Nucleic acid testing (NAT) of organ donors: is the 'best' test the right test? A consensus conference report.

Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood-or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false-positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor-derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss.

Processes influencing seasonal hypoxia in the northern California Current System.

This paper delineates the role of physical and biological processes contributing to hypoxia, dissolved oxygen (DO) < 1.4 mL/L, over the continental shelf of Washington State in the northern portion of the California Current System (CCS). In the historical record (1950-1986) during the summer upwelling season, hypoxia is more prevalent and severe off Washington than further south off northern Oregon. Recent data (2003-2005) show that hypoxia over the Washington shelf occurred at levels previously observed in the historical data. 2006 was an exception, with hypoxia covering ~5000 km(2) of the Washington continental shelf and DO concentrations below 0.5 mL/L at the inner shelf, lower than any known previous observations at that location. In the four years studied, upwelling of low DO water and changes in source water contribute to interannual variability, but cannot account for seasonal decreases below hypoxic concentrations. Deficits of DO along salinity surfaces, indicating biochemical consumption of DO, vary significantly between surveys, accounting for additional decreases of 0.5-2.5 mL/L by late summer. DO consumption is associated with denitrification, an indicator of biochemical sediment processes. Mass balances of DO and nitrate show that biochemical processes in the water column and sediments each contribute ~50% to the total consumption of DO in near-bottom water. At shorter than seasonal time scales on the inner shelf, along-shelf advection of hypoxic patches and cross-shelf advection of seasonal gradients are both shown to be important, changing DO concentrations by 1.5 mL/L or more over five days.

In vivo antigenic modification of tumor cells. I. Introduction of murine leukemia virus antigens on non-virus-producing murine sarcomas.

Murine oncovirus antigens represent excellent targets for immune recognition, and virus-associated tumors are generally susceptible to various immunotherapy protocols. Virus-negative tumors, however, are nonimmunogenic and refractory to immunologic control. Therefore, the feasibility of the introduction of antigens onto non-virus-expressing tumors in situ in inbred C57BL/6J mice by systemic administration of nononcogenic murine retroviruses was investigated. Two classes of murine fibrosarcomas were studied: a 3-methylcholanthrene-induced fibrosarcoma syngeneic to C57BL/6 mice (MCA-FS) and a Harvey murine sarcoma virus-transformed, nonproducer fibrosarcoma syngeneic to C57BL/6 mice (H-NP). Both were found to be devoid of infectious ecotropic murine leukemia virus (MuLV) or MuLV antigens. A single dose of Friend murine leukemia virus (F-MuLV) was used to superinfect MCA-FS- and H-NP-induced tumors in vivo and converted these tumors to a highly productive, virus-positive state. In vivo superinfected tumors were indistinguishable from their preinfected counterparts by competition radioimmunoassays for the virion's major envelope glycoprotein, gp71, and its group-specific antigen, p30, and by assays for infectious virus. Analysis of virus from tumor extracts proved that the antigenic specificity of the superinfected tumor was provided by F-MuLV administered systemically to the animals. Finally, an immunoperoxidase technique, applied to tumor cross sections, demonstrated the uniform appearance of viral antigens in the superinfected tumors.

Partially mismatched related-donor bone marrow transplantation for pediatric patients with acute leukemia: younger donors and absence of peripheral blasts improve outcome.

PURPOSE: To extend access to bone marrow transplantation (BMT), we used partially mismatched related donors (PMRD) for pediatric patients with acute leukemia. In this report we sought to determine pretransplantation factors that might predict outcome. PATIENTS AND METHODS: Of 67 such patients, 43 had acute lymphocytic leukemia and 24 had acute myelogenous leukemia. At the time of transplantation, 41 patients were in relapse. Donors included 40 parents, 24 siblings, and three cousins. HLA disparity of two to three major antigens was detected in two thirds of the donor-recipient pairs. Conditioning therapy, including total-body irradiation and chemotherapy followed by graft-versus-host disease (GvHD) prophylaxis with partial T-cell depletion of the graft using T10B9 or OKT3, was combined with posttransplantation immunosuppression. RESULTS: Estimated probability (EP) of engraftment was 0.96 and was not affected by donor-antigen mismatch (AgMM; P =.732). EP of grades 2 to 4 acute GvHD was 0.24 and was not affected by recipient AgMM (P =.796). EP of disease-free survival was 0.26 at 3 years but improved to 0.45 when donors were younger than 30 years (P<.001). EP of relapse at 3 years was 0.41 and reduced with younger donors' age. For patients who were in relapse at the time of transplantation, absence of blasts was associated with a lower relapse rate (0.46 v. 0.84; P =. 083), similar to that of patients in remission. CONCLUSION: PMRD-BMT in pediatric leukemia resulted in high engraftment and low GvHD rates. To improve outcomes, younger donors should be sought, and clinicians should attempt to reduce peripheral blasts in patients who are in relapse.

The gene locus of the proton-translocating NADH: ubiquinone oxidoreductase in Escherichia coli. Organization of the 14 genes and relationship between the derived proteins and subunits of mitochondrial complex I.

The gene locus nuo of the proton-translocating NADH: ubiquinone oxidoreductase in Escherichia coli was identified by means of a DNA probe made by the polymerase chain reaction. The primers used for the reaction were derived from consensus sequences of the NAD(H)-binding subunit of mitochondrial NADH: ubiquinone oxidoreductase and the NAD(+)-reducing hydrogenase of Alcaligenes eutrophus. The nuo locus lies between minutes 49.2 and 49.6 on the E. coli chromosome and contains a cluster of 14 genes. They are bordered upstream by a sequence resembling sigma 70-dependent promoters and downstream by a sequence resembling rho-independent terminators. All 14 proteins derived from the nuo-genes are related to subunits of mitochondrial NADH: ubiquinone oxidoreductase, among which all subunits presumed to bind the substrates and to harbour the redox groups are found, as well as all seven mitochondrially encoded subunits. The E. coli enzyme seems to represent the minimal form of a proton-translocating NADH: ubiquinone oxidoreductase. The gene order in the nuo locus is conserved in comparison with other bacterial genomes and the chloroplast genome of higher plants. To some extent, the gene order correlates with the topological arrangement of the encoded subunits. The conception of modular evolution of NADH: ubiquinone oxidoreductase is further supported by the arrangement of the nuo-genes.

Characterization of acute bone marrow graft rejection in T cell-depleted, partially mismatched related donor bone marrow transplantation.

The purpose of this study was to characterize the phenotype and clonality of the T cell population in patients who experience acute rejection (AR) following bone marrow transplantation (BMT) from a partially mismatched related donor (PMRD). Phenotypic analysis was performed using flow cytometry, assignment of donor/host lineage by cytogenetics or HLA-specific flow cytometry, and analysis of the T cell receptor (TCR) by reverse-transcriptase polymerase chain reaction (RT-PCR). We have previously reported the initial appearance in the blood of AR patients of host CD8+brightCD3low T cells that progressively express increasing amounts of CD3+ cells. We now report that this cell population can differentiate into either a cytotoxic T cell phenotype (CD3+CD8+HLA-DR+CD57-) usually associated with AR of grafts from matched unrelated donors or a suppressor T cell phenotype (CD3+CD8+CD57+HLA-DR-) usually associated with AR of grafts from matched sibling donors. Analysis of the TCR V beta subsets from two patients revealed sorted host CD3+CD8+ cells (purity 90-95%) from the first patient to express V beta 18 almost exclusively. In a second patient with late rejection (55 days post-BMT), the CD3+CD8+ cells were predominantly restricted to V beta 1, 5.1, 7, 9, and 18. Although CD3+CD8+ T cells are known to be associated with AR, cytotoxic and suppressor lineages in AR from the same type of BMT and clonal distribution of T cells in AR have not been reported. Preliminary results suggest that V beta expression in AR of PMRD grafts is restricted and host T cell phenotype may vary. Further studies will investigate whether specific mismatches correlate with specific V beta usage and/or host T cell phenotype.

Stellar dynamics. The fastest unbound star in our Galaxy ejected by a thermonuclear supernova.

Hypervelocity stars (HVSs) travel with velocities so high that they exceed the escape velocity of the Galaxy. Several acceleration mechanisms have been discussed. Only one HVS (US 708, HVS 2) is a compact helium star. Here we present a spectroscopic and kinematic analysis of US 708. Traveling with a velocity of ~1200 kilometers per second, it is the fastest unbound star in our Galaxy. In reconstructing its trajectory, the Galactic center becomes very unlikely as an origin, which is hardly consistent with the most favored ejection mechanism for the other HVSs. Furthermore, we detected that US 708 is a fast rotator. According to our binary evolution model, it was spun-up by tidal interaction in a close binary and is likely to be the ejected donor remnant of a thermonuclear supernova.

Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1-infected patients.

OBJECTIVE: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome. METHODS: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables. RESULTS: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001). CONCLUSION: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].

HIV-related ocular microangiopathic syndrome and cognitive functioning.

Ocular microangiopathic syndrome is found frequently in patients with AIDS or severe HIV infection. Symptoms of this microvascular syndrome can include cotton-wool spots, hemorrhages, and Roth's spots. The clinical and functional significance of HIV-related ocular microangiopathic syndrome has not been clarified as yet. The objective of this study was to evaluate a possible association between HIV-related ocular microangiopathic syndrome and cognitive functioning. Thirty-seven patients infected with HIV (24 with AIDS) underwent ophthalmological and neuropsychological examination. HIV-related ocular microangiopathic syndrome was measured by counting the number of cotton-wool spots in both eyes. Neuropsychological examination included five standardized tests, with the first three primarily measuring function of short-term memory; these tests were as follows: the Auditory-Verbal Learning Test, the Benton Test, the Stroop Colour Word Test, the Trail-Making Part B test, and the Vocabulary for Measuring Premorbid Intelligence test. HIV-related ocular microangiopathic syndrome was found in 15 patients with AIDS (62.5%), and in one patient, staged Walter Reed 5. In 10 patients, one eye was affected (mean count of cotton-wool spots 1.5). In six patients, both eyes were affected (mean count of cotton-wool spots 7.0). Univariate correlations between the number of cotton-wool spots in both eyes and test scores were as follows: Auditory-Verbal Learning Test: 0.56 (p < 0.001); Benton Test: 0.51 (p < 0.001); Stroop Colour and Word: 0.50 (p < 0.001); Trail-Making Part B: 0.15 (not significant); Vocabulary for Measuring Premorbid Intelligence: -0.05 (not significant). Multiple correlation between the test scores and the number of cotton-wool spots was 0.70 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The seizures of frontal lobe epilepsy. A study of clinical manifestations.

We describe ictal clinical manifestations of frontal lobe epileptic seizures in 22 patients. After examination of all ictal clinical data, 14 catergories of signs and symptoms were established. The validity of the ictal clinical data used was confirmed on the basis of 99 frontal lobe seizures recorded by tele-electroencephalogram or tele-stereo-electroencephalogram. The main conclusion is that the frontal lobe appears to be partially connected with motor acitivity.

Rejection of kidney allografts by MHC class I-deficient mice.

To evaluate the requirement for CD8+ T cells in kidney transplant rejection, we studied class I-deficient (class I-) mice that had received vascularized renal allografts. Because of the absence of MHC class I expression, these mice are grossly deficient in CD4-CD8+ alpha beta TCR+ cells. Despite the deficiency of CD8+ T cells in naive class I- mice, kidney allografts transplanted into class I- recipients developed significant reductions in renal blood flow and glomerular filtration rate to levels comparable to allograft controls. This functional deterioration was associated with histologic changes consistent with cellular rejection. There were no significant differences in the pattern, severity, or phenotypic character of the cellular infiltrate in allografts transplanted into class I- recipients compared to controls. In fact, substantial numbers of CD8+ T cells were present in these allografts, and the intensity and pattern of anti-CD8 staining was not different from controls. Virtually all of the CD8+ cells in the kidney grafts were class I- and CD4- and co-expressed CD8 alpha and beta chains; the majority were alpha beta TCR+. The CD8+ infiltrating cells were cytotoxic to donor targets but also exhibited activity against class I+ cells bearing self-MHC. Despite the marked CD8+ T cell infiltration of grafts, CD8+ T cells could not be detected by flow cytometry in freshly isolated splenocytes from the class I- recipients of allografts. High levels of circulating anti-class I antibodies were present in the serum of class I- recipients of kidney allografts, and these antibodies had unusual specificity in that they appeared to recognize framework epitopes of MHC class I. Thus, class I- mice readily reject kidney allografts. Although the number of CD8+ alloreactive precursors is substantially reduced in class mice, and their specificities are atypical, the pattern and character of the intra-graft CD8+ cellular response is not significantly altered. Thus, factors unrelated to precursor frequency determine the dimension of the intra-graft CD8+ response. Such factors might include cellular and/or biochemical properties of microenvironment within the graft.

HIV-related ocular microangiopathic syndrome and color contrast sensitivity.

PURPOSE: Color vision deficits in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease were reported, and a retinal pathogenic mechanism was proposed. The purpose of this study was to evaluate the association of color vision deficits with HIV-related retinal microangiopathy. METHODS: A computer graphics system was used to measure protan, deutan, and tritan color contrast sensitivity (CCS) thresholds in 60 HIV-infected patients. Retinal microangiopathy was measured by counting the number of cotton-wool spots, and conjunctival blood-flow sludging was determined. Additional predictors were CD4+ count, age, time on aerosolized pentamidine, time on zidovudine, and Walter Reed staging. The relative influence of each predictor was calculated by stepwise multiple regression analysis (inclusion criterion; incremental P value = < 0.05) using data for the right eyes (RE). The results were validated by using data for the left eyes (LE) and both eyes (BE). RESULTS: The only included predictors in multiple regression analyses for the RE were number of cotton-wool spots (tritan: R = .70; deutan: R = .46; and protan: R = .58; P < .0001 for all axes) and age (tritan: increment of R [Ri] = .05, P = .002; deutan: Ri = .10, P = .004; and protan: Ri = .05, P = .002). The predictors time on zidovudine (Ri = .05, P = .002) and Walter Reed staging (Ri = .03, P = .01) were additionally included in multiple regression analysis for tritan LE. The results for deutan LE were comparable to those for the RE. In the analysis for protan LE, the only included predictor was number of cotton-wool spots. In the analyses for BE, no further predictors were included. The predictors Walter Reed staging and CD4+ count showed a significant association with all three criteria in univariate analysis. Additionally, tritan CCS was significantly associated with conjunctival blood-flow sludging. CONCLUSION: CCS deficits in patients with HIV disease are primarily associated with the number of cotton-wool spots. Results of this study are in accordance with the hypothesis that CCS deficits are in a relevant part caused by neuroretinal damage secondary to HIV-related microangiopathy.

Characterization of a novel human corneal endothelial antigen.

The antigenic composition of the human corneal endothelium, a cellular layer essential for maintaining corneal function, has not been well characterized. A novel corneal endothelial antigen was identified by generating a monoclonal antibody (MAb) against normal human corneal endothelial cells. This MAb, designated 2B4.14.1, reacted strongly by immunoperoxidase staining with the endothelium of corneas from all human donors tested but not with other corneal components, including epithelium and stroma. Positive immunohistologic reactions of 2B4.14.1 with several other human tissues, including kidney (parietal epithelium of Bowman's capsule, proximal convoluted tubule, ascending limb of Henle's loop, and distal convoluted tubule), glandular epithelia of numerous organs, and mesothelial linings of several thoracic and abdominal viscera, also were observed. One of the renal antigens recognized by 2B4.14.1 was identified as Tamm-Horsfall glycoprotein (THGP), based on the ability of the antibody to recognize THGP in western immunoblots and the abrogation of immunohistologic reactivity of the antibody by preincubation with purified THGP. These findings raise the possibility that the human cornea expresses a molecule with homeostatic properties similar to those ascribed to THGP. However, it is unlikely that the corneal antigen recognized by 2B4.14.1 is conventional THGP; a MAb specific for THGP did not react with corneal endothelium.

Acute rejection of marrow grafts in patients transplanted from a partially mismatched related donor: clinical and immunologic characteristics.

Bone marrow transplantation (BMT) from a partially mismatched related donor (PMRD) provides a treatment option for patients lacking a matched sibling donor. T lymphocyte depletion of the graft reduces the risk of severe graft-versus-host disease, but may increase the risk of graft failure. We evaluated the pattern of acute graft rejection in eight patients receiving PMRD BMT with respect to the conditioning therapy, diagnosis, age and sex of donor and recipient, degree of HLA mismatch, and peripheral blood immunophenotype at the time of graft failure. All grafts were partially depleted of T lymphocytes. Marrow grafts infused into patients who experienced acute rejection did not differ significantly in nucleated cell dose, degree of T lymphocyte depletion, T cell dose, or CFU-GM/kg infused, from those received by 31 patients who showed durable engraftment. In three of four patients who rejected their grafts, and had sufficient peripheral blood cells for immunophenotyping, a CD3+CD8+ T lymphocyte phenotype was predominant at the time of acute rejection. In one patient rejection was associated with a predominant population of CD3+CD4+ T lymphocytes. Rejection was significantly associated with chronic myelogeneous leukemia and in patients mismatched by more than two antigens.

Donor leukocyte infusion for treatment of graft rejection post partially mismatched related donor bone marrow transplant.

Graft rejection following bone marrow transplantation is more common in patients who receive their grafts from alternative donors and whose marrow is T cell depleted. Rejection in these patients is mediated by persistent host cells that interfere with successful establishment of donor-derived hematopoietic recovery. We describe a patient with chronic myelogenous leukemia in accelerated phase who rejected a T cell-depleted bone marrow graft, 2 months following partially mismatched related donor bone marrow transplant. Unmanipulated peripheral blood donor leukocyte infusion, without additional chemotherapy or immunosuppressive therapy resulted in complete hematopoietic recovery. Cytogenetics and RFLP demonstrated hematopoietic donor chimerism. The patient did not develop graft-versus-host disease.

Human gammadelta(+) T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response.

Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse rates following allogeneic bone marrow transplantation (BMT) remain high. We have reported that patients who develop increased numbers of gammadelta(+) T cells soon after BMT are significantly less likely to relapse. We now show in seven donor/recipient pairs that donor-derived Vdelta1(+)CD4(-)CD8(-)gammadelta(+) T cells are activated and proliferate in response to recipient primary ALL blasts. In addition, these cells have been shown to bind and lyse the recipient ALL blasts. Separately, gammadelta(+) T cells proliferate poorly or not at all in mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These observations suggest that allogeneic gammadelta(+) T cells could be an effective immunotherapeutic strategy against refractory disease without the risk of graft-versus-host disease.

Phenotypic and functional reconstitution of peripheral blood lymphocytes following T cell-depleted bone marrow transplantation from partially mismatched related donors.

Myeloablative chemotherapy followed by transplantation of a T cell-depleted bone marrow graft from a partially mismatched related donor provides a potentially curative option for patients with leukemia and other disorders of hematopoiesis, although the patient is faced with a period of sustained immunodeficiency as well as pharmacologic immunosuppression as a result of prophylaxis against graft-versus-host disease. Thirty patients who received one to three antigen T cell-depleted mismatched grafts were evaluated for immune reconstitution. The percentage and numbers of cells expressing lymphocyte subset antigens were determined by flow cytometry at 14, 28, 60, 100, 180, 270 and 365 days post-BMT and at 6 month intervals thereafter. Lymphocyte reconstitution was characterized by the early appearance of natural killer cells and a low percentage of both T and B cells. During the first year after BMT, the number of NK cells remained constant while T and B cells gradually returned to normal numbers and proportions. Response to the lymphocyte mitogen phytohemagglutinin returned to normal over the course of 2 years, while the response to concanavalin A was slightly depressed and the response to pokeweed mitogen became supranormal at about 1.5 years and continued to increase. These data suggest the need for long-term immunophenotypic monitoring as well as prolonged infection surveillance and prophylaxis.

Deficits in perimetric performance in patients with symptomatic human immunodeficiency virus infection or acquired immunodeficiency syndrome.

PURPOSE: We measured the perimetric performance in patients with either acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease but without AIDS. METHODS: Light-difference sensitivity in the central field was measured in 74 eyes of 37 patients. The Humphrey Field Analyzer 640, program 30-2 was used. Additionally, 143 eyes of 143 normal control subjects were studied. RESULTS: Mean deviation was significantly reduced in patients with HIV disease compared with control subjects (mean +/- S.E.M., -4.30 +/- 0.52 vs -0.77 +/- 0.15, respectively; P < .0001). Analysis of subgroups demonstrated that patients with lymphadenopathy syndrome or AIDS-related complex (N = 40 eyes; -3.52 +/- 0.41; P < .0001) as well as patients with AIDS (N = 34 eyes; -5.23 +/- 0.97; P < .0001) had a reduced mean deviation. Those comparisons remained significant (P < .0001) when data were analyzed independently for the right eyes and for the left eyes. Corrected pattern standard deviation (3.15 +/- 0.30 vs 1.39 +/- 0.09; P < .0001) was higher in patients with HIV disease compared with control subjects. Again, analysis of subgroups disclosed a significant increase in patients with lymphadenopathy syndrome or AIDS-related complex (2.55 +/- 0.36; P < .0001) as well as in patients with AIDS (3.85 +/- 0.51; P < .0001). Both comparisons remained significant when data were analyzed independently for the right and left eyes. CONCLUSIONS: This study demonstrates visual dysfunction despite normal visual acuity in patients with HIV disease. Our results are consistent with the hypothesis of damage at the neuroretinal level.

Impairment of colour contrast sensitivity and neuroretinal dysfunction in patients with symptomatic HIV infection or AIDS.

Ophthalmic and neurological complications are frequent findings in patients with AIDS. Little is known about neuroretinal dysfunction in patients with HIV infection. The purpose of this study was to measure and evaluate colour vision in patients with HIV infection or AIDS. Colour contrast sensitivity tests were performed on 75 patients (150 eyes) in different stages of HIV infection. A highly sensitive computer graphics system was used to measure tritan, deutan, and protan colour contrast thresholds. Patients were classified into three clinical groups: (a) asymptomatic HIV infection, (b) lymphadenopathy syndrome or AIDS-related complex, and (c) AIDS. Overall, tritan (p < 0.0001), deutan (p = 0.003), and protan (p = 0.009) colour contrast sensitivities were significantly impaired in patients with HIV infection compared with normal controls. Colour thresholds in patients with asymptomatic HIV infection (mean tritan threshold: 4.33; deutan: 4.41; protan: 3.97) were not impaired compared with normal controls. Colour vision was slightly impaired in patients with lymphadenopathy syndrome or AIDS-related complex (tritan: 6.25 (p < 0.0001); deutan: 4.99 (p = 0.02); protan: 4.45 (p = 0.05)). In patients with AIDS the impairment was even more marked (tritan: 7.66 (p < 0.0001); deutan: 5.15 (p < 0.0009); protan: 4.63 (p = 0.004)). Analysis of covariance controlling for age demonstrated a close association between impairment of tritan colour contrast sensitivity and progression of HIV disease (p < 0.0001). Following Köllner's rule, our study suggests that neuroretinal dysfunction occurs in patients with symptomatic HIV infection or AIDS. This is emphasised by the finding that the relative impairment in tritan vision compared with deutan/protan vision might reflect the difference in the number of cones or receptive fields. Measurement of tritan colour contrast sensitivity appears to be an appropriate and easily applicable method to detect early neuroretinal dysfunction in patients with HIV disease.