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Biomedical subjects

K Cleary

Publications and source records attributed to K Cleary.

At least 55 records · Page 3Linked to original sources
PubMed1995

Using claims data to measure and improve the MMR immunization rate in an HMO.

BACKGROUND: Health maintenance organizations (HMOs) are increasingly being expected to show evidence of the quality of care provided. One such quality measure is the measles, mumps, and rubella (MMR) immunization rate. This article describes how Blue Choice, an individual practice association (IPA)-model HMO, located in Rochester, New York, with more than 350,000 members, set up a three-phase study to improve immunization compliance rates. METHODS: The first phase of the study amounted to calculating baseline compliance figures consistent with the American Academy of Pediatrics Immunization protocol using paid claims and membership databases. The second phase was to recalculate the MMR immunization rate based on survey information gathered from primary care physicians and to analyze and address reasons for any observed discrepancies. The third phase was to use Blue Choice Quality Assurance nursing staff to follow up with the remaining noncompliant members and determine the impact of intervention on the MMR immunization rate. RESULTS: Our baseline MMR immunization compliance study yielded a rate of 91.7%, which, as a first check of quality, is quite good in comparison to the nationally reported MMR compliance figures of 79.3%. Phase II analysis demonstrated that by seeking chart information, the overall MMR compliance rate was actually 96.7% Reasons for noncompliance are described, as well as the process used and improvements made, in phase III.

Child, Preschool↗
PubMed1994

Patterns of residual disease after preoperative chemoradiation in ultrasound T3 rectal carcinoma.

BACKGROUND: Rectal carcinoma tends to recur locally, with invasion of adjacent organs and significant pelvic pain. Both radiation therapy alone and combined chemoradiation have been used in an attempt to decrease the local recurrence rate and thereby improve survival. Although preoperative chemoradiation can clinically downstage rectal tumors, the pathologic extent of the residual disease has not been studied. METHODS: Thirty-seven patients with T3 rectal cancer diagnosed by transrectal ultrasonography (uT3) received 45 Gy with continuous infusion 5-fluorouracil (300 mg/m2/day). Proctoscopy with mucosal/submucosal biopsy was performed in patients (16 of 37) posttreatment and before definitive surgery. RESULTS: Microscopic evaluation of the 37 resected specimens showed a 30% (11 patients) pathologic complete remission rate. The pattern of residual disease in the remaining 26 patients showed that nine (25%) had microscopic residual tumor without evidence of mucosal involvement. Of the 14 patients with a negative proctoscopic evaluation and biopsy only, five (36%) had no residual tumor on final pathology. CONCLUSIONS: After chemoradiation, the pathologic presentation of rectal cancer may be altered, making endoscopic procedures and mucosal/submucosal biopsies unreliable in detection of residual disease. Despite the relatively good pathologic complete remission rate noted in this study, all patients undergoing chemoradiation for uT3 rectal carcinomas need definitive surgical resection to confirm a complete clinical remission.

Adenocarcinoma↗
PubMed1993

Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b.

BACKGROUND: A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment. METHODS: Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments. RESULTS: Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen. CONCLUSIONS: The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.

Adolescent↗
PubMed1993

Reduction of systemic drug exposure after hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration.

BACKGROUND: Hepatic arterial infusion of doxorubicin has produced tumor response in hepatic malignancies; however, the limited success of these treatments is related in part to dose-limiting systemic toxicities. The purpose of this study was to determine whether a novel venous isolation-chemofiltration system could limit systemic exposure to doxorubicin after hepatic arterial infusion. METHODS: Doxorubicin (1 or 3 mg/kg) was infused in the hepatic arteries of domestic pigs after complete hepatic venous isolation was achieved with a dual-balloon vena cava catheter. The hepatic vein effluent was pumped through an extracorporeal carbon chemofiltration circuit. Doxorubicin levels were measured in prefilter (hepatic vein), postfilter, and systemic serum at intervals up to 1 hour after drug infusion. RESULTS: Complete hepatic venous isolation with extracorporeal chemofiltration significantly reduced (> 90%) the postfilter and systemic levels of doxorubicin compared with prefilter levels (p < 0.01). At the time animals were killed 7 days after infusion of doxorubicin (3 mg/kg), tissue levels of doxorubicin in the liver showed a 16-fold increase compared with levels in the heart (p < 0.01). CONCLUSIONS: For chemotherapeutic drugs like doxorubicin with a low first-pass extraction by the liver, the novel system described herein achieved significant reduction in systemic drug exposure. This system will allow dose intensification of doxorubicin administered by hepatic arterial infusion to treat hepatic malignancies.

Alanine Transaminase↗
PubMed1992

Regional DNA content heterogeneity in colonic adenocarcinoma: prognostic significance in patients with liver metastases.

We retrospectively examined by flow cytometry the DNA ploidy pattern in tissue blocks from 25 primary colon adenocarcinomas and their lymph node and liver metastases. Intratumoral heterogeneity was present in 22% of primary tumors and 21% of metastatic liver deposits. Intertumoral heterogeneity, measured between the primary tumor and its lymph node and liver metastases, was 0% and 20%, respectively. Of 24 patients who underwent successful resection of their liver metastases, 8 neoplasms had uniformly diploid DNA content, while 16 tumors had aneuploid DNA pattern in either the primary tumor, the metastases, or both. Five-year survival was better in the diploid group (38% vs. 7%, P = 0.10 by log rank analysis). Three of eight patients in the diploid group remain free of disease, while all 16 patients with aneuploid cell populations have died of recurrent disease.

Adenocarcinoma↗
PubMed1990

Establishment of a new human pancreatic adenocarcinoma cell line, MDAPanc-3.

A new cell line was established from a liver metastasis of a human pancreatic adenocarcinoma. The cell line, MDAPanc-3, which arose from a moderately differentiated adenocarcinoma, produces carbonic anhydrase II mRNA, but no detectable levels of insulin or alpha amylase mRNA. The stem line chromosome number was determined to be 43, with six marker chromosomes. Growth of MDAPanc-3 is stimulated by cholecystokinin (CCK) fragment 26-33. The cell line will be useful in further studies on the mechanism(s) by which CCK stimulates growth of certain human pancreatic adenocarcinomas and normal human pancreatic exocrine tissue.

Adenocarcinoma↗
PubMed1989

Mutations in the p53 gene occur in diverse human tumour types.

The p53 gene has been a constant source of fascination since its discovery nearly a decade ago. Originally considered to be an oncogene, several convergent lines of research have indicated that the wild-type gene product actually functions as a tumour suppressor gene. For example, expression of the neoplastic phenotype is inhibited, rather than promoted, when rat cells are transfected with the murine wild-type p53 gene together with mutant p53 genes and/or other oncogenes. Moreover, in human tumours, the short arm of chromosome 17 is often deleted. In colorectal cancers, the smallest common region of deletion is centred at 17p13.1; this region harbours the p53 gene, and in two tumours examined in detail, the remaining (non-deleted) p53 alleles were found to contain mutations. This result was provocative because allelic deletion coupled with mutation of the remaining allele is a theoretical hallmark of tumour-suppressor genes. In the present report, we have attempted to determine the generality of this observation; that is, whether tumours with allelic deletions of chromosome 17p contain mutant p53 genes in the allele that is retained. Our results suggest that (1) most tumours with such allelic deletions contain p53 point mutations resulting in amino-acid substitutions, (2) such mutations are not confined to tumours with allelic deletion, but also occur in at least some tumours that have retained both parental 17p alleles, and (3) p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene. These results suggest that p53 mutations play a role in the development of many common human malignancies.

Alleles↗
PubMed1988

Hepatocellular carcinoma. A retrospective analysis of treatments to manage disease confined to the liver.

The histories of 73 patients with hepatocellular carcinoma (HCC) confined to the liver who were seen at M. D. Anderson Hospital between January 1976 and December 1983 were reviewed. In 18 patients the tumor was resected either at the outset or after the patients' response to chemotherapy; nonsurgical treatments consisted of hepatic arterial infusion (HAI) in 10 patients and intravenous (IV) therapy in four patients. Patients who had resection were younger, and their liver functions and performance status were better than the IV and HAI groups. Their median survival was 46 months. Of the patients who had nonresectable tumors, 28 received chemotherapy by HAI and 27 received IV therapy. Of the 28 patients in the HAI treatment group, 25 received uniform infusion of floxuridine (FUDR, Roche, Australia), doxorubicin (Adriamycin), and mitomycin C (FUDRAM). Of the 27 patients in the IV treatment group, 15 received 5-fluorouracil (5-FU) and doxorubicin-containing regimens; in 11 patients 5-FU was combined with other agents. The HAI and IV treatment groups were similar in age and ethnicity, performance status, serum alpha-fetoprotein levels, liver function, presence of hepatitis B antigen, and presence or absence of cirrhosis. The median survival was 9 months for HAI-treated patients and 5 months for the IV-treated group. The statistical differences were resection versus HAI, P less than 0.01; resection versus IV, P less than 0.01; HAI versus IV, P less than 0.01. Thirteen of 18 patients who had resections, six of 28 patients treated with HAI, and two of 27 IV-treated patients survived 2 years or more. It is concluded that for patients with hepatocellular carcinoma confined to the liver, the option of tumor resection either at the beginning of treatment or after chemotherapy offers the best chances for long-term survival. The overall prognosis is poor for patients with nonresectable hepatocellular carcinoma, but arterial infusion chemotherapy may double the median survival as compared to IV chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients.

A preoperative serum carcinoembryonic antigen (CEA) concentration greater than 5 ng/ml portends a poor prognosis for patients with colorectal carcinoma. The purpose of this study was to determine if the tumorigenicity of colorectal carcinomas in nude mice was associated with the preoperative serum CEA concentration. Neoplasms from 53 patients were either implanted as fragments or dissociated with collagenase and DNase, and 3 x 10(6) viable cells were injected into the flanks of BALB/c nude mice. The growth potential of tumors resected from patients with CEA levels exceeding 5 ng/ml was greater than that of tumors from patients with normal serum CEA: 26 of 33 carcinomas from patients with CEA greater than or equal to 5 ng/ml were tumorigenic in nude mice, whereas only 8 of 22 neoplasms from patients with normal serum CEA were tumorigenic in nude mice (P less than 0.001). Primary colorectal cancers, not metastases, were the basis for the association between tumorigenicity and preoperative CEA. Tumorigenicity was also associated with stage of disease, since Dukes' D primary tumors and metastases were more tumorigenic than Dukes' A to C primary tumors. Growth in nude mice was not associated with other prognostic factors such as tumor site, mucin production, local invasion, or stage of histological differentiation. The tumorigenic capability of human colorectal carcinomas may be associated with the preoperative serum CEA concentration and may reflect an increased potential to develop clinical metastases.

Adult↗
PubMed1988

Ulex europeus type I agglutinin detects carcinoembryonic antigen in extracts of human colorectal carcinoma.

Recent interest has focused on fucosylated epitopes expressed on human neoplasms. The plant lectin Ulex europus agglutinin, Type I (UEA) binds fucosylated oligosaccharides, while UEA-reactive substances have a tissue distribution similar to carcinoembryonic antigen (CEA). We sought to determine if UEA reacted with CEA in extracts of fresh primary and metastatic colorectal carcinomas and paired normal tissues. The extracts were electrophoretically transferred to nitrocellulose membranes after the proteins were separated by SDS-PAGE in 10% polyacrylamide gels. The transfer membranes were then stained with peroxidase-conjugated UEA (UEA-P) or antibody to CEA (CEA-P). UEA-P reacted with a 170-190-kDa band in extracts of 22 of 30 primary tumors, 10 of 12 metastases, but only 1 of 5 villous adenomas. UEA-P generally did not react with normal colon or liver extracts. UEA-P also did not bind to 170-190-kDa molecules in Western transfers of a breast carcinoma metastatic to bowel and a focal nodular hyperplasia of liver. CEA-P displayed similar reactivity and detected CEA in a tumor extract negative for UEA. Fucose blocked binding of UEA-P to Western transfers of tumor extracts. CEA-P reacted with a 170-190-kDa substance in tumor extracts eluted with fucose from a column of immobilized UEA. Thus, UEA reacts with fucosylated oligosaccharides on most, but not all, species of CEA and may be a useful adjunct to anti-CEA immunohistochemistry.

Adult↗
PubMed1988

Interorgan glutamine metabolism in the tumor-bearing rat.

The effects of progressive malignant disease on gut/liver glutamine metabolism were studied in order to gain further insight into the altered glutamine metabolism that characterizes the host with cancer and to further elucidate the causes and consequences of glutamine depletion in tumor-bearing rats. Rats were inoculated on Day 0 with 2 X 10(6) viable fibrosarcoma cells and blood glutamine was measured every 6 days. On Day 24 the animals underwent laparotomy and sampling of arterial, portal venous, and hepatic venous blood. Arterial glutamine fell by more than one-third in tumor-bearing rats and the arterial-portal venous concentration difference for glutamine across the intestinal tract was diminished by 50% (P less than 0.01). Simultaneously the fractional extraction of glutamine by the gut was reduced from 21 to 15% (P less than 0.05). The liver switched from an organ of near glutamine balance in control rats to one of marked glutamine output in tumor-bearing rats (P less than 0.01). The wet weight of the small intestine was diminished by 15% in tumor-bearing rats and villous height was uniformly decreased in tumor-bearing rats with an average reduction in villous height of 26% (P less than 0.05). The causes of glutamine depletion in this tumor-bearing rat model remain unclear. The growing tumor may behave as a glutamine trap but also appears to alter glutamine metabolism in vital metabolic processing centers such as the gut and liver. Malignant cells may compete with gut mucosal cells for glutamine resulting in a diminished gut glutamine utilization and detrimental changes in mucosal architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice.

The purpose of these studies was to examine the growth characteristics and metastatic behavior of freshly isolated human colorectal carcinomas implanted into athymic nude mice. Four tumor lines were derived from primary colorectal carcinomas, three lines from hepatic metastases, and one line from a metastasis to a mesenteric lymph node. Subsequent to implantation into the subcutis or the muscularis, tumor lines derived from metastases grew faster in the nude mice than did cells isolated from the primary neoplasms. Regardless of the source of the cells, however, little or no visceral organ metastasis was found. Subsequent to i.v. injection, experimental lung colonies could be produced by some of the cells, but there was no correlation between lung tumor colony formation and the origin of the human colorectal cells. The intrasplenic injection of colorectal carcinoma cells provided a useful procedure to identify human colorectal carcinoma cells with metastatic potential to liver. Extensive tumor burdens in the liver were observed as early as 30 days after injection with two of the three liver metastasis-derived tumor lines. No liver metastases were found after the intrasplenic injection of cells isolated from the lymph node-derived tumor line. Ninety days after the intrasplenic injection of cells from the four primary colorectal carcinomas, limited liver metastases were observed. We conclude that metastasis of human colorectal carcinomas can be studied in nude mice, and its outcome depends upon both the intrinsic metastatic capacity of the human tumor cells and the organ environment of implantation.

Adult↗
PubMed1985

Neuroendocrine (Merkel cell) carcinoma of the vulva: a case report and review of the literature.

The clinical and pathologic features of a vulvar neuroendocrine (Merkel cell) neoplasm are presented. Cytologic studies of material obtained from needle aspiration suggested that the tumor was a small cell neoplasm possibly of neuroendocrine derivation. The light-microscopic findings of sheets of small, uniform cells were consistent with a diagnosis of neuroendocrine tumor. The electron-microscopic characteristics, including the presence of neurosecretory granules, confirmed the diagnosis of a neuroendocrine (Merkel cell) carcinoma. Regional lymph node metastases were present at the time of initial surgery, and both local and distant metastases developed 8 months later. A comprehensive pretreatment metastatic evaluation is recommended. The role of chemotherapy for primary therapy is considered.

Aged↗
PubMed1984

Effect of intraoperative propranolol on serum creatine kinase MB release in patients having elective cardiac operations.

Intraoperative beta blockade has been evaluated as an adjunct to hypothermic cold blood potassium cardioplegia by quantitating serum creatine kinase MB release. Randomization of 80 patients having coronary artery bypass grafting and 18 patients having valve replacement with or without bypass grafting resulted in 46 of the former and seven of the latter receiving propranolol 0.05 mg/kg 4 to 5 minutes before aortic cross-clamping. Among patients having bypass grafting, infarct size (in gram-equivalents) was 7.9 +/- 0.7 gm-Eq for the propranolol group and 10.3 +/- 0.8 (p less than 0.05) for the control group. Ischemic times were 71.6 +/- 2.8 and 78.3 +/- 3/4 minutes (p = NS), respectively. In valve replacement, infarct size was 9.9 +/- 1.9 gm-Eq for those receiving propranolol and 12.6 +/- 2.0 (p = NS) for the control subjects; ischemic times were 99.4 +/- 12.5 and 80.5 +/- 5.7 minutes, respectively. When the two groups receiving propranolol were combined, infarct size was 8.2 +/- 0.6 gm-Eq versus 10.9 +/- 0.7 (p less than 0.01). When ischemic time was plotted against infarct size, analysis by linear regression revealed a significant correlation for patients receiving propranolol and having bypass grafting (p less than 0.01) and for all patients receiving propranolol (p less than 0.01). These data demonstrate a modest reduction of infarct size with intraoperative propranolol as an adjunct to our standard management of patients having aortic cross-clamping. Quantitation of creatine kinase MB release is the best clinically available method for assessing alterations in techniques of myocardial preservation.

Coronary Artery Bypass↗
PubMedDate not supplied

Absence of a relationship of size of primary colon carcinoma with metastasis and survival.

This retrospective study analysed the relationship of tumor size to regional and systemic metastasis and to survival according to stage of disease. Colon cancers (391 cases) that were treated surgically at M. D. Anderson Hospital from 1955 to 1975 were reviewed. Staging of disease was based on the Astler-Coller modification of Dukes' staging classification. The mean diameters (cm +/- s.e.m.) of Dukes' B1, B2, C2 and D tumors were 4.47 +/- 0.34 (n = 46), 6.61 +/- 0.29 (n = 147), 5.39 +/- 0.23 (n = 71) and 5.78 +/- 0.24 (n = 120), respectively. The mean diameter of Dukes' B2 tumors was significantly greater than C2 (P less than 0.001) and D (P less than 0.05) tumors. Within stage B and C, size of the primary tumor showed no relationship to five year adjusted survival. Our findings suggest that colon carcinoma metastasis and survival are independent of tumor size. Because tumor burden does not account for distant disease, specific tumor cell phenotypes and biological processes are probably more important in determining metastatic disease.

Colonic Neoplasms↗
PubMedDate not supplied

Deployable teleradiology and telemedicine for the US military.

The US military has been an effective proponent of digital imaging and teleradiology for the past 15 years. A digital imaging network that can eliminate the use of X-ray film can make the requirements simpler for military medicine. X-ray film requires the storage of new, unexposed films that have a fixed shelf life, and the storage and use of chemicals and water for processing. In some deployed situations, the chemical discharge has to be collected and shipped out of the deployed area. The technology of electronic imaging is therefore intrinsically important to military medicine. In December of 1995, the US government started to deploy 20000 US troops to Bosnia-Herzegovina as part of NATO's peace keeping operation (IFOR). A full complement of medical support facilities was to be established in the Bosnia region and Hungary where the deployment was staged. Primetime III was a project to deploy telemedicine and teleradiology capabilities linking these medical treatment facilities (MTF). The deployment of telemedicine was not the responsibility of our engineering team. This paper deals with the deployable teleradiology (DEPRAD) system that was installed by the ISIS Center at a number of facilities for filmless radiology and teleradiology services.

Evaluation Studies as Topic↗