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R Bell

Publications and source records attributed to R Bell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Ongoing trials with trastuzumab in metastatic breast cancer.

Following the pivotal clinical trials of trastuzumab (Herceptin), further phase II and III studies have been initiated. Preliminary results from a phase II, dose-response study of single-agent trastuzumab in 113 HER2-positive metastatic breast cancer patients without prior chemotherapy for stage IV disease have shown that the overall response rate was 23% (six complete responses and 20 partial responses), with similar results using both standard- and high-dose regimens of trastuzumab. Another phase II study of trastuzumab plus paclitaxel, both given weekly, in 63 HER2-positive and -negative patients with metastatic breast cancer produced an overall response rate of 62% in HER2-positive and 44% in HER2-negative patients. A further phase II study is underway to investigate the combination of trastuzumab plus docetaxel in 30 HER2-positive patients with metastatic breast cancer. Finally, a number of European studies are at an advanced stage of planning or are about to start patient recruitment. These include docetaxel +/- trastuzumab, aromatase inhibitor +/- trastuzumab, CMF (cyclophosphamide, methotrexate, 5-fluorouracil) +/- trastuzumab, vinorelbine + trastuzumab, all in HER2-positive patients, and epirubicin-cyclophosphamide (EC) + trastuzumab in HER2-positive patients vs. EC alone in HER2-negative patients. The results from these trials should be available over the next one to two years.

Antibiotics, Antineoplastic↗
PubMed2001

Duration of therapy in metastatic breast cancer: management using Herceptin.

Despite progressive developments in therapeutic interventions, including surgery, radiotherapy and chemotherapy, there has been no major improvement in the survival of women with metastatic breast cancer (MBC). Based on knowledge of tumor growth patterns, approaches addressing this issue have included increasing chemotherapy dose or dose density and extending the duration of therapy. However, only the latter approach has resulted in improved clinical benefit, although not survival; and its use is restricted by the cumulative toxicity of chemotherapeutic agents. Therefore, the best hope for improved survival lies with new classes of anticancer drug and particularly biological agents. This review focuses on the first oncogene-targeted therapy for human epidermal growth factor receptor-2 (HER2)+ MBC patients. The humanized anti-HER2 monoclonal antibody Herceptin has proven clinical benefits in HER2+ MBC patients, most importantly improved survival, and is rapidly becoming a standard of care for these patients. In contrast to the fixed number of cycles used for chemotherapeutic agents, Herceptin is administered until disease progression, with some data suggesting that continuation beyond disease progression should be investigated. The preclinical and clinical findings on which the current recommended duration of Herceptin therapy are based are reviewed and alternative strategies are discussed.

Antibodies, Monoclonal↗
PubMed2001

Risk factors for posttrauma reactions in police officers: a longitudinal study.

This prospective, longitudinal study investigated risk factors in the development of psychological ill health and posttraumatic stress symptoms in a sample of 223 junior police officers. Participants were assessed using a self-report methodology during training and again 12 months later on a range of personality, trauma exposure, and symptom measures. Risk factors for general psychological ill health at phase 2 of the research were found to comprise mostly stable, preexisting characteristics such as personality style, gender, and trait dissociation. Conversely, specific traumatic stress symptoms were more heavily influenced by experiences in the intervening 12 months, such as severity of incident exposure and peritraumatic dissociation. The implications for differential intervention are discussed.

Adult↗
PubMed2001

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Adolescent↗
PubMed2001

Misoprostol versus dinoprostone for cervical priming prior to induction of labour in term pregnancy: a randomised controlled trial.

A prospective randomised controlled trial was performed to compare the efficacy and safety of intravaginal misoprostol to that of intravaginal dinoprostone when used for cervical priming prior to the induction of labour; 126 women were recruited to the study and randomised to receive either intravaginal dinoprostone (n = 63) or misoprostol (n = 63) for cervical priming prior to induction of labour. The mean time from insertion of the priming agent to vaginal delivery was significantly shorter in the misoprostol group (925.8 versus 1577.6 minutes), the mean duration of the active length of labour was significantly shorter in the misoprostol group (353.7 versus 496.8 minutes) and more women in the misoprostol group delivered in less than 12 hours (92% versus 76.5%). Women in the misoprostol group were less likely to require a repeated dose of prostaglandin for cervical priming and less likely to require oxytocin for augmentation of labour. There was no difference in the number of women who were delivered vaginally or by Ceasarean section between the two groups. More women developed hyperstimulation during labour in the misoprostol group; however there was no difference between the groups in neonatal outcome in respect to low cord pH or Apgar score at delivery or admission to the neonatal special care nursery.

Adult↗
PubMed2001

The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye movements or CANTAB neuropsychological test performance. Haloperidol was associated with impaired SWM, which correlated with the degree of dysphoria/akathisia, but no other drug effects on CANTAB measures were detected. We conclude that the effect of antipsychotics on LI is both modality and pharmacologically dependent and that further research using a wider range of antipsychotic compounds is necessary to clarify the cognitive effects of these drugs, and to determine whether there are important differences between them.

Acoustic Stimulation↗
PubMed2001

The increasing knowledge of the role of periconceptional folate in Victorian women of child-bearing age: follow-up of a randomised community intervention trial.

OBJECTIVES: To determine the changes since 1996 in knowledge of folate for the prevention of neural tube defects (NTDs) among women of child-bearing age and measure the residual effect of an earlier consumer-directed information campaign. DESIGN: A community, randomised trial with three matched pairs of geographically distinct local government areas in Victoria. INTERVENTION: Printed information recommending folate intake to decrease the risk of NTDs was disseminated in 1997 to women of child-bearing age. MAIN OUTCOME MEASURE: The proportion of women aware of the association between folate and spina bifida was established in 1996, 1997 and 2000 (approximately 200 respondents per local government area in each survey). RESULTS: 12.5% (adjusted for population sampling fraction) of 1,196 women interviewed in 1996, prior to the intervention, were aware of folate and NTDs. Independent surveys after the intervention in 1997 and again in 2000 showed that this had increased to 17.4% (n=1204) and 30.2% (n=1227) respectively. The intervention had a significant impact on folate awareness (a 4% difference in 1997 and a residual 3.3% in 2000, ORadj=1.24, 95% CI 1.19-1.37, p=0.007). CONCLUSIONS AND IMPLICATIONS: There has been a continuing increased awareness of folate in women of child-bearing age since 1996. Within this setting, the provision of printed educational material in a brief intervention in 1997 has caused enduring increased awareness of the association between folate and NTDs. The need for ongoing health promotion action on folate remains.

Adolescent↗
PubMed2000

Systematic screening of the 14-3-3 eta (eta) chain gene for polymorphic variants and case-control analysis in schizophrenia.

The neuronal protein 14-3-3 eta is a candidate gene for schizophrenia because it maps chromosome 22q12, a region implicated in the disease by linkage analysis, and is involved in brain development. We systematically screened this gene for polymorphic variants by comparison of public EST sequence data (five cDNAs and 72 ESTs, 21,155 bp of sequence) in parallel with single-stranded conformational polymorphism analysis, and we compared these methods by using a simple power calculation. Twelve potential polymorphisms were identified from EST sequence comparison, and two of these (a 5'-VNTR and 753G/A) were confirmed by SSCP analysis and sequencing. Three additional infrequent polymorphisms (-408T/G; 177 C/G; and 989 A/G) were found by SSCP only. We next examined these variants for association with schizophrenia. One variant in untranslated region of exon 1 (-408 T/G) was found to occur more frequently in the schizophrenic subjects (8%) than the controls (3%; P = 0.01). After fivefold correction of the P value for multiple testing, marginal association was found. Haplotype analysis of pairs of polymorphisms provided no evidence for association of this gene with schizophrenia in the population studied. Am. J. Med. Genet. (Neuropsychiatr. Genet. ) 96:736-743, 2000.

14-3-3 Proteins↗
PubMed2000

Fluorescence properties and functional roles of tryptophan residues 60d, 96, 148, 207, and 215 of thrombin.

Conservative Trp-to-Phe mutations were individually created in human thrombin at positions 60d, 96, 148, 207, and 215. Fluorescence intensities for these residues varied by a factor of 6. Residues 60d, 96, 148, and 215 transferred energy to the thrombin inhibitor 5-dimethylaminonaphthalene-1-sulfonylarginine-N-(3-ethyl-1,5- pentanediyl)amide efficiently, but residue 207 did not. Intensities correlated inversely with exposure to solvent, and measured and theoretical energy transfer efficiencies agreed well. Function was measured with respect to fibrinogen clotting, platelet and factor V activation, inhibition by antithrombin, and the thrombomodulin-dependent activation of protein C and thrombin-activable fibrinolysis inhibitor (TAFI). All activities of W96F and W207F ranged from 74 to 154% of the wild-type activity. This was also true for W148F, except for inhibition by antithrombin, where it showed 60% activity. W60dF was deficient by 30, 57, and 43% with fibrinogen clotting, platelet activation, and factor V cleavage (Arg(1006)), respectively. W215F was deficient by 90, 55, and 56% with fibrinogen clotting, platelet activation, and factor V cleavage (Arg(1536)). With protein C and TAFI, W96F, W148F, and W207F were normal. W60dF, however, was 76 and 23% of normal levels with protein C and TAFI, respectively. In contrast, W215F was 25 and 124% of normal levels in these reactions. Thus, many activities of thrombin are retained upon substitution of Trp with Phe at positions 96, 148, and 207. Trp(60d), however, appears to be very important for TAFI activation, and Trp(215) appears to very important for clotting and protein C activation.

Blood Coagulation↗
PubMed2000

Roles of thermal instability and proteolytic cleavage in regulation of activated thrombin-activable fibrinolysis inhibitor.

We have used site-directed mutagenesis and a recombinant expression system for thrombin-activable fibrinolysis inhibitor (TAFI) in order to identify the thrombin cleavage site in activated TAFI (TAFIa) and to determine the relative contribution of proteolytic cleavage and thermal instability in regulation of TAFIa activity in clots. Arg-330 of TAFIa had been proposed to be the thrombin cleavage site based on studies with trypsin, but mutation of this residue to Gln did not prevent thrombin-mediated cleavage nor did mutation to Gln of the nearby Arg-320 residue. However, mutation of Arg-302 to Gln abolished thrombin-mediated cleavage of TAFIa. All TAFIa variants were susceptible to plasmin cleavage. Interestingly, all Arg to Gln substitutions decreased the thermal stability of TAFIa. The antifibrinolytic potential of the TAFI mutants in vitro correlates with the thermal stability of their respective TAFIa species, indicating that this property plays a key role in regulating the activity if TAFIa. Incubation of TAFIa under conditions that result in complete thermal inactivation of the enzyme accelerates subsequent thrombin- and plasmin-mediated cleavage of TAFIa. Moreover, the extent of cleavage of TAFIa by thrombin does not affect the rate of decay of TAFIa activity. Collectively, these studies point to a role for the thermal instability, but not for proteolytic cleavage, of TAFIa in regulation of its activity and, thus, of its antifibrinolytic potential. Finally, we propose a model for the thermal instability of TAFIa.

Carboxypeptidase B2↗
PubMed2000

Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study.

CONTEXT: Tissue-type plasminogen activator (tPA) is the only therapy for acute ischemic stroke approved by the Food and Drug Administration. OBJECTIVE: To assess the safety profile and to document clinical outcomes and adverse events in patients treated with intravenous tPA for acute stroke in clinical practice. DESIGN AND SETTING: Prospective, multicenter study of consecutive patients enrolled between February 1997 and December 1998 at 57 medical centers in the United States (24 academic and 33 community). INTERVENTION: Intravenous tPA (recombinant alteplase). PATIENTS: Three hundred eighty-nine patients with a mean age of 69 years (range, 28-100 years); 55% were men. MAIN OUTCOME MEASURES: Time intervals between stroke symptom onset, hospital arrival, and treatment with tPA; pretreatment computed tomographic scan results, intracerebral hemorrhage, and major systemic bleeding. The modified Rankin Scale score was used to assess clinical outcomes at 30 days. RESULTS: Median time from stroke onset to treatment was 2 hours 44 minutes, and the median baseline National Institutes of Health Stroke Scale score was 13. The 30-day mortality rate was 13%. At 30 days after treatment, 35% of patients had very favorable outcomes (modified Rankin score, 0-1) and 43% were functionally independent (modified Rankin score, 0-2). Thirteen patients (3.3%) experienced symptomatic intracerebral hemorrhage, including 7 who died. Twenty-eight patients (8.2%) had asymptomatic intracerebral hemorrhage within 3 days of treatment with tPA. Protocol violations were reported for 127 patients (32.6%), and included treatment with tPA more than 3 hours after symptom onset in 13.4%, treatment with anticoagulants within 24 hours of tPA administration in 9.3%, and tPA administration despite systolic blood pressure exceeding 185 mm Hg in 6.7%. A multivariate analysis found predictors of favorable outcome to be a less severe baseline National Institutes of Health Stroke Scale score, absence of specific abnormalities (effacement or hypodensity of >33% of the middle cerebral artery territory or a hyperdense middle cerebral artery) on the baseline computed tomographic scan, an age of 85 years or younger, and a lower mean arterial pressure at baseline. CONCLUSIONS: This study, conducted at multiple institutions throughout the United States, suggests that favorable clinical outcomes and low rates of symptomatic intracerebral hemorrhage can be achieved using tPA for stroke treatment.

Adult↗
PubMed2000

The measurement and diagnostic utility of intrasubtest scatter in pediatric neuropsychology.

Intrasubtest scatter (ISS) is a measure of person's tendency toward inconsistency when responding to test items. It has been claimed that ISS may be suggestive of intellectual inefficiency, difficulty with recall of specific information, or fluctuating levels of arousal/attention. The research investigating these claims has been inconclusive, possibly because traditional indices of ISS may not adequately measure inconsistent responding. Item Response Theory (IRT) approaches to the detection of unusual response sequences appear to have a much firmer psychometric foundation but have been largely ignored in the neurodiagnostic literature. This study compares the utility of traditional and IRT-based indices of ISS in identifying children known to be experiencing information-processing difficulties. The WISC-R item responses of 100 children who have received cranial irradiation treatment for leukemia are compared with those of 100 healthy children. Results confirm the diagnostic utility of an IRT-based measure of unusual test behavior in this clinical group.

Adolescent↗
PubMed2000

PD-135,158, a cholecystokinin(B) antagonist, enhances latent inhibition in the rat.

The antipsychotic potential of cholecystokinin (CCK)-related compounds stems from CCK's colocalization with dopamine (DA). CCK demonstrates excitatory and inhibitory effects on DA in the mesolimbic pathway. Such diverse actions might be mediated by different receptor subtypes (CCK(A) or CCK(B)). Multiple hypotheses have emerged regarding the clinical application of CCK-based drugs. Administering selective nonpeptide antagonists within animal models relevant to schizophrenia would help delineate CCK receptor involvement. One animal model simulating a cognitive dysfunction of schizophrenia is latent inhibition (LI). An animal repeatedly exposed to a stimulus that is devoid of consequence is subsequently inhibited in making new associations with that stimulus. This reflects a process of learning to ignore irrelevant stimuli. The present study examined the effects of the selective CCK(B) antagonist PD-135,158 (0.001, 0. 01, and 0.1 mg/kg) using a conditioned suppression of drinking procedure in rats. For purposes of comparison the effects of haloperidol (0.1 mg/kg) were also investigated. PD-135,158 (0.1 mg/kg), similar to haloperidol (0.1 mg/kg), elicited a clear LI effect under conditions that did not lead to LI in control rats (low number of preexposures). These findings highlight the antipsychotic potential of CCK(B) antagonists, and further illustrate the LI paradigm's capacity to detect novel, antipsychotic-like, drug activity.

Animals↗
PubMed2000

Lead induced alterations in nitrite and nitrate levels in different regions of the rat brain.

Nitric oxide (NO) is a free radical synthesized by nitric oxide synthase (NOS) during the conversion of L-arginine to citrulline. Lead (Pb) affects neuronal functioning in the rat brain. Nitric oxide, a neuronal messenger has a short half life and converts immediately into nitrite and nitrate. The present study is designed to determine lead-induced alterations in NO production by measuring nitrite and nitrate in the cerebellum, the hippocampus, the frontal cortex and the brain stem of the rat brain. Male Sprague-Dawley rats were treated with lead acetate (5 and 15 mg/kg body wt.) by intraperitoneal injection. The control and experimental rats were sacrificed at the end of 7 and 14 days after treatment and different regions of the brain were isolated. Nitrite and nitrate (NOx) levels were estimated by the chemiluminescent method using the NOA 280 (Sievers). The data suggested dose-dependent and region-specific responses to lead. Both treatments of lead reduced NOx levels in the cerebellum and the hippocampus. However, the frontal cortex and the brain stem responded differently to Pb exposure. NOx levels in the frontal cortex were significantly increased in rats treated with low and high doses of Pb for 7 days but not in rats treated for 14 days, whereas in the brain stem, NOx levels were increased in a dose- and time-dependent manner. Although, the response was time-dependent, the variation between 7- and 14-day treatment was not clearly delineated. These results provide additional evidence that Pb exposure alters NO-production in rat brain leading to neuronal dysfunction.

Animals↗
PubMed2000

Determinants and detection of low body mass index in community-dwelling adults with Alzheimer's disease.

OBJECTIVE: To determine the proportion of older adults with Alzheimer's disease presenting to a geriatric clinic with low body mass index (BMI), the proportion of these individuals recognized by clinicians as malnourished, and what patients' characteristics and caregivers' and clinicians' impressions are associated with low BMI. DESIGN: Cross-sectional study. SETTING: An outpatient geriatric clinic located in a university-affiliated teaching hospital. PARTICIPANTS: 340 patients with Alzheimer's disease, average age 75 years. MEASUREMENTS: Individuals with a BMI below 21 were considered at risk of malnutrition. Physical examination and medical information were obtained from patients and caregivers by clinicians using a standardized assessment protocol. Clinicians' impression regarding evidence of malnutrition was obtained. RESULTS: Forty-six patients (16%) had a BMI below 21. Clinicians reported evidence of potential malnutrition in 11 patients, 8 of whom had a BMI below 21. Using logistic regression, we found that women were five times more likely to have a BMI below 21 than men, and that individuals with low cognition were twice as likely to have a BMI below 21 than individuals with higher cognition. CONCLUSION: The proportion of patients with Alzheimer's disease with a BMI below 21 is similar to that encountered in the general population aged 65+. However, clinicians have difficulty identifying persons at risk of malnutrition according to BMI status. Women with low cognition were at increased risk of having a low BMI. Improvement in the detection of malnutrition is desirable. Further exploration of causal links between cognition and malnutrition is required.

Aged↗
PubMed2000

Nutrition in cancer: an overview.

OBJECTIVES: To provide a review of weight loss, cachexia (both primary and secondary), and weight gain in cancer patients. DATA SOURCES: Research reports, review articles, textbooks, and personal communications. CONCLUSIONS: Alterations in nutritional status have the potential to affect mortality, morbidity, and quality of life outcomes. The detection and treatment of malnutrition is important to success of therapy. IMPLICATIONS FOR NURSING PRACTICE: Nursing interventions to help maintain optimal nutritional status in patients with cancer include careful assessment, identification of patients at risk, and management of problems before the initiation of therapy.

Cachexia↗
PubMed2000

Depressive symptoms reduced in individuals with HIV/AIDS treated with highly active antiretroviral therapy: a longitudinal study.

OBJECTIVE: The aims of this study were to investigate the stability of depressive symptoms over time, explore possible reasons for the genesis of depressive symptoms, examine psychosocial adjustment over time and examine the effects of the introduction of highly active antiretroviral therapy (HAART) in a group of HIV infected patients. METHOD: HIV seropositive outpatients were assessed at 6 monthly intervals over a 2-year period. At each assessment patients completed the Beck Depression Inventory, the Life Event Inventory, the Core Bereavement Item questionnaire and the Psychosocial Adjustment to Illness Scale. Details regarding HIV illness progression and antiretroviral treatment were recorded for each follow-up assessment. RESULTS: One hundred and sixty-three patients completed the baseline assessment and proceeded to the 2-year follow-up study. Most patients remained well over the 2-year follow-up period; mean CD4 count for the group increased over the study period. Ten patients developed AIDS and 18 patients died. Antiretroviral medications changed significantly during the follow-up, with most patients changing to combination (triple) therapy, which included the use of a protease inhibitor. Psychosocial stressors (life event distress and number of bereavements) reduced as the study progressed. Reported depressive symptoms decreased over time and psychosocial adjustment to illness tended to improve over the 2-year period. CONCLUSIONS: Over a 2-year follow-up period HIV/AIDS symptoms and illness markers and psychosocial adjustment to illness improved, psychological stressors and depressive symptoms decreased, with a temporal relationship to changes in antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗