Malignant spinal cord compression in the paediatric population-a systematic review, meta-analysis.

BACKGROUND: Malignant spinal cord compression (MSCC) has been noted in 3-5% of children with primary tumours. MSCC can be associated with permanent neurological deficits and prompt treatment is necessary. Our aim was to perform a systematic review on MSCC in children < 18 years to help formulate national guidelines. METHODS: A systematic review of the English language was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search criteria included 'MSCC in children, paediatric and metastases' for papers published between January1999 and December 2022. Isolated case reports/case series with < 10 patients were excluded. RESULTS: From a total of 17 articles identified, a final 7 were analysed (Level III/IV). Neuroblastoma constituted the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%). Soft tissue sarcomas were the most frequent cause of MSCC in children > 5 years old, while for neuroblastomas, the mean age of presentation was 20 months. The median age at time of diagnosis for the entire cohort of patients was 50.9 months (14.8-139). The median follow-up duration was 50.7 months (0.5-204). Motor deficits were the presenting symptom in 95.6% of children followed by pain in 65.4% and sphincter disturbance in 24%. There was a delay of about 26.05 days (7-600) between the onset of symptoms and diagnosis. A multimodality approach to treatment was utilised depending on the primary tumour. The prognosis for neurological recovery was found to be inversely proportional to the degree of neurological deficits and duration of symptoms in four studies. CONCLUSION: Neuroblastoma is the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%), whilst soft tissue sarcomas constituted the most frequent cause of MSCC in children > 5 years old. The majority of patients presented with motor deficit, followed by pain. In children with neuroblastoma /lymphoma, chemotherapy was the primary treatment. Early surgery should be a consideration with rapid deterioration of neurology despite chemotherapy. A multimodality approach including chemo-radiotherapy and surgery should be the treatment of choice in metastatic sarcomas. It is worth noting that multi-level laminectomy/decompression and asymmetrical radiation to the spine can lead to spinal column deformity in the future.

Malpractice litigation and spinal surgery in the National Health Service: a single tertiary-level centre perspective over 12 years.

INTRODUCTION: Medical malpractice litigation is a major concern for all spine surgeons. Our aim was to evaluate the incidence and burden of successful litigation relating to the management of spinal disorders over 12 years within a UK NHS tertiary-level spinal unit and compare these litigation costs with those of other specialties. METHODS: We obtained all data held by our claims department from its inception in January 2008 to December 2019. We also obtained costs for the total financial burden incurred by our Trust during this period. RESULTS: In total, there were 83 closed claims involving spinal pathologies. Over 80% of these comprised negligent surgery (n = 28, 34%), delay to diagnose/treat (n = 25, 30%) and negligent care (n = 18, 22%). The vast majority of claims were withdrawn without incurring any cost to the hospital (n = 59, 71%) and only 24 (29%) resulted in successful litigation for the claimant. The total cost of damages for these 24 successful claims was just over £8 million, including legal costs of £2.5 million, out of total litigation costs of £381 million over this period. DISCUSSION: Fewer than 30% of initial claims against a tertiary spinal surgical referral unit resulted in a successful financial outcome for the claimant. The total costs incurred were just over £8 million, with one-third apportioned to high legal costs, reflecting the complexity of resolving spinal litigation. Our entire legal expenses accounted for only 2% of the total legal bill paid by our hospital over a 12-year period.

Factors associated with care-seeking for low back pain when genetics and the familial environment are considered.

BACKGROUND: Low back pain (LBP) is the leading cause of disability worldwide. Care-seekers for LBP cause substantial economic burden to governments and the healthcare system. OBJECTIVE: To investigate lifestyle and health-related factors associated with care-seeking (including pain medication use) in individuals experiencing LBP, after controlling for important genetic and early environmental confounders through the use of a within-twin pair case-control design. DESIGN: A secondary analysis of observational longitudinal data, derived from the Australian Twin low BACK pain (AUTBACK) study, was performed on 66 twin pairs that presented with similar symptoms of LBP at baseline but became discordant for care-seeking behaviour over one month. METHODS: Subjective and objective assessment of pain intensity, disability, depression, sleep quality, physical activity and body mass index were performed. Data was analysed using stepwise conditional logistic regression in two stages: within-pair case-control for monozygotic and dizygotic twins together; and within-pair case-control analysis of monozygotic twins only. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Higher LBP intensity (OR 2.9; 95% CI 1.3-6.8) and poorer sleep quality (OR 10.9; 95% CI 1.5-77.7) were the main factors that increased the likelihood of care-seeking for LBP. These associations remained significant and increased in magnitude after adjusting for genetic confounding. CONCLUSIONS: Individuals with higher LBP intensity and worse sleep quality are more likely to seek care for LBP, and this relationship is likely to be causal after adjustment of familial and genetic confounding.

Head down tilt 15° in experimental intracerebral hemorrhage: a randomized noninferiority safety trial.

BACKGROUND AND PURPOSE: Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage. METHODS: Intracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized noninferiority trial design was used to assign rats to HDT15° or flat position (n = 64). HDT15° was applied for 1 h during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 h. Secondary outcomes were mass effect, mortality, and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth, and cardiorespiratory parameters in separate sets of randomized animals (n = 32). RESULTS: HDT15° achieved the specified criteria of noninferiority for hematoma volume at 24 h. Mass effect, mortality, and functional deficit at 24 h showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pretreatment values (+2.91 ± 1.76 mmHg). HDT15° had a neutral effect on MRI-based analysis of hematoma growth and cardiorespiratory parameters. CONCLUSIONS: Application of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.

Early effect of dalfampridine in patients with MS: A multi-instrumental approach to better investigate responsiveness.

BACKGROUND: 4-aminopyridine (4-AP) is a potassium-channel blocker able to enhance walking speed in MS improving the action potentials of demyelinated axons on which internodal potassium channels are exposed. OBJECTIVE: to study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools. METHODS: Clinical (Timed 25-Foot Walk - T25FW, Timed Up-And-Go - TUG), subjective (MS Walking Scale-12 - MSWS-12), neurophysiological (Motor Evoked Potentials - MEPs) and imaging (Diffusion Tensor Imaging - DTI) evaluations were performed before (T0) and after (T1) 14days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI. RESULTS: We found a significant difference between T0 and T1 for T25FW, TUG, MSWS-12 (p≤0.001) in the whole patients' sample (23 subjects, median EDSS 6.0) and decrease of Central Motor Conduction Time and increase of mean Amplitude (Amp) at T1 (p=0.008 and p=0.006). We also recorded a significant difference of T25FW, TUG, MSWS-12 and Amp in clinical responder (CR) patients (CR: amelioration >20% at T25FW). TBSS showed a significant Mean and Radial Diffusivity reduction in the corticospinal tracts (p<0.05) of the whole group of patients; this reduction was also found in the CR subgroup. CONCLUSION: Neurophysiological and neuroradiological parameters were modified in MS patients treated with 4-AP, and most of them reported a subjective improvement of their motor performances after treatment. The use of clinical, subjective, neurophysiological and neuroradiological tools could help to better explore MS patients responsiveness to 4-AP.

Oral and endotracheal tubes colonization by periodontal bacteria: a case-control ICU study.

Periodontal infection is a possible risk factor for respiratory disorders; however, no studies have assessed the colonization of periodontal pathogens in endotracheal tubes (ET). This case-control study analyzed whether periodontal pathogens are able to colonize ET of dentate and edentulous patients in intensive care units (ICU) and whether oral and ET periodontal pathogen profiles have any correlation between these patients. We selected 18 dentate and 18 edentulous patients from 78 eligible ICU patients. Oral clinical examination including probing depth, clinical attachment level, gingival index , and plaque index was performed by a single examiner, followed by oral and ET sampling and processing by quantitative polymerase chain reaction (total bacterial load, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia). Data were statistically analyzed by Mann-Whitney U, two-way analysis of variance (p < 0.05). Among dentate, there was no correlation between clinical parameters and ET bacterial levels. Both dentate and edentulous patients showed similar ET bacterial levels. Dentate patients showed no correlation between oral and ET bacterial levels, while edentulous patients showed positive correlations between oral and ET levels of A. actinomycetemcomitans, P. gingivalis, and T. forsythia. Periodontal pathogens can colonize ET and the oral cavity of ICU patients. Periodontal pathogen profiles tend to be similar between dentate and edentulous ICU patients. In ICU patients, oral cavity represents a source of ET contamination. Although accompanied by higher oral bacterial levels, teeth do not seem to influence ET bacterial profiles.

Presence of Mycobacterium leprae DNA and PGL-1 antigen in household contacts of leprosy patients from a hyperendemic area in Brazil.

Leprosy is a highly infectious disease endemic to underdeveloped countries. In Maranhão State, Northeastern Brazil, the hyperendemic rate of 56.11 cases/100,000 inhabitants increased the necessity of better understanding the epidemiological profile of this population, particularly regarding efficient methods for evaluating individuals residing with diagnosed patients to understand disease transmission and the risk of infection. In this study, we examined the percentage of contacts with positive indices for Mycobacterium leprae DNA and phenol-glycolipid-1 antigen (PGL-1). PGL-1 was analyzed by an enzyme-linked immunosorbent assay, the ML-Flow test, and polymerase chain reaction of oral and nasal secretions of 808 leprosy contacts from Maranhão. PGL-1 was detected in 14.0% of patients and differed by operational classification of the index case (P < 0.05). Seropositive results of ML-Flow were 15.0% and identified individuals with and without Bacillus Calmette-Guérin vaccine scars. Molecular diagnosis detected M. leprae DNA in 5.6% of oral samples and 4.6% of nasal tissues, and 87% of subjects resided with high bacillary load patients. This study reinforces the efficacy of combining molecular and serological techniques to identify potential bacillus carriers in the asymptomatic stage of infection, such as in household contacts, highlighting the importance of these meth-ods for monitoring hyperendemic populations.

Aggregatibacter actinomycetemcomitans serotypes infections and periodontal conditions: a two-way assessment.

This study investigated a large population of individuals positive for A. actinomycetemcomitans and performed a two way analysis assessing the relation between the different serotypes of the bacterium and periodontal conditions. The serotypes analysis (serotypes a, b, c, d, e, f) showed that out of the 204 selected individuals positive for A. actinomycetemcomitans, 152 were positive for a single serotype, 27 showed a variable mixed infection and 25 individuals were not positive for any of the serotypes tested. Serotypes a, b and c were largely found (98%), and serotype c was the most prevalent. Serotypes d, e, and f were either not detected or relatively rare. It was also verified that in non-periodontitis individuals, serotypes a and c were more prevalent (p<0.05); in individuals with mild or moderate/severe chronic periodontitis serotype c was also more common (p<0.05); and aggressive periodontitis subjects showed high prevalence of both serotypes b and c (p<0.05). In conclusion, our study showed that serotype c was the most prevalent in both diseased and healthy subjects. Aggressive periodontitis subjects were not exclusively associated with A. actinomycetemcomitans serotype b. Non-typeable strains were either not detected or were relatively infrequent, and serotypes d and f were not detected in the examined Brazilian population.

Oscillatory shear response of dilute ferrofluids: predictions from rotational Brownian dynamics simulations and ferrohydrodynamics modeling.

Ferrofluids are colloidal suspensions of magnetic nanoparticles that exhibit normal liquid behavior in the absence of magnetic fields but respond to imposed magnetic fields by changing their viscosity without loss of fluidity. The response of ferrofluids to constant shear and magnetic fields has received a lot of attention, but the response of ferrofluids to oscillatory shear remains largely unexplored. In the present work we used rotational Brownian dynamics to study the dynamic properties of ferrofluids with thermally blocked nanoparticles under oscillatory shear and constant magnetic fields. Comparisons between simulations and modeling using the ferrohydrodynamics equations were also made. Simulation results show that, for small rotational Péclet number, the in-phase and out-of-phase components of the complex viscosity depend on the magnitude of the magnetic field and frequency of the shear, following a Maxwell-like model with field-dependent viscosity and characteristic time equal to the field-dependent transverse magnetic relaxation time of the nanoparticles. Comparison between simulations and the numerical solution of the ferrohydrodynamic equations shows that the oscillatory rotational magnetoviscosity for an oscillating shear field obtained using the kinetic magnetization relaxation equation quantitatively agrees with simulations for a wide range of Péclet number and Langevin parameter but has quantitative deviations from the simulations at high values of the Langevin parameter. These predictions indicate an apparent elastic character to the rheology of these suspensions, even though we are considering the infinitely dilute limit in which there are negligible particle-particle interactions and, as such, chains do not form. Additionally, an asymptotic analytical solution of the ferrohydrodynamics equations, valid for Pe<<2, was used to demonstrate that the Cox-Merz rule applies for dilute ferrofluids under conditions of small shear rates. At higher shear rates the Cox-Merz rule ceases to apply.

Natural incidence of egg parasitoids of Edessa meditabunda (F.) (Hemiptera: Pentatomidae) on Crotalaria spectabilis in Campo Novo do Parecis, MT, Brazil.

Egg parasitoids of the stink bug Edessa meditabunda (F) were studied on rattlepod Crotalaria spectabilis used in soybean crop rotation in Campo Novo do Parecis, Mato Grosso state, central western Brazil. Seven species of parasitoids were found: two Encyrtidae, one Eurytomidae, and four Platygastridae. The occurrence of Trissolcus euchisti (Ashmead) and Trissolcus elimatus Johnson (Platygastridae) on eggs of E. meditabunda is recorded for the first time. Moreover, this is the first record of T. elimatus and T. euchisti from Brazil.

Basal forebrain involvement in low-functioning autistic children: a voxel-based morphometry study.

BACKGROUND AND PURPOSE: Imaging studies have revealed brain abnormalities in the regions involved in functions impaired in ASD (social relations, verbal and nonverbal communication, and adaptive behavior). We performed a VBM whole-brain analysis to assess the areas involved in autistic children with DD. MATERIALS AND METHODS: Twenty-one developmentally delayed children with ASD (aged 3-10 years) were compared with 21 controls matched for age, sex, and sociocultural background. All ASD cases had been diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, with the Autism Diagnostic Observation Schedule-Generic, and the Autism Diagnostic Interview-Revised. The VBM data, covaried with intelligence quotient, age, and brain volume, were analyzed. RESULTS: ASD patients showed a pattern of regional GM reduction symmetrically affecting the basal forebrain, accumbens nucleus, cerebellar hemispheres, and perisylvian regions, including insula and putamen. Asymmetric involvement of GM was observed in other brain regions functionally connected to the basal forebrain, ie, an area located close to the medial and ventral surface of the frontal lobe. No regional WM differences were observed between the 2 groups. No significant differences between patients and controls were found regarding total brain volume, GM, and WM. CONCLUSIONS: In children with ASD and DD, the novel finding of our VBM study was the demonstration of reduced GM volume in the basal forebrain and the areas connected with it. This system is involved in social behavior, communication, and cognitive skills. Whether the involvement of the basal forebrain is characteristic of ASD or is related to the DD present in our patients needs further investigation.

Prevalence of periodontopathogens in a black Brazilian secluded community matched with a black urban population.

OBJECTIVE: To evaluate the prevalence of periodontopathogens according to periodontal profile in a black Brazilian secluded community matched with an urban black population. PARTICIPANTS: A total of 84 subjects were selected, 42 (mean age 25.7 sd 18.0 years) from a secluded community called Santo Antonio do Guapore (SAG) and 42 (mean age 25.4 sd 18.1 years) from an urban area of Sao Paulo State (SPT). METHODS: Participants received clinical examinations as follows: periodontal pocket depth; clinical attachment loss; plaque and gingival indexes. After examination, the secluded population was classified as periodontal health (13), gingivitis (15) or periodontitis (14). Then, 182 urban volunteers were screened and 42 subjects were selected matched for the variables: periodontal diagnosis, age (+/- 2 years) and gender. Samples were taken for microbial analysis. Genomic DNA for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Tannerella forsythia and Prevotella intermedia was provided by polymerase chain reaction. RESULTS: Except for C. rectus, all pathogens were present in both groups with no statistically significant difference. In particular, C. rectus was more prevalent only in gingivitis subjects from the SPT group (p<0.05). A high frequency of periodontopathogens was related to the severity of periodontal disease. CONCLUSION: In general, the prevalence of the examined periodontopathogens in this study did not differ between a secluded black Brazilian population and an urban black population.

Abnormal ERD/ERS but unaffected BOLD response in patients with Unverricht-Lundborg disease during index extension: a simultaneous EEG-fMRI study.

Electrophysiological studies indicate that Unverricht-Lundborg's disease (ULD), the most common form of progressive myoclonus epilepsy in Europe, is characterized by the involvement of multiple cortical regions in degenerative changes that lead to enhanced excitation and deficient inhibition. We searched for the haemodynamic correlates of these effects using functional MRI (fMRI) of self-paced index extensions, a well-accepted task highlighting significant differences. EEG and fMRI were simultaneously acquired in 11 ULD patients and 16 controls, performing the index extensions individually (event-related task) as well as repetitively (block task). ERD/ERS analysis was performed for the EEG data in the alpha and beta bands. fMRI time-series were analyzed using the traditional general linear model, as well as with an assumption-free approach, and by means of cross-region correlations representing functional connectivity. In line with the existing literature, ULD patients had enhanced desynchronization in the alpha band and reduced post-movement synchronization in the beta band. By contrast, fMRI did not reveal any difference between the two groups; there were no activation intensity, latency or extent effects, no significant engagement of additional regions, and no changes to functional connectivity. We conclude that, so long as the patients are executing a task which does not induce obvious action myoclonus, the hypothesized abnormalities in pyramidal neuron and interneuron dynamics are relatively subtle, embodied in processes which are not metabolically-demanding and take place at a time-scale invisible to fMRI.

Magnetoviscosity in dilute ferrofluids from rotational brownian dynamics simulations.

Ferrofluids are suspensions of magnetic nanoparticles which respond to imposed magnetic fields by changing their viscosity without losing their fluidity. Prior work on modeling the behavior of ferrofluids has focused on using phenomenological suspension-scale continuum equations. A disadvantage of this approach is the controversy surrounding the equation describing the rate of change of the ferrofluid magnetization, the so-called magnetization relaxation equation. In this contribution the viscosity of dilute suspensions of spherical magnetic nanoparticles suspended in a Newtonian fluid and under applied shear and constant magnetic fields is studied through rotational brownian dynamics simulations. Simulation results are compared with the predictions of suspension-scale models based on three magnetization relaxation equations. Excellent agreement is observed between simulation results and the predictions of an equation due to Martsenyuk, Raikher, and Shliomis. Good qualitative agreement is observed with predictions of other equations, although these models fail to accurately predict the magnitude and shear rate dependence of the magnetic-field-dependent effective viscosity. Finally, simulation results over a wide range of conditions are collapsed into master curves using a Mason number defined based on the balance of hydrodynamic and magnetic torques.

Decreased diffusivity in the caudate nucleus of presymptomatic huntington disease gene carriers: which explanation?

BACKGROUND AND PURPOSE: The neostriatum is known to be affected in HD. In this work, our aim was to determine whether microstructural and volumetric alterations occur in the neostriatum of presymptomatic HD gene carriers and in patients with early-stage HD. MATERIALS AND METHODS: We studied a group of 15 presymptomatic gene carriers who were far from the estimated symptom onset (16% probability of developing the disease within 5 years), a group of 9 patients with early symptomatic HD, and 2 groups of age-matched controls. Volumetric MR imaging and DWIs were acquired, and statistical analyses were performed on the volumes of the caudate nucleus and putamen and on the corresponding MD measurements. RESULTS: Neostriatal volumes were significantly smaller in both presymptomatic HD gene carriers and symptomatic patients with respect to controls. However, whereas the diffusivity in the caudate nucleus was increased in the symptomatic patients, it was decreased in the presymptomatic gene carriers. CONCLUSIONS: Altered diffusivity and reduced volume of the caudate nucleus in presymptomatic HD gene carriers indicate that the neostriatum is affected well before the onset of symptoms. The observed initial decrease and subsequent increase of MD might be related to the combined effect of increased oligodendroglial population, putatively a developmental abnormality, and incipient neurodegeneration.

Smoking increases salivary arginase activity in patients with dental implants.

It is believed that an increased arginase activity may lead to less nitric oxide production, which consequently increases the susceptibility to bacterial infection. Considering the hypothesis that smoking may alter the arginase activity and that smoking is considered a risk factor to dental implant survival, the present study aimed at evaluating the effect of smoking on the salivary arginase activity of patients with dental implants. Salivary samples of 41 subjects were collected: ten non-smoking and with no dental implants (group A), ten non-smoking subjects with dental implants (group B), ten smoking subjects with implants (group C), and 11 smoking subjects with no dental implants (group D). The levels of salivary arginase activity were determined by the measurement of L-ornithine and expressed as mIU/mg of protein. A significant increase in the salivary arginase activity was verified in groups C (64.26 +/- 16.95) and D (49.55 +/- 10.01) compared to groups A (10.04 +/- 1.95, p = 0.00001 and p = 0.0110, groups C and D, respectively) and B (11.77 +/- 1.45, p = 0.00001 and p = 0.0147, groups C and D, respectively). No significant difference was found between groups C and D (p = 0.32). Within the limits of the present study, it can be concluded that salivary arginase activity is increased in smoking subjects with dental implants in contrast to non-smoking subjects with dental implants, therefore suggesting a possible mechanism by which cigarette smoking may lead to implant failure. The analysis of salivary arginase activity may represent an important tool to prevent implant failure in the near future.

Concentração alveolar mínima do isoflurano associado ou não ao óxido nitroso durante a maturação pós-natal em cães. Resultados preliminares

O artigo não apresenta resumo.

Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins.

The anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) immunotoxins (ITs) are murine IgG(1) monoclonal antibodies (Mabs) conjugated to a deglycosylated ricin A chain (dgRTA). They are effective in killing B-lineage non-Hodgkin's lymphoma (NHL) cells in vitro, in vivo and in adult patients with B-lineage NHL. The potential of these agents for the treatment of childhood B-precursor acute lymphoblastic leukemia (ALL) is unknown. The anti-CD19 and anti-CD22 ITs should have anti-tumor activity against childhood B-lineage ALL since both target antigens are expressed on the surface of these cells. We have previously shown that, in vitro these two ITs selectively kill leukemia cells obtained from children with leukemia. To evaluate the efficacy of our ITs in an in vivo model we injected the human pre-B ALL cell line, NALM-6-UM1, into severe combined immunodeficient (SCID) mice. We tested the ability of two ITs to prolong survival or cure mice of both early and advanced tumors. In early disease, treatment with HD37-dgRTA, RFB4-dgRTA, or Combotox (an equimolar concentration of the two ITs) significantly improved their survival. In advanced disease, treatment with RFB4-dgRTA or Combotox significantly improved survival. Overall there were 10 long-term survivors who were cured, as determined by survival beyond 150 days with no evidence of disease as determined by polymerase chain reaction (PCR) analysis.

Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry.

Bone marrow hematogones (B-lymphocyte precursors) may cause problems in diagnosis because of their morphologic and immunophenotypic similarities to neoplastic lymphoblasts. The purposes of this prospective, multiparametric flow cytometry study were to quantify hematogones across age groups and a spectrum of clinical conditions, to identify factors that affect the relative quantity of hematogones, and to compare their immunophenotype with that of neoplastic lymphoblasts. A total of 662 consecutive marrow specimens were analyzed for hematogones using one of two 4-color antibody combinations; hematogones were identified in 528 (79.8%). There was a significant decline in hematogones with increasing age (P <.001), but a broad range was found at all ages and many adults had a relatively high number. Specimens processed by density gradient had a higher mean percent hematogones than those processed by erythrocyte lysis (P <.001). There was a direct decline in hematogones with increasing marrow involvement with neoplastic cells. A total of 8% of the 662 specimens contained 5% or more hematogones: 24.6% of specimens from patients aged less than 16 years and 6.3% from those 16 and older (P <.000 01). Increased hematogones were observed most often in patients with lymphoma, marrow regenerative states, immune cytopenias, and acquired immunodeficiency syndrome. Hematogones always exhibited a typical complex spectrum of antigen expression that defines the normal antigenic evolution of B-cell precursors and lacked aberrant expression. In contrast, lymphoblasts in 49 cases of precursor B-ALL showed maturation arrest and exhibited 1 to 11 immunophenotypic aberrancies. Four-color flow cytometry with optimal combinations of antibodies consistently distinguishes between hematogones and neoplastic lymphoblasts.