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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 91 records · Page 5Linked to original sources

Asymptomatic vertebral artery injury after acute cervical spine trauma.

Two recent cases of vertebral artery injury from cervical fracture-dislocation prompted us to review the literature of these wrongly thought uncommon lesions. Extracranial vertebral artery injury during cervical trauma needs to be suspected not only in the case of vertebrobasilar ischemia, but also in asymptomatic patients presenting serious flexion-distraction deformities. Fracture of a transverse foramen or facet joint dislocation should alert the clinician. Magnetic resonance evaluates blood flow and vessel injury, usually unilateral, localized to the traumatized unstable vertebral segment. A four-stage classification is useful to understand and treat vertebral artery injury, also a standardized therapeutic protocol is not documented. Anterior cervical fusion seems indicated to decompress the injured vessel, and to avoid further damage to both vertebral arteries. Unstable spine conditions may also promote clot mobilization at the traumatized vessel leading to vertebrobasilar embolization. The benefit of antithrombotic therapy in reducing neurological morbidity and improving outcome is not yet established and needs long-term follow-up.

Adult↗

Antigens to viral capsid and non-capsid proteins are present in brain tissues and antibodies in sera of Theiler's virus-infected mice.

Recombinant proteins to the LP, VP1, VP2, VP3, VP4, 2A, 2B, 2C, 3A, and 3D genes of Theiler's murine encephalomyelitis virus (TMEV) were generated and antibodies were produced against them for use in analysis of the TMEV epitopes responsible for eliciting the antibody responses observed during acute and chronic disease. Antibodies against recombinant VP1, VP2, and VP3 recognized the corresponding proteins from purified TMEV particles. In immunohistochemical analysis, antibodies against recombinant capsid (VP1, VP2, and VP3), and non-capsid (2A, 2C, 3A) proteins were reactive with PO-2D cells (astrocytes) infected with TMEV in vitro and with brain tissues of acutely infected mice. Antibodies against VP4, 2B, and 3D antigens were not reactive with corresponding viral proteins in infected astrocytes cells or brain tissues, but they reacted with TMEV precursor proteins produced during the early viral replication phase. Sera from SJL/J mice infected with TMEV acutely (14 days) and chronically (45 days) reacted with VP1, VP2, VP4, 2A, and 2C proteins. In an in vitro assay for neutralization, only anti-VP1 antibodies neutralized TMEV infection. These findings suggest that both capsid and non-capsid proteins of TMEV play a role in the immunopathology of the TMEV disease in the central nervous system.

Animals↗

Humoral autoimmunity as a mediator of CNS repair.

Autoimmune responses directed against the central nervous system (CNS) have generally been considered pathogenic in nature. Although there are several well understood conditions in which this is the case, there is also a growing body of experimental evidence to show that both the cellular and humoral immune responses can promote tissue repair following CNS injury and disease. Our laboratory has used a mouse model of chronic demyelinating disease to characterize a class of polyreactive IgM autoantibodies that react with oligodendrocyte surface antigens and promote myelin repair. By screening a large number of human monoclonal antibodies, we have found that IgM antibodies that react with CNS tissue are relatively common. Autoreactive IgM antibodies might constitute an endogenous system for tissue repair, and therefore these antibodies could be of value as therapeutic reagents.

Animals↗

Minifenestration type I thyroplasty using an expanded polytetrafluoroethylene implant.

Several methods have been used to treat laryngeal incompetence, but no ideal technique has been identified. This paper describes a clinical experience with minifenestration type I thyroplasty using a new device made of expanded polytetrafluoroethylene (ePTFE). The device, a thin ribbon of ePTFE, is inserted through a 4-mm fenestration to produce vocal fold medialization. At our center, 26 of these devices have been implanted in the past 3 years. Good or satisfactory results were achieved in 96% of cases. Advantages of this technique include easy insertion of the implant, nominal cost and biocompatibility of the ePTFE device, ready availability of all instruments required for the procedure, and elimination of the need to perform arytenoid adduction.

Adult↗

Stand-off tissue-based biosensors for the detection of chemical warfare agents using photosynthetic fluorescence induction.

Tissue biosensors made from immobilized whole-cell photosynthetic microorganisms have been developed for the detection of airborne chemical warfare agents and simulants. The sensor read-out is based on well-known principles of fluorescence induction by living photosynthetic tissue. Like the cyanobacteria and algae from which they were constructed, the sensors are robust and mobile. The fluorescence signal from the sensors was stable after 40 days, storage and they can be launched or dropped into suspected danger zones. Commercially available hand-held fluorometric detector systems were used to measure Photosystem II (PSII) photochemical efficiency of green algae and cyanobacteria entrapped on filter paper disks. Toxic agents flowing in the gas stream through the sensors can alter the characteristic fluorescence induction curves with resultant changes in photochemical yields. Tabun (GA), sarin (GB), mustard agent, tributylamine (TBA) (a sarin stabilizer), and dibutyl sulfide (DBS) (a mustard agent analog) were tested. Upper threshold limits of detectability for GA, TBA, and DBS are reported. With additional research and development, these biosensors may find application in stand-off detection of chemical and perhaps biological warfare agents under real-world conditions.

Biosensing Techniques↗

Presence of bacterial infection in bleeding cirrhotic patients is independently associated with early mortality and failure to control bleeding.

Bacterial infection is strongly associated with gastrointestinal bleeding in cirrhotic patients and seems to be related with the failure to control bleeding. The aims of this study were to assess the influence of infections on the failure to control bleeding and death in cirrhotic patients without antibiotic prophylaxis. Ninety-one consecutive bleeding cirrhotic patients were analyzed. Bleeding was managed using somatostatin with sclerotherapy for active bleeding. Screening for bacterial infection (analysis and culture of blood, urine, ascitic and other fluids, together with chest radiography) was made at time 0 and when clinical signs suggested infection. The cause of bleeding was variceal in 72 (79%) patients. Failure to control bleeding occurred in 24 (26%) patients, and 10 (11%) of the patients died. Compared with the group without infection, failure to control bleeding (65% vs 15%; P < 0.001) and mortality (40% vs 3%; P < 0.001), were observed more frequently in patients with infection. Multivariate analysis showed that bacterial infection (OR = 9.7; P < 0.001) and the presence of shock (OR = 3.5; P < 0.05) were independently associated with failure to control bleeding. Bacterial infection (OR = 12.6; P < 0.01), encephalopathy (OR = 6.9; P < 0.05), and shock (OR = 5.8; P < 0.05) were identified as predictive of death. In conclusion, in bleeding cirrhotic patients bacterial infection is associated with failure to control bleeding as well as mortality.

Female↗

[125I]-S36057: a new and highly potent radioligand for the melanin-concentrating hormone receptor.

Shortened, more stable and weakly hydrophobic analogues of melanin-concentrating hormone (MCH) were searched as candidates for radioiodination. Starting from the dodecapeptide MCH(6 - 17), we found that: (1) substitution of Tyr(13) by a Phe residue; (2) addition of a 3-iodo-Tyr residue at the N-terminus; and (3) addition of a hydrophilic spacer 8-amino-3,6-dioxyoctanoyl between the 3-iodo-Tyr and MCH(6 - 17) (compound S36057), led to an agonist more potent than MCH itself in stimulating [35S]-GTPgammaS binding at membranes from HEK293 cells stably expressing the human MCH receptor. Specific binding of [125I]-S36057 was found in HEK293 and CHO cell lines stably expressing the human MCH receptor. This radioligand recognized a similar number of binding sites (ca. 800 fmol mg(-1)) than [125I]-[3-iodo Tyr(13)]-MCH. However, the K(D) for [125I]-S36057 obtained from saturation studies (0.037 nM) or from binding kinetics (0.046 nM) was at least 10 fold higher to that of [125I]-[3-iodo Tyr(13)]-MCH (0.46 nM). Affinities determined for a series of MCH analogues were similar with both radioligands, S36057 being the most potent compound tested (K(i)=0.053 nM). Finally, [125I]-S36057 also potently labelled the MCH receptor in membranes from whole rat brain (K(D) 0.044 nM, B(max)=11 fmol mg(-1)). In conclusion, [125I]-S36057 is a more potent and more stable radioligand than [125I]-[3-iodo Tyr(13)]-MCH that will represent a reliable tool for binding assays in the search of novel MCH ligands. It should also provide great help for autoradiographic studies of the MCH receptor distribution in the central nervous system.

Amino Acid Sequence↗

Transient hepatopulmonary syndrome in a patient with acute hepatitis A.

The hepatopulmonary syndrome is defined as the triad of liver disease, hypoxaemia and intrapulmonary vascular dilatation. This syndrome has been described in patients with liver cirrhosis, noncirrhotic portal hypertension, and fulminant hepatic failure, however, there are no previous descriptions of hepatopulmonary syndrome in patients with acute nonfulminant viral hepatitis. We report a 47-year-old, previously healthy man that presented with acute hepatitis A, and developed progressive dyspnoea, platypnoea and orthodeoxia with no evidence of parenchymal or thromboembolic lung disease. PaO2 on room air was 58 mmHg, O2 saturation was 88% and alveolar-arterial O2 gradient was 62%. During his hospitalization serum albumin level decreased to 3.1 g/dl and prothrombin time was prolonged to 16.8 s, however, he remained alert with no signs of hepatic encephalopathy. Contrast echocardiography revealed left heart chamber opacification 3-4 cardiac cycles after the opacification of the right heart chamber, consistent with hepatopulmonary syndrome. During the following days there was a gradual improvement in the patient's condition, with resolution of his dyspnoea and gradual increase of PaO2. Repeat contrast echocardiography and PaO2 determinations, 3 weeks later, were normal. On long-term follow-up the patient remained asymptomatic with normal liver function tests and normal O2 saturation. This report indicates that hepatopulmonary syndrome may be a transient manifestation of acute hepatitis A in the absence of fulminant liver failure.

Acute Disease↗

Immunoglobulin-mediated CNS repair.

Our view of the immune system continues to evolve from a system dedicated primarily to defense against pathogens to a system that monitors the integrity of the organism and aids in repair following damage. Repair following injury to the central nervous system (CNS) is facilitated by both cellular and humoral components of the immune system. Transfer of macrophages or T cells activated against CNS antigens promote axon regrowth and protect axons from further damage. Animals immunized with spinal cord antigens and subsequently challenged with demyelination or transection of the spinal cord demonstrate better repair than animals without prior immunization. In both experimental systems, antibodies are the biologically active immune component. Human mAbs reactive to oligodendrocytes that arise in the absence of neurologic injury promote remyelination. These data support the hypothesis that B-cell clones producing mAbs reactive to CNS epitopes are a normal part of the human antibody repertoire. They challenge the assertion that an immune response to CNS antigens is pathogenic. Treatment with CNS-reactive human mAbs following CNS disease may facilitate CNS regeneration.

Adjuvants, Immunologic↗

Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation and subsequent pregnancy in the treatment of early invasive cervical cancer.

BACKGROUND: Recently, pregnancies in patients after radical vaginal trachelectomy and laparoscopic pelvic lymphadenectomy have been reported. Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation has been previously described; however, subsequent outcome and pregnancy has not. METHODS: Three patients with cervical carcinoma, 1 with stage IA1 with lymph-vascular space invasion and 2 with stage IA2, were treated with radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation. RESULTS: All patients underwent the planned procedure with no significant intraoperative or postoperative complications. All patients had return to normal menstrual function. One patient had a successful pregnancy delivered at 39 weeks by cesarean section and is now subsequently pregnant with a second pregnancy. CONCLUSION: Radical abdominal trachelectomy is a technically feasible operation that uses operative techniques familiar to the American-trained gynecologic oncologist and results in wider parametrial resection than radical vaginal trachelectomy. In young patients desiring to retain fertility, successful pregnancies after radical abdominal trachelectomy are possible. Intraoperative and postoperative complications are likely to be lower with an abdominal versus a vaginal approach. Long-term survival of patients treated with radical trachelectomy for early invasive cervical cancer are yet to be determined.

Adenocarcinoma↗

Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis.

A major question in neurobiology is whether myelin repair can restore neurological function following the course of a severe, progressive CNS demyelinating disease that induces axonal loss. In this study we used Theiler's murine encephalomyelitis virus (TMEV) to induce a chronic progressive CNS demyelinating disease in mice that was immune-mediated and pathologically similar to human multiple sclerosis. Because immunosuppression of chronically TMEV-infected mice has been shown to enhance myelin repair, we first addressed the potential roles of CD4(+) and CD8(+) T cells in the inhibition of CNS remyelination during chronic disease. TMEV infection of susceptible PL/J mice deficient in CD4(+) but not CD8(+) T cells demonstrated a significant increase in severity of pathogenesis when compared with wild-type controls. This was characterized by enhanced demyelination, spinal cord atrophy, neurological deficits, and mortality. Interestingly, the PL/J CD4(-/-) mice that survived to the chronic stage of the disease had nearly complete spontaneous myelin repair mediated by both oligodendrocytes and infiltrating Schwann cells. Therefore, we next addressed whether this spontaneous myelin repair was associated with improved neurological function despite the increased pathology. Of interest, all surviving PL/J CD4(-/-) mice showed partial restoration of motor coordination and gait that coincided temporally with spontaneous myelin repair. Furthermore, functional recovery of motor coordination correlated strongly with the percentage of myelin repair mediated by Schwann cells, whereas restoration of hindlimb gait correlated with oligodendrocyte-mediated myelin repair. This is the first study to demonstrate that spontaneous remyelination correlates with partial restoration of neurological function during the course of a progressive, immune-mediated CNS demyelinating disease. Of greater importance, functional recovery occurred despite previous severe demyelination and spinal cord atrophy.

Animals↗

The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.

Single-cell recording of the subthalamic nucleus (STN) was undertaken in 14 patients with Parkinson's disease submitted to surgery. Three hundred and fifty neurones were recorded and assessed for their response to passive and active movements. Thirty-two per cent were activated by passive and active movement of the limbs, oromandibular region and abdominal wall. All neurones with sensorimotor responses were in the dorsolateral region of the STN. Arm-related neurones were lateral (> or =14 mm plane) to leg-related neurones, which were found more medially (< or =12 mm). Representation of the oromandibular musculature was in the middle of the sensorimotor region (approximately 13 mm plane) and ventral to the arm and leg. Two hundred neurones were adequately isolated for 'off-line' analysis. The mean frequency of discharge was 33 +/- 17 Hz (13-117 Hz). Three types of neuronal discharges were distinguished: irregular (60.5%), tonic (24%) and oscillatory (15.5 %). They were statistically differentiated on the basis of their mean firing frequency and the coefficient of variation of the interspike interval. Neurones responding to movement were of the irregular or tonic type, and were found in the dorsolateral region of the STN. Neurones with oscillatory and low frequency activity did not respond to movement and were in the ventral one-third of the nucleus. Thirty-eight tremor-related neurones were recorded. The majority (84%) of these were sensitive to movement and were located in the dorsolateral region of the STN. Cross power analysis (n = 16) between the rhythmic neuronal activity and tremor in the limbs showed a peak frequency of 5 Hz (4-8 Hz). Neuronal activity of the substantia nigra pars reticulata was recorded 0.5-3 mm below the STN. Eighty neurones were recorded 'on-line' and 27 were isolated for 'off-line' analysis. A tonic pattern of discharge characterized by a mean firing rate of 71 +/- 28 Hz (35-122 Hz) with a mean coefficient of variation of the interspike interval of 0.85 +/- 0.29 ms was found. In only three neurones (11%) was there a response to sensorimotor stimulation. The findings of this study indicate that the somatotopic arrangement and electrophysiological features of the STN in Parkinson's disease patients are similar to those found in monkeys.

Action Potentials↗

Rapid weaning from mechanical ventilator in acute cervical cord multiple sclerosis lesion after steroids.

IMPLICATIONS: We report a patient with multiple sclerosis (MS), who developed neuromuscular respiratory failure requiring ventilation because of a cervical cord relapse. Serial pulmonary function tests documented improvement after steroid treatment. Cervical cord or brainstem relapses should be suspected in MS patients with respiratory failure. Identification and management of this critical condition are discussed.

Acute Disease↗

Engineering a homo-ethanol pathway in Escherichia coli: increased glycolytic flux and levels of expression of glycolytic genes during xylose fermentation.

Replacement of the native fermentation pathway in Escherichia coli B with a homo-ethanol pathway from Zymomonas mobilis (pdc and adhB genes) resulted in a 30 to 50% increase in growth rate and glycolytic flux during the anaerobic fermentation of xylose. Gene array analysis was used as a tool to investigate differences in expression levels for the 30 genes involved in xylose catabolism in the parent (strain B) and the engineered strain (KO11). Of the 4,290 total open reading frames, only 8% were expressed at a significantly higher level in KO11 (P < 0.05). In contrast, over half of the 30 genes involved in the catabolism of xylose to pyruvate were expressed at 1.5-fold- to 8-fold-higher levels in KO11. For 14 of the 30 genes, higher expression was statistically significant at the 95% confidence level (xylAB, xylE, xylFG, xylR, rpiA, rpiB, pfkA, fbaA, tpiA, gapA, pgk, and pykA) during active fermentation (6, 12, and 24 h). Values at single time points for only four of these genes (eno, fbaA, fbaB, and talA) were higher in strain B than in KO11. The relationship between changes in mRNA (cDNA) levels and changes in specific activities was verified for two genes (xylA and xylB) with good agreement. In KO11, expression levels and activities were threefold higher than in strain B for xylose isomerase (xylA) and twofold higher for xylulokinase (xylB). Increased expression of genes involved in xylose catabolism is proposed as the basis for the increase in growth rate and glycolytic flux in ethanologenic KO11.

Bacterial Proteins↗

Assessment of the length of each hemodialysis session by on-line dialysate urea monitoring.

Hemodialysis (HD) prescription is usually based on the periodical measurement of the Kt/V achieved in a midweek dialysis session. The purpose of the study was to assess the duration of each HD session to achieve a target dose of dialysis. This allowed to determine whether a given dialysis session may be considered representative of the other HD sessions. Seventy-two HD sessions were studied in 4 stable patients, who were randomly dialyzed during 3 consecutive periods, each lasting 2 weeks, using a different blood flow rate (Qb) in each period: 400, 300 or 200 ml/min. All HD were prolonged to achieve an on-line dialysate urea monitor (UM) Kt/V of 1.2. The UM Kt/V was compared with the Kt/V calculated using pre-HD, post-HD and rebound (45 min post-HD) plasma water urea concentrations. Comparison of the duration of the second midweek dialysis session with the length of the other HD showed 95% concordance intervals (+/-2 SD) of +/-21.08 min for Qb 400, +/-26.88 min for Qb 300 and +/-37.02 min for Qb 200 ml/min. The 95% concordance intervals for whole body urea clearance were +/-32.0, +/-20.36 and +/-15.62 ml/min for Qb 400, 300 and 200 ml/min, respectively. No differences were observed between UM Kt/V and blood-based double-pool Kt/V obtained by the second-generation Daugirdas (1.18 +/- 0.08) and Garred (1.19 +/- 0.08) Kt/V formulas. In conclusion, a great variability was observed between different HD sessions with regard to the whole body urea clearance and the time required to attain a target Kt/V even when the HD characteristics remained constant. The length of every HD required to achieve a target dose of dialysis can be assessed by on-line dialysate urea monitoring.

Aged↗

Colon-specific delivery of budesonide from microencapsulated cellulosic cores: evaluation of the efficacy against colonic inflammation in rats.

Budesonide (BDS) is a potent corticosteroid that has important implications in the pharmacotherapy of inflammatory bowel disease, especially in the treatment of ulcerative colitis and Crohn's disease. BDS is available on the market in the form of enteric-coated preparations. However these products, similar to other available site-specific dosage forms, are not sufficiently selective to treat colonic inflammatory bowel disease. The objective of this study was to evaluate the efficacy of a new microparticulate system containing BDS, to treat experimentally induced colitis in rats. This microparticulate system consisted of BDS-containing hydrophobic cores, microencapsulated within an enteric polymer, which solubilizes at above pH 7, thus combining pH-sensitive and controlled-release properties. Colonic injury and inflammation were assessed by measuring colon/bodyweight ratio, myeloperoxidase (MPO) activity, and by scoring macroscopic and histological damage in colitic rats. Rats were treated orally with BDS, included in the developed system, once a day for 4 days after the induction of inflammation. A BDS suspension and BDS-containing enteric microparticles were included as control formulations in the experimental design. The administration of the new BDS delivery system significantly reduced the colon/bodyweight ratio compared with the administration of control formulations. Similarly, MPO activity and macroscopic and histological damage of the inflamed colonic segments decreased significantly when the BDS formulation was administered, compared with the results obtained after oral administration of the drug suspension. There were no significant differences, however, when the new treatment was compared with the control formulation consisting of simple enteric microparticles.

Administration, Oral↗

Enhancement of the conversion of toluene by Pseudomonas putida F-1 using organic cosolvents.

Pseudomonas putida F-1 (ATCC700007) was used as a model organism in stirred tank reactors to study conversion enhancement of poorly soluble substrates by organic cosolvents. After a literature study, silicone oil was used as a solvent system to enhance the mass transfer rate. To study the benefits of the organic solvent addition, batch experiments were conducted in two side-by-side fermentation vessels (experimental and control) at three different levels of silicone oil (10, 30, and 50%). Results showed that the presence of silicone oil resulted in a 100% increase in the toluene mass transfer compared to the control. Experiments in continuous stirred-tank reactors showed that improved conversion could be obtained at higher agitation rates.

Bioreactors↗