Biomedical subjects

J Olofsson

Publications and source records attributed to J Olofsson.

At least 19 recordsLinked to original sources

PubMed2006

Modelling lateral beam quality variations in pencil kernel based photon dose calculations.

Standard treatment machines for external radiotherapy are designed to yield flat dose distributions at a representative treatment depth. The common method to reach this goal is to use a flattening filter to decrease the fluence in the centre of the beam. A side effect of this filtering is that the average energy of the beam is generally lower at a distance from the central axis, a phenomenon commonly referred to as off-axis softening. The off-axis softening results in a relative change in beam quality that is almost independent of machine brand and model. Central axis dose calculations using pencil beam kernels show no drastic loss in accuracy when the off-axis beam quality variations are neglected. However, for dose calculated at off-axis positions the effect should be considered, otherwise errors of several per cent can be introduced. This work proposes a method to explicitly include the effect of off-axis softening in pencil kernel based photon dose calculations for arbitrary positions in a radiation field. Variations of pencil kernel values are modelled through a generic relation between half value layer (HVL) thickness and off-axis position for standard treatment machines. The pencil kernel integration for dose calculation is performed through sampling of energy fluence and beam quality in sectors of concentric circles around the calculation point. The method is fully based on generic data and therefore does not require any specific measurements for characterization of the off-axis softening effect, provided that the machine performance is in agreement with the assumed HVL variations. The model is verified versus profile measurements at different depths and through a model self-consistency check, using the dose calculation model to estimate HVL values at off-axis positions. A comparison between calculated and measured profiles at different depths showed a maximum relative error of 4% without explicit modelling of off-axis softening. The maximum relative error was reduced to 1% when the off-axis softening was accounted for in the calculations.

Computer Simulation↗

PubMed2006

Obstructive jaundice due to isolated tuberculosis of the pancreas: endoscopic treatment instead of surgery?

The optimal treatment for relieving biliary obstruction due to isolated pancreatic tuberculosis has not so far been defined, and most previously reported patients were treated surgically. We describe a 17-year-old, immunocompetent girl who was admitted with obstructive jaundice caused by a tuberculous mass in the head of the pancreas. Antituberculous therapy alone failed to alleviate the jaundice, and she was therefore treated by stent insertion and, subsequently, balloon dilation of the common bile duct stricture. At follow-up 5 years later, magnetic resonance cholangiopancreatography showed no evidence of stricture in the common bile duct.

Adolescent↗

PubMed2005

The amount of treatment versus quality of life in patients formerly treated for head and neck squamous cell carcinomas.

The aim of the present study was to investigate the association between the self-reported quality of life (QoL) versus the initial TNM stage and amount of primary and recurrent tumor therapy given in a population of formerly treated head and neck squamous cell carcinoma (HNSCC) patients. We determined QoL by the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ) C30/H&N35 by structured interview. One hundred and twenty-two patients less than 80 years old, who had been diagnosed with HNSCC in western Norway in the period from 1992 to1997, and who had survived until 2000, were identified. Of these patients, 106 were eligible to be included. Ninety-six of these patients agreed to be interviewed. For TNM stage as well as the type of therapy given (local surgery, neck dissection or radiation therapy), T stage predicted the general QoL scores. Both increased TNM stage and all given tumor therapy seemingly caused lower H&N symptom QoL scores. Of the various tumor treatments employed, neck radiation therapy and neck dissection were indicated to be the most closely associated with the H&N QoL scores. Having neck dissection performed seemingly caused impairment beyond what was explained by the initial TNM stage. In conclusion, tumor therapy to HNSCC should not be restricted due to general QoL considerations. Further study of how and when to perform neck treatment is suggested in order to avoid unnecessary reduced H&N QoL.

Carcinoma, Squamous Cell↗

PubMed2005

Psychological coping style versus disease extent, tumour treatment and quality of life in successfully treated head and neck squamous cell carcinoma patients.

OBJECTIVES: To study self-reported coping style by the COPE questionnaire and the association to tumour node distant metastasis (TNM) stage, received treatment and health-related quality of life (HRQoL) in a population of successfully treated head and neck squamous cell carcinoma (HNSCC) patients. DESIGN: Disease free HNSCC patients were interviewed during a regular outpatient visit to the Department. SETTING: All patients <80 years who had been diagnosed with HNSCC, in Western Norway, in the period from 1992 to 1997 and who were disease free in the year 2000 were included. MAIN OUTCOME MEASURES: The HNSCC patients were studied by the European organization for research and treatment of cancer quality of life (QoL) questionnaire and by the COPE questionnaire from which coping styles profiles were extracted. Clinical and socio-demographic variables were also gathered. RESULTS: Level of problem focused coping style was associated with the T stage and whether or not the patient was given neck radiotherapy. An avoidance-focused coping style was generally associated with lowered HRQoL. Employment of emotional focused coping was associated with low HRQoL among the patients treated with surgery only, and associated with increased HRQoL among patients treated with radiation therapy only. The associations between HRQoL and coping style levels were stronger for HRQoL indexes reflecting cognitive/emotional function than for HRQoL indexes reflecting physical function. CONCLUSIONS: In former HNSCC patients, level of problem focused coping style was associated with the T stage and if given neck radiotherapy. Level of avoidance coping was inversely associated with the HRQoL, and level of emotional coping was associated with HRQoL in a complex manner.

Adaptation, Psychological↗

PubMed2003

p53, Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma.

The prognosis in patients suffering from head and neck squamous cell carcinomas depends on many factors. However, regional lymph node metastases are the most important parameter in determining the cure and survival of patients with head and neck cancers. The evaluation of cancer cell biology enables differentiation of their proliferation and tendency of metastases. Immunohistochemical examinations complement the well-established routine histological examination. The aim of this study was to evaluate the prognostic importance of the level of immunoproliferating proteins such as cyclin D1, nuclear antigen Ki67 and suppressor gene p53 for regional lymph node metastases in laryngeal carcinoma. The research was carried out on 73 patients treated for squamous cancer of the larynx in the Department of Otolaryngology University School of Medical Sciences in Poznan in the years 1994-1999. The group was comprised of 4 female and 69 male patients. Their ages ranged from 37 to 79 years, with a mean of 59 years. Clinical data included sex, age, localization and local and regional extent of the tumor, presence or lack of distant metastases, treatment, histological examination as well as immunohistochemical evaluation of suppressor gene p53, proliferative proteins Ki67 and cyclin D1. No statistically significant correlation was found between staining intensity of suppressor gene p53, cyclin D1 and the degree of local advancement (T). There was no correlation between the level of immunoproliferative markers and regional lymph node metastases. Statistically significant correlation was found between T stage and staining for Ki67 (P=0.017) as well as between cyclin D1 level and Ki67 (P<0.05). In conclusion, (1) no significant correlation was found between Ki67 and cyclin D1, p53 and TNM classification; (2) lack of correlation was confirmed between N+, p53, Ki67, cyclin D1 and Jacobsson classification; (3) the degree of histological grading correlated, however, with Jacobsson classification and cyclin D1 expression.

Adult↗

PubMed2003

The personality and quality of life in HNSCC patients following treatment.

The aim of the present study was to investigate the association between self-reported quality of life (QoL) and personality in successfully treated primary head and neck squamous cell carcinoma (HNSCC) patients. We determined QoL using the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ) C30/H and N35, and personality by the Eysenck Personality Inventory (EPI). All patients younger than 80 years who had been diagnosed with HNSCC in Western Norway in the period from 1992 to 1997, and who had survived until 1999, were sampled. 96 patients (a 90% response rate) were included. Questionnaires were also mailed to all Norwegian laryngectomised patients; 104 patients returned the questionnaires (a 50% response rate). The neuroticism scores were test re-test reliable as determined by the neuroticism scores measured at the primary HNSCC diagnosis for a sub-sample (N=22) of the included patients. High neuroticism was associated with a low QoL in both patient samples. The neuroticism score was associated with the QLQ-C30 scales (common variance: 17-25%) and all QoL scores in the laryngectomised group (common variance: 11-25%), and the H and N35 symptom scores in the laryngectomised sample. The associations could still be shown when adjustments were made for gender, age, marital status, educational level, number of children and level of treatment. Extraversion was associated with general QoL, physical and emotional scores in the HNSCC patient sample. Radiation therapy in the HNSCC sample was associated with the H and N35 symptom scores, but different ones to those associated with neuroticism. In conclusion, high neuroticism, but not extraversion, is associated with a lowered QoL.

Adolescent↗

PubMed2002

Relation between mood, social support and the quality of life in patients with laryngectomies.

Two hundred laryngectomized members of the Norwegian Society of Laryngectomies (NSL), a subsidiary of the Norwegian Cancer Society, were invited to answer the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 QOL questionnaires to assess their quality of life (QOL). The Beck Depression Inventory (BDI) scores, their levels of social support and their marital and educational statuses were also determined. In addition, the activity levels of each patient within the NSL were assessed. The questionnaires were returned anonymously by 104 patients. The results of this sample were compared with the responses to the EORTC QLQ C30/H&N35 by all of the survivors of treatment for head and neck squamous cell carcinoma (HNSCC) in western Norway between 1992 and 1997. This sample included 96 of 106 eligible patients. The QLQ-C30 symptom scores include, e.g., dyspnea, smell and taste. However, neither the QLQ-C30 functional scores nor the disease-specific scores of the people with laryngectomies differed from the general HNSCC-treated population. The level of social support by family, friends and neighbors was not associated with the QOL, whereas high BDI scores were associated with reduced QOL by most measured indexes. Furthermore, a positive association was determined between the level of activity within the NSL and QOL. This relation was to some extent secondary to differential BDI scores. In conclusion, the QOL of people with laryngectomies is relatively similar to a general population of patients treated because of HNSCC, is related to the activity level within a patient interest organization and is associated with a lower mood level.

Activities of Daily Living↗

PubMed2002

Mechanisms for monocyte activation in co-culture with autologous tumor spheroids.

Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro secrete interleukin (IL)-6 upon 24h in co-culture. Presently, the aim was to study the mechanisms of this monocyte secretion. Paraformaldehyde (0.1% for 2min) or actinomycin-D (1 microg/ml for 24h) pre-treatment of the F-spheroids abolished the monocyte IL-6 co-culture response. Addition of glucose (100mM) or mannose (100mM), and to some extent galactose (100mM), but not fructose (100mM) to the co-cultures, partly inhibited the monocyte IL-6 co-culture response, but such addition did not inhibit the in vitro monocyte lipopolysaccharide (LPS)-generated IL-6 secretion. When mannose was added to the co-cultures, monocyte IL-6 mRNA expression was eradicated in malignant co-cultures and reduced to a low level in benign co-cultures. Addition of mouse anti-human beta(1)-integrin (anti-CD29) antibody (2 microg/ml) diminished the IL-6 co-culture response but not the monocyte LPS-generated IL-6 response. In conclusion, the monocyte IL-6 co-culture response is dependent on live spheroids and to some extent on direct contact with the F-spheroids, possibly via lectin-like receptor(s), the mannose receptor and beta(1)-integrin.

Animals↗

PubMed2001

Residual human immunodeficiency virus type 1 infection in lymphoid tissue during highly active antiretroviral therapy: quantitation and virus characterization.

HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the residual viral load, repetitive blood and tonsillar samples were collected from 11 HIV-1-positive individuals before and during 96 weeks of therapy with zidovudine, lamivudine, and indinavir. HIV-1 RNA in tonsils was quantified by RT-PCR and infectious HIV-1 provirus by the limiting dilution assay. Genotypic resistance analyses and biological characterization were performed on plasma virus, blood, and tonsillar isolates. Tonsillar infectious HIV-1 provirus and HIV-1 RNA declined by 2 and 3 log(10), respectively, but 10(3)-10(4) cells, less than 0.5% of the total body CD4(+) T cell population carrying infectious HIV-1 provirus, remained involved in active viral replication of drug-sensitive R5 viruses. Thus, the dominant HIV-1 residual infection consists of < or = 10(6) latently infected CD4(+) cells. Plasma HIV-1 RNA decline of > 1.5 log(10) during the first 2 weeks of therapy may indicate low levels of this latent reservoir. Whereas the reservoir of latently infected cells remains stable, actively replicating HIV-1 continuously declines during prolonged antiretroviral therapy. Thus, although viral eradication seems unlikely, antiretroviral therapy may induce an extended period of virologic latency in HIV-1-positive individuals.

Anti-HIV Agents↗

PubMed2001

The Fas/FasL system and T cell apoptosis in HIV-1-infected lymphoid tissue during highly active antiretroviral therapy.

Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. In the present study we have phenotyped apoptotic T cells in tonsillar lymphoid tissue from 11 HIV-1-infected patients by flow cytometry light-scatter characteristics during 48 weeks of highly active antiretroviral therapy (HAART). We found that the decline in tonsillar viral load was associated with a decrease in the proportion of apoptotic CD4+ and CD8+ T cells. CD4 cell apoptosis was predominantly seen within the memory CD28+ Fas+ FasL+ population. The increased level of apoptotic CD8+ T cells was found among activated Fas+ memory cells irrespective of CD28 and FasL expression. These T cell subsets were expanded in untreated infection, but normalized with therapy. We conclude that HIV-1 triggers FasL-mediated apoptosis of uninfected CD4+ T cells, whereas CD8+ T cell apoptosis is driven by chronic immune activation. Virus suppression reverses both of these mechanisms, contributing to immune reconstitution during HAART.

Acquired Immunodeficiency Syndrome↗

PubMed2001

T cell proliferation and apoptosis in HIV-1-infected lymphoid tissue: impact of highly active antiretroviral therapy.

T cell turnover was studied in situ in tonsillar lymphoid tissue (LT) from HIV-1-infected individuals during 48 weeks of highly active antiretroviral therapy (HAART) and compared to that of HIV-1-negative controls. Prior to therapy, CD4 cell proliferation (%CD4+ Ki67+) and apoptosis (%CD4+ TUNEL+) were increased in HIV-1-infected LT and both parameters correlated with tonsillar viral load. CD8 cell proliferation (%CD8+ Ki67+) was increased 4- to 10-fold, mainly in the germinal centers. Apoptotic CD8+ T cell levels (%CD8+ TUNEL+) were raised preferentially in the tonsillar T cell zone. The frequency of CD8+ Ki67+ and CD8+ TUNEL+ T cells correlated with tonsillar viral load and with the fraction of CD8(+) T cells expressing activation markers. During HAART, CD4 cell turnover normalized while CD8 cell turnover was dramatically reduced. However, low level viral replication concomitant with slightly elevated levels of CD8 cell turnover indicated a persistent cellular immune response in LT. In conclusion, enhanced T cell turnover may reflect effector cells related to HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Monocyte and monocyte-derived macrophage secretion of MCP-1 in co-culture with autologous malignant and benign control fragment spheroids.

This study was performed in order to determine how monocytes and macrophages in co-culture with autologous head and neck squamous cell carcinoma (HNSCC) tumor tissue regulate the secretion of monocyte chemotactic protein-1 (MCP-1). The levels of MCP-1 were measured when autologous monocytes or monocyte-derived macrophages (MDMs) were co-cultured in vitro with autologous fragment (F)-spheroids established from HNSCC tumors or benign mucosa serving as control. MCP-1 secretion from co-culture stimulated monocytes and MDMs was increased compared to spontaneous MCP-1 secretion. With prolonged co-culture, MDMs showed a steady-state MCP-1 secretion above background levels for up to 96 h, even with change of co-culture media every 24 h. Addition of an anti-MCP-1 antibody to the medium decreased co-culture-induced monocyte IL-6 secretion. Addition of lipopolysaccharide (LPS) (1 [microg/ml) reduced MCP-1 secretion compared to spontaneous secretion in monocyte cultures. F-spheroids also secrete MCP-1, but at insignificant levels compared to the MCP-1 secretion from monocytes and MDMs. MCP-1 secretion from monocytes/MDMs is regulated differently when co-culture stimulation is compared to LPS-stimulation. Monocytes and MDMs expressed MCP-1 mRNA at a high level in all tested conditions: stimulated in co-culture, not stimulated or stimulated with LPS, indicating post-transcriptional regulation of MCP-1 secretion. The secretion of MCP-1 from tumor-derived F-spheroids, and the maintenance of co-culture MCP-1 secretion from MDMs in vitro, suggests that tumor-associated macrophages are a source of MCP-1 in HNSCC tumors.

Antibodies, Monoclonal↗

PubMed2001

Human autologous monocytes and monocyte-derived macrophages in co-culture with carcinoma F-spheroids secrete IL-6 by a non-CD14-dependent pathway.

The secretion of interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha were compared when freshly isolated autologous monocytes or monocytederived macrophages (MDMs) were co-cultured in vitro with autologous fragment (F)-spheroids established from a series of head and neck squamous cell carcinoma (HNSCC) patients. F-spheroids were generated from the malignant tumour (M-spheroids) or from benign mucosa (B-spheroids) from which the tumour originated control. If monocytes maturated towards MDMs before co-culture, the IL-6 secretion declined dependent on the extent of the MDM maturation by both M- and B-spheroid stimulation. When MDMs maturated in continuous co-culture, a steady-state secretion of IL-6 continued for several days but diminished when the culture medium was changed every 24 h. No co-culture-induced IL-1 beta or TNF-alpha was determined. Both the cytokine secretion and the mRNA gene expression revealed a different monocyte/MDM activation when co-culture and lipopolysaccharide (LPS)-stimulation were compared. Addition of anti-CD14 (10 microg/ml) decreased monocyte LPS-stimulated, but increased monocyte co-culture stimulated IL-6 secretion. In conclusion, M- and B-spheroids similarly stimulated monocytes and to a lesser extent MDMs. MDMs that maturated with F-spheroids present, retained responsiveness at the monocyte level. Co-culture-induced monocyte stimulation, as measured by IL-6 secretion, was not dependent on activation via the CD14 molecule.

Carcinoma, Squamous Cell↗

PubMed2000

Normalization of CD4+ cell numbers and reduced levels of memory CD8+ cells in blood and tonsillar tissue after highly active antiretroviral therapy in early HIV type-1 infection.

Antiretroviral therapy increases the number of both CD4+ and CD8+ T cells in the blood of HIV-1-positive patients with advanced disease. In the present study, we have examined the kinetics of CD4+ and CD8+ T cell restoration in blood and lymphoid tissue in asymptomatic HIV-1-positive individuals with high CD4+ cell counts during highly active antiretroviral treatment. Tonsillar biopsies and blood samples were collected at baseline and at regular intervals during the following 48 weeks and from HIV-1-negative controls. Mononuclear cells from blood and tonsils were phenotyped and quantified by three-color flow cytometry. After 48 weeks of therapy, blood CD4+ cell counts in the HIV-1-infected group were comparable to those found in uninfected controls. Naive CD4+ T cells in blood increased during the initial 2 weeks in parallel with reduced plasma viremia. Both naive and memory CD4+ T cells in blood reached normal numbers by week 48, whereas the CD4+ naive/memory cell ratio in tonsils was within normal range throughout the study. The level of memory CD8+ T cells in blood declined during the first 8 weeks in parallel with a reduction in the tonsillar memory CD8+ T cells. Naive CD8+ T cells in the blood increased after 4 weeks, while the level of naive CD8+ T cells in tonsils remained unaltered. Our data indicate that in the early stages of HIV-1 infection antiretroviral therapy normalizes CD4+ cell counts and causes a decrease in the level of memory CD8+ cells in blood and lymphoid tissue, suggesting reduced CD8+ cell turnover in response to reduced viral replication.

Adult↗

PubMed2000

Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society.

The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of post-operative results. We chose to keep the word "cordectomy" even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke's space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination.

Glottis↗

PubMed2000

Monocytes secrete interleukin-6 when co-cultured in vitro with benign or malignant autologous fragment spheroids from squamous cell carcinoma patients.

Biopsies from tumour and benign mucosa were removed from patients with head and neck squamous-cell carcinoma (HNSCC), chopped into cubes and transferred to a nonadhesive culture system where in vitro fragment (F)-spheroids were established. The F-spheroids stabilized within 14 days of culture in vitro with epithelial cells and fibroblasts on the surface. F-spheroids were co-cultured with freshly isolated autologous monocytes. The monocytes of 10 of 11 patients secreted interleukin (IL)-6 at a level similar to that of the average monocyte endotoxin-stimulated response. Secreted IL-1beta or tumour necrosis factor-alpha (TNF-alpha) levels greater than 0.1 times the endotoxin-stimulated secretion were determined in one and two of the 11 co-culture experiments, respectively. This different monocyte response to F-spheroids compared with endotoxin stimulation was also present at the mRNA expression level. HNSCC monocytes secreted no IL-6 after co-culture with autologous fibroblasts. When monocytes and F-spheroids were cultured separated by a semipermeable membrane, the IL-6 supernatant level was only approximately 25% of that observed during co-culture with direct contact. F-spheroids secreted only trace amounts of IL-6. In conclusion, monocytes of HNSCC patients generally secrete IL-6, but not IL-1beta or TNF-alpha, after stimulation with epithelial-associated components of F-spheroids upon direct contact and in part by a soluble substance.

Aged↗

PubMed2000

Peripheral blood T-lymphocyte and monocyte function and survival in patients with head and neck carcinoma.

OBJECTIVES/HYPOTHESIS: To determine if the T-lymphocyte and monocyte functions of peripheral blood mononuclear cells (PBMCs) from patients with head and neck squamous cell carcinomas (HNSCC) are predictive factors for outcome. STUDY DESIGN: A prospective study describing the outcome, as to total survival and death by disease after at least 40 months observation, of 81 previously untreated male HNSCC patients in relation to PBMC T-lymphocyte and monocyte function. METHODS: T-lymphocyte mitogenesis and the cytokine level in culture supernatants of PBMC as well as monocytes were analyzed. These parameters were related to survival by Cox regression and Kaplan-Meier survival analysis. RESULTS: When patients with high versus low T-lymphocyte mitogen-stimulated proliferations were compared, a decreased proliferation was seen to be related to worse outcome. The predictive value of T-lymphocyte proliferation was shown to be an independent prognostic factor when adjusted for stage and stratified for anatomic location in survival analysis. The predictive value was also retained when the serum values of the major serum proteins and hormones and scores based on the smoking and alcohol history were added to the survival analysis with lymphocyte proliferation. Supernatant levels of gamma-interferon, interleukin (IL)-2, or IL-4 in PBMC cultures were not related to outcome. Monocyte function measured by endotoxin-stimulated IL-1beta, IL-6, IL-12, and tumor necrosis factor-alpha secretion did not relate to outcome of the patients. CONCLUSION: The PBMC T-lymphocyte-stimulated proliferation is an independent prognostic factor for male HNSCC patients.

Aged↗

PubMed1999

Activation of CD8 T cells normalizes and correlates with the level of infectious provirus in tonsils during highly active antiretroviral therapy in early HIV-1 infection.

OBJECTIVES: To study the effects of antiretroviral therapy on T cell activation in blood and tonsils from HIV-1 infected individuals in relation to CD4 cell count, plasma viremia, and infectious HIV-1 provirus. DESIGN: A 48-week study of viral load and T cell subsets in blood and tonsils from 12 HIV-1-positive individuals with a mean CD4 cell number of 400 x 10(6) cells/l treated with a combination of zidovudine, lamivudine, and indinavir. METHODS: Tonsil biopsies and blood samples were collected at regular intervals. Lymphocytes were phenotyped and quantified by three-color flow cytometry; infectious provirus was quantified by a limiting dilution assay. HIV-1-negative individuals were included as controls. RESULTS: The fraction of tonsillar CD8 T cells expressing CD69, CD38, or HLA-DR in the patients with suppressed virus replication declined to levels comparable with that in controls by 48 weeks and showed a strong positive correlation with tonsillar infectious provirus and plasma viremia. The level of CD4 T cell activation was within normal range in tonsils throughout the study. The fraction of HLA-DR+ cells within CD4 and CD8 T cells in blood declined rapidly in parallel with plasma viremia but remained slightly higher compared with that in uninfected individuals. CONCLUSION: Antiretroviral therapy normalizes tonsillar CD8 T cell activation in HIV-1-positive individuals in parallel with suppression of viral replication, indicating reduced CD8 cell turnover. Normal tonsillar CD4 T cell activation suggests limited CD4 cell turnover in early HIV infection. Activated CD8 T cells in lymphoid tissue is superior to that in blood as an immunological marker for the virological response to antiretroviral therapy.

ADP-ribosyl Cyclase↗