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Biomedical subjects

S Wallace

Publications and source records attributed to S Wallace.

At least 19 recordsLinked to original sources

Development of insulin sensitivity in rat skeletal muscle. Studies of glucose transporter and insulin receptor mRNA levels.

Expression of GLUT-4 and insulin receptor mRNAs was investigated in rat skeletal muscle by Northern hybridization. GLUT-4 mRNA was barely detectable in foetal muscle, was expressed at low levels by 1-8 days and at 2-3-fold higher levels during and after weaning (18-40 days). In contrast there was little change in insulin receptor mRNA levels prior to weaning and a reduction in mRNA abundance between 18 and 40 days. Weaning rats on to a diet rich in fat prevented the increase in GLUT-4 abundance seen between 15 and 29 days in animals weaned on a high-carbohydrate diet.

Aging

Regional biologic therapy. Hepatic arterial infusion of recombinant human tumor necrosis factor in patients with liver metastases.

Twenty-two chemotherapy-resistant patients with liver metastases received 46 courses of recombinant human tumor necrosis factor (rhTNF) administered by 5-day continuous infusion through percutaneously inserted hepatic arterial catheters. The maximum tolerated daily dose of rhTNF was 150 micrograms/m2. This is six times the maximum tolerated daily dose of rhTNF that could be given systemically (intravenous) on the same schedule. The dose-limiting toxicity resulted in severe, although transient, hypophosphatemia (less than 1.0 mg/dl) associated with myocardial dysfunction. Objective tumor response (partial tumor response or greater) was observed in 2 of 14 patients (14%) with colorectal cancer and lasted as long as 3 months. Three additional minor responses occurred among these patients with colorectal cancer. Plasma carcinoembryonic antigen levels also decreased significantly (greater than 25%) in 7 of the 14 (50%) patients with colorectal cancer. Regional biologic therapy with rhTNF as a sole modality has definite antitumor activity in colorectal cancer metastatic to the liver and warrants additional study in previously untreated patients.

Adult

Parenchymal changes of the liver in cholangiocarcinoma: CT evaluation.

We evaluated parenchymal changes of the liver in 92 patients (41 peripheral types and 51 hilar types) with cholangiocarcinomas studied by bolus-enhanced computed tomography (CT). In 39% of patients with the peripheral type, a wedge-shaped increased enhancement of the liver was observed peripheral to the tumor on bolus-enhanced CT. Tumor was observed in all cases. In 58.8% of patients with the hilar type, a segmental or lobar increased degree of enhancement of the liver was observed, but the tumor was demonstrated in only 58.8%. Atrophy was accompanied by areas of increased enhancement in 80% of hilar type and 25% of peripheral type. Areas of increased degree of enhancement corresponded to a wedged-shaped perfusion defect on CT during arterial portography. On magnetic resonance imaging (MRI), those lesions showed hyperintensity on T2-weighted images. Most of these changes were considered to be due to reversible hepatic parenchymal ischemia secondary to portal vein invasion by the tumor.

Adenoma, Bile Duct

Phase II study of interferon-alpha and chemotherapy (5-fluorouracil and mitomycin C) in metastatic renal cell cancer.

A total of 49 patients with metastatic renal cell cancer underwent recombinant interferon-alpha 2a therapy combined with chemotherapy. Before therapy the patients without nephrectomy underwent angioinfarction of the primary renal tumor. Combined treatment included interferon at 5 x 10(6) units per m.2 intramuscularly daily, 5-fluorouracil at 750 mg./m.2 daily by continuous infusion intravenously (days 1 to 5) and mitomycin C at 5 mg./m.2 per day intravenously (days 1 and 2) repeated every 28 days. Of the patients 17 (35%, 95% confidence interval 22 to 49%) responded, and all 17 had partial remission that lasted a median of 7.1 months (range 4.2 to 20.9+ months). Response rate differed by metastatic sites: lung 46% (18 of 39 patients), lymph nodes 46% (6 of 13), mediastinum 20% (2 of 10) and liver 18% (2 of 11). Grade 3 to 4 toxicity (World Health Organization) included neutropenia (79% of the patients), thrombocytopenia (45%), stomatitis (34%), diarrhea (8%), nausea (18%) and central nervous system disorders (18%). The overall 35% response rate suggests that the combination of interferon-alpha 2a, 5-fluorouracil and mitomycin C is synergistic. Future studies are needed to confirm this finding and to assess the role of mitomycin C.

Antineoplastic Combined Chemotherapy Protocols

Use of the Gianturco self-expanding stent in stenoses of the superior and inferior venae cavae.

Twenty-eight patients with severe superior and inferior vena cava syndromes were treated with self-expandable Gianturco stents. Nineteen patients responded, seven did not respond, and two were unevaluable. Fourteen of the 19 who responded had complete or near complete resolution of their syndrome, and five had a partial remission. Five of the responders did not derive any benefit from stent placement because of additional problems that led to their death within 3 weeks of the stent placement procedure. The main cause for failure was the relatively weak expansile force of the stent. Complications included stent migrations without untoward effects in one patient, stent misplacement in one patient, fracture of the stent wire in two patients, and hemorrhage that could be attributed to the stent in one patient. This uncontrolled study suggests that caval obstruction syndromes in some patients may be effectively palliated with Gianturco stents.

Adult

Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3.

A total of 116,118 basepairs (bp) derived from three cosmids spanning the ERCC1 locus of human chromosome 19q13.3 have been sequenced with automated fluorescence-based sequencers and analysed by polymerase chain reaction amplification and computer methods. The assembled sequence forms two contigs totalling 105,831 bp, which contain a human fosB proto-oncogene, a gene encoding a protein phosphatase, two genes of unknown function and the previously-characterized ERCC1 DNA repair gene. This light band region has a high average density of 1.4 Alu repeats per kilobase. Human chromosome light bands could therefore contain up to 75,000 genes and 1.5 million Alu repeats.

Amino Acid Sequence

Expressed genes, Alu repeats and polymorphisms in cosmids sequenced from chromosome 4p16.3.

The sequences of three cosmids (90 kilobases) from the Huntington's disease region in chromosome 4p16.3 have been determined. A 30,837 base overlap of DNA sequenced from two individuals was found to contain 72 DNA sequence polymorphisms, an average of 2.3 polymorphisms per kilobase (kb). The assembled 58 kb contig contains 62 Alu repeats, and eleven predicted exons representing at least three expressed genes that encode previously unidentified proteins. Each of these genes is associated with a CpG island. The structure of one of the new genes, hda1-1, has been determined by characterizing cDNAs from a placental library. This gene is expressed in a variety of tissues and may encode a novel housekeeping gene.

Amino Acid Sequence

Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra-arterial cis-platinum.

Ninety-seven patients with primary osteosarcoma of the extremities, all age 16 or older, were treated with adriamycin, 90 mg/m2, continuous i.v. infusion over 96 h, followed by cis-platinum, 120-160 mg/m2 by intra-arterial infusion. The first 37 patients, treated from 1979-1982, had a 59% complete response rate and a 54% 5-year continuous disease free survival (CDFS). Patients with complete response had an 85% 5-year CDFS compared with 13% for patients with partial and poor response. Patients treated between 1983-1988 with an intensified regimen have a 68% complete response rate and a 69% 3-year CDFS. Those who did not achieve complete remission were switched to an alternating chemotherapy program emphasizing the use of high-dose methotrexate. Limb salvage has been accomplished in 59% of patients in the first group and 80% in patients of the second group. Preoperative chemotherapy allows informed decisions to be made in postoperative management which can influence overall cure rates. Long-term follow-up is essential before final interpretation of the data.

Bone Neoplasms

Development and initial experimental evaluation of a prosthetic aortic valve for transcatheter placement. Work in progress.

A prosthetic caged-ball aortic valve that can be placed with transcatheter techniques was designed, constructed, and initially evaluated in 12 adult mongrel dogs. The prosthesis consisted of a ring, cage, and ball. The ring was made of stainless steel wire coiled in a springlike configuration and covered with an expandable nylon mesh. The cage consisted of a self-expanding Gianturco stent with flat stainless steel wires attached across the cranial end. The ball was a detachable latex balloon filled with a radiopaque silicone prepolymer system. The self-expanding valve was easily passed through an 11- or 12-F Teflon sheath and was placed in the ascending aorta by means of the carotid approach. The stability and efficacy of the prosthesis were evaluated radiographically for as long as the valve remained functional (1-3 hours). The competency of the valve and the patency of the coronary arteries were determined angiographically over the same period. The results of these studies indicate that development and transcatheter placement of a prosthetic aortic valve are feasible.

Animals

Current use of lymphography for staging lymphomas and genital tumors.

The current literature and the experience at The University of Texas M.D. Anderson Cancer Center were reviewed to determine the current status of the use of lymphography for staging of malignant disease. Lymphography continues to be used for staging and surveillance of the lymphomas and, to some extent, for staging of carcinoma of the cervix. Testicular tumors are now primarily staged and followed by CT and serum markers. Currently, other abdominal and pelvic tumors are not commonly evaluated with lymphography.

Female

Primary malignant small round cell tumor of the abdomen: CT findings in five cases.

Malignant small round cell tumor of the abdomen is a newly described clinicopathologic entity. The features of this entity include a predilection for young men, predominant abdominopelvic location, and aggressive behavior. Pathologic analysis demonstrates a small-cell tumor unusually coexpressing desmin and keratin. This study describes CT characteristics in five patients with malignant small round cell tumor of the abdomen. All patients were young white men, 20-36 years old (mean, 28 years). In all five cases, CT scans revealed lobulated masses appearing to arise primarily from peritoneal surfaces and predominantly involving the peritoneal cavity of the abdomen (two cases) and pelvis (two cases); diffuse abdominopelvic involvement was noted in one case. The masses were centrally necrotic and enhanced inhomogeneously after administration of iodinated contrast material. Additional CT features included ascites (one case), calcifications in the dominant mass (one case), omental implants (two cases), hydronephrosis (four cases), anterior diaphragmatic lymphadenopathy (two cases), liver metastases (two cases), and retroperitoneal lymphadenopathy (two cases). CT findings of abdominal malignant small round cell tumor are nonspecific and mimic findings noted in other conditions, such as peritoneal carcinomatosis and leiomyosarcomatosis.

Abdominal Neoplasms

Regional lymph node metastases in carcinoma of the left side of the colon and rectum: CT demonstration.

The distribution of regional lymph node metastases in carcinoma of the left side of the colon, rectum, and anus can be well shown by routine CT of the abdomen and pelvis. Recognition of the location of nodes in the mesocolic, left colic, and IMA nodal groups can help in developing a systematic approach to the detection of nodal metastasis. This can be especially important in preoperative planning for cases in which resection may be curative. In addition, an understanding of the distribution of nodal metastasis will make it possible to recognize early recurrent nodal disease, particularly with an increase in associated increase in levels of carcinoembryonic antigen, and to predict certain clinical sequences such as hydronephrosis of the left kidney associated with left colic nodal metastases.

Anus Neoplasms

Pulmonary artery pressure measurement in patients with elevated pressures: effect of backrest elevation and method of measurement.

OBJECTIVE: To determine whether pulmonary artery pressure measurement is accurate if the head of the bed is elevated; to compare the end-expiratory graphic recording and digital monitor methods for pulmonary artery pressure measurement; to determine whether either mean arterial pressure or mixed venous oxygen saturation changes during backrest elevation. DESIGN: Nonrandomized clinical trial. SETTING: A six-bed cardiac surgical intensive care unit of a 540-bed federal facility. POPULATION: Twenty-five postoperative cardiac surgical patients with elevated pulmonary artery pressures (systolic higher than 35 mm Hg). INTERVENTIONS: In supine patients pulmonary artery pressures were measured at each of the following backrest elevations: 0, 20, 30, 45 and again at 0 degrees. Measurements were obtained once during mechanical ventilation and once during normal breathing after extubation. MAIN OUTCOME MEASURES: End-expiratory graphic recording of pulmonary artery pressures; digital monitor values of pulmonary artery pressures; mean arterial pressure; and mixed venous oxygen saturation. RESULTS: No statistical difference was found in pulmonary artery pressures measured at each of the backrest elevations during mechanical ventilation or normal breathing after extubation. Pulmonary artery diastolic and pulmonary capillary wedge pressures obtained with the digital monitor method were significantly lower than the end expiratory graphic recording method during normal breathing after extubation but not during mechanical ventilation. No changes in mean arterial pressure or mixed venous oxygen saturation occurred during backrest elevation. CONCLUSIONS: These results show that pulmonary artery pressures can be measured accurately with the head of the bed in an elevated position. The data indicate that obtaining pulmonary artery pressure measurements from the digital display of the bedside monitor is accurate when respiratory wave form fluctuations are minimal but may lead to inaccurate values with prominent respiratory fluctuations. Further research is needed to validate this finding in different patient populations and with other models of monitoring equipment.

Adult

Hilar cholangiocarcinoma. An evaluation of subtypes with CT and angiography.

Sixty-seven patients had hilar cholangiocarcinomas which were divided into 3 types based on tumor morphology as observed on cholangiography and CT. The pathology, vascularity, and pattern of tumor spread of these types were compared. Most of the infiltrative tumors (n = 44) were scirrhous adenocarcinomas, which on CT showed poor or no contrast enhancement with frequent lymph node metastases and liver atrophy. At angiography, there was vascular encasement in 52%, in rare cases neovascularity, and tumor stain. The exophytic type (n = 19) was divided into 2 subgroups depending on the main location of the tumor. The nodular subtype (n = 16) was mainly inside the liver and somewhat hypervascular similar to peripheral cholangiocarcinoma, often with intrahepatic metastases. The periductal subtype (n = 3) was hypovascular, similar to the infiltrative cholangiocarcinoma, and had a tendency to spread along the portal vein. The intraductal type (n = 4) was observed as a filling defect on cholangiography. CT revealed an intraluminal low density mass. Histologically, they were papillary adenocarcinomas. The radiologic types of hilar cholangiocarcinoma showed different characteristics with regard to pathologic findings, vascularity, and pattern of spread.

Adenoma, Bile Duct

Acanthamoeba meningoencephalitis in a patient with acquired immunodeficiency syndrome.

Several cases of Acanthamoeba encephalitis (ie, granulomatous amebic encephalitis) have been reported in patients with acquired immunodeficiency syndrome from the United States. To our knowledge, none so far has been reported from Europe, and this is the first case of amebic meningoencephalitis due to Acanthamoeba in a patient with acquired immunodeficiency syndrome from Italy. The patient was a 24-year-old, human immunodeficiency virus-positive heterosexual man with a 6-year history of intravenous drug use. He was admitted to the hospital because of severe headache, confusion, nuchal rigidity, jaundice, and ascites. He died 5 days later. At autopsy, the brain showed extensive hemorrhagic necrosis with numerous trophic and cyst forms of Acanthamoeba. The amebas were identified as Acanthamoeba divionensis by the indirect immunofluorescence test.

AIDS-Related Opportunistic Infections

Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization.

Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy.

Aged