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Biomedical subjects

M Hopkins

Publications and source records attributed to M Hopkins.

18 recordsLinked to original sources

Serial cranial and spinal cord magnetic resonance imaging in multiple sclerosis.

Twenty-nine mildly disabled patients with multiple sclerosis underwent serial clinical and magnetic resonance imaging (MRI) evaluations (pre- and postgadolinium cranial and spinal cord MRI) on at least 3 occasions at 13-week intervals and during periods of suspected relapse. Using clinical judgment of the presence of recent active disease as the gold standard, combined MRI studies confirmed the clinical impression of active disease in 93% of follow-up visits (sensitivity) and the absence of active MS in 63% of follow-up visits (specificity). None of the cranial and spinal MRI-detected abnormalities disappeared. Gadolinium administration particularly increased the yield of spinal MRI. Cranial MRI alone detected 80% of the MRI-active visits. Clinical and MRI concordance was significantly better for the presence of recent disease activity than for the anatomical localization of the presumed site of activity. MRI evidence of apparent ongoing disease activity was seen more frequently in patients believed to have active multiple sclerosis in the preceding year (13 of 21) than in patients who had been in clinical remission for at least the 2 preceding years (2 of 8). Although clinical evidence of new disease activity was much less common in patients with active, chronic-progressive disease (1 of 8) than in patients with active, relapsing disease (9 of 13), the proportion of patients with either infrequent relapses, frequent relapses, or slow chronic-progressive disease in the preceding year in whom MRI activity developed and the pattern of this new MRI activity was similar between these types of active patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain

Testicular artery ramification within the inguinal canal.

Testicular arterial anatomy has been well studied because of its important role in testicular physiology and testicular surgery. Contrary to classical anatomical descriptions, we have observed that often more than 1 branch of the internal spermatic artery is present at the level of the proximal inguinal canal. Many surgeons who perform varicocelectomy assume that only 1 artery is present at this level and ligate all other vascular structures once an artery has been identified. We determine the frequency and number of internal spermatic arteries present within the spermatic cord in the proximal inguinal canal. The number of internal spermatic arteries present at this level was studied in 15 spermatic cords of 12 patients undergoing varicocelectomy using loupe magnification and intraoperative Doppler ultrasound. The number of arteries ranged from 1 to 3, with a mean of 2 arteries. Histological studies of the same area of 17 spermatic cords obtained from cadavers revealed a mean of 2.4 arteries (range 1 to 3). Knowledge of the frequent early branching of the internal spermatic artery will prevent inadvertent interruption of testicular arterial blood flow during operations performed upon the spermatic cord within the inguinal canal.

Arteries

Phenotypic characterization, karyotype analysis and in vitro tamoxifen sensitivity of new ER-negative vulvar carcinoma cell lines, UM-SCV-1A and UM-SCV-1B.

Two cell lines (University of Michigan squamous carcinoma of the vulva UM-SCV-1A and UM-SCV-1B) were established from the primary tumor and a malignant pleural effusion of a 62-year-old woman. Both tumor specimens grew vigorously in vitro and could be passaged after only 14 and 10 days in culture, respectively. Both cell lines undergo 3 population doublings in 4 days, reaching saturation densities of 5 x 10(5) cells/cm2, and have been carried through more than 30 in vitro passages. In nude mice the cultured cells initially formed tumors but these regressed 2-3 weeks after inoculation. The regressing mouse tumors consisted of poorly differentiated squamous carcinoma surrounded by an inflammatory lymphoid infiltrate. The UM-SCV-1 cell lines express membrane antigens typically displayed by squamous-cell carcinomas. These include the HLA class-1 light chain beta 2-microglobulin, pemphigus, pemphigoid, and the alpha 6 beta 4 integrin defined by the UM-A9 monoclonal antibody (MAb). In contrast to the A431 vulvar carcinoma, these tumor lines do not have amplified expression of the epidermal growth factor (EGF) receptor. Although tissue from the primary tumor contained low levels of estrogen receptor activity, no receptor activity was detected in the cell lines. Nevertheless, both lines were sensitive to growth inhibition by tamoxifen. This effect was not reversible by estradiol, indicating an estrogen-receptor-independent mechanism. The tumors were both hypotetraploid, contained the same chromosome rearrangements and had stable karyotypes in vitro. Each contained inv(1)(p36.3q32.1), del(4)(q12), dic(4;11)(q12;p11.2), i(5p), der(6)t(3;6)(q25.1;p21.1), several rearrangements involving chromosomes 8 and 14, + i(13), i(18p), a dicentric t(11;19), and 2 or 3 unidentified markers. Since the karyotypes of both tumors were the same, no major karyotypic change was associated with metastatic spread. These paired primary and metastatic SCC lines from an unusually aggressive vulvar carcinoma provide an in vitro model for analysis of the biological basis of this tumor's behavior.

Animals

Optimal coverage of peritoneal surface in whole abdominal radiation for ovarian neoplasms.

Patterns of failure in ovarian carcinoma include early seeding of the entire peritoneal cavity. Inability to encompass the anatomic extent of the peritoneal cavity is a possible factor leading to relapse. However, little has been published regarding technical advances in optimal coverage of the peritoneal surface in whole abdominal radiation. In the Department of Radiation Oncology at the University of Michigan, 21 consecutive patients were analyzed prospectively in regard to adequate coverage of peritoneum in the treatment of advanced ovarian carcinoma. Simulation and focused blocks were designed to treat the whole abdomen. CT treatment planning studies were obtained with the entire peritoneum identified as the target volume. Simulator designed blocks were projected over the CT scans throughout the treatment volume. Dose volume histograms were used to calculate the amount of target volume missed for each treatment plan. All treatment plans demonstrated different degrees of volume miss, ranging from 1 cm3 to 837.3 cm3 with a median of 137.9 cm3 overall. Volume missed directly correlated with increasing patient weight and flatter pelvic shape, but poorly with AP separation. This was especially evident for patients requiring treatment at extended distances in both the supine and prone positions. We conclude that bony landmarks are poor guidelines in designing pelvic blocks, especially in heavy patients and patients requiring treatment in both prone and supine positions. CT treatment planning is helpful to ensure optimal peritoneal coverage.

Abdomen

Clinicopathologic features of ovarian mixed mesodermal tumors and carcinosarcomas.

Over a 27-year period there were 15 patients treated at the University of Michigan Medical center for carcinosarcomas or mixed mesodermal tumors of the ovary. Overall median survival was 11 months. Median survival was 4 months in patients with carcinosarcomas and 13 months in patients with mixed mesodermal tumors (P = 0.066). Patients with a chondrosarcomatous element had a significantly longer median survival than patients with mixed mesodermal tumors lacking cartilaginous differentiation (P = 0.031). The presence of a rhabdomyosarcomatous element did not affect survival. The size of the primary tumor, presence of ascites, FIGO stage, and degree of initial resection (optimal versus suboptimal) did not affect survival. There was no difference in survival between patients receiving postoperative chemotherapy and patients undergoing postoperative irradiation.

Adult

A referendum on clinical trial research in multiple sclerosis: the opinion of the participants at the Jekyll Island workshop.

Sixty-two experienced multiple sclerosis (MS) investigators attending a research workshop were asked their opinions about clinical trial design, outcome measures, and treatment. Respondents favored repeated clinical observations of neurologic function (eg, Expanded Disability Status Scale or Ambulation Index) over the opinion of a blinded physician and changes on magnetic resonance imaging. There was agreement that stable MS should not be treated with immunosuppressives. Corticosteroids were rated the most effective treatment for recent disease activity. Total lymphoid irradiation and immunosuppressives were judged more potent for the long-term management of progressive disease. No treatment, however, received the support of more than 11% of the respondents for being of "considerable efficacy" in the long-term management of MS. Most favored a placebo-controlled design in future trials. In order to judge the acceptability of current trial design, participants were asked to act as patient surrogates and to indicate whether they would agree to participate in 4 randomized trials for which they would be eligible. The majority consented to participate in the 3 major trials currently under way, and most refused to enroll in the 1 trial that had never been initiated.

Clinical Trials as Topic

How reproducible are flow cytometry data from paraffin-embedded blocks?

The purpose of this technical report is to determine the reproducibility of flow cytometry data for ploidy and cell cycle kinetics using paraffin-embedded blocks of breast cancer tissue. One block from each of 39 tumors was studied in this report with each block having multiple sections analyzed independently. All of these sections gave ploidy analyses, while only 34 gave cell kinetic values. The standard deviation for the DNA index value in the multiple analysis study was less than 0.1 in all but three cases. The cell kinetic values gave larger variability, and the actual values were dependent on the method of analysis. Comparison of the variability for each method of analysis could not predict which procedure was superior. These results would indicate that ploidy is a reproducible value, while cell kinetic parameters should only be used as an indicator of proliferative activity that has been normalized to the mean or median of a large set of observations processed and analyzed by the same procedure.

Breast Neoplasms

A report on the EC/IC bypass study.

In 1967 the first extracranial to intracranial (EC/IC) arterial anastomosis was performed. Since that time, EC/IC bypass surgery has become a widely accepted surgical treatment for patients with intracranial stenotic or occlusive atherosclerotic lesions. In 1977 an international multicenter randomized trial was established to determine whether EC/IC bypass surgery reduced the rate of stroke and stroke-related death in patients with recent hemispheric and/or retinal ischemic symptoms. Completed and analyzed in 1985, the International Cooperative Study of Extracranial/Intracranial Arterial Anastomosis of 1,377 patients provides an evaluation of the surgical procedure for stroke prevention. This paper will discuss the study's objectives and organization, the methods employed, the trial results, and implications.

Cerebral Arteries

Meigs's syndrome and ovarian thecoma in pregnancy. A case report.

Ovarian thecoma is a rare tumor, accounting for less than 1% of all ovarian tumors. Thecomas occur even more infrequently during pregnancy, as evident from the fact that there are only 16 such case reports. A 16-year-old, pregnant, black woman presented with ovarian thecoma, pleural effusion and ascites at 32 weeks' gestation. To our knowledge, this was the first reported case that fulfills the criteria of Meigs's syndrome during pregnancy. Ovarian tumors in pregnancy may have very subtle clinical manifestations, making the diagnosis a challenge. Delivery by cesarean section at term is recommended in these patients for the best maternal and fetal outcome.

Adolescent

Relationship of flow cytometry results to clinical and steroid receptor status in human breast cancer.

Flow cytometry (FC), estrogen receptor (ER), and progesterone receptor (PR) analyses were performed on 226 breast cancers. The presence of steroid receptors was inversely proportional to proliferative index and percent aneuploidy. Within the two ER (+ and -) groups, the presence of PR did not add significantly to the comparison. The mean proliferative index for the diploid tumors was 17.5 +/- 6.8 compared to 27.8 +/- 9.8 for aneuploid tumors (p less than .001). The degree of aneuploidy, or DNA index, was not related to cell cycle kinetics or steroid receptor status. In 163 tissues analyzed for percent tumor present, a correlation between the relative number of aneuploid cells and percent tumor in the histologic review was observed. A study of the diploid tumors indicated greater than 75% had at least 10% tumor cells by histologic review. Since with FC one can observe at least 10% aneuploid cells in a tumor sample, it is our opinion that the percent aneuploidy in this study is not artifactually low due to sampling error. There was no significant relationship between nodal status or number of positive nodes and proliferative index, aneuploidy, or steroid receptor status. Metastatic tumors had a higher mean proliferative index, but this was not statistically significant. There was a relationship between age and proliferative index but not between age and ploidy status. In a small group of patients there was a trend for proliferative index and percent aneuploidy to be higher in the poorly differentiated and larger tumors when compared to the well differentiated and smaller tumors.

Age Factors

Malignant placental site trophoblastic tumor.

Placental site trophoblastic tumor is a rare variant of trophoblastic disease. The malignant form of this disease with metastasis and death is even more infrequent, as is evident from only five cases in the literature. A 30-year-old black woman who died from this disease is presented. Patients with metastases are at extremely high risk with no reported survivors and must be treated aggressively with chemotherapy and cytoreductive surgery. This type of trophoblastic tumor apparently exhibits a different biologic behavior as compared with choriocarcinoma.

Adult

An analysis of causes of injuries in workers with leprosy and suggestions for preventive measures.

A study of 20 workers undergoing social and vocational rehabilitation and of 30 patients receiving treatment in Ulcer Ward reveals bio-social data and endeavours to uncover the causes of injuries to anaesthetic areas. Suggestions are put forward for prevention of injuries which often lead to ulcers and these suggestions are examined in the light of short trials of various methods.

Extremities

Sperm banking.

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Adolescent

Cytologic features of ovarian tumors of low malignant potential in peritoneal fluids.

The distinction of ovarian tumors of low malignant potential (OTLMP) from invasive ovarian carcinomas has significant therapeutic and prognostic implications. This study was undertaken to define the cytologic features of OTLMP in peritoneal fluids and to compare them with the cytologic features of invasive carcinomas. Peritoneal fluids from 13 patients with OTLMP and 10 patients with invasive ovarian carcinoma contained neoplastic cells and were reviewed with attention to papillary fragment morphology, cellular pleomorphism and cytoplasmic and nuclear characteristics. Cytologic preparations from patients with OTLMP contained large, cohesive papillary fragments with smooth borders. The neoplastic cells were relatively small and uniform, with high nuclear-cytoplasmic (N/C) ratios (greater than 1:2), few intracytoplasmic vacuoles and inconspicuous nucleoli. Mitotic figures were rare. Peritoneal fluids from patients with invasive ovarian carcinoma contained smaller discohesive papillary fragments with irregular borders. The neoplastic cells were relatively large and pleomorphic, with low N/C ratios (less than or equal to 1:2), abundant intracytoplasmic vacuoles and prominent nucleoli; most preparations contained many single cells and mitotic figures.

Adult