Anisotropic energy gaps of iron-based superconductivity from intraband quasiparticle interference in LiFeAs.

If strong electron-electron interactions between neighboring Fe atoms mediate the Cooper pairing in iron-pnictide superconductors, then specific and distinct anisotropic superconducting energy gaps Δ(i)(k) should appear on the different electronic bands i. Here, we introduce intraband Bogoliubov quasiparticle scattering interference (QPI) techniques for determination of Δ(i)(k) in such materials, focusing on lithium iron arsenide (LiFeAs). We identify the three hole-like bands assigned previously as γ, α(2), and α(1), and we determine the anisotropy, magnitude, and relative orientations of their Δ(i)(k). These measurements will advance quantitative theoretical analysis of the mechanism of Cooper pairing in iron-based superconductivity.

Nematic electronic structure in the "parent" state of the iron-based superconductor Ca(Fe(1-x)Co(x))2As2.

The mechanism of high-temperature superconductivity in the newly discovered iron-based superconductors is unresolved. We use spectroscopic imaging-scanning tunneling microscopy to study the electronic structure of a representative compound CaFe1.94Co0.06As2 in the "parent" state from which this superconductivity emerges. Static, unidirectional electronic nanostructures of dimension eight times the inter-iron-atom distance a(Fe-Fe) and aligned along the crystal a axis are observed. In contrast, the delocalized electronic states detectable by quasiparticle interference imaging are dispersive along the b axis only and are consistent with a nematic alpha2 band with an apparent band folding having wave vector q vector congruent with +/-2pi/8a(Fe-Fe) along the a axis. All these effects rotate through 90 degrees at orthorhombic twin boundaries, indicating that they are bulk properties. As none of these phenomena are expected merely due to crystal symmetry, underdoped ferropnictides may exhibit a more complex electronic nematic state than originally expected.

Glycosylation of proteinase 3 (PR3) is not required for its reactivity with antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis.

OBJECTIVE: The glycosylation status of autoantigens appears to be crucial for the pathogenesis of some autoimmune diseases, since carbohydrates play a crucial role in the distinction of self from non-self. Proteinase 3 (PR3), the main target antigen for anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener's granulomatosis (WG), contains two Asn-linked glycosylation sites. The present study explores the influence of the glycosylation status of PR3 on the PR3 recognition by ANCA in a well characterized population of patients with WG. METHODS: Forty-four patients with WG (459 serum samples) who participated in a multicenter randomized trial, were tested by capture ELISA for ANCA against PR3 and deglycosylated recombinant variants of PR3. RESULTS: The patients were followed for a median of 27 months, and the median number of serum samples per patient was 10. At baseline, the correlation between the levels of ANCA against PR3 and against all the deglycosylated recombinant variants of PR3 were greater than 0.94 (?<0.001 for all the comparisons). Longitudinal analyses comparing the levels of ANCA against PR3 versus all the deglycosylated recombinant variants of PR3, using linear mixed models, showed no significant statistical differences (rho >or=0.90 in all cases). CONCLUSION: The glycosylation status of PR3 has no impact on its recognition by ANCA in WG.

Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept.

OBJECTIVE: To investigate the effect of etanercept therapy on radiographic progression in patients with ankylosing spondylitis (AS). METHODS: Patients with AS who had previously participated in a 24-week randomized, double-blind, placebo-controlled trial of etanercept therapy were enrolled in a 72-week open-label extension. Radiographs of the cervical and lumbar spine from patients who received etanercept (25 mg twice weekly) for up to 96 weeks were compared with radiographs from patients in a large prevalence cohort (Outcome Assessments in Ankylosing Spondylitis International Study [OASIS]) who had not been treated with anti-tumor necrosis factor alpha (anti-TNFalpha) agents. Radiographs obtained at 2 time points up to 96 weeks apart from patients in both study populations were digitized and read by 2 independent readers who were blinded with regard to patient group and sequence. The primary end point was the 96-week change in the modified Stoke AS Spine Score (mSASSS). RESULTS: A total of 257 patients treated with etanercept were compared with 175 unselected patients from the OASIS study. There was no significant difference in the change in the mSASSS from baseline among patients who received etanercept (mean +/- SD 0.91 +/- 2.45) versus those from the OASIS group (0.95 +/- 3.18). CONCLUSION: Unlike other inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis, structural progression in AS seems to be independent of TNF, despite the fact that TNF is responsible for the signs and symptoms due to inflammation in this disease.

Adalimumab effectively reduces the signs and symptoms of active ankylosing spondylitis in patients with total spinal ankylosis.

OBJECTIVE: To evaluate the long-term safety and efficacy of adalimumab in patients with ankylosing spondylitis (AS) and total spinal ankylosis (TSA). DESIGN: Patients (n = 315) with active AS were randomised in a 2:1 ratio to receive adalimumab 40 mg every other week or placebo for 24 weeks followed by open-label adalimumab for up to 5 years. Two-year efficacy and safety data for 11 patients with investigator-defined TSA were evaluated. The primary end point was the ASsessment in AS International Working Group criteria for 20% improvement (ASAS20) at Week 12. On or after Week 12, ASAS20 non-responders could switch to open-label adalimumab. Other efficacy measurements included ASAS40, ASAS 5/6, ASAS partial remission, and 50% improvement in the Bath AS Disease Activity Index (BASDAI 50). RESULTS: 6 of 11 TSA patients were randomised to adalimumab and 5 to placebo. At Week 12, 50% of the adalimumab-treated patients achieved an ASAS20 response and 33% achieved an ASAS40, ASAS 5/6 and BASDAI 50. No placebo-treated patients achieved any response criteria at Week 12. 4 placebo- and 2 adalimumab-treated patients switched to open-label adalimumab before Week 24. After 1 year of adalimumab treatment, 8 of 11 patients achieved an ASAS20 response. After 2 years, 6 of the remaining 8 patients with TSA reported an ASAS20 response. There were no serious adverse events or adverse event-related study discontinuations. CONCLUSION: In patients with TSA, adalimumab treatment resulted in rapid and clinically significant improvement in the signs and symptoms of active disease. Adalimumab effectiveness and safety were sustained for at least 2 years. TRIAL REGISTRATION NUMBER: NCT00085644.

Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis.

OBJECTIVE: Evaluate long-term safety and efficacy of etanercept treatment in patients with ankylosing spondylitis (AS). METHODS: Patients with AS who previously participated in a randomised controlled trial (RCT) of etanercept were eligible to enroll in a 168-week open-label extension (OLE). Safety end points included rates of adverse events (AE), serious adverse events (SAE), infections, serious infections and death. Efficacy end points included Assessment in Ankylosing Spondylitis (ASAS20) response, ASAS 5/6 response and partial remission rates. RESULTS: A total of 257 of 277 patients (92%) enrolled in the OLE. After up to 192 weeks of treatment with etanercept, the most common AEs were injection site reactions, headaches and diarrhoea. The exposure-adjusted rate of SAEs was 0.08 per patient-year. The rate of infections was 1.1 per patient-year, and the rate for serious infections was 0.02 per patient-year. No deaths were reported. Of patients who received etanercept in both the RCT and OLE and were still in the trial, 71% were ASAS20 responders at week 96, and 81% were responders at week 192. ASAS 5/6 response rates were 61% at week 96 and 60% at week 144, and partial remission response rates were 41% at week 96 and 44% at week 192. Placebo patients who switched to etanercept in the OLE showed similar patterns of efficacy maintenance. CONCLUSIONS: Etanercept was well tolerated for up to 192 weeks in patients with AS, with no unexpected AEs or SAEs observed. No deaths were reported. Improvements in the signs and symptoms of AS were maintained for up to 192 weeks.

ASAS/EULAR recommendations for the management of ankylosing spondylitis.

OBJECTIVE: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.

Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks.

OBJECTIVE: To evaluate the continued safety and durability of clinical response in patients with ankylosing spondylitis receiving etanercept. METHODS: 277 patients who had participated in a previous randomised, double blind, placebo controlled 24 week trial were eligible to continue in this open label extension study. All patients who enrolled in the open label extension (n = 257) received subcutaneous etanercept 25 mg twice weekly for up to 72 weeks, for a combined 96 weeks of cumulative trial and open label experience. For the patients who had received etanercept for 24 weeks in the double blind trial, this represented almost 2 years of continuous etanercept treatment. RESULTS: Patients continuing etanercept treatment had a sustained response for almost 2 years, with 74% achieving an ASsessments in Ankylosing Spondylitis 20% (ASAS 20) response after 96 weeks of etanercept treatment. Patients who had received placebo in the preceding double blind trial had similar responses, with 70% of patients attaining an ASAS 20 response after 24 weeks of etanercept treatment and 78% achieving an ASAS 20 response after 72 weeks. Improved spinal mobility was seen in both groups. Etanercept was well tolerated in patients treated for up to 96 weeks. CONCLUSION: The subcutaneous administration of twice weekly doses of etanercept provided sustained durability of response in the improvement of signs and symptoms of ankylosing spondylitis for nearly 2 years.

Lamivudine is not effective in primary Sjögren's syndrome.

BACKGROUND: Retroviral infection has been implicated in the pathogenesis of primary Sjögren's syndrome. OBJECTIVE: To examine the efficacy of the reverse transcriptase inhibitor lamivudine in patients with this syndrome. METHODS: 16 patients with primary Sjögren's syndrome were randomised to receive either lamivudine 150 mg twice daily or placebo for three months. Measures of lacrimal and salivary function, including minor salivary gland biopsies, were obtained before and after treatment. RESULTS: Treatment with lamivudine did not result in significant improvement in the primary outcome measure of unstimulated whole salivary flow or other secondary measures, including minor salivary gland biopsy focus scores. CONCLUSION: Lamivudine is not effective in patients with primary Sjögren's syndrome, suggesting either that a retroviral aetiology is not present or that it may be important only in early disease.

Lymphocyte depletion with fludarabine in patients with psoriatic arthritis: clinical and immunological effects.

OBJECTIVE: To obtain preliminary information on the safety and efficacy of fludarabine in PsA and analyse its immunomodulatory effects in peripheral blood and synovial tissue. METHODS: 15 patients with active PsA who did not respond to DMARDs were randomly allocated to receive fludarabine every four weeks or placebo. Primary outcomes were the proportion of patients who met the ACR20 and the psoriatic arthritis response criteria (PsARC) at 16 weeks. Secondary outcomes were changes in tender or swollen joint counts and scores of the psoriasis area and severity index (PASI). Phenotypic analysis of peripheral blood mononuclear cells (PBMC), synovial immunohistochemistry, and functional analysis of PBMC were used to determine the immunomodulatory effects of fludarabine. RESULTS: At 16 weeks the ACR20 criteria were met by 3/7 (43%) fludarabine treated v 0/8 placebo treated patients (p=0.08); the PsARC was achieved by 4/7 (57%) fludarabine treated v 2/8 (25%) placebo treated patients; and 3/7 (43%) fludarabine treated v 0/7 placebo treated patients had > or =20% improvement in the PASI. Marked peripheral lymphopenia involving naive (CD4(+) CD45RA(+)) and memory (CD4(+) CD45RO(+)) T cells, CD8(+) T cells, and B cells was seen in fludarabine treated patients. CONCLUSIONS: In PsA fludarabine induces significant peripheral, but modest, synovial lymphopenia, and a trend towards improved clinical response.

The treatment of ankylosing spondylitis.

Ankylosing spondylitis is an inflammatory disorder affecting the axial skeleton and periphery. Symptoms can often be debilitating. Current therapy for the disease include physical therapy, non-steroidal anti-inflammatory drugs (NSAIDS, anti-rheumatic disease modifying drugs (DMARDS), and the newly developed biologic agents targeting tumor necrosis factor alpha (TNF-alpha). This paper will provide a comprehensive review of these treatments which focusing on evidence based medicine for the daily clinical practice of rheumatology.

The role of etanercept in ankylosing spondylitis.

Ankylosing spondylitis is a chronic inflammatory disease that leads to significant loss of function and disability in patients. Current conventional therapies have not demonstrated improvement in axial symptoms and progressive ankylosis of the spine. The use of new biologic agents that block the actions of tumor necrosis factor-alpha have, for the first time, reported significant improvement in axial symptoms and reduction in spinal inflammation in short-term studies. Future studies with larger numbers of patients over long periods of time will eventually determine the long-term success and safety of these agents.

A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS).

OBJECTIVE: To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease-specific activity index for Wegener's granulomatosis (WG). METHODS: Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease-specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG. RESULTS: We removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73-0.87). The interobserver reliability using intraclass (within-case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43-0.83). CONCLUSION: The BVAS/WG is a valid, disease-specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter- and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.

Phase I clinical trial of a monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the safety and pharmacology of a humanized monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus (SLE). METHODS: Cohorts of 3 to 5 patients with symptomatic lupus each received 0.05, 0.25, 1.0, 5.0, or 15.0 mg/kg of IDEC-131 as a single intravenous infusion. Patients were followed for 3 months to evaluate toxicity and pharmacokinetics. RESULTS: This phase I, single dose, dose-escalating study was conducted in 23 patients at a single institution. All patients experienced at least 1 adverse event (AE) during a 3 month followup period, although 58 AE in 17 patients were considered possibly or probably related or of unknown relationship to treatment. No dose relationship in the distribution of AE was apparent. No infusion related cytokine-release syndrome was observed; no infusions were interrupted, and all patients completed treatment. Eight mild (grade 1 or 2) infections were reported in 8 patients. All infections were considered unrelated to drug administration and all resolved uneventfully. No patient developed detectable antibodies to IDEC-131. Flow cytometry revealed no apparent treatment related depletion of lymphocyte subsets. Pharmacokinetic analysis indicated that the maximum serum concentration and the area under the concentration curve of IDEC-131 were proportional to the dose administered. At doses between 1.0 and 15.0 mg/kg, the serum half-life ranged from 299 to 320 h. Efficacy was not formally evaluated in this single dose study. CONCLUSION: IDEC-131 (humanized Mab against CD40L) administered in a single intravenous infusion at doses of 0.05-15.0 mg/kg is safe and well tolerated in patients with SLE.

Multicentric reticulohistiocytosis: case report with immunohistochemical analysis and literature review.

This report describes the case of a patient with multicentric reticulohistiocytosis. Immunohistochemical analysis revealed prominent markers of monocyte/macrophage origin, as well as the presence of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12; the occurrence of the latter in this disease has not previously been reported. Clinical, laboratory, radiographic, and histologic findings in multicentric reticulohistiocytosis are reviewed. In addition, all published cases of multicentric reticulohistiocytosis which included reports of cytokine and immunohistochemical analysis are reviewed, and evidence for a monocyte/macrophage origin and role in disease pathogenesis is provided.

High dose versus low dose fludarabine in the treatment of patients with severe refractory rheumatoid arthritis.

OBJECTIVE: Fludarabine, a nucleoside analog that targets both resting and proliferating lymphocytes, is a promising drug for the treatment of autoimmune diseases. We conducted a 2 dose, open label clinical trial to evaluate the toxicity/safety of the fludarabine treatment and its clinical and immunological effects. METHODS: Twenty-six patients with severe rheumatoid arthritis (RA) refractory to treatment with at least one slow acting antirheumatic drug were treated with intravenous fludarabine [20 mg/m2 body surface area (n=12) or 30 mg/m2 body surface area (n=14) per day for 3 consecutive days] given monthly for 6 months. Second line agents with the exception of glucocorticoids were discontinued at least 4 weeks before study entry. Measurements included toxicity and tolerability monitored at monthly intervals: efficacy, by both a 50% reduction in tender or swollen joint count and American College of Rheumatology (ACR) criteria for 20% response; and phenotypic analysis of peripheral blood mononuclear cells and T cell functional assays. RESULTS: Using intention-to-treat analysis, 2 of 12 (17%) patients in the low dose and 7 of 14 (50%) in the high dose groups had 50% or greater reduction in tender and/or swollen joint count after 6 months of therapy compared to baseline (p=0.09). Two of 12 (17%) in the low dose group and 5 of 14 (36%) in the high dose group met ACR criteria for 20% improvement (p=0.28). No immediate toxicity was observed. Several infections occurred, including 4 episodes of limited Herpes zoster, which responded to standard therapy. Significant lymphopenia involving T and B cells was observed in all patients. Both naive (CD4+CD45RA+) and memory CD4+ T cells (CD4+CD45RO+) were reduced (naive > memory). No significant regeneration of naive T cells was observed, which may suggest limited thymic regenerative capacity. Fludarabine decreased the proliferative response of peripheral blood lymphocytes to mitogens, as well as the production of T cell (interleukin 2 and interferon-gamma) and monocyte derived (tumor necrosis factor-alpha and IL-10) cytokines. CONCLUSION: Fludarabine treatment of patients with severe, refractory RA resulted in significant lymphopenia, suppression of lymphocyte function, and clinical improvement in the high dose group. There was no immediate toxicity; however, several infections occurred. Controlled trials are needed to substantiate the clinical improvement observed in this open label trial.

An outbreak of vancomycin-resistant Enterococcus faecium in liver transplant recipients.

Vancomycin-resistant Enterococcus faecium (VREF) has become a significant nosocomial pathogen for immunosuppressed patients. During a 5-month period in 1993, 8 cases of invasive infection with VREF (7 with bacteremia) were identified in liver transplant recipients, half of whom were adults. Epidemiology and microbiology studies were designed to identify the source and to determine the risk factors for this infection. Overall mortality was 50% (3 adults and 1 child). Mortality in bacteremic patients was 57%. A case-control study showed that cases were more likely to have been treated with a third-generation cephalosporin or vancomycin and to have undergone more than four biliary tract procedures. Environmental surveillance cultures yielded only one VREF isolate from a rectal temperature probe, but this device was used in only 2 of the cases. Cultures from all surgery and radiology suites were negative. All VREF isolates were genotyped by contour-clamped homogenous electric field electrophoresis of chromosomal DNA restriction fragments. These studies showed that a single clone was responsible for the outbreak, although other clones could be detected in the hospital. After implementing strict contact isolation on the liver transplant unit, only 1 additional patient with VREF was identified during this outbreak. In conclusion, it was found that antibiotic use and biliary tract manipulation were risk factors for developing invasive infections with VREF after liver transplantation. Optimal treatment is still unclear but most likely includes a combination of two or more antibiotics. Prompt institution of infection control measures can preclude rapid spread of this nosocomial pathogen.

Measurement of serum levels of exogenously administered FSH and LH during ovulation induction therapy.

We conducted a prospective study of blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) following daily intramuscular injection of human menopausal gonadotropin (hMG) containing equal proportions of FSH and LH. Blood samples were collected on alternate days and the resulting changes in the blood levels of the ovarian hormone estradiol were also monitored. Twenty-eight consecutive patients with polycystic ovary syndrome who were between the ages of 25 and 35 years and attending our infertility clinic for ovulation induction therapy and assisted pregnancy were studied. Polycystic ovary syndrome was diagnosed on laparoscopy and as evidenced by high serum LH which was three times greater than FSH in the follicular phase of the menstrual cycle. A male factor for infertility was excluded. Twenty-five out of 28 women (89.3%) receiving hMG responded to therapy by a rise in serum estradiol level (> 1200 pmol/l on day 9). Of the 25 women who responded to hMG, four had live single babies (16%). All four women showed a cumulative rise in mean serum FSH with treatment when measured by standard radioimmunoassay, reaching statistical significance on day 5 (p < 0.05). The remaining 21 who failed to become pregnant showed variable changes in mean serum FSH with a sharp rise on day 3 (p < 0.02) and a significant fall on day 7 (p < 0.02). However, mean serum LH measured by standard radioimmunoassay in all women remained unchanged throughout the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvant hyperbaric oxygen in malignant external otitis.

Necrotizing invasive pseudomonal infection of the external auditory canal (malignant external otitis) is an uncommon but important disorder in the elderly. The high morbidity, and even mortality, of this disorder has been reduced by the early and intensive use of combination antipseudomonal antibiotics. However, in severely immunocompromised patients or in infection involving the base of the skull, multiple cranial nerves, or the meninges, conventional therapy has been prolonged, intensive, and relatively ineffective. We treated 16 patients with malignant external otitis with adjuvant hyperbaric oxygen therapy. In six patients, infection was in advanced stages, infections were recurrences after previous treatment, and repeated treatment with antipseudomonal antibiotics had failed. All 16 cases responded promptly when a 30-day course of hyperbaric oxygen was added to the antibiotic regimen, and all patients remained free of infection or neurologic deficit during 1 to 4 years of follow-up. No complications of this treatment modality were noted. Hyperbaric oxygen therapy reverses tissue hypoxia, which enhances phagocytic killing of aerobic microorganisms, and stimulates neomicroangiogenesis. In addition, hyperbaric oxygen augments the action of aminoglycoside antibiotics. Adjuvant hyperbaric oxygen therapy should be considered in advanced or recurrent cases of malignant external otitis.

Vertical transmission of human immunodeficiency virus from seronegative or indeterminate mothers.

UNLABELLED: OBJECTIVE--To describe the identification of human immunodeficiency virus (HIV)-infected infants born to women who were seronegative or indeterminate during pregnancy. RESEARCH DESIGN--Longitudinal cohort study. SETTING--Inner-city medical center. PARTICIPANTS: A series of children born to women with histories of risk factors for HIV infection were followed up for studies of the natural history of HIV-infected infants. These children were identified through risk factor assessment of pregnant women presenting for obstetric care. INTERVENTIONS--Counseling and testing to detect HIV. RESULTS--Three women were retrospectively identified who were infected with HIV during pregnancy but whose test results showed them to be either seronegative or indeterminate. Two of these women transmitted HIV infection to their children. Subsequently, all three women were confirmed to be infected. CONCLUSIONS--Standard serologic testing to detect HIV infection will not identify all infected pregnant women. Perinatal transmission of HIV can occur in women with negative results of enzyme-linked immunosorbent assay or indeterminate results of Western blot analysis during pregnancy.