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Biomedical subjects

A Park

Publications and source records attributed to A Park.

At least 91 records · Page 5Linked to original sources

Influence of CO2 pneumoperitoneum on systemic and peritoneal cell-mediated immunity.

Port site metastases could be due to mechanical reasons or impairment of host defenses. As it is known that carbon dioxide is toxic for lymphocytes in vitro we decided to investigate lymphocyte stress during laparoscopy. Blood samples and peritoneal fluids were obtained before and after pneumoperitoneum from 16 patients undergoing laparoscopic cholecystectomy. Lymphocyte subsets were determined by flow cytometry. Propidium iodide was used as a lymphocyte vitality test. Cytokines were measured by an ELISA system. Significant falls in the absolute lymphocyte count and T3 and T4 lymphocytes occurred on postoperative day 1 with a quick return to the preoperative value on day 2. T8, natural killer cells, T4/T8, and T4+/T8+ counts were stable. Interleukins 1 beta and 6 and tumor necrosis factor-alpha were depressed during the two postoperative days. Peritoneal lymphocytes were not destroyed by pneumoperitoneum as demonstrated by the propidium test, nor were they locally impaired by carbon dioxide. The circulating lymphocyte subpopulation decrease favors moderate, brief immunodepression. The origin of port site metastases is not immunologic depression but, rather, facilitated implantation of malignant cells by hyperpressure into raw tissues.

Carbon Monoxide↗

The lateral approach to laparoscopic splenectomy.

BACKGROUND: Laparoscopic splenectomy has been shown to result in shorter hospital stays and a quicker return to work than conventional splenectomy. Having tried the anterior 5 trocar approach, we developed a 4 trocar lateral approach and now present our experience with 22 cases. METHODS: All patients were placed in the right lateral decubitus position. A 10-mm trocar was inserted in the left subcostal region, 2 in the flank, and a 5-mm trocar dorsally. A 30 degrees laparoscope was used. Splenectomy was performed for varying pathologies. RESULTS: Operating room (OR) time averaged 169 minutes, spleen weight 513 grams, and postoperative (post-op) stays 5.4 days (median 3 days). One patient was converted to laparotomy. There were no deaths, post-op abscesses, pancreatic injuries, or bleeding complications. CONCLUSIONS: The lateral approach affords superior exposure, allowing easier dissection of splenic hilar structures. Over varying patient habitus and spleen size it has been demonstrated to be the approach of choice for laparoscopic splenectomy.

Adolescent↗

Systematic mutational analysis of the death domain of the tumor necrosis factor receptor 1-associated protein TRADD.

Tumor necrosis factor receptor 1 (TNF-R1) mediates most of the biological properties of TNF including activation of the transcription factor NF-kappaB and programmed cell death. An approximately 80-amino acid region within the intracellular domain of the receptor, termed the death domain, is required for signaling NF-kappaB activation and cytotoxicity. A TNF-R1-associated protein TRADD has been discovered that interacts with the death domain of the receptor. Elevated expression of TRADD in cells triggers both NF-kappaB activation and programmed cell death pathways. The biological activities of TRADD have been mapped to a 111-amino acid region within the carboxyl-terminal half of the protein. This region shows sequence similarity to the death domain of TNF-R1 and can self-associate and bind to the TNF-R1 death domain. We have performed an alanine scanning mutagenesis of TRADD's death domain to explore the relationship among its various functional properties. Mutations affecting the different activities of TRADD do not map to discrete regions but rather are spread over the entire death domain, suggesting that the death domain is a multifunctional unit. A mutant that separates cell killing from NF-kappaB activation by the TRADD death domain has been identified indicating that these two signaling pathways diverge with TRADD. Additionally, one of the TRADD mutants that fails to activate NF-kappaB was found to act as dominant negative mutant capable of preventing induction of NF-kappaB by TNFalpha. Such observations provide evidence that TRADD performs an obligate role in TNF-induced NF-kappaB activation.

Alanine↗

Heterotopic brain in the parapharyngeal space.

There have been numerous reports of various types of heterotopic tissue in the head and neck. Heterotopic cartilage, gastric tissue, thyroid, and salivary gland in such various locations as tongue, gingiva, palate, nasopharynx, parapharyngeal space, and neck have been frequently reported. Heterotopic brain in the parapharyngeal space causing airway obstruction in the neonate has been rarely described. These benign masses are capable of expansion and because of their location, can lead to significant airway and feeding difficulties. We describe 3 cases of heterotopic brain tissue in the parapharyngeal space causing feeding difficulties and airway obstruction in the neonatal period. Two were initially misdiagnosed as lymphatic malformations. In the third, a nine month delay in diagnosis occurred. The diagnostic features of heterotopic brain in this location and some management suggestions in treating such a lesion are discussed.

Airway Obstruction↗

Objective assessment of the response to treatment of severe heart failure using a 9-minute walk test on a patient-powered treadmill.

BACKGROUND: No previous studies have demonstrated the changes in exercise capacity that occur during treatment of decompensated severe heart failure. The authors assessed the efficacy and safety of using a patient-powered treadmill to objectively measure exercise capacity and its relationships, if any, to symptom scores and body weight. METHODS AND RESULTS: Changes in time-limited exercise capacity on a patient-powered treadmill were assessed during inpatient treatment of 12 patients with decompensated chronic heart failure (New York Heart Association classes III and IV). Patients performed a 9-minute walk test daily for 7 days and again at the 6-week follow-up examination. They also completed a 24-item symptom score questionnaire. After treatment, there was a rapid, significant increase in total distance walked, with the increase beginning as early as the second day after admission (mean distance walked +/- SEM, 54 +/- 27 m and 174 +/- 54 m on admission and on day 2, respectively, P < .05). Improvement was maintained throughout the period in the hospital and at 6 weeks (P < .001). Patients reported symptomatic improvement, but this did not reach significance until 4 days after admission (P < .05). Weight loss was not significant. Improved exercise capacity correlated with reduced symptoms and weight loss, but preceded these by several days. CONCLUSIONS: In patients with decompensated chronic heart failure, this exercise test provides a safe, practical, inexpensive, and objective assessment of functional capacity, providing certain advantages over other indices of response to therapy, such as symptom scores and weight loss. Improvement of exercise capacity does not occur concurrently with relief of symptoms and weight loss.

Adult↗

Laparoscopic repair of large incisional hernias.

Conventional repair of large incisional hernias is often associated with a painful postoperative recovery and a delayed return to normal activities. We describe here a technique of laparoscopic incisional hernia repair and review our experience with 30 cases. Hernias ranging in size from 10 to 420 cm2 (mean, 104 cm2) were repaired using a polytetrafluoroethylene patch (16 cases) and a Prolene mesh (14 cases). Operating room time ranged from 45 mins to 190 min (mean 108 mins). Postop stay ranged from 1 to 17 days (mean, 4.3 days; median, 3 days). Follow-up extends beyond 18 months. Postoperative complications included ileus (three cases) trocar site infection (one case) and urinary retention (two cases). There has been one hernia recurrence to date. Our experience with the laparoscopic repair of incisional hernias reveals it to be technically feasible with minimal morbidity, allowing patients prompt resumption of regular activities. Prospective comparison with conventional repair and longer follow-up are needed.

Adult↗

In vitro cell response to differences in poly-L-lactide crystallinity.

Many different processing techniques are currently being used to produce tissue regeneration devices from polyesters in the polylactide/polyglycolide family. While it is generally well recognized that processing techniques influence bulk mechanical and degradation properties of these materials, the effects on surface properties are relatively less well studied. We thus investigated the effects of processing conditions that are known to change bulk properties, but not composition, on the surface properties of poly-L-lactide (PLLA). Specifically, we investigated the role of bulk crystallinity of PLLA substrates on several physiochemical aspects of the surface and on the attachment, morphology, and differentiated function of cultured primary hepatocytes and growth of 3T3 fibroblasts. We fabricated smooth, clear PLLA films of 13-37% crystallinity. Glancing angle X-ray diffraction indicated that low crystallinity films lacked order in the first 50 A of the surface while relatively high crystallinity films had detectable order in this range. In other aspects, the surfaces of all PLLA substrates appeared identical with XPS, SEM, and advancing contact angle analysis, but contact angle hysteresis was slightly greater for more crystalline films. Although the physicochemical properties of the surfaces appeared almost identical, we observed differences in cell behavior on less crystalline versus more crystalline films. Hepatocytes formed spheroids on all PLLA substrates, but spheroid formation was faster (24-48 H) on crystalline substrates. quantitative image analysis was used to assess the average cell area as a function of time in culture, and our data confirm previous reports that retention of differentiated function is inversely related to cell spreading where function was assessed by P-450 enzyme activity. In addition, the growth rate of 3T3 fibroblasts was lower on crystalline substrates than on amorphous substrates. An important conclusion from this work is that processing techniques that lead to seemingly inconsequential changes in bulk and surface properties of these polymers may influence biological response.

3T3 Cells↗

Sp1 is a component of the cytokine-inducible enhancer in the promoter of vascular cell adhesion molecule-1.

Transcription of the vascular cell adhesion molecule-1 (VCAM-1) gene in endothelial cells is induced by the inflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, and lipopolysaccharide. Previous studies demonstrated that the cytokine-response region in the VCAM1 promoter contains binding sites for the transcription factors nuclear factor-kappa B (NF-kappa B) and interferon regulatory factor-1. Using a saturation mutagenesis approach, we report that the cytokine-inducible enhancer consists of these previously characterized elements and a novel region located 3' of the NF-kappa B sites. Electrophoretic mobility shift assays and DNase I footprint studies with endothelial nuclear extracts and recombinant protein revealed that the transcriptional activator Sp1 interacts with this novel element in a specific manner. Transient transfection assays using vascular endothelial cells revealed that site-directed mutations in the Sp1 binding element decreased tumor necrosis factor-alpha-induced activity of the VCAM1 promoter. The cytokine-induced enhancer of the VCAM1 gene requires constitutively bound Sp1 and induced heterodimeric NF-kappa B for maximal promoter activity.

Base Sequence↗

A porcine model for laparoscopic adrenalectomy.

Laparoscopic adrenalectomy has been successfully performed and described in humans. Though it is presently not widely employed it offers tremendous potential for adrenal surgery. It remains, however, an advanced technique requiring demonstration and practice. The aim of this study is to develop a porcine model of adrenalectomy for teaching and advancing the technique applicable to human surgery. Five female pigs weighing 10-20 kg underwent bilateral adrenalectomy by the lateral approach using endotracheal intubation. The left adrenal was resected with the pig in the right decubitus position. The animal was repositioned to left decubitus and the right adrenal was resected. In each case four 10-mm trochars were placed over the respective flanks. There was no need to mobilize the colon or liver (in the pig model). The peritoneum over each gland was incised and the gland dissected in a cephalocaudal manner. The vessels were ligated and divided particularly those from the vena cava. Upon completion blood loss (< 100 cc) and operating times (mean 60 min for the left and 90 min for the right) were assessed and the animal was sacrificed. The glands were weighed (mean 1.23 g R and 1.15 g L) and measured. Using this model, experience is gained in positioning the subject as well as trocars, in fine dissection in a lateral orientation, and in techniques of hemostasis. Although porcine and human adrenal anatomy differ in some details the pig constitutes an excellent model for the development of the technical experience required to perform adrenalectomy in humans.

Adrenalectomy↗

Lymphatic regulation of hematocrit during hypoxia in the toad Bufo woodhousei.

Hypoxia rapidly increases hematocrit (Hct) in anuran amphibians by reducing plasma volume, but the mechanism(s) mediating this response is unknown. We tested the hypothesis that, during hypoxia, plasma volume is reduced by impaired lymph heart (LH) function, decreasing lymph flow into the circulation. In Bufo woodhousei, we measured the effects of hypoxia on Hct, lymph heart rate (LHR), LH pressure, the movement of dye from the dorsal lymph sac to the arterial blood, and flow through an open LH cannula. We also tested whether splenic contraction or cholinergic nerves contribute to the hypoxia-induced changes. Graded hypoxia between 21 and 4% O2 produced graded increases in Hct (P < 0.0001) and decreases in LHR (P = 0.01). Hypoxia reduced the rate of increase in arterial Evans blue concentration after injection into the dorsal lymph sac (P = 0.041) and decreased flow through an open LH cannula (P < 0.012). Hypoxia increased Hct and reduced LHR similarly in control, splenectomized, and sham-splenectomized toads. Atropine had no significant effect on Hct and LHR. These results indicate that the LHs play a regulatory role in hypoxia-induced hemoconcentration.

Animals↗

Laparoscopic-assisted vagotomy and distal gastrectomy.

This is a report of the techniques used on and outcome for three patients who underwent laparoscopic-assisted vagotomy and distal gastrectomy for complicated peptic ulcer disease. The first patient had a Billroth I anastomosis in 2 h 42 min with an estimated blood loss of 200 ml. Oral fluids were started on day 3 and the diet progressed to a soft food by day 5. The patient was discharged 11 days after his gastrectomy following a transurethal prostatic resection on day 6. The second patient had a Billroth II anastomosis. The operation was completed in 4 h 40 min with an estimated blood loss of 350 ml. Oral fluids were commenced on the 1st postoperative day and the patient was tolerating a soft diet by day 4. The patient was discharged 5 days after his gastrectomy. The third patient had a Billroth I anastomosis with an estimated blood loss of less than 150 ml. The surgery took 2 h 35 min; the patient was tolerating oral fluids on the first postoperative day and was discharged on the 4th postoperative day on soft diet. Laparoscopic-assisted vagotomy and gastrectomy has the advantages of a minimal-access procedure without the risks of an intracorporeal anastomosis.

Aged↗

Child, parent, and physician perceived satisfaction with pediatric outpatient visits.

Patient satisfaction has been linked empirically to a variety of health care outcomes (e.g., treatment adherence). Unfortunately, there is a paucity of data regarding the assessment of children's satisfaction with pediatric care. This lack of instrumentation was the impetus for the development and preliminary validation of the Metro Assessment of Child Satisfaction (MACS). Findings indicated the MACS is internally consistent and easily administered and understood by children as young as 6 years of age. Factor analysis yielded four distinct factors that appear to be statistically valid and clinically meaningful. Findings are discussed in relation to maternal ratings of satisfaction and physician perceptions of patient and parent satisfaction.

Adolescent↗

Characterization of the mmsAB operon of Pseudomonas aeruginosa PAO encoding methylmalonate-semialdehyde dehydrogenase and 3-hydroxyisobutyrate dehydrogenase.

A 5417-base pair (bp) region of Pseudomonas aeruginosa PAO chromosomal DNA containing the mmsAB operon and an upstream regulatory gene (mmsR) has been cloned and characterized. The operon contains two structural genes involved in valine metabolism: mmsA, which encodes methylmalonate-semialdehyde dehydrogenase; and mmsB, which encodes 3-hydroxyisobutyrate dehydrogenase. mmsA and mmsB share the same orientation and are separated by a 16-bp noncoding region. The transcriptional start site for the operon has been pinpointed to a cytidine residue located 77 bp from the translational start site of the operon. mmsR is located on the opposite strand and begins 134 bp from the translational start site of mmsA. MmsR has been identified as a member of the XylS/AraC family of transcriptional regulators and appears to act as a positive regulator of the mmsAB operon. Sequence comparison of MmsA to other proteins in the data bases revealed that MmsA belongs to the aldehyde dehydrogenase (NAD+) superfamily. MmsB shares a 44% amino acid identity with 3-hydroxyisobutyrate dehydrogenase from rat liver. Mutants with insertionally inactivated mmsR, mmsA, and mmsB grow slowly on valine/isoleucine medium and exhibit reduced enzyme activity in cell-free extracts compared to P. aeruginosa PAO.

Alcohol Oxidoreductases↗

The cell-type-specific activator region of c-Jun juxtaposes constitutive and negatively regulated domains.

Dissection of the cell-type-specific activation region in c-Jun reveals two functionally separable regulatory subdomains. One subdomain (a1) functions as a transcriptional activator; adjacent to it is a newly identified domain (epsilon) which, together with the previously defined delta region, interacts with a cellular factor that modulates the action of a1. Mutants that lack epsilon are constitutively active and do not interact with the cell-type-specific repressor, whereas mutants that have sustained changes in a1 exhibit a reduced trans-activation potential but retain the ability to interact with the repressor. This bipartite and modular organization of the a1/epsilon domain is further established by demonstrating that a1 can be replaced by the heterologous acidic activator of VP16 and retain proper negative regulation by the cell-specific c-Jun inhibitor along with epsilon and delta. Repression of Jun activity by the inhibitor is not caused by a change in stability, nuclear localization, or DNA-binding activity of the protein. Instead the inhibitor apparently regulates transcriptional activation by interacting directly with delta/epsilon and perhaps masking the a1 domain. These studies suggest that multifunctional activation domains, which are structurally complex, may play an important role in the mechanisms that govern inducible tissue-specific gene expression.

Amino Acid Sequence↗