Early screening for chronic liver disease: impact of a FIB-4 first integrated care pathway to identify patients with significant fibrosis.

Liver fibrosis is often undetected whereas it is the determinant of liver-related mortality. We evaluate a pathway based on the systematic calculation of FIB-4 to screen for advanced hepatic fibrosis. Systematic calculation of FIB-4 was implemented in the centralized laboratory of a French University Hospital in 4 pilot departments. If ≥ 2.67, the FIB-4 result was returned to the prescribers, for patients between 18 and 70 years of age, with an incentive to measure liver stiffness by vibration controlled transient elastography. During a 2-years period, a FIB-4 was calculated in 2963 patients and 135 were ≥ 2.67 (4.6%). After exclusion of patients with a known cause of elevated FIB-4, 47 patients (34.8%) were eligible for elastography. Forty patients underwent elastography, but only 15% (7/47) at the spontaneous request of the referring physician. Fifteen patients were identified with significant fibrosis, among which 8 attended the scheduled specialist consultation, all with a confirmed diagnosis of cirrhosis. A sequential pathway based on the systematic calculation of FIB-4 enables the identification of patients with significant unknown liver fibrosis, allowing to refer them to specialized care. Raising awareness is essential to improve the care pathway.

Role of social status and social environment on net survival in patients with chronic lymphocytic leukemia: A high-resolution population-based study.

BACKGROUND: The prognostic roles of social status and social environment in chronic lymphocytic leukemia have been highlighted in some solid tumors but remain unclear in hematological malignancies. The objective of this study was to evaluate the influence of individual social status (with socioprofessional category, SPC) and social environment (with European deprivation index, EDI) on net survival in a high-resolution population with CLL. METHODS: We included CLL patients from the Regional Register of Hematological Malignancies in Normandy belonging to the French Network of Cancer Registries (Francim). The SPC variable was divided into 5 categories: farmers, craftsmen, higher employment, intermediate employment, and workers/employees. Net survival was used to estimate the excess of mortality in CLL independent of other possible causes of death using French life tables. Net survival was estimated with a nonparametric method (Pohar-Perme) and with a flexible excess mortality hazard model. Missing data were handled with multiple imputation. RESULTS: A total of 780 patients were included. The median follow-up was 7.9 years. The crude survival at 10 years was 50%, and the net survival at 10 years was 80%. In multivariate analysis, a higher age (EHR: 1.04 [1.01-1.07]), being a craftsman (EHRcraftsmen/higher.employment: 4.15 [0.86-20.15]), being a worker or an employee (EHRworkers.employees/higher.employment: 3.57 [1.19-10.7]), having a Binet staging of B or C (EHR: 3.43 [1.84-6.42]) and having a lymphocyte count > 15 G/L (EHR: 3.80 [2.17-6.65]) were statistically associated with a higher risk of excess mortality. EDI was not associated with excess mortality (EHR: 0.97 [0.90-1.04]). CONCLUSION: Socioprofessional category was a prognostic factor for an excess of mortality in CLL. Craftsmen and workers/employees shared a worse prognosis than workers with higher employment. The social environment was not a prognostic factor. Further work should be performed to explore causal epidemiologic or biological factors and other hematological malignancies.

Potential lung cancer screening outcomes using different age and smoking thresholds in the ANRS-CO4 French Hospital Database on HIV cohort.

OBJECTIVES: In most lung screening programmes, only subjects ≥ 55 years old and smoking ≥ 30 pack-years are eligible to undergo chest low-dose computed tomography. Whether the same criteria should apply to people living with HIV (PLHIV) is uncertain, given the increased lung cancer risks associated with immunodeficiency and high rates of smoking. We assessed different outcomes obtained from simulating one round of lung cancer screening in PLHIV using different age and smoking thresholds for eligibility. METHODS: Data from the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS)-CO4 French Hospital Database on HIV (FHDH) cohort of PLHIV and a national representative survey of PLHIV in care in 2011 (the ANRS-VESPA2 [enquête sur les personnes atteintes] study) were used to estimate the maximum proportion of incident lung cancers occurring between 2012 and 2016 that would have potentially been detected by screening in 2011. Secondary outcomes were numbers of eligible subjects in the cohort and numbers of subjects needed to screen (NNS) to detect one lung cancer. RESULTS: Among 77819 PLHIV in 2011 (median age 46 years; 66% men), 285 subjects subsequently developed lung cancer. Adoption of the US Preventive Services Task Force (USPSTF) recommendations (55-80 years; ≥ 30 pack-years) would have detected 31% of lung cancers at most. Lowering the minimum age to 50 and 45 years would have detected 49% and 60% of cancers, respectively, but would have greatly increased the number of eligible subjects and the NNS to detect one case of lung cancer. CONCLUSIONS: Use of the USPSTF criteria would have detected only a minority of lung cancers in a large French cohort of PLHIV in 2011. Screening PLHIV at younger ages (45 or 50 years) and/or the use of lower smoking thresholds (20 pack-years) may be beneficial, despite the consequently higher numbers of eligible subjects and NNS to detect one case of lung cancer, and should be evaluated in future studies.

Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors.

BACKGROUND: Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. DESIGN: This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. RESULTS: Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. CONCLUSIONS: CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer.

Behavioral cardiovascular risk factors in HIV-infected people in France: Diversity of profiles across groups requires an urgent and tailored preventive approach.

BACKGROUND: Among people living with HIV, cardiovascular risk could be markedly reduced through lifestyle improvement. However, to date behavioral cardiovascular risk factors (other than tobacco smoking) have been poorly investigated among them. Additionally, although co-occurrence of risk factors might amplify the deleterious effects of each risk factor, little is known about such risk factors clustering in this population. We aimed to examine levels, determinants and clustering of the major behavioral cardiovascular risk factors in the French HIV-infected population, in order to better target individuals with high risk profiles. METHODS: The ANRS-Vespa2 survey was conducted among a national representative sample of HIV-infected people followed at hospital in France in 2011. Frequency and co-occurrence of tobacco smoking, alcohol intake, low physical activity and obesity were assessed in the HIV-infected population, overall and in each of the distinctive socio-epidemiological group composing it (men who have sex with men, intravenous drug users, sub-Saharan African migrants, non-African heterosexuals). Individual characteristics associated with each of these indicators were investigated using multivariable Poisson regression models. RESULTS: The 2537 participants (median time since HIV-diagnosis: 12 years) included 39.4% men who have sex with men, 11.0% intravenous drug users, 23.5% sub-Saharan African migrants and 26.1% non-African heterosexuals. Overall, 29.4% were regular smokers, 13.8% were heavy drinkers, 14.8% lacked physical activity and 8.6% were obese. Half of the participants reported at least one risk factor with co-occurrence observed in 13.8% of the sample. However, those figures varied markedly across the groups. Main risk factors profiles were 1) regular smoking, heavy drinking, low physical activity alone or combined among intravenous drug users and men who have sex with men, 2) obesity and low physical activity usually alone among sub-Saharan African migrant women, 3) occurrence of the four risk factors separately or sometimes combined among sub-Saharan African migrant men and non-African heterosexuals. These risk factors were correlated with lower socioeconomic status and poorer health status. CONCLUSIONS: Those findings highlight the need to focus on all behavioral cardiovascular risk factors and co-occurrence (and not only on tobacco smoking) in HIV-infected people and to implement preventive approach tailored to the specific needs of the different socio-epidemiological groups.

Levels and determinants of breast and cervical cancer screening uptake in HIV-infected women compared with the general population in France.

OBJECTIVES: Cancer is a growing concern for HIV-infected people, and screening plays a major role in alleviating the burden it causes. We sought to investigate the levels and determinants of breast cancer screening (BCS) and cervical cancer screening (CCS) in HIV-infected women as compared with the general population. METHODS: The Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS)-Vespa2 study was conducted in 2011 in a national representative sample of 3022 HIV-infected hospital out-patients in France. The rates and correlates of BCS and CCS among HIV-infected women were compared with those in the general population using multivariate Poisson regression models. RESULTS: The BCS rate during the 2 years preceding the survey interview was 80.7% among HIV-infected women vs. 89.1% in the general population (P = 0.146). The CCS rate during the preceding 3 years was 88.1% among HIV-infected women vs. 83.1% in the general population (P = 0.021). During the preceding year, the CCS rate among HIV-infected women was 76.5%. The barriers to BCS and CCS were a low educational level [BCS: adjusted prevalence rate ratio 0.88; 95% confidence interval (CI) 0.80-0.97; CCS: adjusted prevalence rate ratio 0.91; 95% CI 0.83-0.99], not having supplementary health insurance (CCS: adjusted prevalence rate ratio 0.92; 95% CI 0.86-0.98), an irregular gynaecological follow-up (BCS: adjusted prevalence rate ratio 0.77; 95% CI 0.64-0.92; CCS: adjusted prevalence rate ratio 0.72; 95% CI 0.64-0.81) and a low CD4 count (BCS: adjusted prevalence rate ratio 0.83; 95% CI 0.71-0.97; CCS: adjusted prevalence rate ratio 0.78; 95% CI 0.63-0.98). The disparities in CCS uptake in terms of age, employment and gynaecological follow-up were less pronounced among HIV-infected women than in the general population. CONCLUSIONS: BCS and CCS uptake was not lower among HIV-infected women than in the general population, but CCS was suboptimal. Specificities in the profile of barriers to screening emerged.

Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long term follow-up results.

Determining the viability of residual tumor masses is a great challenge after primary treatment of Hodgkin lymphoma. FDG-PET may play a crucial role in this procedure. In this study, files of 128 Hodgkin lymphoma patients were reviewed, who were treated in three Hungarian hematology centers between January 1995 and February 2005. CT scan showed residual tumor mass by all of them. Their median follow-up was 75.5 months from PET examination. The number of true-positive, true-negative, false-positive, false-negative subjects were 29, 83, 10, 6, respectively. Sensitivity of post-treatment FDG-PET was 83 %, specificity 93 %, positive predictive value 74 %, negative predictive value 93 %, and accuracy 88 %. The difference between the event free survival of PET positive and negative cases is highly significant (p=0.0000), according to the Mantel-Cox test. Our results in the largest cohort of patients, in accordance with literature, clearly indicates that patients with negative FDG-PET results are unlikely to progress or relapse during the longest follow-up.

Angiography-proven liver metastases explain low efficacy of lymph node dissections in medullary thyroid cancer patients.

AIM: To report the role of liver angiography in the staging of medullary thyroid cancer (MTC) patients. MATERIAL AND METHODS: Sixty MTC patients with persistent or recurrent hypercalcitonemia (n=49), a characteristic general symptom (diarrhea, n=4) or a normal basal calcitonin level without general symptoms (n=7) were investigated by dynamic liver CT, MRI and angiography between 06/1998 and 06/2002. RESULTS: Dual-phase CT and MRI investigations identified hepatic metastases with relatively low frequency (8/58 on MRI, and 7/60 on CT). Angiography indicated liver involvement in 54/60 cases. The hepatic metastases were typically multiple, hypervascular, small foci (only 13 foci measured >/=10 mm). With one exception significant disease progression was not observed over 5 years of follow-up. CONCLUSIONS: Liver angiography is a powerful tool to reveal hepatic metastases in MTC patients. Frequent, inoperable liver metastases in hypercalcitoninemic MTC patients demonstrate that secondary lymph node dissection is an inefficient technique for restoration of a normal calcitonin level.

Characteristics of radiogenic lower motor neurone disease, a possible link with a preceding viral infection.

OBJECTIVE: To investigate the pathogenesis of the rare radiogenic lower motor neurone disease (LMND) on the basis of a meta-analysis of the published case histories. MATERIALS AND METHODS: The authors reviewed 47 well-documented radiogenic LMND cases from the English literature. RESULTS: The disease typically occurs following the irradiation of radiosensitive cancers situated near the spinal cord. It arises predominantly (46 cases) in the lower extremities; only one case involved the upper extremities. There is a male predominance (male:female ratio 7.8:1), and the patients are characteristically young (13-40 years, with four exceptions). An overdose does not seem to be a particular risk factor for the development of the disease, as total dose, fraction size and biologically effective dose are typically below 50 Gy, 2 Gy and 128 Gy2, respectively, which are regarded as safe doses. Other risk factors (chemotherapy, operations, etc) have been identified only rarely. Radiogenic LMND is manifested in an apparently random manner, 4-312 (mean 48.7) months after the completion of radiotherapy. DISCUSSION: The complete lack of a dose-effect relationship argues strongly against a pure radiogenic nature of the pathological process. The latency period is typically several years and it varies extremely, which excludes a direct and complete causal relationship between radiotherapy and LMND. As the interaction of ionizing radiation with living tissues is highly unspecific, thus a selective motor injury due to irradiation alone, without comparable effects on the sensory and vegetative fibers, seems improbable. CONCLUSIONS: On analogy with the viral motor neurone diseases, we suppose that radiogenic LMND may be preceded by viral (enterovirus/poliovirus) infection. Based on the meta-analysis, it is suggested that irradiation may be only a single component of the set of factors jointly resulting in the clinical state regarded as radiogenic LMND.

FDG PET imaging in hereditary thyroid cancer.

AIM: To report the role of different imaging methods in staging individuals with multiple endocrine neoplasia 2A (MEN2A) or familial medullary thyroid carcinoma (FMTC). MATERIAL AND METHODS: Fourteen newly diagnosed gene carriers underwent cervical ultrasound scanning (US), cervical and mediastinal CT, MRI and whole-body meta-[131I]iodobenzylguanidine (MIBG) scintigraphy and [18F]fluorodeoxyglucose (FDG) PET scanning. RESULTS: US identified seven true primary cancer. CT and MRI located only tumors > or =5 mm in diameter. MIBG scintigraphy and FDG PET could not identify MTC foci within the thyroid. Whole-body FDG PET identified two true-positive and one false-positive lymph node metastases. MIBG scintigraphy did not identify lymph node metastases. Total thyroidectomy was performed in 12 cases, and subtotal thyroidectomy in two subjects. CONCLUSIONS: Whole-body FDG PET and cervical US help stage individuals carrying mutant genes verifying MEN2A or FMTC.

Autopsy verifies demyelination and lack of vascular damage in partially reversible radiation myelopathy.

STUDY DESIGN: Case report of recovering radiation myelopathy. OBJECTIVE: To present autopsy and functional imaging findings on a unique case of slowly recovering radiation myelopathy with the aim of the clarification of the underlying mechanism. PATIENT: The cervical spinal cord and the distal part of the medulla oblongata of a 36-year-old thyroid cancer patient had been incorrectly irradiated with a total dose of 61 Gy and a fraction size of 3.4 Gy (J Neurol Sci 1999; 163:39-43), resulting in incomplete cervical transection with a 5-month latency period following the termination of radiotherapy. This was followed by a 9.5-year spontaneous improvement until her demise, during which the check-ups were supplemented by positron emission tomography (PET) investigations; these indicated increased [18F]deoxyglucose and [15O]butanol uptakes, but a diminished [11C]methionine accumulation by the irradiated spinal cord segment. RESULTS: Autopsy revealed demyelination (with axonal loss) and neuronal damage in the cervical spinal cord and the distal part of the medulla oblongata. In the same region, only minimal vascular injury (thickening of some of the capillary walls) was detected, but not cell proliferation or chronic inflammation. Bilateral, secondary pyramidal tract degeneration caudal to the irradiated segment was observed. The PET and autopsy findings, although separated by 2 years, are consistent. CONCLUSIONS: The pathological state of the spinal cord revealed by the autopsy is concordant with the incomplete cervical transection, implying that the functional recovery is supported by a process that probably differs from the restoration of the mechanism destroyed by the radiotherapy. For the restoration of the function, we suggest an altered conduction mechanism of the action potential, involving an increased number of sodium channels along the demyelinated segments of the injured axons, which is fully congruent with the PET findings.

Changes in brain activation caused by caloric stimulation in the case of cochleovestibular denervation--PET study.

There are a number of well-known stimulation methods for the investigation of the central projection of the vestibular system. In addition to optokinetic, galvanic and neck vibration tests, the most widespread method is caloric stimulation. These listed methods cause not only vestibular, but also other effects on the central nervous system (CNS) (acoustic, tactile and nociceptive). In this paper, positron emission tomography (PET) was used to investigate whether caloric stimulation contains a non-vestibular (extravestibular) component, which would cause a distortion in the cortical activity and therefore in the vestibular effect on the CNS. Caloric stimulation was carried out in six patients who had been operated on due to cerebello-pontine angle tumour. These patients suffered post-operatively from a complete lesion of the vestibular system and anacusis on the operated side. Ipsilaterally activated areas were the inferior pole of the post-central gyrus and temporoparietal junction, caudal part of the post-central gyrus (SI, SII), inferior parietal lobule and medial frontal gyrus. Contralaterally activated areas were the anterior cingulate gyrus, medial frontal gyrus, posterior part of the insula, post-central gyrus and temporoparietal junction (SII). Ipsilaterally deactivated areas were the caudal and cranial part of the medial occipital gyrus (V2, V3, V4, V5). Contralaterally deactivated areas were the lingual gyrus, inferior occipital gyrus (V2, V3) and fusiform gyrus. On the basis of these data, it was postulated that, during caloric stimulation, extravestibular reaction also occurs, which corresponds to the subjective feeling of heat and pain. The deactivation of the occipital cortex due to an extravestibular effect was demonstrated. This is the first observation to suggest the possibility of nociceptivevisual interaction.

A PET study on the characterization of partially reversible radiogenic lower motor neurone disease.

OBJECTIVE: To investigate the pathomechanism of the rare radiogenic lower motor neurone disease (LMND) on the basis of a case history involving a partial functional recovery. PATIENT: A 31-year-old seminoma patient received postoperative para-aortic and para-iliac telecobalt irradiation with a biologically effective dose of 88 Gy(2) (44 Gy in 2 Gy fractions/day, with an estimated alpha/beta of 2 Gy) delivered to the spinal cord following a single cycle of chemotherapy. LMND developed 4 months after the completion of radiotherapy. The patient exhibited flaccid paraparesis of the lower extremities (without sensory or vegetative signs), followed by a worsening after further chemotherapy, due to pulmonary metastatization. A gradual spontaneous functional improvement commenced and led several years later to a stabilized state involving moderately severe symptoms. METHODS: In the 15th year of the clinical course, magnetic resonance imaging (MRI) and positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) and [(11)C] methionine were conducted. Four lines of experiments (clonogenic assay using fibroblasts isolated from a skin biopsy sample of the patient, comet assay, micronucleus assay, and the testing of chromosome aberrations after in vitro irradiation of peripheral blood samples) were performed in a search for an increased individual radiosensitivity. RESULTS: MRI investigations failed to reveal any pathological change. PET demonstrated an increased FDG accumulation, but a negligible [(11)C] methionine uptake in the irradiated spinal cord segments. The radiobiological investigations did not indicate any sign of an increased individual radiosensitivity. CONCLUSIONS: We suggest that the observed partial functional recovery and stabilization of the symptoms of radiogenic LMND may be explained by the higher than normal density of sodium channels expressed along the demyelinated axons of the restored conduction. The increased energy demands of this type of conduction are proved by a higher metabolic rate (increased FDG uptake) of the irradiated spinal cord segments without a substantial regenerative process (lack of detectable protein synthesis).

Angiography effectively supports the diagnosis of hepatic metastases in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) belongs in the group of neuroendocrine tumors with early lymphatic and hepatic dissemination. A high rate of undetectable metastases is hypothesized to be responsible for the frequent mismatch between the apparent relatively small tumor burden and the elevated plasma tumor marker level. METHODS: Thirty-six MTC patients with residual/recurrent biochemical signs (elevated basal calcitonin level) and/or characteristic general symptoms (diarrhea and/or flushing) were systematically examined by conventional radiology, whole-body 18F-deoxyglucose positron emission tomography (PET), dynamic liver computed tomography and magnetic resonance imaging, and hepatic angiography. RESULTS: Conventional diagnostic imaging revealed lymph node (LN) involvement in the cervical, mediastinal, supraclavicular, and axillary regions (16 cases), and multiple pulmonary (3 cases), bony (1 solitary and 1 multiple case), and breast (1 case) metastases. (18)F-deoxyglucose PET identified all these extralymphatic metastatic lesions (except 2 cases with multiple pulmonary metastases), and also supradiaphragmatic LN involvement in 34 (94%) patients. In 32 (89%) cases, multiple small (generally < or = 1 cm) hypervascular, hepatic metastases undetectable by other imaging methods were localized angiographically. Of the 23 original pathologic specimens investigated, 18 (78%) exhibited LN involvement. The smallest primary tumor in patients with hepatic metastases was 1 cm. CONCLUSIONS: Hepatic angiography is recommended for primary staging in MTC patients with a primary tumor measuring 1 cm or larger, and/or pathologically proven LN involvement, and also during restaging for suspected recurrences to avoid unnecessary extensive surgical LN dissection in the neck and mediastinum.

[PET scanning in head and neck cancer] / Pozitronemissziós tomográfia a fej-nyaki tumorok diagnosztikájában.

INTRODUCTION: FDG (fluorine-labeled deoxy-glucose) and 11C-methionine positron emission tomography was evaluated in the diagnostics of head and neck cancer. PET scans were applied for identifying/staging relapse after oncotherapy or searching unknown primary tumor with metastatic lymph nodes of the neck. METHODS: Retrospective analysis of 22 patients examined by 17 (18)FDG and 15 (11)C-methionine PET scan. In 9 cases indication was unknown primary tumor with positive neck, in 13 cases previously treated head and neck cancer patients were examined for recurrence/restaging. RESULTS: In searching for unknown primary tumor not detectable with conventional methods, PET was effective in 22%, however, false positivity and uncertain results were found as well. In restaging PET proved to be very effective (85%) to discover recurrences and to differentiate them from post-treatment (mainly irradiation) effects. In two cases silent distant metastase were detected. CONCLUSION: PET can provide valuable information about unknown primary tumors, recurrences after oncotherapy and distant metastases as well. Simultaneous use of FDG/methionine scans does not improve the results.

Membrane permeability changes induce hyperpolarization in transformed lymphoid cells under high-density culture conditions.

BACKGROUND: Membrane potential changes in cells from the human lymphoid B cell line, JY, evoked by increasing cell density in culture were investigated, as data published on other cell types are controversial. An attempt was also made to clear the underlying mechanism. METHODS: Nonadherent JY cells were isolated from high-density plateau-phase cultures (type A cells), medium-density log-phase cultures (type B cells), and low-density lag-phase cultures (type C cells). They were analyzed for transmembrane potential, intracellular free concentration of potassium and sodium, membrane permeability for monovalent cations, cell cycle distribution by measuring DNA content, and glucose uptake. RESULTS: C type cells proved to be relatively depolarized (-41 +/- 3 mV) and cells obtained from the highest density cultures hyperpolarized (-60 +/- 3 mV). Intracellular concentrations ([K](i) = 92-97 mM and [Na](i) = 34-35 mM) were almost identical for each type of cell. The sodium/potassium permeability constant ratio in the A and C type of cells was 0.047 and 0.094, respectively. High-density culture conditions resulted in a pronounced G(1)-phase arrest. CONCLUSIONS: Differences in the membrane potential values induced by high-density culture conditions were maintained by changes in the membrane permeability for the monovalent cations.

[Current diagnostic method, prognosis estimation and therapy of papillary thyroid cancer: recommendations of the medical universities and the National Oncologic Institute of Budapest]. / A papillaris pajzsmirigy-carcinoma korszerü kivizsgálása, prognózisbecslése és kezelése: az orvostudományi egyetemek és az Országos Onkológiai Intézet ajánlása.

Physical examination, cervical ultrasonography (US) and aspiration cytology are the mainstays of the preoperative diagnostics of papillary thyroid carcinoma. For the staging of suspected malignant cases, cervical and mediastinal CT (MRI for inconclusive results) is indicated before any surgery. The end-result of primary treatment is assessed by total-body iodine scintigraphy and the serum human thyroglobulin (hTG) level. For long-term follow-up, physical examination and the serum hTG level are the most reliable tools (6-monthly), supplemented by cervical US and chest X-ray (yearly), and total-body iodine scintigraphy (2-yearly). If these furnish positive results, further examinations may be indicated. In suspected relapses of hTG non-producing and iodine non-accumulating papillary carcinomas, 201thallium chloride or 99mTc-sesta-MIBI (methoxy-isobutyl-isonitrile) scintigraphy, and positron emission tomography with 18fluoro-deoxyglucose or 11C-methionine may be of help. For estimation of the prognosis (cause-specific survival) of the patients, the MACIS score system of the Mayo Clinic is widely accepted, the patients being divided into low-risk and intermediate/high-risk categories. The recommended standard surgical intervention is near-total thyroidectomy (2-4 g residual glandular tissue left at the upper pole of the less-involved lobe), with a central cervical lymph node dissection for diagnostic purposes. In cases of lymph node dissemination, dissection (radical, modified radical, selective or microdissection) of any of the involved compartments (central, right or left cervical, or upper mediastinal) is indicated for therapeutic reasons, the method of which is depending on the extent of the metastatic involvement. Following adequate surgical intervention, no adjuvant radioiodine therapy is indicated for low-risk cases with a tumour of less than 1 cm diameter. For other low-risk or intermediate/high-risk patients, radioiodine ablation (R0N0M0) or a therapeutic radioiodine dosage (R2N1M1) is indicated. In cases at high-risk of local/regional relapse and in radioiodine non-accumulating tumorous cases, external radiotherapy may be applied. Thyroid hormone medication in a TSH suppressive dose is indicated during the first 5 postsurgical years: the goal is to achieve a TSH level below 0.1 (determined by a 3rd generation assay). If no relapse occurs or the case is a low-risk one, following the 5 years, it is enough to maintain the TSH level in a subnormal range (0.1-0.3).

Membrane hyperpolarization removes inactivation of Ca2+ channels, leading to Ca2+ influx and subsequent initiation of sperm motility in the common carp.

Change of osmolality surrounding spawned sperm from isotonic to hypotonic causes the initiation of sperm motility in the common carp. Here we show that membrane-permeable cAMP does not initiate motility of carp sperm that is quiescent in isotonic solution, and that motility of the demembranated sperm can be reactivated without cAMP. Furthermore, the cAMP level does not change during the initiation of sperm motility, and inhibitors of protein kinase do not affect sperm motility, suggesting that no cAMP-dependent system is necessary for the regulation of sperm motility. Sperm motility could not be initiated in Ca(2+)-free hypoosmotic solutions, and significant increase in the intracellular Ca(2+) level was observed by a Ca-sensitive fluorescence dye during hypoosmolality-induced active motion period. The demembranated sperm cells were fully reactivated in the solutions containing 10(-7) to 10(-5) M Ca(2+). Ca(2+) channel blockers such as verapamil and omega-conotoxin reversibly inhibited the initiation of sperm motility, suggesting that Ca(2+) influx is the prerequisite for the initiation of carp sperm motility. Motility of intact sperm was completely blocked; however, that of the demembranated sperm was not inhibited by the calmodulin inhibitor W7, suggesting that the calmodulin bound close to the plasma membrane participated in the initiation of sperm motility. Flow cytometric membrane potential measurements and spectrophotometric measurements by using fluorescence dyes showed transient membrane hyperpolarization on hypoosmolality-induced motility. This article discusses the role of membrane hyperpolarization on removal of inactivation of Ca(2+) channels, leading to Ca(2+) influx at the initiation of carp sperm motility.

The application of image fusion in stereotactic brachytherapy of brain tumours.

BACKGROUND: The visualization of any morphological volume (i.e. CT, MRI) together with an additional second morphological volume (i.e. CT, MRI) or functional data set, which may come from SPECT or PET, is a new method for treatment planning, verification and follow-up of interstitial irradiation. METHOD: The authors present their experience on interstitial irradiation of brain tumours with stereotactically implanted I-125 seeds supported by image fusion. The image fusion was performed by the BrainLab-Target 1.13 software on Alfa 430 (Digital) workstation before, during, and after interstitial irradiation of brain tumours with Iodine125 seeds. RESULTS AND INTERPRETATION: On the basis of 20 brachytherapeutic image fusion of stereotactic CT (slices with fiducials) with additional stereotactic CT, MRI, PET and SPECT images provides more accurate and precise target volume, more exact localization of catheters and isotope seeds (verification fusion), differentiation between the localization and amount of the necrotic and proliferating parts of the tumours and shows the volume changes in consequence of interstitial irradiation. The image fusion should help to improve the accuracy and minimize the perifocal morbidity of interstitial irradiation.

[Evaluation of the nature of brain tumors using methods of nuclear medicine]. / Agydaganatok természetének vizsgálata nukleáris medicinai módszerekkel.

FDG-PET studies permit an assessment of the degree of brain tumour malignancy and detection of tumour recurrence. MIBI-SPECT also affords promising results in this respect. In this work, the diagnostic value of MIBI-SPECT was compared with that of FDG-PET for the determination of primary brain tumours malignancy and the detection of recurrent brain tumours. SPECT and PET examination were carried out within a week in 14 patients (12 males, 2 females, mean age: 40 years, range 16-61 years) with brain tumours. Seven patients had a primary tumour, and in a further 7 MRI or the clinical signs and symptoms let to a suspicion of tumour recurrence. All tumours were verified histologically to be gliomas of grades I-IV. The SPECT and PET images were analysed visually and semiquantitatively. In 3 of the investigated 7 primary glioma patients, there was a visibly enhanced MIBI-positive cases, only one had an increased FDG uptake. In 4 of the 7 tumour recurrence cases, either the MIBI or the FDG uptake was visibly increased. All of these were histologically high-grade gliomas. In the remaining low grade tumours (primary of recurrent), neither MIBI nor FDG revealed a pathologically increased uptake. The intensity of radiopharmaceutical uptake at the site of the tumours was visually and semiquantitatively higher for MIBI that for FDG. It is concluded that MIBI-SPECT is a valuable and simple tool for evaluation of the biological characteristics of brain tumours, showing increased uptake of MIBI according to the malignancy and tumour recurrence of brain tumours.