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Biomedical subjects

L Kuhn

Publications and source records attributed to L Kuhn.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evaluation of alternative methods of cervical cancer screening for resource-poor settings.

BACKGROUND: Noncytologic methods of screening for cervical carcinoma and its precursor lesions are needed for resource-poor settings in which cervical carcinoma continues to be an important cause of morbidity and mortality. METHODS: Two thousand nine hundred forty-four women ages 35-65 years were recruited from Cape Town, South Africa and screened using a combination of a Papanicolaou (Pap) smear, human papillomavirus (HPV) DNA testing, direct visual inspection after the application of a 5% acetic acid solution (DVI), and cervicography. Cervicography was considered primarily as a method with which to quality control the DVI examinations. Women with squamous intraepithelial lesions (SIL) or carcinoma on Pap smear, positive DVI examination (acetowhite lesion or cervical ulcer/growth), high levels of high risk HPV DNA (relative light units [RLU] > 10x positive control), or positive Cervigramtrade mark were referred for colposcopy and cervical biopsy. RESULTS: Pap smears were positive in 8.1% of all women screened and identified 65 (78%) of all cases of biopsy confirmed high grade disease (high grade SIL or invasive carcinoma). DVI and cervicography were classified as positive in 18.1% and 10.5%, respectively, of women screened and identified 58 (67%) and 46 (58%) of all cases of high grade disease, respectively. The results of HPV DNA testing varied depending on the cutoff value used to define a positive result. At the standard cutoff level (RLU > 1x positive control), 16.2% of women screened were classified as high risk HPV DNA positive, as were 63 women with high grade disease (73%). CONCLUSIONS: DVI and HPV DNA testing identified similar numbers of high grade SIL (cervical intraepithelial neoplasia Grade 2,3) and invasive carcinoma cases as Pap smears. However, both classify considerably more women without cervical disease as being test positive.

Adult↗
PubMed2000

Cell-free virus in breast milk of HIV-1-seropositive women.

To examine the prevalence, quantification, and factors that influence HIV in the cell-free compartment of breast milk, we performed reverse transcription polymerase chain reaction (RT-PCR) on samples obtained from HIV-1-infected study subjects. Virus was detected in 86 of 136 samples (63.2%) from 79 study subjects. HIV RNA quantity ranged from undetectable to 227,586 copies/ml. Prevalence and mean viral load were not affected by postnatal ages or maternal vitamin A supplementation. Among study subjects with multiple samples, breast milk viral load did not change at different postnatal ages. Breast milk viral load correlated positively with plasma viral load (r = 0.47; p =.005) and negatively with maternal CD4 count at entry to the study (r = -0.26; p =.02). Mothers of HIV-infected children had a higher proportion of detectable HIV RNA in their breast milk than mothers of uninfected children (p =.03) and higher mean log10 HIV RNA quantities (p =.04). In a multivariate logistic regression model, log10 HIV RNA quantity in breast milk was significantly associated with the risk of mother-child transmission (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.22-6.51). Thus, prevention and treatment of opportunistic infections and of mastitis and early weaning may be important elements of a public health policy that is relevant to women in developing countries with HIV infection. Where available, antiretrovirals may also have an impact on opportunistic infections and mastitis.

Adult↗
PubMed2000

Cocaine use during pregnancy and intrauterine growth retardation: new insights based on maternal hair tests.

Prenatal cocaine use is more accurately measured by maternal hair assay than by urine toxicology screening or self-report. To investigate the consequences of improved measurement, the authors ascertained cocaine use during pregnancy by maternal hair test, urine test, and self-report in a sample of 691 patients recruited from one New York City hospital in 1990-1992. Associations with intrauterine growth retardation, head circumference, and length of gestation were investigated. A positive hair test at delivery was not more strongly associated with birth weight (-38.1 g; 95% CI: -164, 88.3) or head circumference (-1.73 mm; 95% CI: -5.91, 2.44) than a positive urine test at delivery (-182 g (95% CI: -295, -69.8) and -6.11 mm (95% CI: -9.99, -2.24), respectively). Cocaine concentration in hair (which was higher if urine tests were positive) had a dose-response relationship with birth weight: a 27-g decrease (95% CI: -51.9, -1.04) with each log-unit increase in concentration. Birth weights were similar among infants of never users and infants of users who stopped using cocaine before delivery. Heavier use of cocaine, but not lighter use, was associated with intrauterine growth retardation, and exposure in late pregnancy was necessary to the association. Although maternal hair tests were instrumental in clarifying these relations, their clinical use is probably not warranted.

Adult↗
PubMed2000

Disease progression and early viral dynamics in human immunodeficiency virus-infected children exposed to zidovudine during prenatal and perinatal periods.

Zidovudine (Zdv) is widely used to reduce maternal-infant human immunodeficiency virus transmission (HIV), but its consequences for disease progression among children infected despite Zdv exposure remain unknown. In a multicenter observational cohort study of 325 HIV-infected children born during 1986-1997, clinical progression was compared among infected children exposed or unexposed to Zdv during prenatal and perinatal periods. Zdv exposure was associated with 1.8-fold (95% confidence interval, 1.02-3.11) increased risk of progressing to AIDS or death after adjusting for year of birth, maternal CD4 cell count, maternal AIDS diagnosis, and subsequent antiretroviral therapy of the child. Mean log(10) viral copies at 7-12 weeks were higher among Zdv-exposed children (P=.004). No infected child treated early with multidrug therapy progressed to AIDS or died by 1 year, regardless of early Zdv exposure. More rapid disease progression was observed among infected children exposed during pregnancy or birth to Zdv if effective multidrug therapy was not initiated.

Anti-HIV Agents↗
PubMed2000

Human papillomavirus DNA testing for cervical cancer screening in low-resource settings.

BACKGROUND: In many low-resource settings, there are barriers to cytologic screening for cervical cancer. This study evaluates human papillomavirus (HPV) DNA testing as an alternative screening method. METHODS: Cervical samples from 2944 previously unscreened South African women aged 35-65 years were tested for high-risk types of HPV with the use of the Hybrid Capture I (HCI) assay. Women also had a Pap smear, direct visual inspection of the cervix, and Cervicography(TM). Women positive on any screening test were referred for colposcopy. Samples from women with biopsy-confirmed, low-grade squamous intraepithelial lesions (SILs) (n = 95), high-grade SILs (n = 74), or invasive cervical cancer (n = 12) and a random sample of women with no cervical disease (n = 243) were retested for HPV DNA with the use of the more sensitive Hybrid Capture II (HCII) assay. All P values are two-sided. RESULTS: High-risk HPV DNA was detected in 73.3% and 88.4% of 86 women with high-grade SIL or invasive cancer and in 12.2% of 2680 and 18.1% of 243 women without evidence of cervical disease, with the use of the HCI and HCII assays, respectively. HPV DNA testing with the HCII assay was more sensitive than cytology for detecting high-grade SIL and invasive cancer (McNemar's test, P =.04), and testing with the HCI assay was of equivalent sensitivity (P =.61). Cytology had a statistically significantly better specificity (96.8%) than either the HCI assay (87.8%) or the HCII assay (81.9%) (P<.01). Receiver operating characteristic curves identified test cutoff values that allow HPV DNA testing to identify 57% of women with high-grade SIL or cancer, while classifying less than 5% of women with no cervical disease as HPV DNA positive. CONCLUSIONS: HPV DNA testing has a sensitivity equivalent to, or better than, that of cytology. Since HPV DNA testing programs may be easier to implement than cytologic screening, HPV testing should be considered for primary cervical cancer screening in low-resource settings.

Adult↗
PubMed2000

Randomized controlled trial assessing the effect of vitamin A supplementation on maternal morbidity during pregnancy and postpartum among HIV-infected women.

OBJECTIVE: To determine whether low-cost treatment of HIV using vitamin A would be beneficial, we examined the effect of vitamin A supplementation on morbidity of HIV-1 infected women. METHODS: We conducted a randomized, double blind placebo-controlled trial at King Edward VIII Hospital, in Durban, South Africa. In total, 312 HIV-seropositive pregnant women between 28 and 32 weeks' gestation were recruited into this trial. Patients were randomized to receive placebo or 5,000 IU retinyl palmitate and 30 mg beta-carotene daily. At delivery of their children, patients received placebo or 200,000 IU retinyl palmitate. The main outcome measures were pre- and postnatal report of HIV-related symptoms. RESULTS: Vitamin A did not confer any significant beneficial effect on the report of either HIV or pregnancy-related symptoms during the pre- or postnatal period. CONCLUSION: In this study of HIV-infected pregnant women, vitamin A supplementation given in doses designed to decrease mother-to-infant transmission did not result in significant beneficial effect on reported symptoms pre- or postnatally. Further investigation with larger number of participants, tailoring supplementation for specific clinical conditions, outside the context of pregnancy, is required to help clarify the possible clinical benefits of vitamin A.

Adult↗
PubMed2000

HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer.

CONTEXT: More than half of the women diagnosed as having cervical cancer in the United States have not been screened within the last 3 years, despite many having had contact with the health care system. In many other regions of the world, there is only limited access to cervical cancer screening. OBJECTIVE: To determine whether testing of self-collected vaginal swabs for human papillomavirus (HPV) DNA can be used to screen for cervical disease in women aged 35 years and older. DESIGN: Cross-sectional observational study comparing Papanicolaou smears with HPV DNA testing of self-collected vaginal swabs. SETTING: Outpatient clinics in a periurban settlement outside of Cape Town, South Africa, between January 1998 and April 1999. PARTICIPANTS: Screening was performed on 1415 previously unscreened black South African women aged 35 to 65 years. INTERVENTION: Women self-collected a vaginal swab for HPV testing in the clinic and were then screened using 4 different tests: Papanicolaou smear, direct visual inspection of the cervix after the application of 5% acetic acid, cervicography, and HPV DNA testing of a clinician-obtained cervical sample. Women with abnormal results on any of the screening tests were referred for colposcopy. MAIN OUTCOME MEASURE: Biopsy-confirmed high-grade cervical squamous intraepithelial lesions or invasive cancer. RESULTS: High-grade squamous intraepithelial lesions were identified in 47 (3.4%) of 1365 women adequately assessed, and there were 9 cases of invasive cancer. Of women with high-grade disease, 66.1% (95% confidence interval [CI], 52.1%-77.8%) had high risk for HPV detected in self-collected vaginal samples, and 67.9% (95% CI, 53.9%-79.4%) had an abnormal Papanicolaou smear (P = .78). The false-positive rates for HPV DNA testing of self-collected vaginal samples and Papanicolaou smears were 17.1% (95% CI, 15.1%-19.3%) and 12.3% (95% CI, 10.5%-14.2%), respectively (P<.001). A high-risk type of HPV DNA was detected in 83.9% (95% CI, 71.2%-91.9%) of women with high-grade disease and 15.5% (95% CI, 13.6%-17.7%) of women with no evidence of cervical disease using a clinician-obtained cervical sample. CONCLUSIONS: These results indicate that HPV testing of self-collected vaginal swabs is less specific than but as sensitive as Papanicolaou smears for detecting high-grade cervical disease in women aged 35 years and older, and HPV testing offers an important new way to increase screening in settings where cytology is not readily performed.

Adult↗
PubMed2000

Global analysis of gene expression in cells of the immune system II. Cell-free translation products and high-density filter hybridization data.

We have developed an experimental system for linking information on cell-free transcription and translation products from cDNA clones with data obtained from hybridization signals from complex probes. The work described in this paper consists of two distinct processes, one being the construction of a system of clonal addresses and the other the identification of expressed genes involved in the studied processes. We describe the use of this system to identify genes involved in thymus development. Complex probes from fetal thymuses (GD15, 17 and newborn) of Balb/c mice were used to identify genes, which are up- or downregulated during the process of differentiation. The full set of information is available in the Clone-base of the Basel Institute for Immunology and will be retrievable from the website of the collaborating laboratories.

Animals↗
PubMed2000

Two-stage cervical cancer screening: an alternative for resource-poor settings.

OBJECTIVE: We sought to introduce 2-stage cervical cancer screening in which 2 screening tests are performed sequentially (the second test is performed only if the first result is positive), followed by treatment if both test results are abnormal. STUDY DESIGN: A total of 1423 women from Cape Town, South Africa, were screened by direct visual inspection, human papillomavirus deoxyribonucleic acid testing, cytologic testing, and cervicography. If an abnormality was identified with any test, women were referred for colposcopy. RESULTS: Direct visual inspection, cytologic testing, human papillomavirus deoxyribonucleic acid testing, and cervicography, when used alone, identified 24, 26, 23, and 23 cases of disease (high-grade squamous intraepithelial lesion or cancer) per 1000 women, respectively, and would classify 182, 71, 137, and 112 women without disease as having abnormal results. Two-stage screening with direct visual inspection first, followed by cytologic testing, human papillomavirus deoxyribonucleic acid testing, or cervicography, would detect 18, 16, and 18 cases per 1000 women, respectively, and would substantially reduce the number of women without disease who were classified as having abnormal results. CONCLUSION: Two-stage screening for cervical cancer provides an attractive alternative to conventional screening for low-resource settings.

Adult↗
PubMed2000

Vitamin A and HIV infection: disease progression, mortality, and transmission.

Among HIV-infected individuals, many nutritional factors that influence disease progress, mortality, and transmission are not well understood. Of particular interest is the role of vitamin A. The benefits of vitamin A have been recognized since ancient times by Egyptian physicians who successfully treated night blindness with vitamin A. Contemporary scientists have since recognized the importance of vitamin A and have provided evidence that it may help in repairing damaged mucosal surfaces; what remains unclear, however, is its role during HIV infection. In this review, we examine the evidence provided in both observational studies and randomized controlled trials that assessed the effect of vitamin A during HIV infection.

CD4 Lymphocyte Count↗
PubMed2000

Exclusive breast-feeding: does it have the potential to reduce breast-feeding transmission of HIV-1?

Exclusive breast-feeding is unambiguously the optimal infant feeding practice and is universally promoted in the absence of human immunodeficiency virus (HIV-1). It is associated with reduced morbidity and mortality from diarrheal and respiratory diseases. Recent findings suggest that exclusive breast-feeding may pose less risk of HIV-1 transmission than the more common practice of mixed feeding (i.e., breast-feeding concurrent with the feeding of water, other fluids, and foods), which has important infant feeding policy implications for low-resource settings. This paper reviews the biologic mechanisms associated with exclusive breast-feeding that provide protection against gastrointestinal, respiratory, and atopic diseases, and evaluates the relevance of these mechanisms for HIV-1 transmission. Potential mechanisms include reduction in dietary antigens and enteric pathogens that may maintain integrity of the intestinal mucosal barrier and limit inflammatory responses of the gut mucosa; promotion of beneficial intestinal microflora that may increase resistance to infection and modulate the infant's immune response; alteration in specific antiviral or anti-inflammatory factors in human milk that may modulate maternal hormonal or immunologic status; and maintenance of mammary epithelial integrity that may reduce viral load in breast milk.

Breast Feeding↗
PubMed2000

Effect of vitamin A supplementation on morbidity of low-birth-weight neonates.

BACKGROUND: Low-birth-weight (LBW) infants (< 2,500 g) are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation, deficiency could result in pathological changes in the respiratory epithelium, with respiratory problems. OBJECTIVE: A randomised, double-blind, placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life. METHOD: One hundred and thirty LBW infants (gestational age < 36 weeks and birth weight 950-1,700 g) were enrolled in the study. The infants were randomly allocated to a vitamin A or placebo group. Infants in the vitamin A group received 25,000 IU of vitamin A (retinyl palmitate, Arovit drops, Roche, Basle, Switzerland) on study days 1, 4 and 8. Study day 1 was between 36 and 60 hours after delivery. Infants in the placebo group received a placebo (formulated by Roche) with a similar appearance and packed in the same dropper bottles as the vitamin A drops. RESULTS: Vitamin A supplementation markedly improved serum retinol levels. After the last vitamin A dose, the vitamin A group had higher mean serum retinol concentrations than the placebo group (45.77 +/- 17.07 micrograms/dl v. 12.88 +/- 6.48 micrograms/dl, P = 0.0001). There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation. Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen. There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life. There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation. The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6% (7 hospitalisations) in the vitamin A group compared with 7.4% (2 hospitalisations) in the placebo group (log rank test P = 0.04). After adjusting for risk factors this difference was no longer significant. CONCLUSION: Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections. These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections.

Chi-Square Distribution↗
PubMed1999

Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group.

OBJECTIVE: Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome. We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1. DESIGN AND METHODS: In Durban, South Africa 728 pregnant HIV infected women received either vitamin A (368) or placebo (360) in a randomized, double-blind trial. The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery. HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis. Results are reported on mother-to-child transmission rates up to 3 months of age. RESULTS: There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [20.3%; 95% confidence interval (CI), 15.7-24.9] and placebo groups (22.3%; 95% CI, 17.5-27.1), nor were there differences in foetal or infant mortality rates between the two groups. Women receiving vitamin A supplement were, however, less likely to have a preterm delivery (11.4% in the vitamin A and 17.4% in the placebo group; P = 0.03) and among the 80 preterm deliveries, those assigned to the vitamin A group were less likely to be infected (17.9%; 95% CI, 3.5-32.2) than those assigned to the placebo group (33.8%; 95% CI, 19.8-47.8). CONCLUSION: Vitamin A supplementation, a low-cost intervention, does not appear to be effective in reducing overall mother-to-child transmission of HIV; however, its potential for reducing the incidence of preterm births, and the risk of mother-to-child transmission of HIV in these infants needs further investigation.

Adult↗
PubMed1999

Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study. South African Vitamin A Study Group.

BACKGROUND: The observation that mother-to-child transmission of HIV-1 can occur through breastfeeding has resulted in policies that recommend avoidance of breastfeeding by HIV-1-infected women in the developed world and under specific circumstances in developing countries. We compared transmission rates in exclusively breastfed, mixed-fed, and formula-fed (never breastfed) infants to assess whether the pattern of breastfeeding is a critical determinant of early mother-to-child transmission of HIV-1. METHODS: We prospectively assessed infant-feeding practices of 549 HIV-1-infected women who were part of a vitamin A intervention trial in Durban, South Africa. The proportions of HIV-1-infected infants at 3 months (estimated by use of Kaplan-Meier life tables) were compared in the three different feeding groups. HIV-1 infection was defined by a positive RNA-PCR test. FINDINGS: At 3 months, 18.8% (95% CI 12.6-24.9) of 156 never-breastfed children were estimated to be HIV-1 infected compared with 21.3% (17.2-25.5) of 393 breastfed children (p=0.5). The estimated proportion (Kaplan-Meier) of infants HIV-1 infected by 3 months was significantly lower for those exclusively breastfed to 3 months than in those who received mixed feeding before 3 months (14.6% [7.7-21.4] vs 24.1% [19.0-29.2], p=0.03). After adjustment for potential confounders (maternal CD4-cell/CD8-cell ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV-1 transmission than mixed feeding (hazard ratio 0.52 [0.28-0.98]) and a similar risk to no breastfeeding (0.85 [0.51-1.42]). INTERPRETATIONS: Our findings have important implications for prevention of HIV-1 infection and infant-feeding policies in developing countries and further research is essential. In the meantime, breastfeeding policies for HIV-1-infected women require urgent review. If our findings are confirmed, exclusive breastfeeding may offer HIV-1-infected women in developing countries an affordable, culturally acceptable, and effective means of reducing mother-to-child transmission of HIV-1 while maintaining the overwhelming benefits of breastfeeding.

Adult↗