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Biomedical subjects

G Steele

Publications and source records attributed to G Steele.

At least 91 records · Page 5Linked to original sources
PubMed1989

Splenectomy. The treatment of choice for human immunodeficiency virus-related immune thrombocytopenia?

Immune thrombocytopenia is a well-recognized part of the clinical spectrum of infection with the human immunodeficiency virus. From November 1985 to February 1988, 15 patients who were human immunodeficiency virus-positive underwent splenectomy for refractory immune thrombocytopenia. Eight patients had thrombocytopenia only, and 7 others were pancytopenic prior to splenectomy. Three of the 15 patients fulfilled criteria for acquired immunodeficiency syndrome before splenectomy, and acquired immunodeficiency syndrome developed in 5 patients during the follow-up period. The median duration of thrombocytopenia prior to surgical therapy was 6 months. A bone marrow biopsy specimen showed hypercellularity with increased megakaryocytes. All patients had a therapeutic response to splenectomy. Long-term remission from thrombocytopenia/pancytopenia was achieved in 14 of the 15 patients during a follow-up period of 2 to 21 months. Splenectomy can be accomplished with an acceptable morbidity. Pneumonia developed postoperatively in 2 patients, but they did not manifest the characteristic picture of overwhelming postsplenectomy sepsis. They had received vaccinations against encapsulated organisms preoperatively. We conclude that splenectomy provides a durable and lasting response for HIV-related thrombocytopenia. Vaccination for Streptococcus pneumonia and Haemophilus influenzae should be given prior to splenectomy although its efficacy is not clear in this group.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Receptor-mediated endocytosis of carcinoembryonic antigen by rat alveolar macrophages in vitro.

Uptake of carcinoembryonic antigen (CEA) by isolated rat alveolar cells was time, temperature, and concentration dependent (Kuptake = 2.4 x 10(-7) M). Pretreatment of the alveolar cells with colchicine inhibited internalization of CEA. Uptake of 125I-labeled CEA by alveolar cells required divalent cations and was inhibited by cold CEA and nonspecific cross-reacting antigen (NCA). The carbohydrate portion of CEA was modified by neuraminidase treatment and Smith degradation. The modified glycoproteins inhibited endocytosis by the alveolar macrophages, thus excluding nonreducing terminal carbohydrate residues as the recognition site of the receptor. Endocytosis of CEA was independent of native protein conformation since performic acid oxidized CEA and glycopeptides produced by pepsin digestion were inhibitory. Rat alveolar macrophages bound CEA with similar specificity to that of rat Kupffer cells. Alveolar macrophages, unlike Kupffer cells, did not rapidly exocytose the internalized CEA. Neither P388D1, a macrophage-like murine cell line, nor murine peritoneal exudate cells were capable of endocytosing CEA in vitro.

Animals↗
PubMed1989

Ras gene activation and epidermal growth factor receptor expression in human colon cancer.

The expression of various epitopes of epidermal growth factor receptor (EGFr) and mutational activations of ras gene product p21 in colorectal primary cancers from 16 patients have been analyzed in this study. Eight noncancerous colons were used as controls. Indirect immunoperoxidase staining was performed using Avidin-Biotin Complex assay. Monoclonal antibodies against carbohydrate and polypeptide epitopes of EGFr and monoclonal antibodies against "wild-type" and "mutant" ras p21 were used as specific probes. There was no specific expression of the polypeptide epitope of EGFr observed in any of the colon cancers or normal colon tissues. Four of the sixteen tumors (25%) expressed the carbohydrate epitope of EGFr. Glycine----arginine mutation and glycine----valine mutation of codon 12 in ras p21 was observed in 40 and 31% of colon cancers, respectively. Although normal colon showed expression of wild-type ras in about half the cases studied, there was no mutational activation of the ras genes. The morphologically adjacent normal colon mucosa in cancer patients expressed varying levels of mutational activation involving the codon 12. The presence of unusual carbohydrates relating to the EGFr and the products of ras gene activation by point mutations in colon cancers may imply a functional role in transformation.

Antibodies, Monoclonal↗
PubMed1989

Resection of hepatic metastases from colorectal cancer. Biologic perspective.

During the past decade the results of slightly fewer than 1000 resections of liver metastases from colorectal carcinoma have been analyzed, retrospectively reanalyzed, and reviewed. The following are confirmed conclusions: major liver resection can be performed safely (less than a 5% operative mortality rate); 20% to 25% of these patients are cured; no other regional therapy options have any curative potential. The following caveats are also obvious: most patients who are operated on are not cured; although predictors have been proposed to select patients most likely to benefit from surgery, none is discriminating in and of itself; most therapy questions in this group of patients have not been addressed in any formal way; surgery for isolated regionally recurrent colon and rectum carcinoma remains an important stopgap only until effective systemic therapy is discovered. This review of our own and other single and multi-institutional prospective and retrospective data will be framed by the following questions. (1) Does resection of liver metastases cure patients or simply select those who would have survived in the long-term without any therapy? (2) In the absence of any formalized, properly designed trial, how can one judge the benefit of resection? (3) Why do metastases recur only in the liver? (4) What new therapies should focus on the predominant secondary failure sites in the majority of patients who do not benefit from hepatic metastasis resection?

Colorectal Neoplasms↗
PubMed1989

Prospective comparison of preoperative imaging and intraoperative ultrasonography in the detection of liver tumors.

A prospective evaluation of the accuracy of preoperative computed tomography (CT), ultrasonography (US), and angiography was performed in 54 patients undergoing resection of hepatic neoplasms. The results were compared with surgical findings and intraoperative ultrasonography (IOUS). A total of 167 lesions was seen by means of IOUS, of which preoperative US enabled detection of 127 (76%). In 48 patients CT allowed detection of 91 of 150 lesions (61%), and in 35 patients angiography showed 56 of 107 lesions (52%). When the detection rate is analyzed according to hepatic segment, the greater overall accuracy of preoperative US may be attributed to a markedly better detection rate in lateral segment of the left lobe of the liver. Lesion size also represented a factor, with preoperative US allowing detection of a greater number of small (less than 2 cm) lesions compared with CT. In patients studied with both CT and US, the combined lesion-detection rate increased to 81% in the right lobe and 76% in the left lobe. Because of this we recommend that preoperative assessment include both CT and US evaluation of the liver. IOUS showed 25% to 35% additional lesions compared with preoperative US and CT. More importantly, 40% of the lesions demonstrated by IOUS were neither visible nor palpable at surgery. We recommend that IOUS be considered in all patients in whom resection of hepatic neoplasm is planned.

Angiography↗
PubMed1989

Expression of the c-erbB-2 gene product (p185) at different stages of neoplastic progression in the colon.

The c-erbB-2 gene has been found amplified in a number of human adenocarcinomas leading to elevated levels of expression of the p185 protein product. Increased expression of this putative growth factor receptor has been reported to occur by molecular mechanism other than gene amplification and for this reason we have studied the expression of the p185 protein in normal colon and in lesions representing different stages of neoplastic progression. We report amplification of the c-erbB-2 gene in 3 of 44 colon carcinomas and 1 of 5 preneoplastic polyps studied. Confirmation of expression of the p185 protein product was established in Western blot analysis and by immunocytochemical staining of tissue sections. An extended study, involving adenomatous polyps and carcinomatous material in immunostaining, revealed detectable presence of the p185 protein in 20% of carcinomas, consistent with immunoprecipitation data derived using established cell lines. In contrast, a high percentage of polyps showed strong staining with both p185 antibodies used, indicating elevated levels of expression of the c-erbB-2 protein associated with preneoplastic lesions. Staining of normal human colon revealed a restricted localization of this putative receptor to cells on the luminal colonic surface, with no expression in cells of the crypt. Histologically normal mucosa, adjacent to the tumor, showed a more extensive distribution involving the crypt suggestive of a disturbance in the normal expression of c-erbB-2. These results indicate that elevated expression of the c-erbB-2 protein is associated with early stages of colonic neoplasia but do not establish it as a primary factor in these events. The occurrence of multiple copies of the c-erbB-2 in a percentage of colon lesions, however, suggests a possible role for this gene in some colon malignancies.

Antibody Specificity↗
PubMed1989

Detection of altered H-ras proteins in human tumors using western blot analysis.

H-ras p21 protein expression was investigated in bladder and colonic tumor tissues using an H-ras specific antibody in Western blot analysis. The specificity of this antibody to H-ras proteins was established using NIH/3T3 transfectants expressing oncogenic counterparts of the different ras gene family members. Use of this antibody to detect altered H-ras proteins was demonstrated using a panel of transfectants bearing different mutated H-ras genes and established cell lines previously characterized in transfection assays. Extension of this technique to direct analysis of human tumor material confirmed previous observations of H-ras activation within a group of bladder tumors and identified three more urothelial tumors expressing altered H-ras proteins. The altered migrational properties of these three were suggestive of point mutational events in 12 (1 case) and 61 (2 cases) codon hot spots. This study extends previous observations on the preferential activation of H-ras in urinary tract tumors and provides a rapid technique for evaluating the status of H-ras proteins in human tumor tissue.

Antibody Specificity↗
PubMed1989

Intraoperative radiation therapy for biliary tract carcinoma: results of a 5-year experience.

The results of a 5-year experience with use of intraoperative radiation therapy (IORT) in the management of locally advanced bile duct carcinoma are presented. Fifteen patients received IORT doses between 5 and 20 Gy for localized disease, which was either primary and resected with microscopic residual (2 patients), primary and unresected (10 patients), or recurrent (3 patients). Thirteen patients also received postoperative radiation therapy. The median survival of the 12 patients with primary disease was 14 months, with disease controlled in the porta hepatis in 5 of 10 evaluable patients. The three patients with recurrent disease survived 2, 9, and 11 months. There were two operative deaths, for an operative mortality of 13%. Acute and chronic complications are reviewed. Cholangitis is the most frequent in both categories. This aggressive approach in the therapy for advanced disease has an acceptable level of morbidity and may warrant the use of IORT as part of the management of biliary tract cancer.

Acute Disease↗
PubMed1988

A cell surface glycoprotein expressed by colorectal carcinomas including poorly differentiated, noncarcinoembryonic antigen-producing colorectal tumors.

A monoclonal antibody to a cell surface glycoprotein on human colorectal carcinomas was raised using the undifferentiated colon carcinoma cell line MIP 101 as the immunogen. This antibody, ND4, is an IgG2a which does not cross-react with carcinoembryonic antigen (CEA), non-specific cross-reacting antigen, or blood group substances A, B, and H. Immunoprecipitation using lysates of cells grown in [35S]methionine or [3H]glucosamine and lysates of cells surface labeled with 125I showed binding to a cell surface glycoprotein with a molecular weight of approximately 160,000. Indirect immunofluorescence showed binding to the cell surface of 14 of 15 human colorectal carcinoma cell lines including six of six that do not secrete CEA. Two of seven human noncolorectal carcinoma lines and one of six nonhuman cell lines also bound antibody. Immunoperoxidase staining of formalin-fixed tissues showed prominent antibody binding with 19 of 33 (58%) human colorectal carcinomas, including five of six poorly differentiated tumors, five of 43 (12%) normal colonic mucosal biopsies, and one of 17 (6%) normal noncolonic tissues. One of 11 (9%) noncolonic tumors, a gastric adenocarcinoma, stained with ND4. Preliminary data obtained by a nonquantitative nitrocellulose dot-immunoassay have tentatively identified this glycoprotein in the serum of 15 of 37 (41%) patients with colorectal cancer. Three of the 15 patients had early stage disease and normal CEA levels (less than 2.5 ng/ml). Three patients had circulating antigen detectable preoperatively but not after tumor resection. Only one of 11 (9%) sera samples from normal subjects was positive. The characteristics of ND4 suggest that it may be of value in monitoring patients with colorectal carcinomas who do not have plasma CEA elevations. It may also be of value in the differential diagnosis of metastatic, poorly differentiated adenocarcinomas of unknown primary origin.

Animals↗
PubMed1988

Search for useful biomarkers of pre- or early malignant colonic tumors.

1. CEA, a well established marker for benign and malignant colonic tumors is widely used for tissue staining and body fluid measurement. Highly specific monoclonal antibodies are now available. It is likely that CEA gene(s) will be available soon. 2. Monoclonal antibodies to blood group precursor antigens, especially extended LeX and LeY are also available and are known to detect premalignant lesions. 3. The demonstration that LeY is expressed in purified CEA specimens suggests a complementary relationship between the two markers of possible clinical utility. 4. Systematic comparison of both families of marker is timely. 5. Experienced pathologists have classified and standardized the histology of adenomatous polyps and their premalignant counterparts. The use of serial sections of identical tissues will permit comparison of several candidate markers in the same lesion. Selection of lesions which contain benign, malignant, and invasive components in the same section will provide best control, minimizing the need for exhaustive studies. 6. Laminin staining gives useful indication of early invasion through the basement membrane. It will complement morphologic and marker evidence for early malignancy and invasion. 7. It is unnecessary to investigate all polyps. Focus should be on high risk patients with (1) large polyps, severe dysplasia and advanced villous change, (2) synchronous polyps and invasive cancer, and (3) familial and other multiple polyposis disorders. 8. A plethora of other candidate markers is available, only a few of which are mentioned.

Antibodies, Monoclonal↗
PubMed1987

Hepatic cryosurgery with intraoperative ultrasound monitoring for metastatic colon carcinoma.

We utilized cryosurgery with intraoperative ultrasound (IOUS) monitoring in ten patients to treat multiple unresectable hepatic metastases from colorectal carcinoma. The liver was exposed at laparotomy, and tumors were subjected to three cycles of freezing (eight minutes each) and thawing. Freezing was monitored by IOUS, which visualized frozen tumor as a hyperechoic rim with posterior acoustic shadowing. Frozen normal liver appeared hypoechoic after thawing compared with normal unfrozen liver. There were no significant complications. The follow-up ranged from four months to 17 months (median, 7.5 months). Tumor response was documented by pathologic findings (coagulative necrosis), progressive fall of carcinoembryonic antigen levels, and computed tomographic scan evidence of necrosis and shrinkage of tumor. One patient underwent repeated laparotomy five months after cryosurgery and had the frozen lesions resected; there was no residual tumor. This study establishes the technical feasibility and antitumor response of hepatic cryosurgery and the use of IOUS for precise localization and monitoring of cryoablations.

Adult↗
PubMed1987

Management of recurrent pelvic tumors.

The management of regional tumor recurrence in the pelvis traditionally has been a difficult problem for surgeons and oncologists. The only meaningful therapy for these patients is a potentially curative re-resection. The records and operative reports of 29 patients with regional pelvic tumor recurrence treated between 1981 and 1986 were reviewed. The operative procedures performed included three bowel resections, six abdominoperineal resections, eight pelvic exenterations, eight resections of tumor recurrence, and four conservative procedures. There was one operative death in this group. Significant morbidity was noted in the group but was clustered in a small number of patients operated on early in the series. The median follow-up in this series was 13 months (range, two to 51 months). Nineteen (65%) of the patients are surviving at a median follow-up of ten months (range, two to 51 months). The median survival (following resection) in the ten patients (35%) who died was 18 months. In 15 (52%) of the patients, a complete resection was performed. In this group, the survival is 80% with a median follow-up of 11 months. Seven (37%) are surviving with no evidence of disease. Palliation of symptoms occurred in 23 (79%) of the 29 patients. Radical resection of tumor recurrence in the pelvis can be performed with acceptable mortality and complication rates. This therapy should be considered for further clinical trials combining surgical and adjuvant therapy in patients with regional pelvic tumor recurrence.

Adult↗
PubMed1987

Resection of tumors in irradiated fields with subsequent immediate reconstruction.

With increased use of primary radiation therapy for treatment of cancer and adjuvant radiation therapy after surgical removal of a bulk tumor, recurrence in these fields has posed significant new and increasingly technical and biologic problems. We report our experience with ten such cases in which difficult wounds were reconstructed immediately after major regional resections of advanced or recurrent tumors in fields of previous irradiation. All of these patients could undergo extirpation of their recurrent tumors in irradiated fields because of improved techniques in reconstructive flap surgery allowing large amounts of well-vascularized tissue to be transferred, sometimes over a significant distance. Follow-up of these patients has ranged from three to 18 months (median, nine months). Primary healing, decreased deformity, reduced morbidity, and prolonged disease-free intervals have been achieved with the combination of extirpative and reconstructive techniques.

Abdominal Neoplasms↗
PubMed1987

Management of the urinary tract involved by recurrent cancer.

We present our experience from 1982 to the present in treating 33 patients with recurrent cancers (colorectal, 22; gynecologic, six; breast, two; melanoma, two; and lung, one) secondarily involving the genitourinary tract. All patients had severe symptoms that required palliation. Endoscopically placed stents relieved ureteral obstruction in 18 (75%) of 24 patients with widespread metastatic disease. Two patients required percutaneous nephrostomy tubes, and five required open operations. Good to excellent palliation was achieved in 23 of 24 patients. Mean survival in the group with diffuse metastases was 13 months (range, six to 29 months). Nine patients with localized recurrences underwent surgical procedures. For localized pelvic recurrences, total exenteration (with or without intraoperative radiotherapy) provided excellent palliation with low morbidity. At the time of this report, five of six such patients had no evidence of disease, and one had a small asymptomatic pelvic recurrence, with a mean follow-up of 13 months (range, five to 19 months).

Adult↗
PubMed1987

Human immune response to monoclonal antibody administration is dose-dependent.

When mouse monoclonal antibodies (MAbs) are injected into patients they usually induce an immune response. The resultant human anti-mouse-immunoglobulin antibody (Hu-aMAb) limits multiple injections of these reagents. A strategy to decrease the production of Hu-aMAb was tested in 20 patients with advanced gastrointestinal carcinoma. Ten patients received 700 mg of MAb as their initial exposure to mouse immunoglobulin, while the other ten patients received 100-mg of immunoglobulin initially. Each group received the same maintenance regimen until Hu-aMAb or disease progression was detected. Six patients in the high-dose group did not produce detectable Hu-aMAb for up to five months after initial exposure. All ten of the patients who received the low initial dose developed Hu-aMAb. Allergic reaction did not occur in the absence of Hu-aMAb. This larger initial dose in vivo injection strategy may allow repetitive exposure to MAb reagents without Hu-aMAb limiting further diagnostic or therapeutic use of murine immunoglobulin.

Animals↗
PubMed1987

Effect of 13-cis-retinoic acid on tumor prevention, tumor growth, and metastasis in experimental colon cancer.

The effect of 13-cis-retinoic acid (13-cis-RA) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male, random bred, Sprague-Dawley (S-D) and inbred Wister/Furth (W/Fu) rats and on isograft tumor growth and metastases in a Brown Norwegian (BN) X W/Fu F1 rat was studied. 13-cis-RA (300 mg/kg diet) was administered to S-D rats 1 week before commencing DMH injections and for the duration of the experiment. W/Fu rats received 13-cis-RA (10 mg/kg weight X 5 days) 6 weeks after DMH injection had begun and monthly thereafter. Primary tumors were detected by serial laparotomy under ether anesthesia in both strains. The time to tumor onset was significantly delayed in treated groups, S-D and W/Fu, P = 0.0339 and 0.0322, respectively (Mantel-Haenszel test), compared with placebo-treated controls. 13-cis-RA (15 mg/kg weight) administered 2 days before and for the duration of isograft tumor growth (DMH 2054, a well-differentiated mucin-producing colon adenocarcinoma that spontaneously metastasized to lung) had no effect on tumor growth or metastasis in the BN X W/Fu F1 rat. The findings suggest that the role of 13-cis-RA is in colon cancer prevention and not in its treatment either in an adjuvant or established setting.

Animals↗