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Biomedical subjects

M Munoz

Publications and source records attributed to M Munoz.

At least 19 recordsLinked to original sources

[Early prediction of functional outcome one year after initial unilateral hemispheric stroke].

BACKGROUND AND PURPOSE: Several prognostic factors have been identified for outcome after stroke. We conducted a study to determine early predictive factors of functional outcome one year after stroke and to evaluate which factors are independent predictors, with an aim of specifying the role of age, aphasia, unilateral neglect, cognitive impairment and family social support. METHODS: Observational cohort study of 156 patients. All patients admitted to the university hospital for initial unilateral hemispheric stroke were included. The study duration was two years (inclusion, one year, and follow-up, one year) . The initial evaluation of stroke was conducted at day 2 and day 15 and included the Motricity Index and Trunk Control Test, New Functional Ambulation Classification, Frenchay arm test, Mini-Mental State Examination, Boston Diagnostic Aphasia Examination, unilateral neglect evaluation, and depression. Data on functional recovery (Barthel Index) were collected at day 360. RESULTS: The average age of patients was 72 years. Age was correlated to social situation (P<0.01) and previous neurological impairment (P<0.01). A multiple regression analysis, including 14 initial clinical factors correlated with the Barthel Index score at day 360, revealed 4 independent early predictive factors of outcome: initial score of Barthel Index at day 2 and its progression from day 2 to day 15, disorders of the executive functions and previous neurological impairment. CONCLUSION: In our cohort, in accordance with previous studies, age, cognitive impairment, unilateral neglect, aphasia, depression and social situation are not independent factors of poor outcome after stroke as evaluated by the Barthel Index.

Aged↗

Involvement of penaeidins in defense reactions of the shrimp Litopenaeus stylirostris to a pathogenic vibrio.

The present study reports for the first time the involvement of an antimicrobial peptide in the defense reactions of a shrimp infected by a pathogenic Vibrio, Vibrio penaeicida. New members of the penaeidin family were characterized in the shrimp Litopenaeus stylirostris by RT-PCR and RACE-PCR from hemocyte total RNAs, and by mass spectrometry detection and immunolocalization of mature peptides in shrimp hemocytes. In infected shrimps, bacteria and penaeidin distribution colocalized in the gills and the lymphoid organ that represented the main infected sites. Moreover, the shrimp immune response to infection involved massive hemocyte recruitment to infection sites where released penaeidin may participate in the isolation and elimination of the bacteria, We show that the ability of the shrimps to circumvent shrimp infections is closely related to a recovery phase based on the hematopoietic process.

Amino Acid Sequence↗

[Epidemiology of pes varus and/or equinus one year after a first cerebral hemisphere stroke: apropos of a cohort of 86 patients].

OBJECTIVE: To determine the frequency and the functional consequences of varus equinus in stabilized vascular hemiplegia. METHODS: Prospective cohort study of 86 hemiplegic patients. All patients consecutively admitted for a first hemispheral stroke between July 2001 and January 2002 were included. The evaluation consisted in a clinical examination and a descriptive study of gait. The functional capacity of patients with and without varus equinus were compared using the Barthel index, the New Functional Ambulation Classification (NFAC), the confortable ten meters gait speed and gait perimeter. RESULTS: The incidence of varus equinus was 18%. There was no difference in gait speed (0.8 m/s), NFAC or Barthel index between patients with or without varus equinus. Patients with varus equinus had had more specialized, intensive and prolonged rehabilitation. The only prognostic factor that could be identified was the motor impairment and the existence of spasticity. DISCUSSION: The mechanism of varus equinus is thought to be mainly the over-activity of gastrocnemius and solaris compared to that of the tibialis anterior, associated to the weakness of fibular muscles. The role of tibialis posterior is thought to be less important. The frequency of varus equinus after a first hemispheral stroke was low and the consequences were limited. This could be in part explained by the access of these patients to early, specialized and prolonged rehabilitation care.

Aged↗

[Epidemiology and prognostic significance of bladder sphincter disorders after an initial cerebral hemisphere vascular accident].

OBJECTIVE: To document incidence of poststroke urinary incontinence and retention and to determine its effect on 3 months outcome. METHODS: Prospective cohort study. One hundred fifty-five cases of first hemispherical stroke were classified by continence status, retention or incontinence, at D2 after stroke. Age, sex, stroke location and aetiology, hypertension, diabetes were noted. Outcome data collected at D15 and D90 included impairments, disabilities, quality of life and case fatality rates. Disabilities were measured with Barthel Index (BI), Franchay Arm Test (FAT), New Functional Ambulation Classification (NFAC) and quality of life with EuroQol. RESULTS: Of the 155 patients, 62 had initial urinary disorders. The incidence was 40% at D2, 32% at D15 and 19% at D90. Retention represented 36% of urinary disorders at D2 and D15 and only 19% at D90. Urinary disorders were associated with motor weakness, lower Barthel Index, dysphasia, aphasia, apraxia and unilateral neglect. There was no relation with sex, age, stroke aetiology and diabetes. At D90, patients with initial urinary disorders had higher case fatality rates 22% versus 16% (P < 0.0001) and greater disabilities: BI of 60 versus 90 (P < 0.0001), NFAC of five versus seven (P < 0.0001), FAT of four versus six (P = 0.0019). CONCLUSION: Poststroke urinary disorders were associated with stroke gravity and adversely affected D90 stroke survival rates and functional outcome. Retention was strongly associated with D90 survival rates.

Adult↗

[Clinical factors associate with shoulder subluxation in stroke patients].

OBJECTIVE: This study explores whether shoulder subluxation after stroke is related to age, hemiplegic side motor impairment, spasticity, sensory deficit, depression, unilateral neglect and length of stay in acute ward. METHOD: This prospective study included 57 patients with hemiplegia. The shoulder subluxation was systematically detected by radiography and quantified according to de Bats score. The complete clinical assessment of the upper limb on day 15 analyzed motricity (motricity index), spasticity of shoulder adductors and biceps (Ashworth), sensory deficit, unilateral neglect and depression (MADRS). Age, side of hemiplegia and the aetiology were also noted. We researched relations between shoulder subluxation and these clinical factors. Means were compared using Mann Whitney and chi(2) tests. Coefficients of correlation were estimated between two quantitative variables. A multiple regression analysis was also conducted including all significant parameters, the dependent variable being the shoulder subluxation. RESULTS: Shoulder subluxation was observed in 32% of hemiplegic patients. After multiple regression analysis, the main clinical factors related to subluxation were motor (p < 0.0001), spasticity of shoulder adductors (p = 0.028) and age (p = 0.036). Statistically, the risk of subluxation was divided by 1.62 (1.07, 2.43) for every five years age growth and by two (1.33, 2.94) when the motricity index went up by ten points. CONCLUSION: This study shows that the age could play an independent part. The loss of elasticity of the periarticular tissues when ageing could have a protective role.

Age Factors↗

Adaptive loss of ultraviolet-sensitive/violet-sensitive (UVS/VS) cone opsin in the blind mole rat (Spalax ehrenbergi).

In previous studies, fully functional rod and long-wavelength-sensitive (LWS) cone photopigments have been isolated from the eye of the subterranean blind mole rat (Spalax ehrenbergi superspecies). Spalax possesses subcutaneous atrophied eyes and lacks any ability to respond to visual images. By contrast this animal retains the ability to entrain circadian rhythms of locomotor behaviour to environmental light cues. As this is the only known function of the eye, the rod and LWS photopigments are thought to mediate this response. Most mammals are dichromats possessing, in addition to a single rod photopigment, two classes of cone photopigment, LWS and ultraviolet-sensitive/violet-sensitive (UVS/VS) with differing spectral sensitivities which mediate colour vision. In this paper we explore whether Spalax is a dichromat and has the potential to use colour discrimination for photoentrainment. Using immunocytochemistry and molecular approaches we demonstrate that Spalax is a LWS monochromat. Spalax lacks a functional UVS/VS cone photopigment due to the accumulation of several deleterious mutational changes that have rendered the gene nonfunctional. Using phylogenetic analysis we show that the loss of this class of photoreceptor is likely to have arisen from the visual ecology of this species, and is not an artefact of having an ancestor which lacked a functional UVS/VS cone photopigment. We conclude that colour discrimination is not a prerequisite for photoentrainment in this species.

Adaptation, Biological↗

Identifying the photoreceptive inputs to the mammalian circadian system using transgenic and retinally degenerate mice.

The endogenous circadian clock of mammals retains synchrony with the external light:dark cycle through ocular photoreceptors. To date the identity of the photoreceptors responsible for mediating this response is unknown. This review outlines attempts using transgenic mouse models to address this deficit. Mice bearing specific inherited lesions of both rod and cone photoreceptors retain circadian photosensitivity as assessed by photoentrainment of behavioural rhythms and the light-induced suppression of pineal melatonin. These findings indicate that as yet unidentified non-rod, non-cone ocular photoreceptors are capable of contributing to circadian light responses. Nevertheless, the possibility that circadian photosensitivity is the responsibility of multiple photoreceptor classes including both rod/cone and novel photopigments remains. There is some indirect evidence in favour of this hypothesis. A definitive resolution of this issue is likely to employ comparisons of circadian action spectra in wild type and retinally degenerate mice.

Animals↗

[Reliability of TcPO(2) measurement in the upper limb].

INTRODUCTION: Several reports suggest the usefulness of transcutaneous oxygen tension (TcPO(2)) in assessing the shoulder hand syndrome in stroke patients. But the literature presents a number of conflicting views on the variation of TcPO(2) values in this case. We found no report demonstrating the reliability of TcPO(2) measurements in the upper limb. The aim of this study was to evaluate the reliability of TcPO(2) measurements and investigate whether TcPO(2) can be used to evaluate the shoulder hand syndrome after stroke. MATERIAL AND METHODS: The TcPO(2) values were obtained on two separate occasions at one-day interval on 18 normal volunteers. Basal TcPO(2), local vasomotor reflex and reaction to ischemia were assessed. RESULTS: Thirty-six upper limbs were tested. The reliability was bad. We found that measurements of TcPO(2) varied by an average of 7.89 +/- 7.6 mmHg for a coefficient of variation of 96%. CONCLUSION: The reliability of TcPO(2) measurement was not sufficient to recommend this method in this indication.

Blood Gas Monitoring, Transcutaneous↗

[The shoulder-hand syndrome after stroke: clinical factors of severity and value of prognostic score of Perrigot].

PURPOSE: The purposes of this study were to evaluate the prognostical factors of reflex sympathetic dystrophy in stroke patients in attempt to improve the Perrigot prognostical score. MATERIAL AND METHOD: This prospective study included 28 stroke patients with reflex sympathetic dystrophy. An initial clinical assessment including Perrigot score was made at the time of admission (before the end of the first month) and a second evaluation of reflex sympathetic dystrophy at the end of the third month. Patients were assessed using Motricity Index, Ashworth scale, de Bats grading (for glenohumeral alignment), Labrousse criteria (for reflex sympathetic dystrophy severity), and MADRS depression scale. Sensory deficit and unilateral neglect were noted. RESULTS: The length of stay in acute ward was 16 days. The Perrigot score was correlated with the reflex sympathetic dystrophy severity (r = 0.7, p < 0.0001). It predicted the result of therapy. A significant correlation was found between reflex sympathetic dystrophy severity and motor deficit (r = -0.591, p = 0.0007) and spasticity (p < 0.05). No relation was found with stroke side, unilateral neglect, depression or shoulder subluxation. It wasn't possible to improve the Perrigot prognostical score. CONCLUSION: Perrigot score predict reflex sympathetic dystrophy severity and the result of therapy. The shoulder subluxation which is not included in this score appears to be not predictive. Shoulder subluxation is simply a marker of a severe paresis.

Aged↗

Radioisotopic control for baclofen pump catheter failure.

STUDY DESIGN: Case report of Baclofen pump catheter failure investigated by radioisotope injection. OBJECTIVES: To report a safe and reliable method for evaluating catheter dysfunction. SETTING: France. METHODS: Single case report of failure of Baclofen pump investigated by radioisotope injection. RESULTS: The injection demonstrated the block in the catheter. The catheter failure was not visualised by plain X-ray nor by filling the pump with radio-opaque solution. CONCLUSION: Catheter failure is a common cause of intrathecal drug delivery problems and may be difficult to diagnose. When catheter disconnection, kink, or dislodgement is not visible on X-ray, radioisotopic control is a safe and reliable method for assessment.

Adult↗

Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease (PR) and reverse transcriptase (RT) inhibitors may display impaired infectivity and replication capacity. The individual contributions of mutated HIV-1 PR and RT to infectivity, replication, RT activity, and protein maturation (herein referred to as "fitness") in recombinant viruses were investigated by separately cloning PR, RT, and PR-RT cassettes from drug-resistant mutant viral isolates into the wild-type NL4-3 background. Both mutant PR and RT contributed to measurable deficits in fitness of viral constructs. In peripheral blood mononuclear cells, replication rates (means +/- standard deviations) of RT recombinants were 72.5% +/- 27.3% and replication rates of PR recombinants were 60.5% +/- 33.6% of the rates of NL4-3. PR mutant deficits were enhanced in CEM T cells, with relative replication rates of PR recombinants decreasing to 15.8% +/- 23.5% of NL4-3 replication rates. Cloning of the cognate RT improved fitness of some PR mutant clones. For a multidrug-resistant virus transmitted through sexual contact, RT constructs displayed a marked infectivity and replication deficit and diminished packaging of Pol proteins (RT content in virions diminished by 56.3% +/- 10.7%, and integrase content diminished by 23.3% +/- 18.4%), a novel mechanism for a decreased-fitness phenotype. Despite the identified impairment of recombinant clones, fitness of two of the three drug-resistant isolates was comparable to that of wild-type, susceptible viruses, suggestive of extensive compensation by genomic regions away from PR and RT. Only limited reversion of mutated positions to wild-type amino acids was observed for the native isolates over 100 viral replication cycles in the absence of drug selective pressure. These data underscore the complex relationship between PR and RT adaptive changes and viral evolution in antiretroviral drug-resistant HIV-1.

Animals↗

Immunological and virological responses in HIV-1-infected adults at early stage of established infection treated with highly active antiretroviral therapy.

OBJECTIVE: To evaluate the immunological and virological responses to highly active antiretroviral therapy (HAART) in blood and lymphoid compartments of HIV-1-infected patients at an early stage of infection. DESIGN: An open-label, observational, non-randomized, prospective trial of outpatients attending the Centre of Clinical Investigation in Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. SUBJECTS: Forty-one antiretroviral-naive HIV-1-infected adults with 400 CD4 T cells/microl or greater and 5000 plasma HIV-1-RNA copies/ml or greater were enrolled, and 32 finished the study. Forty-nine HIV-negative individuals were included as controls. All subjects gave written informed consent. INTERVENTIONS: All patients received abacavir 300 mg by mouth every 12 h and amprenavir 1200 mg by mouth every 12 h for 72 weeks. MAIN OUTCOME MEASURES: The extent of immune reconstitution in blood and lymph nodes after 72 weeks of HAART was evaluated, and compared with immunological measures of 49 HIV-negative subjects. RESULTS: Virus replication was effectively suppressed (-3.5 log10 at week 72). Substantial increments of CD4 T cell count in blood and percentage in lymph nodes were observed over time, and these measures were comparable to HIV-negative subjects by week 24 in blood and by week 48 in lymph nodes. The increase was equally distributed between naive and memory CD4 T cells. Recovery of HIV-specific CD4 responses occurred in 40% of patients. CONCLUSION: The initiation of HAART at an early stage of established HIV infection induces systemic quantitative normalization of CD4 T cells, a partial recovery of HIV-specific CD4 cell responses, and effective and durable suppression of virus replication.

Adolescent↗

Recombinant respiratory syncytial viruses with deletions in the NS1, NS2, SH, and M2-2 genes are attenuated in vitro and in vivo.

Respiratory syncytial virus (RSV) encodes several proteins that lack well-defined functions; these include NS1, NS2, SH, and M2-2. Previous work has demonstrated that NS2, SH, and M2-2 can each be deleted from RSV genome and thus are considered as accessory proteins. To determine whether RSV can replicate efficiently when two or more transcriptional units are deleted, we removed NS1, NS2, SH, and M2-2 genes individually and in different combinations from an infectious cDNA clone derived from human RSV A2 strain. The following six mutants with two or more genes deleted were obtained: DeltaNS1NS2, DeltaM2-2SH, DeltaM2-2NS2, DeltaSHNS1, DeltaSHNS2, and DeltaSHNS1NS2. Deletion of M2-2 together with NS1 was detrimental to RSV replication. It was not possible to obtain a recombinant RSV when all four genes were deleted. All of the double and triple deletion mutants exhibited reduced replication and small plaque morphology in vitro. Replication of these deletion mutants was more reduced in HEp-2 cells than in Vero cells. Among the 10 single and multiple gene deletion mutants obtained, DeltaM2-2NS2 was most attenuated. DeltaM2-2NS2 formed barely visible plaques in HEp-2 cells and had a reduction of titer of 3 log(10) compared with the wild-type recombinant RSV in infected HEp-2 cells. When inoculated intranasally into cotton rats, all of the deletion mutants were attenuated in the respiratory tract. Our data indicated that the NS1, NS2, SH, and M2-2 proteins, although dispensable for virus replication in vitro, provide auxiliary functions for efficient RSV replication.

Animals↗

Penaeidins, a family of antimicrobial peptides from penaeid shrimp (Crustacea, Decapoda).

The production of antimicrobial peptides represents a first-line host defense mechanism of innate immunity that is widespread in nature. Only recently such effectors were isolated in crustacean species, whereas numerous antimicrobial peptides have been characterized from other arthropods, both insects and chelicerates. This review presents findings on a family of antimicrobial peptides, named penaeidins, isolated from the shrimp Penaeus vannamei. Their structure and antimicrobial properties as well as their immune function will be discussed through analyses of penaeidin gene expression and peptide distribution upon microbial challenge.

Amino Acid Sequence↗

Gene transfer into stimulated and unstimulated T lymphocytes by HIV-1-derived lentiviral vectors.

Genetic modification of T lymphocytes holds great potential for treatments of cancer, T cell disorders and AIDS. While in the past recombinant murine retroviruses were the vectors of choice for gene delivery to T cells, vectors based on lentiviruses can provide additional benefits. Here, we show that VSV-G pseudotyped HIV 1 vector particles delivering the enhanced green fluorescent protein (EGFP) efficiently transduce human T lymphocytes. Transduction efficiency was optimal when infection included centrifugation of cells with concentrated vector supernatant in the presence of Polybrene. In contrast to previous reports describing murine retrovirus-mediated gene transfer to T lymphocytes, fibronectin did not improve the transduction efficiency of the VSVG-pseudotyped HIV-1 particles. Similar gene transfer efficiencies were observed following stimulation of cells with PHA/IL-2 or anti-CD3i/CD28i antibodies, although greater transgene expression was observed in the latter case. Interestingly, production of vectors in the absence of the accessory proteins Vif, Vpr, Vpu and Nef was accompanied by a 50% decrease in transduction efficiency in activated T cells. Transduction of T cells that were not stimulated before infection was achieved. No transduction of non-prestimulated cells was observed with a GAL V-pseudotyped murine retroviral vector. The requirement for accessory proteins in non-prestimulated cells was more pronounced. Our results have implications for lentiviral vector targeting of other cells of the hematopoietic system including stem cells.

Cell Line↗

Total body water and percentage fat mass measurements using bioelectrical impedance analysis and anthropometry in spinal cord-injured patients.

BACKGROUND AND AIMS: Spinal cord injured patients may be adversely affected by disturbances of nutritional status, particularly malnutrition and fat mass overload. Malnutrition increases the risk for development of pressure sores, and fat mass excess increases the cardiovascular and respiratory risks of these patients, as well as predisposing to the development of diabetes mellitus, pressures sores and bony fractures. Body impedance analysis and anthopometry are easy bedside methods for body composition assessment. The aims of the study were to validate, in 20 spinal cord injured patients, body impedance analysis as a means to estimate total body water, and to validate a skinfold measurement of percentage fat independent of hydration of fat-free mass in the same population. METHODS: Total body water was measured by (18)O dilution as a reference method. Impedance and anthropometric measurements (four different skinfolds) were obtained. The results of total body water given by impedance analysis and calculated with three formulas were compared to the reference method. The fat mass percentage obtained with each of the skinfolds using the 3-compartment Siri's formula was compared to a reference value using the sum of the skinfolds. RESULTS AND CONCLUSION: The formula using 100 kHz resistance, height, weight and gender overestimated total body water by only 0.76 +/- 1.85 L, with an acceptable concordance with labeled water results. The formula with 50 kHz resistance was less accurate and concordant. Each skinfold may be used for assessing percentage fat mass. Based on these findings, we feel that the triceps skinfold, whose the variability is the lowest compared to the reference values, can be used alone in clinical practice.

Adipose Tissue↗

Sampling lymphoid tissue cells by ultrasound-guided fine needle aspiration of lymph nodes in HIV-infected patients. Swiss HIV Cohort Study.

OBJECTIVE: To establish the feasibility of using ultrasound-guided lymph node needle aspiration as a means to obtain lymphoid tissue cells for the determination of a series of immunologic and virologic measures in HIV-infected patients. DESIGN: First, a comparison of the characteristics of cell populations obtained by simultaneous needle aspiration and standard excisional biopsy in six patients. Second, use of lymph node needle aspiration to assess longitudinally T-cell subset changes in patients initiating highly effective antiretroviral treatment. METHODS: T-cell subsets (CD4 and CD8) and percentage Ki67+ cycling T cells were measured in lymph node cell populations harvested by ultrasound-guided aspiration or standard biopsy by flow cytometry. Cellular RNA content was assessed by a modification of the Roche Amplicor HIV-1 Monitor test. RESULTS: CD4 and CD8 T-cell percentage and HIV RNA cell content of lymph node cell suspensions obtained from the simultaneous performance of ultrasound-guided needle aspiration and excisional biopsy in the same patients were correlated (n = 6). Among the 87 aspiration sessions reported here, mononuclear cell suspensions were obtained in 100% of the sessions, in numbers ranging between 4x10(4) to 6.7x10(6) cells (median: 7x10(5)). This limited number of cells did not allow to perform all type of analyses in all patients. By prioritizing the cells for the determination of T-cell subsets and proliferation rate, this approach was instrumental for demonstrating the normalization of the T-cell subset ratio and the kinetic of normalization of proliferating rates of CD4 and CD8 T cells, as well as the decrease in HIV-1 viral load in the lymph node following HAART initiation. CONCLUSION: Ultrasound-guided aspiration appears to be a non-invasive and ad libitum, safe and repeatable procedure for the longitudinal monitoring of changes in lymph nodes.

Anti-HIV Agents↗

The nef gene controls syncytium formation in primary human lymphocytes and macrophages infected by HIV type 1.

nef, the 3'-most open reading frame of HIV, has been reported to enhance HIV replication in various host cell types and to promote in vivo replication and pathogenesis. The mechanism underlying the increased in vivo viral replication is still unclear. We have examined the effect of a nef deletion on the infection of primary human CD4+ T lymphocytes and macrophages, using clones with nef and env sequences derived, respectively, from T cell- and macrophage-tropic viruses. The deletion of nef enhanced the formation of syncytia in CD4+ T lymphocytes infected with macrophage-tropic clones, despite a severalfold reduced viral production. No such enhancement of syncytium formation was observed in CD4+ T lymphocytes infected with a T cell line-tropic clone, but in this clone, the deletion of nef imparted a more severe replication defect. A similar increase in syncytium formation was observed in primary human macrophages infected with nef-deleted clones compared with wild-type counterparts, except under conditions in which the deletion of nef markedly reduced viral replication. We could not demonstrate an enhanced cell surface expression of HIV-1 envelope in lymphocytes infected with nef-deficient clones to explain the increased syncytium formation. In enhancing the HIV-1 cytopathic effect, the deletion of nef might curtail virus production by infected cells, and thus explain in part the reduced viral load observed in vivo in hosts infected with nef-deficient viruses.

Animals↗