Food system development pathways for healthy, nature-positive and inclusive food systems.

Sustainable food systems require the integration of and alignment between recommendations for food and land use practices, as well as an understanding of the political economy context and identification of entry points for change. We propose a food systems transformation framework that takes these elements into account and links long-term goals with short-term measures and policies, ultimately guiding the decomposition of transformation pathways into concrete steps. Taking the transition to healthier and more sustainable diets as an example, we underscore the centrality of social inclusion to the food systems transformation debate.

Quantifying risks of preterm birth in the Arkansas Medicaid population, 2001-2005.

OBJECTIVE: The objective of this study was to examine risks of preterm births, quantify the explanatory power achieved by adding medical and obstetric risk factors to the models and to examine temporal changes in preterm birth due to changes in Medicaid eligibility and the establishment of a maternal-fetal medicine referral system. STUDY DESIGN: The study used data from the 2001 to 2005-linked Arkansas (AR) Medicaid claims and birth certificates of preterm and term singleton deliveries (N=89 459). Logistic regression modeled the association among gestational age, demographic characteristics and risk factors, pooled and separately by year. RESULT: Physiological risk factors were additive with demographic factors and explained more of the preterm birth ≤32 weeks than later preterm birth. Changing eligibility requirements for Medicaid recipients and increasing the financial threshold from 133 to 200% of federal poverty level had an impact on temporal changes. The proportion of births ≤32 weeks declined to 33%, from 3.0 to 2.0. However, later preterm births declined and then increased in the last year. CONCLUSION: Physiological conditions are strongly associated with early preterm birth. Maternal behaviors and other stressors are predictive of later preterm birth. Unmeasured effects of poverty continue to have a role in preterm birth. Further examination of the referral system is needed.

Calcified cerebral emboli.

Intracranial calcifications may represent calcified cerebral emboli. Calcified emboli may be overlooked even though cerebral CT is widely used as a stroke assessment. We report 4 cases of calcified cerebral emboli and demonstrate the value of CT in the diagnosis and temporal evaluation of such emboli.

Diffusion-weighted imaging findings in Balo concentric sclerosis.

Balo concentric sclerosis is a rare demyelinating disease. Pathognomonic features have been previously described. Diffusion-wighted imaging findings have not been previously described in Balo concentric sclerosis. We describe the diffusion-weighted imaging findings in a 45-year-old lady with Balo concentric sclerosis. Diffusion-weighted imaging offers insight into the possible pathophysiology of this rare disease.

Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review.

BACKGROUND/AIMS: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorly understood. Adult onset xanthogranuloma (AOX), adult onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD) are the four syndromes within this disorder, which is diagnosed by characteristic histopathology. Experience with eight cases prompted a multi-institutional effort to study the histopathology, immunohistochemistry, clinical findings, and systemic associations in this disorder. METHODS: 22 cases, including histopathological slides, were compiled. Published reports were identified by an English language Medline search (1966-2005) and review of reference citations. Each case in this series and the literature was classified as one of four syndromes and then analysed for age onset, sex, skin xanthoma, orbital location, immune dysfunction, internal organ and bone lesions, treatment, and outcome. The histopathology in each of these cases was reviewed by two pathologists. Immunhistochemical stains (CD3, CD4, CD8, L26) were performed in 14 cases where unstained slides were available. RESULTS: 137 cases were compiled. There was no sex or age difference between syndromes. AOX, AAPOX, NBX affect the anterior orbit, ECD tends to be diffuse and intraconal. Skin lesions are found in all the syndromes. Immune dysfunction was noted in all cases of AAPOX and NBX; 11% of NBX and all ECD patients had internal organ disease. Treatment included surgery, corticosteroids, other chemotherapeutic agents, radiotherapy, and combinations of these. No AOX or AAPOX deaths occurred; 66% of ECD patients died. All 22 cases had xanthoma cells; most had Touton giant cells. Lymphocytes were present in all cases and occurred as aggregates (mostly in AAPOX) or diffuse populations mixed with fibroblasts (mostly in ECD). Immunohistochemistry revealed the majority of these to be CD8+. Necrosis was most marked in NBX. CONCLUSION: Adult xanthogranuloma of the orbit is rare, making prospective evaluation or meta-analysis impossible. The best treatment is unknown but seems to be with multiagent chemotherapy guided by histopathological, immunohistochemical, and systemic findings.

Localised invasive sino-orbital aspergillosis: characteristic features.

BACKGROUND/AIM: To describe the characteristic constellation of historical, clinical, radiographic, and histopathological findings of localised invasive sino-orbital aspergillosis based on the authors' recent experience of four consecutive cases presenting over a 6 month period. Treatment and outcome are reviewed. METHODS: A case series of four patients with review of the English language literature. RESULTS: There have been 17 reported cases of invasive sino-orbital aspergillosis in healthy individuals over the past 33 years. The authors report four patients who presented during a 6 month period with persistent and significant pain followed by progressive ophthalmic signs-clinical histories reflecting the literature. Similar imaging findings were also noted: focal hypodense areas within apical infiltrates on contrasted computed tomography correspond to abscesses seen at surgery, and sinus obliteration or involvement of the adjacent sinus lining was noted on magnetic resonance imaging. Bone erosion (often focal) was also seen. There is frequently a delay in making the correct diagnosis, and often disease progression occurs despite treatment. CONCLUSIONS: The authors encountered four cases of invasive sino-orbital aspergillosis, three of which occurred in otherwise healthy individuals. The clinician must be aware of the characteristic presentation so that earlier diagnosis, management, and improved outcomes can be achieved.

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.

Heritability of body length and measures of body density and their relationship to backfat thickness and loin muscle area in swine.

The objective of this study was to estimate heritability for body length (LEN) at the end of performance testing and to estimate genetic correlations with backfat (BF) thickness and loin muscle area (LMA) in Landrace, Yorkshire, Duroc, and Hampshire breeds of swine. Also examined were two measures of body density involving body length and weight and their relationships to backfat and loin muscle area. Data consisted of performance test records collected in a commercial swine operation from 1992 to 1999. Boars from 60% of the litters were culled at weaning based on a maternal breeding value of the dam. Remaining boars and all females were grown to 100 d of age (15,594, 55,497, 12,267, and 9,782 Landrace, Yorkshire, Duroc, and Hampshire pigs, respectively). At this time, all pigs were weighed (WT100) and selected for performance testing based on a combination of maternal and performance indexes, which differed by breed. All pigs were weighed at the end of the 77 d performance test (WT177) when BF, LMA, and LEN were measured. Two measures of body density involving length were calculated: Body mass index (BMI) = WT177/LEN2 and body density (DENSITY) = WT177/LEN. For each breed, genetic parameters were estimated using an animal model with random litter effects and multiple-trait REML procedures. A series of three-trait models including WT100 and combinations of two other traits in each analysis was conducted. Fixed effects included contemporary group and age as a covariate. Average estimates of heritability were 0.16 to 0.32 for LEN (unadjusted for WT177), 0.12 to 0.26 for LEN (adjusted for WT177), 0.23 to 0.33 for DENSITY, and 0.16 to 0.25 for BMI. Genetic correlations between LEN and LMA were low. Genetic correlations between LEN (unadjusted for WT177) and BF were 0.10 to 0.41. Adjusting LEN for WT177 gave correlations of 0.11 for Landrace and Hampshire and negative correlations (-0.06 and -0.19, respectively) for Yorkshire and Duroc. Genetic correlations between LMA and DENSITY and between LMA and BMI were comparable and ranged from 0.44 to 0.54. Genetic correlations between BF and DENSITY were slightly higher (0.53 to 0.68) than those between BF and BMI (0.37 to 0.67). In these data, not much relationship between BF and body length at a constant weight and age was found. There was a negative relationship between LMA and LEN at a constant weight and age, implying that longer pigs had smaller LMA.

Maternal effects on traits measured during postweaning performance test of swine from four breeds.

The objective of this study was to investigate the importance of maternal genetic effects on postweaning performance traits of Yorkshire, Landrace, Duroc, and Hampshire breeds of swine. Data consisted of performance test records collected in a commercial swine operation from 1992 to 1999. Boars from 60% of the litters were culled at weaning based on a combination of maternal and performance indexes that differed by breed. Remaining boars and all females were grown to 100 d of age. At this time all pigs were weighed (WT100) and selected for testing using recalculated breed-specific indexes (n = 15,594, 55,497, 12,267, and 9,782 for Landrace, Yorkshire, Duroc, and Hampshire, respectively). All pigs were weighed at the end of the 77-d test, and backfat (BF) and loin eye area (LEA) were measured over the 12th rib by ultrasound. Average daily feed intake was calculated for boars, and ADG was calculated for all animals. Genetic parameters were estimated for each breed and trait using multiple-trait DFREML procedures. Fixed effects were contemporary groups and either initial or final test age as a covariate. Four models were examined. Model 1 included only the additive genetic effect of the animal. Model 2 added the common litter environmental effect; Model 3 added the maternal genetic value assumed to be uncorrelated with additive genetic effects. Model 4 was the same as Model 3 with additive and maternal genetic effects assumed to be correlated. All models were two-trait models with WT100 as the second trait. Ratios of likelihoods were used to compare models. Maternal effects were important (P < 0.05) for WT100, ADG, ADFI, LEA, and BF in Landrace; for WT100, ADG, LEA, and BF in Yorkshire; for WT100 and ADG in Duroc, and for WT100 in Hampshire. Estimates of heritabilities for direct additive effects using the appropriate model for ADG, ADFI, LEA, and BF were 0.28, 0.34, 0.48, and 0.63 for Landrace; 0.26, 0.31, 0.39, and 0.65 for Yorkshire; 0.14, 0.20, 0.26, and 0.35 for Duroc; and 0.17, 0.23, 0.25, and 0.31 for Hampshire, respectively. Heritability estimates for maternal genetic effects for ADG, ADFI, LEA, and BF were 0.02, 0.05, 0.06, and 0.07 for Landrace and 0.02, 0, 0.04, and 0.06 for Yorkshire, respectively. They were zero for all traits except ADG (0.03) in Duroc and for all traits in Hampshire. Maternal effects may need to be considered in genetic evaluation of performance traits in some breeds of swine.

Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.

BACKGROUND: Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. METHODS: We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. RESULTS: Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). CONCLUSIONS: Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.

Baló's concentric sclerosis: surviving normal myelin in a patient with a relapsing-remitting dinical course.

Baló's concentric sclerosis is a demyelinating disorder in which bands of demyelination alternate with concentric bands of myelin preservation. The pathogenesis of the lesion is unknown. Previous reports using modern histopathologic techniques have shown the bands of myelin preservation to be comprised of remyelinated or partially demyelinated myelin. Here we report a case of Baló's concentric sclerosis in a 24-year-old East Indian patient with a previous history of relapsing-remitting multiple sclerosis (MS). Pathologically, the bands of myelin preservation showed myelin sheaths of normal thickness, with focal areas of demyelination. The findings, taken together with those of previously reported cases, suggest that Baló's concentric sclerosis is a variant of MS, and the concentric lesion may be an intermediary form in evolution of a chronic active MS plaque. The pathogenesis of this concentric lesion may be explained by periodic suppression of demyelination in the rapidly expanding border, allowing remyelination or only transient incomplete demyelination to occur.

A prospective randomized comparison of CT and MRI pre-operative localization for pallidotomy.

OBJECTIVE: During the pallidotomy procedure, is pre-operative localization with MRI more accurate than CT and does it result in a significant difference in surgical outcome? METHODS: Twenty-four Parkinson's Disease patients received a unilateral pallidotomy for their motor symptoms. Dyskinesia was scored pre- and six weeks postoperatively. All patients had a pre-operative CT scan and MRI to calculate the target co-ordinates. Patients were then randomly selected to proceed with either the CT or MRI coordinates. The final position for the lesion was determined with intraoperative macrostimulation and impedance measurements. The percentage improvement of dyskinesia was noted for each patient and the two groups compared by the Mann-Whitney test. The distance from the final target to the MRI and CT pre-operative co-ordinates were calculated for each patient. The mean distance for each modality was then compared by Student's t-test. The number of electrode repositionings was also recorded for each patient and the two groups compared by the nonparametric Mann-Whitney test. RESULTS: Although the MRI co-ordinates were significantly (p<0.023) closer to the final target, this did not translate into a significant reduction in electrode repositionings. There was no significant difference in the improvement in dyskinesia between the two groups. CONCLUSIONS: The pre-operative MRI co-ordinates were significantly (p=0.023) closer to the final target than those from the CT. The potential advantages and disadvantages of both imaging modalities are reviewed. There was no significant difference in surgical outcome using either MRI or CT for pre-operative localization in pallidotomy.

Quantification of human immunodeficiency virus type 1 p24 antigen and antibody rivals human immunodeficiency virus type 1 RNA and CD4+ enumeration for prognosis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

BACKGROUND: The sensitivity, specificity and positive predictive value of baseline serum concentrations of HIV-1 immune complex-dissociated (ICD) p24 antigen for predicting disease progression and mortality were assessed and compared with results obtained for HIV-1 ICD p24 antigen with HIV-1 p24 antibody and for HIV-1 RNA with CD4+ lymphocyte percent. METHODS: Data from HIV-infected children enrolled in a North American clinical trial (National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial) were analyzed. Disease progression was defined as growth failure, CD4+ lymphocyte percent decline to <15% after study entry or development of an AIDS-defining opportunistic infection. RESULTS: Baseline samples were available for ICD p24 antigen testing (median concentration, 319 pg/ml; range, <50 to 15,640) in 240 children. The combination of detectable ICD p24 antigen and low p24 antibody was more sensitive but less specific than the combination of high HIV-1 RNA and low CD4+ lymphocyte percent in predicting disease progression and mortality. Using receiver operating characteristic curves, the specificity of ICD p24 antigen with p24 antibody for classifying children's disease progression or mortality was as great as, or greater than, HIV-1 RNA with CD4+ lymphocyte percent at points on the curve corresponding to higher sensitivity. CONCLUSIONS: The use of ICD p24 antigen with p24 antibody to identify children at high risk of disease progression or mortality could be a viable alternative to the more expensive and technically difficult HIV-1 RNA and CD4+ lymphocyte assays in resource-poor settings, including developing countries where the majority of children with HIV-1 infection reside.

Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

BACKGROUND: Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence. METHODS: To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation. RESULTS: Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available for 953 women in the metronidazole group and 966 in the placebo group. Preterm delivery occurred in 116 women in the metronidazole group (12.2 percent) and 121 women in the placebo group (12.5 percent) (relative risk, 1.0; 95 percent confidence interval, 0.8 to 1.2). Treatment did not prevent preterm deliveries that resulted from spontaneous labor (5.1 percent in the metronidazole group vs. 5.7 percent in the placebo group) or spontaneous rupture of the membranes (4.2 percent vs. 3.7 percent), nor did it prevent delivery before 32 weeks (2.3 percent vs. 2.7 percent). Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit. CONCLUSIONS: The treatment of asymptomatic bacterial vaginosis in pregnant women does not reduce the occurrence of preterm delivery or other adverse perinatal outcomes.

SNIP, a novel SNAP-25-interacting protein implicated in regulated exocytosis.

Synaptosome-associated protein of 25 kDa (SNAP-25) is a presynaptic membrane protein that has been clearly implicated in membrane fusion in both developing and mature neurons, although its mechanisms of action are unclear. We have now identified a novel SNAP-25-interacting protein named SNIP. SNIP is a hydrophilic, 145-kDa protein that comprises two predicted coiled-coil domains, two highly charged regions, and two proline-rich domains with multiple PPXY and PXXP motifs. SNIP is selectively expressed in brain where it co-distributes with SNAP-25 in most brain regions. Biochemical studies have revealed that SNIP is tightly associated with the brain cytoskeleton. Subcellular fractionation and immunofluorescence localization studies have demonstrated that SNIP co-localizes with SNAP-25 as well as the cortical actin cytoskeleton, suggesting that SNIP serves as a linker protein connecting SNAP-25 to the submembranous cytoskeleton. By using deletion analysis, we have mapped the binding domains of SNIP and SNAP-25, and we have demonstrated that the SNIP-SNAP-25 association is mediated via coiled-coil interactions. Moreover, we have shown that overexpression of SNIP or its SNAP-25-interacting domain inhibits Ca(2+)-dependent exocytosis from PC12 cells. These results indicate that SNIP is involved in regulation of neurosecretion, perhaps via its interaction with SNAP-25 and the cytoskeleton.

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.

Genetic parameters for production traits and measures of residual feed intake in large white swine.

The purpose of this study was to estimate genetic parameters for ADG, backfat thickness and loin eye area (LEA), and measures of feed intake and efficiency for purebred Large White boars born from 1990 to 1997. Boars from 60% of the litters were culled at weaning based on a maternal breeding value (index) of the dam, and remaining boars (n = 26,706) were grown to 100 d of age. Selection of boars for individual pen testing was based on a combination of growth and maternal indices. Boars were fed a corn-soybean meal diet that was 1.14% lysine, 19% protein, and 3,344 kcal/kg ME for approximately 77 d. Boars were weighed at the beginning and end of the test, and feed intake was recorded. Daily feed intake (DFI), ADG, and feed:gain ratio (FG) were computed. Four measures of residual feed intake (RFI) were estimated as the difference between actual feed intake and that predicted from models that included 1) initial test age and weight and test ADG (RFI1); 2) initial test age and weight, test ADG, and backfat (RFI2); 3) initial test age and weight, test ADG, and LEA (RFI3); and 4) initial test age and weight, test ADG, backfat, and LEA (RFI4). Genetic parameters were estimated using an animal model and single- or multiple-trait DFREML procedures. Models included fixed effects of contemporary groups and initial test age as a covariate and random animal and litter effects. Heritability estimates for test ADG, DFI, FG, backfat, LEA, RFI1, RFI2, RFI3, and RFI4 were .24, .23, .16, .36, .24, .17, .11, .15, and .10, respectively. Genetic correlations between ADG and backfat, ADG and LEA, ADG and DFI, and ADG and FG were .37, .36, .82, and -.32, respectively. Genetic correlations between ADG and measures of residual feed intake ranged from .11 to .18. Genetic correlations of backfat with LEA, DFI, and FG were -.27, .64, and .40, respectively. Genetic correlations of backfat with RFI measures were higher when backfat was not included in the estimation of RFI. Genetic correlations for LEA with DFI and FG were 0 and -.52, respectively. Genetic correlations for LEA with RFI measures were all negative and ranged from -.31 to -.51. Genetic correlations indicate that selection for reduced RFI could be made without adversely affecting ADG. Backfat should also decrease, and LEA should increase. The amount of change in backfat or LEA would depend on the measure of RFI used.

Changes in immune activation markers during pregnancy and postpartum.

Changes in CD4 + cell levels and other immune parameters have been reported to occur during pregnancy but the timing of these alterations and their relationship to changes in immune function have not been well characterized. In addition, the influence of sociodemographic, obstetric, and other covariates on these relationships is largely unknown. We measured three immune activation markers, soluble interleukin-2 receptor (sIL-2Ralpha), soluble CD8 antigen (sCD8), and neopterin during pregnancy and postpartum in 170 HIV-1-seronegative women enrolled in the Mothers and Infants Cohort Study. Ante-partum and postpartum changes in these markers were examined using multivariable longitudinal random effects models. Neopterin levels began to rise well before delivery and were in decline by 2 months postpartum. sIL-2Ralpha and sCD8 levels increased at or near delivery and peaked by 2 months postpartum. After adjustment for other variables, the peak in sIL-2Ralpha was greater among women with pre-term than full-term deliveries (P = 0.05). All three markers were higher in whites than non-whites and in 'hard' drug users than non-users (P < or = 0.001 for each). After adjustment for these and other variables, hepatitis C virus (HCV) seropositivity was associated with higher levels of sCD8 and neopterin (P < or = 0.001 for each) but not sIL-2Ralpha (P = 0.27). These longitudinal data indicate that a state of broad immune activation develops at or near delivery. A number of maternal variables appear to influence the magnitude of these changes.

Serum HIV-1 p24 antibody, HIV-1 RNA copy number and CD4 lymphocyte percentage are independently associated with risk of mortality in HIV-1-infected children. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: The role of HIV-1 antibody in modulating disease progression must be assessed in the context of other immune and viral load markers. We evaluated the association between HIV-1 p24 antibody, HIV-1 RNA, immune complex-dissociated (ICD) p24 antigen, CD4 cell percentage, and mortality in a cohort of 218 HIV-infected children enrolled in a trial of intravenous immunoglobulin prophylaxis of bacterial infections. METHODS: CD4 cell percentage was measured and sera collected and stored at baseline and every 3 months on study (1988-1991). Stored sera were assayed for HIV-1 p24 antibody, HIV-1 RNA, and ICD p24 antigen. Mortality was recorded during the trial and updated through 1996 (mean total follow-up, 6.3 years). RESULTS: Eighty-one (37%) children died; probability of mortality for children with baseline HIV-1 p24 antibody concentrations of undetectable (< 1), 1-4, 5-124, and > or = 125 reciprocal titer units (RTU) was 61, 50, 24, and 10%, respectively. A 3.5-fold increase in the relative risk (RR) of death [95% confidence interval (CI), 2.2-5.5] was observed among children with baseline HIV-1 p24 antibody concentration < 5 RTU compared with > or = 5 RTU. In multivariate analyses, p24 antibody, HIV-1 RNA, and CD4 cell percentage but not ICD p24 antigen were independently associated with mortality; the RR of death increased by 1.7 (95% CI, 1.3-2.1) for each log10 decrement in baseline HIV-1 p24 antibody. CONCLUSIONS: HIV-1 p24 antibody, HIV-1 RNA and CD4 cell percentage independently predict mortality amongst infected children. Whereas CD4 cell percentage provides an estimate of the general degree of immune suppression, HIV-1 p24 antibody could provide an easily obtained, inexpensive assessment of CD4 cell function and could augment prognostic information provided by CD4 cell count and viral load for clinical management of infected children.

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 /=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.