Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital-acquired pressure ulcers: a pragmatic noncommercial multicentre randomized open-label parallel-group medical device trial.

BACKGROUND: Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs). OBJECTIVES: To determine whether silicone foam dressings in addition to standard prevention reduce the incidence of PUs of category 2 or worse compared with standard prevention alone. METHODS: This was a multicentre, randomized controlled medical device trial conducted in eight Belgian hospitals. At-risk adult patients were centrally randomized (n = 1633) to study groups based on a 1 : 1 : 1 allocation: experimental groups 1 (n = 542) and 2 (n = 545) - pooled as the treatment group - and the control group (n = 546). The experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on the relevant body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU of category 2 or worse at the studied body sites. RESULTS: In the intention-to-treat population (n = 1605), PUs of category 2 or worse occurred in 4·0% of patients in the treatment group and 6·3% in the control group [relative risk (RR) 0·64, 95% confidence interval (CI) 0·41-0·99, P = 0·04]. Sacral PUs were observed in 2·8% and 4·8% of the patients in the treatment group and the control group, respectively (RR 0·59, 95% CI 0·35-0·98, P = 0·04). Heel PUs occurred in 1·4% and 1·9% of patients in the treatment and control groups, respectively (RR 0·76, 95% CI 0·34-1·68, P = 0·49). CONCLUSIONS: Silicone foam dressings reduce the incidence of PUs of category 2 or worse in hospitalized at-risk patients when used in addition to standard of care. The results show a decrease for the sacrum, but no statistical difference for the heel and trochanter areas.

[«KCE Trials¼ : innovation based on practice oriented clinical trials]. / «KCE Trials¼ : des essais cliniques plus proches de la pratique.

Many questions in healthcare can only be answered after the conduct of clinical trials. For medicinal products and medical devices the industry finances most studies to bring their products to market. However, there is a need for further research in certain areas e.g. children, older people and comparative research of different treatment options (comparative effectiveness). In addition, interventions that are less industry-driven such as surgery, radiotherapy, psychotherapy, diet, physical medicine, needappropriately funded large scale clinical trials. Such clinical trials can be a good investment for the government and the healthcare payer. At the end of 2015 the Belgian Healthcare Knowledge Centre (KCE) received the mission and budget to run a programme of practice-oriented comparative clinical trials. Two years later the recruitment of patients in the first trials is ongoing. In addition to its yearly national calls for trial proposals, early in 2018 KCE launched its first international common call for comparative clinical trials with its Dutch counterpart ZonMw (BeNeFIT).

Les études cliniques financées par l'industrie, essentiellement effectuées dans le but d'obtenir la mise sur le marché de médicaments et de dispositifs médicaux, laissent de nombreuses questions cliniques sans réponse satisfaisante. Ainsi, par exemple, les produits y sont généralement comparés à un placebo, alors que la question réellement pertinente pour le clinicien serait une comparaison avec d'autres options thérapeutiques. De même, les domaines qui présentent un intérêt moindre pour l'industrie sont rarement explorés par des études à large échelle; c'est le cas, notamment, de la chirurgie, de la radiothérapie, des psychothérapies, de l'alimentation et de la médecine physique. Un programme d'études cliniques non commerciales, financé par les pouvoirs publics, permet de remédier à ces problèmes tout en constituant un excellent investissement pour les autorités de santé et le contribuable. Fin 2015, le Centre fédéral d'Expertise des Soins de Santé (KCE) a été chargé de mettre sur pied un tel programme d'études cliniques comparatives et axées sur la pratique. Deux ans plus tard, le recrutement des premiers essais bat son plein. Un appel annuel à sujets d'études a été mis en place et, début 2018, un premier appel international conjoint du KCE et de son homologue néerlandais le ZonMw a également été lancé (BeNeFIT).

[Introduction of innovative high-risk medical devices in Europe: are clinical efficacy and safety guaranteed?]. / Mise sur le marché européen des dispositifs médicaux innovants à haut risque: l'efficacité clinique et la sécurité sont-elles garanties?

BACKGROUND: Innovative high-risk medical devices, such as new types of heart valves or hip prostheses, become available on the European market more rapidly than in USA. This is due to the European legislation allowing early marketing of innovative high-risk medical devices before high-quality clinical evidence is obtained from randomized controlled trials. METHODS: We studied the premarket clinical evaluation of innovative high-risk medical devices in Europe compared with the USA. We also discussed patient safety and the transparency of information. The literature and regulatory documents were checked. Representatives from industry, competent authorities, notified bodies, ethics committees, and health technology assessment agencies were consulted. RESULTS: In contrast to the US, there is no requirement in Europe to demonstrate the clinical efficacy of high-risk devices in the premarket phase. For the patient, this implies earlier access to innovative technology, but at the risk of potential safety issues. At this moment, European requirements for clinical studies are lower for medical devices than for drugs, and data from premarket clinical trials are scarce or remain unpublished. The European Medical Device Directives are currently being reworked. CONCLUSIONS: For innovative high-risk devices, and while awaiting a reworked Medical Device Directive, patient risk should be minimized by limiting the market introduction of novel high-risk devices with minimal clinical data to physicians with the necessary training and expertise. The new European legislation should require the premarket demonstration of clinical efficacy and safety, using a randomized controlled trial if possible, and a transparent clinical review, preferably centralized.

Hospital-acquired infections in Belgian acute-care hospitals: an estimation of their global impact on mortality, length of stay and healthcare costs.

Assessing the overall burden of disease which can be attributed to hospital-acquired infections (HAIs) remains a challenge. A matched cohort study was performed to estimate excess mortality, length of stay and costs attributable to HAIs in Belgian acute-care hospitals, using six matching factors (hospital, diagnosis-related group, age, ward, Charlson score, estimated length of stay prior to infection). Information was combined from different sources on the epidemiology and burden of HAIs to estimate the impact at national level. The total number of patients affected by a HAI each year was 125 000 (per 10·9 million inhabitants). The excess mortality was 2·8% and excess length of stay was 7·3 days, corresponding to a public healthcare cost of €290 million. A large burden was observed outside the intensive-care unit setting (87% of patients infected and extra costs, 73% of excess deaths).

Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting.

PURPOSE: This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. PATIENTS AND METHODS: One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. RESULTS: Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. CONCLUSION: The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.

Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies.

Children acquire neuropsychologic dysfunctions after chemotherapy for hematologic malignancy. In this study, putative changes in levels of CSF-tau (a marker of neural dysintegrity) in leukemic children prior to and during chemotherapy were studied. Cerebrospinal fluid (CSF) samples were obtained before and during treatment from patients with B cell non-Hodgkin's lymphoma (NHL, n = 10), non-B cell acute lymphoblastic leukemia/NHL (non-B-ALL, n = 48), acute myeloid leukemia (AML, n = 9), other malignant diseases (n = 9), and six control children. A sandwich-type ELISA (INNOTEST hTAU-Ag) was used for measuring CSF-tau. Sixteen out of 50 patients with hematological malignancies, including the patients with proven leukemic CNS invasion, already showed high CSF-tau levels at baseline (>300 pg/ml). The pre-induction treatment for non-B-ALL, consisting of only corticosteroids and methotrexate (MTX), resulted in a significant increase of tau at day 8 (on average to 535 pg/ml). Larger increases as compared to baseline levels of CSF-tau were observed in patients treated for B-NHL with systemic vincristine, corticosteroids and cyclophosphamide, and intrathecal MTX (mean 776 pg/ml at day 8). In two AML patients with CNS invasion, CSF-tau increased during chemotherapy up to 1,500 and 948 pg/ml, respectively. In one non-B-ALL patient with MTX-induced clinical neurotoxicity, CSF-tau was above the detection limit of 2,000 pg/ml. Almost one-third of the patients with hematological malignancies had elevated CSF-tau levels at diagnosis. Transient high levels of CSF-tau, reaching levels observed in other neurodegenerative disorders, were observed during induction chemotherapy for non-B-ALL, B-NHL and CNS+ AML. The clinical implications of both observations will be the subject of further study.

A prospective multicenter study of the efficacy and tolerability of cryopreserved allogenic human keratinocytes to treat venous leg ulcers.

Allogeneic human keratinocyte cultures have been used to treat burn wounds, donor sites, and chronic skin ulcers with some success. Cryopreservation of these cultures allows for the production of large standardized batches that are readily available for use. The aim of the study presented in this report was to study effects of cryopreserved cultured allogenic human keratinocytes (CryoCeal) on chronic lower extremity wounds. Parameters were measured to study efficacy, tolerability, pain associated with chronic wounds, and quality of life of patients. Twenty-seven patients with hard-to-heal venous leg ulcers received a maximum of 9 applications of CryoCeal in a prospective, uncontrolled multicenter study lasting 48 weeks. Eleven out of 27 patients (41%; 95% CI: 22%-61%) had complete wound closure within 24 weeks (1 week). The time required for complete wound closure in these 11 patients ranged from 4.1 to 24.9 weeks. Only 1 patient had recurrence of the ulcer at 48 weeks. Local (wound) pain scores decreased from a mean of 2.5 at baseline to 0.9 at week 24. Fifty percent of the patients attained a pain score of 0 after 12 weeks and remained stable at this score until the end of the study. Overall, the patient quality of life was better at week 24, compared to baseline values. The treatment was well tolerated, and wound infection was the most frequently occurring adverse event.

Expression of activation antigens, HLA-DR and CD38, on CD8 lymphocytes during HIV-1 infection.

OBJECTIVE: To study the expression of the activation markers human leukocyte antigen (HLA)-DR and CD38 antigen on CD8+ T-lymphocytes in HIV-infected subjects and HIV-negative controls. DESIGN: Two- and three-colour flow-cytometric analysis. METHODS: Fresh peripheral venous blood was obtained from 16 HIV-infected subjects, representing four different stages of HIV disease, and from six HIV-negative controls. Three-colour lymphocyte immunophenotyping was performed using peridinyl chlorophyll-A protein (PerCP)-conjugated anti-CD8 monoclonal antibody (MAb) in combination with anti-HLA-DR (phycoerythrin) and anti-CD38 (fluorescein isothiocyanate) MAb. RESULTS: The relative percentage of the lymphocyte populations thus defined differed between HIV-negative and HIV-positive subjects and between HIV-infected subjects at different clinical stages of disease. Simultaneous expression of HLA-DR and CD38 within the CD8 T-lymphocyte compartment increased from 8% in controls to 49% in asymptomatic HIV-infected subjects (P less than 0.005). Symptomatic patients differed from asymptomatic seropositives by a further increase in the HLA-DR+ CD38+ CD8 subset. In AIDS patients, the HLA-DR+ CD38- CD8 subset decreased (P less than 0.05) and the HLA-DR- CD38+ CD8 subset increased (P less than 0.05), compared with the other HIV disease stage patients. CONCLUSION: There is a stage-associated pattern of HLA-DR and CD38 expression on CD8 T-lymphocytes during HIV infection; specific phenotypic patterns may have functional correlates in the host response to the virus.

Cerebrospinal fluid tau and beta-amyloid(1-42) in dementia disorders.

The reliability of cerebrospinal fluid (CSF)-tau and CSF-beta-amyloid assays for diagnosis of Alzheimer's disease and other dementing disorders such as frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) and Creutzfeldt-Jakob disease (CJD) is reviewed. CSF assessment of the two proteins is useful in early diagnosis of AD and to differentiate it from FTD and DLB. Extremely high CSF-tau levels can discriminate CJD from AD.

Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF.

OBJECTIVE: To evaluate CSF levels of beta-amyloid(1-42) (Abeta42) alone and in combination with CSF tau for distinguishing AD from other conditions. METHODS: At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD). Sandwich ELISA techniques were used on site for measuring Abeta42 and tau. RESULTS: Median levels of Abeta42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001). Discrimination of AD from CON and ND was significantly improved by the combined assessment of Abeta42 and tau. At 85% sensitivity, specificity of the combined test was 86% (95% CI: 81% to 91%) compared with 55% (95% CI: 47% to 62%) for Abeta42 alone and 65% (95% CI: 58% to 72%) for tau. The combined test at 85% sensitivity was 58% (95% CI: 47% to 69%) specific for NAD. The APOE e4 gene load was negatively correlated with Abeta42 levels not only in AD but also in NAD. CONCLUSIONS: The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.

Distribution and composition of HDL subclasses in students whose parents suffered prematurely from a myocardial infarction in comparison with controls.

The purpose of this study was to analyze the distribution and composition of the HDL subclasses in students whose parents suffered from a premature coronary heart disease (CHD), in comparison with a control group without any familial history of CHD. In the first part of this study, we observed significantly lower apo A-I concentrations in the cases than in the controls. Since there was a significant difference in smoking habits between cases and controls, and since we wanted to study the effect of a parental history of premature CHD on the composition of the HDL subclasses independently of smoking, the present study was conducted on the 17 pairs of non-smokers male cases and controls. In agreement with the results on total serum, we observed lower apo A-I concentrations in the HDL2b and HDL2a + 3a fractions in the cases compared to the controls. The apo A-II and cholesterol levels in these fractions were not significantly different between the 2 groups. The selective decrease of apo A-I in the HDL subclasses with the lowest density might be due to a decreased number of particles containing only apo A-I, with which a protective effect against atherosclerosis might be associated.

The immune profile of multiple sclerosis: T-lymphocyte effects predominate over all other factors in cyclophosphamide-treated patients.

It is widely believed that multiple sclerosis is a T-cell mediated autoimmune disease associated with abnormalities in immunoregulation. This large, prospective study evaluated the lymphocyte immunophenotypic profile of 246 MS patients, divided clinically into a remitting/relapsing group (n = 176) and a progressive group (n = 70), and compared their results to those of 117 healthy controls. All patients were found to have significantly elevated percentage and absolute numbers of IL2R+CD3+ cells as well as depressed percentages of CD45RA+CD4+ cells. However, when the factor of treatment with cyclophosphamide (CY) versus no treatment or treatment with other agents was used to group patients, dramatic declines in both percentages and absolute numbers of CD45RA+CD4+ cells were discovered. These declines were associated specifically with CY and and could be explained by this factor independent of the clinical state of the patient. The effects were seen in patients undergoing current treatment or in those exposed to CY in the near or remote past. These findings highlight the confounding effect of specific treatments on the immune profile of MS patients groups and suggest that there may be important implications for cellular function and clinical outcome in these and other patient groups.

Clinical optimization and multicenter validation of antigen-specific cut-off values on the INNO-LIA ANA update for the detection of autoantibodies in connective tissue disorders.

OBJECTIVES: The INNO-LIA ANA Update is a qualitative multiparameter line immunoassay for detection of autoantibodies to several different antigens associated with connective tissue disorders. We sought to optimize and validate the cut-off values for its antigen-specific components: SmB, SmD, RNP-70k, RNP-A, RNP-C, SSA/Ro52, SSA/Ro60, SSB/La, Cenp-B, Topo-I, Jo-1, ribosomal P, and histones. Our aim was to achieve 98% specificity for each of the markers, with respect to differential disease controls, while maintaining sensitivity. METHODS: For optimization, the cut-off value of the different antigen lines was fixed to achieve this specificity using an in-house set of 955 patient samples. Specificity was validated at multiple sites using a different set of 330 samples obtained from 158 apparently healthy blood donors, 100 patients with a variety of infections, 20 each with Wegener's granulomatosis, inflammatory bowel disease, and primary antiphospholipid syndrome, and 12 with psoriatic arthritis. Sensitivity was evaluated, using this optimized cut-off control, in 147 patients with scleroderma, 93 with Sjögren's disease, 40 with systemic lupus erythematosus, 40 with rheumatoid arthritis, 39 with mixed connective tissue disease, and 19 with polymyositis. Sensitivity and specificity of the INNO-LIA ANA Update were determined using the clinical diagnosis as reference. RESULTS: The optimized cut-off values resulted in a specificity 98% or more for all LIA markers except one (histones 97.8%) in the validation set of 330 samples. The sensitivity for each marker tested in 378 samples from the target patient groups was comparable to that reported in the literature. CONCLUSION: The INNO-LIA ANA Update shows uniformly high specificities combined with sensitivities very similar to those of reference assays, in a single test format.

The 2007 Belgian national prevalence survey for hospital-acquired infections.

Despite ongoing targeted surveillance efforts, no overall in-hospital prevalence data for hospital-acquired infections (HAIs) have been published for Belgium. Sixty-three Belgian acute hospitals participated in a point-prevalence study among either all patients admitted in their institution or 50% of the patients in each ward. HAIs were registered bed-site at a single day per ward during the period October-November 2007. The diagnosis was made according to the Centers for Disease Control and Prevention (CDC) criteria implemented in a custom-made rule-based software expert system available on a portable computer. The total number of patients surveyed nationally was 17 343, from 543 distinct hospital wards. The overall prevalence of HAIs was 7.1% (95% confidence interval: 6.7-7.4%); 6.2% (5.9-6.5%) of the patients suffered from at least one HAI. Prevalence of HAIs on adult intensive care was 31.3%. The major proportion of HAIs was observed among patients admitted on non-intensive care unit (non-ICU) wards, mainly on the wards of internal medicine, surgery, geriatrics and rehabilitation. Urinary tract infections were the most common type of HAI at geriatric and rehabilitation wards. This study demonstrates that the use of a portable computer system with a designated expert system for diagnosing HAIs according to the CDC criteria in a large point prevalence study is feasible and may reduce the within-subject variation. In Belgium, the prevalence of HAIs in acute hospitals thus identified is similar to that of neighbouring countries. As more than 80% of all HAIs occur on non-ICU wards, preventive efforts need to extend beyond the ICU.

Hospital-acquired, laboratory-confirmed bloodstream infections: linking national surveillance data to clinical and financial hospital data to estimate increased length of stay and healthcare costs.

This matched cohort study estimates the effect of hospital-acquired bloodstream infection (HA-BSI) on length of stay (LOS) and costs during hospitalisation of 1839 patients (age range <1 to >80 years) gathered from 19 acute hospitals in Belgium. A second objective was to evaluate the impact of the choice of matching criteria. Data from national surveillance of HA-BSI were linked to hospital administrative discharge data, with respect for the patients' right to confidentiality of their health record. Controls were identified based on a set of matching factors: hospital, All-Patient Refined Diagnosis Related Groups, age, principal diagnosis, Charlson Comorbidity Index and time to infection. The results showed that, depending on the choice of matching factors, the estimation of additional LOS decreased from 26 to 10 days, with the most critical factor being the time to infection. The additional LOS attributable to HA-BSI was 9.9 days [95% confidence interval (CI): 7.8, 11.9]. The additional cost per infection was euro4900 [95% CI: euro4035, euro5750]; 58% of those costs were due to LOS, 10% were due to antibiotics, 10% due to other pharmaceutical products and 15% were due to billed medical acts. The main conclusion is that laboratory-confirmed HA-BSIs increase the LOS by 10 days for patients surviving the infection, and that the time to infection plays a crucial role in this estimation.

Tropisetron in the prevention of acute and delayed nausea and vomiting over six courses of emetogenic chemotherapy.

Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).

Flow cytometric analysis of peripheral blood lymphocytes in ulcerative colitis and Crohn's disease.

Using two colour immunofluorescence with fluorescein isothiocyanate and phycoerythrin labelled monoclonal antibodies, multi-parameter flow cytometry was used to examine the antigenic characteristics of peripheral blood lymphocytes in whole blood of patients with ulcerative colitis and Crohn's disease who were not taking immunosuppressive drugs. The numbers of CD4+ and CD8+ lymphocytes in patients with ulcerative colitis and Crohn's disease remained unchanged so that the CD4/CD8 ratio was the same as that of normal control subjects. In Crohn's disease there were many activated T cells (CD3+, CD25+). Although natural killer cells in active Crohn's disease were lower than in normal control subjects, cytotoxic T lymphocytes, as defined by CD3+, CD16+, did not differ in patients with inflammatory bowel disease compared with normal control subjects. For B cell subsets, there were differences in Leu-1+ B cells, Leu-8+ B cells, Fc epsilon R+B cells (Leu-16+, Leu-20+), and activated B cells (Leu-12+, Leu-21+) between patients with inflammatory bowel disease and normal control subjects. These differences are compatible with local activation of B cells in the inflamed colon.

The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value.

The objective of this prospective cohort study was to evaluate the expression of activation markers on CD8 lymphocytes at various clinical stages of HIV infection and to determine the value of these markers in identifying patients likely to have rapidly progressive disease. One hundred and three HIV+ patients, divided into four disease stages, and 34 seronegative controls were evaluated at study entry using flow cytometric immunophenotyping. The HIV patients were followed clinically for disease progression during the following 2 years. CD8 cell numbers and percentage of lymphocytes are increased after HIV infection. Expression of the CD38, HLA-DR and CD57 markers on CD8 cells was significantly increased in asymptomatic HIV-infected patients when compared with controls, as was the CD8 cell population which did not coexpress Leu-8. These activation markers were observed to be further increased in patient groups with more clinically advanced infection. The percentage of CD38 on CD8 cells emerged not only as a discriminator of disease severity, but was a strong predictor of progression in asymptomatic, lymphadenopathy and ARC patients. Given the utility of activation markers on CD8 lymphocytes in staging disease and predicting clinical outcome, the measurement of these parameters should be considered in the monitoring and management of HIV patients.

Two-color immunofluorescence and flow cytometric analysis of peripheral blood lymphocyte subsets in Caucasian and Japanese healthy subjects.

Two-color immunofluorescence using multiparameter flow cytometry was employed to examine the antigenic characteristics of peripheral blood lymphocytes in whole blood of healthy Caucasians and Japanese. The CD4/CD8 ratio in Japanese was significantly decreased compared with that in Caucasians, because of the increased number of CD8+ cells. Although the proportions of suppressor-inducer T cells (CD4+, Leu-8+) and helper-inducer T cells (naive T cells) (CD4+, CD45RA-) were low in Japanese subjects, there were no differences in the absolute numbers of suppressor-inducer T cells and helper-inducer T cells (naive T cells) in circulation. The level of activated T cells in Japanese was similar to that in Caucasians. NK cells, CD57+, CD8+ cells and CD57+, CD3+ cells were high in Japanese. Regarding B cell subsets, CD5+ B cells and activated B cells remained unchanged. However, there were slight differences in Leu-8+ B cells and Fc epsilon R+ B cells (CD20+, CD23+) between the two groups. Thus, a differing influence of racial and environmental background between healthy Caucasians and healthy Japanese on human lymphocyte subsets is present in the lymphocyte immunophenotype.