Effect of trunk exercise upon lumbar IVD height and vertebral compliance when performed supine with 1 g at the CoM compared to upright in 1 g.

BACKGROUND: Spinal unloading in microgravity is associated with stature increments, back pain, intervertebral disc (IVD) swelling and impaired spinal kinematics. The aim of this study was to determine the effect of lateral stabilization, trunk rotation and isometric abdominal exercise upon lumbar IVD height, and both passive and active vertebral compliance when performed supine on a short-arm human centrifuge (SAHC)-a candidate microgravity countermeasure-with 1 g at the CoM, compared to that generated with equivalent upright exercise in 1 g. METHODS: 12 (8 male) healthy subjects (33.8 ± 7 years, 178.4 ± 8.2 cm, 72.1 ± 9.6 kg) gave written informed consent. Subjects performed three sets of upper body trunk exercises either when standing upright (UPRIGHT), or when being spun on the SAHC. Lumbar IVD height and vertebral compliance (active and passive) were evaluated prior to SAHC (PRE SAHC) and following the first SAHC (POST SPIN 1) and second Spin (POST SPIN 2), in addition to before (PRE UPRIGHT), and after upright trunk exercises (POST UPRIGHT). RESULTS: No significant effect upon IVD height (L2-S1) when performed UPRIGHT or on the SAHC was observed. Trunk muscle exercise induced significant (p < 0.05) reduction of active thoracic vertebral compliance when performed on the SAHC, but not UPRIGHT. However, no effect was observed in the cervical, lumbar or across the entire vertebral column. On passive or active vertebral compliance. CONCLUSION: This study, the first of its kind demonstrates that trunk exercise were feasible and tolerable. Whilst trunk muscle exercise appears to have minor effect upon IVD height, it may be a candidate approach to mitigate-particularly active-vertebral stability on Earth, and in µg via concurrent SAHC. However, significant variability suggests larger studies including optimization of trunk exercise and SAHC prescription with MRI are warranted. TRIAL REGISTRATION: North Rhine ethical committee (Number: 6000223393) and registered on 29/09/2020 in the German Clinical Trials Register (DRKS00021750).

Spring-loaded body mass equivalent horizontal reactive countermovement jump ground contact and flight times, but not peak forces, are comparable to vertical jumping.

Horizontal (cylinder-based) sledge jumping has been shown to ameliorate multi-system deconditioning induced by long-term bed-rest. However, biomechanics differ from 1 g vertical jumping, in particular prolongation of ground contact times (GCT), reduction of peak force, rate of force development (RFD) (and presumably stretch shortening cycle [SSC] efficacy) and stiffness, whilst also requiring relatively complex equipment. Thus, we sought to determine if horizontal spring-loaded countermovement jumps were more analogous to vertical jumping. 9 healthy (5 female) subjects (27 ± 7yrs; 169.0 ± 5.3 cm; 63.6 ± 2.6 kg) performed 10 reactive countermovement jumps vertically, and horizontally (randomized) when lay on a spring-loaded carriage performed against loading (at lift-off) equivalent (±6%) to their body weight. Jump kinetics, kinematics and lower limb/trunk electromyographic activity were compared between conditions (paired t-tests). Mean flight and GCTs did not differ, however, peak jump height (p = 0.003; d = -0.961) was greater when jumping horizontally. In contrast, ground reaction forces (zGRF) during take-off (p < 0.001; d = 1.645) and landing (p = 0.002; d = 1.309), peak acceleration (p = 0.001; d = 1.988), leg stiffness (p = 0.001; d = 2.371) and RFD (p = 0.023; d = 1.255) were lower horizontally. Mean rectus femoris activity was lower during landing (p = 0.033; d = 0.691) when horizontal, but did not differ during either take-off or land-lift. Mean medial gastrocnemius activity was significantly (p = 0.018; d = 0.317) lower during horizontal take-off. Spring-loading (1 g at take-off) maintained short GCTs and flight times presumably maintaining muscle SSC efficacy in a manner that appears intuitive (in young active subjects), simple, robust and potentially compatible with spaceflight. Whether appropriate jump characteristics can be achieved in older subjects and in µg/hypogravity needs to be determined. However, greater jump height, lower peak zGRF, RFD and leg stiffness along with reduced lower limb and trunk muscle activity suggests that 1 g at take-off is insufficient to replicate vertical jump biomechanics. Thus, further investigation is warranted to optimize, and evaluate spring-loaded jumping as a gravity-independent multi-systems countermeasure on Earth, and in Space.

Detection of multiple hypervirulent Klebsiella pneumoniae strains in a New York City hospital through screening of virulence genes.

OBJECTIVES: The 'hypervirulent' variant of Klebsiella pneumoniae (hvKp) is a predominant cause of community-acquired pyogenic liver abscess in Asia, and is an emerging pathogen in Western countries. hvKp infections have demonstrated 'metastatic' dissemination in immunocompetent hosts, an unusual mode of infection associated with severe complications. Two cases alerted us to the possible presence of hvKp at our hospital, both involving elderly Hispanic males who presented with recurrent fever, bacteraemia, epigastric pain and liver abscesses/phlegmon, thus prompting an assessment of hvKp prevalence. METHODS: A surveillance of K. pneumoniae blood, body fluid and wound isolates was conducted using real-time PCR to detect virulence-associated genes (uni-rmpA, iucA and peg344). Positive isolates were further characterized by wzi gene sequencing to determine capsular types (K-type) and by multilocus sequence typing and pulsed-field gel electrophoresis to determine strain relatedness. RESULTS: Four-hundred and sixty-three K. pneumoniae isolates, derived from 412 blood, 21 body fluids and 30 abdominal wound specimens, were screened over a 3-year period. Isolates included 98 multidrug-resistant strains. Eighteen isolates from 17 patients, including two from the index patient, screened positive for all three virulence genes. Sixteen of 18 positive isolates had K-types associated with hvKp, and isolates from different patients were unrelated strains, indicating likely community acquisition. Of 13 patients with significant morbidity, five died; eight patients had co-existing hepatobiliary disease, and six had diabetes mellitus. CONCLUSIONS: Multiple strains of hvKp are emerging in New York City and are associated with high mortality relative to multidrug-resistant and classical Klebsiella infections. Co-existing hepatobiliary disease appears to be a potential risk factor for these infections.

MR Angiographic-Guided Percutaneous Sclerotherapy for Venous Vascular Malformations: A Radiation Dose-Reduction Strategy.

We present a new technique using MRA instead of the usual DSA to provide guidance in the treatment of venous vascular malformations. When one performs this embolization procedure, appropriate needle positioning within the malformation must be confirmed before injection of the sclerosing agent to prevent untoward complications. Time-resolved imaging of contrast kinetics-MRA can accurately depict the angioarchitecture of the lesion, which substantially reduces the total radiation dose in these patients who are commonly in the pediatric age group and usually require numerous treatment episodes.

Wide-pulse electrical stimulation to an intrinsic foot muscle induces acute functional changes in forefoot-rearfoot coupling behaviour during walking.

Interventions for strengthening intrinsic foot muscles may be beneficial for rehabilitation from overuse injuries. In this study the acute effects of high-frequency, low-intensity wide-pulse electrical stimulation (WPS) over an intrinsic muscle on subsequent foot function during walking was assessed in healthy participants. WPS was delivered to the m. abductor hallucis (m.AH) of the non-dominant foot during relaxed standing. 3-dimensional forefoot (FF)--rearfoot (RF) coordination was quantified with a vector coding technique within separate periods of the stance phase to study WPS functional effects on foot motion. 4 types of coordinative strategies between the FF and RF were interpreted and compared PRE-to-POST-WPS for both the experimental and control feet. Bilateral electromyography (EMG) from m.AH was analysed during the intervention period for evidence of acute neuromuscular adaptation. The results showed that WPS significantly modulated FF-RF coordination during mid-stance, indicative of a more stable foot. Specifically, a statistically significant increase in FF eversion with concomitant RF inversion in the frontal plane and RF-dominated adduction in the transverse plane was observed. Subject-specific increases in post-stimulus m.AH EMG activation were observed but this was not reflected in an overall group effect. It is concluded that the structural integrity of the foot during walking is enhanced following an acute session of WPS and that this mechanical effect is most likely due to stimulation induced post-tetanic potentiation of synaptic transmission.

Risk stratification of pT1-3N0 patients after radical cystectomy for adjuvant chemotherapy counselling.

BACKGROUND: In pT1-T3N0 urothelial carcinoma of the bladder (UCB) patients, multi-modal therapy is inconsistently recommended. The aim of the study was to develop a prognostic tool to help decision-making regarding adjuvant therapy. METHODS: We included 2145 patients with pT1-3N0 UCB after radical cystectomy (RC), naive of neoadjuvant or adjuvant therapy. The cohort was randomly split into development cohort based on the US patients (n=1067) and validation cohort based on the Europe patients (n=1078). Predictive accuracy was quantified using the concordance index. RESULTS: With a median follow-up of 45 months, 5-year recurrence-free and cancer-specific survival estimates were 68% and 73%, respectively. pT-stage, ge, lymphovascular invasion, and positive margin were significantly associated with both disease recurrence and cancer-specific mortality (P-values ≤ 0.005). The accuracies of the multivariable models at 2, 5, and 7 years for predicting disease recurrence were 67.4%, 65%, and 64.4%, respectively. Accuracies at 2, 5, and 7 years for predicting cancer-specific mortality were 69.3%, 66.4%, and 65.5%, respectively. We developed competing-risk, conditional probability nomograms. External validation revealed minor overestimation. CONCLUSION: Despite RC, a significant number of patients with pT1-3N0 UCB experience disease recurrence and ultimately die of UCB. We developed and externally validated competing-risk, conditional probability post-RC nomograms for prediction of disease recurrence and cancer-specific mortality.

What does autonomic arousal tell us about locomotor learning?

Walking onto a stationary sled previously experienced as moving induces locomotor aftereffects (LAE, or "broken escalator phenomenon"). This particular form of aftereffect can develop after a single adaptation trial and occurs despite subjects being fully aware that the sled will not move. Here, we investigate whether such strong LAE expression may relate to arousal or fear related to instability during the gait adaptation process. Forty healthy subjects were allocated to three sled velocity groups; SLOW (0.6 m/s), MEDIUM (1.3 m/s), or FAST (2.0 m/s). Subjects walked onto the stationary sled for five trials (BEFORE), then onto the moving sled for 15 trials (adaptation or MOVING trials) and, finally, again onto the stationary sled for five trials (AFTER). Explicit warning regarding sled status was given. Trunk position, foot-sled contact timing, autonomic markers (electrodermal activity [EDA], ECG, respiratory movements) in addition to self-reported task-related confidence and state/trait anxiety were recorded. Trunk sway, EDA, and R-R interval shortening were greatest during the first MOVING trial (MOVING_1), progressively attenuating during subsequent MOVING trials. A LAE, recorded as increased gait velocity and trunk sway during AFTER_1, occurred in both MEDIUM and FAST sled velocity groups. The amplitude of forward trunk sway in AFTER_1 (an indicator of aftereffect magnitude) was related to EDA during the final adaptation trial (MOVING_15). AFTER_1 gait velocity (also an indicator of aftereffect magnitude) was related to MOVING_1 trunk sway. Hence, gait velocity and trunk sway components of the LAE are differentially related to kinematic and autonomic parameters during the early and late adaptation phase. The finding that EDA is a predictor of LAE expression indicates that autonomic arousal or fear-based mechanisms can promote locomotor learning. This could in turn explain some unusual characteristics of this LAE, namely its resistance to explicit knowledge and its generation with just a single adaptation trial.

Depersonalisation/derealisation symptoms and updating orientation in patients with vestibular disease.

BACKGROUND: Patients with vestibular disease have an increased rate of reporting symptoms of depersonalisation/derealisation (DD) and similar symptoms can be provoked in healthy subjects during caloric vestibular stimulation. OBJECTIVE: To assess the relationship between DD symptoms in patients with peripheral vestibular disease and their ability to update orientation in the environment. METHODS: Sixty healthy subjects and 50 patients with peripheral vestibular disease completed a DD questionnaire (Cox and Swinson, 2002) and a General Health Questionnaire (GHQ)-12 (Goldberg and Williams, 1988). This was followed by a test of updating spatial orientation in which subjects were exposed to 10 manually driven whole body rotations of 45 degrees, 90 degrees or 135 degrees in a square room, which contained distinctive features on the walls, in such a way that the features and corners subtended 45 degrees with respect to the subject. After each rotation subjects reported which wall or corner they were facing. Estimation error was calculated by subtracting the reported rotation from the actual rotation. RESULTS: DD scores were significantly higher in vestibular patients than in healthy subjects (p<0.05, t test). In patients, the lowest symptom scores and the lowest estimation errors were found in those with a unilateral canal paresis without balance symptoms whereas the highest scores and largest estimation errors were found in those with bilateral vestibular loss (p<0.05, ANOVA). Across all patients, DD scores were related to estimation errors (adjusted r2 = 0.25, p<0.05, ANCOVA). CONCLUSIONS: Patients with peripheral vestibular disease have a deficit in the ability to update orientation on the environment and a high prevalence of DD symptoms, which may imply a high order effect of the vestibular impairment. Derealisation symptoms in vestibular disease may be a consequence of a sensory mismatch between disordered vestibular input and other sensory signals of orientation.

Mineral dust exposure in young Indian adults: an effect on lung growth?

BACKGROUND/OBJECTIVE: Long-term occupational exposure to mineral dusts including quartz is known to cause pneumoconiosis but little is known about the effects of such exposure during the period of lung development in childhood. The objective of this study was to investigate the effects on young people of exposure to mineral dusts. METHODS: We carried out a cross-sectional study of a group of 81 Indian stone crushers (average age 21) and a control group of 72 nearby slum dwellers (average age 21) in order to assess dust exposures, respiratory symptoms and lung function. RESULTS: Stone crushers' corrected 8-hour time weighted average concentrations of total inhalable dust, respirable dust and respirable crystalline silica were 143 mg/m(3), 39.7 mg/m(3) and 2.29 mg/m(3) respectively, which are 14, 10 and 23 times the UK workplace exposure limits, respectively. Both groups also had high exposures to outdoor and general domestic particulate matter. Compared to controls, stone crushers had significantly more symptoms, lower levels of forced vital capacity (FVC) and forced expiratory time (FET) and higher levels of forced expiratory volume in one second (FEV(1))/FVC ratio and mid-expiratory flow rate (MEF). There were no differences in FEV(1) levels. Symptoms and lung function were not associated with time lived on site or time spent in job. A selection of chest radiographs showed no silicosis by International Labour Office (ILO) criteria. CONCLUSION: Individuals exposed to mixed mineral dust in childhood and early adult life had excess symptoms and reduced vital capacity without airflow obstruction compared with control subjects. We interpret this as evidence of stunting of lung growth caused by exposure to respirable dust.

Exposure to particulate matter on an Indian stone-crushing site.

BACKGROUND/OBJECTIVES: A large number of labourers work in the stone-crushing industry in India. Many of these workers are also exposed to high levels of particulate matter in their homes from the use of biomass fuels. As part of our investigations to examine the health of these workers we characterised their exposure to respirable crystalline silica and a number of other particulate matter exposure metrics in both occupational and domestic settings. METHODS: We used a combination of direct reading and gravimetric sampling of respirable dust, total inhalable dust and particulate matter <2.5 mum in diameter (PM(2.5)) at work (n = 19), within the general environment (n = 6) and inside the home (n = 7). We used x-ray diffraction to quantify the level of crystalline silica in the respirable dust samples. RESULTS: After correcting for the length of the working week, the arithmetic mean 8-hour time-weighted average (TWA) total inhalable dust exposure for this group was 143 mg/m(3), the mean 8-hour TWA respirable dust exposure was 39.7 mg/m(3) and the 8-hour TWA crystalline silica exposure was 2.29 mg/m(3). Our real-time data showed peaks in exposure under certain environmental and/or working conditions. General environmental and domestic PM(2.5) exposures were also high. CONCLUSIONS: Particulate matter exposures experienced by this group of workers and their families are likely to produce impaired lung function within a short time-frame. There is a need to introduce simple measures to reduce particulate matter exposure from both occupational sources and the use of biomass fuels in homes on this and similar sites.

Care centre visits to married people living with HIV: an indicator for measuring AIDS-related stigma & discrimination.

We tested whether observation of the presence and relationship of attendants (i.e. those that accompany upon admission) and visitors to a sample of 230 (128 male, 102 female) married HIV-positive people in an HIV care centre provides an indicator of caregiving, AIDS-related stigma and discrimination. Sensitivity to gender, location (urban vs. rural), age (<35 yrs vs. >35) and source of infection (spouse vs. non-spouse) were factors considered to modulate AIDS-related stigma and assess discrimination. HIV-positive people were accompanied by their spouse (53%), mother (14%), father (7%), with only 7% attending alone. Immediate family most commonly accompanied on admission (80%), but visitors were mainly from the 'extended' family (32%) with many receiving no visitors (48%). Females (11%) were more likely than males to attend alone (11% vs. 4%; p<0.05). No effect of location, age or infector was obtained. Females were more likely to be visited by their mother (14% vs. 6%; p<0.01) and non-immediate family (39% vs. 27%; p<0.05) than males were. In contrast, fathers (0% vs. 6%; p <0.05) and spouses were less likely (3% vs. 10%; p<0.05) to visit females than males. No effect of location or age upon visitation was obtained. Non-spouse infected persons were less likely than spouse-infected to be visited by their spouse (3% vs. 10%; p<0.05) but more likely to receive 'extended' family visitation (43% vs. 24%; p<0.01). Spouse-infected persons had a higher rate of no visitors than persons not infected by their spouse (54% vs. 40%; p<0.05). Observation of the presence and relationship of attendants and visitors to HIV-positive people has potential as an indicator of caregiving AIDS-related stigma and discrimination. The measure appears particularly sensitive to the gender of the HIV-positive person. Such a measure may aid healthcare professionals to focus resources such as relational counselling upon the family and close friends of people experiencing AIDS-related stigma and discrimination, with the aim of improving the provision of care within the community.

Audit of nurse-led-training for epipen in a District General Hospital.

BACKGROUND: A community-based study in the London Borough of Hounslow, which included patients in our District General Hospital (DGH) Paediatric Department, found that most families who had been prescribed adrenaline auto-injectors could not use them properly. This prompted the establishment of a new protocol for doctors and an Allergy Clinic where one nurse was responsible for training all patients. AIM: This audit was done to reassess this service 3 years after the changes were made. METHODS: 68 of the 81 (83%) patients followed up in our District General Hospital Nurse led Allergy Clinic agreed to participate. They were compared with the District General Hospital sub-group of the previous study. RESULTS: We found that most patients now reported they were trained to use the devise, had written instructions, were able to demonstrate competence on a dummy and would appropriately call an ambulance. This was significantly better than the previous situation. CONCLUSION: The study shows that training can be improved in a DGH setting with the strategy of protocolised prescribing and a Nurse led Allergy Clinic.

Depersonalisation/derealisation symptoms in vestibular disease.

BACKGROUND: Depersonalisation is a subjective experience of unreality and detachment from the self often accompanied by derealisation; the experience of the external world appearing to be strange or unreal. Feelings of unreality can be evoked by disorienting vestibular stimulation. OBJECTIVE: To identify the prevalence of depersonalisation/derealisation symptoms in patients with peripheral vestibular disease and experimentally to induce these symptoms by vestibular stimulation. METHODS: 121 healthy subjects and 50 patients with peripheral vestibular disease participated in the study. For comparison with the patients a subgroup of 50 age matched healthy subjects was delineated. All completed (1) an in-house health screening questionnaire; (2) the General Health Questionnaire (GHQ-12); (3) the 28-item depersonalisation/derealisation inventory of Cox and Swinson (2002). Experimental verification of "vestibular induced" depersonalisation/derealisation was assessed in 20 patients and 20 controls during caloric irrigation of the labyrinths. RESULTS: The frequency and severity of symptoms in vestibular patients was significantly higher than in controls. In controls the most common experiences were of "déjà vu" and "difficulty in concentrating/attending". In contrast, apart from dizziness, patients most frequently reported derealisation symptoms of "feel as if walking on shifting ground", "body feels strange/not being in control of self", and "feel 'spacey' or 'spaced out'". Items permitted discrimination between healthy subjects and vestibular patients in 92% of the cases. Apart from dizziness, caloric stimulation induced depersonalisation/derealisation symptoms which healthy subjects denied ever experiencing before, while patients reported that the symptoms were similar to those encountered during their disease. CONCLUSIONS: Depersonalisation/derealisation symptoms are both different in quality and more frequent under conditions of non-physiological vestibular stimulation. In vestibular disease, frequent experiences of derealisation may occur because distorted vestibular signals mismatch with the other sensory input to create an incoherent frame of spatial reference which makes the patient feel he or she is detached or separated from the world.

Neonatal hypothermia detection by ThermoSpot in Indian urban slum dwellings.

OBJECTIVE: To look at the performance of ThermoSpot liquid crystal thermometry in detecting neonatal hypothermia. DESIGN: A comparison was made between skin temperatures taken by ThermoSpot and axillary temperatures taken by digital electric thermometry. Non-medically trained local volunteers performed daily paired recordings on infants on days 1, 2, 3, 4, 5, 6, and 7 of life. SETTING: This is a non-hospital based study set in the homes of neonates in an underprivileged urban slum community in the developing world. INCLUSION CRITERIA: babies born at home. EXCLUSION CRITERIA: hospital admission; parental refusal. INTERVENTIONS: The ThermoSpot was stuck to the neonate's abdomen over the liver area on day 1 and removed on day 7. MAIN OUTCOME MEASURES: Fixed test properties of ThermoSpot. RESULTS: Over 180 paired observations, the fixed test properties of ThermoSpot in the detection of hypothermia were: sensitivity 88%; specificity 97%; positive likelihood ratio 29; negative likelihood ratio 0.13. CONCLUSIONS: ThermoSpot performed well when used by non-medically trained volunteers for the detection of neonatal hypothermia in the homes of an urban slum community.

Rapid diagnosis of bacterial meningitis using nitrite patch testing.

Urine reagent strips have been used to test cerebrospinal fluid (CSF) in areas where laboratory facilities are unavailable. Protein, glucose and leukocyte esterase patches have been shown to be useful in this context. We propose that the nitrite patch also has a contribution to make: it could provide clinically useful information, at no extra cost. We tested CSF samples from 200 children with suspected meningitis. In a pragmatic approach chosen to reflect the clinical dilemma of whether or not to use parenteral antibiotics, the final laboratory diagnosis was dichotomized into either 'bacterial meningitis' or 'not bacterial meningitis'. These diagnostic categories were compared with nitrite patch results, which were either positive or negative. Nitrite patch testing of all CSF, clear CSF and bloody CSF gave positive likelihood ratios of 49, 'infinity' and 5.8, respectively.

Lung function changes in teenage carpet weavers.

Lung function was measured with a Microlab 3500 Spirometer in 17 teenage carpet weavers, their 17 non weaving sisters and 13 age/sex matched controls in a carpet making community in Gwalior in late 2001. All subjects were asymptomatic. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and mid-expiratory flow rate (MEF) were expressed as percentages of expected values for the subjects age and height using prediction equations for healthy North-Indian girls (FVC% FEV1% and MEF%). There was no significant difference in FVC% FEV1% or FEV1/FVC ratio between the 3 groups but weavers had a significantly lower mean MEF% than their sisters (p< 0.01 by paired "t" test) and the age-matched control group (p< 0.002 by "t" test). The reduction in MEF% was correlated with duration of employment (Spearmans correlation = 0.5 with p < 0.05).

Inhibition of malignant cell growth by 311, a novel iron chelator of the pyridoxal isonicotinoyl hydrazone class: effect on the R2 subunit of ribonucleotide reductase.

The key roles of iron and iron proteins in cell proliferation make them potential targets for cancer therapy. However, clinical trials directed toward perturbation of tumor iron homeostasis by iron chelation have been limited to the use of deferoxamine (DFO). There is thus a need to develop agents with greater efficacy. In the present study, we investigated the mechanism of cytotoxicity of 311 (2-hydroxy-1-naphthylaldehyde benzoyl hydrazone), a novel iron chelator of the pyridoxal isonicotinoyl class. We found that 311 inhibited the growth of CCRF-CEM cells in a time- and concentration-dependent fashion with an IC(50) that was approximately 20-fold lower than that of DFO. 311 also inhibited the growth of breast, bladder, and head and neck cancer cell lines. Using electron spin resonance (ESR) spectroscopy analysis, we found that a 12-h exposure of CCRF-CEM cells to 311 inhibited the tyrosyl radical ESR signal of the R2 subunit of ribonucleotide reductase. However, overproduction of the R2 subunit in hydroxyurea-resistant CCRF-CEM cells was associated with a decrease in sensitivity of cells to 311 but not to DFO. Our studies show that 311 is a more potent cytotoxic agent than DFO, with activity against both hematopoietic and nonhematopoietic cell lines regardless of their p53 status. Furthermore, the ESR studies suggest that inhibition of the R2 subunit of ribonucleotide reductase is at least one mechanism by which 311 blocks cell proliferation.