I promoter fused to the secreted placental alkaline phosphatase (SPAP) reporter gene, we showed that the SPAP activity was decreased to 50% when Hep G2 cells were incubated in the presence of TPA. The inhibitory effect of TPA was still maintained when fragment -253 to -4 of apo A-I promoter was linked to the CAT reporter gene. These data indicate that transcriptional modulation of apolipoprotein A-I gene expression following phorbol ester treatment is transduced by gene elements located between -253 and -4 of the apo A-I promoter.

Apolipoprotein A-I↗

PubMed1995

Comparison of methods of estimating the mother-to-child transmission rate of human immunodeficiency virus type 1 (HIV-1). New York City Perinatal HIV Transmission Collaborative Study Group.

Four methods of estimating mother-to-child transmission rates of human immunodeficiency virus type 1 (HIV-1), based on the 1992 Ghent workshop, were compared in a multicenter New York City prospective cohort study in 1986-1992. Of 833 infants born to women at risk of HIV-1 infection, 388 were born HIV-1 seropositive and 445 were HIV-1 seronegative. The four methods, the Antibody Only, Indirect, Direct, and Virologic Methods, yielded transmission rate estimates of 19-25%, classifying 59-89% of the cohort. Estimation based on persistence of HIV-1 antibody and clinical assessment yielded transmission rates similar to those methods that incorporated virologic testing.

Adult↗

PubMed1995

Efficacy of antenatal zidovudine in reducing perinatal transmission of human immunodeficiency virus type 1. The New York City Perinatal HIV Transmission Collaborative Study Group.

New York City women (321) enrolled during 1986-1993 in an observational cohort study were analyzed retrospectively to determine the effectiveness of antenatal zidovudine in reducing perinatal transmission of human immunodeficiency virus type 1 (HIV-1) in women with various CD4+ lymphocyte counts (< 200, 200-499, > 499/microL). When CD4+ lymphocyte level was controlled for, women prescribed zidovudine during pregnancy were less likely to transmit HIV-1 to their infants (adjusted odds ratio, 0.36; 95% confidence interval, 0.14-0.92). There was no conclusive evidence that efficacy of zidovudine depended on CD4+ lymphocyte level, suggesting that women with severe CD4+ cell depression, who are at highest risk of transmitting HIV-1, may also benefit from zidovudine. Antenatal zidovudine treatment alone may substantially lower the risk of perinatal HIV-1 transmission. These data are consistent with the results of AIDS Clinical Trial Group protocol 076 and suggest that a substantial portion of zidovudine's protective effect may occur when used during the antenatal period.

CD4-CD8 Ratio↗

PubMed1995

Regional epinephrine kinetics in human heart failure: evidence for extra-adrenal, nonneural release.

A number of neurohumoral processes are activated in heart failure, including an increase in the plasma concentration of epinephrine. Radiotracer methods were applied in 42 patients with severe heart failure and 31 healthy volunteers to ascertain the rate at which epinephrine is released to plasma and to evaluate the contribution of extra-adrenal sources. The increase in arterial plasma epinephrine observed in the heart failure patients was explained principally by a 34% (P < 0.001) reduction in the whole body clearance rate of epinephrine from plasma. Regional venous sampling from the heart, lungs, and hepatomesenteric beds was performed in a subgroup of the study population, revealing a significant increase in the release rate of epinephrine to plasma from these organs in heart failure which accounted for 26% of the whole body plasma epinephrine appearance rate. To establish whether the cardiac epinephrine release was of neuronal origin, a physical (cycling) or mental (difficult mental arithmetic) stressor was applied as a sympathoexcitatory stimulus, given that a proportional release of norepinephrine and epinephrine could be expected if sympathetic nerves were the source. These interventions caused significant increases in the regional spillover of norepinephrine to plasma but not that of epinephrine. These findings suggest that nonadrenal tissues contribute significantly to the whole body epinephrine release rate in heart failure and that this may arise from a site other than sympathetic neurons.

Adrenal Glands↗

PubMed1995

Effects of aging on epinephrine secretion and regional release of epinephrine from the human heart.

In contrast to the sympathetic nervous system, which is activated by aging in at least some sympathetic nervous outflows, epinephrine release from the adrenal medulla appears to be either normal or low in the elderly. Using isotope dilution methodology, we studied the effect of aging on the secretion of epinephrine in 19 men, aged 20-30 yr, and 15 men, aged 60-75 yr. Measurements were made both at rest and during the application of laboratory stressors, as diminished adrenal medullary responsiveness possibly contributes to the impairment of some cardiovascular and metabolic responses to stress described previously in the elderly. Epinephrine secretion at rest was lower in the older men (mean +/- SEM, 0.86 +/- 0.10 nmol/min) than in the younger men (1.45 +/- 0.17 nmol/min; P < 0.05). Due to 20% lower plasma epinephrine clearance in the older men (P < 0.01), the reduction in the plasma concentration of epinephrine (0.37 +/- 0.03 vs. 0.52 +/- 0.06 nmol/L; P = 0.06) was proportionally less than that in epinephrine secretion. In the younger men, epinephrine secretion doubled or tripled during mental stress, isometric exercise, and dynamic exercise. Epinephrine responses to the stressors were reduced in older men, being equivalent to only 44% (P < 0.05), 44% (P = 0.1), and 33% (P = 0.01) of the corresponding responses in the younger men. After uptake from plasma, in some circumstances epinephrine is released from sympathetic nerves as a cotransmitter, where it can augment the release of the major sympathetic transmitter, norepinephrine. We also measured regional extraadrenal release of epinephrine from the heart to test whether the previously described increased release of norepinephrine from the cardiac sympathetic nerves with aging might result from facilitator effects of epinephrine released as a cotransmitter. At rest, epinephrine was released from the heart (9.4 +/- 2.6 pmol/min) in older men only (P < 0.01) despite the fact that adrenal medullary secretion of epinephrine was reduced. Failure of epinephrine and norepinephrine spillover from the heart to increase in parallel in the elderly during the sympathetic excitation accompanying exercise suggested that epinephrine lay outside the sympathetic nerves, perhaps arising from extraneuronal synthesis in the heart. We have not yet tested whether extraneuronal, in contrast to neuronal, epinephrine release in the heart could contribute to the observed higher rates of norepinephrine release in the elderly.

Adult↗

PubMed1995

Neonatal predictors of infection status and early death among 332 infants at risk of HIV-1 infection monitored prospectively from birth. New York City Perinatal HIV Transmission Collaborative Study Group.

BACKGROUND AND METHODS: Differences in newborn outcome measures for human immunodeficiency virus (HIV)-1-infected and HIV-1-exposed but uninfected infants have been found in several studies, but not in others. Eighty-four infected and 248 uninfected children born to HIV-1-seropositive mothers followed prospectively in a multicenter, perinatal HIV-1 transmission cohort study were compared for differences in maternal demographics, health status, and newborn outcome measures, including delivery complications, physical examination findings, neonatal complications, and laboratory results. RESULTS: Mothers of HIV-1-infected infants were more likely than those of uninfected infants to have acquired immunodeficiency syndrome (AIDS) diagnosed through 2 weeks postpartum (21% vs 11%, P = .04); the transmission rate for the 38 women with AIDs was 37% compared with 22% for the 245 women without AIDS. Two of 27 (7%) women receiving zidovudine during pregnancy had infected infants compared with 73 (27%) of 275 women who did not receive zidovudine (P = .033). Mean gestational age was significantly lower among HIV-1-infected (37 weeks) than among uninfected infants (38 weeks; P < .001). Infected infants had significantly higher rates of prematurity (gestational age less than 37 weeks) (33% vs 19%, P = .01) and extreme prematurity (gestational age less than 34 weeks) (18% vs 6%, P = .001) than uninfected infants. Infection was associated with lower birth weight (2533 g vs 2862 g, P < .001) and smaller head circumference (32.0 cm vs 33.1 cm, P = .001). HIV-1-infected infants were significantly more likely to be small for gestational age (26% vs 16%, P = .04) and low birth weight (less than 2500 g) (45% vs 29%, P = .006) than infants who were uninfected. Twenty-two (26%) HIV-1-infected children died during a median follow-up of 27.6 months (range 1.9 to 98.3 months). Prematurity was predictive of survival: by Kaplan-Meier, an estimated 55% (95% confidence interval, 31% to 72%) of preterm infected children survived to 24 months compared with 84% (95% confidence interval, 70% to 92%) of full-term infected children (P = .005). CONCLUSION: Infants born to women with AIDS are at higher risk for HIV-1 infection than are infants born to HIV-1-infected women with AIDS not yet diagnosed. Women receiving zidovudine appear less likely to transmit HIV-1 to their infants. Significantly higher rates of prematurity and intrauterine growth retardation were found among HIV-1-infected infants than among those in the uninfected, HIV-1-exposed control group. Prematurity was associated with shortened survival in HIV-1-infected infants. Measures of intrauterine growth and gestation appear to be important predictors of HIV-1 infection status for seropositive infants and of prognosis for the infected infant.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Virologic, immunologic, and clinical evaluation of human immunodeficiency virus antibody status of symptom-free children born to infected mothers.

STUDY OBJECTIVE: To determine the prevalence of infection by the human immunodeficiency virus (HIV) in a population of symptom-free children who were born to HIV-infected mothers and who subsequently underwent seroreversion from an HIV antibody-positive to an HIV antibody-negative status. DESIGN: Cohort. SETTING: Pediatric HIV program in a community setting. PATIENTS: We used HIV DNA polymerase chain reaction (PCR) and coculture to detect the presence or absence of HIV in peripheral blood mononuclear cells of 134 children aged 6 to 53 months. All children had HIV antibody at birth and underwent a subsequent seroreversion to antibody-negative status. RESULTS: In 134 children with HIV antibody-negative status, 219 of 220 culture results and 242 of 247 HIV-1 DNA PCR assay results were negative. Six positive laboratory results were obtained for six different children, each of whom had negative results on multiple assays. For HIV-infected children, 56 of 62 cultures and 99 of 104 PCR evaluations showed positive results. There was no clinical or laboratory evidence of HIV infection in the group with HIV antibody-negative status. CONCLUSION: We were unable to find evidence of latent HIV type 1 infection in this cohort of symptom-free children who underwent seroreversion to HIV antibody-negative status. The loss of maternal HIV antibody in these children indicates the absence of HIV infection. False-positive PCR and culture results occurred sporadically, indicating that repeated analysis of HIV seropositivity in infants and children is necessary.

Adolescent↗

PubMed1994

Morphological transformation and DNA adduct formation by dibenz[a,h]anthracene and its metabolites in C3H10T1/2CL8 cells.

The major routes of metabolic activation of dibenz[a,h]-anthracene (DBA) have been studied in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. The morphological transforming activities of three potential intermediates formed by metabolism of DBA by C3H10T1/2 cells, trans-3,4-dihydroxy-3,4-dihydro-DBA-(DBA-3,4-diol), trans-dihydroxy-3,4-dihydro-DBA-anti-1,2-oxide (DBA-3,4-diol-1,2-oxide) and DBA-5,6-oxide were determined. DBA-3,4-diol-1,2-oxide was a strong morphological transforming agent giving a mean of 73% dishes with Type II or III foci and 1.63 Type II and III foci per dish at 0.5 microgram/ml. DBA-3,4-diol produced a mean of 42% dishes with Type II or III foci and 0.81 Type II and III foci per dish at 2.5 micrograms/ml. DBA gave a mean of 24% dishes with Type II or III foci and 0.29 Type II and III foci per dish at 2.5 micrograms/ml. DBA-5,6-oxide was found to be inactive. DNA adducts of DBA, DBA-3,4-diol, DBA-3,4-diol-1,2-oxide, DBA-1,4/2,3-tetrol and DBA-5,6-oxide in C3H10T1/2 cells were analyzed by 32P-postlabeling method. DBA gave 11 adducts, nine of which were observed in the DNA of cells treated with DBA-3,4-diol and seven from cells treated with DBA-3,4-diol-1,2-oxide. Two of these adducts that appear in each of the treatment groups have been identified as the product of the interaction of DBA-3,4-diol-1,2-oxide with 2'-deoxyguanosine. Furthermore, there is evidence for DBA-DNA adducts in cells treated with DBA, DBA-3,4-diol and DBA-3,4-diol-1,2-oxide arising from metabolism to (+,-)-trans,trans-3,4,10,11-tetrahydroxy-3,4,10,11-tetrahydro-DBA (DBA-3,4,10,11-bis-diol). These results are based on co-migration of C3H10T1/2 DNA adducts with skin DNA adducts formed after topical treatment of mice with DBA-3,4,10,11-bis-diol. In C3H10T1/2 cells, DBA is metabolically activated through DBA-3,4-diol, which is further activated via the DBA-3,4-diol-1,2-oxide and DBA-3,4,10,11-bis-diol pathways. No evidence is provided for the metabolism of DBA by the K-region pathway.

Animals↗

PubMed1994

A 12-month study of the effects of oral zidovudine on neurodevelopmental functioning in a cohort of vertically HIV-infected inner-city children.

OBJECTIVE: To examine the effects of oral zidovudine on the neurodevelopmental functioning of HIV-infected children. METHODS: Oral zidovudine was administered to 54 symptomatic children with vertically transmitted HIV infection (Centers for Disease Control and Prevention class P2). All children were recruited from an inner-city pediatric HIV/AIDS outpatient clinic and ranged in age from 2 months to 12 years and 11 months (mean age, 3 years) at entry. Neurodevelopmental functioning, height and weight, and lymphocyte subpopulation data were ascertained for all the children pretherapy, and 6 and 12 months post-therapy initiation. RESULTS: Analysis of the 6- and 12-month post-initiation drug data found no significant change in neurodevelopmental functioning. Height and weight percentiles remained the same or improved in the majority of children. CD4+ cell counts declined over the treatment period with CD4+ counts < 500 x 10(6)/l observed in 15% of the children pre-therapy, and 33% after 1 year. CONCLUSION: In contrast with previously published data, the present study observed no improvement in neurodevelopmental functioning in HIV-infected children treated with oral zidovudine.

Black or African American↗

PubMed1994

Aerosolized pentamidine for prophylaxis of Pneumocystis carinii pneumonia in infants with human immunodeficiency virus infection.

Aerosolized pentamidine is widely used in adult patients with human immunodeficiency virus as both prophylaxis and therapy for Pneumocystis carinii pneumonia. The aim of this study was to evaluate the safety of a monthly regimen of aerosolized pentamidine in human immunodeficiency virus-infected infants. Seven human immunodeficiency virus-infected infants, ages 3.5 to 11 months, were given a total of 45 monthly treatments of aerosolized pentamidine. The infant's dose of pentamidine was based on an adult dosage of 300 to 600 mg/month, adjusted for minute ventilation and weight. There were no discernible clinical side effects in 62% (28 of 45) of the treatments. Observed toxicity included mild to moderate coughing, mild wheeze and transient arterial desaturation as measured by pulse oximetry. Pulmonary function data revealed an increased tidal volume (P < 0.005) and an increased pulmonary resistance (P < 0.02) post-pentamidine treatment. Urinary pentamidine concentrations were obtained and pentamidine was detected in all tested samples suggesting pulmonary deposition and systemic absorption. In conclusion aerosolized pentamidine appears to be a relatively safe, well-tolerated treatment in infants, with side effects similar to those seen in adults.

AIDS-Related Opportunistic Infections↗