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Biomedical subjects

N H Patel

Publications and source records attributed to N H Patel.

At least 37 records · Page 2Linked to original sources

Percutaneous transmyocardial intracardiac retroperfusion shunts: technical feasibility in a canine model.

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.

Anastomosis, Surgical↗

Functional conservation of the wingless-engrailed interaction as shown by a widely applicable baculovirus misexpression system.

BACKGROUND: The expression patterns of the segment polarity genes wingless and engrailed are conserved during segmentation in a variety of arthropods, suggesting that the regulatory interactions between these two genes are also evolutionarily conserved. Hypotheses derived from such comparisons of gene expression patterns are difficult to test experimentally as genetic manipulation is currently possible for only a few model organisms. RESULTS: We have developed a system, using recombinant baculoviruses, that can be applied to a wide variety of organisms to study the effects of ectopic expression of genes. As a first step, we studied the range and type of infection of several reporter viruses in the embryos of two arthropod and one vertebrate species. Using this system to express wingless, we were able to induce expression of engrailed in the anterior half of each parasegment in embryos of the fruit fly Drosophila melanogaster. Virus-mediated wingless expression also caused ectopic naked ventral cuticle formation in wild-type Drosophila larvae. In the flour beetle, Tribolium castaneum, ectopic wingless also induced engrailed expression. As in Drosophila, this expression was only detectable in the anterior half of the parasegment. CONCLUSIONS: The functional interaction between wingless and engrailed, and the establishment of cells competent to express engrailed, appears to be conserved between Drosophila and Tribolium. The data on the establishment of an engrailed-competent domain also support the idea that prepatterning by pair-rule genes is conserved between these two insects. The recombinant baculovirus technology reported here may help answer other long-standing comparative evolutionary questions.

Animals↗

Morphological innovation and developmental genetics.

How do the actions of individual genes contribute to the complex morphologies of animals and plants? How widespread are these genes taxonomically? How many genes are involved in the morphological differences observed between species, and can we identify them? To what extent can empirical data and theory be reconciled? We provide an overview of some recent attempts to answer these questions, answers that have taken us to the threshold of understanding the mechanistic basis and evolutionary factors that underlie morphological innovation.

Animals↗

Neural cell fate in rca1 and cycA mutants: the roles of intrinsic and extrinsic factors in asymmetric division in the Drosophila central nervous system.

In the central nervous system (CNS) of Drosophila embryos lacking regulator of cyclin A (rca1) or cyclin A, we observe that several ganglion mother cells (GMCs) fail to divide. Whereas GMCs normally produce two sibling neurons that acquire different fates ('A/B'), non-dividing GMCs differentiate exclusively in the manner of one of their progeny ('B'). In zygotic numb mutants, sibling neuron fate alterations ('A/B' to 'A/A') occur infrequently or do not occur in some sibling pairs; we have determined that depletion of both maternal and zygotic numb causes sibling neurons to acquire equalized fates ('A/A') with near-complete expressivity. In rca1, numb mutant embryos, we observe binary cell fate changes ('B' to 'A') in several GMCs as well. Finally, we have demonstrated that expression of Delta in the mesoderm is sufficient to attain both sibling fates. Our results indicate that the intrinsic determinant Numb is absolutely required to attain differential sibling neuron fates. While the extrinsic factors Notch and Delta are also required to attain both fates, our results indicate that Delta signal can be received from outside the sibling pair.

Animals↗

Treatment of inferior vena cava anastomotic stenoses with the Wallstent endoprosthesis after orthotopic liver transplantation.

PURPOSE: To evaluate the efficacy of the Wallstent endoprosthesis for treatment of stenotic or occlusive inferior vena cava (IVC) lesions refractory to balloon angioplasty in patients after orthotopic liver transplantation. MATERIALS AND METHODS: Wallstent endoprostheses were implanted in six patients with IVC anastomotic stenoses or occlusions that were refractory to balloon angioplasty. Follow-up included both duplex ultrasound (US) and clinical evaluations. RESULTS: Ten stents were successfully implanted in six patients. Five of six patients (83%) demonstrated primary patency on duplex US for a mean period of 11 months (range, 4-17 months). One patient's symptoms recurred within 3 weeks after intervention. This patient underwent repeated stent placement. Follow-up duplex US in this patient demonstrated primary assisted patency at 7 months. Mean clinical follow-up was 12 months (range, 7-18 months). Other than the previously described case, no patient developed recurrent symptoms of IVC stenosis or occlusion. Two patients who experienced hemorrhagic complications secondary to anticoagulation were treated successfully. CONCLUSIONS: The Wallstent endoprosthesis is a useful adjunct for treatment of IVC stenosis or occlusions in patients who have undergone orthotopic liver transplantation when these lesions are refractory to simple balloon angioplasty.

Adult↗

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↗

Analysis of molecular marker expression reveals neuronal homology in distantly related arthropods.

Morphological studies suggest that insects and crustaceans of the Class Malacostraca (such as crayfish) share a set of homologous neurons. However, expression of molecular markers in these neurons has not been investigated, and the homology of insect and malacostracan neuroblasts, the neural stem cells that produce these neurons, has been questioned. Furthermore, it is not known whether crustaceans of the Class Branchiopoda (such as brine shrimp) or arthropods of the Order Collembola (springtails) possess neurons that are homologous to those of other arthropods. Assaying expression of molecular markers in the developing nervous systems of various arthropods could resolve some of these issues. Here, we examine expression of Even-skipped and Engrailed, two transcription factors that serve as insect embryonic CNS markers, across a number of arthropod species. This molecular analysis allows us to verify the homology of previously identified malacostracan neurons and to identify additional homologous neurons in malacostracans, collembolans and branchiopods. Engrailed expression in the neural stem cells of a number of crustaceans was also found to be conserved. We conclude that despite their distant phylogenetic relationships and divergent mechanisms of neurogenesis, insects, malacostracans, branchiopods and collembolans share many common CNS components.

Animals↗

The origin and evolution of segmentation.

Arthropods, annelids and chordates all possess segments. It remains unclear, however, whether the segments of these animals evolved independently or instead were derived from a common ancestor. Considering this question involves examining not only the similarities and differences in the process of segmentation between these phyla, but also how this process varies within phyla, where the homology of segments is generally accepted. This article reviews what is known about the segmentation process and considers various proposals to explain its evolution.

Animals↗

Hepatic transcatheter arterial chemoembolization alternating with systemic protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium (PSOC 1104).

We assessed a regimen of alternating regional and systemic therapy in patients with gastrointestinal malignancies with liver-dominant metastases for feasibility, toxicity, response rate, response duration, patterns of progression, and progression-free and overall survival. Regional therapy comprised selective hepatic transcatheter arterial chemoembolization (TACE) using a suspension of cisplatin and particulate polyvinyl alcohol. This procedure was delivered between cycles of protracted continuous infusion 5-fluorouracil (PCI-5FU) as systemic chemotherapy. Patient eligibility criteria included: (a) having histologically documented adenocarcinoma arising from a gastrointestinal primary site with unresectable liver metastases bidimensionally measurable on computerized tomography scan; (b) age greater than 18 years; and (c) performance status 0-2 (Zubrod). PCI-5FU (250 mg/m2/day) was administered i.v. for 28 days, followed by the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe with the greatest tumor burden. Restaging was performed before TACE 2 and TACE 3, which followed at monthly intervals. PCI-5FU for 21 days was sandwiched between each of the TACE treatments. After the final TACE, maintenance PCI-5FU was given for 28 days of each 35-day cycle until toxicity or progression. Between December 23, 1991, and January 19, 1995, 32 patients were registered in this trial, of whom 27 were eligible; 20 completed one or more treatment cycles and were evaluable for radiographic response. Patients with colorectal liver metastases predominated (74%). Twelve (44%) of 27 patients had failed one or more prior treatment regimens. There were no treatment-related deaths, and hematological and hepatic toxicities were generally manageable and reversible. Two patients, however, developed hepatic abscesses requiring drainage, and one patient developed an infarcted gallbladder, which necessitated cholecystectomy. There were no patients with complete responses; there were 8 (40%) with partial responses, 4 (20%) with minor responses, 2 (10%) with stable disease, and 6 (30%) who progressed on the treatment. The median duration of response for partial responders was 4.2 months (127 days; range, 56-245 days). The median reduction in carcinoembryonic antigen for responders was 87.5%. Two patients underwent subsequent resection of residual metastases; one of them is still alive at 58.4 months follow-up. The predominant site of disease progression was the liver; 25% of the patients progressed in extrahepatic sites. The median overall survival for the whole group is 14.3 months (95% confidence interval, 7.2-16.2). Actuarial overall survival for the whole group at 1 year and 2 years is 57 and 19%, respectively. Alternating systemic PCI-5FU and regional TACE (cisplatin/polyvinyl alcohol) is an active and feasible regimen with manageable toxicities in patients with metastatic gastrointestinal malignancies with liver-dominant disease and merits further investigation. The complications seen were in line with those reported at other specialized centers.

Adenocarcinoma↗

Evolution of the interaction between Hox genes and a downstream target.

Segmental identities along the insect body depend on the activities of Hox genes [1,2]. In Drosophila melanogaster, one well-studied Hox regulatory target is Distal-less (Dll), which is required for the development of distal limb structures [3]. In abdominal segments, Dll transcription is prevented when Hox proteins of the Bithorax Complex (BX-C) bind to cis-regulatory elements upstream of the Dll transcription start site [4,5]. Previous evolutionary comparisons of gene expression patterns suggest that this direct repression is conserved between Diptera and Lepidoptera, but is absent in the Crustacea [6,7]. We examined gene expression patterns in three orders of hexapods, all of which develop abdominal appendages, in order to determine when the strong repressive interaction between BX-C proteins and Dll appeared during evolution. In each of the species examined, Dll expression was initiated in abdominal cells despite the presence of high levels of BX-C proteins. It appears that the strong repressive effects of BX-C proteins on Dll expression arose relatively late in insect evolution. We suggest that the regulatory interaction between the BX-C genes and Dll has evolved within the hexapods in a complex, segment-specific manner.

Animals↗

Catheter-directed thrombolysis in the treatment of phlegmasia cerulea dolens.

Phlegmasia cerulea dolens is a potentially devastating complication of extensive deep venous thrombosis for which there is currently no consensus for treatment. Heparin anticoagulation, surgical thrombectomy, thrombolytic therapy, fasciotomy, and amputation have each been advocated. We present two cases of phlegmasia cerulea dolens successfully treated with catheter-directed venous thrombolytic therapy.

Adult↗

Rotational imaging of complex acetabular fractures.

Understanding complex acetabular fractures is difficult and may require three-dimensional reformatted computed tomographic (CT) images. This paper evaluates a technique, digital rotational imaging (DRI), that displays multiple oblique images of the pelvis and acetabulum. When viewed statically, DRI provides optimal iliac and obturator oblique projections, often differing in obliquity from the conventional 45-degree orthogonal views. Dynamic DRI viewing in rapid sequence provides a three-dimensional effect that improves perception of acetabular fracture relationships.

Acetabulum↗

Current status of transjugular intrahepatic portosystemic shunts.

The use of the transjugular intrahepatic portosystemic shunt (TIPS) has emerged as an important nonoperative modality for variceal bleeding, intractable ascites, and for selected cases of hepatic venous obstruction. We believe that TIPS should be viewed as a 'bridge' to liver transplantation and should be carried out only in experienced centres. The adverse haemodynamic changes on the cardiopulmonary system after TIPS should be borne in mind. Prospective trials to evaluate the role of TIPS versus sclerotherapy in variceal bleeding will be watched with interest. There is, however, an urgent need to improve long-term results of TIPS as stent thrombosis and stenosis occur frequently. We advocate routine surveillance to detect these problems at an early stage.

Hemodynamics↗