[Cemented stems in revision total knee arthroplasty on patients older than 75 y/o. Clinical and radiological analysis]. / Vástagos cementados en recambios de prótesis total de rodilla en pacientes mayores de 75 años. Análisis clínico y radiológico.

BACKGROUND: The purpose of this study was to analyze the clinical and radiological evolution of the total knee revision arthroplasty with cemented stems in patients over 75 years. MATERIAL AND METHODS: A retrospective analysis was performed in all the subjects who underwent revision of total knee arthroplasty with cemented stems between 2008 and 2014 in our center. Twenty-seven individuals over 75 years met the inclusion criteria. We assessed the Knee Society Score and range of motion for clinical outcome. We evaluated the implant stability with radiographs through radiolucent lines according to the modified radiological scale of the Knee Society; we registered the complications and prosthetic survival. RESULTS: With an average age of our participants of 82.6 ± 4.4 years and a follow-up of 43 ± 14.4 months, we did not find any mechanical failure of the components. The functional average score was 115 ± 32 in the total KSS, of which 77 ± 17.5 points were in the KSS knee and 42 ± 24 in the KSS function. The average range of motion was 98º ± 17. Radiologically, 18 patients presented radiolucent lines, but only three needed follow-up using the modified Knee Society radiographic scoring system. CONCLUSIONS: The results revealed that cemented stems are a good method for fixation in the revision of total knee arthroplasty in people over 75 years. We observed acceptable medium-term clinical results with a low risk of radiological failure, despite the high number of radiolucencies.

Analizar la evolución funcional y radiológica de los pacientes mayores de 75 años intervenidos de cirugía de revisión de rodilla con vástagos cementados.

Vástagos cementados en recambios de prótesis total de rodilla en pacientes mayores de 75 años. Análisis clínico y radiológico / Cemented stems in revision total knee arthroplasty on patients older than 75 y/o. Clinical and radiological analysis

Resumen: Antecedentes: Analizar la evolución funcional y radiológica de los pacientes mayores de 75 años intervenidos de cirugía de revisión de rodilla con vástagos cementados. Material y métodos: Mediante análisis retrospectivo, hemos revisado a 27 individuos mayores de 75 años a quienes se les ha implantado una prótesis total de rodilla de revisión con vástagos cementados en nuestro centro entre 2008-2014. Durante el seguimiento, se realizó un análisis clínico mediante la escala Knee Society Score y de movilidad de la rodilla, un análisis radiológico de la estabilidad de los implantes por medio de la escala radiológica modificada de la Knee Society, el registro de las complicaciones y la supervivencia protésica. Resultados: Con una edad media de los participantes de 82.6 ± 4.4 años y un seguimiento medio de 43 ± 14.4 meses, no hemos observado ningún caso de aflojamiento mecánico de los componentes. La valoración funcional ha sido de 115 ± 32 puntos en la escala total KSS, de los cuales 77 ± 17.5 puntos pertenecen al KSS rodilla y 42 ± 24 puntos al KSS función. El rango medio de movilidad fue de 98o ± 17. A nivel radiológico, 18 sujetos mostraron radiolucencias periprotésicas; según los criterios de la escala radiológica de la Knee Society, solo tres requirieron seguimiento clínico-radiológico estricto. Conclusiones: La cementación de los vástagos en prótesis totales de rodilla de revisión se trata de un buen sistema de fijación en personas mayores de 75 años, con elevada supervivencia del implante, buen resultado funcional y bajo porcentaje de aflojamiento radiológico a pesar de la aparición frecuente de radiolucencias.

Abstract: Background: The purpose of this study was to analyze the clinical and radiological evolution of the total knee revision arthroplasty with cemented stems in patients over 75 years. Material and methods: A retrospective analysis was performed in all the subjects who underwent revision of total knee arthroplasty with cemented stems between 2008 and 2014 in our center. Twenty-seven individuals over 75 years met the inclusion criteria. We assessed the Knee Society Score and range of motion for clinical outcome. We evaluated the implant stability with radiographs through radiolucent lines according to the modified radiological scale of the Knee Society; we registered the complications and prosthetic survival. Results: With an average age of our participants of 82.6 ± 4.4 years and a follow-up of 43 ± 14.4 months, we did not find any mechanical failure of the components. The functional average score was 115 ± 32 in the total KSS, of which 77 ± 17.5 points were in the KSS knee and 42 ± 24 in the KSS function. The average range of motion was 98o ± 17. Radiologically, 18 patients presented radiolucent lines, but only three needed follow-up using the modified Knee Society radiographic scoring system. Conclusions: The results revealed that cemented stems are a good method for fixation in the revision of total knee arthroplasty in people over 75 years. We observed acceptable medium-term clinical results with a low risk of radiological failure, despite the high number of radiolucencies.

Importance of early absolute lymphocyte count after allogeneic stem cell transplantation: a retrospective study.

INTRODUCTION: Early lymphocyte recovery after allogeneic hematopoietic stem cell transplantation (HSCT) is related to the prevention of serious infections and the clearing of residual tumor cells. METHODS: We analyzed the absolute lymphocyte count at 20 (D+20) and 30 (D+30) days after HSCT in 100 patients with malignant hematologic diseases and correlated with the risk of transplant-related mortality, overall survival (OS), disease-free survival (DFS), nonrelapsed mortality (NRM), and risk of infection. RESULTS: Patients presenting with lymphocyte counts of <300 × 103/µL on D+30 have a 3.76 times greater risk of death in <100 days. Over a medium follow-up of 20 months OS, DFS, and NRM were similar between the groups. CONCLUSION: In our group of patients delayed lymphocyte recovery after HSCT was a predictor of early death post-HSCT.

Quality of life and motor impairment in ALS: Italian validation of ALSAQ.

OBJECTIVES: To evaluate the validity and reliability of the amyotrophic lateral sclerosis assessment questionnaire (ALSAQ) in an Italian cohort of ALS patients and to further characterize the relationship between motor impairment and quality of life (QoL) in ALS. METHODS: Seventy-six patients completed the Italian version of ALSAQ-40 and ALSAQ-5. To verify test-retest reliability, 30 patients were revaluated after 3 months. The medical outcome study short form 36 (MOS SF-36) questionnaire and revised ALS functional rating scale (ALSFR-R) scale were used to assess Italian ALSAQ-40 construct validity. The limb muscles' Medical Research Council (MRC) score and forced vital capacity (FVC) were used to measure the degree of motor impairment. RESULTS: The Italian ALSAQ-40 showed a very good internal consistency (all subscales Cronbach's alpha>0.86) and a good construct validity as shown by the patterns of correlation between the subscales and SF-36 (resp. ALSFRS-R) scores. ALSAQ-5 showed a positive correlation with the corresponding ALS patient total score and subscale scores of the ALSAQ-40 (Spearman's correlation coefficient>0.73). The emotional functioning subscale did not correlate with any motor impairment measures. DISCUSSION: Italian ALSAQ-40 and ALSAQ-5 psychometric properties are reliable and similar to those showed by the original English version. We observed emotional aspects to be distinct from physical involvement.

In-vacuum optical isolation changes by heating in a Faraday isolator.

We describe a model evaluating changes in the optical isolation of a Faraday isolator when passing from air to vacuum in terms of different thermal effects in the crystal. The changes are particularly significant in the crystal thermal lensing (refraction index and thermal expansion) and in its Verdet constant and can be ascribed to the less efficient convection cooling of the magneto-optic crystal of the Faraday isolator. An isolation decrease by a factor of 10 is experimentally observed in a Faraday isolator that is used in a gravitational wave experiment (Virgo) with a 10 W input laser when going from air to vacuum. A finite element model simulation reproduces with a great accuracy the experimental data measured on Virgo and on a test bench. A first set of measurements of the thermal lensing has been used to characterize the losses of the crystal, which depend on the sample. The isolation factor measured on Virgo confirms the simulation model and the absorption losses of 0.0016 +/- 0.0002/cm for the TGG magneto-optic crystal used in the Faraday isolator.

Upper limits on gravitational-wave emission in association with the 27 Dec 2004 giant flare of SGR1806-20.

At the time when the giant flare of SGR1806-20 occurred, the AURIGA "bar" gravitational-wave (GW) detector was on the air with a noise performance close to stationary Gaussian. This allows us to set relevant upper limits, at a number of frequencies in the vicinities of 900 Hz, on the amplitude of the damped GW wave trains, which, according to current models, could have been emitted, due to the excitation of normal modes of the star associated with the peak in x-ray luminosity.

Memory deficits and retrieval processes in ALS.

Subtle neuropsychological deficits have been described in patients affected by amyotrophic lateral sclerosis (ALS) without dementia. Overall, selective impairment in memory function has been reported, but the source of memory impairment in ALS has yet to be defined. We performed neuropsychological screening in 20 ALS patients. Semantic encoding and post-encoding cue effects on the retrieval of word lists were investigated in the ALS patients and normal controls. Severity of memory impairment was correlated to cerebral blood perfusion detected by single photon emission computed tomography (SPECT). ALS patients showed moderate impairments in frontal and memory tests. Short-term memory was normal, while serial position retrieval of word lists with normal recency effect but poor primacy effect showed long-term memory deficit. ALS patients performed better in cued encoding than in cued post-encoding recall condition. In the cued post-encoding condition, the primacy effect in word list recall improved significantly in controls, but not in ALS patients, as compared with both the free recall and cued encoding conditions. SPECT hypoperfusion was observed in frontal and temporal areas in ALS patients. ALS patients showed a long-term memory deficit which did not improve in cued post-encoding condition as it does for controls. We hypothesize abnormal retrieval processes related to frontal lobe dysfunction which entails difficulties in generating stable long-memory traces at encoding.

Cellular specificity of proexendin-4 processing in mammalian cells in vitro and in vivo.

Glucagon-like peptide-1 (GLP-1) is a potent stimulator of glucose-dependent insulin secretion. Exendin-4(1-39) (Ex-4), isolated from Gila monster venom, is a highly specific GLP-1 receptor agonist that exhibits a prolonged duration of action in vivo. Although the processing mechanisms underlying liberation of GLP-1 from its prohormone have been elucidated, those for Ex-4 remain unknown. To examine the requirements for proEx-4 processing in mammalian cells, BHK fibroblasts, InR1-G9 islet A cells, and AtT-20 corticotropes, which express different prohormone convertases (furin, prohormone convertase 2, and prohormone convertase 1, respectively) were transfected with full-length lizard proEx-4, and the processing of proexendin was examined by HPLC and RIA (n = 3). All of the transfected cell lines exhibited Ex-4-like immunoreactivity in the media, and Ex-4-like immunoreactivity was detected in extracts of InR1-G9 and AtT-20 cells. However, only media and extracts from AtT-20 cells (not InR1-G9 and BHK cells) contained a single peak by HPLC corresponding to synthetic Ex-4. To establish whether proEx-4 can be processed to Ex-4 in nonimmortalized mammalian cells in vivo, the molecular forms of exendin-4 were examined in mice expressing a metallothionein-proEx-4 transgene (n = 3-6 for both males and females). ProEx4 mRNA transcripts were detected by RT-PCR in a broad range of both endocrine and nonendocrine tissues. Ex-4-like immunoreactivity was detected in pituitary, fat, adrenals, and testes; however HPLC analyses demonstrated that processed Ex-4 was found only in adrenals and testes. These results indicate that lizard proEx-4 is processed to mature bioactive Ex-4 in both rodent endocrine and nonendocrine mammalian cell types in vitro and in murine tissues in vivo. These findings may be useful for engineering cells that express a lizard pro-Ex4 transgene for the treatment of type 2 diabetes.

Relative biological effectiveness of light ions in human tumoural cell lines: role of protein p53.

Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type.

Radiosensitivity of V79 cells after alpha particle radiation at low doses.

Low dose hyper-radiosensitivity (HRS) of V79 cells was demonstrated after irradiation with gamma rays and 4He2+ ions of various linear energy transfer (LET) values (58.9, 79.3 and 101.7 keV.micron-1). In parallel, the cytogenetic analysis showed an LET dependence of aberrations at a dose of 1 Gy, while the observed chromatid fragments appeared to vary with the number of 4He2+ ions traversing the cell nucleus. The results of both studies are correlated so as to achieve a better understanding of the so-called induced radioresistance. The cell mechanism of radioresistance appears to be induced after a certain amount of energy is deposited in the cell nucleus. This amount depends both on the radiation quality as well as the number of particles traversing the cell, inducing chromosome alterations and chromatid damage.

Low-dose hypersensitivity of V79 cells under exposure to gamma-rays and 4He ions of different energies: survival and chromosome aberrations.

PURPOSE: To examine the low-dose sensitivity of V79 cells under exposure to gamma-rays and 4He ions of different energies. MATERIALS AND METHODS: Cell survival and cytogenetic analysis using the Giemsa technique were studied following irradiation to doses of 0-3 Gy at the INFN-LNL facilities. RESULTS: Low-dose hyper-radiosensitivity (HRS) of V79 was demonstrated after irradiation with gamma-rays and alpha-particles of various linear energy transfers (LET) (58.9, 79.3 and 101.7 keV microm(-1)). Cytogenetic analysis showed an LET dependence of aberrations at a dose of 1Gy; the frequency of chromatid fragments appeared to vary with the number of alpha-particles traversing the cell nucleus. The results of both studies fit together to give a better understanding of so-called 'induced radioresistance' phenomenon. CONCLUSIONS: The mechanism of induced cellular radioresistance appears to be initiated after a certain amount of energy is deposited in the cell nucleus. This amount depends on both radiation quality and the number of particles traversing the cell.

First search for gravitational wave bursts with a network of detectors

We report the initial results from a search for bursts of gravitational radiation by a network of five cryogenic resonant detectors during 1997 and 1998. This is the first significant search with more than two detectors observing simultaneously. No gravitational wave burst was detected. The false alarm rate was lower than 1 per 10(4) yr when three or more detectors were operating simultaneously. The typical threshold was H approximately 4x10(-21) Hz-1 on the Fourier component at approximately 10(3) Hz of the gravitational wave strain amplitude. New upper limits for amplitude and rate of gravitational wave bursts have been set.

Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, regulates fasting glycemia and nonenteral glucose clearance in mice.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) potentiate glucose-stimulated insulin secretion after enteral nutrient ingestion. We compared the relative incretin and nonincretin actions of GLP-1 and GIP in +/+ and GLP-1R-/- mice using exendin(9-39) and immunopurified anti-GIP receptor antisera (GIPR Ab) to antagonize GLP-1 and GIP action, respectively. Both antagonists produced a significant increase in glycemic excursion after oral glucose loading of +/+ mice (P < 0.05 for antagonists us. controls). Exendin(9-39) also increased blood glucose and decreased glucose-stimulated insulin in +/+ mice after ip glucose loading [0.58 +/- 0.02 vs. 0.47 +/- 0.02 ng/ml in saline- vs. exendin(9-39)-treated mice, respectively, P < 0.05]. In contrast, GIPR Ab had no effect on glucose excursion or insulin secretion, after ip glucose challenge, in +/+ or GLP-1R-/- mice. Repeated administration of exendin(9-39) significantly increased blood glucose and reduced circulating insulin levels but had no effect on levels of pancreatic insulin or insulin messenger RNA transcripts. In contrast, no changes in plasma glucose, circulating insulin, pancreatic insulin content, or insulin messenger RNA were observed in mice, 18 h after administration of GIPR Ab. These findings demonstrate that GLP-1, but not GIP, plays an essential role in regulating glycemia, independent of enteral nutrient ingestion in mice in vivo.

Sustained expression of exendin-4 does not perturb glucose homeostasis, beta-cell mass, or food intake in metallothionein-preproexendin transgenic mice.

Activation of glucagon-like peptide (GLP)-1 receptor signaling promotes glucose lowering via multiple mechanisms, including regulation of food intake, glucose-dependent insulin secretion, and stimulation of beta-cell mass. As GLP-1 exhibits a short t(12) in vivo, the biological consequences of prolonged GLP-1 receptor signaling remains unclear. To address this question, we have now generated metallothionein promoter-preproexendin (MT-Ex) transgenic mice. MT-Ex mice process preproexendin correctly, as is made evident by detection of circulating plasma exendin-4 immunoreactivity using high pressure liquid chromatography and an exendin-4-specific radioimmunoassay. Despite elevated levels of exendin-4, fasting plasma glucose and glucose clearance following oral and intraperitoneal glucose tolerance tests are normal in MT-Ex mice. Induction of transgene expression significantly reduced glycemic excursion during both oral and intraperitoneal glucose tolerance tests (p < 0.05) and increased levels of glucose-stimulated insulin following oral glucose administration (p < 0.05). Despite evidence that exendin-4 may induce beta-cell proliferation, beta-cell mass and islet histology were normal in MT-Ex mice. MT-Ex mice exhibited no differences in basal food intake or body weight; however, induction of exendin-4 expression was associated with reduced short term food ingestion (p < 0.05). In contrast, short term water intake was significantly reduced in the absence of zinc in fluid-restricted MT-Ex mice (p < 0.05). These findings illustrate that sustained elevation of circulating exendin-4 is not invariably associated with changes in glucose homeostasis, increased beta-cell mass, or reduction in food intake in mice in vivo.

Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26.

A subset of prolyl oligopeptidases, including dipeptidyl-peptidase IV (DPP IV or CD26, EC ), specifically cleave off N-terminal dipeptides from substrates having proline or alanine in amino acid position 2. This enzyme activity has been implicated in the regulation of the biological activity of multiple hormones and chemokines, including the insulinotropic peptides glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Targeted inactivation of the CD26 gene yielded healthy mice that have normal blood glucose levels in the fasted state, but reduced glycemic excursion after a glucose challenge. Levels of glucose-stimulated circulating insulin and the intact insulinotropic form of GLP-1 are increased in CD26(-/-) mice. A pharmacological inhibitor of DPP IV enzymatic activity improved glucose tolerance in wild-type, but not in CD26(-/-), mice. This inhibitor also improved glucose tolerance in GLP-1 receptor(-/-) mice, indicating that CD26 contributes to blood glucose regulation by controlling the activity of GLP-1 as well as additional substrates. These data reveal a critical role for CD26 in physiological glucose homeostasis, and establish it as a potential target for therapy in type II diabetes.

New developments in the biology of the glucagon-like peptides GLP-1 and GLP-2.

Glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) are coencoded within a single mammalian proglucagon precursor, and are liberated in the intestine and brain. GLP-1 exerts well known actions on islet hormone secretion, gastric emptying, and food intake. Recent studies suggest GLP-1 plays a central role in the development and organization of islet cells. GLP-1 receptor signaling appears essential for beta cell signal transduction as exemplified by studies of GLP-1R-/- mice. GLP-2 promotes energy assimilation via trophic effects on the intestinal mucosa of the small and large bowel epithelium via a recently cloned GLP-2 receptor. The actions of GLP-2 are preserved in the setting of small and large bowel injury and inflammation. The biological actions of the glucagon-like peptides suggest they may have therapeutic efficacy in diabetes (GLP-1) or intestinal disorders (GLP-2).

The NAD(P)H-utilizing glutamate dehydrogenase of Bacteroides thetaiotaomicron belongs to enzyme family I, and its activity is affected by trans-acting gene(s) positioned downstream of gdhA.

Previous studies have suggested that regulation of the enzymes of ammonia assimilation in human colonic Bacteroides species is coordinated differently than in other eubacteria. The gene encoding an NAD(P)H-dependent glutamate dehydrogenase (gdhA) in Bacteroides thetaiotaomicron was cloned and expressed in Escherichia coli by mutant complementation from the recombinant plasmid pANS100. Examination of the predicted GdhA amino acid sequence revealed that this enzyme possesses motifs typical of the family I-type hexameric GDH proteins. Northern blot analysis with a gdhA-specific probe indicated that a single transcript with an electrophoretic mobility of approximately 1.6 kb was produced in both B. thetaiotaomicron and E. coli gdhA+ transformants. Although gdhA transcription was unaffected, no GdhA enzyme activity could be detected in E. coli transformants when smaller DNA fragments from pANS100, which contained the entire gdhA gene, were analyzed. Enzyme activity was restored if these E. coli strains were cotransformed with a second plasmid, which contained a 3-kb segment of DNA located downstream of the gdhA coding region. Frameshift mutagenesis within the DNA downstream of gdhA in pANS100 also resulted in the loss of GdhA enzyme activity. Collectively, these results are interpreted as evidence for the role of an additional gene product(s) in modulating the activity of GDH enzyme activity. Insertional mutagenesis experiments which led to disruption of the gdhA gene on the B. thetaiotaomicron chromosome indicated that gdhA mutants were not glutamate auxotrophs, but attempts to isolate similar mutants with insertion mutations in the region downstream of the gdhA gene were unsuccessful.

A common integration locus in type B retrovirus-induced thymic lymphomas.

Type-B leukemogenic retrovirus (TBLV) is a replication-competent type-B thymotropic retrovirus which lacks a transforming gene and whose genome is > 98% homologous to that of type-B mouse mammary tumor virus (MMTV). In contrast to MMTV, which induces mammary adenocarcinomas, TBLV induces a high incidence of T-cell thymic lymphomas in mice after a very short latent period. To investigate the molecular mechanisms by which TBLV induces T-cell lymphomas, we screened TBLV-induced tumor DNA for the frequent disruption of a particular cellular locus by TBLV proviral copies. In approximately 20% of the 55 primary tumors screened, the presence of proviruses in a common integration site was detected. This locus spans at least 53 kb of genomic DNA and maps to the mouse X chromosome. The presence of a functional gene at this locus is suggested by the conservation of nucleotide sequences from this locus among diverse animal species and by the expression of these sequences as mRNA in normal mouse tissues and tumors. The majority (17/18) of TBLV-induced primary tumors examined have elevated levels of this expressed mRNA.

[The external saphenous vein and the Doppler effect]. / La saphène externe et le Doppler.

After medium physical exertion, twelve athletes had their venous reflux measured using a Doppler fluxometer. A rise in the speed of the blood flow was recorded. This is due to the hyperactivity of the thoraco-abdominal and cardiac pumps, whose efficiency is boosted by arteriocapillary vasodilation. In some cases, this happens only in the deep system. But in others, this "arterialization" is apparent in the superficial system too, and especially in the region of the short saphenous vein. This occurs in such a way as to suggest that the deep course becomes saturated and so the reflux is redirected along the superficial course. This hypothesis is an argument in favour of the existence of vein to vein anastomosis.