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Biomedical subjects

R Rodriguez

Publications and source records attributed to R Rodriguez.

At least 109 records · Page 6Linked to original sources
PubMed1999

Laparoscopic renal cryoablation: acute and long-term clinical, radiographic, and pathologic effects in an animal model and application in a clinical trial.

OBJECTIVES: To evaluate renal cryosurgery by studying the feasibility of laparoscopic delivery and the radiographic characteristics and histopathologic effects in a porcine model using different freeze cycles. On the basis of the results, a clinical trial of laparoscopic cryosurgical ablation in select patients with clinical stage T1 renal tumors was started. MATERIALS AND METHODS: Twelve kidneys from six farm pigs underwent cryosurgery. Each kidney was treated with two freeze cycles to -180 degrees C. Six kidneys were retroperitonealized, and six were not. An abdominal CT scan was performed at various times to evaluate for the presence of urinoma or hematoma and to monitor lesion changes. Organs were harvested at times ranging from 24 hours to 13 weeks. Radiographic and histopathologic changes were recorded for each time period. Eight patients with small (average 2-cm) exophytic renal masses underwent laparoscopic biopsy and cryosurgical ablation using a 3- or 4.8-mm probe (Cryomedical Sciences Inc., Rockville, MD) for one 15-minute or two 5-minute freeze cycles to a temperature of -180 degrees C to extend the ice ball at least 7 mm beyond the tumor margin. RESULTS: Dense adhesions between the bowel and cryoablated renal tissue were encountered in all non-retroperitonealized kidneys, but no fistula formation was present. The retroperitonealized kidneys had minimal adhesion formation. None of the animals developed a urinary fistula. At 24 hours and 1 week, CT scanning demonstrated an enhancement defect corresponding to the region of the ice ball with no urinoma or hematoma. At 13 weeks, only a nonenhancing cortical defect was seen. At immediate harvest, hemorrhage was noted in the area of the ice ball with a sharp demarcation at the edge of the freeze zone. At 1 week, four distinct zones were seen: central necrosis, inflammatory infiltrate, hemorrhage, and fibrosis with regeneration. At 13 weeks, the necrotic tissue had been replaced with a circumscribed area of fibrosis. There were no intraoperative or postoperative complications in the eight patients. The estimated blood loss was 140 mL, and the mean hospital stay was 3.5 days. At a mean clinical follow-up of 7.7 (range 1-18) months and radiographic follow-up of 5 months; there have been no tumor recurrences or significant changes in the serum creatinine concentration. At 24 hours, there was an enhancement defect in the area of the ice ball. The CT images at 13 weeks showed a nonenhancing cortical defect in the area of the ice ball. CONCLUSIONS: Cryosurgery can be readily delivered laparoscopically, creating a discrete lesion at the time of treatment that appears to be consistent over time. In the animal studies, complete tissue necrosis developed in the freeze zone, followed by reabsorption, and by 13 weeks, fibrous tissue had replaced the defect. In the animal and human trials, there were no operative complications, urinomas, hematomas, or bowel or urinary fistulas. Follow-up imaging in human trials revealed a persistent nonenhancing defect in the area of the freeze zone. Long-term clinical follow-up will be necessary to determine the cancer-free survival rate.

Aged↗
PubMed1999

Evidence for early hematopoietic progenitor cell involvement in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) represents a subtype of acute myeloid leukemia with characteristic morphologic, molecular, and immunophenotypic features. Previous immunophenotypic analyses have shown that leukemic cells in APL typically express the myeloid markers CD33 and CD13 but lack expression of the early hematopoietic progenitor cell antigens CD34 and HLA-DR. We analyzed selected immunophenotypic features of APL by flow cytometry and showed that 7 (41%) of 17 cases contained significant subsets of CD34+ leukemic cells: CD34+ myeloid cells predominated in 2 APL cases. By using a fluorescence-activated cell sorter-fluorescence in situ hybridization approach, we confirmed that the CD34+ cells harbored the t(15;17) translocation characteristic of APL. By using the same experimental approach, CD34+ populations were stratified into primitive CD34+ CD38- and committed CD34+ CD38+ progenitor cell subpopulations; cells in both subsets contained the t(15;17) translocation. The knowledge that APL may be partly or largely CD34+ is important for proper diagnosis. Furthermore, identification of the t(15;17) translocation in CD34+ CD38- blasts indicates that, in at least some cases, the leukemogenic mutation in APL occurs within primitive hematopoietic progenitor cells.

Antigens, CD34↗
PubMed1999

Relationship between ANCA and disease activity in small vessel vasculitis patients with anti-MPO ANCA.

BACKGROUND: We analysed the usefulness of antineutrophil cytoplasmic antibodies (ANCA) as a marker of clinical activity in patients with small vessel vasculitis associated with anti-myeloperoxidase (MPO) ANCA. METHODS: We studied a group of 25 patients, 15 with microscopic polyangitis and 10 with renal limited vasculitis, so-called rapidly progressive glomerulonephritis type III. The clinical and serological follow-up was accomplished quarterly over an average of 2.79 +/- 2.08 years (range 0.25-6 years). ANCA was analysed by indirect immunofluorescence and enzyme-linked immunosorbent assays (ELISAs). RESULTS: At the time of diagnosis, all patients were ANCA positive (P-ANCA and anti-MPO). Following a standardized treatment, all patients except one achieved complete remission of vasculitis in <3 months. One patient suddenly died during the active phase (1 month of follow-up) and with positive ANCA. Seroconversion from positive to negative occurred in 24/25 patients (96%). Eighteen of these 24 patients (75%) achieved the seroconversion within the first 6 months. During the follow-up, two patients had four major relapses, all of them associated with positive ANCA. ANCA seroconversion from negative to positive was observed in one patient with microscopic polyangitis without clinical relapse of vasculitis. CONCLUSION: ANCA should be used in conjunction with other markers of disease activity in the management of microscopic polyangitis and renal limited vasculitis patients with anti-MPO ANCA.

Adult↗
PubMed1999

Fluvoxamine distribution in postmortem cases.

Four postmortem cases are reported in which the selective serotonin re-uptake inhibitor fluvoxamine was identified. Fluvoxamine was detectable using a standard alkaline drug screen, chromatographed well using a HP-1 column, and did not require derivitization for quantitation. Two of the cases reported were drug intoxications; fluvoxamine was only an incidental finding in the other 2 cases. Central and peripheral blood values are reported, as well as antemortem blood, bile, vitreous fluid, and urine values. No solid organs were obtained in any of the cases. Quantitations were performed using both an analytical standard and a fluvoxamine tablet for the preparation of calibrators. A comparison of quantitative values was made to evaluate the feasibility of using a tablet as the drug source for the preparation of calibrators when a pure reference material is unavailable. Postmortem peripheral blood concentrations ranged from approximately 0.5 mg/L in a case of suicidal shooting to approximately 6 mg/L in a case of drug overdose. Evidence of postmortem redistribution was noted in the only case for which both central and peripheral blood were obtained. Quantitations using an extracted drug tablet for the preparation of calibrators correlated well with quantitations using a pure reference material.

Adult↗
PubMed1999

Fungi from geothermal soils in Yellowstone National Park.

Geothermal soils near Amphitheater Springs in Yellowstone National Park were characterized by high temperatures (up to 70 degrees C), high heavy metal content, low pH values (down to pH 2.7), sparse vegetation, and limited organic carbon. From these soils we cultured 16 fungal species. Two of these species were thermophilic, and six were thermotolerant. We cultured only three of these species from nearby cool (0 to 22 degrees C) soils. Transect studies revealed that higher numbers of CFUs occurred in and below the root zone of the perennial plant Dichanthelium lanuginosum (hot springs panic grass). The dynamics of fungal CFUs in geothermal soil and nearby nongeothermal soil were investigated for 12 months by examining soil cores and in situ mesocosms. For all of the fungal species studied, the temperature of the soil from which the organisms were cultured corresponded with their optimum axenic growth temperature.

Acremonium↗
PubMed1999

Effects of feedback projections from area 18 layers 2/3 to area 17 layers 2/3 in the cat visual cortex.

In the absence of a direct geniculate input, area 17 cells in the cat are nevertheless able to respond to visual stimuli because of feedback connections from area 18. Anatomic studies have shown that, in the cat visual cortex, layer 5 of area 18 projects to layer 5 of area 17, and layers 2/3 of area 18 project to layers 2/3 of area 17. What is the specific role of these connections? Previous studies have examined the effect of area 18 layer 5 blockade on cells in area 17 layer 5. Here we examine whether the feedback connections from layers 2/3 of area 18 influence the orientation tuning and velocity tuning of cells in layers 2/3 of area 17. Experiments were carried out in anesthetized and paralyzed cats. We blocked reversibly a small region (300 microm radius) in layers 2/3 of area 18 by iontophoretic application of GABA and recorded simultaneously from cells in layers 2/3 of area 17 while stimulating with oriented sweeping bars. Area 17 cells showed either enhanced or suppressed visual responses to sweeping bars of various orientations and velocities during area 18 blockade. For most area 17 cells, orientation bandwidths remained unaltered, and we never observed visual responses during blockade that were absent completely in the preblockade condition. This suggests that area 18 layers 2/3 modulate visual responses in area 17 layers 2/3 without fundamentally altering their specificity.

Animals↗
PubMed1999

Diabetes risk factors in low-income Mexican-American children.

OBJECTIVE: To learn if Mexican-American children from low income neighborhoods have excess diabetes risk factors. RESEARCH DESIGN AND METHODS: The study involved 173 Mexican-American children aged 9 years. This is the age before type 2 diabetes usually develops in youths and where the disparity in body fat between Mexican-American and non-Hispanic white children is evident. The study also targets poor children because diabetes and being overweight are more common in Mexican-American adults from a lower than from a higher socioeconomic status. The diabetes risk factors measured were percent body fat, dietary fat intake, daily fruit and vegetable intake, and physical fitness. Body fat was measured by bioelectric impedance, dietary intake was measured by three 24-h dietary recalls, and physical fitness was measured by a modified Harvard step test. RESULTS: According to self-reported dietary recalls, Mexican-American children ate higher than recommended fat servings and had higher percent energy from fat and saturated fat. On the other hand, their reported daily fruit and vegetable intake was half of that recommended by national dietary guidelines. A large percentage of these children were at unacceptable physical fitness levels. Percent body fat was higher in these Mexican-American children than that reported for non-Hispanic white children. Finally, 60% of the children had a first- or second-degree relative with diabetes. CONCLUSIONS: Because diabetes is highly prevalent in Mexican-American adults, type 2 diabetes in increasing in Mexican-American youths, and diabetes risk factors are more common in Mexican-American children, a prudent measure would be to explore early-age diabetes risk factor prevention programs in this population.

Adolescent↗
PubMed1999

In vitro fertilization is associated with an increased risk of hypospadias.

PURPOSE: The purpose of this study was to determine if there is an increased incidence of hypospadias in male offspring conceived by in vitro fertilization (IVF). MATERIALS AND METHODS: A retrospective institutional chart review from 1988 to 1992 and data from the Maryland Birth Defects Registry were statistically analyzed to assess the risk of hypospadias with IVF. RESULTS: The data for the 5-year period indicated a 5-fold increased risk of hypospadias after IVF, with an incidence of approximately 1.5% in the IVF group and 0.3% in the control group. The only recognized difference between the groups was maternal progesterone administration in the IVF group but the cause of the increased risk of hypospadias was unknown. The distribution of hypospadias severity was similar in both groups. CONCLUSIONS: Male newborns conceived by IVF have a 5-fold increased risk of hypospadias, which may be related to maternal progesterone administration, or other maternal or fetal endocrine abnormalities that may or may not be related to infertility. Health care providers should be aware of this risk so that they can properly counsel infertile couples seeking assisted reproduction by IVF technology.

Female↗
PubMed1999

Sickle cell disease and aortic valve replacement: use of cardiopulmonary bypass, partial exchange transfusion, platelet sequestration, and continuous hemofiltration.

Sickle cell disease in patients undergoing open heart procedures presents a multitude of challenges to the medical staff. With improved techniques of cardiopulmonary bypass, surgery, and anesthesia for treating patients with sickle cell disease, perfusionists will likely encounter patients with this genetic disorder on a more frequent basis. A 40-year-old black woman was admitted to our institution with recurrent Staphylococcus epidermidis and sepsis. She underwent transesophageal echocardiography and cardiac catheterization and was subsequently diagnosed with severe aortic insufficiency. The aortic valve was replaced. Herein, we report our experience in the preoperative, perioperative, and postoperative management of this patient. We present a concise update on the current literature and techniques used by others in similar cases, and we provide a brief section on future considerations to assist fellow practitioners in recognizing this disease and meeting the accompanying challenges.

Adult↗
PubMed1998

Schistosoma mansoni infection in owl monkeys (Aontus nancymai): evidence for the early elimination of adult worms.

Detailed parasitologic, serologic, clinical and histopathologic studies were conducted in owl monkeys (Aotus nancymai) exposed to varying numbers of cercariae of Schistosoma mansoni. All the experimental animals had clinical symptoms suggestive of infection (weight loss diarrhoea, mucus in stools, etc.) which were not seen in uninfected individuals. The only A. vociferans included in this study passed S. mansoni eggs 8 weeks after infection. None of the A. nancymai passed eggs in their faeces. No adult worms were recovered following perfusion of the sacrificed experimental monkeys, suggesting that they were early eliminated. Serological techniques (ELISA-SEA and COPT) allowed diagnosis of infection, starting 9 weeks post challenge, in all but one A. nancymai exposed to 100 cercariae. Granulomas containing eggs were observed predominantly in liver and less extensively in intestine, suggesting that adult worms were mainly lodged in the intrahepatic portal system. We conclude that A. nancymai is susceptible to infection with S. mansoi, with the worms reaching sexual maturity, but being eliminated shortly after oviposition.

Animals↗
PubMed1998

Identification of diphtheria toxin via screening as a potent cell cycle and p53-independent cytotoxin for human prostate cancer therapeutics.

BACKGROUND: Metastatic human prostate cancer requires novel therapeutic strategies in order to overcome its low proliferative rate and its resistance to conventional chemotherapeutic agents. To identify potential cytotoxin gene products for use in experimental therapeutics such as in vivo gene therapy, an in vitro screen was designed. METHODS: Eight recombinant cellular toxins were tested for activity against a spectrum of metastatic human prostate cancer cell phenotypes. Pseudomonas exotoxin A, ricin, tumor necrosis factor alpha (TNF-alpha), diphtheria toxin (DT), Crotalus durissus terrificus toxin, crotalus adamenteus toxin, Naja naja toxin, and Naja mocambique toxin were evaluated. Comparative survival distinguished the relative potencies of these cytotoxins for irreparable prostate cancer cell death. RESULTS: Of the phospholipase A2 toxins, Crotalus durissus terrificus and Naja mocambique are active against the PSA secreting LNCaP cell line; however, the effect is reversible, and no other hormone refractory prostate cell line tested is sensitive. Screening identified toxin-specific differences: dose-dependent cytotoxic activity against all human prostate cancer cell lines tested was only identified for ricin and diphtheria toxin (DT) as highly potent. DT has an IC50 in the range of 20-00 pM by clonogenic survival and kills irreversibly by both apoptosis as well as nonapototic pathways. Acquisition of p53 mutant status conferred no reduction in sensitivity to DT cytotoxicity. Cell cycle arrest by aphidicolin did not protect human prostate cells from irreversible DT-induced cell death. TNF-alpha had modest cytostatic activity in the screen; however, the combination of TNF-alpha and DT resulted in marked acceleration of the time to prostate cancer cell death. CONCLUSIONS: The rational screening of cytotoxins allows the identification of cell cycle-independent agents of variable potency against human prostate cancer. DT-mediated cell death is cell cycle independent, and p53 independent, making it particularly attractive for application to cytoreductive gene therapy, targeted monoclonal antibodies, and prodrug delivery of toxins applied to human prostate cancer therapeutics.

Antineoplastic Agents↗
PubMed1998

Reverse Micelle Systems Composed of Water, Triton X-100, and Phospholipids in Organic Solvents

Enzymes entrapped in systems formed with water, phospholipids, toluene, and Triton X-100 show a catalytic activity that is much lower and a thermostability that is much higher than that observed in totally aqueous systems or in other types of reverse micelles. By phase boundary titrations and dynamic light scattering, this work characterizes reverse micelle systems formed in either toluene or propylbenzene with Triton X-100 and water. Four regions with distinct structural features were encountered. Up to one molecule of water per one Triton X-100 molecule, the system was transparent; light scattering measurements of this region indicated that water hydrated Triton X-100 monomers. A turbid region was formed as water content was increased to water:Triton X-100 ratios of 7.6 in toluene and 4.2 in propylbenzene. This thermodynamically unstable region was formed by large polydisperse structures. Transparent systems containing small size (27-150 A) thermodynamically stable reverse micelles were formed when the ratio of water to Triton X-100 molecules in the reverse micelle was in the range of 7.6 to 26.8 in toluene and 4.2 to 15.1 in propylbenzene. In this region, micellar size increased with water content. Water concentrations higher than the latter values resulted in phase separation. A similar titration of the aforementioned systems in the presence of phospholipids revealed that in the first region of transparency up to 10 molecules of water hydrated a phospholipid molecule. The inclusion of phospholipids to the Triton X-100 systems caused a displacement of the boundaries of the second region of transparency toward higher water contents. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed1998

Reverse Micelle Systems Composed of Water, Triton X-100, and Phospholipids in Organic Solvents

Catalysis, stability, and thermostability of yeast hexokinase were determined in the microenvironments of two organic solvent/Triton X-100/phospholipids systems. In the abscence of enzyme, phase diagrams showed two transparent/turbid transitions, and reverse micelles were only observed in the second region of transparency (T2), where particle size as a function of water content shows a minima (see previous paper in this issue). In the present work, enzyme activity was detected throughout the four regions of the phase diagrams of these systems. Catalysis increased with water content; nevertheless, the maximum activities that were reached in the toluene and propylbenzene systems were 30 and 1.6%, respectively, of the activity in all aqueous media. Because in the T2 region in the propylbenzene system, micelles are much smaller than in toluene (see preceding paper), it would appear that expression of catalysis depends on the size of the micelles. However, a comparison of the dimensions of hexokinase and those of reverse micelles in the T2 region, suggests that in this region, hexokinase entrapment increases the inner volume of the micelle. High enzyme thermostability was only observed in the first transparent region (T1) of the system that contained phospholipids. In this region, hexokinase induced the formation of reverse micelles from dispersed surfactant monomers. There is a striking similarity in the dimensions of hexokinase entrapped in reverse micelles as determined by dynamic light scattering measurements in the T1 region with those of hexokinase as obtained from X ray diffraction studies of the enzyme in a crystalline environment. This suggest that high thermostability, and low catalytic rates result from restrictions in mobility imposed by a low water environment. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed1998

Analytical and simulation results for stochastic Fitzhugh-Nagumo neurons and neural networks.

An analytical approach is presented for determining the response of a neuron or of the activity in a network of connected neurons, represented by systems of nonlinear ordinary stochastic differential equations--the Fitzhugh-Nagumo system with Gaussian white noise current. For a single neuron, five equations hold for the first- and second-order central moments of the voltage and recovery variables. From this system we obtain, under certain assumptions, five differential equations for the means, variances, and covariance of the two components. One may use these quantities to estimate the probability that a neuron is emitting an action potential at any given time. The differential equations are solved by numerical methods. We also perform simulations on the stochastic Fitzugh-Nagumo system and compare the results with those obtained from the differential equations for both sustained and intermittent deterministic current inputs with superimposed noise. For intermittent currents, which mimic synaptic input, the agreement between the analytical and simulation results for the moments is excellent. For sustained input, the analytical approximations perform well for small noise as there is excellent agreement for the moments. In addition, the probability that a neuron is spiking as obtained from the empirical distribution of the potential in the simulations gives a result almost identical to that obtained using the analytical approach. However, when there is sustained large-amplitude noise, the analytical method is only accurate for short time intervals. Using the simulation method, we study the distribution of the interspike interval directly from simulated sample paths. We confirm that noise extends the range of input currents over which (nonperiodic) spike trains may exist and investigate the dependence of such firing on the magnitude of the mean input current and the noise amplitude. For networks we find the differential equations for the means, variances, and covariances of the voltage and recovery variables and show how solving them leads to an expression for the probability that a given neuron, or given set of neurons, is firing at time t. Using such expressions one may implement dynamical rules for changing synaptic strengths directly without sampling. The present analytical method applies equally well to temporally nonhomogeneous input currents and is expected to be useful for computational studies of information processing in various nervous system centers.

Action Potentials↗