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T M Murad

Publications and source records attributed to T M Murad.

At least 19 recordsLinked to original sources
PubMed1993

Acquired megacolon is associated with alteration of vasoactive intestinal peptide levels and acetylcholinesterase activity.

Based upon previous morphologic studies, we hypothesized that the development of acquired megacolon was associated with abnormalities of enteric neurotransmitter concentrations and enzymatic activities. Specimens were obtained at surgery from patients with normal descending-sigmoid colon (n = 13) and patients with sigmoid megacolon (n = 6; defined by radiologic measurement). Radioimmunoassays were used to measure the non-adrenergic, non-cholinergic inhibitory neuropeptide, vasoactive intestinal peptide, and the non-adrenergic, non-cholinergic excitatory neuropeptide, substance P, while spectrophotometric assays were used to quantitate acetylcholinesterase activity and choline acetyltransferase activity. There were significantly decreased concentrations of vasoactive intestinal peptide and decreased acetylcholinesterase activity in muscularis externa from patients with acquired megacolon. In megacolon, vasoactive intestinal peptide-containing nerve fibers appeared to be diminished in circular and longitudinal smooth muscle, and immunostaining of nerve cell bodies in the plexus submucosus externus appeared diminished. These results suggest the hypothesis that production of vasoactive intestinal peptide is altered allowing secondary colonic hypertrophy to develop from prolonged cholinergic nerve-mediated contractions of circular smooth muscle. As a corollary to this hypothesis, colonic dilatation might result from prolonged contraction of longitudinal smooth muscle.

Acetylcholinesterase↗
PubMed1993

Flow cytometric evaluation of early invasive cervical cancer.

OBJECTIVE: To define the role of flow cytometry as a prognostic indicator in early cancers of the uterine cervix. METHODS: Flow cytometry was used to determine ploidy, DNA index, and S-phase fraction on 141 samples from the tumors of 53 women with stage IB cancers of the cervix treated by radical hysterectomy and pelvic lymphadenectomy as primary therapy. Multiple samples of the same tumor were analyzable for 47 (89%) of the subjects. One-way analysis of variance for the multiple samples was used to compare the heterogeneity of flow cytometry data, both within each tumor and between patients. Flow cytometry results, as well as previously described clinical and pathologic prognostic factors, were correlated to recurrence and survival using Cox regression hazard ratios and Kaplan-Meier estimates. RESULTS: We found DNA aneuploidy in 25 (47%) of the cancers, with a mean (+/- standard error) DNA index of 1.52 +/- 0.07. The mean S-phase fraction was 7.6 +/- 0.4% for diploid tumors and 9.2 +/- 0.4% for aneuploid tumors. The cancers from 24 women (45%) were homogeneously diploid, 18 (34%) were consistently aneuploid, and five (9%) had mixed diploid/aneuploid samples. Analysis of variance of the multiple samples for each woman revealed a greater standard deviation (SD) between patients than within any individual tumor for both DNA index (ratio of between SD to within SD 2.1; P < .0001) and S-phase fraction (ratio 1.6; P < .0001). Of the previously described clinical and pathologic prognostic factors, only depth of invasion, expressed as either percent of cervical wall thickness or as thirds, was correlated with recurrence or survival. Neither the DNA index nor S-phase fraction correlated significantly with recurrence or survival. CONCLUSIONS: These results suggest that alterations in the DNA content or proliferative activity of early invasive cancers of the uterine cervix do not reflect biologic behavior in terms of recurrence or survival, and that this behavior is not due to tumor heterogeneity.

Adenocarcinoma↗
PubMed1991

Dual-parameter flow cytometric analysis coupling the measurements of forward-angle light scatter and DNA content of archival ovarian carcinomas of low malignant potential.

Paraffin-embedded archival specimens from 45 cases of ovarian carcinoma of low malignant potential (OCLMP) were analyzed by flow cytometry (FCM) using propidium iodide (PI) staining. Since single-parameter FCM analysis is often deficient in the resolution of subtle near-diploid DNA-aneuploid populations, forward-angle light scatter (FALS) was measured as a second parameter. DNA aneuploidy was identified in 15 cases (33%). In 7 of those 15 cases, aneuploidy was resolved with single-parameter FCM; in the remaining 8 cases, DNA aneuploidy was resolved only following dual-parameter analysis coupling DNA content and FALS. In all 15 cases, a single near-diploid aneuploid population was observed (mean DNA index = 1.2); there were no tetraploid aneuploid cases. The proliferative activity for all 45 cases studied ranged from 1.0% to 8.9%, with a mean of 3.5%. No difference in mean proliferative activity was observed between the aneuploid and diploid tumors (P greater than .05). To exclude the possibility that PI staining artifacts caused the observed aneuploidy, five of the eight cases shown to be aneuploid by dual-parameter analysis were further studied using an alternate DNA-binding dye, DAPI, yielding similar results. To exclude the possibility that contaminating stromal and/or inflammatory cells caused the observed aneuploidy, samples from a subset of the dual-parameter cases were sorted, revealing the aneuploid populations to be composed primarily of tumor nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1990

Flow cytometric evaluation of epithelial ovarian cancer.

We investigated the prognostic significance of deoxyribonucleic acid content and proliferative activity of tumor cell populations as measured by flow cytometry of the tumor specimens from 115 women with epithelial ovarian cancer. Deoxyribonucleic acid aneuploidy was found in 87 of 115 (76%) of these cancers with a mean deoxyribonucleic acid index of 1.6 and S-phase fraction of 14.7%. The S-phase fraction of the 28 (24%) diploid tumors was 7.0%. Deoxyribonucleic acid ploidy was significantly correlated with survival. S-phase fraction was significantly correlated with ploidy, residual tumor, histology, grade, ascites, time to recurrence, and survival. Diploidy versus aneuploidy were the best discriminating values for deoxyribonucleic acid index and an S-phase fraction of greater or less than 18% for that parameter. Multivariate analysis revealed stage, S-phase fraction, residual tumor, and grade to be independently associated with time to recurrence, and stage, age, S-phase fraction, and largest metastases were factors associated with survival. Deoxyribonucleic acid ploidy did not significantly improve either model. These results suggest that abnormalities of deoxyribonucleic acid content and the proliferative activity of tumor cell populations are reflective of their biologic activity.

Aneuploidy↗
PubMed1990

Hydatidiform mole: clinicopathologic associations with the development of postevacuation trophoblastic disease.

Clinical information and histopathologic material for 165 patients with hydatidiform mole referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School during one year were reviewed in order to identify characteristics more likely to be associated with the development of gestational trophoblastic tumors. Twenty-nine patients (18%) required chemotherapy for invasive mole or choriocarcinoma. Patients with uterine enlargement beyond that expected for dates and patients with ovarian theca-lutein cysts were much more likely to require treatment after molar evacuation (47% vs. 18% and 40% vs. 16%, respectively). There was no correlation between the initial human chorionic gonadotropin level, gestational age, uterine size per se, maternal age or gravidity and the subsequent clinical course. Histologically, the following factors were associated with an increased incidence of postmolar gestational trophoblastic tumor: (1) progressive nuclear atypia (26.7% if atypia present vs. 40% if absent); (2) necrosis and hemorrhage (39.1% if extensive vs. 12.8% if limited); (3) decreased trophoblast maturation (48% if less than 20% mature vs. 8.7% if greater than or equal to 20% mature); (4) trophoblast proliferation (50% if marked vs. 13.9% if limited); (5) increased ratio of cytotrophoblast to syncytium (33.3% if greater than 1 vs. 6.4% if less than 1); and (6) absence of Nitabuch's layer (21.4% if absent vs. 11.6% if present). Hydatidiform moles which demonstrate clinical or histopathologic evidence of excessively abnormal proliferative activity, as indicated by these features, are more likely to develop invasive mole or choriocarcinoma and should be considered for prophylactic chemotherapy.

Adolescent↗
PubMed1988

Histopathological and clinical correlations of cystosarcoma phyllodes.

We performed a detailed retrospective analysis of 25 patients treated primarily at Northwestern Memorial Hospital, Chicago, for cystosarcoma phyllodes. Histopathological evaluation correlated well with malignancy, but clinical suspicion did not. Pathological studies indicated that high-grade tumors, necrosis, infiltrating margin, and the presence of more than one mesenchymal element were often associated with aggressive behavior. Flow-cytometric analyses of DNA aneuploidy and proliferative index supported the grading system we used, since all four malignant cases examined showed high proliferative index, and three of the four cases showed aneuploidy. None of the low-grade cases, including the recurrent ones, showed increased proliferative index or aneuploidy. We believe that flow-cytometric analysis ought to be performed on cases in which there is doubt regarding the potential malignancy.

Adolescent↗
PubMed1987

Prognostic indicators in cystosarcoma phylloides.

Cystosarcoma phylloides is a breast neoplasm that has a frequently unpredictable clinical course. We made a retrospective study of 25 patients with this disease in an attempt to evaluate the indicators of aggressive behavior. In our series, older patient age, nulliparity, rapid tumor growth, pain, and large size of tumors increased the suspicion of malignancy but were not always reliable indicators of malignancy. Skin ulceration, tumor necrosis, and infiltrating tumor margins were the most ominous characteristics. High-grade tumors, that is, those with increased cellularity, vascularity, mitotic figure, and pleomorphism, often indicated aggressive behavior. Mixed mesenchymal components were sometimes related to a malignant course. We found a 24 percent incidence of associated breast cancer. Carcinoma of the ipsilateral breast was found in four patients and later in the contralateral breast in two patients. Of our 25 patients, 10 (40 percent) had recurrence and 4 (16 percent) died from disease. Recurrences after treatment usually occurred within 3 years. Patients must be followed carefully for local recurrence or metastases, since the clinical course is not predictable. Forty percent of the lesions were diagnosed as being malignant. Local excision was associated with recurrence in six of eight patients and was clearly inadequate treatment. Quadrantectomy was effective for benign peripheral lesions when a generous margin could be obtained. From these data, we believe that mastectomy is indicated in all patients with malignant lesions and in those with large benign lesions.

Breast Neoplasms↗
PubMed1985

Benign breast lesions with malignant clinical and mammographic presentations.

Nine cases of benign breast disease in which mammograms had been false-positive were collected at Northwestern Memorial Hospital. In all but one case the patients had presented initially with questionable masses that required biopsies with requests for frozen section diagnoses. Included in the study were three cases of indurative mastopathy, three cases of fibrocystic disease with sclerosing adenosis, and one case each of sclerosing papillary proliferation, infarcted intraductal papilloma, and fat necrosis with foreign body giant cell reaction. The mammographic and histologic findings for all cases were reviewed. Indurative mastopathy is a poorly known entity with radiologic features highly suggestive of malignancy. As described previously (Cancer 47:561, 1981), the lesion consists of a central nidus of elastosis with irregular projections radiating into the adjacent breast tissue. Peripheral areas of the infarcted papilloma and sclerosing papillary proliferation could be confused with infiltrating carcinoma in frozen sections. Familiarity of pathologists with these lesions is essential for avoiding the overdiagnosis of carcinoma.

Adult↗
PubMed1985

Multiple focal extraovarian serous carcinoma.

Nine cases of multiple focal extraovarian serous carcinoma were studied, and their gross, light microscopic, and ultrastructural features were compared with those of three serous ovarian tumors and three malignant mesotheliomas. On light microscopy, the multiple focal extraovarian serous carcinoma shared many features of the serous ovarian tumors. However, they also displayed some ultrastructural features shared by both serous ovarian tumors and malignant mesotheliomas, and other features more specific for malignant mesotheliomas. We concluded that the multiple focal extraovarian serous carcinomas probably arise from mesothelial cells modified by various müllerian influences and should be classified separately from the other two entities.

Adult↗
PubMed1984

Head and neck melanoma in 534 clinical Stage I patients. A prognostic factors analysis and results of surgical treatment.

Single and multifactorial analyses were used to evaluate prognosis and results of surgical treatment in 534 clinical Stage I patients with head and neck cutaneous melanoma treated at the University of Alabama in Birmingham (U.S.A.) and the University of Sydney (Australia). This computerized data base was prospectively accumulated in over 90% of cases. Melanomas were about equally distributed between men and women. They were located on the skin of the face in 47%, neck in 27%, scalp in 13%, and the ear in 13% of patients. Both the results of the prognostic factors analyses and the surgical treatment demonstrated that lentigo maligna melanoma (LMM) was distinct from the other two growth patterns, superficial spreading melanoma and nodular melanoma (SSM and NM). In a multifactorial analysis of the 453 patients with SSM and NM, the dominant prognostic variables were tumor thickness (p less than 0.00001), anatomic subsite (p = 0.0213), and ulceration (p = 0.0289). Patients with melanomas on the scalp or neck subsites fared worse than those with tumors located on the face or ear. The results differed for LMM, where thickness was not a significant predictor of survival, and the most dominant prognostic variable was ulceration (p = 0.0042). Local recurrence rates were low, being 2.4% for tumors less than 2.5 mm in thickness, but were 12.3% for tumors greater than or equal to 4.0 mm in thickness. Patients with SSM and NM lesions located on the head and neck had a lower survival rate than those with extremity melanomas in every tumor thickness category, although only those in the 0.76 to 1.49 mm thickness subgroup were significantly different (p = 0.0007). After 5 years of follow-up, patients who underwent an elective lymph node dissection for SSM and NM with a thickness range of 1.5 to 3.99 mm had a better survival (72%) than patients with melanomas of equivalent thickness whose initial treatment was wide excision alone (45%). LMM had a less aggressive biologic behavior compared to SSM or NM and was treated more conservatively. Thus, LMM lesions had an 85% 10-year survival rate with wide excision only, and there was no significant improvement in survival with ELND. Growth patterns, tumor thickness, ulceration, and anatomic subsites should be considered when evaluating risk factors and when making treatment decisions in head and neck melanoma patients.

Head and Neck Neoplasms↗
PubMed1984

Malakoplakia and malakoplakialike lesions of the upper gastrointestinal tract.

This report describes the clinical and pathologic features of 3 cases of unusual lesions that bear a striking similarity to malakoplakia. The lesions were located in the stomach, submental region, and oropharyngeal soft tissues. The cellular infiltrates were composed of sheets of mononuclear cells with abundant, granular, eosinophilic cytoplasm. Nuclei were small and bland, and mitoses were extremely rare. Lymphocytes and plasma cells were present in varying numbers. Ultrastructural studies revealed unusual crystalline structures within dilated cisternae of rough surfaced endoplasmic reticulum of plasmacytoid cells in all 3 cases. The 3 cases may represent a morphologic spectrum of chronic immunologic stimulation, with the crystalline structures limited to stimulated lymphocytes of gastrointestinal tract lesions.

Aged↗
PubMed1983

Changing trends in cutaneous melanoma over a quarter century in Alabama, USA, and New South Wales, Australia.

Clinical and pathologic characteristics of melanoma were compared among 1647 clinical Stage I patients treated at the University of Alabama in Birmingham (USA) and The University of Sydney (Australia) between 1955 and 1980 to determine what changes occurred over a quarter century. Over this period, the number of patients treated annually has increased substantially. There was a steady increase in the proportion of patients presenting with localized disease (clinical Stage I). Melanomas became thinner, less invasive, less ulcerative and thus more curable. They also exhibited more of a radial growth phase. The median thickness of melanomas decreased in Australia from 2.5 mm prior to 1960 to 1.1 mm during the period 1976 to 1980, while in Alabama it has decreased from 3.3 to 1.4 mm. There was a significant increase in melanomas located on the trunk in males and a corresponding decrease in male head and neck melanomas. No significant change in the site distribution was observed for any major anatomical area on female patients. There were minimal differences in the incidence of both clinical and pathologic parameters among melanoma patients in Alabama, USA and in New South Wales, Australia even when accounting for their year of diagnosis. Long-term survival rates in patients with localized disease were found to increase slightly during the 25 year time frame of this analysis. The changes that have occurred are likely due to earlier diagnosis and changes in the biological nature of the disease.

Adult↗
PubMed1983

A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III).

A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.

Actuarial Analysis↗
PubMed1982

Nipple discharge from the breast.

Abnormal nipple discharge is rare, constituting only 3-5% of mammary consultation. In the present paper 267 patients with primary nipple discharge operated on at Institut Gustave-Roussay (IGR) in Villejuif, France, between January 1, 1960 and December, 1974 were evaluated. In all cases, the nipple discharge was symptomatic, spontaneous, and represented the primary reason for the patient's consultation. During the same period 1,145 cases of nipple discharge were treated at IGR. Of the 1,145 cases with symptomatic nipple discharge, 267 patients (23%) required surgical intervention. Among these, fibrocystic disease and duct ectasia were the leading causes of nipple discharge occurring in 42% of surgical specimens. Twenty one per cent of the patients had carcinoma and 35% were found to have intraductal papilloma. The overall incidence of malignancy, however, was 4.8% among the 1,145 women with nipple discharge. On the average, patients with nipple discharge due to malignancy were ten years older than those with benign lesions (Table 2). Approximately 25% of patients with malignant discharge and 5% with benign discharge have associated tumor. Over 60% of the patients with both discharge and a mass had malignancy.

Adolescent↗
PubMed1982

A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia.

Twelve clinical and pathologic parameters were compared in two series of Stage I melanoma patients treated at the University of Alabama in Birmingham, USA (676 patients) and at the University of Sydney in New South Wales, Australia (1,110 patients). Actuarial survival rates were virtually the same at the two institutions over a 25-year follow-up period. The incidence of thin melanomas (less than 0.76 mm) was also similar at both geographic locations (25% vs. 26%). Other similarities of these two patient populations included the following: 1) tumor thickness (Breslow Microstaging). 2) level of invasion (Clark Microstaging), 3) surgical results, 4) sex distribution, and 5) age distribution. The greatest differences between the two patient populations were their 1) anatomic distribution, 2) growth pattern, and 3) incidence of ulceration. The trunk was the most common site of melanoma, and occurred more frequently among Australian patients (37% vs. 28%). A multifactorial analysis (Cox's regression model) was then performed that included a comparison of the two institutions as a variable (Alabama vs. Australia). The dominant prognostic factors (p less than 0.0001) were 1) ulceration, 2) tumor thickness, 3) initial surgical management (wide excision +/- node dissection), 4) anatomic location, 5) pathologic stage (I vs. II), and 6) level of invasion. The benefit of elective lymph node dissection was demonstrated in both series for patients with intermediate thickness melanoma (0.76 to 3.99 mm.) For melanomas ranging from 0.76 to 1.5 mm in thickness, the benefit of node dissection was primarily in male patients. Survival rates for melanoma at the two institutions were not significantly different in the multifactorial analysis, even after adjusting for all other variable. Thus, the biologic behavior of melanoma in these two different parts of the world was virtually the same, with only minor differences that did not significantly influence survival rates. Long-term follow-up exceeding eight to ten years after surgery is critical in the interpretation of these prognostic factors and the surgical results.

Adult↗