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Biomedical subjects

D M Ho

Publications and source records attributed to D M Ho.

At least 19 recordsLinked to original sources

Synthesis of an extremely crowded naphthalene via a stable norbornadienone.

Computational studies at the HF/3-21G and B3LYP/6-31G(d) levels suggest that 5,6,8-tri(tert-butyl)-1,2,3,4-tetraphenylnaphthalene (2) is perhaps the most crowded naphthalene derivative that will show normal stability; more highly congested naphthalenes will prefer to exist as the corresponding Dewar isomers. Initial attempts to prepare 2 by reacting 3,4,5,6-tetraphenylbenzyne with 2,3,5-tri(tert-butyl)cyclopentadienone at 83 degrees C gave instead a stable norbornadienone, 1,2,4-tri(tert-butyl)-5,6,7,8-tetraphenyl-9-oxo-1,4-dihydro-1,4-methanonaphthalene (3), which was characterized by X-ray crystallography. The experimental and calculated (HF/3-21G) activation energies (E(a)) for the decarbonylation of 3 were quite high: 39 and 46 kcal/mol, respectively, a manifestation of the substantially increased strain in the transition state as the tert-butyl groups are forced together. The naphthalene 2 was obtained in good yield by heating 3 in refluxing toluene, and its X-ray structure showed exceptional distortions from a normal naphthalene geometry. However, 2 is not completely stable, and it decomposes upon prolonged heating in xylenes.

Journal Article↗

Determining absolute configuration in flexible molecules: a case study.

Assigning absolute configuration of molecules continues to be a major problem. Determining absolute configuration in conformationally flexible systems is challenging, even for experts. Here, we present a case study in which we use a combination of molecular modeling, solution NMR, and X-ray crystallography to illustrate why it is difficult to use solution methods alone for configuration assignment. For the case examined, a comparison of calculated and experimental optical rotatory dispersion (ORD) data provides the most straightforward way to assign the absolute configuration.

Benzoates↗

A comparative MR and pathological study on fetal CNS disorders.

OBJECT: We used MR after sonography to help us in prenatal counseling in 58 complicated pregnancies from 1998 to 2000. METHODS: All fetal MR examinations were undertaken with a 1.5-T magnet using a body-phased-array coil and an ultrafast imaging technique, half-Fourier single-shot turbo spin-echo (HASTE). Twelve fetuses were found to have major anomalies, and in each of these cases either delivery was induced or the pregnancy was terminated. In 6 of the fetuses, with anomalies of the central nervous system, postmortem examinations were then performed after they failed to survive, and these constitute the patient sample investigated in the current study. The fetal gestational ages in these 6 cases ranged from 24 to 32 weeks. MR imaging demonstrated morphological details of the anomalies. They were: alobar holoprosencephaly in 2, middle interhemispheric fusion in 1, alobar holoprosencephaly with Dandy-Walker malformations in 1, a Dandy-Walker variant in 1 and twin-twin transfusion syndrome with hypoxic-ischemic injury to the brain in 1. CONCLUSIONS: Postmortem examinations confirmed the MR diagnoses, and these observations support us in improving our understanding of the pathogenesis of fetal CNS anomalies.

Abnormalities, Multiple↗

A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma.

Optimal histologic criteria for the classification of and grading of ependymomas, including their anaplastic forms, remain elusive. This is especially true because of the poor correlation of these criteria with clinical outcome. The aim of this study was to identify the histopathologic parameters that could distinguish different prognostic groups of patients with ependymomas. Eighty-one patients with ependymal tumors, including those originally diagnosed ependymomas, anaplastic ependymomas and myxopapillary ependymomas, were enrolled in this study. Thirteen histologic parameters, including hypercellularity, nuclear pleomorphism, mitoses, endothelial proliferation, necrosis, clear cell, thrombi, dystrophic calcification, psammoma bodies, bone, cartilage, Rosenthal fibers and MIB-1 labeling index (LI), were evaluated in each patient and correlated with clinical outcome. We assigned one score for each histopathologic parameter evaluated and used a stepwise selection method with entry model based on the significance of the log-rank statistic to formulate a scoring model. Four parameters were chosen in this process, including mitoses > or = 4/10 hpf (1.7/mm2), hypercellularity, endothelial proliferation and necrosis. The sum of these four parameters (scores) was the histopathologic score of the tumor. The progression-free survival (PFS) and overall survival (OS) of patients with histopathologic scores 0 and 1 were significantly better than those with histopathologic scores 2, 3 and 4 (p < 0.001 and p = 0.005, respectively). Because of the latter finding, we proposed that anaplastic ependymoma could be diagnosed by the presence of any two of the aforementioned four parameters. Multivariate analyses including clinical and histopathologic variables showed that histopathologic score > or = 2 and subtotal resection were the factors related to increased risk of recurrence, while histopathologic score > or = 2 was the only factor related to overall survival. Based on the above findings, we concluded that histopathology is an important prognostic indicator for patients with ependymomas.

Adolescent↗

Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification.

AIMS: We studied the clinicopathological characteristics of plurihormonal pituitary adenomas. METHODS AND RESULTS: The study material included 167 plurihormonal adenomas, which consisted of 31% of the surgically removed pituitary adenomas that we collected during a 12-year period. The mean age of patients with plurihormonal adenoma was 45.7 years (range 13-75 years). There were 86 men and 81 women. All tumours were fully classified by immunohistochemical staining for seven pituitary hormones or subunits. Thirty immunohistochemical subtypes of plurihormonal adenomas were recognized. Hormonal symptoms were present in 70% of patients, while serum hormonal levels were increased in 89% of patients. Most patients had symptoms related to only one of the hormones and only 7% of patients had symptoms related to two hormones. The most common hormonal symptom was acromegaly (50%); symptoms related to hyperprolactinaemia ranked second (20%). Double immunostaining of all the possible combinations of the hormones was performed in 30 selected tumours, and they all showed mixtures of hormones in individual adenoma cells in any hormonal combinations studied. The latter finding supported the view that plurihormonal adenomas are monomorphous adenomas. CONCLUSIONS: Plurihormonal adenomas are common pituitary adenomas. Immunohistochemical staining of all pituitary hormones is mandatory for correct classification.

Adenoma↗

A metastatic pituitary carcinoid tumor successfully treated with gamma knife radiosurgery.

Intracranial metastasis occurs in a certain number of patients with carcinoid tumor. However, carcinoid tumor with metastasis to the pituitary gland is extremely rare. Up to the present, no effective treatment for either a metastatic intracranial carcinoid tumor or a metastatic pituitary lesion of any origin has been documented. We have treated a case of metastatic carcinoid tumor of the pituitary gland with transsphenoidal tumor resection followed by gamma knife radiosurgery. A 59-year-old man presented with headache and left oculomotor palsy. He was treated at the same hospital for bronchial atypical carcinoid tumor one and a half years ago. Magnetic resonance image of the brain showed a pituitary tumor. There were no signs of recurrent or metastatic lesion elsewhere despite thorough investigation. Transsphenoidal approach for removal of tumor was done and the pathology turned out to be a metastatic carcinoid tumor. Subsequent gamma knife radiosurgery was given for residual tumor. The oculomotor palsy improved after radiosurgery. No neurological deficit occurred. Follow-up CT scan of the brain showed complete resolution of the tumor. We concluded that gamma knife radiosurgery could be used to treat a metastatic intracranial carcinoid tumor. It can also be used to treat a metastatic lesion of the pituitary gland without causing neurological deficit.

Carcinoid Tumor↗

MIB-1 labeling index as a prognostic indicator for survival in patients with FIGO stage IB squamous cell carcinoma of the cervix.

OBJECTIVE: The goal of this study was to assess whether the MIB-1 labeling index (LI) and conventional parameters could distinguish between a good and a poor prognosis in patients with squamous cell cervical carcinoma of the same FIGO stage. METHODS: The study included 97 cases of stage IB squamous cell cervical carcinoma which were treated with radical hysterectomy between 1989 and 1991. The relation of the MIB-1 LI, conventional clinicopathologic parameters, and survival was evaluated. RESULTS: The MIB-1 LI of the entire group of tumors was 57.1 +/- 15.9 (mean +/- SD). The MIB-1 LI was significantly different only in living and dead patients, while it was not related to conventional clinicopathologic prognostic parameters. The 5- and 10-year survival rates of patients with an MIB-1 LI </=55 were 90.0 and 88.6%, respectively, which were significantly better than the survival rates of patients with LI >55, which were 73.1 and 66%, respectively. Multivariate analyses showed that MIB-1 LI >55, lymph node metastasis, and tumor size >/=40 mm were powerful predictors of shorter survival. CONCLUSIONS: Lymph node metastasis, tumor size, and MIB-1 LI were significant prognostic markers in patients with stage IB squamous cell cervical carcinoma.

Adult↗

Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma.

Eleven atypical teratoid/rhabdoid tumors (AT/RT) and 121 primitive neuroectodermal tumors/medulloblastomas (PNET/MB) were included in this study for evaluation of the histopathological features of AT/RT and comparison between AT/RT and PNET/MB. Histopathological studies of AT/RT showed that in addition to the commonly recognized components, i.e., rhabdoid cells, small (PNET/MB) cells, spindle cells and epithelial components, there was a previously unrecognized component, sickle-shaped embracing cells, which were present in all cases and could be useful as a histological marker of this tumor. Immunohistochemical studies showed divergent differentiation of the tumor cells and among the 16 antibodies studied, vimentin, neuron-specific enolase, epithelial membrane antigen and glial fibrillary acidic protein were most commonly reactive. The frequency of AT/RT expressed as a ratio of AT/RT to PNET/MB was 1:11 in general and increased to 1:3.8 among patients younger than 3 years old. The AT/RT patients were younger than those with PNET/MB and had a female predominance. The MIB-1 labeling index of AT/RT was significantly higher than that of PNET/MB (mean 63.9 vs 40.1), which correlated with a shorter survival in patients with AT/RT than those with PNET/MB (median survival time 15.4 months vs 156.4 months).

Antigens, Nuclear↗

Spuriously high CK-MB isoenzyme activity mimicking acute myocardial infarction in a patient with adenocarcinoma of the rectum.

A 58-year-old Chinese male presented with precordial distress and was found to have elevated creatine kinase (CK)-myocardial bound (MB) (determined by the Kodak Ektachem Clinical Chemistry Slide method) activity and an abnormal electrocardiogram. Eventually, the patient was diagnosed with an annular ulcerative tumor 10 cm above the anal orifice. The tumor was an adenocarcinoma of the rectum and was immunoreactive for CK-BB (brain type). CK isoenzyme electrophoresis disclosed both BB and MM (muscle type) bands. We concluded that the level of CK-MB determined using the Kodak Ektachem Clinical Chemistry Slide method was spuriously elevated in our patient with adenocarcinoma of the rectum, without evidence of myocardial injury. Institutions using the Kodak Ektachem Clinical Chemistry Slide system for CK should be aware of this possibility.

Adenocarcinoma↗

Abdominal wall necrosis following transcatheter arterial chemoembolization for hepatocellular carcinoma.

A 76-year-old man, who had inoperable hepatocellular carcinoma, had been treated with transcatheter arterial chemoembolization (TACE) 11 times, percutaneous ethanol injection therapy three times and conformal radiotherapy once, all in other hospitals. At this admission, he developed myocutaneous necrosis in the right abdominal wall after TACE, via the collateral of the right internal mammary artery (IMA). Necrosis of the abdominal wall was due to ischemic changes caused by embolization of the distal branches of the IMA, which were aggravated by previous radiation therapy. We advise that embolization of the IMA in patients who have received radiotherapy should be avoided, if possible.

Abdominal Muscles↗

Pediatric intracranial germinoma treated with chemotherapy alone.

BACKGROUND: Pediatric intracranial germinoma treated with radiotherapy is considered a standard treatment, but may cause significant delayed damage to the central nervous system. Chemotherapy has been shown to be effective for the treatment of an intracranial germinoma. In the past 10 years, we treated 11 cases of primary intracranial germinoma with chemotherapy alone. The purpose of this retrospective study is to review the clinical outcome of these patients. METHODS: Eleven children with newly diagnosed, previously untreated primary intracranial germinomas were treated with six courses of chemotherapy (vinblastine bleomycin, cisplatin and etoposide, VBPE). The response to chemotherapy, relapses and outcomes are reviewed and evaluated. RESULTS: All 11 assessable children achieved a complete response and are alive, with a median follow-up of 61 months. Five patients with tumors located in the midline position of the brain, including pineal, sellar, suprasellar and hypothalamic areas, had no relapse. Six patients had relapses, and all of them achieved a second complete remission after salvage focal radiotherapy. The time of onset of relapse was from nine to 24 months after chemotherapy, with an average of 16.8 months. CONCLUSIONS: VBPE chemotherapy was effective for treating newly diagnosed intracranial germinomas. Although a high rate of relapse (6/11) was observed, all of these patients survived with first or second complete remissions. It was beneficial for five children that focal radiation was eliminated and delayed post-irradiation neurologic sequelae were avoided.

Adolescent↗

MIB-1 labeling index in nonpilocytic astrocytoma of childhood: a study of 101 cases.

BACKGROUND: The prognosis of pediatric patients with nonpilocytic astrocytoma, and in particular those with anaplastic astrocytoma, is somewhat unpredictable. This study used MIB-1 monoclonal antibody, a proliferative marker that can be used in formalin fixed paraffin embedded tissues, to study nonpilocytic pediatric astrocytoma. METHODS: Astrocytoma, anaplastic astrocytoma, and glioblastoma specimens excised from a total of 101 pediatric patients during the period from January 1975 to September 1996 were retrieved from the authors' surgical pathology file. Histologic grading of the specimens was performed based on a modified Ringertz system. The proliferative potential of the tumors was estimated by using the MIB-1 labeling index (LI), which was evaluated with morphologic grades of tumors and survival of the patients. RESULTS: Of the 101 patients, 34 had astrocytoma, 33 had anaplastic astrocytoma, and 34 had glioblastoma. Their mean survival times were 165.2+/-14.9 months (mean+/-standard error; SE), 46.1+/-9.9 months, and 21.8+/-5.6 months, respectively. The mean MIB-1 LI of different tumor grades were as follows: astrocytoma, 3.9+/-4.3 (mean+/-standard deviation; range, 0.0-21.6); anaplastic astrocytoma, 24.3+/-15.6 (range, 1.7-62.8); and glioblastoma, 35.9+/-16.4 (range, 7.36-63.3). The mean survival of the entire group of patients with LIs < or = 11 was 173.2+/-12.2 months (mean+/-SE), and the mean survival of those with LIs > 11 was 20.3+/-4.1 months. The survival of anaplastic astrocytoma patients with LIs < or = 11 was similar to that of astrocytoma patients, whereas the survival of anaplastic astrocytoma patients with LI > 11 was similar to that of patients with glioblastoma. CONCLUSIONS: The results of the current study show that histopathologic grading can predict the outcome for patients with astrocytomas and glioblastomas, whereas MIB-1 LI can separate better and worse prognostic groups in patients with anaplastic astrocytoma.

Adolescent↗

Expression of E-cadherin and alpha- and beta-catenins in thymoma.

Expression of the cell adhesion molecules including E-cadherin and its cytosolic binding proteins, alpha- and beta-catenins, has been widely studied in a variety of tumours, but not, to date, in thymic epithelial tumours. To observe the expression pattern of these adhesion molecules, immunohistochemical stains for E-cadherin (E-CD) and alpha- and beta-catenins were performed on 89 cases of thymoma which were classified as cortical (57 cases), mixed (18 cases), and medullary (14 cases), based on the classification of Marino and Müller-Hermelink. The majority of cortical thymomas showed diffuse and homogenous membrane immunoreactivity for these molecules (88 per cent for E-CD; 86 per cent for alpha-catenin; 91 per cent for beta-catenin) and the remaining cases showed heterogeneous immunoreactivity, whereas almost all mixed and medullary thymomas revealed decreased expression or were negative. In each histological subtype of thymoma, the expression did not correlate with invasion or with the presence of myasthenia gravis. These results indicate that the expression of E-CD and alpha- and beta-catenins is more closely associated with the histological subtypes of thymoma than with their biological behaviour.

Adult↗

Ki67 labelling index correlates with stage and histology but not significantly with prognosis in thymoma.

AIMS: There have been several cell kinetic studies of thymoma, but the effectiveness of using Ki67 antibody as a tool to measure proliferative activity in this tumour was rarely evaluated. We carried out an immuno-histochemical study using this antibody to assess the clinicopathological correlation and the prognostic significance of this technique. METHODS AND RESULTS: Ninety-one cases of thymoma were collected. Double immunostaining with Ki67 and cytokeratin KL-1 antibodies was performed on paraffin sections. Ki67 labelling index (LI) was expressed as a percentage of Ki67 immunopositive nuclei by counting at least 1000 epithelial cells. The LIs were correlated with stages, histological subtypes based on both Lattes-Bernatz and Müller-Hermelink-Kirchner classifications, and length of survival. There were statistically significant differences of LIs between stage I and stage III and between stage I and stage IV tumours. Histologically, statistically significant differences were identified between predominantly epithelial thymoma and every other subtype of the Lattes-Bernatz classification and between well-differentiated thymic carcinoma and medullary or mixed thymomas of the Müller-Hermelink-Kirchner classification. Regarding the prognostic implication of Ki67 LI, although there appeared a trend that patients with tumours of higher LIs had slightly worse survival, the difference was not statistically significant in both univariate and multivariate survival analyses. CONCLUSIONS: We have demonstrated the proliferative potential in thymoma is associated with stage and histology. However, its clinical usefulness is limited on account of the overlap of LIs and lack of prognostic significance.

Adult↗

Hemichorea-hemiballism: an explanation for MR signal changes.

PURPOSE: Some cases of hemichorea-hemiballism (HCHB) are associated with a hyperintense putamen on T1-weighted MR images, the cause of which remains unclear. Our purpose was to determine the cause and significance of these MR signal changes. METHODS: We analyzed the clinical and neuroimaging findings in 10 patients with HCHB, focusing on locations of the hyperintense lesions on T1-weighted images, comparing them with those on CT scans, and evaluating their changes after years of follow-up. A biopsy was performed in one patient. RESULTS: Seven patients had hyperglycemia and two had cortical infarcts. HCHB recurred in four patients. A hyperintense putamen preceded the occurrence of HCHB in two patients. T1-weighted MR images revealed hyperintense lesions limited to the ventral striatum in six patients. Hyperintense lesions extended to the level of the midbrain in one patient and persisted for as long as 6 years in another patient. T2-weighted MR images revealed slit-shaped cystic lesions in the lateral part of the putamina 2 to 6 years after the onset of symptoms in two patients. A biopsy specimen from the hyperintense putamen in one patient revealed a fragment of gliotic brain tissue with abundant gemistocytes. Proton MR spectroscopy of the specimen showed an increase in lactic acid, acetate, and lipids, and a decrease in N-acetylaspartate and creatine, suggesting the presence of pronounced energy depletion and neuronal dysfunction. CONCLUSION: Gemistocytes are sufficient to explain the shortening of T1 relaxation time. Our investigation suggests that neurons in the ventral striatum and striatonigral pathway may play a critical role in generating ballism.

Adolescent↗

Primary cerebellar extramedullary myeloid cell tumor mimicking oligodendroglioma.

Extramedullary myeloid cell tumors (EMCTs) are tumors consisting of immature cells of the myeloid series that occur outside the bone marrow. Most of them are associated with acute myelogenous leukemia or other myeloproliferative disorders, and a small number occur as primary lesions, i.e., are not associated with hematological disorders. Occurrence inside the cranium is rare, and there has been only one case of primary EMCT involving the cerebellum reported in the literature. The case we report here is a blastic EMCT occurring in the cerebellum of a 3-year-old boy who had no signs of leukemia or any hematological disorder throughout the entire course. The cerebellar tumor was at first misdiagnosed as an "oligodendroglioma" because of the uniformity and "fried egg" artifact of the tumor cells. The tumor disappeared during chemotherapy consisting of 12 treatments. However, it recurred and metastasized to the cerebrospinal fluid (CSF) shortly after the therapy was completed. A diagnosis of EMCT was suspected because of the presence of immature myeloid cells in the CSF, and was confirmed by anti-myeloperoxidase and anti-lysozyme immunoreactivity of the cerebellar tumor. The patient succumbed 1 year and 3 months after the first presentation of the disease.

Cerebellar Neoplasms↗