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Biomedical subjects

T M Murad

Publications and source records attributed to T M Murad.

At least 37 records · Page 2Linked to original sources

Papillary tumors of large lactiferous ducts.

The breast pathology files at the Institut Gustave-Russy in Villejuif, France, were searched for papillary cystadenomas and papillary carcinomas diagnosed between January 1, 1960, and December 31, 1974. A total of 158 cases were selected for this study; they were subclassified into 74 papillary cystadenomas, 63 papillary carcinomas, and 21 multiple papillomas. Spontaneous nipple discharge was the primary reason for consultation in 88% of solitary cystadenoma patients, 48% of multiple papilloma patients, and 23% of the carcinoma patients. The data support the benign nature of papillary cystadenoma inasmuch as none of the 73 patients treated with local excision developed cancer of the same breast, with only one patient having recurrence of the lesion. In contrast, multiple papilloma was associated with a high recurrence rate and malignant transformation. According to Scarff and Bloom's grading system, papillary carcinoma was found to be of low grade malignancy with a five-year survival rate of over 90%.

Adult↗

Megalocytic interstitial nephritis, xanthogranulomatous pyelonephritis, and malakoplakia. An ultrastructural comparison.

Light-microscopic and ultrastructural examinations of megalocytic interstitial nephritis, xanthogranulomatous pyelonephritis, and malakoplakia of the kidney were compared. The cases of megalocytic interstitial nephritis and xanthogranulomatous pyelonephritis represent the first reported electron-microscopic studies on human kidney of these diseases. The study confirmed the presence of a polymorphous cellular infiltrate with predominate histiocytes containing crystalloid material in the case of megalocytic interstitial nephritis; a polymorphous cellular infiltrate with histiocytes predominating in the case of xanthogranulomatous pyelonephritis; and macrophages containing Michaelis-Gutmann bodies in the case of malakoplakia. The characteristic sites of involvement within the kidney by each of the three lesions are discussed. It is believed that the lesions are distinct entities, but related to one another, and represent varied and unusual host responses to inflammation.

Female↗

Polypoid melanoma, a virulent variant of the nodular growth pattern.

Thirty-two patients who had polypoid melanoma were identified in a registry of 552 melanoma patients. The tumor is regarded as a variant of nodular melanoma and is associated with an increased thickness, more frequent ulceration than the nodular variant of melanoma, younger patient age, and higher probability of occult metastasis. Polypoid melanomas were most frequently present on the trunk, and were also encountered in unusual sites, such as the mucosa of the nose, hard palate, and anorectal junction. In terms of survival, the patients with the polypoid nodular variant fared significantly worse than those with nonpolypoid nodular (P = 0.05) and those with superficial spreading (P = 0.003) melanomas. The five-year survival rate for polypoid variant was 42%, in contrast to 57% for the nonpolypoid nodular and 77% for the superficial spreading melanomas. The poor prognosis of patients who have polypoid melanoma is most likely due to its being the type of melanoma with the deepest penetration at the time of surgical excision.

Acute Disease↗

A multifactorial analysis of melanoma: III. Prognostic factors in melanoma patients with lymph node metastases (stage II).

Twelve prognostic features of melanoma were examined in a series of 185 patients with nodal metastases (Stage II), who underwent surgical treatment at our institution during the past 20 years. Forty-four per cent of the patients presented with synchronous nodal metastases (substage IIA), 44% of the patients had delayed nodal metastases (substage IIB), and 12% of the patients had nodal metastases from an unknown primary site (substage IIC). The patients with IIB (delayed) metastases had a better overall survival rate than patients with IIA (synchronous) metastases, when calculated from the time of diagnosis. These differences could be explained on the basis of tumor burden at the time of initial diagnosis (microscopic for IIB patients versus macroscopic for IIA patients). Once nodal metastases became evident in IIB patients, their survival rates were the same as for substage IIA patients, when calculated from the onset of nodal metastases. The survival rates for both subgroups was 28% at five years and 15% for ten years. Substage IIC patients (unknown 1 degrees site) had better five-year survival rates (39%), but the sample size was small and the differences were not statistically significant. A multifactorial analysis was used to identify the dominant prognostic variables from among 12 clinical and pathologic parameters. Only two factors were found to independently influence survival rates: 1) the number of metastatic nodes (p = 0.005), and the presence or absence of ulceration (p = 0.0019). Additional factors considered that had either indirect or no influence on survival rates (p > 0.10) were: anatomic location, age, sex, remission duration, substage of disease, tumor thickness, level of invasion, pigmentation, and lymphocyte infiltration. All combinations of nodal metastases were analyzed from survival differences. The combination that showed the greatest differences was one versus two to four versus more than four nodes. Their five-year survival rates were 58%, 27% and 10%, respectively (p < 0.001). Ulceration of the primary cutaneous melanoma was associated with a <15% five-year survival rate, while nonulcerative melanomas had a 30% five-year survival rate (p < 0.001). The combination of ulceration and multiple metastatic nodes had a profound adverse effect on survival rates. While tumor thickness was the most important factor in predicting the risk of nodal metastases in Stage I patients (p < 10(-8)), it had no predictive value on the patient's clinical course once nodal metastases had occurred (p = 0.507). The number of metastatic nodes and the presence of ulceration are important factors to account for when comparing surgical results, and when analyzing the efficacy of adjunctive systemic treatments.

Adult↗

Treatment of secondary hyperparathyroidism in patients with chronic renal failure by total parathyroidectomy and parathyroid autograft.

Sixty-one patients with chronic renal failure and secondary hyperparathyroidism underwent total parathyroidectomy and parathyroid autograft. Symptoms relieved by parathyroidectomy included bone pain, pruritus, soft tissue calcification, muscle weakness and healing of fractures. Serum parathormone levels measured before and after operation in 48 patients returned to normal in all but two patients. Serum alkaline phosphatase levels also returned toward normal after operation, except in one patient with a retained parathyroid gland. Complete radiographic studies before and after operation were available in 30 of 61 patients. Twenty-three of 24 patients with osteitis fibrosa had evidence of healing, and in one patient no change occurred. Osteosclerosis noticed in 23 patients improved slightly in eight patients, did not change in 14 and became worse in one. Pathologic examinations revealed 45 patients to have diffuse hyperplasia and 16 nodular hyperplasia. There were two early postoperative deaths, in the first 30 days, and 16 late postoperative deaths, from four months to four years afterward. In no case did the operation contribute to death. Some patients required the administration of supplemental calcium after operation, but in no instance did profound hypocalcemia occur. No patient developed recurrent hyperparathyroidism.

Adolescent↗

The prognostic significance of ulceration of cutaneous melanoma.

Ulceration of a cutaneous melanoma on microscopic sections is an adverse prognostic finding. The five-year survival rate is reduced from 80% for non-ulcerated melanomas to 55% in the presence of ulceration for Stage I melanoma patients and from 53 to 12% for Stage II melanoma patients (P less than 0.001). As a group, ulcerated lesions are thicker and more likely to have a nodular growth pattern. However, survival rates were still worse for ulcerated melanomas when matched with nonulcerated lesions for thickness and stage of disease. The width but not the depth of surface ulceration significantly correlated with survival. The median ulcer depth was 0.08 mm (range 0.01-1.2 mm). In those few lesions with ulcer craters more than 0.2 mm in depth, the melanomas were so thick they had the same poor prognosis regardless of whether thickness was measured to the base of the ulcer or to the top of the lesion. The Breslow microstaging method of measuring thickness is therefore a valid prognostic indicator, even for ulcerated lesions. The incidence of ulceration for the entire patient group ranged from 12.5% for melanomas less than 0.76 mm thickness to 72.5% for melanomas greater than 4.0 mm thick (P of correlation = 0.0001); from 12% for Level II invasion to 63% for Level V lesions (P = 0.005); from 23% for superficial spreading growth patterns to 49% for nodular and 74% for polypoid lesions (P = 0.0001); and from 27% for lesions with a heavy lymphocyte infiltration to 60% for minimal or absent host response (P = 0.005). There was no significant correlation with anatomic location, pigmentation of the melanomas, or with the patient's age and sex. Since ulceration appears to have such an important influence on survival rates, this parameter should be considered as a stratification criterion in clinical trials and accounted for when analyzing results of melanoma treatment.

Adult↗

Multiple myeloma masquerading as chromophobe adenoma.

A 62-year-old woman presenting with intracranial lesion eroding the sella with compression of optic chiasma was found to have plasmacytoma of the pituitary area. At the time of initial surgery, the patient had no biochemical, immunologic or marrow findings of multiple myeloma. The intracranial tumor was interpreted initially as chromophobe adenoma on light microscopy, but the diagnosis of plasmacytoma was established by electron microscopic examination of the tumor. The case illustrates the usefulness of electron microscopy as a diagnostic tool.

Adenoma, Chromophobe↗

Villous polyps of the urethra: a report of two cases.

Two patients with villous polyps of the prostatic urethra are described. The article supports previous observations that the lesion has the morphologic appearance of prostatic tissue. A review of the literature reveals that this rare lesion appears to be specific for the prostatic urethra and behaves as a benign tumor.

Adult↗

Pulmonary toxicity associated with bischloroethylnitrosourea (BCNU).

Ten patients developed pulmonary fibrosis after bischloroethylnitrosourea (BCNU) therapy for malignancy. This was lethal in seven patients, four of whom had no evidence of tumor at autopsy. Presenting symptoms were either the insidious onset of cough and dyspnea or the sudden onset of respiratory failure. Physical findings were unremarkable. Chest roentgenogram usually showed interstitial infiltrates. Pulmonary function studies showed resting hypoxia with diffusion and restrictive defects. This complication of therapy does not appear to be dose related and may be made more likely by the concomitant administration of cyclophosphamide. Prednisone therapy did not benefit most patients. The literature and the implications of the use of BCNU alone or in combination are reviewed.

Adolescent↗

A multifactorial analysis of melanoma. II. Prognostic factors in patients with stage I (localized) melanoma.

Stage I melanoma encompasses an extraordinary diversity of biologic behavior. In such a setting where numerous parameters appear to influence survival, a multifactorial analysis using Cox's regression model is a valuable statistical model. Using a computerized data base of 394 clinical stage I melanoma patients treated at this institution during the past 20 years, a multifactorial analysis was used to compare the relative prognostic strength of 11 parameters. Two pathological factors (tumor thickness and ulceration) and two clinial factors (initial surgical treatment and anatomic location) were identified as the dominant prognostic variables. Other factors examined simultaneously that did not provide additional predictive influence on survival included the level of invasion, pigmentation, growth pattern, lymphocyte infiltration, pathological state, sex, and age. Melanoma thickness was the most important factor for predicting survival in patients with stage I melanoma (P less than 10(-8). This parameter is easy to measure and provides a quantitative estimate of clinically occult regional and distant metastases. Contrary to other reports using single factor analysis, the type of initial surgical treatment, in fact, did influence survival after other variables were taken into consideration. Thus the multifactorial analysis supports the observation that patients with intermediate thickness melanoma thickness of 1.5 to 3.99 mm had a 78% 8-year survival rate with wide excision of the melanoma and elective node dissection, while none survived more than 8 years if a melanoma of the same thickness was only widely excised. Multifactorial analysis is a useful and important statistical method when comparing treatment alternatives and prognostic factors in patients with melanoma.

Adult↗

A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods.

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (>/=4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors.

Aged↗

A proposed selective cell carcinogenesis in mammary tumors.

The present study was done to ascertain whether a specific carcinogenic agent has a causal effect on the initial proliferation of only one cell type or whether it acts indiscriminately on all cells in the breast secretory unit. Enzymes histochemistry and electron microscopy were performed on DMBA-induced mammary tumors in female Sprague-Dawley rats and on virus-associated spontaneous mammary tumors in C3H/HEJ mice. The results showed that the chemical carcinogen DMBA affects initial myoepithelial cell proliferation, while virus-associated mammary carcinoma originated from ductular epithelial cell proliferation. To determine whether a specific tumor is composed of a single cell type, tumors were grown in tissue culture. The monolayer was fixed in the usual manner for electron microscopy while in Falcon tissue culture plates. The plates were dissolved in xylene and the monolayer was cut into small pieces and embedded in the plastic media. Electron microscopy performed on the tissue culture and the original tissue from the virus-induced tumors showed the presence of viruses in large numbers. It also suggested the differentiation of basal membrane to form basal lamina and apical plasma membrane into microvilli. This study strongly suggests the presence of selective cell carcinogenesis in the mammary gland.

9,10-Dimethyl-1,2-benzanthracene↗