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Biomedical subjects

M Cibull

Publications and source records attributed to M Cibull.

9 recordsLinked to original sources
PubMed2006

Primary appendiceal cancer: gynecologic manifestations and treatment options.

OBJECTIVE: To determine the presenting symptoms, gynecologic manifestations, and optimal intraoperative management of women with primary appendiceal cancer. METHODS: A multi-institutional investigation was performed to identify female patients with primary appendiceal cancer who were treated from 1990 to present. RESULTS: Forty-eight women with primary appendiceal cancer were identified from the tumor registries of participating institutions. The most common symptoms were abdominal pain (40%) and bloating (23%), but only 8% experienced rectal bleeding. Serum CEA was elevated (>2.5 U/ml) in 67% of patients, and serum Ca-125 was elevated (>35 U/ml) in 50% of patients. Thirty-one patients (65%) presented with a right adnexal or right lower quadrant mass and were operated on initially by a gynecologic oncologist. Ovarian involvement by metastatic appendiceal cancer was documented in 18 patients (38%). All of these patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging, but only 8 had a right hemicolectomy at the time of initial surgery. Forty-one patients (85%) presented with advanced stage appendiceal cancer (Stage III or IV) and 19 patients (46%) received postoperative chemotherapy, most commonly with a combination of 5-FU/Leukovorin. Following surgery, 22 patients (46%) experienced disease progression or recurrence, and 14 have died of disease. The most common sites of recurrence were abdominal or pelvic peritoneum (18), colon (2), and ovary (2). Patient survival was 70% at 2 years, and 60% at 5 years. CONCLUSION: Women with primary appendiceal cancer frequently present with ovarian metastases, and initial surgical intervention is often performed by a gynecologic oncologist. All patients with mucinous epithelial ovarian cancer should undergo appendectomy at the time of surgical staging. The appendix should be examined intraoperatively, and if appendiceal carcinoma is identified, a right hemicolectomy and appropriate surgical staging should be considered.

Adult↗
PubMed2005

The efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC).

OBJECTIVE: To determine the efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC). METHODS: A retrospective multi-institutional investigation was performed to identify surgically staged patients with Stage I UPSC who were (1) treated after surgery with 3-6 courses of platinum-based chemotherapy without radiation from 1990-2003, and (2) followed for a minimum of 12 months, or until recurrence. RESULTS: Six patients (IA-2, IB-3, IC-1) were treated with carboplatin (AUC 6) or cisplatin (50 mg/m2) alone. One patient recurred to the vagina, was treated with chemo-radiation, and is alive and well at 122 months. One patient recurred to the lung, liver, and brain, and died of disease at 24 months. The remaining 4 patients are alive with no evidence of disease 15-124 months (mean 62 months) after treatment. Two patients (IB-1, IC-1) were treated with cisplatin (50 mg/m2) and cyclophosphamide (1000 mg/m2), and both are alive and well with no evidence of disease 75 and 168 months after treatment. Twenty-one patients (IA-5, IB-13, IC-3) were treated with a combination of carboplatin (AUC 6) and paclitaxel (135 mg/m2-175 mg/m2). One patient recurred to the vagina after 3 cycles of carboplatin/paclitaxel, and was treated with chemo-radiation. She is now without evidence of disease 10 months after treatment. At present, all 21 patients with Stage I UPSC treated following surgical staging with carboplatin/paclitaxel chemotherapy are alive and well with no evidence of disease 10-138 months (mean 41 months) after treatment. CONCLUSION: Combination carboplatin/paclitaxel chemotherapy following surgery is effective in the treatment of Stage I UPSC.

Aged↗
PubMed1998

Thyroid lymphoma: is there a role for surgery?

The role of surgery in the treatment of Stage I and II non-Hodgkin's thyroid lymphoma (NHTL) is not well defined. At our institution, we have treated seven patients (six women and one man) with NHTL during the past 6 years. Three patients (43%) had a prior history of thyroid disease, usually lymphocytic thyroiditis. Clinical symptoms included a rapidly enlarging neck mass (86%), dysphagia (71%), dyspnea (71%), and hoarseness (71%). Five patients (71%) had hypothyroidism; one patient, hyperthyroidism; and one patient, normal thyroid function. Five patients underwent fine-needle aspiration (FNA) at our institution. In three instances, FNA results were indicative of NHTL; the remaining FNA tests yielded no diagnosis. Surgical procedures were varied: incisional biopsy (n = 4), limited tumor debulking with tracheostomy (n = 2), and thyroidectomy (n = 1). Each of the seven patients was found to have large cell lymphoma. Treatment consisted of combination chemotherapy with consolidative irradiation. All tumors dramatically decreased in size soon after the initiation of therapy. One patient refused radiotherapy. All patients except one are still alive (median follow-up, 24 months). In conclusion, 1) a diagnosis of NHTL, although rare, should be considered when patients have rapidly growing goiters; 2) FNA is a useful first step in diagnosing NHTL; 3) NHTL is exquisitely sensitive to both chemotherapy and radiation; 4) surgical intervention is generally confined to incisional biopsy with occasional limited pretracheal tumor debulking; and 5) when a biopsy is obtained from a patient suspected of having NHTL, immediate processing by the pathologist is recommended so that material can be obtained for special studies as needed.

Aged↗
PubMed1993

Acetaminophen hepatotoxicity: influence of phenobarbital and beta-naphthoflavone treatment in obese and lean Zucker rats.

The effect of phenobarbital (PB) and beta-naphthoflavone (beta-NF) on acetaminophen (APAP)-induced hepatotoxicity was evaluated in obese and lean Zucker rats. In addition, the consequences of APAP overdose on hepatic CYP2B1/2B2 enzyme activities following PB treatment were assessed. A single oral dose of APAP 3 g/kg (total body weight) was administered to both littermates 24 hr after the last dose of PB or beta-NF. Histologic evidence of hepatocellular necrosis and serum hepatic aminotransferase enzymes 48 hr after APAP administration was utilized to evaluate hepatic damage. Hepatic microsomal total cytochrome P450 concentrations, alkoxyresorufin O-dealkylase activities, and 16 beta-testosterone hydroxylase activities were determined to evaluate the effect of APAP overdose on cytochrome P450 enzyme-substrate activities in the presence and absence of PB treatment. APAP overdose produced lower hepatotoxicity in the obese Zucker rat compared to lean controls. A similar trend was observed in animals treated with PB prior to APAP administration. In contrast, beta-NF treatment produced potentiation of APAP toxicity and/or death of both obese and lean Zucker rats. Generally, APAP overdose produced reduction of hepatic cytochrome P450 enzyme-substrate activities. However, obese Zucker rats retained a higher percentage of their pre-APAP-treated enzyme activities which is consistent with the observation that obese Zucker rats are less affected by the hepatotoxic effects of APAP overdosage.

Acetaminophen↗
PubMed1990

Human recombinant interleukin-2 provokes acute pulmonary vascular endothelial injury in rabbits.

Human recombinant interleukin-2 (rIL-2), with or without lymphokine-activated killer cells, has been shown to mediate tumor regressions in animals and in humans. A well-recognized adverse effect of rIL-2 is the development of a generalized vascular leak syndrome that involves the pulmonary microvasculature. We present a rabbit model for the study of rIL-2 pulmonary toxicity that closely reflects the human situation. Rabbits were treated with rIL-2 (Cetus) by two dose/schedule schemata. Separate control groups received rIL-2 excipient (Cetus) or 5% dextrose in water (D5W). In a short-term model, animals were treated with 10(6) Cetus units of rIL-2 in five bolus injections of 200,000 Cetus units each. In a long-term model, rabbits were treated with 3 (x) 10(6) Cetus units/kg of rIL-2 daily in three divided doses every 8 h for 9-11 doses (a schedule analogous to one used in human trials). Following treatment, animals were killed and examined for evidence of pulmonary toxicity. Among the treatment and control groups, there was no evidence of pulmonary leukostasis as determined by mean alveolar septal wall granulocytes per high power field or mean lung myeloperoxidase activity per gram of tissue. While there were no differences among the three treatment groups with regard to pulmonary edema formation (wet/dry weights), there was a tendency toward statistically significant differences between the rIL-2 and control groups. Pulmonary vascular permeability was assessed using i.v.-administered [125I]rabbit serum albumin (RSA) and expressed as mean bronchoalveolar lavage fluid/plasma [125I]RSA ratios. The rIL-2-treated animals had significantly increased pulmonary extravasation of [125I]RSA compared to controls, but there were no differences between the excipient- and D5W-treated controls. Lungs from rIL-2-treated (but not controls) animals displayed marked ultrastructural changes by electron microscopy in the arteriolar segment to include intracellular and subcellular blebs throughout the arteriole with separation of endothelial cells from basement membrane, interstitial edema, endothelial adhesion, and transmigration of lymphocytes into interstitium. Immunoperoxidase stains using an antirabbit T-cell monoclonal antibody demonstrated significant T-cell infiltration into the pulmonary interstitium of rIL-2-treated animals compared to controls. The long-term treatment model described appears to be highly suited for studies of rIL-2-induced pulmonary toxicity.

Animals↗
PubMed1989

Effects of coumarin (1,2-benzopyrone) and cimetidine on peripheral blood lymphocytes, natural killer cells, and monocytes in patients with advanced malignancies.

The combination of coumarin and cimetidine has yielded objective tumor regressions in patients with metastatic renal cell carcinoma and malignant melanoma. While the mechanism of action of cimetidine appears to be immunomodulatory, coumarin appears to have direct effects on tumor cells as well as immunomodulatory activity. We utilized monoclonal antibody labeling techniques to monitor peripheral blood lymphocyte, natural killer (NK) cell, and monocyte phenotypes in patients treated with coumarin and cimetidine. Patients received coumarin 100 mg orally daily for 14 days; on day 15 cimetidine 300 mg four times daily was added and both drugs were continued until disease progression. Studies were performed pre treatment and at 2, 4, and 8 weeks on therapy. There were no alterations in T-cells, helper/inducer T-cells, cytotoxic/suppressor T-cells, B-cells, Ia + lymphocytes, or NK cells. However, an increase was noted by 2 weeks on therapy in the percentage of monocytes and the percentage of DR+ monocytes. This change in the monocyte population occurred in the presence of coumarin alone, before the institution of cimetidine. While this treatment appears to increase DR expression by monocytes, further studies with larger numbers of patients are needed to determine if this observed change is related to antitumor response.

Adult↗
PubMed1987

Phenobarbital induction and acetaminophen hepatotoxicity: resistance in the obese Zucker rodent.

The obese Zucker rodent appears to lack a significant induction response after phenobarbital pretreatment. Induction of the hepatic cytochrome P-450 system with phenobarbital is known to enhance acetaminophen hepatotoxicity. The purpose of this study was to evaluate the influence of phenobarbital enzyme induction on acetaminophen hepatotoxicity in the obese and lean Zucker rodent. A preliminary study was performed evaluating the pharmacokinetics of acetaminophen in both the obese and lean Zucker rats. Data were utilized to calculate appropriate loading doses of acetaminophen during the subsequent hepatotoxicity study. Phenobarbital enzyme-inducing regimens were administered p.o. to achieve similar steady-state phenobarbital plasma concentrations. Control rats received appropriate placebo solutions. Serum hepatic transaminase enzymes and histologic evidence of hepatocellular necrosis were utilized to evaluate hepatic damage after p.o. administration of 1300 mg of acetaminophen to both obese and lean Zucker rats. Obese Zucker control animals had approximately 2.5 times the total hepatic glutathione content compared to their lean control (164.9 +/- 43.2 vs. 65.3 +/- 18.4 mumol/whole liver). Obese Zucker animals receiving only acetaminophen showed a trend toward a reduced incidence of hepatocellular necrosis compared to similarly treated lean littermates. Obese Zucker rodents pretreated with phenobarbital had an even more pronounced resistance to acetaminophen-induced hepatocellular necrosis (P less than .01) when compared to similarly treated lean littermates. Thus, acetaminophen hepatotoxicity is reduced in the obese Zucker rat and pretreatment with phenobarbital offers further protection against hepatocellular damage. We suggest that the previously unrecognized increase in hepatic glutathione plays a major role in the resistance of the obese Zucker rat to acetaminophen hepatotoxicity.

Acetaminophen↗
PubMed1986

Evaluation of a new enzyme-linked immunoassay for terminal deoxynucleotidyl transferase in haematologic malignancies.

We have evaluated a new solid phase enzyme immunoassay (EIA) for detection of terminal deoxynucleotidyl transferase (TDT). The EIA is greater than 100 times more sensitive than previously used tests for enzyme activity. In 284 clinical specimens of human peripheral blood and bone marrow, the EIA detected TdT antigen in 97% of peripheral blood and 100% of bone marrow samples that were positive for enzymatic activity. The excellent sensitivity and specificity of this new test suggests that it can be used in clinical situations where quantitative TdT measurements are desired.

Antigens↗