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Biomedical subjects

A M Cohen

Publications and source records attributed to A M Cohen.

At least 19 recordsLinked to original sources

Reducing workload in systematic review preparation using automated citation classification.

OBJECTIVE: To determine whether automated classification of document citations can be useful in reducing the time spent by experts reviewing journal articles for inclusion in updating systematic reviews of drug class efficacy for treatment of disease. DESIGN: A test collection was built using the annotated reference files from 15 systematic drug class reviews. A voting perceptron-based automated citation classification system was constructed to classify each article as containing high-quality, drug class-specific evidence or not. Cross-validation experiments were performed to evaluate performance. MEASUREMENTS: Precision, recall, and F-measure were evaluated at a range of sample weightings. Work saved over sampling at 95% recall was used as the measure of value to the review process. RESULTS: A reduction in the number of articles needing manual review was found for 11 of the 15 drug review topics studied. For three of the topics, the reduction was 50% or greater. CONCLUSION: Automated document citation classification could be a useful tool in maintaining systematic reviews of the efficacy of drug therapy. Further work is needed to refine the classification system and determine the best manner to integrate the system into the production of systematic reviews.

Artificial Intelligence↗

Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts.

BACKGROUND: Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction. RESULTS: Performance was measured on a test set consisting of about 50,000 abstracts from one year of MEDLINE. Synonyms retrieved from curated genomics databases were used as a gold standard. The system obtained a maximum F-score of 22.21% (23.18% precision and 21.36% recall), with high efficiency in the use of seed pairs. CONCLUSION: The method performs comparably with other studied methods, does not rely on sophisticated named-entity recognition, and requires little initial seed knowledge.

Algorithms↗

Neuroendocrine carcinomas of the colon and rectum.

PURPOSE: This study was designed to review experience with neuroendocrine carcinomas of the colon and rectum at a single institution, with emphasis on the pathology and clinical characteristics of this uncommon malignancy. METHODS: A study group of patients was identified from a prospective colorectal service database. Pathology was reviewed and neuroendocrine tumors were classified by a single pathologist. Medical records were retrospectively reviewed. RESULTS: From March 1975 to September 1998, 38 patients with neuroendocrine carcinomas were identified from the colorectal service database comprising 6495 patients (0.6 percent). These neuroendocrine carcinomas did not include carcinoid tumors. Average patient age was 57 years (range, 29-86 years). There were 17 males (44.7 percent) and 21 females (55.3 percent). Tumors were located as follows: 17 colon, 14 rectum, 6 anal canal, and 1 appendix. The diagnosis of neuroendocrine carcinoma was suggested preoperatively from tissue biopsy in 59.3 percent (16/27) of patients evaluable. Pathology was reviewed and tumors were categorized as small cell carcinoma (n = 22) or large cell neuroendocrine carcinoma (n = 16). Most tumors (20/25 evaluable, 80 percent) stained positive by means of immunohistochemistry for neuroendocrine markers, including chromogranin (18/19), synaptophysin (10/15), and/or neuron-specific enolase (14/15). Metastatic disease was detected at the time of diagnosis in 69.4 percent of the patients (25/36). Tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer (AJCC) Stage I (n = 6), Stage III (n = 7), and Stage IV (n = 25) tumors. As a group, these tumors had a poor prognosis, with a median survival of 10.4 months. One-year, two-year, and three-year survival was 46 percent, 26 percent, and 13 percent, respectively. There was no significant difference in survival based on pathologic subtypes. Median follow-up time was 9.4 months (range, 0.6-263.7 months). CONCLUSIONS: Neuroendocrine carcinomas of the colon and rectum are uncommon, comprising less than 1 percent of colon and rectal cancers. Pathologically, these tumors are poorly differentiated carcinomas with distinctive cytoarchitectural features and are often immunoreactive for markers of neuroendocrine differentiation. The prognosis for high-grade neuroendocrine carcinomas is poor, as most patients have metastatic disease at the time of diagnosis.

Adult↗

On the mechanism of post-splenectomy leukocytosis in mice.

BACKGROUND: Increased number of peripheral white blood cells (PWBCs) has been noted after removal of the spleen. DESIGN: To clarify the possible mechanisms by which splenectomy affects the PWBC number, the percentage of apoptotic PWBCs, the number and migration rate of peritoneal cells, as well as the 3H-TdR incorporation into PWBCs, were examined in splenectomized, sham-operated and control mice. In addition, the effect of control plasma injected to splenectomized animals on the number of PWBCs was examined. RESULTS: One and two months after splenectomy the PWBC counts significantly increased, whereas the percentage of apoptotic PWBCs and the number of cells in the peritoneal cavity decreased in comparison with that of the control and sham-operated mice. Seventeen days after injection of carboxy-fluorescein diacetate succinimidyl ester (CFSE)-labelled peritoneal cells into the peritoneal cavity of the animals, their number was significantly higher in the peripheral blood and lower in the peritoneal cavity of the splenectomized animals in comparison with that of the control and sham-operated mice. Injection of control plasma into the splenectomized mice prevented the development of postsplenectomy leukocytosis. Finally, 3H-TdR incorporation into nonstimulated and Con A stimulated PBMCs from the splenectomized mice was higher as compared with cells from the control and sham-operated mice. CONCLUSIONS: The results of the study present several mechanisms that may clarify the cause of postsplenectomy leukocytosis.

Animals↗

Results after rectal cancer resection with in-continuity partial vaginectomy and total mesorectal excision.

BACKGROUND: Although sharp mesorectal excision reduces circumferential margin involvement and local recurrence, a concomitant partial vaginectomy may be required in women with locally advanced rectal cancer. METHODS: Sixty-four patients requiring a partial vaginectomy during resection of primary rectal cancer were identified. Survival was determined by the Kaplan-Meier method, and distributions were compared by the log-rank test. RESULTS: Locally advanced disease was reflected by presentation with malignant rectovaginal fistulae (n = 6) or cancers described as bulky or adherent/tethered to the rectovaginal septum (n = 32). Thirty-five patients received adjuvant radiation with or without chemotherapy. At a median follow-up of 22 months, 27 (42%) patients developed recurrent disease, with most of these occurring at distant sites. The 5-year overall survival was 46%, with a median survival of 44 months. The 2-year local recurrence-free survival was 84%. The crude local failure rate was 16% (10 of 64), and local recurrence was more common in patients with a positive as opposed to a negative microscopic margin (2 [50%] of 4 vs. 8 [13%] of 60, respectively). Positive nodal status had a significant effect on overall survival (P <.001). CONCLUSIONS: Partial vaginectomy is indicated for locally advanced rectal cancers involving the vagina. The results are most favorable in patients with negative surgical margins and node-negative disease.

Adult↗

Resection of locally recurrent colorectal cancer in the presence of distant metastases: can it be justified?

BACKGROUND: We aimed to determine the outcome of resections for local recurrence of colorectal carcinoma in the presence of distant (M1) disease. METHODS: Patients who underwent resection of local recurrence in the presence of potentially resectable M1 disease were identified from the colorectal database. Outcome was determined by chart review. RESULTS: Forty-two patients (23 men) of mean age 60 years (range, 34-88 years) underwent complete gross resection of their local recurrence in the presence of M1 disease. Thirteen of the 42 underwent synchronous M1 resections to render them free of gross disease (R0). Nine of the 29 patients who left with residual disease (R1) subsequently underwent staged M1 resection, so that 22 of 42 were rendered R0 by surgery. The median survival of all patients was 14.5 months (interquartile range, 6-30 months), and that of patients rendered R0 was 23 months (interquartile range, 10-37 months), in comparison with 7 months (interquartile range, 3-25 months) for those of R1 status (P =.006; log-rank method). Ability to achieve R0 status by synchronous or staged resection was the only factor predictive of survival. CONCLUSIONS: The presence of M1 disease per se should not preclude resection of local recurrence, although case selection is problematic.

Adult↗

Preoperative radiation with or without chemotherapy and full-thickness transanal excision for selected T2 and T3 distal rectal cancers.

BACKGROUND AND AIMS: To evaluate the clinical outcome of selected patients with distal rectal cancer treated by preoperative radiation with or without chemotherapy and full-thickness local excision (FTLE). PATIENTS AND METHODS: Ten patients with invasive distal rectal cancer (six T2, four T3) were treated with preoperative radiotherapy (3600-5040 cGy) with or without 5-fluorouracil based chemotherapy. FTLE was performed 4-6 weeks after completion of radiotherapy, primarily because of comorbid diseases or patient refusal of a permanent colostomy. Median follow-up was 28.5 months. RESULTS: There were no prolonged wound complications, and only one positive microscopic margin was detected. Among three cases of complete pathological response, two remain without evidence of disease. All patients retained sphincter function and avoided creation of a stoma. Two patients developed recurrence, one with widespread disease including pelvic recurrence 26 months after surgery and the other with distant disease only at 23 months. There were four deaths: two unrelated to cancer, one of undetermined cause after 7 years, and one after widespread recurrence at 26 months, with death 4 months later. Two-year actuarial survival was 78%. CONCLUSIONS: This pilot study demonstrates that preoperative radiotherapy and FTLE avoids major abdominal surgery yet facilitates sphincter preservation, excision with negative margins, and short-term local control in selected patients with distal rectal cancer.

Adenocarcinoma↗

Characterisation of global protein expression by two-dimensional electrophoresis and mass spectrometry: proteomics of Toxoplasma gondii.

The development of tools for the analysis of global gene expression is vital for the optimal exploitation of the data on parasite genomes that are now being generated in abundance. Recent advances in two-dimensional electrophoresis (2-DE), mass spectrometry and bioinformatics have greatly enhanced the possibilities for mapping and characterisation of protein populations. We have employed these developments in a proteomics approach for the analysis of proteins expressed in the tachyzoite stage of Toxoplasma gondii. Over 1000 polypeptides were reproducibly separated by high-resolution 2-DE using the pH ranges 4-7 and 6-11. Further separations using narrow range gels suggest that at least 3000-4000 polypeptides should be resolvable by 2-DE using multiple single pH unit gels. Mass spectrometry was used to characterise a variety of protein spots on the 2-DE gels. Peptide mass fingerprints, acquired by matrix-assisted laser desorption/ionisation-(MALDI) mass spectrometry, enabled unambiguous protein identifications to be made where full gene sequence information was available. However, interpretation of peptide mass fingerprint data using the T. gondii expressed sequence tag (EST) database was less reliable. Peptide fragmentation data, acquired by post-source decay mass spectrometry, proved a more successful strategy for the putative identification of proteins using the T. gondii EST database and protein databases from other organisms. In some instances, several protein spots appeared to be encoded by the same gene, indicating that post-translational modification and/or alternative splicing events may be a common feature of functional gene expression in T. gondii. The data demonstrate that proteomic analyses are now viable for T. gondii and other protozoa for which there are good EST databases, even in the absence of complete genome sequence. Moreover, proteomics is of great value in interpreting and annotating EST databases.

Animals↗

Classification of lymphoproliferative disorders by spectral imaging of the nucleus.

Spectral nuclear morphometry was used for the classification of lymphocytes in lymphoproliferative disorders. May-Grunwald-Giemsa-stained blood specimens were taken from thirty patients with infectious mononucleosis, non-Hodgkin lymphoma or chronic lymphocytic leukemia, and from ten healthy individuals. Blood specimens were analyzed by spectral imaging. Seventeen distinct spectra were collected into a spectral library and a distinct pseudo color was assigned to each one of them. The library was used to scan all the cells in the database and to create a spectrally classified image of each cell. The spectral map, per cell, reveals distinct spectral-response regions in each cellular compartment, via the distinct region colors. Computational analysis of the spectral maps allows for the objective quantification of a set of parameters, or features, representing the cell. The features used in this work include the area and perimeter of the nucleus, circularity, edginess and the spectral pattern. The analysis pursued showed that each class of cells is associated with a set of unique parameters. We conclude that spectral analysis combined with feature analysis provides significant information in the analysis of lymphoproliferative disorders and may serve as an additional tool for the histopathological evaluation of disease.

Cell Division↗

Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma.

PURPOSE: To determine the acute toxicity, outcome, and sphincter preservation rates in patients with clinically resectable uT3 adenocarcinoma of the rectum treated with preoperative combined modality therapy. METHODS AND MATERIALS: A total of 72 patients were treated from 12/90-7/98 with preoperative 50.4 Gy plus 2 cycles of concurrent 5-fluorouracil (5-FU) and leucovorin (LV) bolus daily x 5 followed by sharp or total mesorectal excision and 4 cycles of postoperative 5-FU and LV. RESULTS: Individual Grade 3+ toxicities during preoperative therapy included diarrhea, 11%; bowel movements, 9%; leukopenia, 18%; tenesmus, 1%; and thrombocytopenia, 1%. Total Grade 3+ toxicity was 28%. The pathologic complete response (CR) rate was 13%, and an additional 9% had a clinical CR for a total CR rate of 22%. Of the 35 patients who were judged clinically by their operating surgeon to require an abdominoperineal resection (APR) and were therefore treated with the goal of sphincter preservation, 89% were able to undergo sphincter-preserving surgery. Of the 21 patients eligible for analysis, 81% had good to excellent sphincter function. The 3-year actuarial patterns of failure were 2% local, 8% abdominal, and 13% distant. The 3-year actuarial survival was 95%. CONCLUSIONS: Our data confirm our preliminary reports of encouraging rates of acute toxicity, local control, survival, sphincter preservation and function with preoperative combined modality therapy. It is an alternative approach for the treatment of uT3 clinically resectable rectal cancer.

Adenocarcinoma↗

Impact of a surgeon-trained observer on accuracy of colorectal surgical site infection rates.

PURPOSE: The aims of this study were 1) to establish accurate and reproducible baseline surgical site infection rates for our department and 2) to identify risk factors associated with surgical site infection in patients undergoing surgery on a colorectal service. METHODS: Phase I--Surgical site infection grading between the surgeon-trainer and the observer-trainee was validated using a four-point scale for wound evaluation previously used by our institution. Phase II--Patients undergoing colorectal surgery were prospectively monitored. The observed surgical site infection rate was compared with morbidity and mortality reports. Patient and perioperative variables were analyzed for their effect on surgical site infection using the chi-squared test. Risk factors approaching significance on univariate analysis (P < 0.2) were entered into a multivariate stepwise logistic regression model. RESULTS: Concordance on surgical site infection grading between the surgeon-trainer and the observer-trainee improved from an initial 79 percent to 96 percent during the validation period. The surgeon-trained observer reported a surgical site infection rate of 7.2 percent vs. a morbidity and mortality reported rate of 3.3 percent. Among the variables examined, obesity and surgical procedure category were significantly associated with surgical site infection rates. The effect of prophylactic antibiotics and prior chemotherapy, radiation, or steroid therapy on surgical site infection rates approached significance. A logistic regression analysis incorporating these risk factors for surgical site infection accurately predicted infection status 93 percent of the time. CONCLUSION: Use of a surgeon-trained observer doubles the detection rate of postoperative surgical site infection. Accurate, prospective assessment identifies risk factors significantly associated with increased surgical site infection rates in colorectal surgical patients.

Aged↗

Abdominoperineal resection for rectal cancer at a specialty center.

PURPOSE: Although sphincter-preservation procedures have replaced abdominoperineal resection as the treatment of choice for rectal cancer, a subset of patients with rectal cancer will still require abdominoperineal resection. The use of adjuvant radiotherapy has been shown to reduce local recurrence, and combined modality therapy (chemoradiation) improves survival. Sharp mesorectal excision compared with the classic teaching of blunt retrorectal dissection is also an important component of local control. The primary aim of the present study was to evaluate the postoperative complications associated with neoadjuvant therapy in patients requiring complete rectal excision. Oncologic outcomes for all patients with abdominoperineal resection are also provided. METHODS: A prospective database of 5,634 patients who underwent surgery for colorectal cancer at Memorial Sloan-Kettering Cancer Center between the years 1987 and 1997 was reviewed. Patients with primary adenocarcinoma of the rectum who underwent abdominoperineal resection were identified. In 1,622 patients who were operated on for primary rectal cancer, 292 patients (18 percent) underwent abdominoperineal resection and the rest had a sphincter-preserving procedure. Ten patients were excluded from the study because of prior pelvic irradiation for other cancer (8 patients) and insufficient radiation dose (<4,000 cGy; 2 patients). Neoadjuvant radiotherapy was given to 123 patients and postoperative adjuvant radiotherapy to 65 patients, whereas 94 did not receive radiotherapy. Intraoperative radiotherapy combined with preoperative radiotherapy was administered to 23 of the 123 patients given neoadjuvant radiotherapy. RESULTS: The duration of the operation was significantly longer in both neoadjuvant radiotherapy and intraoperative radiotherapy groups compared with the nonradiotherapy group (P = 0.01 and P < 0.0001, respectively). Estimated blood loss, mean number of blood units transfused per patient, and the percentage of patients being transfused were similar among the groups. Early postoperative complications were significantly higher in the neoadjuvant radiotherapy groups compared with the nonradiotherapy group. Late complications, overall survival, disease-free survival, and local recurrence were not significantly different among the groups. CONCLUSIONS: In patients with cancer of the lower one-third of the rectum, sharp pelvic dissection can result in a low rate of local recurrence even without radiotherapy. The role of preoperative radiotherapy, although associated with higher perineal wound complications, is important in increasing resectability and sphincter-preservation rate. Randomized, prospective trials will be needed to establish the role of adjuvant radiotherapy in patients undergoing sharp mesorectal excision for rectal cancer.

Abdomen↗

Waldenström's macroglobulinemia associated with AA amyloidosis.

It is widely accepted that amyloidosis in Waldenström's macroglobulinemia (WM) is exclusively due to amyloid light-chain deposition. However, only a small number of previous reports have actually characterized the type of amyloid in WM. We now report the third patient with WM and amyloid A protein (AA) amyloidosis. This patient developed malabsorption, nephrotic syndrome, and orthostatic hypotension. AA was immunohistochemically demonstrated in the rectal biopsy. In conjunction with previous examples of AA amyloidosis, the present report raises the possibility that AA amyloidosis may also occur in WM patients.

Aged↗

The effect of different oil spill remediation techniques on petroleum hydrocarbon elimination in Australian bass (Macquaria novemaculeata).

Petroleum hydrocarbons were investigated in juvenile Australian bass, Macquaria novemaculeata, following exposure to the water accommodated fraction (WAF) of Bass Strait crude oil, chemically dispersed crude oil, and burnt crude oil. Each treatment was administered for 16 days either through the water column or through the diet (amphipod, Allorchestes compressa). Polycyclic aromatic hydrocarbon (PAH) elimination was determined by measuring biliary benzo(a)pyrene (B(a)P) and naphthalene-type metabolites. Biliary PAH-type metabolite concentrations varied with the type of oil spill remediation technique, route of exposure (food versus water), and exposure concentration. Fish exposed to chemically dispersed crude oil via the water exhibited the highest PAH-type biliary metabolite concentrations, relative to fish exposed to other treatments. In fish exposed via the diet, the highest concentration of both types of biliary metabolites also appeared in the dispersed oil-exposed individuals. The results suggest that chemically dispersing oil may have the greatest effect on bioavailability of hydrocarbons, both through waterborne and food chain exposures.

Animals↗

Surgical debulking and intraperitoneal chemotherapy for established peritoneal metastases from colon and appendix cancer.

BACKGROUND: Aggressive treatment of peritoneal metastases from colon cancer by surgical cytoreduction and infusional intraperitoneal (IP) chemotherapy may benefit selected patients. We reviewed our institutional experience to assess patient selection, complications, and outcome. METHODS: Patients having surgical debulking and IP 5-fluoro-2'-deoxyuridine (FUDR) plus leucovorin (LV) for peritoneal metastases from 1987 to 1999 were evaluated retrospectively. RESULTS: There were 64 patients with a mean age of 50 years. Primary tumor sites were 47 in the colon and 17 in the appendix. Peritoneal metastases were synchronous in 48 patients and metachronous in 16 patients. Patients received IP FUDR (1000 mg/m2 daily for 3 days) and IP leucovorin (240 mg/m2) with a median cycle number of 4 (range, 1-28). The median number of complications was 1 (range, 0-5), with no treatment related mortality. Only six patients (9%) required termination of IP chemotherapy because of complications. The median follow-up was 17 months (range, 0-132 months). The median survival was 34 months (range, 2-132); 5-year survival was 28%. Lymph node status, tumor grade, and interval to peritoneal metastasis were not statistically significant prognostic factors for survival. Complete tumor resection was significant on multivariate analysis (P = .04), with a 5-year survival of 54% for complete (n = 19) and 16% for incomplete (n = 45) resection. CONCLUSIONS: Surgical debulking and IP FUDR for peritoneal metastases from colon cancer can be accomplished safely and has yielded an overall 5-year survival of 28%. Complete resection is associated with improved survival (54% at 5 years) and is the most important prognostic indicator.

Adenocarcinoma↗