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Biomedical subjects

M Hopkins

Publications and source records attributed to M Hopkins.

At least 19 recordsLinked to original sources
PubMed1995

Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators.

BACKGROUND: Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are unsuccessful. METHODS: We conducted a double-blind, placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn's disease despite a minimum of three months of prednisone therapy. Patients were randomly assigned to treatment with intramuscular methotrexate (25 mg once weekly) or placebo for 16 weeks. The patients also received prednisone (20 mg once a day), which was tapered over 10 weeks unless their condition worsened. The primary outcome measure was clinical remission at the end of the 16-week trial. Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn's Disease Activity Index. RESULTS: A total of 141 patients were randomly assigned in a 2:1 ratio to methotrexate (94 patients) or placebo (47 patients). After 16 weeks, 37 patients (39.4 percent) were in clinical remission in the methotrexate group, as compared with 9 patients (19.1 percent) in the placebo group (P = 0.025; relative risk, 1.95; 95 percent confidence interval, 1.09 to 3.48). The patients in the methotrexate group received less prednisone overall than those in the placebo group (P = 0.026). The mean (+/- SE) score on the Crohn's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group (162 +/- 12) than in the placebo group (204 +/- 17, P = 0.002). The changes in quality-of-life scores and serum orosomucoid concentrations were similar. In the methotrexate group, 16 patients (17 percent) withdrew from treatment because of adverse events (including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6), as compared with 1 patient (2 percent) in the placebo group. CONCLUSIONS: In a group of patients with chronically active Crohn's disease, methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone.

Adult↗
PubMed1995

Uterine cervix adenocarcinoma with both human papillomavirus type 18 and tumor suppressor gene p53 mutation from a woman having an intact hymen.

Human papillomavirus (HPV) type 18 DNA was found in an aggressively invasive adenocarcinoma tumor from a woman who had an intact hymen and denied any prior sexual intercourse. The viral DNA was detected within the tumor tissue by polymerase chain reaction (PCR) using consensus primers for the L1 region of oncogenic high-risk genital HPVs. In order to determine mutations within the tumor suppressor gene p53, the gene exons were amplified by PCR followed by single-stranded conformation polymorphism (SSCP) analysis. The appearance of a mutation in exon 8 of the p53 gene suggested by SSCP was directly confirmed by DNA sequencing of the exon. The sequencing showed a single base deletion that may truncate the protein by introducing a early stop codon in the messenger RNA. This early truncation could be expected to affect the proper oligomerization of the p53 protein and hence its DNA-binding activity. The results show that genital oncogenic human papillomaviruses may be passed by nonsexual routes and suggest that the virus may work in concert with p53 mutations to help the infected tissue progress toward invasive cancer.

Adenocarcinoma↗
PubMed1994

Crystallization and preliminary X-ray analysis of C-reactive protein from rat.

Crystals of C-reactive protein from rat have been grown both with and without calcium. Two major components of the protein have been resolved on the basis of their calcium-dependent fine specificity for monophosphate esters. Crystals grown without calcium are tetragonal, space group P42(1)2 with unit cell parameters a = b = 163.81(9)A and c = 125.21(6)A, and diffract X-rays to 3.0 A resolution. The rotation function specifies a molecular 5-fold symmetry axis at 24 degrees away from c in the (110) plane.

Animals↗
PubMed1994

Hard choices: the gynecologic cancer patient's end-of-life preferences.

Few reports in gynecologic literature have addressed patient preferences about terminal care. In light of the current discussions about end-of-life decision-making, a study was designed to assess the desires of patients with gynecologic cancer. A questionnaire was completed by 108 patients under treatment for gynecologic cancer at the University of Michigan Medical Center and by 39 patients from the routine gynecology clinic at the same institution. Participants were asked about their reactions to a poor prognosis, their desires for the location of terminal care, and their preferences for withdrawing or withholding life-sustaining technologies. Five percent of these cancer patients anticipated giving up the fight against their disease. Seventy-eight percent specifically expressed resolve to continue the fight against their disease. Feedback from these patients about their end-of-life preferences served to define the concept "fight." A majority preferred to receive care at home. Ninety percent of these cancer patients could envision their conditions deteriorating to the point that they would not want ventilator support. Thirty-four percent could envision refusing surgery for another life-threatening condition; 37%, a time when artificial nutrition would be refused; 22%, a time when antibiotics would be rejected. This study suggests that limiting the use of artificial respiratory support while continuing the use of artificial nutrition and hydration support would be consistent with the preferences of gynecologic cancer with end-stage disease.

Adult↗
PubMed1993

Simulated home delivery in hospital: a randomised controlled trial.

OBJECTIVES: To compare the outcome of two methods of maternity care during the antenatal period and at delivery. One was to be midwife-led for both antenatal care and delivery, the latter taking place in rooms similar to those in one's own home to simulate home confinement. The other would be consultant-led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence, monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out. DESIGN: Randomised controlled trial. SETTING: Leicester Royal Infirmary Maternity Hospital. SUBJECTS: Of 3510 women who were randomised, 2304 were assigned to the midwife-led scheme and 1206 were assigned to the consultant-led scheme. MAIN OUTCOME MEASURES: Complications in the antenatal, intrapartum and postpartum periods were compared as was maternal morbidity and fetal mortality and morbidity. Satisfaction of the women with care over different periods of the pregnancy and birth were assessed. RESULTS: There were few significant differences in antepartum, intrapartum and postpartum events between the two groups. There was no difference in the percentage of mothers and babies discharged home alive and well. Generally higher levels of satisfaction with care antenatally and during labour and delivery were shown in those women allocated to midwife care.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗