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PubMed1998

Serum lipids and apolipoprotein E phenotypes in identical twins reared apart.

Lipid and lipoprotein metabolism is controlled by genes, the environment and the gene environment interaction. We studied monozygotic twin pairs reared apart (MZA) and an age sex matched group of twins reared together (MZT) to evaluate the effects of the genotype and the rearing environment on lipids. The intraclass correlations for low density lipoprotein (LDL) cholesterol were 0.21 and 0.50 for the MZA and MZT groups, respectively, suggesting that the rearing environment possibly had an impact on the variability in LDL cholesterol later in life. The intraclass correlations for total cholesterol (0.26 and 0.47 for the MZA and MZT groups, respectively) reflected those for LDL cholesterol. The intraclass correlations for high density lipoprotein (HDL) cholesterol did not show any difference between the twin groups, suggesting that the rearing environment does not have major long-term effects on the variability of HDL levels. The intrapair differences for LDL cholesterol were smallest in the twins heterozygous for the apolipoprotein E allele epsilon2 (E2/3 and E2/4 phenotypes), intermediate in the pairs with the common E3/3 phenotype and enhanced in the pairs with E4/3 phenotype. To conclude, these data suggest that the rearing environment may play a role in the variability of LDL cholesterol levels, although variance difference between MZAs and MZTs, and the small number of available monozygotic twins reared apart limits the generalizability of the results.

Apolipoproteins E↗
PubMed2004

alpha-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases.

Abnormal neuronal aggregates of alpha-internexin and the three neurofilament (NF) subunits, NF-L, NF-M, and NF-H have recently been identified as the pathological hallmarks of neuronal intermediate filament (IF) inclusion disease (NIFID), a novel neurological disease of early onset with a variable clinical phenotype including frontotemporal dementia, pyramidal and extrapyramidal signs. alpha-Internexin, a class IV IF protein, a major component of inclusions in NIFID, has not previously been identified as a component of the pathological protein aggregates of any other neurodegenerative disease. Therefore, to determine the specificity of this protein, alpha-internexin immunohistochemistry was undertaken on cases of NIFID, non-tau frontotemporal dementias, motor neuron disease, alpha-synucleinopathies, tauopathies, and normal aged control brains. Our results indicate that class IV IF proteins are present within the pleomorphic inclusions of all cases of NIFID. Small subsets of abnormal neuronal inclusions in Alzheimer's disease, Lewy body diseases, and motor neuron disease also contain epitopes of alpha-internexin. Thus, alpha-internexin is a major component of the neuronal inclusions in NIFID and a relatively minor component of inclusions in other neurodegenerative diseases. The discovery of alpha-internexin in neuronal cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and other neurological diseases with pathological filamentous neuronal inclusions.

Adult↗
PubMed2001

Genetic variability in Brazilian populations of Biomphalaria straminea complex detected by simple sequence repeat anchored polymerase chain reaction amplification.

Biomphalaria glabrata, B. tenagophila and B. straminea are intermediate hosts of Schistosoma mansoni, in Brazil. The latter is of epidemiological importance in the northwest of Brazil and, due to morphological similarities, has been grouped with B. intermedia and B. kuhniana in a complex named B. straminea. In the current work, we have standardized the simple sequence repeat anchored polymerase chain reaction (SSR-PCR) technique, using the primers (CA)8RY and K7, to study the genetic variability of these species. The similarity level was calculated using the Dice coefficient and genetic distance using the Nei and Li coefficient. The trees were obtained by the UPGMA and neighbor-joining methods. We have observed that the most related individuals belong to the same species and locality and that individuals from different localities, but of the same species, present clear heterogeneity. The trees generated using both methods showed similar topologies. The SSR-PCR technique was shown to be very efficient in intrapopulational and intraspecific studies of the B. straminea complex snails.

Animals↗
PubMed1991

Immunohistochemistry of endometrial stromal sarcoma.

Twenty-three cases (12 low grade, 11 high grade) of endometrial stromal sarcoma were studied with monoclonal antibodies to vimentin, keratin, desmin, muscle actin, epithelial membrane antigen, and collagen type IV, using the avidin-biotin immunoperoxidase method. Tumors were highly variable in the expression of these antigens. Some tumors contained both epithelial and smooth muscle-related antigens; others were immunoreactive only for the intermediate filament vimentin. Immunoreactivity patterns for metastases or recurrences were similar to the respective primary tumor and no correlation was observed between tumor grade and antigen expression. Normal myometrium, when present, was keratin-positive and variably epithelial membrane antigen-positive. We conclude that endometrial stromal sarcoma, as well as normal myometrium, may express both epithelial and/or muscle-related antigens. These findings most likely reflect a common mesodermal-mullerian derivation and illustrate the intimate relationship of the endometrial stromal cell to the endometrial glands and myometrium. Knowledge of these immunoreactivity patterns is essential when evaluating poorly differentiated uterine tumors or spindle cell tumors presenting in extrauterine locations.

Actins↗
PubMed2004

Population structure and genetic variability within isolates of Grapevine fanleaf virus from a naturally infected vineyard in France: evidence for mixed infection and recombination.

The nematode-borne Grapevine fanleaf virus, from the genus Nepovirus in the family Comoviridae, causes severe degeneration of grapevines in most vineyards worldwide. We characterized 347 isolates from transgenic and conventional grapevines from two vineyard sites in the Champagne region of France for their molecular variant composition. The population structure and genetic diversity were examined in the coat protein gene by IC-RT-PCR-RFLP analysis with EcoRI and StyI, and nucleotide sequencing, respectively. RFLP data suggested that 55 % (191 of 347) of the isolates had a population structure consisting of one predominant variant. Sequencing data of 51 isolates representing the different restrictotypes confirmed the existence of mixed infection with a frequency of 33 % (17 of 51) and showed two major predominant haplotypes representing 71 % (60 of 85) of the sequence variants. Comparative nucleotide diversity among population subsets implied a lack of genetic differentiation according to host (transgenic vs conventional) or field site for most restrictotypes (17 of 18 and 13 of 18) and for haplotypes in most phylogenetic groups (seven of eight and six of eight), respectively. Interestingly, five of the 85 haplotypes sequenced had an intermediate divergence (0.036-0.066) between the lower (0.005-0.028) and upper range (0.083-0.138) of nucleotide variability, suggesting the occurrence of homologous RNA recombination. Sequence alignments clearly indicated a mosaic structure for four of these five variants, for which recombination sites were identified and parental lineages proposed. This is the first in-depth characterization of the population structure and genetic diversity in a nepovirus.

Base Sequence↗
PubMed1992

Intestinal absorption of peptides and peptide analogues: implications of fasting pancreatic serine protease levels and pH on the extent of oral absorption in dogs and humans.

In order to describe and predict the impact of intestinal metabolism on peptide absorption, intestinal chymotrypsin activity, flow rate, and pH were characterized in fasted, duodenally fistulated dogs as a function of gastrointestinal (GI) motility phase. GI motility was classified as either active or quiescent. Cumulative volume, F(t), and volumetric flow rate, Q(t), curves were constructed and the data were sorted according to motility phase. The mean +/- SE active phase pH was 6.4 +/- 0.3, whereas the quiescent phase pH was 7.3 +/- 0.3. The difference between the mean active and the mean quiescent phase pH values was significant. The active and quiescent phase flow rates (ml/min) were also significantly different, at values of 1.2 +/- 0.2 and 0.28 +/- 0.07, respectively. The active phase flow rates were consistent among the dogs studied; however, the quiescent phase flow rates were highly variable among the dogs. The variability of the quiescent phase flow rates was expected since phase II of the GI motility cycle is characterized by intermediate, irregular spike activity. The mean active and quiescent phase chymotrypsin activities were 1.87 x 10(-5) +/- 0.53 x 10(-5) and 1.56 x 10(-5) +/- 0.65 x 10(-5) M, respectively. The active phase values were not statistically different among dogs, however, the quiescent phase values were found to be highly variable among dogs. The difference between the active and the quiescent phase chymotrypsin mean levels, however, was not statistically significant. The chymotrypsin levels determined in dogs were found to be approximately 10 times greater than those reported in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2004

Prediction of indoor climbing performance in women rock climbers.

In an attempt to more clearly understand the strength characteristics of female rock climbers and whether those variables affect and predict climbing performance, 2 indoor climbing performance tests (route and bouldering) were compared to a series of muscular strength tests performed by moderate (n = 6), intermediate (n = 6), and expert (n = 6) female rock climbers. Significant differences (p < 0.05) were found between the expert group and the moderate and intermediate groups for climbing specific hand strength, as well as 1-arm lock-off strength when expressed as a strength-to-weight ratio. Multiple correlations showed that these variables (r > 0.426) as well as a questionnaire of past climbing performance (r > 0.86) significantly correlated to the tests of indoor climbing performance. In conclusion, climbing-specific tests of hand strength and of one arm lock-off strength reliably and sensitively measured 2 significant variables in the performance of indoor rock climbing, and a questionnaire of past best performance may be an accurate tool for the prediction of indoor climbing performance.

Adolescent↗
PubMed1999

Atrazine removal by ozonation processes in surface waters.

Atrazine (6-chloro-N-ethyl-N'-isopropyl-1,3,5-triazinedyl-2,4-diamine) was treated with ozone alone and in combination with hydrogen peroxide or UV radiation in three surface waters. Experiments were carried out in two bubble reactors operated continuously. Variables investigated were the ozone partial pressure, temperature, pH, mass flow ratio of oxidants fed: hydrogen peroxide and ozone and the type of oxidation including UV radiation alone. Residence time for the aqueous phase was kept at 10 min. Concentrations of some intermediates, including deethylatrazine, deisopropylatrazine and deethyldeisopropylatrazine, were also followed. The nature of water, specifically the alkalinity and pH were found to be important variables that affected atrazine (ATZ) removal. Surface waters with low alkalinity and high pH allowed the highest removal of ATZ to be reached. There was an optimum hydrogen peroxide to ozone mass flow ratio that resulted in the highest ATZ removal in each surface water treated. This optimum was above the theoretical stoichiometry of the process. Therefore, to reach the maximum removal of ATZ in a O3/H2O2 process, more hydrogen peroxide was needed in the surface waters treated than in ultrapure water under similar experimental conditions. In some cases, UV radiation alone resulted in the removal of ATZ higher than ozonation alone. This was likely due to the alkalinity of the surface water. Ozonation and UV radiation processes yield different amounts of hydrogen peroxide. Combined ozonations (O3/H2O2 and O3/UV) lead to ATZ removals higher than single ozonation or UV radiation but the formation of intermediates was higher.

Atrazine↗
PubMed1977

Effect of major motor seizure frequency upon cognitive-intellectual functions in adults.

Wechsler Aandult Intelligence Scale and Halstead neuropsychological performances were investigated in three groups of adult subjects with major motor epilepsy classified according to low, moderate, and high seizure frequency. The groups were equated on seizure duration and age at onset variables. On 7 of the 14 psychological measures employed, significant between-group differences were obtained, with poorest, intermediate, and best test scores associated with the high, moderate, and low seizure frequency groups, respectively. Similar performance comparisons were made on two additional groups: a "high risk" group characterized by early onset age, long seizure duration, and high seizure frequency, and a "low risk" group characterized by late onset age, short seizure duration, and low seizure frequency. Highly significant differences were obtained between the high risk and low risk groups on 12 of 14 variables, with the high risk subjects demonstrating severe cognitive and adaptive impairment in comparison to the low risk subjects. The results support the conclusion that increased frequency of major motor seizures is associated with increasing levels of adaptive impairment, and that the probability of severe cognitive-adaptive dysfunction is further and substantially increased when high seizure frequency is accompanied by a history of early onset and long duration of the disorder.

Adult↗
PubMed1991

Analysis of replicative intermediates produced during bacteriophage phi 29 DNA replication in vitro.

Replication of bacteriophage phi 29 DNA initiates at either end of its linear double-stranded DNA molecule and proceeds by a strand-displacement mechanism. In the present paper we have used an in vitro phi 29 DNA replication system to analyse by electron microscopy the replicative intermediates produced at different reaction times. Two types of replicative intermediates were observed: type I (full-length double-stranded phi 29 DNA molecules with one or more single-stranded DNA branches) and type II (full-length phi 29 DNA molecules formed by a double-stranded DNA portion of variable length from one end plus a single-stranded DNA portion spanning to the other end). Thus, the types of replicative intermediates produced in vivo were also formed in the in vitro phi 29 DNA replication system. Analysis of type I intermediates indicated that initiation of DNA replication occurs preferentially at both ends of the same DNA template, in a non-simultaneous manner. Type II intermediates appeared as early as two minutes after the reaction started, well before unit-length single-stranded phi 29 DNA molecules were synthesized. In addition, replication of recombinant phi 29 DNA templates lacking terminal protein at one end did not produce type II intermediates and led to an accumulation of full-length single-stranded phi 29 DNA molecules. These two observations strongly suggest that type II intermediates appear when two growing DNA chains, running from opposite ends, merge.

Bacillus subtilis↗
PubMed2005

Subcutaneous insulin: pharmacokinetic variability and glycemic variability.

The therapeutic goal in insulin-treated diabetic patients is to maintain on the long-term a tight glucose control (HbA1, < 6.5-7% or less) through an insulin regimen which "mimic" the physiological insulin profile: a basal insulin secretion to maintain glucose homeostasis and an acute post-prandial secretion in response to meal intake. Such goal represents a challenge for the clinician as conventional human insulins have major drawbacks: slow absorption and too late peak with regular insulins, delayed peak and often occuring at an unwanted time with intermediate and long-acting insulins. Furthermore, these insulins are characterised by a large within- and between-subjects variability, which complicate patients' task to self-adapt their daily doses, even for those well educated and compliants. These limitations and unpredictable variations in insulin action are responsible for an increased risk of hypoglycemic events, between meals as well as during the night period. As a consequence, glucose control is frequently insufficient in type 1 diabetic patients, and these limitations may contribute also to the delayed initiation of insulin therapy in type 2 diabetics when oral antidiabetic agents fail. This variability and the non-reproducibility of the conventional insulin pharmacodynamics are explained by several exogenous and endogenous factors describe in this review. Availability of new short-acting (lispro, aspart and glulisine) and long-acting analogs (glargine, detemir) of human insulin, with improved pharmacokinetic characteristics, and a lesser variability and better reproducibility, should facilitate a tight glucose control in insulin-treated patients. The main pharmacokinetic and pharmacodynamic characteristics of these new insulin analogs are presented and discussed in the light of there intra- and inter-individual variability. Their reduced variability should permit to reinforce near "physiological" insulin regimen such as "basal-bolus" technique and to consider new approaches and therapeutic strategies in type 1 and type 2 diabetic patients.

Blood Glucose↗
PubMed2006

Usefulness of translesional pressure gradient and pharmacological provocation for the assessment of intermediate renal artery disease.

OBJECTIVE: We sought to determine the hemodynamic significance of intermediate RAS by measuring translesional systolic pressure gradients (TSPG), using a pressure-sensing guidewire at baseline and after acetylcholine (ACh) induced hyperemia, following selective renal artery angiography. BACKGROUND: Renal artery stenosis (RAS) is a cause of reversible hypertension and nephropathy. Stenting effectively relieves RAS, however improvement in blood pressure control or renal function is variable and unpredictable. Hemodynamic significance is usually present with RAS when diameter stenosis is >75%, but is less predictable in intermediate (30%-75%) RAS. METHODS: Twenty-two patients (26 renal arteries) with uncontrolled hypertension underwent invasive hemodynamic assessment because of intermediate RAS, defined as radiocontrast angiographic diameter stenosis (DS) between 30% and 75% (quantitative DS was measured prospectively). Translesional pressure gradients were measured using a 0.014" pressure-sensing wire. Hyperemia was induced by administration of intrarenal ACh. RESULTS: Visual and measured angiographic lesion severity did not correlate with TSPG either at baseline (visual DS, R(2) = 0.091, P = 0.13; measured DS, R(2) = 0.124, P = 0.07) or with hyperemia (visual DS, R(2) = 0.057, P = 0.24; measured DS, R(2) = 0.101, P = 0.12). Baseline and maximal hyperemic gradient did correlate (R(2) = 0.567; P < 0.05). Pharmacological provocation produced a significant increase in TSPG (mean; baseline, 18 +/- 21 vs. hyperemia, 34 +/- 41 mm Hg; P < 0.05). A hemodynamically significant lesion (TSPG > 20 mm Hg) was found in 14/26 (54%) arteries (13 patients); 13 (60%) patients subsequently underwent renal artery stenting for hemodynamically significant RAS. At follow-up (at least 30 days), there was a significant decrease in systolic blood pressure (mean; 167 +/- 24 vs. 134 +/- 19 mm Hg; P < 0.001). CONCLUSIONS: Intrarenal administration of ACh induces hyperemia and can be used to unmask resistive renal artery lesions. Gradient measurement and induced hyperemia may be warranted in the invasive assessment of intermediate renal artery stenoses, rather than relying on stenosis severity alone. Further study is needed to determine whether translesional pressure gradients and pharmacological provocation predict clinical benefit after renal artery stenting.

Acetylcholine↗
PubMed1998

Low CD3+CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells.

The capacity of neonatal T cells to secrete interleukin-2 (IL-2) has been reported to be variable. We analysed IL-2 production in purified neonatal and adult T cells using polyclonal activator phorbol ester + calcium ionophore (PDBu + iono) or receptor-mediated anti-CD3/anti-CD3+ anti-CD28 stimulation. PDBu + iono induced equally high IL-2 levels in both groups and, when stimulated with plate-bound anti-CD3 monoclonal antibody (mAb), the IL-2 secretion by neonatal cells was undetectable and adult cells produced low amounts of IL-2 (mean 331 +/- 86 pg/ml). The addition of anti-CD28 mAb to anti-CD3-stimulated cells markedly increased IL-2 production in both cell types, but levels of IL-2 in neonatal T cells remained clearly lower than those of adult T cells (respective mean values: 385 +/- 109 pg/ml and 4494 +/- 1199 pg/ml). As NF-kappa B is a critical transcription factor in the control of IL-2 expression, we next analysed its nuclear translocation in neonatal and adult T cells using the electrophoretic mobility shift assay and, because induction of reactive oxygen intermediates (ROI) is required for the activation of NF-kappa B, we also analysed levels of intracellular ROI in these cells using the ROI-reactive fluorochrome DCFH-DA and flow cytometry. In neonatal T cells NF-kappa B activation and ROI formation after anti-CD3 stimulation were low compared with adult T cells and, although addition of anti-CD28 mAb increased induction of NF-kappa B and ROI formation, levels similar to those of adults were not achieved. After PDBu + iono stimulation, the cells showed similar ROI formation and IL-2 secretion. Our results suggest that reduced IL-2 production by neonatal T cells is specific for anti-CD3 and anti-CD3+ anti-CD28-mediated stimulation and that these activators cannot effectively activate the ROI-NF-kappa B signalling pathway in neonatal T cells.

Adult↗
PubMed2001

An effective approach to violence prevention: traditional martial arts in middle school.

This study replicated and extended the design and outcome measures of several small studies. In these studies, juveniles at high risk for violence and delinquency showed decreased violence and positive changes in psychological risk factors after being required to take a school-linked course in traditional martial arts. In the present study, 60 boys in a large urban middle school were required to take a traditional martial arts course in their school. They were paired on problematic behavior profiles and assigned to a treatment group or to a wait-list control group. Thirty classes, three per week (45 minutes each), were taught by a master of Koga Ha Kosho Shorei Ryu Kempo and his assistant (neither was a public school teacher). Results are reported here for 14 variables from the following measures: four teacher rating scales from the Sutter-Eyberg Student Behavior Inventory, five self-report scales of the Piers-Harris Self-Concept Scale, four computerized measures of attentional self-control from the Intermediate Visual and Auditory Continuous Performance Test, and a count of permanent expulsions from school. The treatment students improved over baseline on 12 variables, while the controls improved on 5 by small amounts and deteriorated from baseline on 8, including teacher-rated violence. There were significant differences between the groups on self-reported happiness and schoolwork and on one measure of attention. After controls took the course, their scores resembled the postcourse scores of the treatment group. Importantly, the control group's increase in teacher-rated violence was reversed. Both groups were then pooled to compare baseline and postcourse teacher ratings. Their scores improved significantly in the areas of resistance to rules, impulsiveness, and inappropriate social behavior. There was also improvement in regard to violence, but the change in scores was not statistically significant. Follow-up on teachers' ratings showed that improvement remained, and in some cases increased, four months after completion of the course. Interestingly, all 6 permanent expulsions were among the control group students who had not yet taken, or had only begun taking, the martial arts course.

Adolescent↗
PubMed1991

Proteolytic processing of pol-TYB proteins from the yeast retrotransposon Ty1.

Using antibodies directed against the TYB1 protein of the transpositionally competent retrotransposon Ty1-H3, we have identified three mature proteins of 23, 60, and 90 kDa and processing intermediates of 140 and 160 kDa that are derived from the 190-kDa TYA1-TYB1 polyprotein. Mature proteins and variable amounts of the precursors cofractionate with Ty viruslike particles. The map locations and precursor-product relationships of mature TYB1 polypeptides suggest that p23 is Ty1 protease, p90 is integrase, and p60 contains reverse transcriptase and RNase H. Immunoprecipitation and immunoblot analyses of Ty1 proteins show that p190 is cleaved to form p160. The p160 intermediate is cleaved to form p23 and p140, and p140 is cleaved to form p90 and p60. Processing of TYB1 proteins is dependent on Ty1 protease. Immunoblot analysis of TYB proteins from different Ty1 isolates reveal that correct processing of TYB1 proteins is a characteristic of functional Ty1 elements, whereas aberrant processing is a common defect found in transposition-incompetent elements.

Amino Acid Sequence↗
PubMed1997

Procainamide induced change of the width of the zone of entrainment and its relation to the inducibility of reentrant ventricular tachycardia.

Procainamide depresses conduction velocity and prolongs refractoriness in myocardium responsible for reentrant VT, but the mechanism by which the induction of VT is suppressed after procainamide administration remains to be determined. In the present study, the relationship between electrophysiological parameters and the noninducibility of VT was assessed during procainamide therapy with a special reference to the change of an excitable gap. Clinically documented monomorphic sustained VT was induced in 30 patients and, utilizing the phenomenon of transient entrainment, the zone of entrainment was measured as the difference between the cycle length of VT and the longest paced cycle length interrupting VT (block cycle length) which was determined as the paced cycle length decreased in steps of 10 ms, and used as an index of the excitable gap. The effective refractory period was measured at the pacing site and the paced QRS duration was used as an index of the global conduction time in the ventricle. The cycle length of VT, the block cycle length, and the width of the zone of entrainment were determined and compared between the responders and nonresponders. In 15 patients, these parameters were determined at the intermediate dose and related to subsequent noninducibility at the final dose. At the final doses of procainamide, VT was suppressed in 8 (26.7%) of 30 patients. However, the cycle length of VT, the block cycle length, and the width of the zone of entrainment were unable to predict the drug efficacy, i.e., noninducibility. The change in the effective refractory period at the pacing site or the width of the paced QRS duration was not different between the responders and nonresponders. Among the variables, only the width of the zone of entrainment showed a significant narrowing in the responders at the intermediate dose of procainamide, and it was smaller than that of the nonresponders. The significant narrowing of the width of the zone of entrainment was associated with the subsequent noninducibility of VT at the final dose. The present study showed that the baseline cycle length of VT, the block cycle length, the drug induced change of the effective refractory period, or the paced QRS duration was not a predictor of the noninducibility after procainamide administration. However, a significant narrowing of the width of the zone of entrainment at the intermediate dose was associated with the noninducibility of VT at the final dose.

Adolescent↗
PubMedDate not supplied

Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells.

The variable regions of immunoglobulin heavy chains are encoded in the germ line by three discrete DNA segments: VH (variable) elements, D (diversity) elements and JH (joining) elements. During the differentiation of B lymphocytes, individual segments from each group are brought together by recombination to form the complete VHDJH variable region. To understand these processes better, we have now isolated and sequenced molecular clones representing intermediates (DJH fusions) and final products (VH-to-DJH joins) of heavy-chain gene rearrangement in two cell lines that represent analogues of cells at early stages of B-lymphocyte differentiation. Heavy-chain gene assembly in one cell line but not in the other is accompanied by the appearance of short nucleotide insertions at the recombinational junctions. The generation of such insertions is positively correlated with the expression of terminal deoxynucleotidyl transferase in these lines.

Animals↗
PubMed2006

Follicular lymphoma in early stages: high risk of relapse and usefulness of the Follicular Lymphoma International Prognostic Index to predict the outcome of patients.

BACKGROUND AND OBJECTIVES: Patients with follicular lymphoma (FL) in advanced stages are currently deemed incurable with standard treatments. However, FL is considered to be eradicable in the small group of patients presenting with localized disease. The objective of this study was to analyze the clinical features and the outcome of a series of patients with FL in early stages with a long follow-up. PATIENTS AND METHODS: A total of 48 patients (25m/23f; median age: 50 yr) diagnosed consecutively with FL in Ann Arbor stage I (25 cases) or II (23) at a single institution with a median follow-up of 9.5 yr were included in the study. Main biological and clinical characteristics at diagnosis, including Follicular Lymphoma International Prognostic Index (FLIPI) were analyzed; treatment and response were assessed and analyzed for prognosis. RESULTS: The histologic subtypes were: FL type I, 20 cases (42%); type II, 24 (50%); type III, three (6%); and unclassifiable, one (2%). Distribution according to FLIPI was: low risk (36 cases) and intermediate risk (five cases). Treatment mainly consisted of combination chemotherapy (CHOP in 34 cases) plus involved-field radiotherapy in 26 cases. Forty patients (89%) achieved a complete response (CR), three (7%) a partial response, and two (4%) were non-responders; the remaining three patients did not receive therapy. No initial variable predicted CR achievement. About 57% of the patients in CR eventually relapsed with a relapse risk of 46% at 10 yr. Intermediate-risk FLIPI predicted failure-free survival. Histologic transformation was observed in six patients with a 10-yr risk of transformation of 13%. Twelve patients died during follow-up, in two cases as a result of unrelated causes. Overall survival (OS) at 10 yr was 79%. The FLIPI was the sole variable predicting OS. CONCLUSIONS: Although the majority of patients with localized FL achieve CR, the risk of relapse is high. The FLIPI is of prognostic value in these patients.

Adult↗