Vasoconstrictor stimulus determines the functional contribution of myoendothelial feedback to mesenteric arterial tone.

KEY POINTS: In isolated resistance arteries, endothelial modulation of vasoconstrictor responses to α1 -adrenoceptor agonists occurs via a process termed myoendothelial feedback: localized inositol trisphosphate (InsP3 )-dependent Ca2+ transients activate intermediate conductance Ca2+ -activated K+ (IKCa ) channels, hyperpolarizing the endothelial membrane potential to limit further reductions in vessel diameter. We demonstrate that IKCa channel-mediated myoendothelial feedback limits responses of isolated mesenteric arteries to noradrenaline and nerve stimulation, but not to the thromboxane A2 mimetic U46619 or to increases in intravascular pressure. In contrast, in the intact mesenteric bed, although responses to exogenous noradrenaline were limited by IKCa channel-mediated myoendothelial feedback, release of NO and activation of endothelial small conductance Ca2+ -activated K+ (SKCa ) channels in response to increases in shear stress appeared to be the primary mediators of endothelial modulation of vasoconstriction. We propose that (1) the functional contribution of myoendothelial feedback to arterial tone is determined by the nature of the vasoconstrictor stimulus, and (2) although IKCa channel-mediated myoendothelial feedback may contribute to local control of arterial diameter, in the intact vascular bed, increases in shear stress may be the major stimulus for engagement of the endothelium during vasoconstriction. ABSTRACT: Constriction of isolated resistance arteries in response to α1 -adrenoceptor agonists is limited by reciprocal engagement of inhibitory endothelial mechanisms via myoendothelial feedback. In the current model of feedback, agonist stimulation of smooth muscle cells results in localized InsP3 -dependent Ca2+ transients that activate endothelial IKCa channels. The subsequent hyperpolarization of the endothelial membrane potential then feeds back to the smooth muscle to limit further reductions in vessel diameter. We hypothesized that the functional contribution of InsP3 -IKCa channel-mediated myoendothelial feedback to limiting arterial diameter may be influenced by the nature of the vasoconstrictor stimulus. To test this hypothesis, we investigated the functional role of myoendothelial feedback in modulating responses of rat mesenteric resistance arteries to the adrenoceptor agonist noradrenaline, the thromboxane A2 mimetic U46619, increases in intravascular pressure and stimulation of perivascular sympathetic nerves. In isolated arteries, responses to noradrenaline and stimulation of sympathetic nerves, but not to U46619 and increases in intravascular pressure, were modulated by IKCa channel-dependent myoendothelial feedback. In the intact mesenteric bed perfused under conditions of constant flow, responses to exogenous noradrenaline were modulated by myoendothelial feedback, but shear stress-induced release of NO and activation of endothelial SKCa channels appeared to be the primary mediators of endothelial modulation of vasoconstriction to agonists and nerve stimulation. Thus, we propose that myoendothelial feedback may contribute to local control of diameter within arterial segments, but at the level of the intact vascular bed, increases in shear stress may be the major stimulus for engagement of the endothelium during vasoconstriction.

Evaluation of a group programme of mindfulness-based cognitive therapy for women with fertility problems.

Mindfulness-based cognitive therapy (MBCT) has proved helpful for a number of health-related conditions but there is relatively little published literature about its use with fertility problems. The aim of this paper is to describe a pilot group programme adopted by a Clinical Health Psychology department, and to present findings from the routine outcomes data gathered by the service, evaluating its effectiveness. Data from nine women with fertility problems that took part in the programme were analysed. They completed measures of wellbeing and psychological distress before and after the treatment. The results showed clinically significant improvements in participants' wellbeing scores and psychological distress. It was a limitation of the study that the impact of concurrent treatments could not be assessed and so could also have contributed to this outcome in half of the cases. Nevertheless, these results suggest that MBCT may be a helpful treatment for women presenting with fertility-related distress.

Effects on condom use of an HIV prevention programme 36 months postintervention: a cluster randomized controlled trial among Bahamian youth.

Data are lacking on long-term effects of HIV behavioural intervention programmes. In this study, we report intervention effects 36 months postintervention on condom use and relevant outcome variables from the theory-based programme 'Focus on Youth in the Caribbean' (FOYC). Participants (1360 sixth-grade youth) were randomized by school into: (1) FOYC, plus one of two brief parent interventions or (2) the control condition 'Wondrous Wetlands', plus a brief parent intervention. Mixed effect analysis demonstrated significant programme effects, including enhanced HIV/AIDS knowledge (effect size D = 0.44, 95% confidence interval [CI]: 0.43, 0.46), increased self-efficacy of (D = 0.42, 95% CI: 0.30, 0.54), skills for (D = 0.62, 95% CI: 0.56, 0.64) and intention to use a condom (D = 0.20, 95% CI: 0.03, 0.37). Youth who received FOYC plus the parental monitoring intervention had higher condom use rates (odds ratio = 1.49, 95% CI: 0.97, 2.28). Feedback effects from key variables were also detected, supporting the sustained effect.

Condom-use skills checklist: a proxy for assessing condom-use knowledge and skills when direct observation is not possible.

Because of the continued importance of correct condom-use in controlling the HIV epidemic and the limited availability of tools for assessing correct condom-use, methods for assessing condom-application skills, especially when direct observation is not feasible, are needed. Accordingly, in the context of a high-risk population (The Bahamas) for HIV, a 17-item scale--the Condom-use Skills Checklist (CUSC)--was developed for use among young adolescents and adults. The rationale and approach to developing the scale and some measures of internal consistency, construct validity, and criterion-related validity have been described. It is concluded that the scale offers a reasonable alternative to direct observation among older subjects and that further development may make it more useful among pre-adolescents.

At greatest risk: pre- and early adolescent Bahamian youth experiencing anal intercourse.

Although anal intercourse carries great risk for HIV transmission, little research has focused on it among the general population, particularly pre- and early adolescents. This study describes the prevalence of anal and vaginal intercourse among Bahamian pre- and early adolescents and associations with other risk behaviours, family interactions and intrapersonal correlates. Data were from 1274 sixth-grade students aged 9-14 years who completed self-administered questionnaires at baseline of a larger school-based behavioural intervention study. Youth who reported having had anal intercourse engaged in significantly higher rates of several risk behaviours and were significantly more likely to engage in risk behaviours over the next six months, compared with youth with a history of vaginal intercourse only, who in turn were more likely than virgin adolescents. Youth indulging in anal intercourse also perceived significantly lower levels of parental monitoring. Multivariate analyses revealed that anal intercourse, vaginal intercourse, reduced parental monitoring, depression and perceived friend high-risk involvement were associated with both past involvement and future intention to engage in other risk behaviours. Anal intercourse poses a direct threat to the health of these children and is a flag for a constellation of other risks.

Structure of the corpus luteum in the ovulatory polycystic ovary.

BACKGROUND: Women with polycystic ovaries (PCO) have a wide spectrum of presentation from anovulation and amenorrhoea to apparently regular, ovulatory menstrual cycles. We have recently reported a subtle defect in steroidogenic function in the luteal phase in the latter and an increase in the number of degenerating corpora lutea (CL) were observed in ovulatory PCO (ovPCO) during dissection. The possibility was therefore investigated of differences in structure or degeneration in CL formed during ovulatory cycles in women with PCO. METHODS: This study compared the histology of the CL in ovPCO with that in the normal ovary. Corpora lutea were collected from nine normal ovaries (days 1-27 of the cycle) and from 13 women with ovPCO (days 5-38). RESULTS: Variations in the degree of regression, both in relation to onset of menses and between different areas within individual CL, were recorded in both groups. During development and regression no obvious differences were observed between either group apart from an apparent increase in luteal haemorrhage, which was more common and more extensive in CL from PCO. CONCLUSIONS: The findings suggest that possible luteal phase abnormalities of steroid secretion in women with ovulatory PCO are not associated with obvious morphological defects in the CL, however it is possible that the persistence of luteal structures seen in PCO was a consequence of increased luteal haemorrhage.

Psychosocial aspects of human immunodeficiency virus (HIV) infection in a pre-HAART sample.

The psychosocial consequences of HLV-infection were studied using a semi-structured interview and the psychiatric questionnaire SCL-90-R, in 3 matched groups of homosexual men: 20 patients with Aids, 20 asymptomatic HIV-infected and 20 non-infected controls. The data was collected before the HAART (Highly Active Anti-retroviral Therapy) era. The results showed that the infected subjects more often concealed their homosexuality, engaged in more risky sexual behavior and were less inclined to regard AIDS as a serious problem. The infected subjects also revealed more psychopathology on 5 of the 9 indexes on the SCL-90. Across all 3 groups, contact ability was correlated to being open about homosexuality and to psychological well-being. These results indicate that HIV has considerable impact on psychological well-being among the infected and point to the need for health-care workers to be especially attentive to those HIV-infected who have difficulty in talking to others about their situation.

Luteal angiogenesis: prevention and intervention by treatment with vascular endothelial growth factor trap(A40).

The possibility of stimulating or inhibiting paracrine factors regulating angiogenesis may lead to new approaches for the treatment of pathological conditions of the female reproductive tract. We examined the effects of a clinical candidate, a soluble truncated form of the Flt-1 receptor, vascular endothelial growth factor trap(A40) (VEGF trap), in a primate model to determine its ability to prevent the onset of luteal angiogenesis or intervene with the on-going process. Marmosets were treated from the day of ovulation until luteal day 3 (prevention regimen) or on luteal day 3 for 1 day (intervention regimen). Effects of VEGF inhibition were studied by obtaining a proliferation index using bromodeoxyuridine incorporation, quantifying endothelial cell area using CD31, and assessing luteal function by plasma progesterone. After both treatments, intense luteal endothelial proliferation was suppressed, a concomitant decrease in endothelial cell area confirmed the inhibition of vascular development, and a marked fall in plasma progesterone levels showed that luteal function was compromised. In situ hybridization was used to localize and quantify compensatory effects on the expression of angiogenic genes. VEGF messenger ribonucleic acid (mRNA) expression in luteal cells was increased, whereas expression of its receptor, Flt, was decreased. Inhibition of VEGF resulted in localized increased expression of angiopoietin-2 mRNA and its receptor, Tie-2. The results show that the VEGF trap can prevent luteal angiogenesis and inhibit the established process with resultant suppression of luteal function. Luteal Flt mRNA expression is dependent upon VEGF, and VEGF inhibition results in abortive increases in expression of VEGF, angiopoietin-2, and Tie-2.

Regulation and manipulation of angiogenesis in the primate corpus luteum.

Intense physiological angiogenesis occurs during the early stages of luteal development, providing a model in which the complex processes regulating the angiogenic pathway may be studied. Here, a working hypothesis is presented to explain the diverse changes in the vasculature of the corpus luteum that occur over a short period, based around changes in vascular endothelial growth factor, the angiopoietins and matrix metalloproteinases. An illustration is given of how angiogenesis can be monitored in a primate model and how the role of individual angiogenic factors such as vascular endothelial growth factor may be explored in vivo. Because of the marked effect of inhibition of angiogenesis on luteal function, it is predicted that the normal processes of follicular development, ovulation and luteal function could all be profoundly influenced by the manipulation of angiogenesis.

Endocrine-immune interaction: alteractions in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates.

PROBLEM: The effect of neonatal gonadotropin releasing hormone (GnRH) antagonist (Ant) treatment and seasonality on immune system development and function was investigated in male primates. METHOD OF STUDY: Neonatal male rhesus monkeys and marmosets were treated with Ant, and its effect on immune system morphology, circulating lymphocyte subsets, and cell- and humorally-mediated immune responses was assessed during development. In adult rhesus monkeys, we correlated seasonal changes in immune function with circannual fluctuations in immunoactive hormones. RESULTS: In neonatal marmosets, Ant reduced the number of B cells and T cells in the thymic medulla and T cells in the periarterial lymphatic sheaths (PALS) of the spleen. Ant also altered the development of, but did not permanently impair, the proliferative index (PI) of blood lymphocytes to mitogens. In vitro treatment of control lymphocytes with GnRH analogues altered their response to these proliferative agents. In neonatal rhesus monkeys, Ant treatment increased the frequency of clinical problems, lowered circulating levels of lymphocytes, total T cells, CD8+ T cells and B cells, and altered the PI of lymphocytes to mitogens. As adults, the cell- and humorally-mediated immune responses remained impaired. We also documented seasonal fluctuations in the prevalence of diseases, circulating immune cells and immune function in rhesus monkeys. The number of cases of campylobacteriosis and shigellosis was lowest in the winter and highest in the spring. Circulating numbers of white blood cells (WBC) and neutrophils and the PI of lymphocytes to mitogens were higher in the winter than in the summer. Natural killer cell activity also varied with season. Cortisol and leptin secretion exhibited circannual rhythms, rising in concert with decreasing photoperiod and increasing testicular activity in the fall. Conversely, prolactin levels declined with decreasing photoperiod and then rose in the spring. CONCLUSION: Neonatal exposure of male primates to Ant appears to alter early postnatal programming of immune function. In the rhesus monkey, immune function shows seasonal fluctuations that may be driven by circannual changes in the secretion of immunoactive hormones.

Comparison of microembolism detected by transcranial Doppler and neuropsychological sequelae of carotid surgery and percutaneous transluminal angioplasty.

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty (PTA) is currently being assessed for the treatment of carotid stenosis. In comparison with carotid endarterectomy (CEA), there is evidence of an increased risk of cerebral microembolism during the procedure. We have sought evidence of any neuropsychological sequelae of carotid PTA and compared it with CEA to demonstrate the relative safety of the 2 treatment options. METHODS: The neuropsychological outcomes after CEA and PTA were compared in 2 matched groups of patients with severe symptomatic carotid stenosis, 96% of whom had been randomized in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), at a single center. Transcranial Doppler insonation of the middle cerebral artery was used to measure cerebral reactivity in response to carbon dioxide inhalation before treatment and then to detect microembolization of the ipsilateral cerebral hemisphere and measure changes in blood flow velocity during the procedures. The performance on a neuropsychological test battery administered before, 6 weeks after, and 6 months after the procedure was compared in 20 patients undergoing PTA and 26 having CEA. RESULTS: At 6 weeks, 5 patients in each group showed a similar decline in neuropsychological performance; global measures showed no significant difference between the 2 procedures, despite a significantly higher incidence of microemboli during PTA. Both groups showed a marked reduction in anxiety after treatment. CONCLUSIONS: The findings provide some reassurance that PTA is not associated with greater cerebral complications than CEA, despite the higher embolic load recorded by transcranial Doppler ultrasonography during angioplasty.

Changes in insulin-like growth factor-binding protein-3 messenger ribonucleic acid in endothelial cells of the human corpus luteum: a possible role in luteal development and rescue.

In the human menstrual cycle, extensive angiogenesis accompanies luteinization; and the process is physiologically important for corpus luteum (CL) function. During luteolysis, the vasculature collapses, and the endothelial cells die. In a conceptual cycle, the CL persists both functionally and structurally beyond the luteoplacental shift. Although luteal rescue is not associated with increased angiogenesis, endothelial survival is extended. Despite the central role of the luteal vasculature in fertility, the mechanisms regulating its development and demise are poorly understood. There is increasing evidence that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important effectors of luteal function. Here, we have found that IGFBP-3 messenger RNA is expressed in the endothelium of the human CL and that the levels of message change during luteal development and rescue by human CG. The signal was strong during the early luteal phase, but it showed significant reduction during the mid- and late luteal phases. Interestingly, administration of human CG caused a marked increase in the levels of IGFBP-3 messenger RNA in luteal endothelial cells that was comparable to that observed during the early luteal phase. We conclude that endothelial cell IGFBP-3 expression is a physiological property of the CL of menstruation and pregnancy. These observations raise the intriguing possibility that the regulated expression of endothelial IGFBP-3 may play a role in controlling angiogenesis and cell responses in the human CL by autocrine/paracrine mechanisms.

Suppression of luteal angiogenesis in the primate after neutralization of vascular endothelial growth factor.

Manipulation of angiogenesis may have a profound effect on female reproductive function, but this has not yet been demonstrated by direct experiment in species with ovulatory cycles similar to those in women. To investigate whether angiogenesis could be inhibited in the primate corpus luteum, and the consequences of such inhibition on luteal function, marmosets were treated with an antibody to vascular endothelial growth factor (VEGF). Treatment commenced at the time of ovulation and was continued for 3 days (early luteal group) or 10 days (midluteal group). Bromodeoxyuridine was used to label proliferating cells, being administered 1 h before collecting ovaries from control and treated animals in the early or midluteal phase. Ovarian sections were stained using an antibody to bromodeoxyuridine, and a proliferation index was obtained; endothelial cell quantification was performed using factor VIII as an endothelial cell marker. Intense proliferation in the early luteal phase was suppressed by anti-VEGF treatment. This resulted in blockade of development of the normally extensive capillary bed, as in the animals treated until the mid-luteal phase the numbers of endothelial cells were reduced. The hormone-producing cells remained largely unaltered in the posttreatment corpus luteum, although the presence of lipid accumulation, and small pockets of cells showing basophilia and nuclear condensation were observed. Significantly, luteal function, as judged by secretion of progesterone, was markedly compromised by the treatment, being reduced by 60% in comparison with controls. It is concluded that VEGF-mediated angiogenesis is an essential component of luteal function in primates and therefore has the potential to be regulated.

Angiogenesis and its control in the female reproductive system.

The rapid, controlled and cyclical nature of angiogenesis in the female reproductive tract suggests that interference with this process should provide a novel approach to manipulation of reproductive function. Many factors involved in the regulation of angiogenesis have been identified, and the possibility of stimulating or inhibiting these paracrine control mechanisms is being addressed using current advances in the development of angiogenic and anti-angiogenic compounds. Studies with animal models indicate that the normal processes of folliculogenesis, ovulation and corpus luteum function in the ovary, and the control of menstruation and implantation in the endometrium could be profoundly influenced by manipulation of angiogenesis. Novel therapeutic agents targeted to the angiogenic pathway may also have a wide range of applications in pathological processes in the reproductive tract such as cancer, endometriosis, fibroid growth, and ovarian hyperstimulation syndrome.

Luteal regression in the primate: different forms of cell death during naturaland gonadotropin-releasing hormone antagonist or prostaglandin analogue-induced luteolysis.

Morphological changes in the corpus luteum following natural and induced luteolysis in the marmoset were investigated by light and electron microscopy. Functional corpora lutea were studied in the mid and late luteal phase, naturally regressed corpora lutea in the early and late follicular phase, and corpora lutea induced to regress by administration of GnRH antagonist or prostaglandin F(2alpha) analogue in the midluteal phase. Natural luteolysis was associated with lutein cell atrophy, condensation of cytoplasmic inclusions and organelles, and accumulation of lipid. GnRH antagonist treatment resulted in aggregations of smooth membranes and myelin-like bodies in the cytoplasm of the lutein cells together with complex aggregations of degenerative cells. After prostaglandin treatment, the lutein cells contained numerous small and large vesicles; as the degenerative changes advanced, these vesicles coalesced into alveolar-type vacuoles, and nuclei involuted. These results show that in the marmoset, natural luteolysis and the two luteolytic treatments reveal different forms of luteal degeneration and cell death, none of which fit the ultrastructural criteria for apoptosis. More emphasis needs to be placed on understanding these predominant nonapoptotic forms of cell death in order to elucidate the process of luteolysis in the primate.

Effect of neonatal treatment with a GnRH antagonist on development of the cell-mediated immune response in marmosets.

PROBLEM: We examined the effect of neonatal treatment with a gonadotropin-releasing hormone (GnRH) antagonist (antide) on the development of cell-mediated immunity in male marmosets. METHOD OF STUDY: Neonatal marmoset twins were treated with either vehicle or antide, and the proliferative response (PR) of lymphoid tissue to mitogens was assessed during infancy, the peripubertal period, and adulthood. RESULTS: Basal proliferation of peripheral blood mononuclear cells (PBMC) from treated peripubertal twins was elevated above control values, but the PR of the cells to T and B cell mitogens was subnormal. Conversely, PBMC from treated infants exhibited an enhanced PR to some of the mitogens employed. In vitro culturing of thymocytes (control or treated) from the three developmental stages with either antide or a GnRH agonist increased basal proliferation, but decreased the PR to mitogens by 60-80%. CONCLUSION: Neonatal treatment with antide alters development of, but does not permanently impair, cell-mediated immunity in the marmoset. GnRH appears to modulate immune responses throughout development in the primate.

The effect of the angiogenesis inhibitor TNP-470 on luteal establishment and function in the primate.

Angiogenesis during luteal development is probably essential for normal lutein cell function. Since the angiogenesis inhibitor TNP-470 inhibits pregnancy in mice, the current study investigated its effects on the establishment and function of the primate corpus luteum. Regularly ovulating macaques were treated with TNP-470 (6 mg/kg), i.v. in three doses, 48 h apart. Serum progesterone concentrations, as indicators of treatment effect, were normal in four macaques where treatment commenced at the onset of the ovulatory progesterone rise, and in five of eight in which treatment commenced a few days before ovulation. In the other three the normal progesterone rise was absent. To investigate the direct effect on luteal angiogenesis of a daily dose over a longer period, four marmosets received 18 mg/kg/day of TNP-470 i.v. for 9 days starting at ovulation. On day 10, luteal cell proliferation was determined by nuclear bromodeoxyuridine incorporation. Luteal microvasculature was examined using immunocytochemical factor VIII staining, and endothelial cell and luteal function assessed by in-situ hybridization of insulin-like growth factor binding protein-3 mRNA and plasma progesterone concentrations respectively. None of these parameters were affected by the TNP-470 treatment. The results show that, with the treatment regimens employed, TNP-470 had no significant effect on the expression of the differentiated state of the primate corpus luteum.

Impact of carotid endarterectomy upon cognitive functioning. A systematic review of the literature.

BACKGROUND AND PURPOSE: The extent to which carotid endarterectomy (CEA) influences cognitive functioning has been the subject of a number of studies often with conflicting conclusions. This paper systematically reviews the literature in an attempt to clarify this issue. RESULTS: Although the majority of studies (16/28) reported an improvement in cognition after surgery, a substantial minority (12/28) found no change. Studies before 1984 tended to report an improvement, while later studies tended to report no change in cognition. Cognitive improvement was also more likely the longer the time interval between CEA and assessment. The studies were found to differ on many methodological factors, e.g. sample size, type of patient and control group, severity and side of carotid stenosis, the range of cognitive tests and timing of postoperative assessment. CONCLUSION: Given the conflicting findings, and the methodological issues, it is not possible to draw a clear conclusion regarding the impact of carotid endarterectomy upon cognition. Future research which pays attention to these methodological factors is needed in order to adequately resolve the current debate.

Insulin-like growth factor binding protein-3 mRNA expression in endothelial cells of the primate corpus luteum.

Luteinization is associated with endothelial cell proliferation as part of the extensive angiogenesis necessary to maintain corpus luteum function. However, following luteal demise, the vasculature regresses and the endothelial cells disappear. In the rat corpus luteum, the endothelial cells express high concentrations of insulin-like growth factor-binding protein-3 (IGFBP-3) during luteolysis, suggesting a role of IGFBP-3 during endothelial cell loss. The aim of the present study was to determine the occurrence and location of the messenger ribonucleic acid (mRNA) for IGFBP-3 in the primate corpus luteum, and to determine whether or not induction of luteal regression is associated with changes in localization of the message. Marmoset corpora lutea were studied throughout the cycle. The effects of induced luteolysis were examined 12 h or 24 h after treatment with either a gonadotrophin-releasing hormone antagonist or a prostaglandin F2alpha analogue, administered during the mid-luteal phase. High IGFBP-3 expression was recorded in the endothelial cells of the majority of microvessels and a minority of capillaries surrounding the lutein cells in all functionally active corpora lutea. Expression declined markedly in regressing corpora lutea of the late follicular phase. Expression of the IGFBP-3 mRNA in lutein cells in the control corpus luteum was extremely rare. There were no major differences in the degree and pattern of IGFBP-3 expression as a consequence of induced luteal regression although there was an apparent increase in the number of capillary endothelial cells expressing. Induction of luteolysis resulted in expression in a minority of lutein cells. These results support the concept that IGFBP-3 has an autocrine/paracrine role in regulating various cell types in the primate corpus luteum, including endothelial cells. However, expression of IGFBP-3 mRNA throughout the luteal phase suggests it may regulate angiogenesis and luteal function rather than endothelial cell death and luteolysis.

Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study.

OBJECTIVES: To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression. METHODS: The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (<350), and seropositive asymptomatic subjects, both groups being followed up in a longitudinal study. Control groups consisted of seronegative subjects from the same genitourinary medicine clinics. RESULTS: This report sets out the cross sectional findings at the seventh visit in the longitudinal study. Patients with AIDS had more signs of neurological dysfunction, poorer performance on a neuropsychological test battery, were more likely to have an abnormal EEG, and to have abnormalities on MRI. They more often had cerebral atrophy, abnormal appearing white matter, and abnormal relaxometry and spectroscopy. There was little evidence of abnormality in seropositive people who had a CD4 count >350 compared with seronegative people from a similar background. CONCLUSIONS: Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychological assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.