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Biomedical subjects

T J Welch

Publications and source records attributed to T J Welch.

At least 19 recordsLinked to original sources

CT colonography: single- versus multi-detector row imaging.

PURPOSE: To compare respiratory artifacts, colonic distention, and polyp detection at computed tomographic (CT) colonography by using single- and multi-detector row helical CT systems. MATERIALS AND METHODS: A total of 237 consecutive patients received subcutaneously administered glucagon and underwent prone and supine CT colonography with single-detector row CT (n = 77) and multi-detector row CT (n = 160), followed by colonoscopy. Examination results were graded for colonic distention, respiratory artifacts, and polyp depiction by two radiologists working independently. RESULTS: Suboptimal colonic distention was significantly more common with single-detector row CT and was present in at least one segment in 52% (40 of 77 patients) of examinations versus only 19% (30 of 160 patients) with multi-detector row CT (P <.001). Mild respiratory artifacts were present in 61% (47 of 77 patients) of single-detector row CT examinations versus only 16% (26 of 160 patients) of multi-detector row CT examinations (P <.001). Depiction of polyps larger than 10 mm was 89% (eight of nine polyps) for single-detector row CT and 80% (eight of 10 polyps) for multi-detector row CT (P >.05). CONCLUSION: CT colonography performed with multi-detector row CT significantly improved the demonstration of colonic distention and depicted fewer respiratory artifacts compared with single-detector row CT. No significant differences in the depiction of polyps larger than 10 mm were demonstrated between single- and multi-detector row CT for a small number of polyps. Studies with a larger prevalence of clinically important polyps are needed for further evaluation of differences in polyp detection.

Adult↗

The overlapping angB and angG genes are encoded within the trans-acting factor region of the virulence plasmid in Vibrio anguillarum: essential role in siderophore biosynthesis.

Products encoded in the trans-acting factor (TAF) region are necessary for the biosynthesis of anguibactin and for maximal expression of iron transport and biosynthesis genes in the plasmid-encoded iron-scavenging system of Vibrio anguillarum. Here we identify angB, a locus located in the TAF region, which encodes products essential for anguibactin biosynthesis. We demonstrate that a 287-amino-acid polypeptide, encoded by angB and designated AngB, has an isochorismate lyase activity necessary for the synthesis of 2, 3-dihydroxybenzoic acid, an anguibactin biosynthesis intermediate. Complementation of various angB mutations provided evidence that an additional, overlapping gene exists at this locus. This second gene, designated angG, also has an essential biosynthetic function. The angG gene directs the expression of three polypeptides when overexpressed in Escherichia coli, all of which are translated in the same frame as AngB. The results of site-directed mutagenesis and in vivo phosphorylation experiments suggest that the carboxy-terminal end of AngB and the AngG polypeptide(s) function as aryl carrier proteins involved in the assembly of the anguibactin molecule. Our results also show that the regulatory functions of the TAF are encoded in a region, TAFr, which is distinct from and independent of the angB and angG genes.

Alleles↗

Incidental extracolonic findings at CT colonography.

PURPOSE: To determine the frequency of extracolonic findings at computed tomographic (CT) colonography and the effect of these findings on subsequent patient treatment and cost. MATERIALS AND METHODS: Conventional transverse CT colonographic scans in 264 consecutive patients were evaluated independently by two radiologists. Extracolonic findings were classified as having high, moderate, or low clinical importance. The effect of CT findings on patient treatment was assessed with chart review. The cost of additional examinations was calculated by using 1999 Medicare reimbursements. RESULTS: Thirty (11%) patients had highly important extracolonic findings, which resulted in further examinations in 18 (7%) patients, including ultrasonography in 10, CT in 13, and intravenous pyelography in one. Six patients underwent surgery because of incidentally discovered CT colonographic findings. Two patients with findings of moderate or low importance underwent additional imaging. A total of $7,324 was required for work-up for extracolonic findings (mean of an additional $28 per examination). Three extracolonic malignancies were overlooked at CT colonography. CONCLUSION: Additional work-up of extracolonic CT colonographic findings was relatively infrequent but was often worthwhile when performed for lesions classified as highly important. The evaluation of extracolonic structures at CT colonography has definite limitations with regard to solid organs but can help detect serious disease without substantially increasing the cost per patient.

Abdomen↗

Optimization of CT colonography technique: prospective trial in 180 patients.

PURPOSE: To assess the added benefits of prone positioning in addition to supine positioning and oral iodinated contrast medium for help in the detection of colonic polyps at computed tomographic (CT) colonography. MATERIALS AND METHODS: CT colonography was performed in prone and supine positions in 180 patients with polyps or risk factors for colonic neoplasia. Patients were randomly assigned to receive a standard bowel preparation or a standard preparation plus oral iodinated contrast medium. One radiologist interpreted supine images alone, and another analyzed supine and prone images. All patients subsequently underwent colonoscopy. RESULTS: At colonoscopy, 121 large (> or =1-cm-diameter) polyps and 142 smaller (0.5-0.9-cm) polyps were identified. Prone positioning resulted in increased sensitivity for identification of patients with large (> or =1-cm) polyps (increase from 70% to 85%, P: =.004) and of patients with polyps 0.5 cm or larger (increase from 75% to 88%, P: <.005), with no change in specificity. Use of oral contrast medium did not significantly improve polyp detection even in the subset of patients in whom colonic fluid attenuation was markedly increased. CONCLUSION: Acquisition and review of supine and prone CT colonographic images significantly improves the ability to identify patients with polyps 0.5 cm in diameter or larger. Administration of oral iodinated contrast medium does not significantly improve polyp detection.

Colon↗

Renal cell carcinoma metastatic to the pancreas: clinical and radiological features.

OBJECTIVE: To review the clinical features, computed tomographic (CT) appearance, and treatment outcomes in a case series of patients with renal cell carcinoma (RCC) metastatic to the pancreas. PATIENTS AND METHODS: We retrospectively reviewed the records of 23 patients (15 men and 8 women) with RCC metastatic to the pancreas, detected by CT examination between 1986 and 1996. All patients had undergone a previous nephrectomy for RCC. RESULTS: Isolated mild elevation in liver function test results (in 5 patients) or in serum amylase level (in 8 patients) was observed. New-onset diabetes was detected in 3 patients. The CT characteristics of the pancreatic metastases generally resembled those of primary RCC with well-defined margins and greater enhancement than normal pancreas with a central area of low attenuation. The mean interval between resection of the primary RCC and detection of the pancreatic metastases was 116 months (range, 1-295 months). In 18 patients (78%), the pancreatic metastases were diagnosed more than 5 years after nephrectomy. The pancreas was the initial metastatic site in 12 patients (52%). Survival was shortened with higher tumor grade (mean survival time of 41 months and 10 months in patients with grade 2 and 3, respectively). Surgical resection was carried out in 11 patients (7 distal and 3 total pancreatectomies and 1 distal pancreatectomy followed 4 years later by total pancreatectomy), with 8 patients alive at a mean follow-up of 4 years, 6 of whom remained free of recurrence. Overall, 12 patients (52%) were alive at a mean of 42 months after diagnosis of metastatic disease. CONCLUSIONS: The appearance of metastatic RCC lesions in the pancreas closely resembles the appearance of primary RCC on CT images. Pancreatic metastases from RCC are frequently detected many years after nephrectomy. Patient survival correlates with tumor grade. Histologic analysis of pancreatic masses in patients with a history of resected primary RCC is important since the prognosis for RCC metastatic to the pancreas is much better than that for primary pancreatic adenocarcinoma.

Aged↗

Characterization of the interaction between Fur and the iron transport promoter of the virulence plasmid in Vibrio anguillarum.

The expression of iron transport genes fatDCBA in Vibrio anguillarum strain 775 is negatively regulated by two iron-responsive repressors, the Fur protein and the antisense RNA, RNAalpha. Here we report the identification of the promoter for the iron transport genes and studied the interaction between the V. anguillarum Fur protein and this promoter. The iron transport promoter was localized in a region approximately 300 base pairs upstream of fatD by both primer extension and S1 mapping analysis. High activity of the promoter was measured in response to iron depletion in the wild-type strain when a promoter-lacZ fusion was examined, whereas the promoter was constitutive in the Fur-deficient strain. Gel retardation and DNase I footprint analysis showed that Fur binds specifically to two contiguous sites comprising the promoter region and the region downstream of the transcription start site. The identified Fur binding sites showed a low degree of homology to each other as well as to the consensus sequence for the Escherichia coli Fur protein. DNase I footprints pattern suggested a sequential interaction of Fur with these two sites that renders a protection in the template strand and a hypersensitivity to the nuclease in the nontemplate strand. The periodicity of the hypersensitive sites suggested that the promoter DNA undergoes a structural change upon binding to Fur, which might play a role in the repression of gene expression.

Bacterial Proteins↗

Pituitary desensitization to gonadotropin-releasing hormone increases abdominal adiposity in hyperandrogenic anovulatory women.

OBJECTIVE: To determine whether hyperandrogenism in anovulatory women affects body fat distribution. DESIGN: Prospective nonrandomized study. SETTING: An academic research environment. PATIENT(S): Ten hyperandrogenic anovulatory patients and 10 healthy women matched by body mass index. INTERVENTION(S): Regional body fat analysis was performed before and after 3 months of GnRH analogue (GnRH-a) therapy. MAIN OUTCOME MEASURE(S): Body fat distribution was measured by waist-to-hip circumference ratio, single-slice computed tomography imaging (L2-3 interspace), and total body dual-energy x-ray absorptiometry. RESULT(S): Weight, body mass index, waist-to-hip circumference ratio, total body and leg fat mass, and subcutaneous adipose area were unaffected by the presence of hyperandrogenism or the use of GnRH-a therapy. Basal abdominal fat mass, abdomen-to-leg fat mass ratio, visceral adipose area, and total visceral adipose volume were comparable in both study groups. The abdominal fat mass increased in both groups during GnRH-a therapy, whereas the abdomen-to-leg fat mass ratio rose significantly only in the hyperandrogenic patients. During GnRH-a therapy, the hyperandrogenic patients demonstrated a significant increase in visceral adipose area compared with the healthy women so that total visceral adipose volume increased significantly in the former but not the latter. CONCLUSION(S): Three months of GnRH-a administration preferentially increased abdominal fat, as measured by single-slice computed tomography imaging and total body dual-energy x-ray absorptiometry, in hyperandrogenic anovulatory women.

Abdomen↗

Identification of a regulatory protein required for pressure-responsive gene expression in the deep-sea bacterium Photobacterium species strain SS9.

Here, we report the characterization of a gene necessary for hydrostatic pressure regulation of gene expression in the deep-sea bacterium Photobacterium species strain SS9. The deduced amino acid sequence of the gene product shares extensive similarity to ToxR, a transmembrane DNA-binding protein first discovered as a virulence determinant in the pathogenic bacterium Vibrio cholerae. Changes in hydrostatic pressure induce changes in both the abundance and the activity of the SS9 ToxR protein (or the activity of a ToxR-regulated protein). As with other high-pressure-inducible phenomena observed in higher organisms, anaesthetics antagonize high-pressure signalling mediated by ToxR. It is suggested that SS9 ToxR has evolved the ability to respond to pressure-mediated alterations in membrane structure. V. cholerae and SS9 also share similarity in a ToxR-regulated protein, indicating that part of the ToxR regulon is conserved in diverse members of the family Vibrionaceae. The SS9 ToxR system represents a useful model for studies of signal transduction and environmental adaptation in the largest portion of the biosphere, the deep sea.

Amino Acid Sequence↗

Acute pulmonary embolism: assessment of helical CT for diagnosis.

PURPOSE: To determine the sensitivity and specificity of helical computed tomography (CT) for the diagnosis of acute pulmonary embolism. MATERIALS AND METHODS: This prospective study included 47 patients who underwent pulmonary arteriography for evaluation for possible acute pulmonary embolism. Tailored helical CT and pulmonary arteriography were performed within 24 hours of each other. Each CT scan was interpreted by two chest radiologists, blinded to arteriographic results, at two institutions. CT scan interpretations were compared with findings on bilateral selective pulmonary arteriograms interpreted by two vascular radiologists at one institution. RESULTS: Fifteen (32%) of 47 patients had angiographically proved pulmonary embolism. For the readers at the first institution, helical CT had 60% sensitivity, 81% specificity, 60% positive predictive value, 81% negative predictive value, and 75% overall accuracy. For the readers at the second institution, helical CT had 53% sensitivity, 97% specificity, 89% positive predictive value, 82% negative predictive value, and 83% accuracy. CONCLUSION: Detection of pulmonary embolism with helical CT may be less accurate than previously reported. Given its high specificity but relatively low sensitivity, helical CT may not have the ideal attributes of a first-line imaging study for the diagnosis of pulmonary embolism.

Acute Disease↗

Cloning, sequencing and overexpression of the gene encoding malate dehydrogenase from the deep-sea bacterium Photobacterium species strain SS9.

The gene encoding malate dehydrogenase (mdhA) was obtained from the psychrophilic, barophilic, deep-sea isolate Photobacterium species strain SS9. The SS9 mdhA gene directed high levels of malate dehydrogenase (MDH) production in Escherichia coli. A comparison of SS9 MDH to three mesophile MDHs, a MDH sequence obtained from another deep-sea bacterium, and to other psychrophile proteins is presented.

Amino Acid Sequence↗

Fast CT for pulmonary embolus.

Recent technical advances in CT have led to the ability to scan a volume in a shorter period with optimal contrast opacification of blood vessels, including the pulmonary arteries. Initially, there were isolated instances of an accidental detection of a filling defect because of pulmonary embolus in the pulmonary arteries. Gradually, directed examinations were introduced to diagnose or exclude pulmonary embolus. These examinations were successful. Radiologists and clinicians now are turning to fast CT for this purpose for a variety of reasons, including the proven accuracy and reliability of the method and the relative deficiencies of traditional noninvasive methods. Accurate interpretation of CT scans for possible pulmonary embolus depends on the ability to conduct a high-quality examination and to recognize the spectrum of findings for both acute and chronic emboli. This article reviews the history of fast CT pulmonary angiography, and it presents both technical and diagnostic information germaine to the performance of this technique.

Acute Disease↗

Isolation and characterization of the structural gene for OmpL, a pressure-regulated porin-like protein from the deep-sea bacterium Photobacterium species strain SS9.

Transposon-directed cloning was used to isolate the ompL gene from the deep-sea bacterium Photobacterium species strain SS9. The deduced amino acid sequence of OmpL displays sequence homology to porin proteins from enteric bacteria. Gene fusion and primer extension analyses indicate that ompL is transcriptionally regulated by pressure.

Amino Acid Sequence↗

ompH gene expression is regulated by multiple environmental cues in addition to high pressure in the deep-sea bacterium Photobacterium species strain SS9.

Photobacterium species strain SS9 is a moderately barophilic (pressure-loving) deep-sea bacterial species which induces the expression of the ompH gene in response to elevated pressure. Here we demonstrate that at 1 atm (1 atm = 1.01325 x 10(5) Pa), ompH expression increases with cell density in 2216 marine medium batch culture and is subject to catabolite repression and the OmpH synthesis is inducible by energy (carbon) starvation. Regulatory mutants which are impaired in ompH gene expression at high pressure are also impaired in cell density regulation of ompH gene expression, indicating that the two inducing conditions overlap in their signal transduction pathways. The same promoter was activated by high cell density at 1 atm of pressure as well as during low-cell-density growth at 272 atm. Catabolite repression of ompH gene expression was induced by a variety of carbon sources, and this repression could be partially reversed in most cases by the addition of cyclic AMP (cAMP). Surprisingly, glucose repression of ompH transcription occurred only at 1 atm, not at 272 atm, despite the fact that catabolite repression was operational in SS9 under both conditions. It is suggested that ompH expression is cAMP and catabolite repressor protein dependent at 1 atm but becomes cAMP and perhaps catabolite repressor protein independent at 272 atm. Possible mechanisms of ompH gene activation are discussed.

Bacterial Outer Membrane Proteins↗

Renal artery angioplasty: technical results and clinical outcome in 320 patients.

OBJECTIVE: To review the results of percutaneous transluminal renal artery angioplasty (PTRA), including technical success and clinical outcome, at Mayo Clinic Rochester. DESIGN: We retrospectively reviewed our experience with 320 patients who underwent PTRA for stenosis of 396 arteries during a 14-year period. MATERIAL AND METHODS: We reviewed medical records and angiograms of patients who underwent PTRA at Mayo Clinic Rochester between January 1980 and December 1993. The patients were divided into four groups, based on clinical history and angiographic appearance of the stenosing lesion: renal artery atherosclerosis (ASO group), fibromuscular dysplasia (FMD group), previous renal artery bypass or endarterectomy, and renal artery stenosis in a solitary kidney. Technical results of the PTRA were determined by evaluation of angiograms obtained before and after the procedure. Data on patient demographics, blood pressure, antihypertensive medications, and serum creatinine were recorded for the period preceding PTRA, after the procedure, and at last follow-up. RESULTS: All groups had statistically significant reductions in mean arterial pressure and antihypertensive medications after PTRA. The percentage of patients who benefited after renal artery angioplasty was 70% for patients with ASO (8.4% cured), 63% for patients with FMD (22% cured), 53.8% for patients with prior surgical revascularization (23.1% cured), and 91.7% for patients with a solitary kidney (0% cured). No significant overall change in serum creatinine level was noted after the procedure in any group. Complications were comparable to those reported in other studies. The 30-day all-cause mortality rate was 2.2% for the current study, all deaths occurring in the ASO group. CONCLUSION: PTRA rarely leads to a "cure" of renovascular hypertension but provides effective control of blood pressure and decreases the medication requirements in selected patients.

Adult↗

Diagnosis of acute deep venous thrombosis of the lower extremities: prospective evaluation of color Doppler flow imaging versus venography.

PURPOSE: To determine the value of color Doppler flow imaging in identification of deep venous thrombosis (DVT) of the femoropopliteal system without use of venous compression. MATERIALS AND METHODS: Color Doppler flow imaging was compared with venography in 103 lower extremities in 101 patients. Results of each examination were recorded as positive or negative for acute DVT or consistent with chronic DVT. RESULTS: Color Doppler flow imaging in 97 of 103 cases had a sensitivity of 95%, specificity of 99%, positive and negative predictive values of 95% and 99%, respectively, and accuracy of 98% in detection of acute DVT and was also helpful in differentiation of chronic from acute DVT. Color Doppler flow imaging prospectively identified six of eight patients with chronic DVT and correctly identified acute DVT in two patients with underlying chronic DVT. No results were false-positive for acute DVT in a patient with chronic DVT. CONCLUSION: Color Doppler flow imaging is complementary to compression ultrasonography in evaluation of suspected acute DVT and may be helpful in evaluation of suspected DVT in patients with previous or chronic DVT.

Acute Disease↗

Percutaneous adrenal biopsy: review of a 10-year experience.

PURPOSE: To evaluate the indications for and complications, accuracy, and techniques of percutaneous adrenal biopsy performed from 1982 through 1991 at the authors' institution. MATERIALS AND METHODS: Two hundred seventy-seven percutaneous adrenal biopsies were performed in 270 patients (175 male and 102 female patients, aged 31-84 years). Imaging studies and histories were reviewed, and each patient's case was followed up for at least 1 year after the biopsy. A patient was excluded from the study only if follow-up data could not be obtained. RESULTS: The accuracy of percutaneous adrenal biopsy was 90% (249 of 277 biopsies). In the first 5 years of the study, the accuracy was 85% (87 of 102 biopsies); in the latter 5 years it was 93% (163 of 175 biopsies). The sensitivity was 81%, and the specificity was 99%. The positive predictive value was 99%, and the negative predictive value was 80%. The complication rate was 2.8%. CONCLUSION: Percutaneous biopsy is a safe, accurate procedure for the diagnosis of pathologic conditions of the adrenal glands. The most common indication for a biopsy is the presence of an adrenal mass in a patient with lung cancer.

Adrenal Gland Neoplasms↗