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Biomedical subjects

W F Bennett

Publications and source records attributed to W F Bennett.

At least 73 records · Page 4Linked to original sources
PubMed1993

Magnetic resonance angiography in the preoperative evaluation of abdominal aortic aneurysms.

Magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) are noninvasive techniques of visualizing blood vessels without the use of intravenous contrast or ionizing radiation. This prospective study assessed preoperative MRA and MRI in the evaluation of 28 patients with abdominal aortic aneurysm (AAA). MRI and MRA accurately predicted the extent of cephalad AAA, the patency of the superior mesenteric artery, and the course of the left renal vein, but were less accurate in defining the extent of caudal AAA, flow of the inferior mesenteric artery, and multiple renal arteries. This study suggests that MRI and MRA are alternatives to the combination of angiography and computed tomographic scan in the preoperative evaluation of patients with suspected AAA and no evidence of mesenteric or renal ischemia. When combined with preoperative segmental Doppler arterial studies, an accurate surgical plan may be formulated. Further refinements in image acquisition and postprocessing software analysis will advance the use of MRI and MRA for complete evaluation prior to elective AAA repair.

Aged↗
PubMed1993

Making tissue-type plasminogen activator more fibrin specific.

The fibrin specificity of tissue-type plasminogen activator can be increased by mutagenesis within at least four sites in the protease domain. These sites include residue I276, the new N-terminus formed by conversion to a two-chain structure, residues on either side of the active site cleft, KHRR 296-299 or DDD 364-366, a charged surface involved in fibrin interactions, which includes residues H432, R434, D460, R462 and a loop structure, PQANL 466-470, near the fibrin-binding patch. Variants with mutations at any of these sites have low fibrinogen-stimulated activity, whereas fibrin-stimulated activity is at least normal. Kinetic analysis reveals that mutations at these positions reduce the kcat in the presence of fibrinogen, but leave the molecules with normal kinetic constants in the presence of fibrin. A significant exception is found at positions 296-299, where the presence of fibrin manifests significant increases in both kcat and Km. Combinations of mutations at these sites appear to be additive with respect to fibrin specificity.

Amino Acid Sequence↗
PubMed1993

Idiopathic eosinophilic esophagitis.

A retrospective review was performed of 13 patients with the diagnosis of idiopathic eosinophilic esophagitis (IEE) occurring alone or in conjunction with idiopathic eosinophilic gastroenteritis (IEG) to identify clinical, radiographic, endoscopic, manometric, and therapeutic similarities. All patients presented with esophageal symptoms, predominantly dysphagia. An allergic disorder was present in 10 (77%) patients, and peripheral eosinophilia was present in 12 (92%) patients. Clinical investigation disclosed esophageal strictures in 10 patients, motility disorders in three, ulcerations in two, a cervical web in one, and a mucosal ring in one as the cause of esophageal symptoms. A proximal esophageal stricture was the single most common esophageal abnormality demonstrated. IEE should be included in the differential diagnosis of dysphagia and should be suggested in a patient with an allergic disorder, peripheral eosinophilia, and concurrent abdominal symptoms, especially in conjunction with IEG. Prompt diagnosis is extremely important since treatment with steroids produces rapid clinical remission in most patients.

Adolescent↗
PubMed1993

Antispasmodic drugs to reduce discomfort and colonic spasm during barium enemas: comparison of oral hyoscyamine, i.v. glucagon, and no drug.

OBJECTIVE: Parenterally administered glucagon is currently the agent of choice for reducing abdominal discomfort and colonic spasm during a barium enema. Because glucagon is expensive and frequently causes nausea, we evaluated the use of oral hyoscyamine sulfate as an alternate agent and compared it with IV glucagon and no medication. SUBJECTS AND METHODS: A total of 349 adult patients undergoing barium enema examinations were randomly assigned in a prospective fashion to one of four groups: (1) no medication (87 patients); (2) 1 mg of IV glucagon (88 patients); (3) 0.125 mg of oral hyoscyamine sulfate (87 patients); and (4) 0.25 mg of oral hyoscyamine sulfate (87 patients). The degree of distension of the colon on radiographs obtained after fluoroscopy, the amount of abdominal distress after the procedure, and the number of side effects (nausea, palpitations, blurred vision, dry mouth) were analyzed. To evaluate the amount of abdominal discomfort more completely, we asked the last 248 patients to estimate the level of severity of the discomfort (none, mild, moderate, or severe). RESULTS: We found no difference in the degree of distension of the colon in the four groups (p = .63). Most patients (79%) had some degree of abdominal discomfort. Fewer patients in the group who received no medication (10%) had no or mild pain compared with those given glucagon (15%, p < .05), 0.125 mg of hyoscyamine (14%, p < .05), or 0.25 mg of hyoscyamine (12%, p = .15). Less nausea occurred in the group that received 0.125 mg of hyoscyamine than in the other groups (p < .03). No patients in any of the groups had allergic or severe side effects. CONCLUSION: When compared with IV glucagon, oral hyoscyamine had fewer side effects, but the degree of colonic distension or abdominal distress was not significantly different. In addition, hyoscyamine is considerably less expensive than glucagon and can be given orally. Patients who received medications had less discomfort than those who did not. However, the degree of distension was not different.

Abdominal Pain↗
PubMed1993

Optimized thrombolysis of cerebral clots with tissue-type plasminogen activator in a rabbit model of embolic stroke.

The dose-dependent effects of tissue-type plasminogen activator (t-PA) on the kinetics of cerebral clot lysis in a rabbit model of middle cerebral artery embolic stroke were investigated. The clots were formed in vitro and tagged with 99Tc for gamma-scintigraphic imaging. After embolization, groups of animals were treated with t-PA. Dose-response curves for the t-PA were generated, and in addition, long and short dosing schedules were assessed. The optimal doses for frequency and rate of cerebral clot lysis in this model are approximately 6.3 mg/kg given over 2 hr or 3.3 mg/kg given over 30 min. These dosing regimens for t-PA were accompanied by approximately 50% consumption of plasma plasminogen, fibrinogen and alpha 2-antiplasmin. Doses of t-PA on either side of this optimum caused attenuation in both the frequency and rate of cerebral clot lysis. Treatment with t-PA under either dosing regimen did not augment the frequency of hemorrhagic transformation, but the size of the resultant hemorrhage in those animals where intracranial bleeding occurred was reduced by 3.3 mg/kg t-PA given over 30 min.

Animals↗
PubMed1992

Computed tomography of primary transitional cell carcinoma of upper urinary tracts.

Preoperative computed tomography (CT) was utilized to evaluate 20 patients with primary transitional cell carcinoma of the upper urinary tracts. Of the 20 patients, 18 (90%) had CT visualization of the tumor as either a discrete mass or local ureteral and/or renal pelvic wall thickening; 2 (10%) had false-negative examinations. Seven of the 20 patients (35%) had CT evidence of tumor extension demonstrated by frank tumor invasion beyond the urothelium or by perirenal pelvic and/or periureteral fat streaks. Of the 4 patients with fat streaks, 2 (50%) had superficial tumors (T(A)T2), 1 had a T1 (25%) tumor, and 1 had a T3 (25%) tumor. All 3 patients with CT findings of direct extension of tumor through the wall of the ureter or renal pelvis had T3 tumors. Among the 13 with localized noninvasive tumor on CT, 5 (38%) had superficial tumors (TA, TIS, T1), 5 (38%) had T2 tumors, and 3 (21%) had T3 tumors. Of the 5 patients with enlarged regional lymph nodes (greater than or equal to 1.5 cm) on CT, 2 had tumor confirmed histologically, 2 had subsequent negative CT-guided biopsies, and 1 had a negative lymphadenectomy. Distant metastasis was discovered in 1 patient. The data suggest that when CT demonstrates direct tumor extension through the renal pelvic or ureteral wall, it is a sensitive indicator of high-stage disease. However, in the absence of this finding, CT is of limited value in staging patients with primary transitional cell carcinoma of the pyeloureteral system.

Carcinoma, Transitional Cell↗
PubMed1992

Radioiodination of the active site of tissue plasminogen activator: a method for radiolabeling serine proteases with tyrosylprolylarginyl chloromethyl ketone.

Tyrosylprolylarginyl chloromethyl ketone (YPRck) is a radioiodinatable inhibitor that irreversibly binds the active site of tissue plasminogen activator (tPA). A two-step reaction is employed where (1) the YPRck reagent is iodinated and (2) the 125I-YPRck is reacted with the tPA sample; therefore the oxidative effects of conventional protein iodination are avoided. Using fibrin binding as a probe of native tPA binding function, YPRck labeling was shown to be superior to other types of surface iodination. 125I-YPRck was prepared at a high specific radioactivity; i.e., one 125I per 3.5 molecules of peptidyl chloromethyl ketone. Labeled YPRck formed a one to one covalent, sodium dodecyl sulfate stable, complex with tPA resulting in a preparation of 10 mCi per milligram protein, which corresponded to an incorporation ratio of 1:3.5 (125I-YPRck:tPA). Both one-chain and two-chain forms of tPA reacted with YPRck. Radiolabeling tPA with 125I-YPRck occurred in a time-dependent manner with half-maximal incorporation at approximately 30 min under the conditions employed in these studies. The pH optimum for the reaction of tPA with 125I-YPRck was 7.4. Solutions of tPA at less than 1 microgram/ml were efficiently labeled with 125I-YPRck, thus allowing the quantitation of functional protease by incorporation of radiolabel. Significantly, 125I-YPRck specifically labeled tPA in cell culture supernatants after transient transfection of cells with plasmid DNA containing the gene for tPA. Other serine proteases were tested for their relative reactivity with 125I-YPRck. Thrombin and Factor Xa incorporated 125I-YPRck to higher levels than two-chain tPA; whereas plasmin, urokinase, and other plasma proteases were not as efficiently radiolabeled. The use of 125I-YPRck allows rapid and specific radiolabeling of a large number of tPA samples in a nondenaturing environment with a known localization of the radiolabeling reagent.

Amino Acid Chloromethyl Ketones↗
PubMed1991

High resolution analysis of functional determinants on human tissue-type plasminogen activator.

Sixty-four variants of human tissue-type plasminogen activator (tPA) were produced using recombinant DNA techniques. Charged residues were converted to alanine in clusters of from one to four changes per variant; these clusters spanned all the domains of the molecule. The variants were expressed by mammalian cells and were analyzed for a variety of properties. Variants of tPA were found that had reduced activity with respect to each tested property; in a few cases increased activity was observed. Analysis of these effects prompted the following conclusions: 1) charged residues in the nonprotease domains are less involved in fibrin stimulation of tPA activity than those in the protease domain, and it is possible to increase the fibrin specificity (i.e. the stimulation of tPA activity by fibrin compared to fibrinogen) by mutations at several sites in the protease domain; 2) the difference in enzymatic activity between the one- and two-chain forms of tPA can be increased by mutations at several sites on the protease domain; 3) binding of tPA to lysine-Sepharose was affected only by mutations to kringle-2, whereas binding to fibrin was affected most by mutations in the other domains; 4) clot lysis was influenced by mutations in all domains except kringle-2; 5) sensitivity to plasminogen activator inhibitor-1 seems to reside exclusively in the region surrounding residue 300. A model of the tPA protease domain has been used to map some of the critical residues and regions.

Amino Acid Sequence↗
PubMed1991

Magnetic resonance imaging detection of early experimental periostitis. Comparison of magnetic resonance imaging, computed tomography, and plain radiography with histopathologic correlation.

This study characterizes the appearance of periosteal reaction by magnetic resonance imaging (MRI), and evaluates the efficacy of MRI versus computed tomography (CT), and plain film radiography (PF) in detecting early, experimentally induced periostitis. Acute Staphylococcus aureus osteomyelitis was induced in 30 legs of 20 New Zealand white rabbits. The rabbits were then imaged with MR, contrast-unenhanced CT, and PF 4 days after infection. Histologically, periosteal elevation was present in 27 cases. Periosteal ossification was seen in 23 cases, and cellular reaction without ossification in 4 cases. Periosteal reaction was demonstrated by PF in 21 (78%) and by CT in 20 (74%) cases. Evidence of periostitis was seen by MR in all 27% (100%) cases. MR resulted in two false-positive diagnoses. Multiple concentric, alternating high and low signal arcs demonstrated by MR in 19 (70%) cases represented periosteal ossification surrounded by fibrous or granulation tissue. These findings demonstrate the ability of MR to detect periostitis despite the absence of periosteal ossification. MR was more sensitive than CT (P less than .05) or PF (P less than .05) in the detection of experimentally induced periostitis.

Acute Disease↗
PubMed1990

Review of hepatic imaging and a problem-oriented approach to liver masses.

We believe that imaging of the liver is complicated. The sporadic appearance of incidental benign lesions and variability in scanning techniques, equipment and artifacts add difficulties to the evaluation of liver masses. Therefore we emphasize the need to define the problem for which the patient is being imaged. This information helps in choosing the procedure of choice and the technique needed to give the most expedient, accurate answer. This will also help apply the lowest risk and most cost-efficient care. Imaging algorithms vary depending on the suspected pathological conditions. Dynamic bolus-enhanced CT is the modality of choice in most situations. Tc99m sulfur-colloid liver-spleen scans are helpful in patients with suspected FNH, and Tc99m-tagged-RBC-SPECT scans are recommended to confirm cavernous hemangiomas. Cysts are easily confirmed by US. Although MRI is competitive with CT, it has not become a primary modality because of cost, availability, patient selection and variability of scanner capabilities among the many manufacturers and models. It is hard to predict what future development of imaging techniques will bring. Many feel that significant advances have plateaued. Time and money will more likely be concentrated on improving image resolution, speed of scanning and ability to transfer this information to sites outside of the radiology department. In addition to faster scanning, we expect to soon have available safe intravenous and enteric contrast agents for MRI. Certainly this will lead to a new round of investigations to compare MRI with CT scanning.

Bile Duct Neoplasms↗
PubMed1990

Properties of a cleaved two-chain form of recombinant human growth hormone.

Escherichia coli cells transformed with plasmids engineered for the expression of recombinant human growth hormone as a secreted product also produced a proteolytically cleaved form of rhGH. This variant is isolated at a high resolution anion exchange chromatography stage during the manufacturing process. The higher isoelectric point of this form is demonstrated by isoelectric focusing and chromatofocusing and the two-chain nature by tryptic mapping, N- and C-terminal sequence analyses, and sodium dodecyl sulfate polyacrylamide gel electrophoresis. These data indicate that the single site of cleavage is between Thr-142 and Tyr-143, in contrast to the two-chain variant isolated from human pituitary glands, which has a clip after residue Phe-139. The recombinant two-chain form was further characterized by reversed-phase high performance liquid chromatography at both acidic and basic pHs. The assay utilizing bicarbonate-containing mobile phases was determined to be the most efficient and sensitive method. The bioactivity of this two-chain form was measured by the in vivo rat weight gain assay and by the in vitro Nb2 cell bioassay. Its immunological similarity to intact one-chain rhGH was demonstrated with an enzyme-linked immunosorbent assay.

Amino Acid Sequence↗
PubMed1990

Acute experimental osteomyelitis and abscesses: detection with MR imaging versus CT.

Acute experimental osteomyelitis and abscesses were induced in the proximal tibia and surrounding soft tissues, respectively, in 67 New Zealand white rabbits. Fifty-three rabbits were injected with a Staphylococcus aureus solution and 26, with sterile saline in tibial medullae and/or surrounding soft tissues. Contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging were performed 7 days after inoculation. Immediately after imaging, the animals were killed and necropsy was performed. MR imaging was more sensitive than CT in the detection of osteomyelitis (94% vs 66%, P less than .025) and abscesses (97% vs 52%, P less than .001). MR imaging was equally specific as CT in the exclusion of osteomyelitis (93% vs 97%, chi 2 = 0) but less specific than CT in the exclusion of abscesses (77% vs 100%, P less than .025). The overall accuracy of MR imaging was somewhat, although not significantly, greater than that of CT in the detection of both osteomyelitis (93% vs 80%) and abscesses (87% vs 75%).

Abscess↗
PubMed1989

Periplasmic secretion of human growth hormone by Escherichia coli.

The gene coding for human growth hormone (hGH) was fused to the coding sequence for the signal peptide of a secreted Escherichia coli protein. STII heat-stable enterotoxin. This hybrid gene was expressed in E. coli. The signal peptide is properly processed and hGH is secreted in to the periplasmic space. In E. coli, some of the material made is proteolytically clipped or deamidated. The effect of culture conditions on the expression and secretion of hGH was studied and several important parameters were identified, including culture temperature and duration, cultivation pH, K+ levels, plasmid structure, and nutrient supplements. Alteration of culture conditions significantly improves the recovery yield and product quality of human growth hormone.

Culture Media↗
PubMed1988

Experimental infections of the musculoskeletal system: evaluation with MR imaging and Tc-99m MDP and Ga-67 scintigraphy.

Acute osteomyelitis, soft-tissue infection, or both were experimentally produced in 38 New Zealand white rabbits, and three-phase technetium-99m methylene diphosphonate, gallium-67, and magnetic resonance (MR) images were obtained 7 or 14 days after infection. There was no significant difference between radionuclide studies and MR images in the detection of osteomyelitis, but MR imaging was significantly more sensitive (100% vs. 69%; P less than .01) in the detection of soft-tissue infection. In addition, cellulitis could not be distinguished from soft-tissue abscess on radionuclide studies, whereas MR imaging was 92% accurate in depicting soft-tissue abscesses. Further research is necessary to determine how to relate these findings to true human clinical situations.

Abscess↗