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Biomedical subjects

H Shah

Publications and source records attributed to H Shah.

At least 19 recordsLinked to original sources

Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein.

The postjunctional alpha(2)-adrenoceptor-mediated contractility was characterized in human saphenous vein derived from coronary artery bypass graft surgery. Human saphenous vein contracted to alpha(2)-adrenoceptor selective agonists BHT-920 (5,6,7,8-Tetrahydro-6-(2-propenyl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride; pD(2)=6.7+/-0.1) and UK 14,304 (5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline; pD(2)=7.2+/-0.1). BHT-920-induced contractions were inhibited by the alpha(2)-adrenoceptor antagonist yohimbine (17-Hydroxy-yohimban-16-carboxylic acid methyl ester hydrochloride; pA(2)=8.7+/-0.5), but not by the alpha(1)-adrenoceptor antagonist prazosin (1-[4-Amino-6,7-dimethoxy-2-quinazolinyl]-4-[2-furanylcarbonyl]-piperazine hydrochloride; 300 nM). In contrast, prazosin (pK(b)=7.9+/-0.2) potently antagonized contractions elicited by the alpha(1)-adrenoceptor agonist phenylephrine ((R)-3-Hydroxy-alpha-[(methylamino)methyl] benzenemethanol hydrochloride; pD(2)=4.9+/-0.1), indicating that both alpha(2)- and alpha(1)-adrenoceptor evoke human saphenous vein contractions. Functional antagonist activity estimates (pA(2) or pK(b)) obtained for the alpha-adrenoceptor antagonists ARC 239 (2-[2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione dihydrochloride), WB 4101 (2-(2,6-Dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) and HV 723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy) ethyl)amino)propyl)benzeneacetonitrile) against BHT-920-induced human saphenous vein contractions were 7.0+/-0.6, 8.3+/-0.6 and 7.7+/-0.3, respectively. The alpha(2)-adrenoceptor subtype affinities (pK(i)) obtained in recombinant human alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor competition binding assays were 8.6, 8.3 and 8.6 for yohimbine; 6.3, 8.4 and 7.0 for ARC 239; 8.4, 7.5 and 8.4 for WB 4101 and 7.5, 7.4 and 7.9 for HV 723, respectively. Taken together, the binding and functional antagonist activity estimates obtained in these investigations indicate that alpha(2C)-adrenoceptor is the predominant postjunctional alpha(2)-adrenoceptor subtype in human saphenous vein.

Adrenergic alpha-Agonists↗

Receptor reserve analysis of the human alpha(2C)-adrenoceptor using.

Here we determine for norepinephrine, (5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline) (UK14,304), 5,6,7,8-tetrahydro-6-(2-propenyl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (BHT-920), (2-[3-hydroxy-2,6-dimethyl-4-t-butylbenzyl]-2-imidazoline) (oxymetazoline), and ((R)-3-Hydroxy-alpha-[(methylamino)methyl]-benzenemethanol hydrochloride) (phenylephrine), affinities using a radiolabeled agonist and antagonist, and potency and efficacy values in membrane [(35)S]guanosine-5'-O-(3-thiotriphosphate) ([(35)S]GTP gamma S) binding and cAMP cellular inhibition assays, in Chinese hamster ovary cells (CHO-K1) expressing the human alpha(2c)-adrenoceptor. These cells express a high ratio of receptor to G-protein because each agonist, but not several antagonists, displaced [(3)H]UK14,304 with higher affinity than [(3)H]rauwolscine. The rank order of potency of high affinity K(i) and EC(50) in both functional assays was norepinephrine > or =UK14,304>BHT-920>oxymetazoline>phenylephrine. The receptor reserve of G-protein activation and cAMP responses was measured with the irreversible antagonist, benextramine; K(A) values of norepinephrine or UK14,304 were similar (289, 271 or 150, 163 nM, respectively). A 20-fold greater receptor occupancy was required for agonist-induced half-maximal [(35)S]GTP gamma S binding compared to cAMP inhibition, indicating significant signal amplification in cells. Therefore, the G-protein activation assay is better at distinguishing full and partial agonists.

Adrenergic alpha-Agonists↗

Initiation of nonselective alpha1-antagonist therapy and occurrence of hypotension-related adverse events among men with benign prostatic hyperplasia: a retrospective cohort study.

BACKGROUND: Treatment of benign prostatic hyperplasia (BPH) with nonselective alpha1 antagonists such as terazosin, doxazosin, and prazosin results in blood pressure reduction due to vasodilation. OBJECTIVE: Using claims data from a large Medigap plan, we examined the effect of initiating nonselective alpha1-antagonist therapy on the incidence of hypotension-related adverse events likely to be associated with vascular alpha-adrenoreceptor antagonism in patients with BPH. METHODS: Medical and prescription claims data were obtained from the MEDSTAT Group for 53,824 men with a diagnosis code for BPH during the study period (January 1995-December 1997). We examined the rate of possible hypotension-related adverse events (diagnosis codes for hypotension, syncope, dizziness, fractures, and other injuries) per 10,000 person-days for men who began therapy with alpha1 antagonists and for a random sample of nonusers, stratified by prior use of other antihypertensive agents. RESULTS: After adjusting for baseline differences in event rates, those who initiated alpha1-antagonist therapy (n = 1564) had a significantly greater increase in hypotension-related adverse-event rates in the 4 months after initiation (vs the 4 months before initiation) than randomly selected nonusers (n = 8641) (increase of 1.82 vs decrease of 0.02 events per 10,000 person-days among those not taking antihypertensive agents; increase of 0.94 vs 0.69 events per 10,000 person-days among those taking other antihypertensive agents; P < 0.01). This increase began earlier and lasted longer among patients taking other antihypertensive agents. Those who discontinued their alpha1 antagonist had a higher rate of hypotensive events at baseline than those who did not (5.09 vs 3.19 events per 10,000 person-days among those using other antihypertensive agents; 3.62 vs 2.27 events per 10,000 person-days among those not using other antihypertensive agents; P < 0.05). CONCLUSIONS: Initiation of nonselective alpha1-antagonist therapy for the treatment of BPH increases the risk of a cluster of clinical events consistent with vascular alpha-adrenoreceptor antagonism. This effect is seen during a 4-month period around the initiation date. Prior initiation of other antihypertensive medication increases this effect. Urologists should consult with a patient's primary care physician about use of other antihypertensive agents before initiating nonselective alpha1-antagonist therapy for BPH.

Accidental Falls↗

Increase in hepatic arterial blood flow after transjugular intrahepatic portosystemic shunt creation and its potential predictive value of postprocedural encephalopathy and mortality.

PURPOSE: To determine (i) whether there is a significant increase in hepatic artery blood flow (HABF) after transjugular intrahepatic portosystemic shunt (TIPS) creation and (ii) whether the extent of incremental increase in HABF is predictive of clinical outcome after TIPS creation. MATERIALS AND METHODS: Prospective, nonrandomized, nonblinded duplex Doppler ultrasound (US) examinations were performed on 24 consecutive patients (19 men; Child Class A/B/C: 4/12/8, respectively) with a mean age of 52.8 years who were referred for TIPS creation for variceal bleeding. Peak hepatic artery velocity and vessel dimensions were used to calculate the hepatic arterial blood flow (HABF) before and after TIPS creation. Patients were clinically followed in the gastrohepatology clinic and TIPS US surveillance was performed at 1 and 3 months to assess shunt function. The extent of incremental increase in HABF was analyzed as a predictor of post-TIPS encephalopathy and/or death. RESULTS: The technical success rate of TIPS creation was 100%. The shunt diameters were either 10 mm (n = 11) or 12 mm (n = 13). TIPS resulted in a significant reduction in the portosystemic gradient from 24.3 mm Hg +/- 5.7 to 9.3 mm Hg +/- 2.9 (P <.001). The hepatic artery peak systolic velocity and HABF increased significantly after TIPS creation, from 60.8 cm/sec +/- 26.7 to 121 cm/sec +/- 51.5 (P <.001) and from 254.2 mL/min +/- 142.2 to 507.8 mL/min +/- 261.3 (P <.001), respectively. The average incremental increase in HABF from pre-TIPS to post-TIPS was 253.6 mL/min +/- 174.2 and the average decremental decrease in portosystemic gradient was 15.0 mm Hg +/- 5.3, but there was no significant correlation (r = 0.04; P =.86) between the two. All shunts were patent at 30 and 90 days without sonographic evidence of shunt dysfunction. After TIPS creation, new or worsened encephalopathy developed in five patients at 30 days and in an additional three at 90 days. They were all successfully managed medically. Three patients (12.5%) died within 30 days of the TIPS procedure. The extent of incremental increase in HABF after TIPS was variable and did not correlate with the development of 30-day and 90-day encephalopathy (P =.41 and P =.83, respectively) or 30-day mortality (P =.2). CONCLUSIONS: HABF increases significantly after TIPS but is not predictive of clinical outcome. The significance of the incremental increase is yet to be determined.

Adult↗

Diagnostics of neisseriaceae and moraxellaceae by ribosomal DNA sequencing: ribosomal differentiation of medical microorganisms.

Fast and reliable identification of microbial isolates is a fundamental goal of clinical microbiology. However, in the case of some fastidious gram-negative bacterial species, classical phenotype identification based on either metabolic, enzymatic, or serological methods is difficult, time-consuming, and/or inadequate. 16S or 23S ribosomal DNA (rDNA) bacterial sequencing will most often result in accurate speciation of isolates. Therefore, the objective of this study was to find a hypervariable rDNA stretch, flanked by strongly conserved regions, which is suitable for molecular species identification of members of the Neisseriaceae and Moraxellaceae. The inter- and intrageneric relationships were investigated using comparative sequence analysis of PCR-amplified partial 16S and 23S rDNAs from a total of 94 strains. When compared to the type species of the genera Acinetobacter, Moraxella, and Neisseria, an average of 30 polymorphic positions was observed within the partial 16S rDNA investigated (corresponding to Escherichia coli positions 54 to 510) for each species and an average of 11 polymorphic positions was observed within the 202 nucleotides of the 23S rDNA gene (positions 1400 to 1600). Neisseria macacae and Neisseria mucosa subsp. mucosa (ATCC 19696) had identical 16S and 23S rDNA sequences. Species clusters were heterogeneous in both genes in the case of Acinetobacter lwoffii, Moraxella lacunata, and N. mucosa. Neisseria meningitidis isolates failed to cluster only in the 23S rDNA subset. Our data showed that the 16S rDNA region is more suitable than the partial 23S rDNA for the molecular diagnosis of Neisseriaceae and Moraxellaceae and that a reference database should include more than one strain of each species. All sequence chromatograms and taxonomic and disease-related information are available as part of our ribosomal differentiation of medical microorganisms (RIDOM) web-based service (http://www.ridom.hygiene.uni-wuerzburg.de/). Users can submit a sequence and conduct a similarity search against the RIDOM reference database for microbial identification purposes.

DNA, Ribosomal↗

Outcome of polyester cuff retention following traction removal of tunneled central venous catheters.

PURPOSE: To elucidate the factors that contribute to cuff retention during traction removal of tunneled catheters, as well as to determine the risk of complication associated with polyester cuff retention. MATERIALS AND METHODS: A total of 428 tunneled, cuffed catheters were removed with traction and local anesthesia. Polyester cuff retention was recorded when it occurred, and the effects of cuff retention were determined at a mean follow-up of 250 days. Statistical analysis was performed to determine the variables influencing cuff retention. RESULTS: Traction removal was successful in 428 (100%) patients. Of 428 catheters removed, 41 (10%) cuffs were retained. Silicone 10-F double-lumen and 9.6-F single-lumen catheters had a higher rate of cuff retention (27 [32%] of 84 and nine [39%] of 23, respectively) than did the split-tip polyurethane hemodialysis catheter (two [1%] of 196; P <.001). Cuff retention rates among other catheter types compared with that of the polyurethane catheter were not significantly different. Duration of catheter dwell did not significantly influence cuff retention. Of 41 retained cuffs, three required removal with cutdown for cuff migration to the exit site, which inhibited healing (n = 1); for suspected infection (n = 1); or for cosmetic purposes as requested by the patient (n = 1). The remaining patients had no complications associated with cuff retention. CONCLUSION: Traction removal of smaller-bore silicone catheters is more likely to result in cuff retention than removal of larger silicone and polyurethane catheters, and cuff retention is usually inconsequential.

Catheterization, Central Venous↗

Renal arterial stenosis in renal allografts: retrospective study of predisposing factors and outcome after percutaneous transluminal angioplasty.

PURPOSE: To determine the predisposing factors to transplant renal arterial stenosis (TRAS) and assess the outcome of percutaneous transluminal angioplasty (PTA) as the primary treatment. MATERIALS AND METHODS: Of 831 renal allograft recipients (584 cadaveric, 247 living related) between January 1991 and December 1998, 72 had hypertension and/or renal dysfunction. All 72 underwent arteriography, and their medical charts were retrospectively reviewed. RESULTS: Prevalence of TRAS was 3.1% (26 of 831). Technical success rate of PTA was 94% (16 of 17), and clinical success rate was 82% (14 of 17). Those with renal dysfunction had a mean pre-PTA creatinine value of 2.6 mg/dL (230 micromol/L) +/- 0.5 (SD) versus a 1-week post-PTA value of 1.7 mg/dL (150 micromol/L) +/- 0.3 (P <.001). Of those with hypertension, all but one had substantial improvement in mean diastolic blood pressure. At 26.9 months mean follow-up in 16 patients with successful PTA, two stenoses reoccurred, and two grafts were lost to chronic rejection. TRAS was present in 14 of 45 end-to-side anastomoses and 12 of 27 end-to-end anastomoses (P =.31), and TRAS was more prevalent in cadaveric grafts (24 of 584) than in living related grafts (two of 247). In cadaveric grafts, the mean cold ischemia time was 29.0 hours +/- 6.9 in those with TRAS (n = 24), as compared with 25.5 hours +/- 8.1 in those with no TRAS (n = 39; P = .35). Seven of 17 patients with acute rejection and six of 35 with chronic rejection had TRAS. CONCLUSION: Primary treatment of TRAS with PTA has good intermediate-term results. TRAS is more prevalent in cadaveric allografts with long cold ischemia time.

Adult↗

Dialysis membrane-induced neutrophil apoptosis is mediated through free radicals.

Patients on hemodialysis are prone to infection. Neutrophils are the host's first line of defense against certain invading pathogenic microorganisms. Since apoptotic neutrophils are functionally compromised we examined the effect of dialysis membranes on neutrophil apoptosis. Dialysis patients showed greater (p < 0.001) neutrophil apoptosis when compared with control subjects. Cellulose acetate membranes directly promoted (p < 0.001) neutrophil apoptosis. Cellulose acetate membrane-treated neutrophils exhibited greater apoptosis (p < 0.01) when compared with polysulfone membrane-treated neutrophils. Superoxide dismutase (SOD) partly inhibited the cellulose acetate membrane-induced neutrophil apoptosis, whereas both catalase and dimethylthiourea (DMTU) inhibited the polysulfone membrane-induced neutrophil apoptosis. Similarly, L-NAME, a nitric oxide synthase inhibitor, attenuated both the cellulose acetate and the polysulfone membrane-induced neutrophil apoptosis. In addition, cellulose acetate and monocyte interaction products promoted (p < 0.001) neutrophil apoptosis. These results suggest that dialysis membranes can promote neutrophil apoptosis directly as well as through their interaction with monocytes. The direct effect of dialysis membranes seems to be mediated partly through the generation of reactive oxygen species.

Analysis of Variance↗

Receptor reserve analysis of the human CCR3 receptor in eosinophils and CCR3-transfected cells.

A novel pharmacological study of CCR3 receptor reserve in a CCR3-transfected cell (CREM3) and human eosinophils was done; functional responses measured were increases in intracellular calcium and chemotaxis. Eotaxin, eotaxin-2, monocyte chemoattractant protein-4 (MCP-4), RANTES, and MCP-3 induced similar maximal eosinophil chemotaxis, whereas MCP-3 and RANTES induced submaximal calcium responses in eosinophils compared to eotaxin, MCP-4, and eotaxin-2. This suggested a receptor reserve in the chemotaxis response. Receptor reserve was quantitated for eotaxin. Occupancy of all CCR3 receptors was required for a maximal calcium response in both CREM3 and eosinophils (reserve = 1.0 or 0.17, respectively); the stimulus-calcium response relationship was linear, indicating no receptor reserve. In contrast, in eosinophils a large receptor reserve (6.5) was found for chemotaxis, where occupancy of 15% receptors drove half-maximal responses. These studies indicate that CCR3 interacts with G-proteins that are poorly coupled to the calcium response, whereas coupling efficiency and/or amplification to the chemotaxis apparatus in human eosinophils is significantly greater.

Animals↗

Aspirin plus extended-release dipyridamole or clopidogrel compared with aspirin monotherapy for the prevention of recurrent ischemic stroke: a cost-effectiveness analysis.

OBJECTIVE: The goal of this health economic analysis was to asses the cost-effectiveness of a fixed combination of aspirin plus extended-release dipyridamole (ASA/ER-DP) or clopidogrel compared with ASA monotherapy for prevention of recurrent ischemic stroke. BACKGROUND: The second European Stroke Prevention Study (ASA/ESPS-2), a large-scale clinical trial, demonstrated that a new therapy--a fixed combination of ASA/ER-DP--is more effective than ASA monotherapy for the prevention of recurrent ischemic stroke. METHODS: We used data from ESPS-2 to create a health economic model that estimates the incremental cost and cost-effectiveness of ASA/ER-DP during the 2-year time frame after an ischemic stroke. The model was developed from a payor perspective. The analysis used direct cost estimates for stroke from a Medicare claims database analysis. Efficacy data were obtained from clinical trials to determine the incremental cost per stroke averted for ASA/ER-DP or clopidogrel versus ASA. Sensitivity analyses also were conducted to test the reliability and robustness of the model. RESULTS: The results of the analysis demonstrated that ASA/ER-DP was cost-effective compared with ASA monotherapy for the secondary prevention of stroke, with a cost-effectiveness ratio of $28,472. The model remained robust over a range of assumptions and cost estimates. Clopidogrel, however, was not cost-effective compared with ASA (cost per stroke averted, $161,316) in either the base-case analysis or any of the sensitivity analyses. CONCLUSION: ASA/ER-DP thus offers a cost-effective alternative to ASA monotherapy for the prevention of recurrent ischemic stroke.

Aspirin↗

Receptor mediated endocytosis by mesangial cells modulates transmigration of macrophages.

BACKGROUND: Accumulation of immune complexes in the mesangium is a common finding. Since migration of macrophages (Mphi) in the mesangium has been demonstrated to be an important event in the development of glomerular lesions, we studied the role of immune complexes and mesangial cell (MC) interaction in the transmigration (Tm) of Mphi. METHODS: To determine the effect of MC and immune complexes (aggregated IgG, IgGAg) on transmigration of Mphi. MC were incubated with or without IgGAg in the lower compartment of a modified Boyden Chamber. To determine the effects of the secretory products (as a result of endocytosis of IgGAg by mesangial cells), MC-IgAg conditioned media was prepared and placed in the lower compartment of the Boyden chamber. We evaluated the effects of MC alone, MC + IgGAg, or MC-IgGAg conditioned media on the transmigration of macrophages across a filter. To determine the effect of free radicals on MC-IgAg endocytosis-induced Mphi migration we evaluated the effect of free radical scavengers such as dimethyl thiourea (DMTU) and tetramethylthiourea (TMTU) in MC-IgAg endocytosis-induced Mphi migration. To determine the role of chemokines in MC-IgAs endocytosis-induced Mphi migration we evaluated the effect of ani-MCP-1 antibodies on MC-IgAg endocytosis-induced Mphi migration, and also studied the effects of IgAg on MC mRNA expression of MCP-1 and RANTES. In addition, we evaluated the role of Fc receptors and actin cytoskeleton of MC in transmigration of Mphi. RESULTS: Mesangial cell endocytosis of IgG aggregates (IgGAg) is associated with enhanced (P < 0.001) transmigration of Mphi (control, 11.2 +/- 0.2 vs. MC + IgGAg, 22.1 +/- 0.9 migrated Mphi/field). IgGAg also induced MC mRNA expression for RANTES and MCP-1 on MC. DMTU and TMTU attenuated (P < 0.001) the MC + IgGAg-induced migration of Mphi as well as IgGAg-induced mRNA expression for RANTES and MCP-1. MC and IgGAg interaction products (MC-IgGAg conditioned media) also increased (P < 0.01) transmigration of Mphi (control, 18.3 +/- 1.7 vs. MC-IgGAg conditioned media, 30.7 +/- 0.6 Mphi/field). This effect of MC-IgGAg conditioned media on the migration of macrophages was dose dependent. Anti-MCP-1 antibody partially inhibited MC-IgGAg-induced migration of macrophages. MC and monomeric IgG (MIgG) interaction (MC-MIgG conditioned media) showed a lower (P < 0.05) migration of Mphi, when compared to the MC-IgGAg conditioned media. MC-IgGAg conditioned media prepared from cytochalasin B pretreated MCs also showed a lower (P < 0.001) migration of Mphi when compared with MC-IgGAg conditioned media-induced migration. CONCLUSIONS: These results indicate that MC-IgGAg conditioned media-induced transmigration of macrophages may be mediated through the generation of RANTES and MCP-1 by MC.

Animals↗

Oncogenic transformation in C3H10T1/2 cells by low-energy neutrons.

PURPOSE: Occupational exposure to neutrons typically includes significant doses of low-energy neutrons, with energies below 100 keV. In addition, the normal-tissue dose from boron neutron capture therapy will largely be from low-energy neutrons. Microdosimetric theory predicts decreasing biological effectiveness for neutrons with energies below about 350 keV compared with that for higher-energy neutrons; based on such considerations, and limited biological data, the current radiation weighting factor (quality factor) for neutrons with energies from 10 keV to 100 keV is less than that for higher-energy neutrons. By contrast, some reports have suggested that the biological effectiveness of low-energy neutrons is similar to that of fast neutrons. The purpose of the current work is to assess the relative biological effectiveness of low-energy neutrons for an endpoint of relevance to carcinogenesis: in vitro oncogenic transformation. METHODS: Oncogenic transformation induction frequencies were determined for C3H10T1/2 cells exposed to two low-energy neutron beams, respectively, with dose-averaged energies of 40 and 70 keV, and the results were compared with those for higher-energy neutrons and X-rays. RESULTS: These results for oncogenic transformation provide evidence for a significant decrease in biological effectiveness for 40 keV neutrons compared with 350 keV neutrons. The 70 keV neutrons were intermediate in effectiveness between the 70 and 350 keV beams. CONCLUSIONS: A decrease in biological effectiveness for low-energy neutrons is in agreement with most (but not all) earlier biological studies, as well as microdosimetric considerations. The results for oncogenic transformation were consistent with the currently recommended decreased values for low-energy neutron radiation weighting factors compared with fast neutrons.

Animals↗

Tunneled infusion catheters: increased incidence of symptomatic venous thrombosis after subclavian versus internal jugular venous access.

PURPOSE: To compare the incidence of symptomatic venous thrombosis after tunneled infusion catheter placement via the internal jugular vein (IJV) versus the subclavian vein (SCV). MATERIALS AND METHODS: A retrospective analysis was performed of 774 catheters placed. Only patients with complete follow-up were included, which yielded a population of 279 catheters in 238 patients (166 in the SCV, 113 in the IJV; total of 26,242 catheter days). All catheters were placed by interventional radiologists with ultrasonographic (in IJV) or venographic (in SCV) guidance. RESULTS: Initial complications were limited to one pneumothorax in the SCV group and one episode of oversedation in the IJV group. There was no difference in infection rates between the two sites (SVC vs IJV: 0.25 vs 0.32 per 100 catheter days; P >.99). The mean dwell time was slightly longer for SCV catheters (103 days) than for IJV catheters (79 days) (P =.04). Venous thrombosis developed in 13% of patients (0.12 per 100 catheter days) with an SVC catheter placed as compared with in 3% (0.04 per 100 catheter days) with an IJV catheter (P =.018). This difference persisted after adjustment for catheter size and side of placement (P =.025). The mean time to thrombosis was 36 days for SCV catheters and 142 days for IJV catheters. CONCLUSION: The IJV is the preferred site for tunneled infusion catheter placement because of the lower incidence of symptomatic venous thrombosis.

Catheterization, Central Venous↗

Direct measurement of pulsatile insulin secretion from the portal vein in human subjects.

Insulin is secreted in a high frequency pulsatile manner. These pulses are delivered directly into the portal vein and then undergo extraction and dilution before delivery into the systemic circulation. The reported frequency of these insulin pulses estimated in peripheral blood varies from an interpulse interval of 4-20 min. We postulated that this discrepancy is due to the attenuation of the pulse signal in the systemic circulation vs. the portal circulation. In the present study we measured pulsatile insulin release directly in the portal circulation of human subjects who had indwelling transjugular intrahepatic portasystemic stent shunts (TIPSS) to decompress portal hypertension. We quantitated pulsatile insulin secretion in both the overnight fasted state (fasting) and during a hyperglycemic clamp (8 mmol/L). Direct portal vein sampling established that pulsatile insulin secretion in humans has an interval (periodicity) of approximately 5 min. The amplitude (and mass) of the insulin concentration oscillations observed in the portal vein was approximately 5-fold greater than that observed in the arterialized vein and was similar to that observed in the dog. Increased insulin release during hyperglycemia was achieved through amplification of the insulin pulse mass. In conclusion, direct portal vein sampling in humans revealed that the interpulse interval of insulin pulses in humans is about 5 min, and this frequency is also observed when sampling from the systemic circulation using a highly specific insulin assay and 1-min sampling, but is about 4-fold greater than the frequency observed at this site using single site RIAs. We confirm that enhanced insulin release in response to hyperglycemia is achieved by amplification of these high frequency pulses.

Adult↗

Randomized comparison between low-pressure laparoscopic cholecystectomy and gasless laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy using low-pressure pneumoperitoneum (8 mmHg) minimizes adverse hemodynamic effects, reduces postoperative pain, and accelerates recovery. Similar claims are made for gasless laparoscopy using abdominal wall lifting. The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery. METHODS: Thirty-six patients were randomized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system (Laparotenser). RESULTS: The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the low-pressure group, but two patients in the gasless group were converted to pneumoperitoneum. There were no significant differences in postoperative pain and analgesic consumption, but patients in the gasless group developed shoulder pain more frequently (50% vs 11%, p < 0.05). Gasless operation took longer to perform (95 vs 72.5 min, p = 0.01). CONCLUSIONS: Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery. The gasless technique provided inferior exposure and the operation took longer, but the technique may still have value in high-risk patients with cardiorespiratory disease.

Adult↗

Modified use of the arrow-trerotola percutaneous thrombolytic device for the treatment of thrombosed hemodialysis access grafts.

PURPOSE: To assess the safety and efficacy of using the Arrow-Trerotola percutaneous thrombolytic device (PTD) as the sole means of mechanical thrombolysis in hemodialysis access grafts, including in situ treatment of the arterial plug. PATIENTS AND METHODS: Fifty consecutive patients (22 women, 28 men; mean age, 58 years; mean graft age, 29 months), in whom mechanical thrombolysis of a thrombosed hemodialysis access graft using the PTD was planned, were included in the study. In all patients, the PTD was used to treat the arterial plug in situ at the arterial anastomosis, instead of using a Fogarty catheter to reposition the plug, as indicated in the PTD product labeling. Prospective data collection included demographic information, technical details of the procedure, immediate outcomes, and complications. Patients were followed for 3 months using definitions and data forms that were identical to those used in the original clinical trial of the PTD. A sample of procedures drawn from the PTD clinical trial database (n = 54) served as control. RESULTS: Immediate technical patency was 100%. Complications included arterial embolization (6% versus 2% control; P = NS; all successfully treated with backbleeding); venous rupture (6% versus 2% control; P = NS); and sepsis (n = 1), probably due to occult graft infection. Adjunctive therapy with an Adherent Clot catheter was needed in two procedures (4%). Three month patency using life-table analysis was 42% (versus 39% control; P = NS). The number of subsequent interventions (surgical/percutaneous) to the arterial limb of the graft did not differ from the PTD trial, and no native arterial stenoses were detected during the follow-up period. CONCLUSIONS: The PTD is safe and effective when used as the sole means of mechanical thrombolysis of hemodialysis grafts. Treating the arterial plug in situ with the PTD eliminates the need for a Fogarty or Adherent Clot catheter in 96% of procedures. A slight increase in arterial embolic complications was observed but these were easily treated with backbleeding.

Adult↗

Randomized comparison of high-flow versus conventional hemodialysis catheters.

PURPOSE: To evaluate short-term flow rates achieved with a new split-tip polyurethane hemodialysis catheter. PATIENTS AND METHODS: This was a prospective, randomized, nonblinded study. Patients referred for a tunneled-dialysis catheter received either a conventional silicone (Bard Hickman 13.5 F) if randomized to the control group, or a split-tip, high-flow polyurethane (MedComp AshSplit 14.5 F) catheter if randomized to the study group. Effective flow rates (QbEff) and recirculation were measured with use of ultrasonic dilution at pump settings (Qb) of 200, 300, 350 and 400 mL/min, as well as maximum Qb (QbMax, up to 500 mL/min) sustainable for at least 3 minutes. Measurements were repeated weekly for 6 weeks. Procedure times and initial and late complications were recorded. RESULTS: Twelve patients were enrolled in each group, 11 and eight completed the study in the test and control groups, respectively. Insertion complications, limited to the split-tip group, included asymptomatic air embolus (n = 1), prolonged tunnel bleeding (n = 2), and kinking (n = 2). Recirculation in both groups was low (mean < 6% at all flow rates). QbMax was 499 mL/min in the Ash group and 470 mL/min in the Hickman group. A repeated measures analysis of variance was used. Adjusted (for week) mean effective flow rates (Qbeff, mL/min) were as follows: at Qb = 200, Ash = 211, Bard = 211, P = .93; at Qb = 300, Ash = 301, Bard = 292, P = .28; at Qb = 350, Ash = 341, Bard = 314, P = .03; at Qb = 400, Ash = 375, Bard = 329, P = .01; at QbMax, Ash = 422, Bard = 359, P = .0005. CONCLUSION: Both catheters delivered flows within the acceptable range indicated by the Dialysis Outcomes Quality Initiative. The split-tip catheter is capable of higher flow rates (Qb and QbEff) compared with the conventional catheter, which may allow more efficient dialysis. Insertion complications appear to be higher with the new design.

Blood Flow Velocity↗