Functional connectivity of limbic system and prefrontal cortex years after pre-eclampsia: 7-Tesla functional magnetic resonance imaging study.

OBJECTIVE: Pre-eclampsia is a vascular complication of pregnancy, associated with a long-term risk of cerebrovascular and mental disorders. We explored whether formerly pre-eclamptic women exhibit differences in functional brain organization, especially in regions that may explain the commonly reported emotional symptoms and cognitive complaints even years after the pregnancy. METHODS: Formerly pre-eclamptic women and control women with a history of normotensive pregnancy underwent structural and functional 7-Tesla magnetic resonance imaging scans. Using graph theoretical analysis, the efficiency and clustering coefficient of the functional brain network were investigated. The study included local analysis focusing on particular brain structures, such as the limbic system and the prefrontal cortex, and global analysis of the whole cerebrum. Univariable and multivariable linear regression was used to investigate the relationship between brain network-related graph measures and the group (formerly pre-eclamptic or control). RESULTS: A total of 17 control parous women and 55 women with a history of pre-eclampsia were recruited. The time intervals between the index pregnancy and recruitment were 8.0 and 5.6 years for the two groups, respectively. Compared with control women, formerly pre-eclamptic women had higher local efficiency in the prefrontal cortex (P = 0.048) and anterior cingulate cortex (P = 0.03) but lower local efficiency and local clustering coefficient in the amygdala (P = 0.004 and P = 0.02, respectively) and parahippocampal cortex (P = 0.007 and P = 0.008, respectively). No differences were found in the global functional brain organization. CONCLUSIONS: Compared to controls with a history of normotensive pregnancy, formerly pre-eclamptic women displayed a different local functional brain organization. These differences in functional connectivity, especially in the limbic regions and the prefrontal cortex, are in line with the psychological and cognitive complaints reported commonly by women with a history of pre-eclampsia. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Blood-brain barrier leakage years after pre-eclampsia: dynamic contrast-enhanced 7-Tesla MRI study.

OBJECTIVE: Pre-eclampsia is a hypertensive complication of pregnancy that is associated with an increased risk of long-term cardiovascular and cerebrovascular disorders. Although the underlying mechanism of persistent susceptibility to cerebral complications after pre-eclampsia remains largely unclear, impaired blood-brain barrier (BBB) integrity has been suggested to precede several cerebrovascular diseases. In this study, we aimed to investigate the integrity of the BBB years after pre-eclampsia. METHODS: This was an observational study of premenopausal formerly pre-eclamptic women and controls with a history of normotensive pregnancy who underwent cerebral magnetic resonance imaging (MRI) at ultra-high field (7 Tesla) to assess the integrity of the BBB. Permeability of the BBB was determined by assessing leakage rate and fractional leakage volume of the contrast agent gadobutrol using dynamic contrast-enhanced MRI. BBB leakage measures were determined for the whole brain and lobar white and gray matter. Multivariable analyses were performed, and odds ratios were calculated to compare women with and those without a history of pre-eclampsia, adjusting for potential confounding effects of age, hypertension status at MRI and Fazekas score. RESULTS: Twenty-two formerly pre-eclamptic women (mean age, 37.8 ± 5.4 years) and 13 control women with a history of normotensive pregnancy (mean age, 40.8 ± 5.5 years) were included in the study. The time since the index pregnancy was 6.6 ± 3.2 years in the pre-eclamptic group and 9.0 ± 3.7 years in controls. The leakage rate and fractional leakage volume were significantly higher in formerly pre-eclamptic women than in controls in the global white (P = 0.001) and gray (P = 0.02) matter. Regionally, the frontal (P = 0.04) and parietal (P = 0.009) cortical gray matter, and the frontal (P = 0.001), temporal (P < 0.05) and occipital (P = 0.007) white matter showed higher leakage rates in formerly pre-eclamptic women. The odds of a high leakage rate after pre-eclampsia were generally higher in white-matter regions than in gray-matter regions. CONCLUSION: This observational study demonstrates global impairment of the BBB years after a pre-eclamptic pregnancy, which could be an early marker of long-term cerebrovascular disorders. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The association between first trimester placental biomarkers and placental lesions of maternal vascular malperfusion.

INTRODUCTION: Abnormal levels of first trimester placental biomarkers are associated with the development of placental syndrome (PS). However, prediction performance is moderate, possibly explained by the clinical heterogeneity of PS. Aim of this study is to investigate the association between first trimester biomarkers and the presence of maternal vascular malperfusion (MVM), as a marker for placental insufficiency. METHODS: This retrospective study included 195 women with available first trimester blood sample and placenta histological sections for examination at the Maastricht University Medical Centre. Women were divided into 4 groups, based on the presence of having MVM lesions and/or PS. Levels of PAPP-A, PlGF and sFlt-1 were measured and MVM lesions were classified according to the Amsterdam Placental Workshop Group Consensus Statement. RESULTS: MVM occurrence was observed in 32% of the uncomplicated pregnancies. Women with MVM (regardless of the PS) had lower levels of PAPP-A (p = 0.038) and sFLt-1 (p = 0.006), and a non-significant trend for lower PlGF and sFlt-1/PlGF ratio compared to women without MVM. Low PAPP-A levels individually and in combination with the presence of PS was significantly associated with MVM lesions (aOR = 3.0 and 6.1, respectively), as did the combination of low PlGF levels and PS (aOR = 4.6). In women with PS, having MVM increased the incidence of fetal growth restriction, small for gestational age neonates, lower birthweight and adverse neonatal outcome. DISCUSSION: Our findings suggest that MVM lesions were found to be associated with increased obstetric risks due to early placental dysfunction that can potentially be predicted by the use of first trimester biomarkers.

Feasibility of three dimensional power Doppler ultrasonography methods to assess placental perfusion.

OBJECTIVES: Given the crucial role of the placenta in establishing a healthy pregnancy, reliable non-invasive methods to measure placental perfusion are desirable. The aim of this study is to determine the reproducibility and potential bias in different three-dimensional power Doppler (3DPD) methods assessing placenta perfusion. METHODS: Ten singleton pregnancies around 16 weeks of gestation, with an anteriorly located placenta and centrally inserted umbilical cord were included in this study. Eight different combinations of a specific placental sweep and sonobiopsy method were used to evaluate placental perfusion. Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) were determined offline using the 4D-view program. Reproducibility and repeatability of the methods, expressed as correlation coefficients and Bland-Altman mean differences, were calculated. Differences between sampling methods were analyzed using t-test or Mann-Whitney U test. RESULTS: Intra- and inter-class correlation coefficient (CC) was highest when using a spherical centrally placed sonobiopsy of 2 cm3 in a whole placenta sweep (method 1; IntraCC VI 0.985, FI 0.769, VFI 0.993, InterCC VI 0.986, FI 0.784, VFI 0.987). Overall, intraCCs were higher compared to interCCs. Lowest mean differences in VI and FI were found comparing spherical to manual sonobiopsies, whereas the mean differences in VFI were lowest when comparing central versus peripheral located sonobiopsies. Comparing the three vascular indices, best median intra- and interCC and lowest mean differences were found for VFI. CONCLUSIONS: Three dimensional placental vascularization analysis showed best reproducibility using whole placental sweep volume and centrally located, spherical sonobiopsy of 2 cm3.

Lipodystrophy and weight changes: data from the Swiss HIV Cohort Study, 2000-2006.

BACKGROUND AND OBJECTIVES: Combination antiretroviral therapy (cART) is changing, and this may affect the type and occurrence of side effects. We examined the frequency of lipodystrophy (LD) and weight changes in relation to the use of specific drugs in the Swiss HIV Cohort Study (SHCS). METHODS: In the SHCS, patients are followed twice a year and scored by the treating physician as having 'fat accumulation', 'fat loss', or neither. Treatments, and reasons for change thereof, are recorded. Our study sample included all patients treated with cART between 2003 and 2006 and, in addition, all patients who started cART between 2000 and 2003. RESULTS: From 2003 to 2006, the percentage of patients taking stavudine, didanosine and nelfinavir decreased, the percentage taking lopinavir, nevirapine and efavirenz remained stable, and the percentage taking atazanavir and tenofovir increased by 18.7 and 22.2%, respectively. In life-table Kaplan-Meier analysis, patients starting cART in 2003-2006 were less likely to develop LD than those starting cART from 2000 to 2002 (P<0.02). LD was quoted as the reason for treatment change or discontinuation for 4% of patients on cART in 2003, and for 1% of patients treated in 2006 (P for trend <0.001). In univariate and multivariate regression analysis, patients with a weight gain of >or=5 kg were more likely to take lopinavir or atazanavir than patients without such a weight gain [odds ratio (OR) 2, 95% confidence interval (CI) 1.3-2.9, and OR 1.7, 95% CI 1.3-2.1, respectively]. CONCLUSIONS: LD has become less frequent in the SHCS from 2000 to 2006. A weight gain of more than 5 kg was associated with the use of atazanavir and lopinavir.

[Treatment of HIV infection in 2006: highlights]. / VIH--sida. Traitement de l'infection à VIH en 2006: points forts.

In developed countries, drug therapy has turned HIV infection into a chronic disease. More is known about viral replication and new, easily tolerated drugs will enter the marketplace in 2007 and 2008. For the majority of patients who suffer neither resistance nor intolerance, older molecules are combined in the same pill. Very effective triple therapy, combining efavirenz, emtricitabine, and tenofovir in one pill (Atripla - Gilead) is already available in the United States and will become the standard of therapy in 2007. Since the eradication of the virus remains impossible even under effective antiretroviral therapy, the scheduled treatment interruptions as well as simplified maintenance therapies represent still a topic of interest for well selected patients, with an aim of reducing the costs and toxicities.

Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy.

Discontinuation of maintenance therapy against toxoplasma encephalitis (TE) for individuals infected with human immunodeficiency virus (HIV) who are receiving successful anti-retroviral therapy is considered safe. Nevertheless, there are few published studies concerning this issue. Within the setting of the Swiss HIV Cohort Study, this report describes a prospective study of discontinuation of maintenance therapy against TE in patients with a sustained increase of CD4 counts to > 200 cells/microL and 14% of total lymphocytes, and no active lesions on cerebral magnetic resonance imaging (MRI). In addition to clinical evaluation, cerebral MRI was performed at baseline, and 1 and 6 months following discontinuation. Twenty-six AIDS patients with a history of TE agreed to participate, but three patients (11%) could not be enrolled because they still showed enhancing cerebral lesions without a clinical correlate. One patient refused MRI after 6 months while clinically asymptomatic. Among the remaining 22 patients who discontinued maintenance therapy, one relapsed after 3 months. During a total follow-up of 58 patient-years, there was no TE relapse among the patients who had remained clinically and radiologically free of relapse during the study. Thus, discontinuation of maintenance therapy against TE was generally safe, but may fail in a minority of patients. Patients who remain clinically and radiologically free of relapse at 6 months after discontinuation are unlikely to experience a relapse of TE.

[Primary HIV infection: an update]. / Primo-infection VIH: mise au point.

Acute HIV infection is a frequently symptomatic event. Presenting as a mononucleosis-like disease with fever, lymphadenopathy, myalgias, rash and headache, it is insufficiently identified. Since acute HIV infection is associated with high viral loads it is important to diagnose patients with this entity, in order to prevent transmission. An evolution towards AIDS can happen more rapidly according to length and severity of the symptoms, but it is still controversial whether very early therapy during acute seroconversion is beneficial on the long-run. Randomised controlled trials of early short-term antiretroviral treatment versus deferred therapy are both ethically justifiable and necessary.

[HIV-AIDS 2004: New substances, new targets for treatment, future therapeutic strategies]. / Sida. Molécules récentes, strategies thérapeutiques d'avenir et nouvelles cibles du traitement.

In developed countries, drug therapy has turned HIV infection into a chronic disease. Follow-up of patients who take antiretroviral therapy is becoming more and more complex and individualised, often multidisciplinary approach is warranted. Problems with compliance to treatment and viral drug resistance have encouraged research of new substances. More is known about viral replication and other targets for treatment are under investigation. Improvements to therapeutic strategies practised in the last few years provide new possibilities in the fight against HIV infection.

Recent changes in the management of primary HIV-1 infection: results from the French PRIMO cohort.

OBJECTIVES: To describe the management of primary HIV infection (PHI), focusing on changes in the design of therapies and time to initiation of antiretroviral treatment, the clinical outcome, and the immuno-virological response over time to highly active antiretroviral therapy (HAART) and its tolerance. DESIGN AND METHODS: In the French PRIMO multicentre cohort, 291 patients presenting with PHI were enrolled between 1996 and 2001. Data were analysed to describe treatment prescription habits over a period of 5 years, and response to and tolerance of treatment. RESULTS: The proportion of patients who initiated treatment during PHI decreased from 92% in 1996 to 56% in 2001. At 6 months, whatever the initiated treatment, 74% of treated patients achieved a plasma viral load<400 HIV-1 RNA copies/mL and 53% achieved a viral load of<50 copies/mL. Prescription of protease inhibitor (PI)-sparing regimens has become more frequent since 1999. Despite a similar virological response, patients in the PI-containing group tended to experience a greater 1-year increase in CD4 cell count than those in the non-nucleoside reverse transcriptase (NNRTI)-containing group (218 cells/microL versus 157 cells/microL, respectively). An adverse event was recorded in 51% of treated patients. The most frequent events were gastrointestinal disorders (71%), lipodystrophy (27%) and mood disorders (19%). The main reason for modifying or stopping therapy was the occurrence of an adverse event. CONCLUSIONS: Limitations of therapy and poor tolerance to antiretroviral regimens have changed physician attitudes in PHI. This suggests the need for evaluation of better-tolerated regimens and new therapeutic strategies.

[Treatment of cutaneous human papilloma virus, poxvirus and herpes simplex virus infections with topical cidofovir in HIV positive patients]. / Traitement par cidofovir topique d'infections cutanées à papillomavirus humain, poxvirus et herpes simplex virus chez des malades séropositifs pour le VIH.

INTRODUCTION: Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100. PATIENTS AND METHODS: Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes. RESULTS: Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially. COMMENTS: In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

BACKGROUND: Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. QUESTIONS UNDER STUDY: (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. SETTING: The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. METHODS: Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. RESULTS: 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). CONCLUSION: Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

Modern anti-HIV therapy.

Highly active antiretroviral therapies (HAART), usually consisting of two nucleoside reverse transcriptase inhibitors (NRTI) plus an HIV protease inhibitor (PI), have been widely used since 1996. They produce durable suppression of viral replication with undetectable plasma levels of HIV-RNA in more than half of patients. Immunity recovers, and morbidity and mortality fall by more than 80% [1, 2]. Treatment was thought to be particularly effective when started early; therefore, HAART was recommended for essentially all HIV-infected persons willing to commit themselves to lifelong therapy [3, 4]. Besides these successes, however, HAART also produces problems. HIV is not eradicated by present-day drugs, and patients often cannot comply with long-term combination treatment [5, 6]. Moreover, HAART causes unexpected and ill-understood side effects [7]. The dogma of earliest possible treatment has therefore come under attack. Ten principles governing anti-retroviral treatment are summarised in Table 1. Starting and maintaining HAART is complex. Within the last few years, the numbers of antiretrovirals, their known and potential interactions with each other and with non-HIV drugs, and the list of their side effects have all increased exponentially. As a rule a physician specialising in HIV care should be consulted whenever HAART is started or changed. It is his task to ensure that the treatment chosen is optimal for the particular patient.

Discontinuation of primary prophylaxis in HIV-infected patients at high risk of Pneumocystis carinii pneumonia: prospective multicentre study.

OBJECTIVES: To assess the safety of discontinuation of primary prophylaxis in HIV-infected patients on antiretroviral combination therapy at high risk of developing Pneumocystis carinii pneumonia. DESIGN: Prospective multicentre study. PATIENTS AND METHODS: The incidence of P. carinii pneumonia after discontinuation of primary prophylaxis was studied in 396 HIV-infected patients on antiretroviral combination therapy who experienced an increase in their CD4 cell count to at least 200 x 10(6)/l and 14% of total lymphocytes; the study population included 191 patients with a history of CD4 cell counts below 100 x 10(6)/l (245 person-years) and 144 patients with plasma HIV RNA above 200 copies/ml (215 person-years). RESULTS: There was one case of Pneumocystis pneumonia, an incidence of 0.18 per 100 person-years [95% confidence interval (CI), 0.005--1.0 per 100 person-years]. No case was diagnosed in groups with low nadir CD4 cell counts (95% CI, 0--1.2 per 100 person-years) or detectable plasma HIV RNA (95% CI, 0--1.4 per 100 person-years). CONCLUSIONS: Discontinuation of primary prophylaxis against Pneumocystis pneumonia is safe in patients who have responded with a sustained increase in their CD4 cell count to antiretroviral combination therapy, irrespective of the CD4 cell count nadir and the viral load at the time of stopping prophylaxis.

Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997.

OBJECTIVE: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe. METHODS: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop. RESULTS: Subpopulations of genetically related HIV strains were observed in Italy, France, Scotland and Spain, in contrast to the Netherlands, Austria and Switzerland. This difference between the two groups of countries suggests that the HIV epidemics amongst IDU in the latter group was caused by multiple virus introductions. In Edinburgh and the surrounding area, most IDU were infected with the same GGC strain over the 12-year study period. The epidemic among IDU in north-western Europe started with GGC viruses, whereas in south-western Europe non-GGC viruses predominated. This geographical separation has faded during the course of the epidemic, most likely because of virus exchange among IDU populations.

Salvage therapy with abacavir plus a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor in heavily pre-treated HIV-1 infected patients. Swiss HIV Cohort Study.

BACKGROUND: Highly active antiretroviral therapy (HAART) may fail, especially in pre-treated patients. OBJECTIVE: To examine retrospectively whether heavily pre-treated patients not responding to HAART at least once respond to a salvage therapy with abacavir, a nucleoside reverse transcriptase inhibitor (NRTI) plus a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) and one or two protease inhibitors (PI). PATIENTS: We retrospectively identified and analysed patients followed in the Swiss HIV Cohort Study with > 1000 HIV RNA copies/ml on HAART, naive to abacavir who were switched to abacavir plus one NNRTI (efavirenz or nevirapine) and one or two PI which had not been used in the previous HAART. RESULTS: Of 23 identified HIV-infected patients with four (median) therapy changes before salvage, 10 patients (43%) achieved a decrease of plasma HIV RNA > 0.5 log10 at 6 months of therapy. After 6 months only two patients had an HIV-1 RNA < 500 copies/ml, one of them < 50 copies/ml. Seven patients increased their CD4 cell counts by > 30% above baseline. Three patients, all with CD4 cell counts < 100 x 10(6)/l before salvage therapy had a > 30% decline in CD4 cell count. An extended number of resistance-associated mutations was found in almost all patients at baseline. One patient had two new AIDS-defining events. Five patients (22%) discontinued treatment because of side-effects, mainly occurrence of a rash. CONCLUSION: Salvage therapy in intensively pre-treated patients has a low virological success rate despite usage of abacavir and NNRTI. Nevertheless, this did not correlate with immunological and clinical course. This study emphasizes the difficulty of second-line treatment in HIV-1 infection and stresses the need for new compounds.

[Cytomegalovirus in liver transplantation: incidence and groups at risk]. / Le cytomégalovirus chez les transplantés du foie: incidence et groupes à risques.

Cytomegalovirus (CMV) belongs to the family of Herpes viridae and has become the single most important viral pathogen in clinical transplantation. This is an endemic and ubiquitous virus. After transplantation it is necessary to distinguish CMV infection (positive seroconversion and/or isolation of the virus in the blood, urine, sputum or tissues in the absence of clinical symptoms) from CMV disease, which is a clinical expression of viremia in association with a documented CMV infection. The overall incidence of CMV infection in transplant recipients is about 50% and the incidence of CMV disease ranges from 15 to 25% whatever the transplanted organ. In this study (52 liver transplantations in 48 patients), 12 patients had CMV infection and 10 patients developed CMV disease (24%). The onset of CMV disease was 33 +/- 7 days after transplantation. Cytomegalovirus hepatitis was observed 7 times, CMV pneumonia once and 2 CMV infections characterized by oscillating fever in association with a hematological syndrome. 8 patients were treated with intravenous gancyclovir (DHPG, 9-[1,3-dihydroxy-2-propoxymethyl]-guanine) for 15 days and 2 patients by reduction of their immunosuppressive therapy only. There were significantly more (p < 0.05) opportunistic infections and/or bacteremia in patients with CMV disease. The association of CMV IgG negative recipients and CMV IgG positive donors appeared to be a significant factor (p < 0.05) for CMV disease. The number of transfusions, the level of immunosuppression and the absence of prophylaxis did not influence the incidence of CMV disease. Despite prolonged hospitalization and increased morbidity, there were no deaths in patients who developed CMV disease, which is good evidence of the efficacy of gancyclovir.(ABSTRACT TRUNCATED AT 250 WORDS)