Perioperative continuation or ultra-early resumption of antithrombotics in elective neurosurgical cranial procedures.

OBJECTIVE: Discontinuation of antithrombotics (AT) prior to elective cranial procedures is common practice, despite the higher risk of thromboembolic complications in these patients. The aim of this study was to investigate the risks and benefits of a new perioperative management protocol of continuation or ultra-early AT resumption in elective cranial procedures. METHODS: This study was an analysis of a prospectively collected cohort of patients undergoing elective cranial surgery with (AT group) and without (control group) AT. For extraaxial or shunt surgeries, acetylsalicylic acid (ASA) was continued perioperatively. For intraaxial pathologies, ASA was discontinued 2 days before surgery and resumed on postoperative day 3. All other AT were discontinued according to their pharmacokinetics, and resumed on postoperative day 3 after unremarkable postoperative imaging. Additionally, the authors performed a retrospective analysis of patients with AT who underwent surgery before implementation of this new AT management protocol (historical AT group). Primary and secondary outcomes were the incidence of hemorrhagic and thromboembolic complications within 3 months after surgery. RESULTS: Outcomes of 312 patients were analyzed (83 [27%] in the AT group, 106 [34%] in the control group, and 123 [39%] in the historical AT group). For all 3 patient groups, the most common type of surgery was craniotomy for intraaxial tumors (14 [17%] in the AT group, 28 [26%] in the control group, and 60 [49%] in the historical AT group). The most commonly used AT were ASA (38 [46%] in the AT group and 78 [63%] in the historical AT group), followed by non-vitamin K oral anticoagulants (32 [39%] in the AT group and 18 [15%] in the historical AT group). The total perioperative discontinuation time in the AT group was significantly shorter than in the historical AT group (median of 4 vs 16 days; p < 0.001). The rate of hemorrhagic complications was 4% (95% CI 1-10) (n = 3/83) in the AT group, 6% (95% CI 2-12) (n = 6/106) in the control group, and 7% (95% CI 3-13) (n = 9/123) in the historical AT group (p = 0.5). The rate of thromboembolic complications was 5% (95% CI 1-12) (n = 4/82) in the AT group, 8% (95% CI 3-15) (n = 8/104) in the control group, and 7% (95% CI 3-13) (n = 8/120) in the historical AT group (p = 0.7). CONCLUSIONS: The presented perioperative management protocol of continuation or ultra-early resumption of AT in elective cranial procedures does not seem to increase the hemorrhagic risk. Moreover, it appears to potentially protect patients from thromboembolic complications.

Stem Cell-Enriched Hybrid Breast Reconstruction Reduces Risk for Capsular Contracture in a Hybrid Breast Model.

BACKGROUND: Hybrid breast reconstruction (HBR) combines silicone implants with fat grafting to improve implant coverage, treating local tissue deficiencies and leading to a more natural breast appearance. Recent data also indicated less capsular contracture after HBR. The authors developed a novel technique and animal model of cell-assisted (CA) HBR to illuminate its effects on capsular contracture. METHODS: Animals received silicone implants in a dorsal submuscular pocket. Although animals of the HBR group received fat grafting around the implant without stem cell enrichment, rats of the CA-HBR1 and the CA-HBR2 groups received stem cell-enriched fat grafting with 2 × 10 6 and 4 × 10 6 adipose-derived stem cells immediately after implant insertion. On day 60, animals underwent sonography and elastography imaging and were euthanized, and outcome analysis was performed by means of histology, immunohistochemistry, chemical collagen quantification, and gene expression analysis. RESULTS: With this novel technique, long-term survival of adipose-derived stem cells within the implant pocket was demonstrated after 60 days after implant insertion. CA-HBR led to significantly reduced thickness and collagen density of capsular contractures. In addition, CA-HBR resulted in reduced fibrotic responses with less occurrence of collagen type I and transforming growth factor-ß in capsule tissue. Moreover, the addition of stem cells suppressed fibrotic and inflammatory responses on a genetic level with significant underexpression of collagen type I and transforming growth factor-ß1. CONCLUSIONS: With this new technique and animal model, the authors observed a preventive effect on capsular contracture substantiating the basis of clinical outcomes of HBR. The authors propose that the addition of stem cells to HBR might booster its beneficial results. CLINICAL RELEVANCE STATEMENT: Stem cell-enriched fat grafting around silicone implants may reduce the risk for capsular contracture after silicone breast implantation. While fat grafting alone already shows beneficial effects, the addition of stem cells to the fat graft can potentiate this effect.

Long-term sequelae of critical illness in sepsis, trauma and burns: A systematic review and meta-analysis.

BACKGROUND: Sepsis, major trauma, and severe burn injury are life-threatening critical illnesses that remain significant contributors to worldwide morbidity and mortality. The three underlying etiologies share pathophysiological similarities: hyperinflammation, hypermetabolism, and acute immunomodulation. The aims of this study were to assess the current state of long-term outcome research and to identify key outcome parameters between the three forms of critical illness. METHODS: This systematic review and meta-analysis (MA) were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed was searched from January 1, 1975, to December 31, 2019. Studies were assessed for eligibility by independent reviewers. Inclusion criteria were studies reporting at least a 6-month follow-up of health-related quality of life and organ-specific sequelae within the three etiologies: severe burn injury, sepsis, and major trauma. RESULTS: In total, 125 articles could be included in the systematic review and 74 in the MA. The mean follow-up time was significantly longer in burn studies, compared with sepsis and trauma studies. The majority of patients were from the sepsis group, followed by burns, and major trauma studies. In the overall health-related quality of life, as assessed by Short Form 36 and European Quality-of-Life Index, the three different etiologies were comparable with one another. CONCLUSION: The effects of critical illness on survivors persist for years after hospitalization. Well-reported and reliable data on the long-term outcomes are imperative, as they can be used to determine the treatment choice of physicians and to guide the expectations of patients, improving the overall quality of care of three significant patient cohorts. LEVEL OF EVIDENCE: Systematic review and MA, level III.

Effects of 17ß-estradiol on early gonadal development and expression of genes implicated in sexual differentiation of a South American teleost, Astyanax altiparanae.

Gonadal sex differentiation in teleost fish shows greater plasticity as compared to other vertebrates, as it can be influenced by a variety of factors such as exogenous sex steroids. Exogenous estrogens, such as 17ß-estradiol (E2), can induce feminization when administered during early embryonic development. However, the mechanisms underlying the E2-induced feminization are not fully understood, especially in Neotropical species. Therefore, the aim of this study was to evaluate the effects of E2 administration on the phenotypic sex characteristics, histological assessment of the gonads, and the expression of selected genes in Astyanax altiparanae exposed to dietary E2 prior to gonadal differentiation. At 4 days post-hatch (dph), groups of 30-40 undifferentiated larvae were fed with a diet containing varying amounts of E2 for 28 days, and fish were sampled at 90 dph. Previous studies revealed that ovary formation in A. altiparanae occurred at 58 dph, whereas the first sign of testis formation was found at 73 dph. In relation to the control, E2 exposure increased the proportion of phenotypic females in 120% and 148.4% for 4 and 6 mg E2/Kg, respectively. However, histological analysis revealed that treatments did not affect gonadal sex ratio between males and females, but induced intersex (testis-ova) in the group treated with 6 mg E2/Kg food. Treatment with E2 also altered gonadal transcript levels of a selected number of genes implicated in sexual differentiation. Males overexpressed dmrt1, sox9 and amh following E2 treatment as compared to control. Females showed increased mRNA levels of dmrt1 and sox9, which might be related to the down-regulation of cyp19a1a after E2 exposure. In summary, E2 exposure during early gonadal development affected male secondary characteristics without changing the gonadal sex ratio, and altered expression of genes implicated in sexual differentiation.

Radial collateral ligament repair of the thumb: long-term outcomes and predictive factors of postoperative deficits.

BACKGROUND: The thumb's radial collateral ligament (RCL) plays an important role in stabilizing the first metacarpophalangeal joint (MCP-1). RCL injuries are rare and treatment recommendations are inconsistent in the current literature. The aim of this study was to report on long-term outcomes following surgical repair of thumb RCL tear and to identify prognostic risk factors for treatment failure. METHODS: Patients with RCL tear from 10/1998 to 10/2019 were included in the present retrospective single center cohort study. In follow-up visits, participants were assessed regarding pain, range of motion and strength as well as with disability of shoulder, arm and hands (DASH), and the Short-Form 36 (SF36) questionnaires. Finally, predictive factors of postoperative deficits were identified. RESULTS: 43 patients fulfilled inclusion criteria. Median age was 43.5 years (range 18-80 years). The most frequent mechanism of injury was a fall or impact. Bony avulsions were identified in 46.5% (20/43). Time from injury to surgery was 12 days (0-276 days). One Stener-like lesion was observed intraoperatively among our patients. After surgical repair, the MCP-1 joint was stable in every patient. Mean time to follow-up was 5.3 years (1 month to 17 years). Persistency of pain in the MCP-1 joint was reported by 11 patients. Postoperative averaged score was 3.75 on DASH and 44.96 on SF36, respectively. The average grip and pinch strength was 32.7 kg and 8.37 kg, respectively. Predictive factors of postoperative deficits were delay of surgery of > 3 weeks (OR 10.72, p 0.017) and palmar subluxation prior to surgery (OR 8.86, p 0.019). CONCLUSION: Long-term follow-up has proven that surgical repair of RCL enables the patient to regain adequate stability and strength of the MCP-1 joint and minimizes disability. Predictive risk factors of pain persistency after surgery are surgical delay and palmar subluxation of the MCP-1 joint.

Surpassing limits of static RNA modification analysis with dynamic NAIL-MS.

Ribonucleic acids (RNA) are extensively modified. These modifications are quantified by mass spectrometry (LC-MS/MS) to determine the abundance of a modification under certain conditions or in various genetic backgrounds. With LC-MS/MS the steady state of modifications is determined, and thus we only have a static view of the dynamics of RNA modifications. With nucleic acid isotope labeling coupled mass spectrometry (NAIL-MS) we overcome this limitation and get access to the dynamics of RNA modifications. We describe labeling techniques for E. coli, S. cerevisiae and human cell culture and the current instrumental limitations. We present the power of NAIL-MS but we also outline validation experiments, which are necessary for correct data interpretation. As an example, we apply NAIL-MS to study the demethylation of adenine and cytidine, which are methylated by the damaging agent methyl-methanesulfonate in E. coli. With NAIL-MS we exclude the concurrent processes for removal of RNA methylation, namely RNA degradation, turnover and dilution. We use our tool to study the speed and efficiency of 1-methyladenosine and 3-methylcytidine demethylation. We further outline current limitations of NAIL-MS but also potential future uses for e.g. relative quantification of tRNA isoacceptor abundances.

Cochlear implantation in patients with enlarged vestibular aqueduct. A case series with literature review.

OBJECTIVES: To report our institutional experience of the management of patients with enlarged vestibular aqueduct (EVA) and compare it to the literature. METHODS: We carried out a retrospective review of patients' records from 1993 to 2015. The age, sex, associated malformations, relevant past medical history, genetic screening results, possible surgical incident, implant model and duration of follow- up, outcome in terms of Categories of Auditory Performance (CAP scores), and integration or resuming mainstream school or work were recorded. RESULTS: We had 11 patients (six boys and five girls) with EVA who underwent cochlear implant surgery in our center during the 22-year study period, out of a total of 827 implanted (1.3%). The mean age at surgery was 8.9 years ranging from 0.6 to 35 years. EVA was bilateral in 10 cases, isolated anatomical finding in seven cases, and associated with other malformations in four. Cochlear implantation was bilateral in five cases and unilateral in six. The mean follow- up duration was 48.3 months (range: 3-120). No postoperative complication was observed and all the patients could regain a serviceable hearing, attending normal school and working normally. CONCLUSION: EVA is frequently observed in the deaf population without an identifiable cause. The hearing loss is usually progressive and may result in cochlear implantation which has proved its efficiency in rehabilitating EVA patients.

Management of subglottic hemangiomas with carbon dioxide laser: Our 25-year experience and comparison with the literature.

INTRODUCTION: Subglottic hemangiomas (SGH) are rare tumors of infancy arising between the perichondrium and the mucosa of the subglottic space. It is a potential life-threatening condition. Many therapeutic options exist for this disease, including lasers. OBJECTIVE: To report our 25-year experience of laser treatment of SGH. MATERIAL AND METHODS: Retrospective review of charts. SETTING: Clarós' Otolaryngology and Head and Neck Surgery Clinic in Barcelona, Spain. RESULTS: We recruited a total of 97 patients of whom 89 were treated with CO2 laser. Mean age at first contact was 2.1 months (range: 1.5-6.5). Sex ratio was 10 girls for 1 boy. Eighty percent of patients presented with stridor and 30.3% with recurrent acute laryngitis. Forty percent had associated cutaneous hemangiomas. They received an average of 1.85 laser session (range: 1-4) and 78.5% were healed after a maximum of 2. We had a 100% success rate and 1.1% complication rate (subglottic stenosis). CONCLUSION: CO2 laser is a very effective and recommendable tool against subglottic hemangiomas. To achieve good results traditional laser safety measures should be respected besides some useful surgical tips.

Effect of HIV Infection and Highly Active Antiretroviral Therapy on Hearing Function: A Prospective Case-Control Study From Cameroon.

IMPORTANCE: Human immunodeficiency virus (HIV) infection remains a major cause of morbidity and mortality worldwide. Many studies have found a higher prevalence of hearing impairment among HIV-positive individuals. OBJECTIVE: To investigate the effect of HIV and highly active antiretroviral treatment (HAART) on the hearing function in a Cameroonian population. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective case-control study from March 1, 2012, through January 31, 2013. The study took place at the National Social Insurance Fund Hospital in Yaoundé, Cameroon, a public health facility. We included 90 HIV-positive case patients and 90 HIV-negative control patients aged 15 to 49 years without any history of hearing loss or treatment with a known ototoxic drug. The case group was further divided into 3 subgroups: 30 HAART-naive patients, 30 patients receiving first-line HAART, and 30 patients receiving second-line HAART. INTERVENTIONS: Hearing function was assessed by pure-tone audiometry and classified according to the criteria of the Bureau International d'Audio-Phonologie. MAIN OUTCOMES AND MEASURES: Hearing loss due to HIV and HAART. RESULTS: The HIV-positive patients had more otologic symptoms (hearing loss, dizziness, tinnitus, and otalgia) than HIV-negative patients (41 vs 13, P = .04). There were 49 cases (27.2%) of hearing loss in the HIV-positive group vs 10 (5.6%) in the HIV-negative group (P = .04). Compared with HIV-negative individuals, the odds of hearing loss were higher among HIV-infected HAART-naive patients (right ear: odds ratio [OR], 6.7; 95% CI, 4.3-9.7; P = .004; left ear: OR, 6.2; 95% CI, 3.5-8.3; P = .006), patients receiving first-line HAART (right ear: OR, 5.6; 95% CI, 1.9-10.5; P = .01; left ear: OR, 12.5; 95% CI, 8.5-15.4; P < .001), and patients receiving second-line HAART (right ear: OR, 6.7; 95% CI, 3.3-9.6; P = .004; left ear: OR, 3.7; 95% CI, 3.0-5.0; P = .08). CONCLUSIONS AND RELEVANCE: Hearing loss is more frequent in HIV-infected patients compared with uninfected patients. Therefore, HIV-infected patients need special audiologic care. Further studies are needed because controversy remains regarding the factors that lead to ear damage.

Mayak Worker Dosimetry System 2008 (MWDS-2008): assessment of internal dose from measurement results of plutonium activity in urine.

A new modification of the prior human lung compartment plutonium model, Doses-2005, has been described. The modified model was named "Mayak Worker Dosimetry System-2008" (MWDS-2008). In contrast to earlier models developed for workers at the Mayak Production Association (Mayak PA), the new model more correctly describes plutonium biokinetics and metabolism in pulmonary lymph nodes. The MWDS-2008 also provides two sets of doses estimates: one based on bioassay data and the other based on autopsy data, where available. The algorithm of internal dose calculation from autopsy data will be described in a separate paper. Results of comparative analyses of Doses-2005 and MWDS-2008 are provided. Perspectives on the further development of plutonium dosimetry are discussed.

238Pu: a review of the biokinetics, dosimetry, and implications for human exposures.

Plutonium-238 (238Pu) has a half-life of about 87.7 y and thus a higher specific activity than 239Pu. It is used in radioisotope thermoelectric generators and is a substantial source of plutonium alpha-radiation in spent nuclear fuels. Early animal studies demonstrated differences in the biokinetics of inhaled oxides of 238Pu and 239Pu with 238Pu having a substantially more rapid translocation from the lungs to the systemic organs, particularly the skeleton. This resulted in the predominant occurrence of skeletal cancers in animals exposed to 238Pu oxides but lung cancers in those with exposures to 239Pu oxides. The anatomical distribution of osteogenic sarcomas seen in animal studies was similar to that observed with 239Pu and also in plutonium workers but differed from naturally occurring tumors. The in vivo "solubility" of 238Pu has been associated with the relative amounts of 238Pu/239Pu in the particles and calcination temperatures during the preparation of the dioxides. There is experimental evidence of in vivo 238Pu particle fragmentation attributed to nuclear recoil during radioactive decay. The resulting conversion of microparticles to nanoparticles may alter their interactions with macrophages and transport across epithelial barriers. There are few documented cases of human exposures, but the biokinetics appeared to depend on the chemical and physical nature of the aerosols. Robust human biokinetic and dosimetric models have not been developed, due in part to the lack of data. With the acceleration of nuclear technologies and the greater demand for reprocessing and/or disposal of spent nuclear fuels, the potential for human exposure to 238Pu will likely increase in the future.

Uncertainties analysis for the plutonium dosimetry model, doses-2005, using Mayak bioassay data.

The Doses-2005 model is a combination of the International Commission on Radiological Protection (ICRP) models modified using data from the Mayak Production Association cohort. Surrogate doses from inhaled plutonium can be assigned to approximately 29% of the Mayak workers using their urine bioassay measurements and other history records. The purpose of this study was to quantify and qualify the uncertainties in the estimates for radiation doses calculated with the Doses-2005 model by using Monte Carlo methods and perturbation theory. The average uncertainty in the yearly dose estimates for most organs was approximately 100% regardless of the transportability classification. The relative source of the uncertainties comes from three main sources: 45% from the urine bioassay measurements, 29% from the Doses-2005 model parameters, and 26% from the reference masses for the organs. The most significant reduction in the overall dose uncertainties would result from improved methods in bioassay measurement with additional improvements generated through further model refinement. Additional uncertainties were determined for dose estimates resulting from changes in the transportability classification and the smoking toggle. A comparison was performed to determine the effect of using the model with data from either urine bioassay or autopsy data; no direct correlation could be established. Analysis of the model using autopsy data and incorporation of results from other research efforts that have utilized plutonium ICRP models could improve the Doses-2005 model and reduce the overall uncertainty in the dose estimates.

[Bilateral ductal carcinoma in situ of the breast: independent events or bilateral disease?]. / Carcinomes canalaires in situ bilatéraux: événements indépendants ou maladie bilatérale?

OBJECTIVES: In a retrospective study of bilateral Ductal Carcinoma In Situ (DCIS), cases were analysed to determine the relationship between the two events. MATERIAL AND METHODS: From 1971 to 2001, among 812 patients with DCIS in Bergonie Institute, 78 suffering from bilateral DCIS and only19 were treated entirely in our institute. It was either synchronous DCIS or asynchronous (before 6 months). We realised a comparative study between, clinical and pathological characteristics of each DCIS. RESULTS: In case of asynchronous DCIS, contra lateral DCIS occurred after a median 75-months period and until 22 years after the first event. We found at least for one histological subtype an agreement in 53% of cases. In 31% of cases, the grade was the same. For low plus intermediary grade versus high grade, the agreement was 53%. There was a subtype and grade agreement of 32% and a subtype or grade agreement in 63% of cases. CONCLUSION: Histological agreement between the two lesions indicated the possible existence of in situ bilateral disease in these women. The local relapse rate was 20% and all of them were invasive. The risk of relapse in controlateral breast is high and patient needs a long follow up even in case of mastectomy.

Complex chromosome aberrations persist in individuals many years after occupational exposure to densely ionizing radiation: an mFISH study.

Long-lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after and potentially have broad applications in the fields of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations, and some of them can be exploited as biomarkers of exposure. Densely ionizing radiation, for example, alpha particle radiation (from radon or plutonium) and neutron radiation, preferentially induces complex chromosome aberrations, which can be detected by the 24-color multifluor fluorescence in situ hybridization (mFISH) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear-weapons workers, who were exposed many years ago to plutonium, gamma rays, or both, at the Mayak weapons complex in Russia. We analyzed peripheral-blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations. A significantly elevated frequency of complex chromosome translocations was detected in the highly exposed plutonium workers but not in the group exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations represent a long-lived, quantitative, low-background biomarker of densely ionizing radiation for human populations exposed many years ago.

[Psychological adjustment of stereotactic breast biopsy instrumentation procedures: about 73 cases]. / Le vécu psychologique de la procédure de prélèvements percutanés du sein. Etude quasi prospective à propos de 73 cas.

OBJECTIVE: The aim of the study was to investigate patients' perceptions after stereotactic breast biopsy instrumentation, after both procedure and results. PATIENTS AND METHOD: From 1 March 2002 to 31 March 2003, a questionnaire (Likert response type) on stress was given to 73 patients who had breast biopsies procedures, the first time at the end of the procedure (T1) and then after the histological diagnosis (T2). RESULTS: The questionnaire was validated through analysis of principal component with Varimax rotation. Three factors were identified: procedure, quality of life, information and perception after biopsy. Responses were analysed with Chi-square. Two groups of women were identified, the first group (G1) corresponding to patients with a benign diagnosis (N=32) and the second group (G2) to patients with malignant diagnosis (N=32). Only the "procedure" factor was different at T1 and T2 (P=0.022). Compression was found to be painful: 11% at T1 versus 21% at T2. Women were disturbed by local anesthesia: 26% at T1 versus 21% at T2. Biopsy was painful: 6% at T1 versus 13% at T2. Examination was too long: 24% at T1 versus 35% at T2. The procedure was discomfortable: 52% at T1 versus 54% at T2. Information satisfied patients in 90% cases. There was no statistically significant difference according to procedures and histological disease (P=0.357). DISCUSSION AND CONCLUSION: Information and medical empathy conditioned patients' perceptions. Patients tolerated the procedures well.

Stable intrachromosomal biomarkers of past exposure to densely ionizing radiation in several chromosomes of exposed individuals.

A multicolor banding (mBAND) fluorescence in situ hybridization technique was used to investigate the presence inhuman populations of a stable biomarker-intrachromosomal chromosome aberrations-of past exposure to high-LET radiation. Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed from 1949 onward to either plutonium, gamma rays or both. Metaphase spreads were produced and chromosomes 1 and 2 were hybridized with mBAND FISH probes and scored for intra-chromosomal aberrations. A large yield of intrachromosomal aberrations was observed in both chromosomes of the individuals exposed to high doses of plutonium, whereas there was no significant increase over the (low) background control rate in the population who were exposed to high doses of gamma rays. Interchromosome aberration yields were similar in both the high plutonium and the high gamma-ray groups. These results for chromosome 1 and 2 confirm and extend data published previously for chromosome 5. Intrachromosomal aberrations thus represent a potential biomarker for past exposure to high-LET radiations such as alpha particles and neutrons and could possibly be used as a biodosimeter to estimate both the dose and type of radiation exposure in previously exposed populations.

[Non-Hodgkin lymphoma as a cause of intra-hepatic periportal low attenuation at computed tomography]. / Le lymphome malin non-hodgkinien est une cause d'hypodensité péri-portale intra-hépatique au scanner.

The authors report two cases of non-Hodgkin lymphoma in non immunodeficient subjects characterized by periportal low attenuation at CT. Both patients showed gallbladder wall thickening. The different causes of periportal abnormalities are presented and discussed.

Past exposure to densely ionizing radiation leaves a unique permanent signature in the genome.

Speculation has long surrounded the question of whether past exposure to ionizing radiation leaves a unique permanent signature in the genome. Intrachromosomal rearrangements or deletions are produced much more efficiently by densely ionizing radiation than by chemical mutagens, x-rays, or endogenous aging processes. Until recently, such stable intrachromosomal aberrations have been very hard to detect, but a new chromosome band painting technique has made their detection practical. We report the detection and quantification of stable intrachromosomal aberrations in lymphocytes of healthy former nuclear-weapons workers who were exposed to plutonium many years ago. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (>6 Mb) intrachromosomal rearrangements. The yield of these aberrations was highly correlated with plutonium dose to the bone marrow. The control groups contained very few such intrachromosomal aberrations. Quantification of this large-scale chromosomal damage in human populations exposed many years earlier will lead to new insights into the mechanisms and risks of cytogenetic damage.