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Biomedical subjects

H Shah

Publications and source records attributed to H Shah.

At least 37 records · Page 2Linked to original sources

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↗

Hemodialysis graft: use as access for upper and lower extremity arteriography and interventional procedures--initial experience.

Functioning hemodialysis grafts were used as access sites for peripheral vascular arteriography and interventional procedures. In 11 patients with end-stage renal disease and ischemia, upper extremity (n = 8) or lower extremity (n = 3) arteriography was performed successfully. Angioplasty and other interventional procedures were performed via the same route in two of the patients. No bleeding complications occurred, and all patients were ambulatory immediately after the procedure.

Angiography↗

Tunneled jugular small-bore central catheters as an alternative to peripherally inserted central catheters for intermediate-term venous access in patients with hemodialysis and chronic renal insufficiency.

In 34 patients with chronic renal insufficiency or failure, 43 small-bore central catheters were placed via the internal or external jugular veins: right internal jugular vein, 28; left internal jugular vein, 14; right external jugular vein, one. Central venous access was achieved in all patients (mean catheter dwell time, 28 days; range, 3-99 days), with two minor complications (arterial puncture and catheter damage during suturing). Tunneled jugular small-bore central catheters are a vein-preserving alternative to peripherally inserted central catheters in this population.

Adolescent↗

Effects of cyclosporin A and dinactin on T-cell proliferation, interleukin-5 production, and murine pulmonary inflammation.

We compared the effects of cyclosporin A (CSA) and a macrotetrolide antibiotic, dinactin, on human T-cell proliferation and cytokine production induced by stimulation of the T-cell receptor alone (monoclonal antibody [mAb] directed against CD3) or in combination with costimulatory signals (mAbs directed against CD3 and CD28). These agents were also examined in a murine model of interleukin (IL)-5-mediated pulmonary inflammation. Dinactin inhibited T-cell proliferation induced by IL-2, by mAb to CD3, and by mAbs to CD3 plus alpha-CD28 with identical dose-response curves (IC50 = 10-20 ng/ml). Dinactin inhibited cytokine production with IC50 values of 10 ng/ml for IL-4 and IL-5 and 30 or 60 ng/ml for interferon-gamma or IL-2, respectively. Unlike CSA, exogenous IL-2 did not alter the dinactin-mediated effects on T cells, and nuclear run-on and steady-state messenger RNA (mRNA) analysis showed that dinactin inhibited cytokine production through a post-transcriptional mechanism. CSA selectively blocked T-cell receptor-induced T-cell proliferation and cytokine production (IC50 = 10 ng/ml). Under costimulatory conditions, IL-5 synthesis was only minimally inhibited by high concentrations of CSA, and at CSA concentrations of less than 125 ng/ml, IL-5 was significantly increased above control values. Dinactin and CSA reduced pulmonary eosinophilia when administered within 1 d of airway antigen challenge. Of the cytokine mRNAs examined in the lungs of CSA-pretreated, antigen-challenged mice, IL-5 mRNA levels were the least reduced, paralleling the resistance of IL-5 to CSA observed in vitro and suggesting a role for CD28 in the in vivo induction of IL-5.

Animals↗

Possible pulmonary embolus: evaluation with digital subtraction versus cut-film angiography--prospective study in 80 patients.

PURPOSE: To determine whether intraarterial digital subtraction angiography (DSA) is as accurate as cut-film (film hard-copy) angiography (CFA) in the evaluation of suspected pulmonary embolus. MATERIALS AND METHODS: Under a protocol approved by the institutional review board, CFA and DSA images were obtained in identical posteroanterior and oblique projections in one lung of each patient undergoing pulmonary angiography (n = 80). Diagnoses based on results of blinded review of each study (CFA vs DSA) by three separate reviewers (80 patients x three reviewers = 240 diagnoses for each modality) were compared with the diagnoses made by the physician who performed the procedure on the basis of CFA, DSA, and clinical data and with the consensus diagnoses obtained by means of group review of both studies together if necessary. The reviewers' confidence in their diagnoses was graded from 1 (certain) to 10 (uncertain). RESULTS: Pulmonary emboli were present in 13 (16%) of 80 patients. Two hundred thirty-six (98.3%) of 240 DSA diagnoses and 231 (96.3%) of 240 CFA diagnoses were correct. The sensitivity (correct identification of emboli by all three reviewers) of DSA was 92% and of CFA was 69% (P = .083). The specificities of the modalities were not statistically significantly different. The reviewers' confidence was significantly better in their DSA diagnoses than in their CFA diagnoses (P < .004). CONCLUSION: DSA allows more confident detection of pulmonary embolus than does CFA, with no loss in diagnostic accuracy.

Adult↗

Tunneled hemodialysis catheters: use of a silver-coated catheter for prevention of infection--a randomized study.

PURPOSE: To determine whether silver-coated tunneled hemodialysis catheters reduce infection and to determine the frequency of central venous thrombosis and stenosis with percutaneous placement of right internal jugular vein dialysis catheters by interventional radiologists. MATERIALS AND METHODS: Ninety-one patients were randomly assigned to a treatment (silver-coated catheter; n = 47) or control (identical catheter without silver coating; n = 44) arm. Baseline venography was performed. Catheter tips were cultured and venography was repeated at catheter removal. RESULTS: Mean duration of catheter placement was 92 days. Infection occurred in 11 patients (five in the treatment group, six in the control group). Tip cultures in 15 patients (eight treatment, seven control) were positive without clinical infection. Infection and colonization rates were slightly but not significantly higher in the treatment group than in the control group. Silver-coated catheters in two (4%) patients were removed due to reaction to the coating. Completion venograms (n = 72) showed new minor abnormalities in four (6%) patients and major abnormalities (stenosis, thrombosis) in three (4%) patients. Permanent venous abnormalities occurred in two (3%) patients. CONCLUSION: Silver coating does not confer a benefit against clinical infection or colonization. Interventional radiologic placement of tunneled dialysis catheters yields a low frequency of permanent central venous thrombosis and stenosis.

Bacteria↗

Interleukin-5 mRNA stability in human T cells is regulated differently than interleukin-2, interleukin-3, interleukin-4, granulocyte/macrophage colony-stimulating factor, and interferon-gamma.

Interleukin-5 (IL-5) transcriptional activation and mRNA stability were investigated in a human TH0 T-cell clone (SP-B21) and in nonclonal CD4 TH2 cells, differentiated in vitro from peripheral blood T cells. Cells were stimulated with alpha-CD3 monoclonal antibody (mAb) with and without alpha-CD28 mAb. Comparison to other cytokine genes revealed aspects of mRNA regulation unique to IL-5. The half-life (t1/2) of IL-5 mRNA, determined by addition of actinomycin D (ActinoD) or cyclosporin A (CSA) was longer (by >= 2 h) than that of IL-2, IL-3, IL-4, interferon-gamma, or granulocyte/macrophage colony-stimulating factor. With the exception of IL-5, t1/2 values were significantly shorter with CSA as the transcriptional inhibitor than with ActinoD. The t1/2 value of IL-5 mRNA, but not the other cytokine transcripts, determined with either ActinoD or CSA, was longer than predicted from the kinetics of steady-state mRNA decline. Co-stimulation of both cell types with alpha-CD28 mAb increased the stability of cytokine transcripts weakly, and IL-5 remained the most stable transcript. Thus, the degradation pathway that targets IL-5 is distinct from the other cytokine transcripts measured and involves proteins whose transcription is blocked by ActinoD and CSA. From examination of the levels of transcription initiation (nuclear run-on assay) and steady-state mRNA attained in cultures stimulated in the presence of the protein synthesis inhibitor, cycloheximide, only IL-5 transcription initiation had an absolute dependency on new protein synthesis.

Antibodies, Monoclonal↗

Carbon dioxide angiography of the transplanted kidney: technical considerations and imaging findings.

OBJECTIVE: We evaluated the usefulness of carbon dioxide as the primary contrast material for renal transplant arteriography. CONCLUSION: Carbon dioxide accurately showed artery pathology including anastomotic and intrarenal stenoses, arteriovenous shunting, and diffuse arterial disease from chronic transplant rejection. Using carbon dioxide as a contrast agent reduced the volume of iodinated contrast material that needed to be used. There was no procedure-associated nephrotoxicity.

Adult↗