To examine whether moderate hyperhomocyst(e)inemia is associated with coronary artery disease and the number of diseased coronary vessels in Koreans, we investigated 201 patients with angiographically documented coronary artery disease and 187 healthy subjects without evidence of stroke and coronary artery disease. The mean plasma total homocysteine in patients was higher than in controls (10.3 micromol/L; 95% confidence interval, 7.0-13.6 vs. 8.9 micromol/L; 6.0-11.8) (p=0.005). The prevalence of moderate hyperhomocyst(e)inemia, defined as the top 90th percentile in controls (13.2 micromol/L), was higher in patients than in controls (23.9% vs. 10.2%, p=0.001). Plasma homocyst(e)ine levels were not correlated to age, body mass index, levels of serum cholesterol, creatinine, and uric acid. Based on multiple logistic regression analyses with adjustment for total cholesterol, hypertension, smoking status, diabetes, age, and body mass index, the adjusted odds ratio of moderate hyperhomocyst(e)inemia for coronary artery disease was 1.53 (95% confidence interval: 1.39-1.65, p=0.0001). Moderate hyperhomocyst(e)inemia, diabetes mellitus, and old age were more prevalent in patients with triple-vessel disease than in single- or double-vessel disease (p=0.02). Multiple logistic regression analysis revealed that moderate hyperhomocyst(e)inemia was a significant predictor of triple-vessel disease with odds ratio of 2.78 (95% confidence interval: 1.08-7.10, p=0.02). We conclude that moderate hyperhomocyst(e)inemia is an independent risk factor for coronary artery disease, and also related significantly to the presence of triple-vessel disease.

Adult↗

PubMed1999

The fine structure of an iridectomy specimen from a patient with latanoprost-induced eye color change.

Explore the source record for details and available documents.

Aged↗

PubMed1999

Takayasu arteritis: diagnosis with MR imaging and MR angiography in acute and chronic active stages.

Early diagnosis and treatment of Takayasu arteritis is important in prevention of serious complications. Spin-echo magnetic resonance imaging (MRI) can depict early wall thickening of the aorta and cine MRI can evaluate aortic valve function. Significant enhancement in and around the aorta and carotid arteries is observed on postcontrast MR images in acute phase Takayasu arteritis. In the chronic phase, contrast enhancement in the aortic wall stronger than in the myocardium suggests activity of the disease. Breath-hold contrast-enhanced three-dimensional MR angiography is very effective in noninvasive evaluation of luminal change of aortitis. Contrast-enhanced MRI and MR angiography have an important role in early diagnosis, activity determination, and follow-up of Takayasu arteritis. MRI and MR angiography can be utilized for initial diagnosis of Takayasu arteritis and replace catheterization angiography. J. Magn. Reson. Imaging 1999;10:751-757.

Acute Disease↗

PubMed1999

Immunohistochemical examination of an orbital alveolar soft part sarcoma.

BACKGROUND: A 32 year-old male patient had a 6-week history of left-sided proptosis. Computer tomography revealed a 16x15x15 mm smooth and well-defined mass between the optic nerve and the medial and superior rectus muscles in the left orbit. METHODS: The tumour was excised via a cranio-medial orbitotomy approach. RESULTS: Histopathological examination, immunohistochemistry and electron microscopy findings were consistent with an alveolar soft part sarcoma. Immunohistochemical staining showed positive immunoreactivity for neuronespecific enolase, vimentin, p53 (30%), p21 (10%) and cyclin D1 (20%), and negative immunoreactivity for CD45, cytokeratins, S-100 protein, glial fibrillary acidic protein, synaptophysin, chromogranin, calcitonin, serotonin, thyreoglobulin, desmin, myosin, actin, HMB-45, pRB, p16 and BCL-2. The growth fraction of the tumour cells was 3%. At examination 4 years after surgical excision, there was no evidence of local recurrence or for metastases. CONCLUSION: Alveolar soft part sarcoma of the orbit is a rare malignant tumour best controlled by surgery. The unpredictable behaviour of these neoplasms, however, indicates the need for long-term follow-up.

Adult↗

PubMed1999

T-cell and T/natural killer-cell lymphomas involving ocular and ocular adnexal tissues: a clinicopathologic, immunohistochemical, and molecular study of seven cases.

OBJECTIVE: Lymphomas of the eye and its adnexa are frequently of B lineage. This study aims to characterize the clinical and histopathologic features of the rare non-B-cell non-Hodgkin lymphomas (NHL) of these locations. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Seven cases of T- and T/NK-cell lymphomas involving the ocular and ocular adnexal tissues. METHODS: A morphologic, immunohistochemical, and molecular analysis (polymerase chain reaction) of each of the tumors was undertaken. The lesions were classified according to the Revised European-American Lymphoma (REAL) classification. The clinical and follow-up data were collected. RESULTS: The patients included four women and three men ranging in age from 32 to 88 years (mean, 63 years). The presenting ophthalmic symptoms varied from a small nodule on the upper eyelid and conjunctival swellings to dramatic loss of vision associated with gross protrusion of the globe. Five of the cases presented were secondary manifestations of a systemic lymphoma in ocular tissues; two cases represented primary disease. Three cases were "peripheral T-cell lymphomas (PTCL), unspecified" with positivity for CD3, CD8, and betaF1 and negativity for CD56. Two cases were CD3+, CD30+, and CD56- and were classified as "anaplastic large-cell lymphomas of T-cell type" (T-ALCL). The remaining two cases showed an immunophenotype of CD3+, CD56+, and betaF1- and proved to contain Epstein-Barr virus (EBV) by in situ hybridization, consistent with "T/natural killer (NK)-cell lymphoma of nasal type." Clonal T-cell populations were shown in all three of the PTCLs by Southern blot (n = 1) and polymerase chain reaction (n = 2) for the T-cell receptor gamma and beta genes in one case of ALCL but not in the T/NK-cell lymphomas. Five patients died within 2 years; only two patients (one primary PTCL and one cutaneous T-ALCL) were disease free at 4 and 5 years' follow-up, respectively. CONCLUSION: This study shows that a heterogeneous group of T-cell lymphomas can involve the eye and its adnexal tissue. Most T-cell neoplasms are secondary manifestations of systemic disease and carry a poor prognosis. These findings, in conjunction with published data on ocular B-NHL, also indicate that immunophenotypic differentiation between T- and B-NHL in these locations is of clinical importance.

Adult↗

PubMed1999

Needle-in-a-haystack detection and identification of base substitution mutations in human tissues.

Background and induced germline mutagenesis and other genotoxicity studies have been hampered by the lack of a sufficiently sensitive technique for detecting mutations in a small cluster of cells or a single cell in a tissue sample composed of millions of cells. The most frequent type of genetic alteration is intragenic. The vast majority of oncogenic mutations in human and mammalian cancer involves only single base substitutions. We have developed universally applicable techniques that not only provide the necessary sensitivity and specificity for site specific mutagenesis studies, but also identify the point mutation. The exponential amplification procedures of polymerase chain reaction (PCR) and ligase chain reaction (LCR) have been combined with restriction endonuclease (RE) digestion to enable the selective enrichment and detection of single base substitution mutations in human oncogenic loci at a sensitivity of one mutant in more than 10(7) wild type alleles. These PCR/RE/LCR procedures have been successfully designed and used for codons 12 and 248 of the Ha-ras and p53 genes, respectively, both of which contain a natural MspI restriction endonuclease recognition sequence. These procedures have also been adapted for the detection and identification of mutations in oncogenic loci that do not contain a natural restriction endonuclease recognition sequence. Using PCR techniques, a HphI site was incorporated into the codons 12/13 region of the human N-ras gene, which was then used for the selective enrichment of mutants at this oncogenic locus. These PCR/RE/LCR procedures for base substitution mutations in codon 12 of the N-ras gene were found to have the sensitivity of detection of at least one mutant allele in the presence of the DNA equivalent of 10(6) wild type cells. Only one peripheral blood leukocyte DNA specimen out of nine normal individuals displayed an observable Ha-ras mutation that was present at frequency between 10(-5) and 10(-6). These PCR/RE/LCR techniques for detecting and identifying base substitution mutations are universally applicable to almost any locus or base site within the human or animal genome. With the added advantage of the adjustability of both the amount of DNA (number of genomes) to be tested and the sensitivity (10(-2) to 10(-7)) of the assay selection or enrichment procedures, these PCR/RE/LCR techniques will be useful in addressing a broad range of important questions in mutagenesis and carcinogenesis.

Base Sequence↗

PubMed1999

Recent advances in the treatment of prostate cancer.

As new evidence for prostate cancer treatment has emerged in the last few years, longstanding controversies in the treatment of prostate cancer have resurfaced. A number of long-held tenets of prostate cancer therapy have been revisited, sometimes with surprising and challenging results. Although neoadjuvant hormonal therapy prior to radical prostatectomy decreases positive surgical margin rates, longer follow-up is needed to support survival improvement of this combined modality therapy. Androgen deprivation combined with radiation therapy appears to improve disease-free survival (and survival in one series) in patients with locally advanced cancer. Another approach to locally advanced prostate cancer using three-dimensional conformal radiation therapy may improve long term outcome. The data are currently insufficient to conclude that interstitial low dose rate brachytherapy is equivalent to conventional treatments: patients with small tumor volumes and low Gleason grade seem to obtain more benefit, whereas for large tumors with higher gleason grades this approach seems inferior to conventional treatments. In advanced prostate cancer recent data suggest that immediate hormonal therapy improves survival. In this group of patients the use of maximum androgen blockade remains controversial but may adversely affect quality of life compared to orchiectomy alone. Intermittent hormonal therapy may improve quality of life, although effect upon survival is unknown. Chemotherapy in combination with androgen deprivation is currently being studied as front-line therapy in advanced prostate cancer. Palliative benefit of chemotherapy for hormone refractory prostate cancer remains an important endpoint; survival advantage has not been seen in any randomized trials. Suramin may delay disease progression in hormone refractory prostate cancer. Many aspects of prostate cancer treatment will remain controversial until results of large, randomized trials with longer follow-up are available.

Antineoplastic Agents, Hormonal↗

PubMed1999

Dimorphic immunohistochemical staining in ocular sebaceous neoplasms: a useful diagnostic aid.

PURPOSE: We studied whether patterns of immunostaining in formalin-fixed, paraffin-embedded tissue could help to distinguish between sebaceous neoplasms of the eyelid and other eyelid neoplasms. METHODS: We applied antibodies to human milk fat globule-1 (HMFG1), cytokeratins (PKK1 and MNF116), epithelial membrane antigen (EMA) and carcino-embryonic antigen (CEA) to normal eyelid tissue and to a range of sebaceous lesions of the eyelid; these included sebaceous hyperplasia, sebaceous adenoma and sebaceous epithelioma, in addition to well to poorly differentiated sebaceous carcinoma. RESULTS: The central and peripheral cellular components of normal sebaceous glands and neoplastic sebaceous lesions showed a distinctive dimorphic staining pattern with the antibody panel used. The central foamy 'sebaceous' cells expressed HMFG1 and EMA, but not PKK1 or MNF116, whereas the smaller, peripheral basal and ductal cells expressed PKK1 or MNF116 but not HMFG1 or EMA. CEA expression in sebaceous cells was unhelpful diagnostically. CONCLUSION: Normal sebaceous glands and all sebaceous neoplasms show a dimorphic cell population that can be identified using a small panel of antibodies on formalin-fixed, paraffin-embedded tissue. This distinctive staining pattern can be assessed retrospectively, even in small biopsies, and largely removes the need for fat stains on frozen sections to differentiate sebaceous lesions from other ocular neoplasms. The results also support the suggestion that ocular sebaceous neoplasms arise from a common stem cell, rather than from either sebaceous or basal/ductal cells.

Adenocarcinoma, Sebaceous↗

PubMed1999

Angiotensin II stimulates proliferation of adventitial fibroblasts cultured from rat aortic explants.

It has been proposed that the local renin-angiotensin system is activated in the adventitia after vascular injury. However, the physiological role of Angiotensin II (Ang II) in the adventitia has not been studied at a cellular level. This study was designed to assess the role of Ang II in the growth response of cultured adventitial fibroblasts (AFs). Adventitial explants of the rat thoracic aorta showed outgrowth of AFs within 5-7 days. Ang II caused hyperplastic response of AF cultures. The Ang II-induced mitogenic response of AFs was mediated primarily by the AT1 receptor. Ang II caused a rapid induction of immediate early genes (c-fos, c-myc and jun B). Induction of c-fos expression was fully blocked by an AT1 receptor antagonist but not by an AT2 receptor antagonist. Epidermal growth factor (EGF), platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) induced DNA synthesis in AFs. Co-stimulation of AFs with the growth factors and Ang II potentiated the incorporation of 3H-thymidine into DNA. Results from this study indicate that Ang II causes mitogenesis of AFs via AT1 receptor stimulation and potentiates the responses to other mitogens. These data suggest that the Ang II may play an important role in regulating AF function during vascular remodeling following arterial injury.

Angiotensin II↗

PubMed1999

Early quality of life assessment in men treated with permanent source interstitial brachytherapy for clinically localized prostate cancer.

PURPOSE: We prospectively assessed quality of life changes with time using validated instruments in men with clinically localized prostate cancer treated with permanent source interstitial brachytherapy. MATERIALS AND METHODS: A total of 46 men consecutively treated with permanent source interstitial brachytherapy between September 1997 and June 1998 completed quality of life (Functional Assessment of Cancer Therapy-Prostate [FACT-P]) and urinary symptom (International Prostate Symptom Score [I-PSS]) questionnaires before (T0), and 1 (T1) and 3 (T3) months after treatment. All participants were treated with 125iodine alone. Repeated measures analyses of variance were conducted on all quality of life and urinary outcome measures for 44 patients with data at all 3 time points. RESULTS: Median patient age was 68 years (range 51 to 80). All men had clinical T1c to T2b prostate cancer, Gleason score was 6 or less in 36 (78%) and median pretreatment prostate specific antigen was 7 ng./ml. (range 1.1 to 20.6). Mean score (and standard deviation) at T0, T1 and T3 for each questionnaire was FACT-P 138.9 (14.4), 128.6 (19.4) and 136.7 (17.4), TO versus T1 p = 0.0005 and T0 versus T3 p = 0.6612, and I-PSS 8.3 (5.4), 19.7 (9.0) and 15.7 (7.2), T0 versus T1 p = 0.0001 and T0 versus T3 p = 0.0001. For the global test across time statistically significant differences were observed for the cumulative scores of FACT-P, I-PSS, physical well-being and prostate cancer subscales of the FACT-P and the Trial Outcome Index. By 3 months all quality of life measures had returned to baseline. Urinary symptoms as measured by I-PSS persisted for at least 3 months. CONCLUSIONS: Clinically meaningful decreases in quality of life, as measured by the FACT-P instrument, were evident within weeks after permanent source interstitial brachytherapy. However, by 3 months FACT-P scores returned to near baseline levels. A validated instrument designed to measure urinary symptoms (I-PSS) demonstrated that moderate to severe urinary symptoms persisted for at least 3 months following permanent source interstitial brachytherapy. An instrument specifically designed to measure urinary symptoms can provide additional clinical information when combined with FACT-P.

Aged↗

PubMed1999

Idiopathic intracranial hypertension: a case report with optic nerve histopathology.

We present the clinical and pathologic findings in an atypical case of idiopathic intracranial hypertension. A 51-year-old man had headaches, visual deterioration, papilloedema, and deafness. Neuroimaging was normal, and cerebrospinal fluid pressure monitoring confirmed increased intracranial pressure. The patient was treated with a ventriculo-peritoneal shunt. Histopathology revealed grossly atrophic optic nerves with almost complete axonal loss. The prelaminar portion of the optic nerves was thickened by gliosis and hyalinized capillaries, which have not been described previously.

Atrophy↗

PubMed1998

Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: a secondary analysis of RTOG 85-27.

PURPOSE: The purpose of the present study is to investigate the strength of association between anemia and overall survival, locoregional failure, and late radiation therapy (RT) complications in a large prospective study of patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer. METHODS AND MATERIALS: Between March 1988 and September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered into a randomized trial examining the addition of etanidazole (SR 2508) to conventional radiation therapy (RT) (66-74 Gy in 33-37 fractions, 5 days a week). Patients with hemoglobin (Hgb) levels measured and recorded prior to the second week of RT were included in this secondary analysis. Hemoglobin levels were stratified as normal (> or = 14.5 gm% for men, > or = 13 gm% for women) or anemic (< 14.5 gm% for men, < 13 gm% for women). Locoregional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of overall survival, locoregional failure, and late complications were tested by the Cox proportional hazard model. RESULTS: Of 504 eligible patients, 451 had a Hgb level measured and recorded prior to the second week of RT. One hundred sixty-two patients (35.9%) were considered to have a normal Hgb level and 289 patients (64.1%) were considered to be anemic. The estimated survival rate is 35.7% at 5 years in patients with a normal Hgb, versus 21.7% in anemic patients (p = 0.0016). The estimated locoregional failure rate is 51.6% at 5 years in patients with a normal Hgb, versus 67.8% in anemic patients (p = 0.00028). The estimated rate of grade 3 or greater toxicity is 19.8% at 5 years in patients with a normal Hgb, versus 12.7% in anemic patients (p = 0.063). On multivariate analysis, several variables were found to be independent predictors of survival including: T stage, Karnofsky performance status, N stage, age, total radiation dose to the primary, and Hgb level. Independent predictors of locoregional control included T stage, Karnofsky performance status, N stage, radiation dose, and Hgb level. The only variables which predicted for the development of late RT complications were gender (p = 0.0109) and age (p = 0.0167). These findings were consistent regardless of whether Hgb level was considered a dichotomous or continuous variable. CONCLUSION: Low Hgb levels are associated with a statistically significant reduction in survival and an increase in locoregional failure in this large prospective study of patients with advanced head and neck cancer. Hgb level should be considered as a stratification variable in subsequent studies of head and neck cancer. Strategies to increase Hgb prior to RT in patients with head and neck cancer may lead to improved survival and loco-regional control.

Analysis of Variance↗

PubMed1998

Magnetic resonance imaging diagnosis of Takayasu arteritis.

Conventional angiography has been used for diagnosis of Takayasu arteritis (TA). In early stage of TA, subtle inflammatory wall thickening of the aorta and its branches without significant stenosis may be the only morphologic change of TA. Magnetic resonance (MR) imaging appears to be useful in the diagnosis of early stage TA by visualizing concentric wall thickening of the vessels. T2-weighted images may show bright signal of edema in and around the inflamed vessel. Contrast media-enhanced MR shows enhanced wall of vessels even in chronic stage, which may indicate the activity of TA at the tissue level. MR angiography allows us noninvasive assessment of the vascular tree and it may replace conventional angiography.

Adult↗

PubMed1998

Distribution of antioxidant enzymes in the normal aged human conjunctiva: an immunocytochemical study.

BACKGROUND: The purpose of the study was to map the precise location of four antioxidant enzymes in the normal human conjunctiva. METHODS: Conjunctival tissue (seventeen specimens) from seven patients was processed for light microscopy and immunogold electron microscopy. Antibodies were used to label glutathione peroxidase, glutathione S-transferase (acidic and neutral forms) and copper/zinc superoxide dismutase. RESULTS: All layers of the epithelium exhibited labelling for all four enzymes, although there were differences in labelling intensities and distribution between the enzymes. Wing cells showed more intense labelling for glutathione peroxidase, glutathione S-transferase (neutral form) and copper/zinc superoxide dismutase than did basal and superficial cells. The strongest immunoreactivity was detected for glutathione S-transferase (acidic) and was equally strong in the superficial and wing cells. Wing cells demonstrated more immunoreactivity in the cell nuclei with antibodies against all four enzymes. A high degree of labelling was also observed in the microplicae and actin cortex of the superficial cells. Leukocytes, fibroblasts, endothelial cells and erythrocytes within the stroma exhibited minimal labelling. CONCLUSION: The subtle changes in distribution of antioxidant enzymes in the normal human conjunctival epithelium most probably reflect exposure to free radicals in the tear film and are based on the different proliferative and functional activities of each of the anatomical layers.

Aged↗