PubMed HealthSearch

Biomedical subjects

N H Patel

Publications and source records attributed to N H Patel.

At least 19 recordsLinked to original sources

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

Imaging of acute thoracic aortic injury due to blunt trauma: a review.

Much recent work on the use of computed tomography (CT) and transesophageal echocardiography in screening for and facilitating the diagnosis of acute thoracic aortic injury in the patient with blunt chest trauma has shown favorable results. This has led some physicians to question whether conventional thoracic aortography is still the reference standard. The purpose of this review article is to summarize the epidemiology and pathophysiology of acute thoracic aortic injury, the current status of the individual imaging modalities in use, and the surgeon's perspective. Despite a burgeoning literature and a confounding array of clinical and imaging advances, timely diagnosis of acute thoracic aortic injury remains a challenge. To overcome this problem, some trauma centers have used CT, transesophageal echocardiography, or both, in their diagnostic algorithm for acute thoracic aortic injury. These diagnostic algorithms are individually tailored by each institution and are still under investigation; therefore, no definite conclusions can be reached.

Acute Disease

Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change.

Experimental investigations of eukaryotic enhancers suggest that multiple binding sites and trans-acting regulatory factors are often required for wild-type enhancer function. Genetic analysis of the stripe 2 enhancer of even-skipped (eve), an important developmental gene in Drosophila, provides support for this view. Given the importance of even-skipped expression in early Drosophila development, it might be predicted that many structural features of the stripe 2 enhancer will be evolutionarily conserved, including the DNA sequences of protein binding sites and the spacing between them. To test this hypothesis, we compared sequences of the stripe 2 enhancer between four species of Drosophila: D. melanogaster, D. yakuba, D. erecta and D. pseudoobscura. Our analysis revealed a large number of nucleotide substitutions in regulatory protein binding sites for bicoid, hunchback, Kruppel and giant, as well as a systematic change in the size of the enhancer. Some of the binding sites in D. melanogaster are either absent or modified in other species. One functionally important bicoid-binding site in D. melanogaster appears to be recently evolved. We, therefore, investigated possible functional consequences of sequence differences among these stripe 2 enhancers by P-element-mediated transformation. This analysis revealed that the eve stripe 2 enhancer from each of the four species drove reporter gene expression at the identical time and location in D. melanogaster embryos. Double staining of native eve protein and transgene mRNA in early embryos showed that the reporter gene mimicked native eve expression and, in every case, produced sharply defined stripes at the blastoderm stage that were coincident with eve stripe 2 protein. We argue that stripe 2 eve expression in Drosophila evolution can be viewed as being under constant stabilizing selection with respect to the location of the anterior and posterior borders of the stripe. We further hypothesize that the stripe 2 enhancer is functionally robust, so that its evolution may be governed by the fixation of both slightly deleterious and adaptive mutations in regulatory protein binding sites as well as in the spacing between binding sites. This view allows for a slow but continual turnover of functionally important changes in the stripe 2 enhancer.

Animals

Gadolinium-enhanced three-dimensional MR angiography of the aorta and peripheral arteries: evaluation of a multistation examination using two gadopentetate dimeglumine infusions.

OBJECTIVE: Three-dimensional gadolinium-enhanced MR angiography is a rapid and accurate method that can at times image only a limited amount of anatomy during an examination. We evaluated a technique that doubled the anatomy imaged by obtaining two separate gadolinium-enhanced MR angiograms during a single examination. MATERIALS AND METHODS: Twenty-three patients referred for MR evaluation of aortic or peripheral vascular disease underwent two successive gadolinium-enhanced three-dimensional MR angiographic examinations during a single MR examination. An injection of 15 ml of gadopentetate dimeglumine was used for the first MR angiogram, and 25 ml was used for the second MR angiogram. The angiograms were quantitatively and qualitatively evaluated to determine the effect of residual gadolinium from the initial MR angiogram on the second angiogram. RESULTS: The two studies depicted either the entire aorta to the femoral arteries (n = 10) or the distal aorta to the popliteal arteries (n = 13). The total mean gadolinium dose was 0.245 mmol/kg per patient. An average of 15 min elapsed between injections. The value of arterial signal-to-noise ratio (mean, 48.8 versus 56.4) and artery-to-vein contrast-to-noise ratio (mean, 45.5 versus 49.0) increased between the first and second angiograms, respectively. Residual gadolinium elevated the values for venous signal-to-noise ratio (mean, 2.3 versus 7.2) and background-to-muscle signal-to-noise ratio (mean, 5.5 versus 10.1) on the second MR angiogram. Qualitative evaluation by three observers showed no significant differences in diagnostic usefulness or overall image quality between the first and second MR angiograms. CONCLUSION: The use of two low-dose gadolinium-enhanced three-dimensional MR angiograms during a single examination is a feasible approach to increase anatomic coverage when performing gadolinium-enhanced three-dimensional MR angiography of the aorta and peripheral vessels. Although background enhancement is slightly elevated on the second angiogram, such enhancement does not significantly change diagnostic usefulness or overall image quality.

Aged

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

Crustacean appendage evolution associated with changes in Hox gene expression.

Homeotic (Hox) genes specify the differential identity of segments along the body axis of insects. Changes in the segmental organization of arthropod bodies may therefore be driven by changes in the function of Hox genes, but so far this has been difficult to demonstrate. We show here that changes in the expression pattern of the Hox genes Ubx and AbdA in different crustaceans correlate well with the modification of their anterior thoracic limbs into feeding appendages (maxillipeds). Our observations provide direct evidence that major morphological changes in arthropod body plans are associated with changes in Hox gene regulation. They suggest that homeotic changes may play a role in the normal process of adaptive evolutionary change.

Animals

Renal artery origins: best angiographic projection angles.

PURPOSE: To determine the best projection angles for imaging the renal artery origins in profile. MATERIALS AND METHODS: A mathematical model of the anatomy at the renal artery origins in the transverse plane was used to analyze the amount of aortic lumen that projects over the renal artery origins at various projection angles. Computed tomographic (CT) angiographic data about the location of 400 renal artery origins in 200 patients were statistically analyzed. RESULTS: In patients with an abdominal aortic diameter no larger than 3.0 cm, approximately 0.5 mm of the proximal part of the renal artery and origin may be hidden from view if there is a projection error of +/-10 degrees from the ideal image. A combination of anteroposterior and 20 degrees and 40 degrees left anterior oblique projections resulted in a 92% yield of images that adequately profiled the renal artery origins. Right anterior oblique projections resulted in the least useful images. CONCLUSION: An error in projection angle of +/-10 degrees is acceptable for angiographic imaging of the renal artery origins. Patients sex, site of interest (left or right artery), and local diameter of the abdominal aorta are important factors to consider.

Angiography

Genetic separation of the neural and cuticular patterning functions of gooseberry.

In addition to their role in the specification of the epidermal pattern in each segment, several segment polarity genes, including gooseberry (gsb), specify cell fate in the Drosophila central nervous system (CNS). Analyses of the gsb CNS phenotype have been complicated by the fact that the previously available gsb mutants, all caused by cytologically visible deficiencies, have severe segmentation defects and also lack a number of additional genes. We have characterized two novel gsb mutants which, due to their hypomorphic nature, have CNS defects, but have only weak or no segmentation defects. These gsb alleles, as well as gsb rescue experiments, have allowed us to determine which aspects of the deficiency mutant phenotypes can be attributed to loss of gsb. gsb mutants lack U and CQ neurons, have duplicated RP2 neurons, and display posterior commissure defects. gsb neural defects, as well as the gsb cuticle defect, are differentially sensitive to the level of functional Gsb. We have used one of the novel gsb alleles in order to understand the genetic interactions between gsb, wingless (wg), and patched (ptc) during the patterning of the ventral neuroectoderm. In contrast to epidermal patterning, where Gsb is required to maintain wg transcription, we find that Gsb antagonizes the Wg signal that confers neuroblast (NB) 4-2 fate.

Animals

Krüppel, a Drosophila segmentation gene, participates in the specification of neurons and glial cells.

We report that the Drosophila segmentation gene Krüppel (Kr) is expressed in neural precursor cells, neurons and glial cells at different stages of neurogenesis and that Kr mutants develop aberrant peripheral (PNS) and central (CNS) nervous systems. Expression derived from a Kr minigene rescues the segmentation defects but these embryos continue to lack most of the neural Kr activity. Phenotypic analysis of the rescued embryos indicates that, in addition to overall effects on the PNS and CNS structure via its segmentation role, Kr expression in the nervous system is functionally required for establishing particular neural and glial fates.

Animals

Neo-Darwinian developmental evolution: can we bridge the gap between pattern and process?

In the past decade, there has been a surge of renewed interest in the study of developmental evolution. One approach that has been taken is to examine the expression patterns of a candidate gene in divergent taxa and to use these results to infer which aspects of a particular genetic pathway are either conserved or altered. Here we consider this approach from the perspective of the neo-Darwinian paradigm for evolutionary change. If adaptations are typically composed of large numbers of gene substitutions that are of small effect individually, then the candidate gene approach is unlikely to bridge the gap between developmental pattern and evolutionary process: changes in gene expression patterns may identify the steps in developmental pathways that have been altered during evolution but fail to identify the actual genetic changes that have occurred. On the other hand, there is growing support for the view that adaptations often involve large-effect genes; fortunately, the candidate gene approach is well suited to this type of genetic architecture.

Animals