Biomedical subjects

Constantin T Yiannoutsos

Publications and source records attributed to Constantin T Yiannoutsos.

18 recordsLinked to original sources

PubMed2007

Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: A Hoosier Oncology Group Trial, HEM01-21.

Thalidomide has direct antimyeloma and immunomodulatory effects. In addition, both thalidomide and metronomic chemotherapy inhibit angiogenesis. The synergy of such a combination may decrease toxicity while maintaining efficacy. The Hoosier Oncology Group conducted a phase II trial of oral cyclophosphamide (50 mg b.i.d. for 21 days), thalidomide (200 mg/day), and prednisone (50 mg q.o.d.) (CTP) per 28-day course in patients with relapsed multiple myeloma (MM). Of the 37 patients enrolled, 16 had prior stem cell transplantation. The median follow-up time was 25.3 months (95% confidence interval [CI] 23.2-27.7). Of 35 patients treated, 22 patients (62.9%) responded: 7 (20.0%) complete responses, 2 (5.7%) near-complete responses, and 13 (37.1%) partial responses. Eight patients (22.9%) had stable disease, and three (8.6%) had disease progression. Two patients withdrew from the study early due to reasons unrelated to progression or toxicity and were treated as nonresponders. The median time to best response and time to progression were 3.6 months (95% CI 2.8-10.9) and 13.2 months (95% CI 9.4-21.0), respectively. The median number of treatment cycles was seven (range 1-12 cycles). Grade III to IV toxicities included leukopenia (42.9%; febrile neutropenia, 11.4%), hyperglycemia (20%), sensory neuropathy (11.4%), thromboses (8%), and motor neuropathy (5.7%). No patient withdrew from the study due to toxicity. The efficacy and low toxicity of the CTP regimen support the future development of such an approach in MM.

Administration, Oral↗

PubMed2006

Outcomes of HIV-infected orphaned and non-orphaned children on antiretroviral therapy in western Kenya.

OBJECTIVES: Determine outcome differences between orphaned and non-orphaned children receiving antiretroviral therapy (ART). DESIGN: Retrospective review of prospectively recorded electronic data. SETTING: Nine HIV clinics in western Kenya. POPULATION: 279 children on ART enrolled between August 2002 and February 2005. MAIN MEASURES: Orphan status, CD4%, sex- and age-adjusted height (HAZ) and weight (WAZ) z scores, ART adherence, mortality. RESULTS: Median follow-up was 34 months. Cohort included 51% males and 54% orphans. At ART initiation (baseline), 71% of children had CDC clinical stage B or C disease. Median CD4% was 9% and increased dramatically the first 30 weeks of therapy, then leveled off. Parents and guardians reported perfect adherence at every visit for 75% of children. Adherence and orphan status were not significantly associated with CD4% response. Adjusted for baseline age, follow-up was significantly shorter among orphaned children (median 33 vs. 41 weeks, P = 0.096). One-year mortality was 7.1% for orphaned and 6.6% for non-orphaned children (P = 0.836). HAZ and WAZ were significantly below norm in both groups. With ART, HAZ remained stable, while WAZ tended to increase toward the norm, especially among non-orphans. Orphans showed identical weight gains as non-orphans the first 70 weeks after start of ART but experienced reductions afterwards. CONCLUSIONS: Good ART adherence is possible in western rural Kenya. ART for HIV-infected children produced substantial and sustainable CD4% improvement. Orphan status was not associated with worse short-term outcomes but may be a factor for long-term therapy response. ART alone may not be sufficient to reverse significant developmental lags in the HIV-positive pediatric population.

Adolescent↗

PubMed2006

A sequential design to estimate sensitivity and specificity of a diagnostic or screening test.

We consider efficient study designs to estimate sensitivity and specificity of a candidate diagnostic or screening test. Our focus is the setting in which the candidate test is inexpensive to administer compared to evaluation of disease status, and the test results, available in a large cohort, can be used as a basis for sampling subjects for verification of disease status. We examine designs in which disease status is verified in a sample chosen so as to optimize estimation of either sensitivity or specificity. We then propose a sequential design in which the first step of sampling is conducted to efficiently estimate specificity. If the candidate test is determined to be of sufficient specificity, then step two of sampling is conducted to estimate sensitivity. We propose estimators based on this sequential sampling scheme, and show that the performance of these estimators is excellent. We develop sample size calculations for the sequential design, and show that this design, in most situations, compares favourably in terms of expected sample size to a fixed size design.

Biometry↗

PubMed2006

Viability and effectiveness of large-scale HIV treatment initiatives in sub-Saharan Africa: experience from western Kenya.

OBJECTIVES: To determine the clinical and immunological outcomes of a cohort of HIV-infected patients receiving antiretroviral therapy. DESIGN: Retrospective study of prospectively collected data from consecutively enrolled adult HIV-infected patients in eight HIV clinics in western Kenya. METHODS: CD4 cell counts, weight, mortality, loss to follow-up and adherence to antiretroviral therapy were collected for the 2059 HIV-positive non-pregnant adult patients treated with antiretroviral drugs between November 2001 and February 2005. RESULTS: Median duration of follow-up after initiation of antiretroviral therapy was 40 weeks (95% confidence interval, 38-43); 111 patients (5.4%) were documented as deceased and 505 (24.5%) were lost to follow-up. Among 1766 (86%) evaluated for adherence to their antiretroviral regimen, 78% reported perfect adherence at every visit. Although patients with and without perfect adherence gained weight, patients with less than perfect adherence gained 1.04 kg less weight than those reporting perfect adherence (P = 0.059). CD4 cell counts increased by a mean of 109 cells/microl during the first 6 weeks of therapy and increased more slowly thereafter, resulting in overall CD4 cell count increases of 160, 225 and 297 cells/microl at 12, 24, and 36 months respectively. At 1 year, a mean increase of 170 cells/microl was seen among patients reporting perfect adherence compared with 123 cells/microl among those reporting some missed doses (P < 0.001). CONCLUSIONS: Antiretroviral treatment of adult Kenyans in this cohort resulted in significant and persistent clinical and immunological benefit. These findings document the viability and effectiveness of large-scale HIV treatment initiatives in resource-limited settings.

Adult↗

PubMed2006

A placebo-controlled study of memantine for the treatment of human immunodeficiency virus-associated sensory neuropathy.

Distal sensory polyneuropathy (DSP) is the most frequent neurological complication of HIV infection. Neuropathic symptoms vary from mild paresthesias to severe pain that respond only partially to symptomatic treatment. Forty-five subjects with human immunodeficiency virus (HIV)-associated symptomatic DSP (SDSP) were enrolled in a randomized, multicenter, 16-week placebo-controlled study of memantine, an N-methyl-D-aspartate (NMDA) uncompetitive antagonist. Although memantine was well tolerated, no trend toward clinical benefit was observed. Results were similar to those of other pilot studies of memantine for neuropathic pain unrelated to HIV, suggesting that memantine is ineffective for the symptomatic treatment of HIV-associated SDSP.

Adult↗

PubMed2005

Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as adjuvant treatment for uterine papillary serous carcinoma and clear cell carcinoma: a phase II Hoosier Oncology Group (HOG 97-01) study.

OBJECTIVE: A phase II study was conducted to evaluate the role of adjuvant intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy in patients with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC), after complete surgical staging. METHODS: Patients were required to have undergone complete surgical staging including maximal surgical resection. Residual < or =3 mm intraperitoneal disease, and pelvic and para-aortic lymph node dissection with negative nodes, were required. A dose of 15 mCi of intraperitoneal 32P was administered within 8 weeks of surgery. Vaginal brachytherapy was delivered using either high dose rate, total dose of 2100 cGy in 3 fractions (700 cGy per fraction prescribed to 0.5 cm depth from the vaginal surface) or low dose rate to 6500 cGy (prescribed to the vaginal surface) in 1-2 fractions. RESULTS: For the 21 evaluable patients, distribution by FIGO stage was as follows: Stages I-IIB (17), Stages III-IV (4). The median follow-up was 39.6 months (range: 5-63 months). No patients experienced grade 2-4 complications from their adjuvant therapy. Five patients suffered a recurrence: intraperitoneal [n = 2], distal vaginal [n = 2], and one at the surgical scar. Following the 2 distal vagina recurrences early in the trial, the entire length of the vagina was treated with intracavitary brachytherapy. No additional vaginal recurrences were observed. The two-year overall survival, cause-specific survival, and disease-free survival for the entire series were 89.2%, 89.2%, and 79.7%, respectively. CONCLUSIONS: Adjuvant therapy for UPSC and CCC with intraperitoneal 32P and vaginal brachytherapy after comprehensive surgical staging is feasible, well tolerated, and warrants further study on a larger scale.

Adult↗

PubMed2005

Clinical validation of the NeuroScreen.

The NeuroScreen comprises two easily administered components: the Brief NeuroCognitive Screen (BNCS), designed to estimate the frequency of human immunodeficiency virus (HIV)-associated cognitive disorders; and the Brief Peripheral Neuropathy Screen (BPNS), for distal sensory polyneuropathy (DSPN) in HIV. In this study, both the NeuroScreen and a more extensive standardized validation neurodiagnostic evaluation were administered to HIV-positive subjects (N = 301) enrolled in two large cohort studies at multiple sites. BNCS performance was summarized in the form of a demographically adjusted mean z-score, the NPZ3. The area under the receiver-operating characteristic (ROC) curve for the BNCS as compared to the reference standard neuropsychological (NP) evaluation was 0.74 (95% confidence interval [CI] 0.69, 0.79). Using a cut-point of -0.33 on the NPZ3 provided a correct classification rate of 68%, with roughly balanced sensitivity (65%) and specificity (72%). Under the assumption of a 30% prevalence of cognitive impairment, the calculated positive predictive value (PPV) of the BNCS was 86%. Relative to its reference standard, a modified Total Neuropathy Score (TNS) administered by a neurologist, the BPNS gave a similar correct diagnostic classification rate of 78%; sensitivity 49% [95%, 60%]; specificity 88% [95% Cl82%, 91%]. Under the assumption of a 40% prevalence of DSPN, the PPV of the BPNS was 72%. These predictive values suggest that the NeuroScreen will be useful for tracking trends in the prevalence of HIV-associated neurologic disease in large cohorts in the era of combination antiretroviral therapy. However, because it yields substantial numbers of false positives and negatives, the NeuroScreen may be less useful in evaluating individual patients.

AIDS Dementia Complex↗

PubMed2004

Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38-/lo cells in G0.

Whether cytokines can modulate the fate of primitive hematopoietic progenitor cells (HPCs) through successive in vitro cell divisions has not been established. Single human marrow CD34+CD38-/lo cells in the G0 phase of cell cycle were cultured under 7 different cytokine combinations, monitored for proliferation on days 3, 5, and 7, then assayed for long-term culture-initiating cell (LTC-IC) function on day 7. LTC-IC function was then retrospectively correlated with prior number of in vitro cell divisions to determine whether maintenance of LTC-IC function after in vitro cell division is dependent on cytokine exposure. In the presence of proliferation progression signals, initial cell division was independent of cytokine stimulation, suggesting that entry of primitive HPCs into the cell cycle is a stochastic property. However, kinetics of proliferation beyond day 3 and maintenance of LTC-IC function were sensitive to cytokine stimulation, such that LTC-IC underwent an initial long cell cycle, followed by more synchronized shorter cycles varying in length depending on the cytokine combination. Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) transplantation studies revealed analogous results to those obtained with LTC-ICs. These data suggest that although exit from quiescence and commitment to proliferation might be stochastic, kinetics of proliferation, and possibly fate of primitive HPCs, might be modulated by extrinsic factors.

ADP-ribosyl Cyclase↗

PubMed2004

Ordered multiple-class ROC analysis with continuous measurements.

Receiver operating characteristic (ROC) curves have been useful in two-group classification problems. In three- and multiple-class diagnostic problems, an ROC surface or hyper-surface can be constructed. The volume under these surfaces can be used for inference using bootstrap techniques or U-statistics theory. In this article, ROC surfaces and hyper-surfaces are defined and their behaviour and utility in multi-group classification problems is investigated. The formulation of the problem is equivalent to what has previously been proposed in the general multi-category classification problem but the definition of ROC surfaces here is less complex and addresses directly the narrower problem of ordered categories in the three-class and, by extension, the multi-class problem applied to continuous and ordinal data. Non-parametric manipulation of both continuous and discrete test data and comparison between two diagnostic tests applied to the same subjects are considered. A three-group classification example in the context of HIV neurological disease is presented and the results are discussed.

AIDS Dementia Complex↗

PubMed2004

Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy.

We performed a prospective observational study to assess the safety of stopping maintenance therapy for disseminated histoplasmosis among human immunodeficiency virus infected patients after response to antiretroviral therapy. All subjects received at least 12 months of antifungal therapy and 6 months of antiretroviral therapy before entry. Negative results of fungal blood cultures, urine and serum Histoplasma antigen level of <4.1 units, and CD4+ T cell count of >150 cells/mm3 were required for eligibility. Thirty-two subjects were enrolled; the median CD4+ T cell count at study entry was 289 cells/mm3. No relapses of histoplasmosis occurred after a median duration of follow-up of 24 months. This corresponded to an observed relapse rate of 0 cases per 65 person-years. The median CD4+ T cell count at final study visit was 338 cells/mm3. Discontinuation of antifungal maintenance therapy appears to be safe for patients with acquired immunodeficiency syndrome with previously treated disseminated histoplasmosis and sustained immunologic improvement in response to antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

PubMed2004

Pancreaticoduodenectomy: a 20-year experience in 516 patients.

HYPOTHESIS: Pancreaticoduodenectomy (PD) is a safe procedure for a variety of periampullary conditions. DESIGN: Retrospective review of a prospectively collected database. SETTING: Academic tertiary care hospital. PATIENTS: A total of 516 consecutive patients who underwent PD. MAIN OUTCOME MEASURES: Patient outcomes and survival factors. RESULTS: Pathological examination demonstrated 57% periampullary cancers, 22% chronic pancreatitis, 12% cystic neoplasms, 4% islet cell neoplasms, and 5% other. Fifty-one percent of patients underwent pylorus preservation. Median operating time was 5 hours; blood loss, 1300 mL; and transfusion requirement, 1.5 U. Postoperative complications occurred in 43% of patients, including cardiopulmonary events (15%), fistula (9%), delayed gastric emptying (7%), and sepsis (6%). Additional surgery was required in 3% of patients, most commonly because of bleeding. Perioperative mortality was 3.9% overall but only 1.8% in patients with chronic pancreatitis; 25% of patients who died had preoperative complications associated with their periampullary condition. Three-year survival was 15% after resection for pancreatic cancer, 42% for duodenal cancer, 53% for ampullary cancer, and 62% for bile duct cancer. Univariate predictors of long-term survival in patients with periampullary adenocarcinoma included elevated glucose levels, liver function test results, abnormal tumor markers, blood loss, transfusion requirement, type of operation, and pathologic findings (periampullary adenocarcinoma type, differentiation, and margin and node status). Multivariate predictors were serum total bilirubin level, blood loss, operation type, diagnosis, and lymph node status. CONCLUSIONS: Pancreaticoduodenectomy continues to be associated with considerable morbidity. With careful patient selection, PD can be performed safely. Long-term survival in patients with periampullary adenocarcinoma can be predicted by preoperative laboratory values, intraoperative factors, and pathologic findings.

Adenocarcinoma↗

PubMed2004

Regional patterns of brain metabolites in AIDS dementia complex.

The relationship of the cellular changes in the HIV-infected brain to the onset and progression of AIDS dementia complex (ADC) remains uncertain. We undertook an in vivo proton magnetic resonance spectroscopy (MRS) study and used factor analysis to identify specific cellular and regional brain changes that may serve as metabolic markers of ADC. The ratio of N-acetyl aspartate (NAA), choline (Cho), and myoinositol (MI) over creatine (Cr), markers of neuronal and glial cell metabolism, were measured in the basal ganglia, centrum semiovale, and parietal cortex from 100 subjects with and without ADC. Three metabolic patterns were identified, which we termed "inflammatory" (mainly MI/Cr elevations in all three regions plus Cho/Cr increases in the centrum semiovale and parietal cortex), "basal ganglia" (mostly NAA/Cr and Cho/Cr elevations in the basal ganglia), and "neuronal" (primarily NAA/Cr reductions in the centrum semiovale and the parietal cortex). Logistic regression analysis revealed that, adjusted for age, basal ganglia and neuronal pattern scores were strongly associated with ADC but inflammatory levels were not. We conclude that by using factor analysis, we are able to combine multiple metabolites across brain regions in a biologically plausible manner and construct a predictive model of ADC adjusting for relevant factors such as age.

AIDS Dementia Complex↗

PubMed2004

Phase II study of low-dose topotecan in myelodysplastic syndromes: a Hoosier Oncology Group (HOG) study.

Topotecan has demonstrable activity in high-risk MDS and CMMoL. However, the significant toxicity of topotecan administered at a dose of 2mg/m2 i.v. daily for 5 days as a continuous infusion limits its use in older patients. Therefore, we studied topotecan 1.5mg/m2 per day i.v. over 2 h for three consecutive days in 20 patients with high-risk MDS (12 RAEB; 4 RAEB-T; 4 CMMoL). Cycles were given every 4-6 weeks. Fifteen patients were evaluable for response. Only one patient achieved a durable complete remission (CR). There were three deaths within the first cycle of therapy. Severe myelosuppression was the most common toxicity. Grades 3-4 infections were documented in four patients. We conclude that topotecan administered at this dose and schedule has no clinically significant activity.

Aged↗

PubMed2003

Assessment of diagnostic markers by goodness-of-fit tests.

Receiver operating characteristic (ROC) curves are useful statistical tools used to assess the precision of diagnostic markers or to compare new diagnostic markers with old ones. The most common index employed for these purposes is the area under the ROC curve (theta) and several statistical tests exist that test the null hypotheses H(0): theta= 0.5 or H(0): theta1=theta2, in the case of two-marker comparisons, against alternatives of interest. In this paper we show that goodness-of-fit of uniformity of the distribution of the false positive (true positive) rates can be used instead of tests based on the area index. A semi-parametric approach is based on a completely specified distribution of marker measurements for either the healthy (F) or diseased (G) subjects, and this is extended to the two-marker case. We then extend to the one- and two-marker case when neither distribution is specified (the non-parametric case). In general, ROC-based tests are more powerful than goodness-of-fit tests for location differences between the distributions of healthy and diseased subjects. However ROC-based tests are less powerful when location-scale differences exist (producing ROC curves that cross the diagonal) and are incapable of discriminating between healthy and diseased samples when theta=0.5 but F not equal G. In these cases, goodness-of-fit tests have a distinct advantage over ROC-based tests. In conclusion, ROC methodology should be used with recognition of its potential limitations and should be replaced by goodness-of-fit tests when appropriate. The latter are a viable alternative and can be used as a 'black box' or as an exploratory first step in the evaluation of novel diagnostic markers.

Biomarkers↗

PubMed2003

Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: genetic analysis of the Milwaukee longitudinal study.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable and common disorder that partly reflects disturbed dopaminergic function in the brain. Recent genetic studies have shown that candidate genes involved in dopamine signaling and metabolism contribute to ADHD susceptibility. We have initiated genetic studies in a unique cohort of 158 ADHD and 81 control adult subjects who have been followed longitudinally since childhood in the Milwaukee study of ADHD. From this cohort, genetic analysis was performed in 105 Caucasian subjects with ADHD and 68 age and ethnicity-matched controls for the DRD4 exon 3 VNTR, the SLC6A3 (DAT1) 3' UTR VNTR, dopamine beta hydroxylase (DBH) TaqI A polymorphism, and the DBH GT microsatellite repeat polymorphism that has been quantitatively associated with serum levels of DBH activity, but not previously studied in ADHD. Results indicate a significant association between the DBH TaqI A1 allele and ADHD (P = 0.018) with a relative risk of 1.33. The DBH GT repeat 4 allele, which is associated with high serum levels of DBH, occurred more frequently in the ADHD group than controls, but the difference did not reach statistical significance. Associations were not found with the SLC6A3 10 repeat or DRD4 7 repeat alleles. These results indicate that the DBH TaqI A allele, or another polymorphism in linkage disequilibrium with this allele, may confer increased susceptibility towards ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Preoperative predictors of malignancy in pancreatic intraductal papillary mucinous neoplasms.

HYPOTHESIS: Malignant intraductal papillary mucinous neoplasms (IPMNs) can be predicted before surgery. DESIGN: Retrospective review of a prospectively collected database. SETTING: Academic, urban, tertiary care hospital. PATIENTS: Sixty-four consecutive patients with a pathological diagnosis of IPMN. INTERVENTIONS: All 64 patients underwent surgical intervention for IPMN between December 8, 1988, and October 16, 2002. MAIN OUTCOME MEASURES: Reliable predictors of malignancy. RESULTS: The 64 patients underwent 69 operations: 39 pancreaticoduodenectomies, 18 distal pancreatectomies, 7 total pancreatectomies, 4 neck and/or body pancreatectomies, and 1 cystgastrostomy with pancreatic biopsy. Twenty-three of 69 specimens were malignant-12 in situ (high-grade dysplasia) and 11 invasive. In a univariate analysis of 12 clinical signs or symptoms recorded, diabetes mellitus and jaundice showed a significant association with malignancy of IPMN. Of 24 serum chemistry studies, hematologic studies, and tumor marker analyses (in serum, bile, and pancreatic fluid), elevation of serum alkaline phosphatase and glucose levels showed correlation with malignancy. Computed tomography, ultrasound, and endoscopic retrograde cholangiopancreatography findings did not distinguish between benign and malignant tumors. Atypia on preoperative cytologic analysis was specific for malignancy (93%) but lacked the same degree of sensitivity (40% in situ, 91% invasive, and 67% overall). CONCLUSIONS: Malignancy of IPMNs is suggested by new-onset diabetes mellitus, jaundice, and elevations in serum glucose or alkaline phosphatase levels. Atypia on preoperative cytologic testing is the finding most predictive of malignancy. The absence of these features does not predict benign disease. These findings may help guide patient and physician decision making.

Adenocarcinoma, Mucinous↗

PubMed2003

A multi-center 1H MRS study of the AIDS dementia complex: validation and preliminary analysis.

PURPOSE: To demonstrate the technical feasibility and reliability of a multi-center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N-acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC). MATERIALS AND METHODS: Using an automated protocol (GE PROBE-P), short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia, and parietal cortex) of normal volunteers and ADC and HIV-negative subjects. RESULTS: A random-effects model of the phantom and volunteer data showed no significant inter-site differences. Feasibility of a multi-center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV-negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC. CONCLUSION: This is the first study to ascertain and validate the reliability and reproducibility of a short echo time (1)H-MRS acquisition sequence from multiple brain regions in a multi-center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting.

AIDS Dementia Complex↗

PubMed2002

Severity of HIV-associated neuropathy is associated with plasma HIV-1 RNA levels.

OBJECTIVE: To determine if there is an association between plasma HIV-1 RNA levels and severity of HIV-associated distal symmetrical polyneuropathy (DSP). DESIGN: Substudy of AIDS Clinical Trials Group Protocol 291, a double-blind, placebo-controlled study of recombinant human nerve growth factor for the treatment of painful DSP. METHODS: Two-hundred and thirty-six subjects had plasma HIV-1 RNA load assayed at baseline. Mean and maximum neuropathic pain was assessed once daily by the Gracely Pain Scale. Other measures included subjects' global pain assessment and quantitative sensory tests (QST). These values were correlated with baseline HIV-1 RNA levels. RESULTS: Among 168 subjects with detectable plasma HIV-1 RNA, there was a significant correlation between plasma HIV-1 RNA and the severity of maximum and global pain, and toe cooling thresholds. Maximum and global pain assessment correlated with plasma HIV-1 RNA in individuals with detectable viral load (r, 0.162 and 0.194; P = 0.04 and 0.01, respectively). CONCLUSIONS: There is an association between plasma HIV-1 RNA levels and the severity of pain and QST results in HIV-associated DSP. Further studies are needed to determine if aggressive use of antiretroviral drugs, including the use of dideoxynucleosides, may be of benefit to prevent or improve peripheral neuropathy.

Adult↗