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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 127 records · Page 7Linked to original sources
PubMed1987

The value of colonoscopic surveillance after curative resection for colorectal cancer or synchronous adenomatous polyps.

Between 1975 and 1984, 270 patients underwent a potentially curative resection for colorectal carcinoma. One hundred eighty-eight patients (70%) underwent preoperative colonoscopy, of which 129 patients (69%) were followed up with at least two postoperative colonoscopies. In 91 patients (70%), preoperative colonoscopy revealed no synchronous adenomatous polyps or cancer. Synchronous adenomatous polyps were found in 35 patients (27%), and three patients (2.3%) had a synchronous invasive cancer. Nineteen (54%) of the 35 patients with synchronous adenomatous polyps developed metachronous adenomatous polyps during the follow-up period compared with 24 (26%) of 91 patients without synchronous adenomatous polyps. The median interval to the development of metachronous adenomatous polyps was 19 months, and all of these polyps were 1 cm or less in size. Patients with synchronous adenomatous polyps less than 30 cm from the primary lesion (68%) developed metachronous polyps more often than did patients whose synchronous adenomatous polyps were more than 30 cm from the primary lesion (37%). Preoperative colonoscopy is important for determining synchronous pathology and identifying patients at risk for metachronous polyps.

Adult↗
PubMed1987

Synchronous and metachronous colon lesions in squamous cell carcinoma of the anal canal.

The charts of 79 patients with a histologic diagnosis of squamous cell carcinoma of the anal canal were reviewed to determine the incidence of synchronous and/or metachronous colon lesions. Forty-six patients underwent an adequate preoperative evaluation of the colon and rectum. Ten patients underwent colonoscopy, 33 patients underwent a barium enema, and three patients underwent colonoscopy and a barium enema. In this group six adenomatous polyps and three hyperplastic polyps were discovered. An adenocarcinoma of the sigmoid colon was found in another patient six months prior to the diagnosis of a squamous cell carcinoma of the anal canal. Twenty-three patients had follow-up evaluation of the large bowel for metachronous lesions following treatment of the squamous cell carcinoma of the anal canal. Ten patients underwent colonoscopy, three patients had a barium enema, and ten autopsies were available for analysis. In this group metachronous lesions consisted of two adenomatous polyps and one hyperplastic polyp.

Adult↗
PubMed1987

Causes of death in patients with familial polyposis coli (FPC).

Autopsy reports from patients with familial polyposis coli were obtained from the Roswell Park Memorial Institute Registry as well as clinical data on patients with familial polyposis coli with regard to their causes of death. Although the latter group did not undergo autopsy they were the subject of a close follow-up. From this data it is clear that diagnosis at an early age may not diminish the chances of the patient with familial polyposis to develop cancer. Removal of the colonic mucosa does not provide absolute assurance that patients with this condition will be cured, as these patients remain at considerable risk for developing other benign and malignant lesions of the gastrointestinal tract and perhaps also of other organs. Close follow-up of FPC patients who have had surgery for colorectal polyps or cancer is necessary. Other proliferative abnormalities of FPC patients include an abnormal fibroblastic response, tendency to develop adhesions, and the propensity for developing desmoids. Desmoids may follow a slow but unrelenting course with a lethal outcome. Autopsy findings support the view that there should be no distinction between familial polyposis coli and Gardner's syndrome.

Adenomatous Polyposis Coli↗
PubMed1987

Phase I clinical trial of ethyl 6-deoxy-3,5-di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809).

A phase I study of single i.v. doses of a new sugar containing nitrosourea 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809, EDMN) has been carried out in 47 patients with advanced solid tumors. Nine dose levels between 200 and 4500 mg/m2 were examined. Nausea and vomiting were seen in most patients but were controlled with antiemetics. Myelosuppression was minimal. The dose-limiting toxicity was hepatotoxicity, occurring early (peak at days 2-4) and resolving rapidly. No cumulative toxicity was seen with an every 6 weeks schedule. Other toxicities were abdominal pain, diarrhea, arm pain, restlessness, and headache. Pharmacokinetic studies in 20 patients using an HPLC assay and in 5 patients using [14C]EDMN showed a short half-life, rapid plasma clearance, rapid metabolism, and minimal excretion of unchanged drug. There was one partial response in a patient with colon carcinoma. The recommended dose for phase II studies in 3750 mg/m2 every 6 weeks.

Adult↗
PubMed1987

Phase I clinical trial of recombinant human tumor necrosis factor.

A phase I and pharmacokinetic study of recombinant tumor necrosis factor (rH-TNF Asahi) was carried out in 29 patients, who received a total of 72 courses with doses ranging from 1 to 48 X 10(4) units/m2. Drug was given as 1-h i.v. infusions. Acute toxicities, taking the form of fever, chills, tachycardia, hypertension, peripheral cyanosis, nausea and vomiting, headache, chest tightness, low back pain, diarrhea and shortness of breath were seen, but were not dose-limiting or dose-related. Some early rise in SGOT, without any change in serum bilirubin, was noted at the highest doses. Eosinophilia, monocytosis, mild hypocalcemia and an increase in fibrin degradation products were seen in a few patients. The dose-limiting toxicity was hypotension, which occurred after the end of the drug infusion and was seen in all 5 patients treated at the highest dose. There was no mortality or long-term morbidity. There were no responses. Pharmacokinetic studies indicated a rapid plasma clearance and a short plasma half-life, generally less than 0.5 h.

Adult↗
PubMed1987

Phase I clinical trial of 1-(2-[2-(4-pyridyl)-2-imidazoline-1-yl]-ethyl)-3-(4-carboxy-phenyl) urea (CGP 15720A).

A phase I clinical trial of the intravenous administration of a novel pyridyl imidazoline ethyl carboxy phenyl urea was carried out in 42 patients with advanced solid tumors. Five schedules were evaluated: I, daily X 5; II, daily X 10; III, daily X 15; IV, continuous infusion for 5 days; V, continuous infusion for 7 days. Toxicity was not seen in schedule I (maximum dose 3 g/m2/day) and was minimal in schedule IV (6 g/m2/day). In schedule II it was seen at 2 and 3 g/m2/day, in schedule III at 2 g/m2/day and in schedule V at 6 g/m2/day. Dose-limiting toxicity consisted of a syndrome of lethargy and fatigue. There were no definitely drug-related changes in hematologic or serum chemistry parameters. No responses were seen, but relief of pain in three patients with prostate cancer was noted. Pharmacokinetics indicate a short half-life, limited volume of distribution, and rapid renal clearance. The recommended dose for phase II studies is 3 g/m2/day X 10 or 2 g/m2/day X 15 days.

Adult↗
PubMed1987

The value of routine preoperative urologic evaluation in patients with colorectal carcinoma.

Routine preoperative intravenous pyelography was performed in a series of 105 consecutive male patients with rectal or rectosigmoid carcinomas who were totally free of urinary symptoms. Abnormal findings were present in 26 percent of those patients. Postoperative intravenous pyelograms were performed in 61 patients. Twenty-one percent of patients with negative preoperative intravenous pyelograms and 42 percent of patients with positive preoperative intravenous pyelograms had abnormal findings in the postoperative intravenous pyelograms. Preoperative cystoscopy was performed in 52 patients. Thirty-one percent of patients with negative preoperative intravenous pyelograms and 76 percent of patients with positive preoperative intravenous pyelograms had abnormal cystoscopic findings. The overwhelming majority of cystoscopic findings in patients with negative preoperative intravenous pyelograms were not related to the primary tumor. The findings of this prospective study suggest that routine preoperative intravenous pyelography is indicated in patients with rectosigmoid or rectal tumors without symptoms related to the urinary tract. Postoperative intravenous pyelography is indicated only in patients with positive preoperative intravenous pyelograms. Preoperative cystoscopy is indicated when the preoperative intravenous pyelogram is positive and especially if intravenous pyelography findings are suggestive of bladder-wall defect or extrinsic pressure.

Colonic Neoplasms↗
PubMed1987

Follow-up colonoscopy in patients with colorectal adenomatous polyps.

Forty-four asymptomatic patients with adenomatous colorectal polyps were followed by repeated colonoscopies and subsequent removal of new polyps. The median follow-up time was 34 months (range, 4 to 131 months). Twenty-six patients (59 percent) developed new adenomatous polyps. The recurrence rate was 69 percent in patients with multiple polyps compared with 54 percent in patients with a single polyp. The location of new polyps was in the same colonic segment in 81 percent of the patients, but not at the same site in the colon where a previous polyp had been removed. The histopathology and size of new polyps compared with the initial polyps showed a significant improvement in histopathology toward more benign polyps (P less than 0.02) and smaller polyps (P less than 0.001). In patients who initially had single adenomatous polyps, new polyp(s) were diagnosed after a mean time of 23 months compared with 13.5 months in patients with two or more adenomatous polyps initially. Patients with atypia in initial polyp(s) developed new polyp(s) after a mean time of 11 months compared with 23 months in patients without atypia. The mean time from a colon with no polyps to the diagnosis of a new adenomatous polyp less than 5 mm in size was 11.5 months, which was a statistically significant shorter time than the 19.4 months observed for the development of polyps 5 mm or larger.

Adult↗
PubMed1987

The role of colonoscopy and flexible sigmoidoscopy in screening for colorectal carcinoma.

Six hundred thirty-two patients were referred to the Colorectal Clinic from February 1983 to February 1986 for screening with the Pentax 65 cm flexible sigmoidoscope. Forty-nine of these patients (8 percent) had adenomatous polyps. There were 27 males and 22 females. The mean distance examined by the 65 cm flexible sigmoidoscope was 55 cm. Five patients were excluded from analysis, leaving 44 patients who underwent colonoscopy to the cecum. At the time of colonoscopy, 15 of the 44 patients (34 percent) had one or more adenomatous polyps beyond reach of the 65 cm flexible sigmoidoscope. The remaining 29 patients who underwent colonoscopy had no polyps beyond reach of the 65 cm flexible sigmoidoscope. Thirty adenomatous polyps, one invasive carcinoma of the ascending colon, and one hyperplastic polyp were found in these 15 patients. In summary, 34 percent of patients found to have adenomatous polyps within reach of the 65 cm flexible sigmoidoscope harbored one or more adenomatous polyps in the proximal colon at the time of colonoscopy. A positive 65 cm flexible sigmoidoscope examination requires colonoscopy to identify and remove proximal premalignant lesions, thereby aborting the polyp-cancer sequence.

Colonic Neoplasms↗
PubMed1987

A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma.

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.

Adenocarcinoma↗
PubMed1987

A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia.

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.

Acute Disease↗
PubMed1987

Biochemical and pharmacologic basis for potentiation of 5-fluorouracil action by leucovorin.

In vitro and in vivo studies have been carried out in mouse and human tumors to investigate the biochemical and pharmacologic basis for the selectivity of 5-fluorouracil (FUra) action. Combination chemotherapy with FUra and thymidine was performed to determine the therapeutic relevance of 5-fluorouridine triphosphate (FUTP) incorporation into RNA. The results of these studies indicate that modulation of FUra cytotoxicity by deoxythymidine (dThd) did occur but failed to produce any significant therapeutic advantages in patients with advanced colorectal cancer. Modulation of FUra bioactivation via the deoxyribonucleotide pathway by coadministration of high-dose folinic acid resulted in enhanced therapeutic response rate of gastrointestinal tumor patients. This manuscript summarizes the preclinical and clinical findings on the metabolic modulation of FUra activity by dThd and folinic acid.

Animals↗
PubMed1987

Cellular interactions in hemopoiesis.

The role of immunocompetent cells in hemopoiesis remains controversial. We used an autologous system in which activated peripheral blood mononuclear cells (LAK) and interleukin-2 (IL-2) are administered to patients with cancer. We found little change in the numbers of circulating erythroid progenitors. Cocultures of these progenitors with LAK or supernatants lead to a decrease in the numbers of detectable burst forming units-erythroid (BFU-E) in culture. However, using an assay for burst promoting activity (BPA) we noted production of this hemopoietin by these LAK cells. We could not detect circulating levels of gamma interferon (IF). Variable levels were found in the LAK supernatants. We could not detect circulating eosinophil progenitors (CFU-Eo), but we did find evidence of production of a colony stimulating factor (CSF), which gave rise to a high number of eosinophil colonies in cultures of bone marrow. These results suggest that administration of LAK/IL-2 has potent effects on hemopoiesis and that these effects may emphasize the anemia and eosinophilia seen in patients receiving this therapy.

Anemia↗
PubMed1987

Increased cytotoxicity and CD16 (Leu 11) expression in long-term, IL-2-activated human peripheral blood mononuclear cells.

CD16 (Leu 11) positive cells are believed to be the effector cells for the so-called LAK phenomenon. Current evidence suggests that this cell population is comprised predominantly of IL-2-activated CD3 negative Leu 11+ NK cells and a minor proportion of Leu 11+ CD3+ MHC unrestricted type II cytotoxic T cells. The current study demonstrates a continuous increase in the frequency of Leu 11+ (and CD8+) cells and a decline of CD3 and CD4 positive cells during prolonged culture of human PMBL with high levels of rIL-2. Cytotoxicity also increases in this time period parallel with Leu 11 to a maximum of activity on the twelfth day of culture. This correlation suggests that the long-term activated killer cells generated in this period are Leu 11+, CD8+, CD3-, CD4- activated NK cells. With regard to tumor therapy, the long-term culture of PMBL in rIL-2 may be of advantage over short-term activation protocols. If the Leu 11+ cells are in fact the mediators of the therapeutic response, the long-term culture generates up to six times more effector cells. In addition, this method allows significant savings in the expense for leukophoresis, cell culture, and laboratory personnel. The efficacy of long-term, cultured rIL-2-activated Leu 11+ cells for tumor therapy is currently being investigated in clinical trails.

Antigens, Surface↗
PubMed1987

Biologic modulation of 5-fluorouracil with high-dose leucovorin and combination chemotherapy of 5-fluorouracil and cisplatin in metastatic colorectal adenocarcinoma.

The data from an ongoing 3-arm prospective study of 72 patients with advanced colorectal carcinoma is presented. The 3 regimens are as follows: Regime 1 (every 4 weeks)--5-fluorouracil (FUra) (450 mg/m2 iv bolus daily for 5 days, then 200 mg/m2 iv bolus every other day for 6 doses); regime 2 (every week for 4 weeks, then every other week)--methotrexate (MTX) (50 mg/m2 in a 4-hour infusion) followed by FUra (600 mg/m2 iv bolus); regime 3 (weekly for 6 weeks followed by a 2-week rest period)--D,L-leucovorin (D,L-CF) (500 mg/m2 in a 2-hour infusion) with FUra (600 mg/m2 iv bolus) 1 hour after the D,L-CF infusion began. All monitoring lesions except lung were documented by tissue biopsy. Thirteen of 18 patients in the FUra + D,L-CF arm were evaluable for response. Six of the 13 patients (46%) have had a partial response. The duration of the 6 responses has been 11, 8, 7, 4, 3 and 3 months. In patients with liver metastases as the monitoring lesion, a dramatic improvement in liver function tests has been seen during the first 2 courses (12 weeks) of treatment, but this was not sustained. The toxicity of FUra + D,L-CF was predominantly gastrointestinal; unlike with FUra alone, myelosuppression was not predominant.

Adenocarcinoma↗