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Biomedical subjects

H Minkoff

Publications and source records attributed to H Minkoff.

At least 37 records · Page 2Linked to original sources

Transport of recombinant human CD4-immunoglobulin G across the human placenta: pharmacokinetics and safety in six mother-infant pairs in AIDS clinical trial group protocol 146.

Recombinant CD4-immunoglobulin G (rCD4-IgG) is a 98-kDa human immunoglobulin-like protein that is produced by fusing the gp120 binding domain of CD4 to the Fc portion of the human IgG1 heavy chain. This hybrid molecule was given to human immunodeficiency virus (HIV)-infected pregnant women at the onset of labor by intravenous bolus at 1 mg/kg of body weight (group A; n = 3) and 1 week prior to and at the onset of labor by the same route and at the same dose (group B; n = 3). In addition to pharmacokinetic studies, safety in the mothers and infants was determined through routine chemistries, hematology, and urinalysis; immunologic and HIV infection statuses in the infants were assessed through lymphocyte cultures, p24 antigen level determination, culture of HIV from plasma, PCR, lymphocyte subset enumeration, quantitative immunoglobulin analysis, and lymphocyte proliferation. Thirty minutes after the rCD4-IgG injection, concentrations in maternal serum were 12 to 23 micrograms/ml. These concentrations declined slowly, with initial and terminal half-lives (mean +/- standard deviation) of 9.95 +/- 3.23 and 47.6 +/- 22.3 h, respectively. Infants were born 2.6 to 46.5 h after rCD4-IgG administration; concentrations of rCD4-IgG in cord blood ranged from 28 to 107 ng/ml. The half-life of rCD4-IgG in infants ranged from 5 to 29 h. These data demonstrate that the transfer of rCD4-IgG from the mother to the fetus is rapid and that newborns do not appear to have any difficulty eliminating rCD4-IgG. No safety concerns in mothers or infants were encountered. Although the study did not address the question of efficacy, none of the infants was HIV type 1 infected 36 months later. In summary, these findings document that bifunctional immune molecules can be transported across the placenta, and this general approach may be used in the future to block vertical transmission of HIV type 1.

Acquired Immunodeficiency Syndrome

Condom use relative to knowledge of sexually transmitted disease prevention, method of birth control, and past or present infection.

The purpose of this study was to assess knowledge regarding STD spread and prevention, and to assess motivational and behavioral factors that influence the use of condoms to prevent STD acquisition among inner-city women at high risk for STD infection. In addition, the effect of past and/or current STD infection on a woman's knowledge of the mechanism of STD acquisition and subsequent use of a condom to prevent STD infection was explored. We utilized three inner-city clinics offering family planning or gynecologic care located in Brooklyn, New York. Our study linked clinical findings regarding current infection with chlamydia or Trichomonas vaginalis. One thousand four hundred and four sexually active black and Hispanic women participated in the study. A past history of STD (37%) or current infection (29%) was recorded for 54% of the study population (12% were positive for both past and current infection). On average, only 60% of women who reported prior treatment for STD infection reported receiving any information regarding prevention of re-infection during the course of treatment. Depending on the specific STD, from 6.8% to 42.9% of women reporting prior treatment for an STD did not know the disease they were being treated for was sexually transmitted. Condom use for disease prevention was more frequently reported by women who had previously been treated for an STD (OR = 1.62, 95% CI 1.23-2.13). However, condom use for contraception was a stronger predictor of use for STD prevention. Women who relied on condoms for contraception were almost 10 times more likely to also report condom use for STD prevention relative to women who did not use condoms for contraceptive purposes (OR = 9.71, 95% CI 7.0-13.5). In addition, condom use was associated with the perceived attitude of their sexual partner toward such use. Condom use to prevent STD acquisition was more than twice as frequently reported when a favorable attitude was perceived by a male sexual partner (OR = 2.30, 95% CI 1.54-3.43). Our findings suggest that prevention of unplanned pregnancy was a stronger motivator for condom use than disease prevention among the women comprising our study group. The findings also indicate the need for more extensive information regarding STD prevention among women at high risk for STD acquisition.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

The role of obstetric interventions in the prevention of pediatric human immunodeficiency virus infection.

By the end of the decade 10 million children will be infected with human immunodeficiency virus. Several potential means of preventing vertical transmission of human immunodeficiency virus are under study. Although the perinatal use of antiretroviral agents can prevent some of these infections, those agents are neither uniformly effective nor universally available. A significant portion of vertical transmission may be an intrapartum phenomenon, potentially amenable to obstetric interventions, such as cesarean section or vaginal virucides. The utility of these obstetric interventions will be determined in large part by the timing of vertical transmission. This work reviews the evidence that human immunodeficiency virus can be transmitted during the intrapartum period and critically reviews the data supporting a role for obstetric interventions. Finally, we outline the necessary elements for the conduct of a conclusive efficacy trial and delineate a mechanism to arrive at a definitive standard of care in the absence or anticipation of a trial.

Acquired Immunodeficiency Syndrome

Cigarette smoking, premature rupture of membranes, and vertical transmission of HIV-1 among women with low CD4+ levels.

To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+ level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4+ lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+ level was < 20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004]. Among mothers who developed premature rupture of membranes, those with a low CD4+ level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4+ level on transmission. Among all mothers without regard to CD4+ level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Intrauterine pressure wave characteristics of the upper and lower uterine segments in parturients with active-phase arrest.

OBJECTIVE: To determine the gradient of pressure between the upper and the lower uterine segments of parturients with non-progressing labor and to see whether the gradient correlates with subsequent successful oxytocin augmentation. METHODS: Fifteen women with active-phase arrest of labor were monitored with two intrauterine pressure transducers before and after oxytocin augmentation. Seven parturients without arrest of labor were evaluated for comparison. One intrauterine pressure transducer was inserted into the upper and one into the lower uterine segment of each subject. Overall, 444 contractions were assessed using the mean active pressure method. RESULTS: A total of 16 patients delivered vaginally. Nine received oxytocin augmentation, and all had significantly higher pressure in the upper segment than in the lower both before and after oxytocin (P < .001). Six women delivered by cesarean had a reversed gradient of uterine activity, with the lower segment contracting significantly more strongly than the upper uterine segment both before (P = .002) and after oxytocin (P = .001). CONCLUSION: Pressure gradients between the upper and lower uterine segments in the active phase might predict the likelihood of success of oxytocin augmentation.

Case-Control Studies

The relationship between the ultrasonographic diagnosis of innocent amniotic band development and pregnancy outcomes.

OBJECTIVE: To determine the importance of amniotic bands diagnosed ultrasonographically and their relationship to pregnancy outcome. METHODS: We reviewed retrospectively the ultrasonographic records at State University of New York Health Science Center at Brooklyn and Kings County Hospital Center, identifying 25 cases of amniotic band diagnosed during 1986-1990. Cases were compared with 50 controls who had ultrasound evaluation at the same gestational age. Outcomes studied included fetal anomalies, obstetric factors or complications, pregnancy outcome, and maternal factors that may have predisposed to the formation of bands. RESULTS: All cases had unrestricted fetal movement on the index sonogram. No fetal abnormalities were observed in either the case or control series. The groups were not significantly different in terms of maternal risk factors, but significant differences were found for delivery at less than 37 weeks and birth weight less than 2500 g. CONCLUSION: Ultrasonographic diagnosis of an amniotic band in connection with sonographic findings of normal fetal anatomy may be a risk factor for preterm delivery and low birth weight. No association between amniotic band development and fetal anomalies was observed.

Adult

A survey of zidovudine use in pregnant women with human immunodeficiency virus infection.

BACKGROUND AND METHODS: The expanding indications for zidovudine treatment make it important to elucidate the safety and toxicity of this drug for pregnant women and their fetuses. We asked pediatricians and obstetricians at the AIDS (acquired immunodeficiency syndrome) Clinical Trials Units to report information about pregnant women infected with the human immunodeficiency virus (HIV) who were continuing their pregnancies and had received, or were receiving, zidovudine during gestation. RESULTS: Reports of 43 women were received from 17 institutions. Doses of zidovudine ranged from 300 to 1200 mg per day, and 24 women took the drug for at least two trimesters. There were two reported instances of maternal toxicity (one gastrointestinal and one hematologic). No teratogenic abnormalities occurred in the 12 infants with first-trimester exposure to zidovudine. All the infants, including two sets of twins, were born alive. The 38 singleton infants born at term for whom birth weights were reported had a mean birth weight of 3287 +/- 670 g; two cases of intrauterine growth retardation were reported among the infants delivered at term. Hemoglobin values, which were available for 31 newborns, ranged from 7.0 to 12.4 mmol per liter (11.2 to 20 g per deciliter); 3 of the 7 newborns with hemoglobin values of less than 8.4 mmol per liter (13.5 g per deciliter) were born prematurely. CONCLUSIONS: Zidovudine was well tolerated by the pregnant women and was apparently not associated with malformations in the newborns, premature birth, or fetal distress. No pattern of hematologic toxicity was observed in the newborns, but the anemia and growth retardation seen in a minority of the infants could, in part, have resulted from their mothers' treatment with zidovudine.

Abnormalities, Drug-Induced

Umbilical and uterine Doppler velocimetry and prostaglandin levels in preeclampsia.

Eleven preterm patients with severe preeclampsia underwent Doppler velocimetry prior to cesarean section. Maternal venous blood and umbilical arterial and venous samples were collected for prostacyclin and thromboxane determination by radioimmunoassay. Umbilical artery pulsatility index correlated positively with umbilical artery thromboxane B2 levels (r = 0.76; P less than 0.05) and maternal thromboxane levels (r = 0.78; P less than 0.05). We conclude that the vasoactive action of thromboxane A2 may alter placental resistance.

6-Ketoprostaglandin F1 alpha

Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection.

OBJECTIVE: To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. DESIGN: Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. SETTING: Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. PATIENTS: Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. MAIN OUTCOME MEASURE: Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. RESULTS: The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%--no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. CONCLUSION: The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms.

Female

Human immunodeficiency virus-1 infection in an infertile population.

OBJECTIVE: The aim of our study was to determine the prevalence of human immunodeficiency virus-1 (HIV-1) in an infertile population. DESIGN: The study design included a retrospective anonymous survey of clinical data and screening for HIV-1 antibody by enzyme-linked immunoabsorbent assay (ELISA) in stored sera. Samples that were ELISA-positive were further tested by Western blot assay. Frequency distributions were analyzed by Fisher's exact test. SETTING: University tertiary care center. PARTICIPANTS: Based on availability of stored frozen sera, the total study population included 182 of 304 consecutively registered infertile couples. RESULTS: Seventy-five percent of the study population were found to have one or more risk factors for HIV infection. Of the 252 sera tested, 10 were repeatedly reactive by ELISA, and Western blot testing confirmed HIV-1 infection in one woman and two men. CONCLUSIONS: This relatively high HIV-1 seroprevalence (male: 2.6%; female: 0.6%) in a low-middle class infertile population emphasizes the urgent need to implement on-site HIV-infection counseling aimed at preventing the spread of disease to the healthy partner and fetus and to discuss therapeutic and reproductive options.

Adolescent

Sexually transmitted diseases and human immunodeficiency virus infection among women with pelvic inflammatory disease.

Both human immunodeficiency virus infections and pelvic inflammatory diseases are sexually acquired illnesses of great consequence to women. This study was undertaken to determine if women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, were at high risk to be infected with human immunodeficiency virus and if human immunodeficiency virus infections altered their hospital course. One hundred ten women hospitalized with pelvic inflammatory disease in Brooklyn (in a hospital in which 2% of parturients are human immunodeficiency virus seropositive) agreed to human immunodeficiency virus testing; 15 (13.6%) were found to be seropositive. Seropositive women were significantly more likely to have an admission white blood cell count less than 10,000/mm3 (p = 0.001). Human immunodeficiency virus seropositivity was not associated with a higher frequency of other sexually transmitted diseases although there was a trend toward more cases of syphilis among human immunodeficiency virus-infected women. Similarly, although there was no significant difference in rates of operative intervention (26.6% among seropositive and 8.4% among seronegative; p = 0.058), there was a trend toward more surgery among those who were human immunodeficiency virus infected. Women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, are at high risk for human immunodeficiency virus infection. More research is needed to verify a trend toward more refractory infections among human immunodeficiency virus-infected women.

Acquired Immunodeficiency Syndrome

Syphilis among parturients at an inner city hospital: association with cocaine use and implications for congenital syphilis rates.

The frequency of positive cord blood rapid plasma reagin (RPR) tests among newborns at an inner city hospital and associations with maternal cocaine use, prenatal care, and adequacy of syphilis therapy were retrospectively assessed. The incidence of positive cord blood RPRs increased from 1.1% of all live births in 1985 to 3.4% in 1988. In 1987, 98 babies were born with positive cord blood RPRs; 86 of their charts were available for review. Four infants had false positive RPRs, and one patient delivered twins, leaving 81 mothers who could be evaluated. Almost 37% of these patients had had no prenatal care. More than 55% had inadequate or not therapy for syphilis. Of these, only 17.4% had prenatal care. Slightly more than 40% of patients acknowledged using drugs during pregnancy, 87.9% of whom used cocaine. Among the patients who used drugs, 75.8% received no prenatal care, in contrast to 10.4% of mothers who did not use drugs (p less than 0.001). It appears that drug use, particularly use of cocaine, is associated with low levels of utilization of prenatal services and inadequate therapy for syphilis. This may lead to increased risk of congenital syphilis in newborns.

Cocaine

Screening with Doppler velocimetry in labor.

Doppler flow velocimetry was performed on 273 nonselected patients in labor. All patients were at least 2 cm dilated and 80% effaced (58% greater than 4 cm) and were delivered of infants within 24 hours. Fetal heart rate tracing performed at the same time was read by another observer and compared with Doppler flow velocity measurements (systolic/diastolic ratio, pulsatility index). A significant correlation was noted (r = 0.234, p less than 0.001) between the two modalities. Both fetal heart rate tracings and umbilical flow velocity measurements were correlated with fetal outcome. Significant associations were noted between the umbilical systolic/diastolic ratio and fetal distress. 5-minute Apgar scores, the need for intubation independent of gestational age, and umbilical arterial cord pH and base excess. It appears that the information obtained from flow velocimetry had additional benefits compared with that of fetal heart rate tracings alone.

Adult

Immunosuppression in pregnant women infected with human immunodeficiency virus.

One hundred two pregnant women at high risk of infection with the human immunodeficiency virus (62 who were drug abusers and 40 of Haitian origin) were prospectively examined for immunologic changes during and after pregnancy. Among the 63 human immunodeficiency virus-negative women, levels of CD4+ (helper) cells fell to a nadir at 8 weeks before delivery and rose rapidly just before delivery. The level of CD8+ (cytotoxic/suppressor) cells rose slowly from midpregnancy to delivery. Among the 37 human immunodeficiency virus-positive pregnant women, levels of CD4+ cells fell during pregnancy (except for a transient weak increase just before delivery) and did not recover in the postpartum period. Levels of CD8+ cells were consistently higher in human immunodeficiency virus-positive than human immunodeficiency virus-negative women. Post partum the CD8+ cells in human immunodeficiency virus-negative women stabilized at delivery levels, whereas they increased greatly in human immunodeficiency virus-positive women. The loss of CD4+ cells in human immunodeficiency virus-positive women appeared to be faster during pregnancy than in the postpartum period. These data support the hypothesis that pregnancy may accelerate human immunodeficiency virus-induced depletion of CD4+ cells and increase the risk of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome