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Biomedical subjects

R Nugent

Publications and source records attributed to R Nugent.

At least 19 recordsLinked to original sources

Alternatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1-infected children in resource-poor settings.

Cheaper, simpler alternatives to CD4 lymphocyte count and HIV-1 RNA detection for assessing the prognosis of HIV-1 infection are needed for resource-poor settings. However, little is known about the predictive value of alternative assays, in particular in children. We assessed the prognostic value of total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume (haematocrit), and serum albumin for mortality in 376 HIV-1-infected, mainly African-American or Hispanic children enrolled during March, 1988 to January, 1991. In a Cox proportional hazards model, including all assay-alternatives to CD4 and RNA, total lymphocyte count (p<0.0001) and serum albumin (p=0.0107) independently predicted mortality. Further assessment of these markers is warranted in resource-poor settings.

Biomarkers↗

Radiation exposure during fluoroscopy: should we be protecting our thyroids?

BACKGROUND: Recent reports on thyroid cancer among Australian orthopaedic surgeons prompted the present study which sought to evaluate the effectiveness of lead shielding in reducing radiation exposure (RE) to the thyroid region during endo-urological procedures. METHODS: Radiation exposure to the thyroid region of the surgeon and scrubbed nurse was monitored for 20 consecutive operations over a 6-week period by thermoluminescent dosimeters (TLD). A TLD was placed over and underneath a thyroid shield of 0.5 min lead equivalent thickness to monitor the effect of shielding. RESULTS: Eight percutaneous nephrolithotomies, seven retrograde pyelograms and ureteric stentings and five ureteroscopies for calculous disease were monitored. Total exposure time was 63.1 min. For the surgeon, the total cumulative RE over and under the lead shield was 0.46 and 0.02 mSv, respectively, equating to a 23-times reduction in RE if shielding was used. This effectively reduced RE to almost background levels, which was represented by the control TLD exposure (0.01 mSv). CONCLUSION: Although RE without thyroid shields did not exceed current standards set by radiation safety authorities, no threshold level has been set below which thyroid carcinogenesis is unlikely to occur. Because lead shields are easy to wear and can effectively reduce RE to the thyroid region to near-background levels, they should be made easily available and used by all surgeons to avoid the harmful effects of radiation on the thyroid.

Fluoroscopy↗

Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185.

Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts </=500/microL (22% had counts <200/microL) and required zidovudine for maternal health (24% received zidovudine before pregnancy). Transmission was associated with lower maternal baseline CD4 cell count (odds ratio, 1.58 per 100-cell decrement; P=.005; 10.0% vs. 3.6% transmission for count <200 vs. >/=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.

Adult↗

Encephalopathy and progression of human immunodeficiency virus disease in a cohort of children with perinatally acquired human immunodeficiency virus infection. Women and Infants Transmission Study Group.

OBJECTIVE: To describe the incidence, predictors, and survival of children with human immunodeficiency virus (HIV) encephalopathy followed in the Women and Infants Transmission Study cohort. STUDY DESIGN: Retrospective review of clinical and immunologic staging of perinatally HIV-infected infants, based on the 1994 Centers for Disease Control and Prevention Classification System. RESULTS: Data were available for 128 HIV-infected children, with a median follow-up of 24 months. HIV encephalopathy was diagnosed in 27 (21%) of children. Median survival after diagnosis was 14 months. Of children with encephalopathy, 74% had at least moderate immunosuppression by the time of diagnosis. Encephalopathy represented the first acquired immunodeficiency syndrome-defining condition in 67%, and the only one in 26% of children. Hepatosplenomegaly or lymphadenopathy during the first 3 months of life was diagnosed in 63%, in contrast to 29% of those without encephalopathy (p value = 0.001). Cardiomyopathy was present in 30% of the children with encephalopathy versus 2% of those without encephalopathy. High viral load in infancy was associated with increased risk of encephalopathy but was not predictive of age at onset. CONCLUSIONS: Encephalopathy in children with HIV is common and is associated with high viral load, immunodeficiency, and shortened survival. Encephalopathy was more likely to develop in infants with early signs and symptoms of HIV, although age at onset could not be predicted.

AIDS Dementia Complex↗

Characteristics of acute pneumonia in human immunodeficiency virus-infected children and association with long term mortality risk. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: To describe the epidemiologic, clinical, radiologic, laboratory and treatment characteristics of acute pneumonia and its association with mortality in HIV-infected children. METHODS: Data were collected during a trial of intravenous immunoglobulin (IVIG) for infection prophylaxis (1988 to 1991); CD4+ percentage was measured and HIV RNA was assessed on stored sera collected at baseline and every 3 months. Mortality was recorded during the trial and updated through 1996. All reported physician-diagnosed pneumonia episodes underwent blinded review for trial endpoint classification as acute (new radiologic findings and presence of clinical symptoms) or nonacute. RESULTS: On blinded clinical trial endpoint review of all reported pneumonia episodes (n = 281), only 47% were classified as acute. One hundred thirty-one episodes of acute pneumonia were reported in 93 children (47 in 31 IVIG and 84 in 62 placebo patients, P < 0.01). The incidence of acute pneumonia was 24 episodes per 100 patient years. Findings associated with an acute bacterial process were uncommon (leukocytosis > or =15000/mm3 in 21% and fever > or =103 degrees F in 32% of episodes). Multiple acute episodes occurred in 34% of the children and were associated with increased risk of mortality in a univariate analysis (risk ratio, 2.1; 95% confidence interval, 1.3 to 3.4, P = 0.002), but in a multivariate model only baseline HIV RNA copy number and CD4+ percentage remained independently associated with mortality (relative risk, 2.0 and 1.4, respectively, P < 0.001). CONCLUSION: Acute pneumonia was a common occurrence in HIV-infected children and was associated with long term mortality risk. Multiple episodes of acute pneumonia likely represent a marker of progressive disease and immunologic dysfunction rather than being causally associated with increased long term mortality.

AIDS-Related Opportunistic Infections↗

The relationship between serum human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 lymphocyte percent, and long-term mortality risk in HIV-1-infected children. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

Association of human immunodeficiency virus type 1 (HIV-1) RNA level, CD4 cell percent, and mortality was examined in stored sera from 254 infected children in an intravenous immunoglobulin infection prophylaxis trial. Ninety-two children (36.2%) died (41 during the study, 51 during long-term follow-up). The geometric mean baseline HIV-1 RNA level was 104,626 copies/mL, and the mean CD4 cell percent was 25%. Relative risk of death (RR) was 2.1 if the baseline RNA level was >100,000 copies/mL (95% confidence interval [CI], 1.4-3.0) and was 3.0 if the baseline CD4 cell percent was <15% (95% CI, 2.2-4.0). If RNA levels increased after baseline, the RR was 1.8 (95% CI, 1.3-2.6), and if the CD4 cell percent dropped to <15%, the RR was 2.8 (95% CI, 1.6-4.9). In a multivariate model, both baseline RNA level and CD4 cell percent were independently associated with mortality risk. In a time-dependent model, the RR per log10 increase in HIV-1 RNA copy numbers was 2.8 (95% CI, 2.1-3.6) and per 5 percentage point decrement in CD4 cell percent was 1.3 (95% CI, 1.2-1.5). Both variables should be considered for in decision-making regarding therapy and evaluation of antiretroviral response.

AIDS-Related Opportunistic Infections↗

Bacterial colonization of the vagina during pregnancy in four ethnic groups. Vaginal Infections and Prematurity Study Group.

OBJECTIVE: Our purpose was determine whether there are ethnic differences in vaginal colonization with organisms reputed to be associated with preterm delivery. STUDY DESIGN: In seven urban medical centers in the United States from 1984 to 1989, 13,747 predominantly low-socioeconomic-status women at 23 to 26 weeks' gestation were grouped according to ethnic origin. Each had a vaginal culture for multiple organisms and Gram's stain and pH test to diagnose bacterial vaginosis. Multivariate analyses with adjustment for maternal age, insurance status, marital status, smoking history, education level, age at first sexual intercourse, and number of male partners in the past year were also performed to determine the odds ratio for a black woman versus a white woman having a positive test result. RESULTS: For nearly every organism studied, Asian-Pacific Islander and white women had the lowest percentages of positive test results whereas black women had the highest. When black and white women are compared, black women were more likely to be colonized with Chlamydia trachomatis, 16% versus 5%; Neisseria gonorrhoeae, 2.5% versus 0.4%; Bacteroides sp., 25% versus 14%; bacterial vaginosis, 23% versus 9%; and the four other organisms evaluated. Adjustment for potential confounders including certain health behaviors did not markedly change the risk of a black woman having a positive test result, with the odds ratios for colonization with each organism ranging from 1.8 to 6.4. CONCLUSIONS: Highly significant differences exist in vaginal colonization patterns among women of different ethnic groups, with the highest rates of potentially pathogenic organisms observed in black women and the lowest in Asian-Pacific Islander women. Differences in health behaviors do not explain the variation in colonization rates.

Adult↗

Sinusitis in children infected with human immunodeficiency virus: clinical characteristics, risk factors, and prophylaxis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

The clinical presentation, radiological and laboratory evaluation, treatment, and risk factors of sinusitis in a cohort of 376 human immunodeficiency virus (HIV)-infected children from a placebo-controlled clinical trial of intravenous immunoglobulin (IVIG) as prophylaxis for infections were examined. Ninety-five episodes of sinusitis were described in 60 patients; one-third of the patients had two or more episodes. Sinusitis episodes were commonly associated with nonspecific, chronic symptoms (67.4%, persistent nasal discharge; 54.7%, nocturnal or persistent cough), whereas symptoms more specific to acute sinusitis were less frequent (17.9%, headache or facial pain; 9.5%, periorbital swelling; 25.3%, temperature of > or = 102 degrees F; 9%, total white blood cell count of > or = 15,000/mm3). The sinuses primarily involved were the maxillary sinus (85.9%) and the ethmoidal sinus (42.3%); 36% of episodes involved two or more sinuses. Preceding respiratory infections did not appear to increase the risk of sinusitis, and CD4+ lymphocyte counts in children with and without sinusitis did not differ. Neither monthly IVIG prophylaxis nor three times weekly trimethoprimsulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia decreased the risk of sinusitis. Sinusitis in HIV-infected children is most often subacute and recurrent. Evaluations of new modalities for prophylaxis for sinusitis are needed.

AIDS-Related Opportunistic Infections↗

MRI and PET studies of manganese-intoxicated monkeys.

Using MRI and PET, we investigated the consequences of manganese intoxication in a primate model of parkinsonism and dystonia. Three rhesus monkeys were injected intravenously with doses of 10 to 14 mg/kg of MnCl2 on seven occasions, each a week apart. Two animals became hypoactive with abnormal extended posturing in the hind limbs. These motor disturbances did not improve with administration of levodopa. In all three monkeys, T1-weighted MRI demonstrated high signal intensities in the regions of the striatum, globus pallidus, and substantia nigra. No significant changes were found on [18F]6-fluoro-L-dopa, [11C]raclopride, or [18F]fluorodeoxyglucose PET. These results are consistent with the pathologic findings, which were primarily confined to the globus pallidus, and indicate that manganese intoxication is associated with preservation of the nigrostriatal dopaminergic pathway, despite clinical evidence of parkinsonian deficits. Chronic manganese intoxication may cause parkinsonism by damaging output pathways downstream to the nigrostriatal dopaminergic pathway. This is consistent with the demonstrated lack of therapeutic response to levodopa.

Animals↗

Crossover of placebo patients to intravenous immunoglobulin confirms efficacy for prophylaxis of bacterial infections and reduction of hospitalizations in human immunodeficiency virus-infected children. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

After completion of a placebo-controlled trial of intravenous immunoglobulin (IVIG) infection prophylaxis, patients were offered open label IVIG and optional participation in a follow-up study. The purpose of the follow-up study was to evaluate the IVIG effect in original placebo recipients and longevity of IVIG benefit in original IVIG recipients. Of 212 human immunodeficiency virus-infected children on study at trial closure, 148 (67 of 98 (68%) placebo and 81 of 114 (71%) IVIG patients) received open label IVIG for a mean of 16 months. When open label IVIG was begun, 45% were receiving trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia (43% of placebo and 47% of IVIG patients) and 54% were receiving zidovudine (55% of placebo and 53% of IVIG patients). In patients who received placebo during the original study, the rate of serious bacterial infections was significantly lower after change to open label IVIG (estimated 15.8 fewer episodes/100 patient years; 95% confidence interval, 3.2 to 28.5; P = 0.014). Similar findings were observed for minor bacterial infections (estimated 61.2 fewer/100 patient years; 95% confidence interval, 29.2 to 93.3; P < 0.001) and hospitalizations (estimated 43.7 fewer/100 patient years; 95% confidence interval, 27.7 to 59.6; P < 0.001). Decreases were observed whether or not trimethoprim-sulfamethoxazole prophylaxis was being given at the time open label IVIG was begun. In patients who received IVIG during the original study, no significant difference was seen in infections or hospitalizations after change to open label IVIG.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Effect of intravenous immunoglobulin (IVIG) on CD4+ lymphocyte decline in HIV-infected children in a clinical trial of IVIG infection prophylaxis. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

Our objective was to evaluate the effect of intravenous immunoglobulin (IVIG) on absolute CD4+ lymphocyte count (CD4+ count) trends in human immunodeficiency virus- (HIV) infected children enrolled in a trial of IVIG for infection prophylaxis. To that end, we conducted a randomized, double-blind, outpatient trial comparing subjects treated with 400 mg per kilogram of IVIG every 28 days with those given 0.1% albumin placebo. CD4+ counts were measured at entry and every 12 weeks. Twenty-eight clinical centers in mainland United States and Puerto Rico participated. Previous reports showed IVIG efficacy for infection prophylaxis in 313 patients with entry CD4+ counts of > or = 0.20 x 10(9)/L (> or = 200/mm3). Two hundred and seventy-seven (89%) of these 313 children had three or more CD4+ counts measured during the trial and were included in evaluation of CD4+ count trends. Rates of CD4+ count decline, as measured by regression slopes, were compared between IVIG and placebo groups using generalized linear models, comparing unadjusted, age-adjusted, and standardized age-adjusted data. Potential covariate effects were assessed by modeling change in CD4+ count in terms of log change between successive measurements. Age-adjusted slope analysis showed slowing of CD4+ count decline by 13.5 cells/mm3 per month in IVIG compared with placebo recipients (95% confidence interval, 3.1-23.9, p = 0.012). Modeling log change between measurements documented a beneficial effect of IVIG that was cumulative over time and independent of other therapies. Occurrence of serious bacterial infection in the interval before CD4+ count measurement or death was independently associated with more rapid CD4+ count decline (p = 0.01 and p = 0.008, respectively). Zidovudine therapy was associated with a transient increase in CD4+ count. Benefits of IVIG include slowing of CD4+ count decline as well as previously reported reductions in serious and minor bacterial and viral infections in subjects with entry CD4+ counts of > or = 0.20 x 10(9)/L. This finding provides corroboration for the hypothesis that immunologic mechanisms contribute to the pathogenesis of CD4+ decline in HIV infection.

Age Factors↗

Reproducibility of the diagnosis of cervicitis in pregnancy.

Cervicitis has been associated with several infections of the female genital tract. Criteria have been established for making the diagnosis of cervicitis in gynecologic populations but there are no well-established criteria for diagnosing cervicitis in obstetrical populations. Because of the association of the cervicitis and sexually transmitted diseases, and because of the association of sexually transmitted diseases and adverse pregnancy outcome, the present study was undertaken in an attempt to establish criteria for the diagnosis of cervicitis in pregnancy. We also attempted to determine the reproducibility of that diagnosis with respect to intra- and interobserver variability. We concluded that intraobserver variability is improved after specific training has been completed and that interobserver variability may be reduced to an acceptable level. On a public health scale, this may allow for identification of a population at high risk for adverse pregnancy outcome when sophisticated microbiologic techniques are unavailable.

Adolescent↗

Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen.

Men with PRL-producing macroadenomas often present with hypogonadism and impotence. This report documents exacerbation of a PRL-secreting tumor after two separate 200-mg testosterone enanthate (T) injections despite continued bromocriptine (BRC) therapy. A 37-yr-old man with a 60-mm invasive tumor and a serum PRL level of 13,969 +/- 332 ng/ml (mean +/- SD) responded to BRC therapy with rapid disappearance of visual field defect, headache, and facial pain as well as decrease in serum PRL to 5,103 +/- 1,446 ng/ml. T injection was followed by severe headache, facial pain, and increase in PRL to 13,471 ng/ml. Visual field deterioration and increased tumor size (height, 40-43 mm) by computed tomography were documented. A relationship between T injection and exacerbation of the prolactinoma was not recognized until after a second T injection 3 months later. After that therapy, baseline PRL increased from 6,900 to 12,995 ng/ml. The hypothesis that T was aromatized to estradiol, directly stimulating lactotrophs, was supported by an increase in serum estradiol from 24 to 51 pg/ml after the second T injection. Although T treatment is accepted as appropriate therapy for hypogonadism in men with prolactinomas, it may not only interfere with the response of the tumor to BRC therapy, but even stimulate tumor growth and secretion.

Adenoma↗

Pathological and clinical study of Müller's muscle in Graves' ophthalmopathy.

Specimens of Müller's muscle from patients with Graves' disease were examined for evidence of morphologic, histochemical, immunohistochemical and electron microscopic changes. No scarring, significant inflammation or shared antigenicity between Müller's muscle and thyroglobulin-related antigens was found. There were moderate numbers of mast cells in 48 of 66 specimens. Computed tomography in 16 patients with Graves' ophthalmopathy showed enlargement of the superior rectus-levator complex in 17 of 28 orbits with lid retraction. However, no correlation was found between the amount of lid retraction and the degree of enlargement of the muscle complex.

Ciliary Body↗