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Biomedical subjects

K R Anderson

Publications and source records attributed to K R Anderson.

At least 37 records · Page 2Linked to original sources

The value of unenhanced helical computerized tomography in the management of acute flank pain.

PURPOSE: We developed an algorithm using unenhanced computerized tomography (CT) for the management of acute flank pain and suspected ureteral obstruction. MATERIALS AND METHODS: During a 25-month interval 417 patients with acute flank pain underwent unenhanced helical CT. The final diagnosis was confirmed by additional imaging or clinical followup. For all patients who underwent additional imaging studies the official dictated radiology reports were used to determine whether the studies were recommended based on CT findings. Cases requiring intervention were evaluated to determine whether additional imaging was performed before the procedure. Medical records were reviewed and/or patients were interviewed to document the course of therapy and long-term outcome. RESULTS: Unenhanced helical CT diagnosed ureteral stone disease with 95% sensitivity, 98% specificity and 97% accuracy. Of the 38 patients requiring intervention, including nephrostomy catheters in 18, lithotripsy in 3 and ureteroscopic stone extraction in 7, additional imaging (excretory urography) was performed in only 1. Additional imaging studies generated by CT were done in 3 cases in which the dictated reports were indeterminate for ureteral stones, including negative excretory urography in 2 and retrograde urography in 1. In 1 patient in whom CT misdiagnosed a ureteral stone unnecessary retrograde urography revealed the calcification to be a gonadal vein phlebolith. Seven patients with false-negative examinations reported spontaneous stone passage with no complications. CONCLUSIONS: Unenhanced helical CT accurately determines the presence or absence of ureterolithiasis in patients with acute flank pain. CT precisely identifies stone size and location. When ureterolithiasis is absent, other causes of acute flank pain can be identified. In most cases additional imaging is not required.

Abdomen, Acute↗

Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium.

Vascular endothelium is an important transducer and integrator of both humoral and biomechanical stimuli within the cardiovascular system. Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7, encoding members of the MAD-related family of molecules, selectively induced in cultured human vascular endothelial cells by steady laminar shear stress, a physiologic fluid mechanical stimulus. MAD-related proteins are a recently identified family of intracellular proteins that are thought to be essential components in the signaling pathways of the serine/threonine kinase receptors of the transforming growth factor beta superfamily. Smad6 and Smad7 possess unique structural features (compared with previously described MADs), and they can physically interact with each other, and, in the case of Smad6, with other known human MAD species, in endothelial cells. Transient expression of Smad6 or Smad7 in vascular endothelial cells inhibits the activation of a transfected reporter gene in response to both TGF-beta and fluid mechanical stimulation. Both Smad6 and Smad7 exhibit a selective pattern of expression in human vascular endothelium in vivo as detected by immunohistochemistry and in situ hybridization. Thus, Smad6 and Smad7 constitute a novel class of MAD-related proteins, termed vascular MADs, that are induced by fluid mechanical forces and can modulate gene expression in response to both humoral and biomechanical stimulation in vascular endothelium.

Amino Acid Sequence↗

Expression of the bumetanide-sensitive Na-K-Cl cotransporter BSC2 is differentially regulated by fluid mechanical and inflammatory cytokine stimuli in vascular endothelium.

In vascular endothelium, the electroneutral Na-K-Cl cotransport system is thought to function in the maintenance of a selective permeability barrier in certain vascular beds (e.g., brain), as well as in the preservation of endothelial homeostasis in the face of fluctuating osmotic conditions that may accompany certain pathophysiological conditions (e.g., diabetes mellitus). Here we demonstrate that the gene encoding the bumetanide-sensitive cotransporter BSC2, one of the two major isoforms of Na-K-Cl cotransporters present in mammalian cells, can be differentially regulated by inflammatory cytokines and fluid mechanical forces in cultured endothelium. Interleukin-1beta and tumor necrosis factor-alpha significantly upregulate expression of BSC2 mRNA and protein in human umbilical vein endothelial cells, a response that is inhibited by pretreatment with interferon-gamma. Steady laminar fluid shear stress, at a physiologic magnitude (10 dyn/cm2), is also able to induce and maintain elevated expression of BSC2 in cultured human umbilical vein endothelial cells, while a comparable time-averaged magnitude of turbulent fluid shear stress is not. In vivo, BSC2 mRNA is upregulated after intraperitoneal administration of bacterial endotoxin (LPS) in murine lung and kidney, but not in cardiac tissue. These results provide the first experimental evidence that the BSC2 gene can be selectively regulated by different inflammatory cytokine and fluid mechanical stimuli in endothelium, and support a role for BSC2 in vascular homeostasis and inflammation.

Animals↗

Endothelial gene regulation by laminar shear stress.

Endothelial cells, because of their unique localization, are constantly exposed to fluid mechanical forces derived by the flowing blood. These forces, and more specifically shear stresses; affect endothelial structure and function, both in vivo and in vitro, and are implicated as contributing factors in the development of cardiovascular diseases. We have demonstrated earlier that the shear stress selectively induces the transcription of several endothelial genes, and have defined a shear stress response element (SSRE) in the promoter of platelet-derived-growth-factor B (PDGF-B), that is shared by additional endothelial shear stress responsive genes. Here we further characterize this SSRE and the nuclear factors that bind to it, and imply the possible role of the endothelium cytoskeleton in transducing shear stress, leading to the expression of PDGF-B/SSRE constructs in transfected endothelial cells exposed to shear stress. We also present, yet a new shear stress response element in the Platelet Derived Growth Factor A promoter, that contains a binding site to the transcription factors egr1/sp1. These results further demonstrate the complexity of gene regulation by hemodynamic forces, and support the important part that these forces have in the physiology and pathophysiology of the vessel wall.

Animals↗

Egr-1 is activated in endothelial cells exposed to fluid shear stress and interacts with a novel shear-stress-response element in the PDGF A-chain promoter.

Exposure of vascular endothelial cells to fluid mechanical forces can modulate the expression of many genes involved in vascular physiology and pathophysiology. Here, we report that platelet-derived growth factor (PDGF) A-chain gene expression is induced at the level of transcription in cultured bovine aortic endothelial cells exposed to a physiologic level of steady laminar shear stress (10 dyn/cm2). 5' Deletion analysis of the human PDGF-A promoter revealed that a GC-rich region near the TATA box was required for shear-inducible reporter gene expression. This element conferred shear inducibility onto a heterologous promoter-reporter construct that was otherwise unresponsive to shear stress. The induction of PDGF-A expression by shear was preceded by rapid and transient induction in the expression of the immediate-early gene, egr-1, which binds to GC-rich sequences. Gel shift studies indicated that shear-induced Egr-1 bound to the proximal PDGF-A promoter in a specific and time-dependent manner, displacing Sp1 from their overlapping recognition elements. Overlapping consensus binding sites for Egr-1 and Sp1 also appear in the proximal promoters of several other endothelial genes, including transforming growth factor-beta 1 and tissue factor, whose expression is modulated by shear stress. These findings define the Egr-1 binding site in the proximal PDGF-A promoter as a shear-stress-responsive element and suggest that shear-stimulated Egr-1 gene expression may be a unifying theme in the induction of various other endothelial genes exposed to biomechanical forces.

Animals↗

Revised antitrust guidelines. Forming physician network joint ventures.

What do physician executives need to know about antitrust guidelines? This article presents an overview of the revised "Statements of Antitrust Enforcement Policy in the Health Care Area," released in late 1996. Antitrust concepts and implicated federal statutes are described, and implications for forming physician network joint ventures are explored. Requirements of the revised standards used by the agencies to determine a permissible integration are addressed, as well as the factors considered in antitrust scrutiny of physician ventures.

Antitrust Laws↗

Laparoscopic evaluation and management of a child with ambiguous genitalia, ectopic spleen, and Meckel's diverticulum.

Laparoscopy may be helpful in the evaluation and management of the child with intersex. Laparoscopic excision of dysgenetic gonads may be necessary due to the increased risk of malignancy. Residual müllerian duct structures are removed to prevent symptomatic complications at puberty. We present the case of a laparoscopic evaluation and management of a 46XY child with ambiguous genitalia, as well as the laparoscopic management of two unrelated anomalies discovered at the time of surgery.

Disorders of Sex Development↗

Physiology and evaluation of ureteropelvic junction obstruction.

Ureteropelvic junction (UPJ) obstruction is not a single anatomic entity but rather a set of processes with multiple causes. In the obstructed system, histologic changes are apparent that have implications for healing. The role of crossing vessels In UPJ obstruction and its treatment is of growing interest. Various methods are available to assess the functional characteristics of the UPJ, of which the diuretic renogram, Whitaker perfusion test, and Doppler ultrasound resistive index may be the most useful. The treatment must be individualized according to the patient's symptoms, the status of renal function, and the potential complications of intervention.

Evaluation Studies as Topic↗

Effect of inhaled salmeterol on sulfur dioxide-induced bronchoconstriction in asthmatic subjects.

UNLABELLED: This study tested the capability of a single 42-microgram dose of inhaled salmeterol xinafoate, a long-acting beta 2-agonist, to protect against bronchoconstrictive effects of exposure to 0.75 ppm sulfur dioxide (SO2) during exercise, for up to 24 h. Ten SO2-responsive adult volunteers with stable asthma were studied under 4 conditions of drug pretreatment/exposure, administered in random order, double-blind: salmeterol/SO2, placebo/SO2, salmeterol/clean air, and placebo/clean air. Each subject underwent 10-min exposure/exercise challenges in a chamber 1, 12, 18, and 24 h after pretreatment. Exercise ventilation rates averaged 29 L/min. Response was measured as the decrement in FEV1 between preexposure and postexposure (lowest value within 30 min). After salmeterol, mean decrement post-SO2 was 7% at 1 h and 12% at 12 h. At 18 and 24 h after salmeterol, and at all times after placebo, mean decrements were 25 to 30%. After 18 and 24 h, salmeterol still improved base-line FEV1 relative to placebo, although improvement was not statistically significant at 24 h. Acute symptom increases accompanied FEV1 decrements. CONCLUSION: In our asthmatic subjects, pretreatment with salmeterol imparted clinically and statistically significant (p < 0.01) protection against bronchoconstriction induced by SO2/exercise for at least 12 h, and maintained an improvement in lung function for as much as 18 h.

Administration, Inhalation↗

Controlled exposures of young asthmatics to mixed oxidant gases and acid aerosol.

To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H-) at an average concentration of 2.6 mumol/m-, equivalent to 127 micrograms/m3 sulfuric acid (H2SO4); some H+ probably was in NH4HSO4 rather than H2SO4. The volunteers were exposed separately to O3/NO2 without acid and to clean air. Exposures lasted 90 min, including three 15-min exercise sessions with ventilation averaging 32 L/min, at 21 degrees C and 50% relative humidity. Asthma medications were withheld before and during exposures. Subjects gargled lemonade to minimize acid neutralization by oral ammonia (NH3). Exercise-induced bronchospasm was evident in all exposures. Differences in group mean lung function response among H2SO4/O3/NO2, O3/NO2, and clean-air exposures were not statistically significant. Individuals' measured oral NH3 concentrations or estimated inhaled doses of H2SO4 did not significantly predict their lung function changes. A few subjects showed unfavorable function changes during pollutant exposures, which might be chance occurrences or might indicate the existence of an acid-pollution-susceptible subgroup among young asthmatic subjects.

Adolescent↗

Laparoscopic assisted continent urinary diversion in the pig.

PURPOSE: The ideal urinary reservoir would be low pressure, nonrefluxing and simple to construct. Hohenfellner recently described creating an in situ ureterosigmoidostomy with a 5 to 6 cm. detubularized portion of sigmoid colon and rectum (sigmoid-rectum pouch). In an effort to further study the reconstructive applications of laparoscopy, we sought to laparoscopically create a sigmoid-rectum pouch in an animal model. In addition, we sought to compare a "dunked" (right ureter) with a hand-sewn end-to-side ureterocolonic anastomosis (left ureter). MATERIALS AND METHODS: Nine male domestic pigs underwent laparoscopic creation of a continent urinary diversion. Pouch creation and the ureterocolonic anastomoses were done extracorporeally; ureteral stents were not used. Average operative time was 122 minutes. Eight pigs survived the 10 to 12 week study period. RESULTS: Mean pouch capacity was 360 cc and pouch pressure remained < 20 cm.H2O. Stones were noted on the bowel staple line in 44% of the animals. Ureterocolonic obstruction occurred in 11% of the right ureters and 33% of the left ureters. CONCLUSIONS: A laparoscopically created continent sigmoid-rectum diversion appears to be feasible. A "dunked" ureterocolonic anastomosis provides equivalent or better drainage than a traditional hand-sewn ureterocolonic anastomosis. Problems with stone formation on the titanium staple line need to be resolved.

Animals↗

Laparoscopic pneumodissection: a unique means of tissue dissection.

PURPOSE: To study the acute and chronic tissue effects of using high pressure CO2 to dissect tissues during laparoscopic procedures. MATERIALS AND METHODS: A 5-mm. laparoscopic pneumodissector, capable of delivering brief bursts of high pressure CO2 (20 to 100 psi), was discharged on a variety of porcine tissues including the renal hilum. Acute and chronic histological sections, intraoperative blood gases and perioperative renal scans were obtained. RESULTS: The only tissue with significant acute damage was the spleen. Acute changes in other tissues were minimal; long-term studies revealed no discernible damage to these same tissues. Intraoperative blood gases revealed no significant changes in the serum pCO2 or pH. Likewise, there was no renal damage discernible by renal scans. CONCLUSIONS: Pneumodissection at 50 psi is a safe method for dissecting the porcine kidney and the vessels of the renal hilum. Clinical studies are pending.

Animals↗

Effect of piezoelectric energy on porcine kidneys using the EDAP LT.02.

EDAP International (Cambridge, Massachusetts) has developed a new piezoelectric lithotripter (LT.02) that differs from their earlier model (LT.01) in two important respects: method of stone visualization and available power. The LT.02 provides both in-line fluoroscopy as well as real time ultrasound. The maximum energy is 1400 Bar (compared with 1100 Bar in the LT.01). The purpose of this study was to determine whether treatment with the EDAP LT.02 piezoelectric lithotripter would cause significant renal injury in minipigs. Accordingly, 18 minipigs were divided into 3 groups of 6. Each group received a treatment of 20, 40 or 60 minutes; the power level and shock wave frequency were kept at maximal levels throughout the treatment period. Three pigs from each group were sacrificed at 72 hours (acute). The remaining 9 pigs were sacrificed 1 month following LT.02 treatment (chronic). Histopathologic analysis of the treated kidney revealed that 33% of the 9 acute pigs developed a small capsular hematoma, whereas 66% showed only a small parenchymal contusion ( < or = 1% of total renal volume). Among the chronic pigs, 66% had a small cortical scar, whereas 33% had no macroscopic pathology. Despite the differences in the number of shock waves delivered, these changes were evenly distributed among the 3 groups. Histologic acute changes included circumscribed areas of hemorrhagic infarction, vascular thrombosis with recanalization and focal tubular obstruction and damage. At 30 days, however, these acute injuries had completely resolved in 3 pigs and were only notable as minute areas of focal tubular loss in 6 pigs.

Animals↗

Optimal therapy for the distal ureteral stone: extracorporeal shock wave lithotripsy versus ureteroscopy.

Extracorporeal shock wave lithotripsy (ESWL not equal to) is the optimal therapy for renal calculi less than 2 cm. in diameter and for proximal ureteral calculi. Controversy continues over the initial approach to distal ureteral calculi (that is below the bony pelvis): in situ ESWL versus ureteroscopy. Since February 1990, 76 distal ureteral calculi were treated at our institution using either in situ ESWL (Dornier HM3 ESWL with a Stryker frame modification in 27 patients or Siemen's Lithostar electromagnetic ESWL in 22) or ureteroscopy (27 patients). Patient age and stone size were similar among the groups. All ESWL treatments were performed with the patient under intravenous sedation and on an outpatient basis. Stone-free rates were 96% for the HM3 device, 84% for the Lithostar and 100% for ureteroscopy. Retreatment was required in 3 Lithostar cases (14%) and 1 HM3 case (4%). When compared to ESWL ureteroscopy for distal ureteral stones was more time-consuming, entailed routine placement of a ureteral stent, often required general anesthesia, more often led to hospitalization and doubled the convalescence period. From a cost standpoint, ESWL on an HM3 unit was a few hundred dollars more expensive than ureteroscopy. In summary, we believe that in situ ESWL provides optimal first line therapy for distal ureteral calculi, while ureteroscopy is better reserved as a salvage procedure should ESWL fail.

Adult↗

Effects of prolonged, repeated exposure to ozone, sulfuric acid, and their combination in healthy and asthmatic volunteers.

To evaluate effects of "acid summer haze" on individuals who exercise extensively outdoors, we exposed 45 adult volunteers (15 normal or atopic, 30 asthmatic) in a chamber to a mixture of 0.12 ppm ozone (O3) and approximately 100 micrograms/m3 of respirable sulfuric acid aerosol (H2SO4). On separate occasions we exposed the same subjects to O3 alone, to H2SO4 alone, and to clean air. In exposures involving H2SO4, excess acid was generated to consume ammonia released by the subjects, and the aerosol therefore contained ammonium salts in addition to H2SO4. Subjects were exposed to each atmosphere on two successive days, for 6.5 h/d, with six 50-min exercise periods at ventilation rates averaging 29 L/min. Exposures were conducted during four successive weeks, in random order. Lung function and symptoms were measured before exposure and hourly during exposure. Bronchial reactivity to inhaled methacholine was measured just after the end of each exposure. Exposure to H2SO4 alone caused no significant changes in lung function, symptoms, or bronchial reactivity relative to clean air. Exposure to O3 alone or O3 + H2SO4 caused a progressive, statistically significant (p < 0.05) decline in forced expiratory function, smaller on the second day than the first, as previously found by others for O3 exposure. Bronchial reactivity increased significantly after exposure to O3 with or without H2SO4. Changes in mean lung function and bronchial reactivity with O3 + H2SO4 exposure were modestly larger than changes with O3 exposure, but the differences were nonsignificant or marginally significant. A minority of individual asthmatic and nonasthmatic subjects showed substantially greater declines in function with exposure to O3 + H2SO4 relative to O3 alone. Repeat exposure studies of these subjects again showed an excess response to O3 + H2SO4 on the average, but there was no significant correlation between the excess responses of individual subjects in the original and repeat studies. We conclude that for typical healthy or asthmatic adults heavily exposed to acid summer haze, O3 is more important than H2SO4 as a cause of short-term respiratory irritant effects.

Adolescent↗