TICI-RANKIN mismatch: Poor clinical outcome despite complete endovascular reperfusion in the ETIS Registry.

INTRODUCTION: Endovascular treatment (EVT) is a well-established technic for acute ischemic stroke, but despite a high recanalization rate of near 80%, at 3 months roughly 50% of patients have a poor functional outcome with a modified Rankin score (mRS) ≥3. The aim of this study was to determine predictive factors of poor functional outcomes in patients with complete recanalization after EVT, defined as modified thrombolysis in cerebral infarction (mTICI) 3. PATIENTS AND METHODS: This retrospective analysis based on the prospective multicenter ETIS registry (endovascular treatment in ischemic stroke) in France included 795 patients from January 2015 and November 2019 with acute ischemic stroke due to anterior circulation occlusion and prestroke mRS 0-1, treated with EVT and who achieved complete recanalization. Univariate and multivariate logistic regression models were used to identify predictive factors of poor functional outcome. RESULTS: 365 patients (46%) showed a poor functional outcome (mRS>2). In backward-stepwise logistic regression analysis, poor functional outcome was independently associated with older age (OR per 10-year increase, 1.51; 95%CI, 1.30 to 1.75), higher admission NIHSS (OR per 1 point increase, 1.28; 95%CI, 1.21 to 1.34), absence of prior intravenous thrombolysis (OR, 0.59; 95%CI, 0.39 to 0.90), and an unfavorable 24-hour NIHSS change (24h-baseline) (OR, 0.82; 95%CI, 0.79 to 0.87). We calculated that patients whose 24h NIHSS decreased by less than 5 points are more at risk of a poor outcome, with a sensitivity and a specificity of 65.0%. CONCLUSION: Despite complete reperfusion after EVT, half of patients had a poor clinical outcome. These patients, who were mainly older with a high initial NIHSS and an unfavorable post-EVT 24h NIHSS change, could represent a target population for early neurorepair and neurorestorative strategies.

A regional strategy to decrease the time to thrombectomy in patients with low probability of treatment by thrombolysis.

BACKGROUND AND PURPOSE: The best transportation strategy for patients with suspected large vessel occlusion (LVO) is unknown. Here, we evaluated a new regional strategy of direct transportation to a Comprehensive Stroke Center (CSC) for patients with suspected LVO and low probability of receiving intravenous thrombolysis (IVT) at the nearest Primary Stroke Center (PSC). METHODS: Patients could be directly transported to the CSC (bypass group) if they met our pre-hospital bypass criteria: high LVO probability (i.e., severe hemiplegia) with low IVT probability (contraindications) and/or travel time difference between CSC and PSC<15 minutes. The other patients were transported to the PSC according to a "drip-and-ship" strategy. Treatment time metrics were compared in patients with pre-hospital bypass criteria and confirmed LVO in the bypass and drip-and-ship groups. RESULTS: In the bypass group (n=79), 54/79 (68.3%) patients met the bypass criteria and 29 (36.7%) had confirmed LVO. The positive predictive value of the hemiplegia criterion for LVO detection was 0.49. In the drip-and-ship group (n=457), 92/457 (20.1%) patients with confirmed LVO met our bypass criteria. Among the 121 patients with bypass criteria and confirmed LVO, direct routing decreased the time between symptom discovery and groin puncture by 55 minutes compared with the drip-and-ship strategy (325 vs. 229 minutes, P<0.001), without significantly increasing the time to IVT (P=0.19). CONCLUSIONS: Our regional strategy led to the correct identification of LVO and a significant decrease of the time to mechanical thrombectomy, without increasing the time to IVT, and could be easily implemented in other territories.

Is off-label thrombolysis safe and effective in a real-life primary stroke center? A retrospective analysis of data from a 5-year prospective database.

BACKGROUND: Intravenous thrombolysis (IVT) use for acute ischemic stroke (AIS) varies among countries, partly due to guidelines and product labeling changes. The study aim was to identify the characteristics of patients with AIS treated with off-label IVT and to determine its safety when performed in a primary stroke center (PSC). METHODS: This observational, single-center study included all consecutive patients admitted to Perpignan PSC for AIS and treated with IVT and patients transferred for EVT, between January 1, 2015 and December 31, 2019. Data of patients treated with IVT according to ("in-label group") or outside ("off-label") the initial guidelines and manufacturer's product specification were compared. Safety was assessed using symptomatic intracerebral hemorrhage (SIH) as the main adverse event. RESULTS: Among the 892 patients in the database (834 screened by MRI, 93.5%), 746 were treated by IVT: 185 (24.8%) "in-label" and 561 (75.2%) "off-label". In the "off-label" group, 316 (42.4% of the cohort) had a single criterion for "off-label" use, 197 (26.4%) had two, and 48 (6.4%) had three or more criteria, without any difference in IVT safety pattern among them. SIH rates were comparable between the "off-label" and "in-label" groups (2.7% vs. 1.1%, P=0.21); early neurological deterioration and systematic adverse event due to IVT treatment were similar in the 2 groups. "Off-label" patients had higher in-hospital (8.7% vs. 3.8%, P=0.05) and 3-month mortality rates (12.1% vs 5.4%, P<0.01), but this is explained by confounding factors as they were older (76 vs 67 years, P<0.0001) and more dependent (median modified Rankin scale score 0.4 vs 0.1, P<0.0001) at admission. CONCLUSIONS: "Off-label" thrombolysis for AIS seems to be safe and effective in the routine setting of a primary stroke center.

Carotid webs associated with ischemic stroke. Updated general review and research directions.

Carotid web (CaW) is an intimal variant of fibromuscular dysplasia strongly associated with ipsilateral cerebral infarction. Although considered rare, it is a recent and increasing concern for physicians involved in stroke diagnosis and management. The present general review relies on a systematic literature analysis and aims to update readers on the latest knowledge in the field of symptomatic CaW (syCaW). CaW associated with ipsilateral cerebral infarction or transient ischemic attack has been identified in 189 patients. Ischemic strokes (IS) mostly occur in middle age (mean 46 years) and predominately in females (66%). The high frequency of African descendant patients among case reports and series (58%) suggests an ethnic susceptibility for CaW development. CaW features are characterised by a shelf-like intraluminal defect on contrast sagittal imaging, a linear defect that splits the lumen on axial section, a post-contrast stagnation rostral to the lesion and a frequent contralateral mirrored CaW (26.6%). An artery-to-artery embolism mechanism is widely accepted via CaW blood stasis, thrombus formation and clot fragmentation scattered by blood flow. Therefore, cerebral infarctions are often large related to a high proportion of proximal occlusion (62.5%). CaW confers a high rate of IS recurrence despite standard anti-platelet treatment that reaches 33.3% of patients prospectively followed with a median time to event of one year. Although no randomised therapeutic studies are available, surgery (n=39) or stenting (n=50) have been often proposed and seem to avoid recurrences. CaW clearly emerges as a cause of cryptogenic embolic stroke and should be systematically investigated in routine. A large number of points remain to be elucidated and CaW patients should be steadily included in registries and randomised therapeutic studies.

Results of a 1-year quality-improvement process to reduce door-to-needle time in acute ischemic stroke with MRI screening.

OBJECTIVE: To determine the effects of a 1-year quality-improvement (QI) process to reduce door-to-needle (DTN) time in a secondary general hospital in which multimodal MRI screening is used before tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke (AIS). METHODS: The QI process was initiated in January 2015. Patients who received intravenous (iv) tPA<4.5h after AIS onset between 26 February 2015 to 25 February 2016 (during implementation of the QI process; the "2015 cohort") were identified (n=130), and their demographic and clinical characteristics and timing metrics compared with those of patients treated by iv tPA in 2014 (the "2014 cohort", n=135). RESULTS: Of the 130 patients in the 2015 cohort, 120 (92.3%) of them were screened by MRI. The median DTN time was significantly reduced by 30% (from 84min in 2014 to 59min; P<0.003), while the proportion of treated patients with a DTN time≤60min increased from 21% to 52% (P<0.0001). Demographic and baseline characteristics did not significantly differ between cohorts, and the improvement in DTN time was associated with better outcomes after discharge (patients with a 0-2 score on the modified rankin scale: 59% in the 2015 cohort vs 42.4% in the 2014 cohort; P<0.01). During the 1-year QI process, the median DTN time decreased by 15% (from 65min in the first trimester to 55min in the last trimester; P≤0.04) with a non-significant 1.5-fold increase in the proportion of treated patients with a DTN time≤60min (from 41% to 62%; P=0.09). CONCLUSION: It is feasible to deliver tPA to patients with AIS within 60min in a general hospital, using MRI as the routine screening modality, making this QI process to reduce DTN time widely applicable to other secondary general hospitals.

[Predictive value of postural and dynamic walking parameters after high-volume lumbar puncture in normal pressure hydrocephalus]. / Intérêt prédictif de l'évolution des facteurs posturaux et locomoteurs après ponction lombaire soustractive dans l'hydrocéphalie chronique de l'adulte.

INTRODUCTION: Normal pressure hydrocephalus (NPH) was described by Adams et al. (1965). The common clinical presentation is the triad: gait disturbance, cognitive decline and urinary incontinence. Although these symptoms are suggestive, they are not specific to diagnosis. The improvement of symptoms after high-volume lumbar puncture (hVLP) could be a strong criterion for diagnosis. We tried to determine a specific pattern of dynamic walking and posture parameters in NPH. Additionally, we tried to specify the evolution of these criteria after hVLP and to determine predictive values of ventriculoperitoneal shunting (VPS) efficiency. PATIENTS AND METHODS: Sixty-four patients were followed during seven years from January 2002 to June 2009. We identified three periods: before (S1), after hVLP (S2) and after VPS (S3). The following criteria concerned walking and posture parameters: walking parameters were speed, step length and step rhythm; posture parameters were statokinesigram total length and surface, length according to the surface (LFS), average value of equilibration for lateral movements (Xmoyen), anteroposterior movements (Ymoyen), total movement length in lateral axis (longX) and anteroposterior axis (longY). RESULTS: Among the 64 patients included, 22 had VPS and 16 were investigated in S3. All kinematic criteria are decreased in S1 compared with normal values. hVLP improved these criteria significantly (S2). Among posture parameters, only total length and surface of statokinesigram showed improvement in S1, but no improvement in S2. A gain in speed greater or equal to 0.15m/s between S1 and S2 predicted the efficacy of VPS with a positive predictive value (PPV) of 87.1% and a negative predictive value (NPV) of 69.7% (area under the ROC curve [AUC]: 0.86). CONCLUSION: Kinematic walking parameters are the most disruptive and are partially improved after hVLP. These parameters could be an interesting test for selecting candidates for VPS. These data have to be confirmed in a larger cohort.

Prevalence of carotid web in a French cohort of cryptogenic stroke.

BACKGROUND AND PURPOSE: Carotid webs (CaW) may be an under-recognized cause of anterior circulation cryptogenic ischemic stroke (ACIS). Prevalence is still unknown in European patients with ACIS. OBJECTIVE: To evaluate the prevalence of CaW in ACIS and describe patients with CaW phenotype in a cohort of patients from a French stroke center. METHODS: We conducted a retrospective monocentric cohort study from 01/01/2015 to 31/12/2019 (Montpellier University Hospital, France), in consecutive anterior ischemic stroke (AIS) patients ≤65 years old from a prospective stroke database. Using ASCOD phenotyping, ACIS patients were selected and cervical CTA were reviewed to find CaW. RESULTS: Among 1053 consecutive AIS patients, 266 ACIS patients with CTA were included. Among patients included (mean age 50, women 58%), CaW was in the ipsilateral carotid (iCaW) in 21 patients: 7.9% (95%CI [4.6-11.1]), (mean age 51, 11 women, 16 Caucasian). iCaW were uncovered during study review of CTA in 6/21 (29%) patients. Comparison between patients with iCaW and those without iCaW showed no differences except that of a higher rate of intracranial large vessel occlusion (LVO) (62.4 vs 37.6%; p = 0.03). Patients with iCaW under conservative medical therapy had an annualized stroke recurrence rate (SRR) of 11.4% (95%CI [8.4-15.1]. CONCLUSIONS: iCaW was identified as a source of stroke in about 8% of a French population ≤65 years with ACIS. iCaW was associated with a higher rate of LVO and a high SRR under conservative medical therapy.

Microangiopathie cérébrale: du diagnostic à la prise en charge small vessel disease of the brain: Diagnosis and management.

Small vessel disease of the brain is commonly identified among ageing people. It causes almost 25% of strokes and is associated with cognitive impairment and dementia as well as gait difficulties. Its diagnosis is usually made on MRI in the presence of deep white matter and basal ganglia hyperintensities as well as deep lacunar infarcts (lacunes), microbleeds and enlarged perivascular spaces. MRI is also of importance to identify the main differential diagnoses including inflammatory disorders, cerebral amyloid angiopathy and other genetic causes of microangiopathy. Small vessel disease is associated with the main vascular risk factors including notably age and hypertension but whether controlling these vascular risk factors is beneficial is still not clear. Here, we provide a comprehensive review underlining the main diagnostic features of cerebral microangiopathy and summarise the main therapeutic approaches (notably blood pressure normalisation and physical activity) used to control its development and prevent strokes as well as the development of cognitive involvement and gait impairment.

Predictors of Favorable Outcome after Endovascular Thrombectomy in MRI: Selected Patients with Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Clinical outcomes after endovascular treatment for acute basilar artery occlusions need further investigation. Our aim was to analyze predictors of a 90-day good functional outcome defined as mRS 0-2 after endovascular treatment in MR imaging-selected patients with acute basilar artery occlusions. MATERIALS AND METHODS: We analyzed consecutive MR imaging-selected patients with acute basilar artery occlusions endovascularly treated within the first 24 hours after symptom onset. Successful and complete reperfusion was defined as modified TICI scores 2b-3 and 3, respectively. Outcome at 90 days was analyzed in univariate and multivariate analysis regarding baseline patient treatment characteristics and periprocedural outcomes. RESULTS: One hundred ten patients were included. In 10 patients, endovascular treatment was aborted for failed proximal/distal access. Overall, successful reperfusion was achieved in 81.8% of cases (n = 90; 95% CI, 73.3%-88.6%). At 90 days, favorable outcome was 31.8%, with a mortality rate of 40.9%; the prevalence of symptomatic intracranial hemorrhage within 24 hours was 2.7%. The median time from symptom onset to groin puncture was 410 minutes (interquartile range, 280-540 minutes). In multivariable analysis, complete reperfusion (OR = 6.59; 95% CI, 2.17-20.03), lower pretreatment NIHSS (OR = 0.77; 95% CI, 0.64-0.94), the presence of posterior communicating artery collateral flow (OR = 2.87; 95% CI, 1.05-7.84), the absence of atrial fibrillation (OR = 0.18; 95% CI, 0.03-0.99), and intravenous thrombolysis administration (OR = 2.75; 95% CI, 1.04-7.04) were associated with 90-day favorable outcome. CONCLUSIONS: In our series of MR imaging-selected patients with acute basilar artery occlusions, complete reperfusion was the strongest predictor of a good outcome. Lower pretreatment NIHSS, the presence of posterior communicating artery collateral flow, the absence of atrial fibrillation, and intravenous thrombolysis administration were associated with favorable outcome.

Assessment of impairment of intelligibility and of speech signal after oral cavity and oropharynx cancer.

BACKGROUND: Perceptual evaluation is a means of assessing speech disorder severity in clinical practice. Although limited in reliability and reproducibility, its ease of application makes it very widely used. Choice of assessment criteria and type of speech sample are key points. OBJECTIVE: To compare a panel's perceptual evaluations on two tasks with different criteria. MATERIAL AND METHOD: The corpus comprised 87 samples from patients treated for oral cavity or oropharynx cancer, assessed by 6 experts on two criteria (impairment of intelligibility and of speech signal) and two kinds of speech sample (semi-spontaneous versus reading speech) RESULTS: Although strong correlations were found between tasks (r>0.8), the speech signal criterion gave a score distribution providing a better metric. Severity was greater in oral cavity (mean, 5.44±2.47) than oropharyngeal cancer (6.46±2.24). Semi-spontaneous speech tended to show less severity score ceiling effect than reading speech (mean, 6.06/10 for picture description and 6.51/10 for reading). CONCLUSION: Speech signal impairment in semi-spontaneous speech seems to be the best clinical measure to assess speech disorder following treatment of oral cavity or oropharynx cancer.

[Writer's cramp secondary to spinocerebellar ataxia type 7]. / Une crampe de l'écrivain associée à une ataxie spinocérébelleuse de type 7.

Spinocerebellar ataxia type 7 (SCA 7) is a rare autosomal dominant neurodegenerative disorder (ADCA) caused by expansion of a highly unstable CAG repeat. Clinical features including progressive cerebellar, retinal degeneration and pyramidal signs. We report a patient with SCA 7 diagnosis revealed by progressive cerebellar ataxia and writer's cramp.

[Influence of acute aggravations on the development of long-term handicap in relapsing remitting multiple sclerosis: a clinical study in 99 patients]. / Influence des poussées sur la survenue d'un handicap au long cours dans la sclérose en plaques de forme rémittente: étude observationnelle de 99 patients.

INTRODUCTION: Rate of relapse occurring during the first 5 years of MS-RR is a prognosis factor of occurrence of disability or secondary progressive (SP) phase. Progressive phase, related to chronic axonal loss, is mainly considered as the principal factor of disability progression. Influence of acute relapses during the relapsing-remitting phase on disability development is not known as a prognosis factor. OBJECTIVES: To determine the influence of the exacerbations among patients with RR-MS after the second clinical event on the disability occurrence. METHODS: Diagnosis of multiple sclerosis was established according to Poser's classification. Disability measurement was made with the use of the Expanded Disability Status Scale (EDSS). The patients included in the study were classified as clinically definite RR-MS, with an EDSS score500 m. The study began at the time of the second clinical event and ended when an EDSS score of 4.0 was reached or when a SP phase was beginning or at the last follow-up visit date if these two stages were not reached. The primary outcome measure was the comparison of the risk and the average time to reach an EDSS>or=4.0 or a SP form according to the annual exacerbation rate (AER) using Kaplan-Meier survival curve. RESULTS: Among the 238 ms patients of the database, 136 patients were classified as having a definite RR-MS. Among these 136 patients, 99 patients could be included in the study according to the inclusion criteria. The median follow up of the patients since the first clinical event was 9.8 years (range 4 to 44). The average EDSS score was 0.7 at the beginning of the study and 2.3 at the end. 20.2p.cent of patients (n=20) reached an EDSS score of 4.0 or a SP-MS. The median AER was 0.4 and the average 0.62 (range 0 to 6.1). The time to reach the primary end point for 25p.cent of the population was 17.8 years in group with an AER<0.4 (group A) and 6.9 years in group with an AER>0.4 (group B) (logrank; p<0.0001). The relative risk for patients of the group B compared to group A to reach an EDSS of 4.0 or a SP form was 8.01 (IC-95p.cent: 2.74-23.46; p=0.0001). CONCLUSIONS: In spite of a limited number of patients, this study gives evidence that a high rate of acute exacerbations in RR-MS patients after the second clinical event may be an independent predictive factor of long-term residual disability progression. High relapse rate leads to a more frequent and faster SP or EDSS>4.0 occurrence.

[Chemotherapy treatment for anti-Hu paraneoplastic syndrome without active malignancy]. / Traitement par chimiothérapie d'un syndrome neurologique paranéoplasique anti-Hu sans cancer actif associé

INTRODUCTION: Anti-Hu associated paraneoplastic neurological syndromes are rare and characterized by poor prognosis. The research and treatment of a related cancer, a small-cell lung cancer most of the time, remains the best therapeutic strategy. CASE REPORT: We describe the clinical course of a paraneoplastic subacute sensory neuronopathy associated with anti-Hu antibodies in a male smoker treated by an early chemotherapy active against a small-cell lung cancer although no tumor could be found at repeated evaluations. In spite of this treatment, the neurological state deteriorated with the appearance of a cerebellar degeneration, and limbic encephalitis which resulted in a loss of autonomy. A small-cell lung cancer was found and treated 65 months after the onset of the neurological symptoms. The treatment of the underlying malignancy, when it can be found, is still considered as the optimal treatment for paraneoplastic neurological syndromes. Although no tumor could be found, we treated our patient with an empirical chemotherapy active against the most frequent malignancy associated to anti-Hu syndrome in a smoker man, without any improvement. CONCLUSION: Active and repeated research for a cancer related to an anti-Hu neurological syndrome and its treatment are undispensable. For our patient without any identified cancer empirical chemotherapy treatment was unable to stop neurological worsening. When no tumor can be identified by conventional imaging techniques, an early FDG-PET scan should be considered and then repeated if normal.

Sirolimus-associated acute respiratory distress syndrome in a renal transplant recipient.

Sirolimus is a new potent immunosuppressive drug used in organ transplantation; its major advantage is the absence of deterioration in renal function. Documented adverse effects include myelosuppression and hyperlipidemia. Recently several cases of sirolimus-associated interstitial pneumonitis have been reported, usually of mild severity. We report a new case that was complicated by a severe acute respiratory distress syndrome, which required several days of mechanical ventilation. No infectious or cardiogenic etiology was documented. Low sirolimus blood levels and acute CD4 lymphocytic alveolitis suggested an immune-related mechanism rather than a direct toxic effect of the drug. The patient recovered after discontinuation of sirolimus and the administration of corticosteroids.

[Lateral bulbar infarction due to intracranial dissection and subarachnoid haemorrhage]. / Infarctus latéro-bulbaire sur dissection intracrânienne suivi d'une hémorragie sous-arachnoïdienne.

INTRODUCTION: Intracranial vertebral artery dissecting aneurysms are a recognized cause of subarachnoid hemorrhage and the hemorrhagic recurrence risk after a first rupture of the dissecting aneurysm is high and of poor prognosis. However, when the dissection is discovered in a patient with vertebrobasilar territory ischemia, little is known about the risk of hemorrhagic rupture risk and there is no consensus on management. OBSERVATION: We report the case of a 49-year-old man who developed subarachnoid hemorrhage 48 hours after the occurrence of a latero-bulbar syndrome caused by a spontaneous dissection with occlusion of the right vertebral artery. The subsequent angiography showed a V4 dissecting aneurysm of the right vertebral artery which was treated by stenting and coiling without any complications. CONCLUSION: This case underlines the hemorrhagic risk of an intradural vertebral artery dissection and its possible progression to aneurysm. Subsequent angiographic imaging must be carefully examined to search for aneurysms which may require early specific treatment because of the high risk of recurrent bleeding.

The initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine.

The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors.

Characterization and radiosensitivity at high or low dose rate of four cell lines derived from human thyroid tumors.

PURPOSE: This study attempted to establish cell lines derived from human differentiated thyroid tumors, and to characterize and evaluate the radiation dose-rate effect. METHODS AND MATERIALS: Two cell lines (K1 and K2) were derived from papillary carcinomas, one (K7) from a follicular less-differentiated carcinoma and one (A14) from a follicular adenoma. Cell-survival curves after irradiation were established by the in vitro colony method. Radiation doses were delivered either at a high (45.9 Gy/h) or low dose rate (0.6 Gy/h) by a 60Co source. The data were analyzed according to the linear quadratic and multitarget model of radiation action. RESULTS: Doubling times were around 24 h. All cell lines were positive for intracellular thyroglobulin. Cyclic adenosine monophosphate (cAMP) response to thyrotropin (TSH) was significant for the cell lines derived from the follicular adenoma and follicular carcinoma. The two cell lines derived from papillary carcinomas were tumorigenic after inoculation into nude mice. After high-dose-rate irradiation, the surviving fraction at 2 Gy (SF2) was not significantly different for the three malignant cell lines K1, K2, and K7, and ranged from 0.39 to 0.42. For the adenoma cell line A14, we found a higher radiosensitivity with a lower SF2 value and a higher alpha parameter. After low-dose-rate irradiation, only one cell line (K2) showed a significant low-dose-rate sparing with a dose reduction factor of 1.35. CONCLUSION: The major result of our study is the weak effect of the dose rate on the survival of thyroid cell lines.

Baseline and treatment-induced chromosomal abnormalities in peripheral blood lymphocytes of Hodgkin's lymphoma patients.

PURPOSE: To study chromosomal abnormalities in 49 patients with Hodgkin's lymphoma (HL), before and after treatment and at several times during a 2-year period. METHODS AND MATERIALS: Simple chromosomal aberrations (CAs) and complex chromosomal rearrangements (CCRs) were counted in peripheral lymphocytes by painting of chromosomes 1, 3, and 4 (fluorescence in situ hybridization). A control population was composed of 20 healthy donors and 69 untreated cancer patients who had undergone various radiologic scans. RESULTS: A greater frequency (p < 10(-4)) of spontaneous cytogenetic abnormalities was observed in untreated HL patients compared with the control populations. CCRs were observed exclusively in the HL population (p < 10(-4)). Chemotherapy was associated with a significant increase in the frequency of CAs (p < 10(-4)), according to the chemotherapy regimen (p = 0.002). Immediately after radiotherapy, a significant increase (p < 10(-4)) was observed in CAs according to the size of the irradiation field. Conversely, the significant increases in the frequency of CCRs observed after treatment did not correlate with the chemotherapy regimens, radiotherapy dose, or size of the irradiation field. The evolution of CAs vs. CCRs over time was also dissociated: during the follow-up of these patients, a significant decrease was observed in the frequency of CAs at 6 months and 1 and 2 years. In contrast, after an initial decrease for up to 6 months after treatment, the frequency of CCRs remained constant for up to 2 years. CONCLUSION: Increased cytogenetic abnormalities were observed in untreated HL patients compared with the control populations. The greater frequency of cytogenetic abnormalities persisted in some patients. The presence of CCRs supports the concept of a unique genetic environment in HL patients that persists in response to potentially noxious treatments.

Radiosensitivity of human normal and tumoral thyroid cells using fluorescence in situ hybridization and clonogenic survival assay.

PURPOSE: By using cell survival as a reference, we evaluated the radiosensitivity of human normal and tumoral thyroid cells using of radiation-induced translocations. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing thyroidectomy. Cell cultures were established, irradiated with 60Co, and metaphases painted using commercial whole-chromosome 4 hybridization probe and pancentromeric probe. The clonogenic survival was assessed by conventional colony forming assay. RESULTS: After irradiation, normal cultured thyroid cells yielded a higher number of translocations than cultures derived from adenomas or thyroid carcinoma. The colony forming assay demonstrated, by way of the mean inactivation dose, a higher survival of thyroid carcinoma and adenoma cells than of normal thyroid cells. This difference between tumoral and nontumoral cells is significant in each method (p = 0.0001), and cannot be explained by apoptosis in irradiated malignant cells. Correlation of the results obtained by both methods is shown by comparing the survival fraction at 2 Gy (SF2) and the percentage of chromosome 4 translocations at 2 Gy. CONCLUSION: These results indicate that the yield of radiation-induced translocations serves as a good and rapid prediction of the intrinsic radiosensitivity of thyroid cells, and that this test could be applied to other tumors.