Early synapsids neurosensory diversity revealed by CT and synchrotron scanning.

Non-mammaliaform synapsids (NMS) represent the closest relatives of today's mammals among the early amniotes. Exploring their brain and nervous system is key to understanding how mammals evolved. Here, using CT and Synchrotron scanning, we document for the first time three extreme cases of neurosensory and behavioral adaptations that probe into the wide range of unexpected NMS paleoneurological diversity. First, we describe adaptations to low-frequency hearing and low-light conditions in the non-mammalian cynodont Cistecynodon parvus, supporting adaptations to an obligatory fossorial lifestyle. Second, we describe the uniquely complex and three-dimensional maxillary canal morphology of the biarmosuchian Pachydectes elsi, which suggests that it may have used its cranial bosses for display or low-energy combat. Finally, we introduce a paleopathology found in the skull of Moschognathus whaitsi. Since the specimen was not fully grown, this condition suggests the possibility that this species might have engaged in playful fighting as juveniles-a behavior that is both social and structured. Additionally, this paper discusses other evidence that could indicate that tapinocephalid dinocephalians were social animals, living and interacting closely with one another. Altogether, these examples evidence the wide range of diversity of neurological structures and complex behavior in NMS.

Childhood disadvantage and adolescent socioemotional wellbeing as predictors of future parenting behaviour.

INTRODUCTION: In extending work on early life antecedents of parenting, we investigate associations between childhood family history of disadvantage, adolescent socioemotional wellbeing, and age at first parenthood and subsequent parenting behaviour. METHODS: Parent-child interactions were recorded when participants in the longitudinal Dunedin Multidisciplinary Health and Development Study (New Zealand) had a three-year-old child. Data were available for 358 mothers and 321 fathers, aged between 17.7 and 41.5 at the time of their child's birth. Associations between parenting and antecedent data on socioeconomic disadvantage, adolescent wellbeing and mental health, as well as current adult mental health and age at parenting, were tested for using structural equation modelling. RESULTS: Family disadvantage in childhood and lower adolescent wellbeing was associated with less positive future parenting, but only adult (not adolescent) anxiety/depression symptoms were directly associated with parenting behaviour. Childhood family disadvantage was associated with further disadvantage across the life course that included less positive parenting of the next generation. In contrast, socioemotional wellbeing during adolescence and later age of onset of parenting were associated with more positive parenting. CONCLUSIONS: Reducing childhood disadvantage and improving socioemotional wellbeing during childhood and adolescence is likely to have intergenerational benefits through better parenting of the next generation.

Telepsychology for Posttraumatic Stress Disorder: A systematic review.

The effectiveness of psychological services provided remotely, telepsychology, for the management of Posttraumatic Stress Disorder (PTSD) was evaluated. Eleven studies (n = 472 participants) were identified from electronic database searches. Study quality was assessed, with studies characterised by small and underpowered samples. Effect sizes and associated confidence intervals (CIs) were calculated to determine the direction and magnitude of treatment change. Short-term treatment gains were reported for internet and video-based interventions. This included significant medium to large improvements (d range = 0.66-3.22) in cognitive and behavioural symptoms of depression, generalised anxiety and posttraumatic stress. However, the equivalence of telepsychology and face-to-face psychotherapy could not be determined, with few comparative studies available. Both treatment gains and deterioration were noted 1 to 6 months following treatment cessation, although this was based on limited follow-up data. Further larger scale and longitudinal research will help to ascertain the minimum requirements for the management and treatment of PTSD in a technology-supported environment.

Pancreatic involvement detected with (18)F-FDG PET/CT in disseminated sarcoidosis.

La sarcoidosis is a granulomatous disease of unknown etiology. It may mimic malignancy and may affect multiple organs, with a variable clinical course. Pancreatic involvement is very rare. We present the case of a 78-year-old woman with systemic sarcoidosis whose (18)F-FDG PET/CT scan showed a pancreatic lesion and multiple lymphatic (thoracic and non-thoracic) and visceral lesions. The abnormal (18)F-FDG uptake in the pancreas was limited to the tail. A second (18)F-FDG PET/CT study performed 4 months and 3 weeks after the first PET/CT, following corticosteroid therapy during three and a half months, evidenced partial regression of the disease, with persistent (18)F-FDG pathological uptake in the pancreatic lesion.

Neuroprotective effects of novel phosphatidylglycerol-based phospholipids in the 6-hydroxydopamine model of Parkinson's disease.

Administration of VP025 (Vasogen Inc.), a novel drug formulation based on phospholipid nanoparticles incorporating phosphatidylglycerol, has previously been shown to have a neuroprotective effect in the brain. We examined the effect of VP025 in a rat model of Parkinson's disease, the 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle. VP025 or phosphate-buffered saline (PBS) was administered to rats 14 days, 13 days and 1 day before the unilateral 6-OHDA lesion. Functional integrity of nigrostriatal dopaminergic neurons was assessed 7 and 21 days later by amphetamine-induced rotational testing and we observed that rotational counts were significantly less in rats that were pretreated with VP025 compared with PBS-pretreated 6-OHDA-lesioned rats. Neurochemical analysis at 10 and 28 days after lesion revealed that VP025 protected against a 6-OHDA-induced decrease in concentrations of striatal dopamine and its metabolites. Immunocytochemical studies of the ipsilateral substantia nigra showed that VP025 significantly inhibited 6-OHDA-induced loss of dopaminergic neurons. We also observed that increases in immunostaining for activated microglia and for activated p38 in dopaminergic neurons of 6-OHDA-lesioned rats were prevented by VP025. This study shows that VP025 has significant protective effects on the 6-OHDA-lesioned nigrostriatal pathway and may therefore have potential for the treatment of Parkinson's disease.

The incidence of occupational skin disease as reported to The Health and Occupation Reporting (THOR) network between 2002 and 2005.

BACKGROUND: Estimated incidence rates for occupational skin disease in the U.K. are provided by voluntary surveillance schemes involving dermatologists and occupational physicians. These rates allow monitoring of occupational dermatoses, and intervention planning aimed at reducing workplace risks. OBJECTIVES: To summarize occupational skin disease reported to The Health and Occupation Reporting (THOR) network (2002-2005), and to provide baseline information for comparison with future studies of occupational skin disease in the U.K. and beyond. METHODS: Incidence rates for occupational dermatoses were calculated using THOR data as numerators, and Labour Force Survey data or information from the most recent U.K. survey on provision of occupational physician services as denominators. RESULTS: In the U.K. (2002-2005) the average annual incidence rate of work-related skin disease reported to THOR by dermatologists was 91.3 [95% confidence interval (CI) 81.8-101.1] per million, and by occupational physicians was 316.6 (95% CI 251.8-381.3) per million. Most reports were of contact dermatitis: dermatologists 68.0 (95% CI 59.8-76.2) per million, occupational physicians 259.7 (95% CI 200.8-318.6) per million. CONCLUSIONS: Information produced by THOR is an important source for calculating incidence rates of occupational skin disease. A range of reporting groups should also be used when building an overall picture of occupational skin disease incidence in the U.K.

Assigning exposure to pesticides and solvents from self-reports collected by a computer assisted personal interview and expert assessment of job codes: the UK Adult Brain Tumour Study.

OBJECTIVES: To compare assignment of occupational pesticide and solvent exposure using self-reported data collected by a computer assisted personal interview (CAPI) with exposure based on expert assessment of job codes. To discuss the advantages and disadvantages of using a CAPI to collect individual occupational exposure data. METHODS: Between 2001 and 2004, 1495 participants were interviewed using a CAPI for a case-control study of adult brain tumours and acoustic neuromas. Two types of occupational data were collected: (1) a full history, including job title from which a job code was assigned from the Standard Occupational Classification; and (2) specific details on pesticide and solvent exposure reported by participants. Study members' experiences of using the CAPI were recorded and advantages and disadvantages summarised. RESULTS: Of 7192 jobs recorded, the prevalence of self-reported exposure was 1.3% for pesticides and 11.5% for solvents. Comparing this with exposure expertly assessed from job titles showed 53.6% and 45.8% concordance for pesticides and solvents respectively. Advantages of the CAPI include no data entry stage, automatic input validation, and a reduction in interviewer bias. Disadvantages include an adverse effect on study implementation as a consequence of resources required for programming and difficulties encountered with data management prior to analysis. CONCLUSIONS: Different methods of exposure assessment derive different exposure levels for pesticide and solvent exposure at work. Agreement between self-reported and expert assessment of exposure was greater for pesticides compared to solvents. The advantages of using a CAPI for the collection of complex data outweigh the disadvantages for interviewers and data quality but using such a method requires extra resources at the study outset.

Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study.

AIMS: This study was designed to investigate the biochemical and physiological covariates or comedications that affect the pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia (CP CML). METHODS: Pharmacokinetic data were analyzed in 371 patients receiving 400 mg imatinib once daily during a phase III trial of imatinib vs interferon-alfa plus cytarabine for the treatment of newly diagnosed CP CML. Covariates included age, weight, sex, ethnicity, haemoglobin (Hb) concentration, white blood cell (WBC) count, liver function, and creatinine concentration. Blood samples for imatinib analysis were taken on treatment days 1 and 29. Nonlinear mixed effects modelling was used for the population pharmacokinetic analysis. RESULTS: Population mean estimates (95% confidence interval) at day 1 for apparent clearance (CL) and apparent volume of distribution (V) of imatinib were 14 (13-15) l h(-1) and 252 (237-267) l, respectively. Modelling suggested that CL decreased by 4 (3-5) l h(-1) from day 1 to day 29, whereas V remained unchanged. Interindividual variability in CL and V was 32% and 31%, respectively. Weight, Hb, and WBC count demonstrated small effects on CL and V. Doubling body weight or Hb or halving the WBC count was associated with a 12%, 86% and 8% increase in CL, respectively, and a 32%, 60% and 5% increase in V, respectively. Comedications showed no clear effects on imatinib CL. CONCLUSIONS: Population covariates and coadministered drugs minimally affected imatinib pharmacokinetics in newly diagnosed CP CML patients.

Surface-expressed mig protein protects Streptococcus dysgalactiae against phagocytosis by bovine neutrophils.

The mig gene of Streptococcus dysgalactiae, a major bovine mastitis pathogen, encodes two plasma protein-binding receptors, alpha2-macroglobulin (alpha2-M) and immunoglobulin G (IgG). In this study, the mig gene from one S. dysgalactiae isolate was cloned and expressed in Escherichia coli. The IgG receptor region encoded by mig was conserved in 16 S. dysgalactiae strains. An isogenic mig mutant was constructed by allele replacement mutagenesis of the wild-type gene in S. dysgalactiae. The IgG-binding activity was lost in the mig mutant strain, whereas the alpha2-M receptor activity was still expressed but was detected only in the culture supernatant. In flow cytometry phagocytosis and bacterial-colony-counting bactericidal assays, the wild-type strain was found to be significantly more resistant to phagocytosis and killing by bovine neutrophils (PMNs) than the mig mutant strain when bacteria were preincubated with bovine serum. We therefore speculate that the Mig protein of S. dysgalactiae plays a role in virulence of the bacteria by binding to the plasma protein alpha2-M or IgG and thus preventing phagocytosis by bovine PMNs.

Deaths and injuries from house fires.

BACKGROUND: We sought to define the factors associated with house fires and related injuries by analyzing the data from population-based surveillance. METHODS: For 1991 through 1997, we linked the following data for Dallas: records from the fire department of all house fires (excluding fires in apartments and mobile homes), records of patients transported by ambulance, hospital admissions, and reports from the medical examiner of fatal injuries. RESULTS: There were 223 injuries (91 fatal and 132 nonfatal) from 7190 house fires, for a rate of 5.2 injured persons per 100,000 population per year. Rates of injury related to house fires were highest among blacks (relative risk, 2.8; 95 percent confidence interval, 2.1 to 3.6) and in people 65 years of age or older (relative risk, 2.6; 95 percent confidence interval, 1.9 to 3.5). Census tracts with low median incomes had the highest rates of injury related to house fires (relative risk as compared with census tracts with high median incomes, 8.1; 95 percent confidence interval, 2.5 to 32.0). The rate of injuries was higher for fires that began in bedrooms or living areas (relative risk, 3.7); that were started by heating equipment, smoking, or children playing with fire (relative risk, 2.6); or that occurred in houses built before 1980 (relative risk, 6.6). Injuries occurred more often in houses without functioning smoke detectors (relative risk, 1.5; 95 percent confidence interval, 1.0 to 2.4). The prevalence of functioning smoke detectors was lowest in houses in the census tracts with the lowest median incomes (P<0.001). CONCLUSIONS: Rates of injuries related to house fires are highest in elderly, minority, and low-income populations and in houses without functioning smoke detectors. Efforts to prevent injuries and deaths from house fires should target these populations.

Identification of the acid phosphatase (acpA) gene homologues in pathogenic and non-pathogenic Burkholderia spp. facilitates TnphoA mutagenesis.

Burkholderia pseudomallei and Burkholderia mallei are pathogens responsible for disease in both humans and animals. Burkholderia thailandensis, while phylogenetically similar, is considered avirulent in comparison. These three species exhibit phosphatase activity when grown on media containing chromogenic substrates such as 5-bromo-4-chloro-3-indolyl phosphate (XP). Tn5-OT182 mutagenesis has been utilized to isolate mutants of B. pseudomallei and B. thailandensis unable to hydrolyse XP. Sequence analysis of these mutants revealed an ORF of 1734 nucleotides demonstrating a high degree of homology to the acpA gene product of Francisella tularensis. PCR primers were designed based on the B. pseudomallei acpA gene sequence and were used to amplify an acpA homologue from B. mallei. The predicted amino acid sequence of B. pseudomallei AcpA differed from those of the predicted B. thailandensis AcpA and B. mallei AcpA by 15 and 3 amino acids, respectively. Allelic exchange was used to construct DeltaacpA mutants in each of these Burkholderia spp. These mutants were shown to be devoid of phosphatase activity and have subsequently allowed for the implementation of phoA fusion transposon mutagenesis systems. Two such systems have been successfully utilized in Burkholderia spp. for the identification of several genes encoding exported proteins.

The effect of VAS972 on allergic contact hypersensitivity.

BACKGROUND: Contact hypersensitivity (CHS) is a Th1-mediated immune response that can be down-regulated by immunosuppressive agents such as cyclosporine and environmental stimuli such as ultraviolet light. Recently, an immunomodulation therapy, VAS972, has been developed which is believed to down-regulate the Th1 arm of the immune response. This VAS972 involves modifying autologous blood by controlled exposure to the oxidizing agent ozone and UVC light, at an elevated temperature ex vivo. The processed blood is then administered by intramuscular injection. OBJECTIVE: To further evaluate the immune modulating effect of VAS972. METHODS: We examined the effect of VAS972 treatment on CHS. Contact hypersensitivity was induced with dinitrofluorobenzene (DNFB) in animals receiving VAS972- processed blood, control blood, or saline. A preliminary study was also conducted to evaluate the effect of plasma and cellular fractions of processed blood. RESULTS: Mice injected with VAS972-processed blood demonstrated a significantly lower (46%) CHS response than controls. Histologic examination of challenged ear skin from control mice displayed edema with a significant lymphocytic infiltration, whereas animals administered processed blood demonstrated a reduction in lymphocytic infiltration. Mice injected with either plasma or the cellular fraction of the VAS972-treated blood also demonstrated a significant suppression (49% and 41%, respectively). CONCLUSION: The results of this study demonstrated that VAS972 suppresses CHS and cellular infiltration. Furthermore, the plasma and cellular components of the VAS972 treatment were also able to induce immunosuppression. This further supports the hypothesis that VAS972 down-regulates the Th1 arm of the immune response.

Reactions of cisplatin hydrolytes with methionine, cysteine, and plasma ultrafiltrate studied by a combination of HPLC and NMR techniques.

The reactions of cis-[PtCl(NH3)2(H2O)]+ with L-methionine have been studied by 1D 195Pt and 15N NMR, and by 2D[1H, 15N] NMR. When the platinum complex is in excess, the initial product, cis-[PtCl(NH3)2(Hmet-S)]+ undergoes slow ring closure to [Pt(NH3)2(Hmet-N,S)]2+. Slow ammine loss then occurs to give the isomer of [PtCl(NH3)(Hmet-N,S)]+ with chloride trans to sulfur. When methionine is in excess, a reaction sequence is proposed in which trans-[PtCl(NH3)(Hmet-S)2]+ isomerises to the cis-isomer, with subsequent ring closure reactions leading to cis-[Pt(Hmet-N,S)2]2+. Near pH 7, methionine is unreactive toward cis-[PtCl(OH)(NH3)2]. By contrast, L-cysteine reacts readily with cis-[PtCl(OH)(NH3)2] at pH 7, but there were many reaction products, including bridged species. Cis-[PtCl(OH)(NH3)2] reacts with reduced thiols in ultrafiltered plasma but these are oxidized if the plasma is not fresh or appropriately stored. With very low concentrations of the platinum complexes (35.5 microM), HPLC experiments (UV detection at 305 nm) indicate that the thiolate (probably cysteine) reactions become simpler as bridging becomes less important.

The abp locus of Streptococcus uberis encodes a protein homologous to polar amino acid and opine binding proteins of gram-negative bacteria.

A gene locus abp was identified immediately upstream of the CAMP factor gene cfu in Streptococcus uberis. An open reading frame capable of coding for a 277-residue protein was identified. On the basis of sequence characteristics, the abp gene product is potentially a polar amino acid and opine binding component of an ATP-binding cassette type (ABC-type) transport system similar to those of Gram-negative bacteria. This membrane protein is likely lipid modified at its amino terminus and was present in five S. uberis strains and one Streptococcus parauberis strain examined.

Effect of combined heat, ozonation and ultraviolet irradiation (VasoCare) on heat shock protein expression by peripheral blood leukocyte populations.

The re-administration of whole blood subjected to heat, ozonation and ultraviolet irradiation (VasoCare therapy) has been shown to elicit clinical benefits in individuals with vascular disease. Given that these stressors induce heat shock protein (Hsp) expression and that heat shock protein reactivity is implicated in the pathogenesis of vascular disease, this study assessed the effect of VasoCare on intracellular expression of Hsp60 and Hsp70 by treated peripheral blood leukocytes. Contrary to expectations, VasoCare induced a significant reduction (approximately 40%) in the proportion of peripheral blood mononuclear cells expressing intracellular Hsp60 and Hsp70, whereas it had no effect on heat shock protein expression by peripheral blood neutrophils. Cell surface heat shock protein expression was not detectable. The reduced expression of Hsp60 by mononuclear cells was concomitant with an increase in the levels of Hsp60 in treated plasma. Although the mechanism underlying the clinical effectiveness of VasoCare therapy has yet to be established, it may be that re-administration of treated blood or soluble factors derived therefrom modifies in vivo immune responsiveness to heat shock proteins or associated molecules.

Treatment of severe Raynaud's syndrome by injection of autologous blood pretreated by heating, ozonation and exposure to ultraviolet light (H-O-U) therapy.

OBJECTIVE: To determine the effect of re-injection of small samples of autologous blood, pretreated with heat, ozone and ultraviolet light (H-O-U therapy) in patients with severe Raynaud's syndrome. EXPERIMENTAL DESIGN: Open trial in 4 patients. SETTING: Temperature/humidity controlled vascular laboratory. PATIENTS: Severe Raynaud's syndrome of more than 5 years duration and defined as more than 5 attacks daily or 10 attacks in one week, at least half of which were painful and lasting for more than 30 minutes. Three patients were refractory to infusions of Iloprost. INTERVENTIONS: Patients were treated daily or on alternate days for a two to three weeks period by re-injection of citrated autologous blood pre-treated with heat, ozone and ultraviolet light (H-O-U therapy). MEASURES: Clinical observations; mean equilibrated hand temperature (infrared thermography); distributive and microcirculatory blood-flow (venous occlusion strain-gauge plethysmography, infrared photoplethysmography, laser Doppler flowmetry) iontophoresis of acetylcholine and sodium nitroprusside; estimations: serum levels of 6-keto-PGF1alpha and serum levels of anti-hsp65 antibody. RESULTS: Reduction or abolition of Raynaud's attacks for at least three months after treatment. Mean equilibrated hand temperature increased but did not normalise. Blood flow parameters improved but did not reach statistical significance. Iontophoresis of acetylcholine showed an increase in laser Doppler flowmetry which was statistically significant. Serum levels of 6-keto-PGF1alpha, fell significantly in three patients. Serum levels of anti-hsp65 antibody fell in the one patient which was followed sequentially. CONCLUSIONS: H-O-U therapy may prove useful in patients with severe Raynaud's syndrome.

Effectiveness of an abdominal obesity reduction programme in men: the GutBuster "waist loss' programme.

OBJECTIVE: To examine the long term (1-2 year), as well as immediate effectiveness of a "waist loss' programme for men. DESIGN: Two preliminary studies are reported; one following a small group of 42 men over two years after a 6 week "GutBuster' course, the second following men for 1 year after having completed the initial 6 week programme (n = 83), or the initial course plus an additional six fortnightly "advanced' course (n = 37). MEASUREMENTS: Waist, hip and weight measures were reported for the 2 year group; waist and hip only in study 2. Dietary fat, exercise and alcohol intake were also recorded in study 2 through the use of questionnaires. The goal for the initial course was a 1% waist loss per week. RESULTS: All groups achieved an average waist loss > 1%/week during the initial programme. Waist sizes reported in study 1 were significantly less after 2 years (t = 8.28, p < 0.001) averaging a 6% loss in the group. This equated with an average weight loss of 5.5 kg. A repeated measures ANOVA also showed a significant main effect (F = 85.35; p < 0.0001) for waist losses and an interaction effect (F = 16.53; p < 0.0001) between initial and advanced groups after 1 year in study 2. Average waist losses were 4% and 10% respectively. There were also significant changes in dietary fat intake, exercise and alcohol consumption. CONCLUSION: Reductions in waist size in men appear to be more feasible than weight losses in women. "Waist loss' may also be a more valid measure of fat loss in men that body mass measures.

The measurement of CA 125 and placental protein 14 in uterine flushings in women with recurrent miscarriage; relation to endometrial morphology.

The concentrations of CA 125 and placental protein 14 (PP14) were measured in uterine flushings obtained throughout the luteal phase of the cycle from eight normal fertile women. The concentrations of both proteins increased in a similar pattern throughout the luteal phase of the cycle, with the most dramatic increase occurring 6 days after their luteinizing hormone surge (day LH +6). However, a greater variation in CA 125 concentrations was seen compared to that seen for PP14. The concentrations were compared to those obtained on day LH +7 of the cycle from a group (n = 35) of women with recurrent miscarriage. The ranges in concentration of PP14 and CA 125 in the flushings of fertile and recurrent miscarriage patients were very similar. However, a greater proportion of women with recurrent miscarriage (55%) had low concentrations (< 5 ng/ml) of PP14 than in the control group (12.5%) and the concentrations of PP14 in the uterine flushings were significantly less (P < 0.05) in women with recurrent miscarriage compared to the normal fertile group. There was no significant difference in the concentration of CA 125 in the uterine flushings between the two groups. Histological observation of the endometrial biopsy samples from recurrent miscarriage patients gave menstrual cycle datings that ranged from day LH +2.5 to LH +6.5 with retarded endometrium (< day LH +5) in 12 of 35 (34%) patients. Of these 12 patients, 10 (83%) had low PP14 concentrations and six (50%) had low CA 125 concentrations in their uterine flushings. In the recurrent miscarriage patients with histologically normal (> or = day LH +5) endometrial development, 10 out of 23 (43%) also had low PP14 concentrations and 8 out of 23 (35%) had low CA 125 in their uterine flushings. The results suggest that PP14 is better than CA 125 as a marker for endometrial function in this group of women. In some cases (52%) the low concentrations of PP14 in the uterine flushings could be explained by retarded endometrial development but for the others the reduction in PP14 concentration in the uterine flushing was not associated with retardation of endometrial development.

Significance of molecular marker-positive cells after autologous peripheral-blood stem-cell transplantation for non-Hodgkin's lymphoma.

PURPOSE: To evaluate the significance of molecular marker-positive cells in a cohort of non-Hodgkin's lymphoma (NHL) patients undergoing high-dose chemotherapy and autologous peripheral-blood stem-cell transplantation (PBSCT). PATIENTS AND METHODS: Twenty-eight PBSC transplants have been performed in 24 patients with poor-prognosis NHL. Molecular analysis of the t(14;18) (q32;q21) translocation (bcl-2/immunoglobulin [Ig] heavy-chain joining locus [JH] fusion) or antigen receptor gene rearrangements was performed to determine the presence of lymphoma cells at presentation, in PBSC harvests, and before and after autologous PBSCT. Kaplan-Meier estimates of survival and Cox regression analyses were used to test the effect of bone marrow involvement, tumor-cell contamination of PBSCs, disease stage, and chemotherapy sensitivity at transplantation, and presence of marker-positive cells post-PBSCT on disease-free and overall survival. RESULTS: Thirteen of 24 patients (54%) are alive following PBSCT at a median follow-up time of 654 days (range, 193 to 1,908). Nine patients are in complete remission (CR) at day 216 to 1,799 (median, 805) and four are alive following relapse (day 440, 573, 1,188, and 1,908). Eleven patients (46%) have died: three of transplant-related complications at day 0, 1, and 13, and eight of recurrent disease (day 132 to 1,330; median, 451). Longitudinal marker studies post-PBSCT showed that of 16 relapse events, 13 (81%) were positive for the lymphoma marker at or before clinically documented relapse. Marker studies became negative post-PBSCT in nine of nine patients who entered and remained in CR. Disease-free survival (DFS) was significantly shortened in patients in whom marker-positive cells were detected in serial samples posttransplantation (P = .006). Cox regression analysis showed that patients in this group had a 24 times higher risk of relapse (P = .03). CONCLUSION: The results show that the reappearance or persistence of marker-positive cells after autologous PBSCT is strongly associated with relapse.