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Biomedical subjects

M L Pearl

Publications and source records attributed to M L Pearl.

At least 19 recordsLinked to original sources
PubMed2000

Identification of tamoxifen-DNA adducts in the endometrium of women treated with tamoxifen.

The risk of developing endometrial cancer increases significantly for women treated with tamoxifen (TAM); the present study was designed to investigate the mechanism of this carcinogenic effect. Endometrial tissue was obtained from 16 women treated for varying lengths of time with TAM and from 15 untreated control subjects. DNA was analyzed with a (32)P-post-labeling/HPLC on-line monitoring assay capable of detecting 2.5 adducts/10(10) nucleotides. Using this sensitive and specific assay, TAM-DNA adducts were detected in eight women. The major adducts found were trans and cis epimers of alpha-(N(2)-deoxyguanosinyl) tamoxifen (dG-N(2)-TAM); levels ranged between 0.2-12 and 1.6-8.3 adducts/10(8) nucleotides, respectively. There was marked inter-individual variation in the relative amounts of cis and trans adducts present. Low levels (0.74-1.1 adducts/10(8) nucleotides) of trans and cis forms of dG-N(2)-TAM N-oxide were detected in one patient. DNA adducts derived from 4-hydroxytamoxifen quinone methide were not observed. We conclude from this analysis that trans and cis dG-N(2)-TAMs accumulate in significant amounts in the endometrium of many, but not all, women treated with this drug. The level of adducts found, coupled with the previous demonstration of their mutagenicity [Cancer Res., 59, 2091, 1999], suggest that a genotoxic mechanism may be responsible for TAM-induced endometrial cancer.

Adult↗
PubMed2000

Panniculectomy in morbidly obese gynecologic oncology patients.

BACKGROUND: It is clear that morbid obesity presents a serious risk to women undergoing major intra-abdominal gynecologic surgery. Unfortunately, many gynecologic malignancies and benign conditions are best treated surgically. Thus, the gynecologic surgeon must choose an incision that permits adequate exposure with acceptables rates of complications. Panniculectomy as an approach to the peritoneal cavity is becoming increasingly popular. Recent reports suggest that panniculectomy is reasonably straightforward to perform, provides adequate exposure and is associated with an acceptable rate of manageable complications. In these circumstances, panniculectomy is not a cosmetic procedure, but medically necessary to perform indicated major gynecologic intra-abdominal surgery. AIMS: To present our experience with panniculectomy in morbidly obese women undergoing major intra-abdominal surgery on a gynecologic oncology service. METHODS: The medical records of 48 morbidly obese women (Quetelet Index > 40 kg/m2) with a large dependent pannus who underwent major intra-abdominal surgery via a panniculectomy between May 1990 and October 1999 were reviewed. Data regarding demographics, concomitant medical conditions, operative indications and results, and postoperative outcomes were abstracted for analysis. RESULTS: The mean age was 54.9 years, the mean body mass was 130.2 kg, the mean height was 1.63 m and the mean Quetelet Index was 49.3 kg/m2. The mean operating time was 188 min and the mean estimated blood loss was 615 ml. Two patients suffered intraoperative urologic injuries which were repaired without sequelae; there were no bowel, vascular or neurologic injuries. Eighteen patients had a suprafascial wound breakdown (3 complete and 15 superficial) and 15 patients developed an infection. There were no documented deep venous thromboses, pulmonary emboli or fascial dehiscences. Two patients died in the postoperative period; one from a myocardial infarction on Day 2 and one from overwhelming sepsis on Day 76. CONCLUSIONS: Morbid obesity is associated with substantial operative and postoperative risks. Panniculectomy provides operative exposure with acceptable risks of complications.

Abdominal Wall↗
PubMed1999

Tamoxifen-DNA adducts detected in the endometrium of women treated with tamoxifen.

Women treated for breast cancer with tamoxifen are at increased risk of developing endometrial cancer. This carcinogenic effect has been attributed to estrogenic stimulation and/or to a genotoxic effect of this drug. To examine genotoxicity, we developed a (32)P-postlabeling TLCL/HPLC procedure for quantitative analysis of tamoxifen-DNA adducts in endometrial tissue. This assay is several orders of magnitude more sensitive than those previously used for this purpose; with it, we can detect five tamoxifen-DNA adducts in 10(11) bases. Endometrial tissue was obtained from women undergoing tamoxifen therapy and from untreated control subjects. DNA adducts, identified as trans and cis epimers of alpha-(N(2)-deoxyguanosinyl)tamoxifen, were detected in six of thirteen patients in the tamoxifen-treated group. Levels of trans and cis adducts ranged from 0.5 to 8.3 and from 0.4 to 4.8 adducts/10(8) nucleotides, respectively. Tamoxifen-DNA adducts were not detected in endometrial tissue obtained from the control subjects. We conclude from this study that one or more tamoxifen metabolites react with endometrial DNA to form covalent adducts, establishing the potential genotoxicity of this drug for women and suggesting the use of TAM-DNA adducts as biomarkers for investigations of tamoxifen-induced endometrial cancer.

Antineoplastic Agents↗
PubMed1999

Transcutaneous electrical nerve stimulation as an adjunct for controlling chemotherapy-induced nausea and vomiting in gynecologic oncology patients.

BACKGROUND: To evaluate the efficacy of a miniaturized portable transcutaneous electrical nerve stimulation (TENS) unit (ReliefBand) as an adjunct to standard antiemetic therapy for controlling nausea and vomiting induced by cisplatin-based chemotherapy in gynecologic oncology patients. METHODS: Forty-two patients were enrolled in a randomized, double-blind, placebo-controlled parallel-subjects trial with a follow-up crossover trial. All patients received a standardized antiemetic protocol, then wore the ReliefBand continuously for 7 days. RESULTS: Thirty-two patients were evaluable for the parallel-subjects component, 16 in each group. The percentage of patients with absent or minimal nausea was 59% overall, which was similar to that for both the active (56%) and placebo (62%) groups. The incidence and severity of nausea and vomiting was similar for each group. Eighteen patients completed two consecutive cycles and were evaluable for the crossover component. The average age of the crossover patients and their dose intensity were comparable with those of the overall study population (56.3 versus 58.6 years and 22.7 versus 22.7 mg/m2/week, respectively). The percentage of cycles with absent or minimal nausea was 47% overall, which was similar to that of the active (50%) and placebo (44%) cycles. However, the severity of nausea was significantly lower in the active cycles during days 2 to 4. Patients averaged less than one episode of vomiting daily in each cycle. CONCLUSIONS: The ReliefBand is an effective adjunct to standard antiemetic agents for controlling nausea induced by cisplatin-based chemotherapy in gynecologic oncology patients.

Antiemetics↗
PubMed1999

Geometric analysis of commonly used prosthetic systems for proximal humeral replacement.

BACKGROUND: The anatomy of the proximal part of the humerus is extremely variable. The extent to which existing prosthetic systems and operative technique allow replication of this variability has not been established. METHODS: Four commonly used press-fit prosthetic systems for shoulder arthroplasty were compared with respect to their ability to match the superior-inferior and medial-lateral dimensions of the articular surface in twenty-one cadaveric humeri. The comparisons were accomplished with a computer optimization algorithm that searched a database of prosthetic geometry and selected the best match to the original anatomy. The algorithm assumed an osteotomy of the humeral head at an angle equivalent to the stem-head angle of the prosthesis, without violation of the greater tuberosity or the metaphyseal bone. The best match was defined as the prosthetic combination (stem and head) that least displaced the center of rotation and the articular surface, with both factors weighted equally. RESULTS: None of the prosthetic systems that were evaluated allowed identical replication of the articular surface. Rather, they displaced the center of rotation a mean of 14.7 millimeters (range, 3.3 to 31.4 millimeters) from its original position. To reach this minimized displacement, the prosthetic combinations that were selected by the algorithm also resulted in a mean diminution of the arc of the articular surface (a smaller head size) of 26 degrees (range, 11 to 41 degrees). In every instance, the selected prosthesis imposed a superior and lateral shift of the center of rotation that in effect shifted a smaller prosthetic humeral head up the slope of the humeral osteotomy. CONCLUSIONS: Press-fit prosthetic systems for shoulder arthroplasty that are commonly used necessitate marked alterations of the original anatomy. To the extent that a shoulder arthroplasty is an attempt to reproduce the normal anatomy, these findings have profound implications for operative technique and future prosthetic design. CLINICAL RELEVANCE: We believe that the superior position of the prosthetic head predicted by the present study plays a role in late complications of shoulder arthroplasty, such as rotator cuff tendinopathy, superior humeral migration, and loosening of the glenoid component.

Aged↗
PubMed1998

A randomized controlled trial of early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery.

OBJECTIVE: To evaluate the safety and efficacy of early oral feeding after intra-abdominal surgery in gynecologic oncology patients. METHODS: During a 1-year period, 200 gynecologic oncology patients undergoing intra-abdominal surgery were enrolled in a randomized controlled trial of early compared with traditional oral postoperative feeding. Patients allocated to early postoperative oral feeding began a clear liquid diet on the first postoperative day and then advanced to a regular diet as tolerated. Patients allocated to traditional postoperative oral feeding received nothing by mouth until return of bowel function (defined as the passage of flatus in the absence of vomiting or abdominal distention), then began a clear liquid diet, and advanced to a regular diet as tolerated. RESULTS: Age, case distribution, surgery length, blood loss, and first passage of flatus were similar in the early and traditional feeding groups. Significantly more patients in the early group developed nausea. Despite this, the incidence of vomiting, abdominal distention, incidence and duration of nasogastric tube use, and percentage of patients who tolerated clear liquid and regular diets on the first attempt were comparable in both groups. Time to development of bowel sounds, time to initiation of clear liquid and regular diets, and hospital stay were significantly longer in the traditional group. Major complications (eg, pneumonia, atelectasis, and wound complications) and febrile morbidity occurred equally in both groups. There were no known anastamotic complications or aspirations in either group. Postoperative changes in hematologic indices and electrolytes were comparable in both groups. CONCLUSION: Early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery is safe and well tolerated.

Abdomen↗
PubMed1998

Panniculectomy and supraumbilical vertical midline incisions in morbidly obese gynecologic oncology patients.

BACKGROUND: We reviewed the outcomes of panniculectomy and supraumbilical vertical midline incisions in morbidly obese women undergoing gynecologic operations. STUDY DESIGN: Medical records were reviewed for 62 morbidly obese women with a large dependent pannus who underwent gynecologic operations on the Gynecologic Oncology Service at the State University of New York at Stony Brook between May 1990 and July 1997. Thirty-five patients underwent panniculectomy and 27 had a supraumbilical vertical midline incision, forming the study groups. The patient charts were abstracted for demographic, perioperative, and postoperative data. RESULTS: For the entire study population, the average age was 56 years, the mean body mass was 128.6 kg, and the mean Quetelet Index was 48.3 kg/m2. The mean operative time and estimated blood loss were similar for both groups. Eight percent of the patients had urologic injuries, evenly distributed between the groups. Postoperative infections, wound breakdowns, and hospital stay were greater for the panniculectomy group than for the supraumbilical vertical midline incision group (p < 0.05). Uniform use of subcutaneous closed-suction drains (since 1995) was associated with a significant reduction in the incidence of wound breakdowns and a shorter hospital stay in the panniculectomy group. CONCLUSIONS: Panniculectomy and supraumbilical vertical midline incision provide reasonable peritoneal access with acceptable rates of postoperative complications for morbidly obese women undergoing gynecologic operations.

Abdominal Muscles↗
PubMed1998

Glenoid deformity secondary to brachial plexus birth palsy.

The association between internal rotation contracture secondary to brachial plexus birth palsy and deformity and posterior dislocation of the glenohumeral joint has been known for a long time. The precise nature of these deformities and their pathogenesis, however, remain unclear. Twenty-five children, ranging in age from 1.5 to 13.5 years, had an operation to release an internal rotation contracture secondary to brachial plexus birth palsy; eleven had a latissimus dorsi transfer to augment external rotation power as well. Arthrograms were made intraoperatively in order to clarify the pathological changes that occur in the glenohumeral joint during growth in patients who have this condition. Seven children had a concentric glenohumeral joint (the humeral head was well centered in the glenoid fossa). The remaining eighteen children (72 per cent) had a deformity of the posterior aspect of the glenoid. Five of these children had flattening of the posterior aspect of the glenoid, seven had a biconcave glenoid with the humeral head articulating with the posterior of the two concavities, and six had a so-called pseudoglenoid (the most severe deformity, in which the humeral head articulated with a distinct, retroverted, posterior articular surface). Internal rotation contracture secondary to brachial plexus birth palsy may lead to glenoid deformity that is severely advanced by the time that the child is two years old. In patients who have such a contracture, we recommend early imaging of the shoulder with arthrography or some other modality to allow visualization of the skeletally immature glenohumeral joint.

Adolescent↗
PubMed1997

The utility of pretreatment barium enema in women with endometrial carcinoma.

OBJECTIVE: The objective of this study was to assess the clinical utility of a pretreatment barium enema in women with endometrial cancer. METHODS: The medical records of 249 patients with endometrial cancer who underwent a pretreatment barium enema were retrospectively reviewed. The patients' charts were abstracted for demographic information, stage, grade, histology, current disease status, and barium enema results. RESULTS: The pretreatment barium enema was normal in 122 (49%) patients. Diverticulosis was the most common abnormality, reported in 112 (45%) patients. Apparent intraluminal abnormalities were found in 15 (6.0%) patients. Each of these patients underwent colonoscopy prior to treatment for endometrial carcinoma. During colonoscopy, benign colonic polyps were removed from 11 (4.4%) patients. Primary colonic adenocarcinoma was discovered in polypoid lesions removed from 2 (0.8%) patients. Significant luminal narrowing from extrinsic lesions was noted in 2 (0.8%) patients, one at the rectosigmoid and the other at the cecum. No patient was found to have colonic mucosal involvement by endometrial cancer. CONCLUSION: The results of this study do not justify routine pretreatment barium enema to assess the colonic mucosa for metastatic involvement by endometrial cancer or as a screening tool for colorectal cancer in women with endometrial cancer.

Adult↗
PubMed1997

Predicting drug interactions in vivo from experiments in vitro. Human studies with paclitaxel and ketoconazole.

This study was performed to evaluate whether concomitant treatment with ketoconazole could reduce the clearance of paclitaxel given to ovarian cancer patients. Paclitaxel, 175 mg/m2, was given as a 3-hour continuous intravenous infusion and repeated every 21 days. Initially, ketoconazole, 100 to 1600 mg, was given as a single oral dose 3 hours after paclitaxel. Later, ketoconazole, 200 mg, was given perorally 3 hours before paclitaxel. Plasma drug concentrations were measured by high-pressure liquid chromatography (HPLC), and cytochrome P450 3A (CYP3A) activity was measured with the erythromycin breath test (ERMBT). Ketoconazole did not alter plasma concentrations of paclitaxel or its principal metabolite, 6 alpha-hydroxypaclitaxel. Although there was marked inter- and intrapatient variability in ketoconazole pharmacokinetics, peak plasma concentrations in all but one course were below the 50% inhibitory concentration (IC50) point determined for inhibition of paclitaxel metabolism in vitro. Therefore, paclitaxel and ketoconazole can be coadministered safely without dose adjustments. There was no correlation between ERMBT measurements and serial plasma concentrations of paclitaxel. The erythromycin breath-test measurements did correlate with the corresponding ketoconazole plasma concentrations. The erythromycin breath test is a valuable tool for measuring instantaneous CYP3A activity in vivo. This clinical study confirms the results of prior studies with human-derived materials in vitro, reinforcing the notion that such studies are useful predictors of drug pharmacokinetics and interactions in vivo.

Antifungal Agents↗
PubMed1996

Primary retroperitoneal mucinous cystadenocarcinoma of low malignant potential: a case report and literature review.

A case of primary retroperitoneal mucinous cystadenocarcinoma of low malignant potential in the presence of normal ovaries is reported. The precise etiology of these neoplasms has not been defined; however, they may arise from heterotopic ovarian tissue, monodermal teratomas, embryonal urogenital remnants, intestinal duplication, or coelomic metaplasia. Although minimal data exist to define the appropriate management, it seems reasonable to extrapolate from the treatment of analogous ovarian neoplasms.

Adult↗
PubMed1996

The practice of surgical staging and its impact on adjuvant treatment recommendations in patients with stage I endometrial carcinoma.

A survey of American gynecologic oncologists was undertaken to assess their compliance with current surgical staging criteria in patients with early endometrial carcinoma. One hundred forty-four members of the Society of Gynecologic Oncologists responded to the survey. Respondents treated an average of 22 new cases annually. Tumor grade and intraoperative determination of depth of myometrial invasion were demonstrated to influence the frequency of lymphatic dissection. In grade 1, 2, and 3 lesions, 76, 60, and 34% of responders, respectively, indicated that depth of invasion influenced their decision to perform lymphadenectomy. In addition, depth of invasion was important in determining type and extent of lymphatic resection. Further, the impact of pathologic lymph node status on postoperative adjuvant radiation therapy recommendations was evaluated for various stratifications of endometrial adenocarcinoma confined to the corpus. The greatest differences in treatment recommendations were noted in the 50-66% invasion category. For grade 1 and 2 cancers, adjuvant therapy recommendations were reduced by 23 and 16% respectively when comparing pelvic and combined therapy versus none and vaginal therapy. The effect of surgical staging data on clinical decisions is clearly evident. The knowledge of pathologically negative lymph node status reduces the recommendation for postoperative adjuvant radiotherapy in patients with adenocarcinoma otherwise confined to the uterine corpus.

Chemotherapy, Adjuvant↗
PubMed1996

A randomized controlled trial of postoperative nasogastric tube decompression in gynecologic oncology patients undergoing intra-abdominal surgery.

OBJECTIVE: To evaluate the effect of nasogastric decompression after extensive intra-abdominal surgery in gynecologic oncology patients. METHODS: Over a 1-year period, 110 gynecologic oncology patients undergoing extensive intra-abdominal surgery were enrolled in a randomized controlled trial of postoperative nasogastric tube versus intra-operative orogastric tube decompression. RESULTS: The nasogastric and orogastric groups were similar in age, case distribution, surgery length, and blood loss. The nasogastric group had significantly longer times to first passage of flatus and tolerance of a clear liquid diet than did the orogastric group. However, both groups were similar in time to tolerance of a regular diet and hospital stay. On average, the nasogastric tube was maintained for 3.2 +/- 2.1 days (range 1-8) after surgery. The average daily nasogastric output was 440 +/- 283 mL (range 68-1565). No patient in the orogastric group required a nasogastric tube postoperatively, but one patient in the nasogastric group had a nasogastric tube reinserted for recurrent nausea and vomiting. Use of a nasogastric tube led to significantly more subjective complaints, eg, ear pain, painful swallowing, and nasal soreness, but did not significantly reduce the incidence of abdominal distention or nausea and vomiting. Major complications, eg, pneumonia, atelectasis, gastrointestinal bleeding, and wound breakdown or infection, occurred equally in both groups. However, the incidence of febrile morbidity was significantly greater in the nasogastric group. There were no known anastamotic complications or aspirations in either group. Postoperative changes in hematological indices and electrolytes were comparable in both groups. CONCLUSION: Postoperative nasogastric tube decompression in gynecologic oncology patients undergoing extensive intra-abdominal surgery does not appear to provide any substantial benefit but significantly increases patient discomfort. As a result of this study, we have eliminated postoperative nasogastric decompression except in highly selected circumstances, such as extensive bowel surgery in patients with prior irradiation or substantial edema from bowel obstruction.

Female↗
PubMed1996

Ovarian lipoma of teratomatous origin.

BACKGROUND: Lipomatous tumors of ovarian origin are rare and may arise from overgrowth of metaplastic fat cells in the stroma. CASE: A 5-cm, circumscribed, grossly yellow tumor was an incidental finding at the time of hysterectomy for endometrial cancer. The ovarian tumor was composed almost exclusively of benign adipocytes. Small collections of benign sweat glands were present at the periphery of the tumor. CONCLUSION: This predominantly lipomatous ovarian tumor likely represents a fat-rich solid teratoma.

Adipocytes↗
PubMed1995

Neovaginal cytology after total pelvic exenteration for gynecological malignancies.

Vaginal reconstruction has become an established method to restore sexual function in women who have undergone ultraradical surgery and/or irradiation for the treatment of gynecologic malignancies. Cytologic evaluation of the neovagina serves a major role in the detection of recurrent disease. The purpose of this retrospective 6-yr study (January 1987-December 1993) was to evaluate the cytologic features of vaginal smear specimens from neovaginas constructed utilizing split-thickness skin grafts. Thirty-four vaginal smears were obtained at regular intervals from nine women (mean age: 51 yr) who underwent total pelvic exenteration with vaginal reconstruction for recurrent malignancies of the vagina and the cervix. Anucleated, keratinizing squames were a constant finding in each smear. Over a 4-mo-6-yr postoperative period, superficial and intermediate squamous cells were present in the majority of the smears and the maturation index showed a shift to the right. In two cases, a squamous cell carcinoma of the cervix recurred within the neovagina. Knowledge of the cytologic features associated with neovaginas is important in order to distinguish normal changes from neoplastic lesions.

Adenocarcinoma↗
PubMed1995

cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle.

The present study was undertaken to determine whether endometrial cancer cell line HEC-1-A differ from nontransformed cells, in that the cAMP and protein kinase C pathways may enhance IGF-I effects in mitogenesis by acting at the G1 phase of the cell cycle instead of G0. Immunofluorescence staining of HEC-1-A cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and flow cytometric analysis determined that HEC-1-A cells do not enter the G0 phase of the cell cycle when incubated in a serum-free medium. Approximately 51% of the cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to treatment. Forskolin and phorbol-12-myristate 13-acetate (PMA) were used to stimulate cAMP production and protein kinase C activity, respectively. IGF-I, forskolin and PMA each increased (P < 0.01) [3H]-thymidine incorporation in a dose and time dependent manner. The interaction of forskolin and PMA with IGF-I was then determined. Cells preincubated with forskolin or PMA followed by incubation with IFG-I incorporated significantly more (P < 0.01) [3H]-thymidine into DNA than controls or any treatment alone. It is concluded that forskolin and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to enhance IGF-I effects in cell proliferation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Treatment of refractory ovarian carcinoma with paclitaxel and cisplatin after treatment failure with single-agent paclitaxel.

The clinical response to paclitaxel and cisplatin was evaluated in fifteen patients with refractory epithelial ovarian cancer who failed to respond to treatment with single agent paclitaxel. Patients received combination chemotherapy every 3 weeks with both 135 mg/m2 (9) or 175 mg/m2 (6) of paclitaxel and 50 mg/m2 (2), 75 mg/m2 (4) or 100 mg/m2 (9) of cisplatin. There was 1 complete clinical response, with 2 partial clinical responses for an overall response rate of 20%. The progression free interval was 6+ months for the complete responder and 9.5+ months for the partial responders. Overall five (33%) patients experienced an improvement in clinical response over that seen with paclitaxel alone, and 5 patients have died. Improvement in clinical response with combination chemotherapy compared to paclitaxel alone was positively associated with the cisplatin dose; while disease progression and death were inversely associated with the paclitaxel dose. Addition of cisplatin to paclitaxel may be useful in the treatment of patients who fail to respond to paclitaxel alone.

Adult↗