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Biomedical subjects

J A Garcia

Publications and source records attributed to J A Garcia.

At least 19 recordsLinked to original sources

Prognostic factors associated with long-term survival in previously untreated metastatic renal cell carcinoma.

PURPOSE: To identify prognostic factors (PF) for long-term survival in metastatic renal cell carcinoma (RCC) patients. METHODS: We retrospectively reviewed a metastatic RCC database at the Cleveland Clinic Foundation consisting of 358 previously untreated patients who were enrolled in institutional review board-approved clinical trials of immunotherapy and/or chemotherapy at our institution from 1987 to 2002. In order to identify patient characteristics associated with long-term survival, we compared 226 'short-term' survivors [defined as overall survival (OS) <2 years] with 31 'long-term' survivors (OS >or=5 years). RESULTS: Using logistic regression models, four adverse PF were identified as independent predictors of long-term survival: hemoglobin less than the lower limit of normal, greater than two metastatic sites, involved kidney (left), and Eastern Cooperative Oncology Group (ECOG) performance status (PS). Using the number of poor prognostic features present, three distinct risk groups could be identified. Patients with 0 or 1 adverse prognostic feature present had an observed likelihood of long-term survival of 32% (21/66) compared with 9% (8/91) for patients with two adverse features present and only 1% (1/93) for patients with more than two adverse features. CONCLUSIONS: Independent predictors of long-term survival in previously untreated metastatic RCC include baseline hemoglobin level, number of involved sites, involved kidney, and ECOG PS. Incorporation of these factors into a simple prognostic scoring system enables three distinct groups of patients to be identified.

Adult↗

Tramadol-associated pericarditis.

Tramadol, marketed as Ultram in the United States, is as a non-scheduled narcotic analgesic based on its low abuse liability. It is indicated for the treatment of moderately severe pain; however, multiple adverse effects have been reported with its use including seizures, anaphylaxis, angioedema, bronchospasm, and serotonin syndrome. An association between tramadol and pericarditis has not been previously reported. We describe the case of an 88 year-old male who developed acute pericarditis 2 days following tramadol initiation. The temporal relationship between drug initiation and pericarditis as well as the resolution of symptoms upon drug discontinuation suggested a potential association. Although pericarditis has not been described with tramadol administration, clinicians should be aware of a possible association.

Aged↗

Application of GFP-tagged Plum pox virus to study Prunus-PPV interactions at the whole plant and cellular levels.

The Sharka disease caused by the potyvirus Plum pox virus (PPV) is one of the most serious viral diseases affecting stone fruit trees. The study of PPV/Prunus interaction under greenhouse controlled conditions is space, time, labor consuming. While the PPV/Prunus interactions are now quite well known at the whole plant level, few data however are available on the interactions between the virus and the Prunus host plants at the cellular level. Using a green fluorescent protein (GFP)-tagged M type PPV strain, combined to an in vitro inoculation procedure, we developed a novel tool to track PPV invasion in Prunus persica (peach) cv. GF305 and Prunus armeniaca (apricot) cv. Screara susceptible hosts. Different graft combinations were performed using in vitro-maintained healthy or GFP-tagged PPV infected 'GF305' and 'Screara'. Contact for 30 days in grafts between the inoculum and the genotype to be tested were found sufficient to allow the systemic spread of the recombinant virus: fluorescence from GFP-tagged PPV could easily be detected in the entire plant under a binocular microscope allowing quick and reliable sorting of infected plants. Using a fluorescence stereomicroscopy or confocal microscopy, GFP could also be observed in stem cross-sections especially in epidermis and pith cells. In vitro grafting inoculation with GFP-tagged PPV provides a new and powerful tool to facilitate mid-term virus maintenance. Moreover, this tool will be of special importance in the study of PPV infection dynamics in Prunus, allowing as well precise observations of cellular events related to PPV/Prunus interactions.

Green Fluorescent Proteins↗

The St. Leger total knee replacement--a 7-year clinical assessment and survivorship analysis.

The St. Leger total knee replacement was developed with the aim of producing an affordable prosthesis which contained the best known features of current designs and also allowed ease of instrumentation. We present the medium term clinical and radiographic outcome and survivorship of the prosthesis. From 1992 to August 1994, 150 St. Leger total knee replacements were performed on 53 male and 72 female patients. Mean age was 67 (Range: 40-86). Sixty-nine percent of operations were for osteoarthritis and 30% for rheumatoid arthritis. Patients were reviewed at 1, 4 and 7 years postoperatively by an independent assessor. One hundred and twenty-three patients were assessed at 4 years and 83 patients at 7 years. The American Knee Association Scores revealed 84% excellent or good, 9% fair, and 7% poor results at 7 years. No patients complained of severe pain, 90% had mild or no pain, 10% had moderate pain. Eighty nine percent of patients were satisfied with their outcome. There were five complications requiring revision: infection (2), loosening (1), valgus instability (1) and knee stiffness (1). Survivorship analysis revealed 95% (95% CI +/-7.2%) survival at 7 years. Total knee replacement using the St. Leger knee prosthesis has comparable results to other condylar knee systems that cost almost twice the price.

Adult↗

Complex fractures of the distal humerus in the elderly. The role of total elbow replacement as primary treatment.

Between 1995 and 2000, 19 consecutive patients with fractures of the distal humerus were treated by primary total elbow replacement using the Coonrad-Morrey prosthesis. No patient had inflammatory or degenerative arthritis of the elbow. The mean age at the time of injury was 73 years (61 to 95). According to the AO classification, 11 patients had suffered a C3 injury, two a B3 and two an A3. One fracture was unclassified. Two patients died from unrelated causes and one was unable to be assessed because of concurrent illness. The mean time to follow-up was three years (1 to 5.5). At follow-up 11 patients (68%) reported no pain, four (25%) had mild pain with activity and one had mild pain at rest. The mean flexion arc was 24 degrees to 125 degrees. The mean supination was 90 degrees (70 to 100) and pronation 70 degrees (50 to 110). No elbow was unstable. The mean Disabilities of the Arm, Shoulder and Hand score was 23 (0.92 to 63.3) and the mean Mayo elbow performance score was 93 (80 to 100). Of the 16 patients, 15 were satisfied with the outcome. Radiological evaluation revealed only one patient with a radiolucent line at the cement-bone interface. It was between 1 and 2 mm in length, was present on the initial postoperative radiograph and was non-progressive at the time of follow-up. Primary total elbow arthroplasty is an acceptable option for the management of comminuted fractures of the distal humerus in elderly patients when the configuration of the fracture and the quality of the bone make reconstruction difficult.

Aged↗

NPAS2: an analog of clock operative in the mammalian forebrain.

Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain. NPAS2 is highly related in primary amino acid sequence to Clock, a transcription factor expressed in the suprachiasmatic nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To investigate the biological role of NPAS2, we prepared a neuroblastoma cell line capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified putative target genes by representational difference analysis, DNA microarrays, and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of the endogenous Per1, Per2, and Cry1 genes, which encode negatively activating components of the circadian regulatory apparatus, and repressed transcription of the endogenous BMAL1 gene. Analysis of the frontal cortex of wild-type mice kept in a 24-hour light-dark cycle revealed that Per1, Per2, and Cry1 mRNA levels were elevated during darkness and reduced during light, whereas BMAL1 mRNA displayed the opposite pattern. In situ hybridization assays of mice kept in constant darkness revealed that Per2 mRNA abundance did not oscillate as a function of the circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of a molecular clock operative in the mammalian forebrain.

ARNTL Transcription Factors↗

Statistical parameters in behavioral tasks and implications for sample size of C57BL/6J:129S6/SvEvTac mixed strain mice.

Most mixed strain progeny from gene-knockout experiments typically originate from C57BL/6J and one of the 129 substrains, frequently 129S6/SvEvTac. The results of this behavioral survey suggest that C57BL/6J:129S6/SvEvTac mixed strain mice are amenable to behavioral testing. The variability in behavioral tasks for subjects arising from this mixed strain genetic background does not preclude screening with a battery of behavioral tests. With clues provided by a screen of mixed strain subjects, follow-up analyses with isogenic, congenic, or F1 hybrid animals may be targeted to specific behavioral themes.

Animals↗

Impaired cued and contextual memory in NPAS2-deficient mice.

Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PAS domain transcription factor expressed in multiple regions of the vertebrate brain. Targeted insertion of a beta-galactosidase reporter gene (lacZ) resulted in the production of an NPAS2-lacZ fusion protein and an altered form of NPAS2 lacking the bHLH domain. The neuroanatomical expression pattern of NPAS2-lacZ was temporally and spatially coincident with formation of the mature frontal association/limbic forebrain pathway. NPAS2-deficient mice were subjected to a series of behavioral tests and were found to exhibit deficits in the long-term memory arm of the cued and contextual fear task. Thus, NPAS2 may serve a dedicated regulatory role in the acquisition of specific types of memory.

Animals↗

The efficacy of cyanoacrylate-derived surgical adhesive for use in the repair of lacerations during competitive athletics.

Octylcyanoacrylate (Dermabond) is approved by the Food and Drug Administration for laceration closure. International studies have shown its utility in wound closure and have shown it to be as good or better than suture closure for speed, patient preference, and cosmesis, with no difference in the rate of dehiscence or infection. We sought to determine whether it retains its tensile strength, durability, and skin apposition when an athlete is allowed to reenter competition, where it is subject to recurrent stress, moisture, and trauma. The study was performed at two professional hockey sites. Wounds were anesthetized, irrigated, and debrided. The skin was closed with Dermabond. The athlete was returned immediately to competition. Wounds were examined at the end of competition and again at 7 days. A total of 32 lacerations on 28 players were studied. The mean size of laceration was 2.3 cm (range 0.8 cm to 4.5 cm). The majority (95%) of wounds were on the face. Of the 32 lacerations, 31 (97.6%) had good results at the conclusion of the game. Of these 31, all had good results at 7 days following repair. Dermabond retained its strength, durability, and skin apposition when the athlete was allowed to reenter competition following wound repair.

Competitive Behavior↗

Assessing bilingual and monolingual Latino students with translations of the MMPI-2: initial data.

This article presents the results of 2 studies conducted with Spanish versions of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) with Latino students. Study 1 compared the results of 2 administrations of the MMPI-2, one in English and the other in Spanish. Study 2 compared the results of administrations of 2 Spanish versions of the MMPI-2, the official Mexican adaptation and the Version Hispana. In both cases, scale score differences were not found. Comparability, as operationally defined by test-retest reliability, was found to be higher for the group that was administered the English and Spanish versions than the group administered the 2 Spanish versions. Overall, the results were found to suggest correspondence. Yet, the authors warn against concluding "perfect" correspondence because other key groups need to be studied, including psychiatric patients and persons from the Latino community. Also, the determination of linguistic equivalence needs further refinement.

Adult↗

Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain.

Adenovirus-mediated gene transfer of interferon gamma (AdIFN) elicits rejection of intracerebral Lewis lung carcinoma. In this system, gene transfer into brain parenchymal cells is both necessary and sufficient to generate the antitumor response. Despite persistent parenchymal inflammation and demyelination, wild-type mice injected intracerebrally with either AdIFN or beta-galactosidase adenovirus (AdBGAL) perform as well as non-injected animals in behavioral, memory, and motor tests. Both AdIFN and AdBGAL elicit demyelination whose incidence rises sharply when the lowest effective dose of AdIFN is exceeded. Therefore, transfer of interferon gamma into brain parenchyma does not seem to elicit detectable cognitive, behavioral or motor deficits. Furthermore, gene transfer into the brain, by adenoviral vectors currently in clinical trials, is associated with a narrow therapeutic window where the incidence of demyelination rises sharply soon after the effective dose is achieved. Gene Therapy (2000) 7, 2094-2098.

Adenoviridae↗

Lack of toxicity to adults of the Mexican fruit fly (Diptera: Tephritidae) of beta-exotoxin in Bacillus thuringiensis endotoxin preparations.

beta-Exotoxin (thuringiensin) was found in high titers in centrifugation supernatants and acetone/lactose powders produced from centrifugation pellets of strains Guat 1 and HD 2 of Bacillus thuringiensis (Berliner). Diets containing powders of either strain were toxic, diets containing Guat 1 supernatant were not toxic, diets containing HD 2 supernatant were slightly toxic, and diets containing powders or supernatants from uninoculated culturing medium spiked with beta-exotoxin were not toxic. Most mortality occurred within 3 d when flies fed on powders but not until 6-7 d when flies fed on HD 2 supernatant. These results indicated that the primary toxic principals of the powders were endotoxins/spores and that beta-exotoxin alone was not toxic to adult flies at the concentrations found in the supernatants or powders.

Adenosine↗

The role of the right ventricle during hypobaric hypoxic exercise: insights from patients after the Fontan operation.

OBJECTIVES: The principal objective of this study was to examine the importance of the right ventricle for maximal systemic oxygen transport during exercise at high altitude by studying patients after the Fontan operation. BACKGROUND: High-altitude-induced hypoxia causes a reduction in maximal oxygen uptake. Normal right ventricular pump function may be critical to sustain cardiac output in the face of hypoxic pulmonary vasoconstriction. We hypothesized that patients after the Fontan operation, who lack a functional subpulmonary ventricle, would have a limited exercise capacity at altitude, with an inability to increase cardiac output. METHODS: We measured oxygen uptake (VO2, Douglas bag), cardiac output (Qc, C2H2 rebreathing), heart rate (HR) (ECG), blood pressure (BP) (cuff), and O2 Sat (pulse oximetry) in 11 patients aged 14.5+/-5.2 yr (mean +/- SD) at 4.7+/-1.6 yr after surgery. Data were obtained at rest, at three submaximal steady state workrates, and at peak exercise on a cycle ergometer. All tests were performed at sea level (SL) and at simulated altitude (ALT) of 3048 m (10,000 ft, 522 torr) in a hypobaric chamber. RESULTS: At SL, resting O2 sat was 92.6+/-4%. At ALT, O2 sat decreased to 88.2+/-4.6% (P < 0.05) at rest and decreased further to 80+/-6.3% (P < 0.05) with peak exercise. At SL, VO2 increased from 5.1+/-0.9 mL x kg(-1) x min(-1) at rest to 23.5+/-5.3 mL x kg(-1) x min(-1) at peak exercise and CI (Qc x m(-2)) increased from 3.3+/-0.7 L x m(-2) to 6.2+/-1.2 L x m(-2). VO2 peak, 17.8+/-4 mL x kg(-1) x min(-1) (P < 0.05), and CI peak, 5.0+/-1.5 L x m(-2) (P < 0.05), were both decreased at ALT. Remarkably, the relationship between Qc and VO2 was normal during submaximal exercise at both SL and ALT. However at ALT, stroke volume index (SVI, SV x m(-2)) decreased from 37.7+/-8.6 mL x min(-1) x m2 at rest, to 31.3+/-8.6 mL x min(-1) x m2 at peak exercise (P < 0.05), whereas it did not fall during sea level exercise. CONCLUSIONS: During submaximal exercise at altitude, right ventricular contractile function is not necessary to increase cardiac output appropriately for oxygen uptake. However, normal right ventricular pump function may be necessary to achieve maximal cardiac output during exercise with acute high altitude exposure.

Adolescent↗

Usefulness of Doppler echocardiography in diagnosing right ventricular coronary arterial communications in patients with pulmonary atresia and intact ventricular septum and comparison with angiography.

Direct and indirect evidence of right ventricular coronary arterial communications has been detected by use of 2-dimensional and Doppler echocardiography in patients with pulmonary atresia and intact ventricular septum. We describe additional consistent and reproducible Doppler echocardiographic findings that were useful for identifying patients in whom abnormal coronary arterial flow patterns were detected angiographically.

Coronary Angiography↗

Ribotyping and plasmid profiling of Yersinia ruckeri.

A total of 183 strains of Yersinia ruckeri, isolated from a wide variety of sources, were studied with respect to their plasmid profile and ribotype patterns. Eight plasmid profiles and 11 ribotypes were demonstrated, with one profile being predominant by both typing methods. The results suggest a clonal structure for this species, with a predominant clone being responsible for most of the outbreaks worldwide. The results of a long-time survey in several fish farms in Spain and Denmark seem to support this idea.

Bacterial Typing Techniques↗

Enalapril does not enhance exercise capacity in patients after Fontan procedure.

BACKGROUND: Angiotensin-converting enzyme inhibitors improve exercise capacity in adults with congestive heart failure by decreasing systemic vascular resistance and improving ventricular diastolic function. Patients who have undergone the Fontan procedure have decreased cardiac output, increased systemic vascular resistance, abnormal diastolic function, and decreased exercise capacity compared with normal people. METHODS AND RESULTS: To test the hypothesis that afterload reduction therapy alters hemodynamic variables and augments exercise capacity in patients after a Fontan procedure, we compared the results of graded exercise with maximal effort from 18 subjects (14.5+/-6.2 years of age, 4 to 19 years after Fontan procedure) in a randomized, double-blind, placebo-controlled crossover trial using enalapril (0.2 to 0.3 mg x kg[-1] x d[-1], maximum 15 mg). Each treatment was administered for 10 weeks. Diastolic filling patterns at rest were assessed by Doppler determination of the systemic atrioventricular valve flow velocity at the conclusion of each therapy. No difference was detected in resting heart rate, blood pressure, or cardiac index. Diastolic filling patterns were also similar. Exercise duration was not different (6.4+/-2.6 [enalapril] versus 6.7+/-2.6 minutes [placebo]). The mean percent increase in cardiac index from rest to maximum exercise was slightly but significantly decreased in subjects after 10 weeks of enalapril therapy (102+/-34% [enalapril] versus 125+/-34% [placebo]; P<.02). At maximal exercise, cardiac index (3.5+/-0.9 [enalapril] versus 3.8+/-0.9 L x min[-1] x m2 [placebo]), oxygen consumption (18.3+/-9 [enalapril] versus 20.5+/-7 mL x min[-1] x kg[-1] [placebo]), minute ventilation (57.5+/-17 [enalapril] versus 55.4+/-19 L/min [placebo]), and total work (247+/-181 [enalapril] versus 261+/-197 W [placebo]) were not different. CONCLUSIONS: We conclude that enalapril administration for 10 weeks does not alter abnormal systemic vascular resistance, resting cardiac index, diastolic function, or exercise capacity in patients who have undergone a Fontan procedure.

Adolescent↗

Unconventional myosins in inner-ear sensory epithelia.

To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined the distribution of four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes. Of the four isozymes, each from a different class, three are expressed in the hair cells of amphibia and mammals. In stereocilia, constructed of cross-linked F-actin filaments, myosin-Ibeta is found mostly near stereociliary tips, myosin-VI is largely absent, and myosin-VIIa colocalizes with crosslinks that connect adjacent stereocilia. In the cuticular plate, a meshwork of actin filaments, myosin-Ibeta is excluded, myosin-VI is concentrated, and modest amounts of myosin-VIIa are present. These three myosin isozymes are excluded from other actin-rich domains, including the circumferential actin belt and the cortical actin network. A member of a fourth class, myosin-V, is not expressed in hair cells but is present at high levels in afferent nerve cells that innervate hair cells. Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt. Our localization results suggest specific functions for three hair-cell myosin isozymes. As suggested previously, myosin-Ibeta probably plays a role in adaptation; concentration of myosin-VI in cuticular plates and association with stereociliary rootlets suggest that this isozyme participates in rigidly anchoring stereocilia; and finally, colocalization with cross-links between adjacent stereocilia indicates that myosin-VIIa is required for the structural integrity of hair bundles.

Animals↗