Biomedical subjects
Publications and source records attributed to N H Patel.
Early patterning of the body during animal development is a fundamental process to subsequent events including cell differentiation, tissue and organ formation, and correct function of the adult body. We focused on two major topics: body segmentation and brain patterning, both of which are essential for conferring a functional complexity to the body, repetition of skeletal elements and complex neural network, respectively.
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.
PURPOSE: To compare, with use of intravascular ultrasound (IVUS) as an internal reference standard in a porcine model, arterial diameters measured from arteriograms obtained with use of CO(2) to those obtained with use of iodinated contrast material (ICM). MATERIALS AND METHODS: In nine pigs, digital subtraction angiograms (DSAs) were obtained in the aorta and iliac arteries to compare vessel diameters measured with use of CO(2) to those measured with use of ICM. These measurements were divided by measurements made with use of intravascular ultrasound (IVUS) to yield a DSA/IVUS ratio. Differences between ICM and CO(2) were compared with analysis of variance to assess the effect of location (aorta vs iliac), contrast material used (ICM vs CO(2)), and position (posteroanterior, right anterior oblique, or left anterior oblique). Secondary analysis compared measurements of dependent and nondependent iliac arteries and compared the use of hand-injected CO(2) to that of CO(2) injected by an injector. RESULTS: The DSA/IVUS ratio was 70.7% +/- 4.4% with ICM use and 69.6% +/- 6.3% with CO(2) use, which did not represent a significant difference (P =.311). Animal position had no effect (P =.477). Underestimation was worse in the iliac arteries than in the aorta (67.4% +/- 1.5% vs 71.4% +/- 1.7%; P =.038). There was no difference in nondependent (P =.163) arteries, but CO(2) underestimated dependent iliac artery size more than ICM did (66.3% +/- 4.8% vs 70.3% +/- 5.4%; P =.051). Vessel diameter was underestimated more with the CO(2) injector than with hand-injected CO(2) (64.3% +/- 2.3% vs 71.7% +/- 1.7%; P <.0001). CONCLUSION: There is no difference in diameter underestimation between CO(2) and ICM in this animal model. Hand-injection of CO(2) causes less underestimation of vessel diameter than does the CO(2) injector.
RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the mortality and morbidity associated with a simple technique for inducing diabetes in dogs--suprarenal intraarterial infusion of alloxan and streptozotocin during balloon occlusion of the juxtarenal abdominal aorta. MATERIALS AND METHODS: The authors attempted to induce diabetes in six purpose-bred dogs. After the dogs were fasted for 12 hours, the abdominal aorta at the level of the origin of the renal arteries was occluded with an angioplasty balloon introduced by means of a femoral approach. A 3-F microcatheter (n = 1) or infusion wire (n = 5) was introduced via the percutaneous transluminal angioplasty catheter and positioned at the level of the celiac axis, and a mixture of streptozotocin (20-25 mg/kg) and alloxan (20-25 mg/kg) was infused. Diabetes was considered to have been induced if the dogs experienced sustained hyperglycemia. RESULTS: There were no deaths during the follow-up period (range, 7 months to 2 1/2 years). A diabetes-like state was induced in five of the six dogs, and no nephrotoxicity was seen. Diabetes was not induced in one dog owing to caudal migration of an undersized balloon during the infusion; this also resulted in reversible renal damage. CONCLUSION: This simple technique is effective for inducing diabetes in dogs, and morbidity and mortality rates are lower than those reported in the literature with other described techniques.
Transjugular intrahepatic portosystemic shunt (TIPS) is performed to treat some complications of cirrhosis. This study investigated the effects of cirrhosis and TIPS on intestinal and hepatic cytochrome P450 3A (CYP3A) activity. Nine volunteers were cirrhotic patients with TIPS, 9 were cirrhotic controls (matched for sex, age, etiology, and Child-Pugh class), and 9 were sex- and age-matched healthy volunteers. Simultaneous doses of midazolam were given intravenously (0.05 mg/kg) and orally (3 mg of [15N3]midazolam). Peripheral and portal venous blood samples were assayed for midazolam and [15N3]midazolam. The systemic clearance of midazolam was significantly greater (P <.05) in healthy volunteers (0.42 +/- 0.10 L x h(-1) x kg(-1)) compared with cirrhotic controls (0.20 +/- 0.05) and with cirrhotic patients with TIPS (0.21 +/- 0.09). Hepatic availability followed the same trend. The bioavailability of midazolam was significantly higher (P <.05) in cirrhotic patients with TIPS (0.76 +/- 0.20) compared with cirrhotic controls (0.27 +/- 0.14) and with healthy volunteers (0.30 +/- 0.10). The intestinal availability was significantly greater (P <.05) in cirrhotic patients with TIPS (0.83 +/- 0.17) compared with cirrhotic controls (0.32 +/- 0.16) and with healthy volunteers (0.42+/-0.15). As expected, hepatic CYP3A activity was reduced in cirrhosis. However, in cirrhotic patients with TIPS, there was a marked loss in first-pass metabolism of midazolam as a result of diminished intestinal CYP3A activity.
Genetic screens in Drosophila melanogaster have helped elucidate the process of axis formation during early embryogenesis. Axis formation in the D. melanogaster embryo involves the use of two fundamentally different mechanisms for generating morphogenetic activity: patterning the anteroposterior axis by diffusion of a transcription factor within the syncytial embryo and specification of the dorsoventral axis through a signal transduction cascade. Identification of Drosophila genes involved in axis formation provides a launch-pad for comparative studies that examine the evolution of axis specification in different insects. Additionally, there is similarity between axial patterning mechanisms elucidated genetically in Drosophila and those demonstrated for chordates such as Xenopus. In this review we examine the postfertilization mechanisms underlying axis specification in Drosophila. Comparative data are then used to ask whether aspects of axis formation might be derived or ancestral.
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.
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.
Pair-rule genes were identified and named for their role in segmentation in embryos of the long germ insect Drosophila. Among short germ insects these genes exhibit variable expression patterns during segmentation and thus are likely to play divergent roles in this process. Understanding the details of this variation should shed light on the evolution of the genetic hierarchy responsible for segmentation in Drosophila and other insects. We have investigated the expression of homologs of the Drosophila Pax group III genes paired, gooseberry and gooseberry-neuro in short germ flour beetles and grasshoppers. During Drosophila embryogenesis, paired acts as one of several pair-rule genes that define the boundaries of future parasegments and segments, via the regulation of segment polarity genes such as gooseberry, which in turn regulates gooseberry-neuro, a gene expressed later in the developing nervous system. Using a crossreactive antibody, we show that the embryonic expression of Pax group III genes in both the flour beetle Tribolium and the grasshopper Schistocerca is remarkably similar to the pattern in Drosophila. We also show that two Pax group III genes, pairberry1 and pairberry2, are responsible for the observed protein pattern in grasshopper embryos. Both pairberry1 and pairberry2 are expressed in coincident stripes of a one-segment periodicity, in a manner reminiscent of Drosophila gooseberry and gooseberry-neuro. pairberry1, however, is also expressed in stripes of a two-segment periodicity before maturing into its segmental pattern. This early expression of pairberry1 is reminiscent of Drosophila paired and represents the first evidence for pair-rule patterning in short germ grasshoppers or any hemimetabolous insect.
While the expression patterns of segment polarity genes such as engrailed have been shown to be similar in Drosophila melanogaster and Schistocerca americana (grasshopper), the expression patterns of pair-rule genes such as even-skipped are not conserved between these species. This might suggest that the factors upstream of pair-rule gene expression are not conserved across insect species. We find that, despite this, many aspects of the expression of the Drosophila gap gene hunchback are shared with its orthologs in the grasshoppers S. americana and L. migratoria. We have analyzed both mRNA and protein expression during development, and find that the grasshopper hunchback orthologs appear to have a conserved role in early axial patterning of the germ anlagen and in the specification of gnathal and thoracic primordia. In addition, distinct stepped expression levels of hunchback in the gnathal/thoracic domains suggest that grasshopper hunchback may act in a concentration-dependent fashion (as in Drosophila), although morphogenetic activity is not set up by diffusion to form a smooth gradient. Axial patterning functions appear to be performed entirely by zygotic hunchback, a fundamental difference from Drosophila in which maternal and zygotic hunchback play redundant roles. In grasshoppers, maternal hunchback activity is provided uniformly to the embryo as protein and, we suggest, serves a distinct role in distinguishing embryonic from extra-embryonic cells along the anteroposterior axis from the outset of development - a distinction made in Drosophila along the dorsoventral axis later in development. Later hunchback expression in the abdominal segments is conserved, as are patterns in the nervous system, and in both Drosophila and grasshopper, hunchback is expressed in a subset of extra-embryonic cells. Thus, while the expected domains of hunchback expression are conserved in Schistocerca, we have found surprising and fundamental differences in axial patterning, and have identified a previously unreported domain of expression in Drosophila that suggests conservation of a function in extra-embryonic patterning.
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The Hox complex is an example of a gene cluster created by tandem duplications. Recent findings suggest the Hox complex may be just part of a larger chromosomal assemblage of homeobox-containing genes that existed in the ancestor to all vertebrates.
Although the mechanisms of anterior-posterior axis formation are well understood in Drosophila, both embryological and molecular studies suggest significant variation in the mechanisms generating this axis within the Insecta class as a whole.
Eukaryotic gene expression is mediated by compact cis-regulatory modules, or enhancers, which are bound by specific sets of transcription factors. The combinatorial interaction of these bound transcription factors determines time- and tissue-specific gene activation or repression. The even-skipped stripe 2 element controls the expression of the second transverse stripe of even-skipped messenger RNA in Drosophila melanogaster embryos, and is one of the best characterized eukaryotic enhancers. Although even-skipped stripe 2 expression is strongly conserved in Drosophila, the stripe 2 element itself has undergone considerable evolutionary change in its binding-site sequences and the spacing between them. We have investigated this apparent contradiction, and here we show that two chimaeric enhancers, constructed by swapping the 5' and 3' halves of the native stripe 2 elements of two species, no longer drive expression of a reporter gene in the wildtype pattern. Sequence differences between species have functional consequences, therefore, but they are masked by other co-evolved differences. On the basis of these results, we present a model for the evolution of eukaryotic regulatory sequences.
Arthropods dominate our seas, land, and air and have done so for hundreds of millions of years. Among the arthropods, crustaceans present us with a rich history of morphological change, much of which is still represented among extant forms. Crustacea largely interact with their environment via their appendages; thus vast amounts of variation exist among the different appendages of a single individual and between appendages from different species. Comparative studies of crustacean appendage development present us with an important story regarding the evolution of morphology over both relatively short (a few million years) and relatively long (a few hundred million years) evolutionary time scales. Recent studies have used the genetic and molecular data from Drosophila development to try to understand the molecular basis for some of the variations seen in crustacean limbs. Here we review some of these data based on the expression patterns of the genes Ultrabithorax, abdominal - A, Sex combs reduced, and Distal-less.
BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) placement is effective in the treatment of complications of portal hypertension. This study evaluated the predictors of mortality in a group of cirrhotic patients with advanced liver disease after placement of TIPS. METHODS: A retrospective analysis of all patients undergoing TIPS placement over a 21/2-year period was undertaken. RESULTS: Fifty-six patients had TIPS placement for variceal hemorrhage, 49 for refractory ascites, and 24 for hepatic hydrothorax (total, 129). Of 21 variables available before TIPS placement, variceal hemorrhage requiring emergent TIPS placement (relative risk [RR], 37.5; 95% confidence interval [CI], 5.4-259) and bilirubin concentration > 3.0 mg/dL (RR, 5.4; 95% CI, 1.4-10.2) were independent predictors of 30-day mortality. Variceal hemorrhage requiring emergent TIPS placement (hazard ratio [HR], 5.1, 95% CI, 2. 2-9.1), alanine aminotransferase level > 100 IU/L (HR, 2.5; 95% CI, 1.2-5.5), bilirubin level > 3.0 mg/dL (HR, 2.6; 95% CI, 1.1-4.6), and pre-TIPS encephalopathy unrelated to bleeding (HR, 2.2; 95% CI, 1.2-4.8) independently predicted death during the follow-up period. A model was developed that separated the patients into 3 groups with significantly different survival rates. CONCLUSIONS: A clinical index consisting of 4 pre-TIPS variables can reliably predict outcome after TIPS.
PURPOSE: Analysis of preprocedural factors that may be helpful in predicting the severity of pain and nausea after hepatic arterial embolization (HAE) for liver neoplasms. MATERIALS AND METHODS: During a 2-year period, 62 patients (33 men, 29 women) underwent 130 palliative lobar HAEs for unresectable liver neoplasms. The hepatic lobe was embolized with 150-250-microm polyvinyl alcohol particulates with or without lipiodol and/or chemotherapeutic agents. Postembolization pain was rated at rest and during movement with use of an 11-point verbal pain scale, and postembolization nausea was assessed with use of a four-point verbal scale, each at two separate time periods. Daily morphine use was also recorded. Primary analysis was made using the first embolization procedure. One-way analysis of variance and Spearman correlation coefficients were used to identify associated predictors. Plots of the outcomes versus the pre-embolization liver function tests and sensitivities and specificities were used to identify the strength of the associations for prediction purposes. A secondary analysis was performed in patients who underwent multiple embolizations. RESULTS: No strong categorical predictors were found from the ANOVA on the severity of postembolization pain or nausea. There were significant (P < .05) associations between the pre-embolization liver function tests and the pain outcomes only. However, while these laboratory values demonstrate strong associations with resultant pain, they are not strong predictors of pain and morphine requirements for any individual patient. The morphine requirements were highly associated (P < .0001) with the pain scores at rest and with movement. The authors did not find significant differences on any of the pain outcomes or morphine requirements between the first and second embolizations. CONCLUSION: Laboratory values and patient age are not predictors for the severity of postembolization pain and nausea. Postembolization pain is a significant complication and poses a continuing challenge to the physician with regards to patient management.
PURPOSE: To test the technical feasibility of creating a left ventricle to coronary sinus shunt using endovascular techniques. MATERIALS AND METHODS: By means of a right jugular vein approach, a needle puncture was made from the coronary sinus to the left ventricle in 10 dogs. The tracts were balloon dilated and lined with 6-mm Wallstents. Shunt patencies, immediate and 4-hours later, were fluoroscopically assessed by contrast material injection into the left ventricle. Blood pressure, pulse, oxygen saturation, and cardiac rhythm were monitored. The dogs were then euthanized. Thoracic cavities and hearts were dissected and inspected. RESULTS: Technical success and immediate shunt patency were 100%. No cardiac dysrhythmias, electrocardiographic changes, or reduction in voltage potential were seen. Eight (80%) of the shunts were patent at 4 hours, one (10%) had thrombosed, and one dog died. Nine (90%) dogs had no pericardial hematoma and one (10%) had minimal pericardial blood from needle passes into the pericardial sac. The coronary sinuses were intact and no injuries to the valve leaflets or chordae tendineae were seen. The puncture sites were from the coronary sinus, 1-2 mm (mean, 1.3) from its auricular orifice, into the left ventricle, just below the inferior margin of the posterior leaflet of the mitral valve. One dog died at 3 hours with no preceding electrocardiographic evidence of impending demise. Autopsy showed no pericardial hematoma and the heart findings were no different from the other nine dogs. CONCLUSIONS: Creation of a left ventricle to coronary sinus shunt with use of endovascular techniques is technically feasible. Study of a transmyocardial intracardiac coronary retroperfusion shunt to deliver oxygenated blood to the ischemic myocardium is warranted.