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Biomedical subjects

I Goldberg

Publications and source records attributed to I Goldberg.

At least 91 records · Page 5Linked to original sources
PubMed1999

The Hettinger hand vibration test, vasospasm, and glaucoma.

Ocular vasospasm in response to local and/or systemic stimuli may contribute to ischemia of the optic nerve. The Hettinger hand vibration test was applied to patients with and without glaucoma to identify subgroups with a high systemic vasospastic tendency. A total of 580 subjects were tested (113 controls, 86 glaucoma suspects, 270 with primary open-angle glaucoma, 71 with secondary open-angle glaucoma, 30 with normal-tension glaucoma, and 10 with angle-closure glaucoma). The frequency distribution curve of Hettinger scores (HS) was bimodal, suggesting two distinct groups. Within each diagnostic group, a subpopulation with a high HS could be identified. Multivariate analysis demonstrated a significant association between the nonselective topical beta-blocker timolol and higher mean HS (P = 0.04) and a significantly higher proportion of subjects with HS of 1.5 or more (P = 0.01). Although subjects taking systemic beta1-selective blockers had significantly lower mean HS (P = 0.04), the proportion of patients with HS of 1.5 or more was not affected significantly by topical and systemic beta1-selective blocker use. Whereas topical nonselective beta-blockers may have an adverse effect on vasospastic tendency, systemic beta1-selective blockers may be partially protective against this effect.

Adrenergic beta-Antagonists↗
PubMed1999

Testing for glaucoma with the spatial frequency doubling illusion.

We examined the performance of tests for glaucoma based on the spatial frequency doubling (FD) illusion. Contrast thresholds for seeing the FD illusion in four large visual field regions were measured from 340 subjects who were tested up to seven times over 2 years. Median sensitivities of 91% at specificities of 95% were obtained. Test-retest variability for the worst hemifield thresholds averaged 2.22 db +/- 0.09 S.E. for all tested groups, and significant progression was observed for glaucoma suspects over the seven visits, indicating that tests based on the FD illusion can detect diffuse early glaucomatous loss.

Adult↗
PubMed1999

Laminin alpha2 deficient congenital muscular dystrophy: prenatal diagnosis.

Laminin alpha2 chain-deficient congenital muscular dystrophy (CMD) is diagnosed by genetic analysis and by immunohistochemistry. Since laminin alpha2 chain is expressed in placental trophoblasts, the demonstration of its deficiency in chorionic villi is a useful aid to prenatal diagnosis. We present our experience with the use of the immunohistochemical method for prenatal diagnosis in four women, all of whom had at least one child with laminin alpha2 chain-deficient CMD. Immunohistochemistry provided a rapid procedure for prenatal diagnosis, and follow-up of these four cases confirmed its reliability.

Antibodies, Monoclonal↗
PubMed1999

High levels of MMP-2, MMP-9, MT1-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma.

The object of this study was to analyze the potential association between the expression of MMP-2, MMP-9, MT1-MMP and TIMP-2, and disease outcome in advanced-stage ovarian carcinomas. Sections from 70 paraffin-embedded blocks (36 primary ovarian carcinomas and 34 metastatic lesions) from 45 patients diagnosed with advanced stage ovarian carcinomas (FIGO stages III-IV) were studied using mRNA in situ hybridization (ISH) technique. Patients were divided retrospectively in two groups based on disease outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period for patients that were diagnosed with advanced-stage carcinoma was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Intense mRNA signals were detected more frequently in tumor cells of short-term survivors with use of all four probes. Comparable findings were observed in peritumoral stromal cells with ISH for MMP-2, MMP-9 and TIMP-2 mRNA. Notably, primary tumors with intense mRNA signal for TIMP-2 (No = 14) were uniformly associated with a fatal outcome. In univariate analysis of primary tumors, mRNA levels of TIMP-2 in stromal cells (P = 0.0002), as well as for MMP-9 (P = 0.012) and TIMP-2 (P = 0.02) in tumor cells, correlated with poor outcome. In univariate analysis of metastatic lesions, mRNA levels of TIMP-2 in stromal cells (P = 0.031), as well as for MMP-2 (P = 0.027) and MT1-MMP (P = 0.008) in tumor cells, correlated with poor outcome. Interestingly, the presence of MT1-MMP in stromal cells correlated with longer survival (P = 0.025). In a multivariate analysis of ISH results for primary tumors, TIMP-2 levels in stromal cells (P = 0.006) and MMP-9 levels in tumor cells (P = 0.011) retained their predictive value. We conclude that MMP-2, MMP-9, MT1-MMP and TIMP-2 are valid markers of poor survival in advanced-stage ovarian carcinoma.

Adult↗
PubMed1999

A randomized phase II trial of interferon-alpha2b versus 5-fluorouracil after trabeculectomy.

PURPOSE: The aim of the present study was to investigate the safety and potential efficacy of subconjunctival interferon-alpha2b (IFN-alpha), either alone or in combination with 5-fluorouracil (5-FU), in reducing the risk of failure of glaucoma surgery METHODS: A prospective, masked randomized phase II study was undertaken in which patients received three subconjunctival injections per week for 3-4 weeks postoperatively. Three treatments were compared: (i) IFN-alpha (1 x 10(6)IU per dose); (ii) 5-FU (5 mg per dose); and (iii) alternating IFN-alpha and 5-FU (BOTH). The primary outcome measures were: (i) rate of successful control of intra-ocular pressure without further surgery; and (ii) the incidence of side effects. RESULTS: Fifty-seven patients undergoing glaucoma surgery with an increased risk of failure were evaluated, including 23 patients (40%) undergoing trabeculectomy combined with extracapsular cataract extraction as well as other conventional high-risk groups. With 53 patients (93%) completing 2 years follow up,there was no significant difference in success rates among the three groups. Intra-ocular pressure was controlled without further surgery in 79% of patients (95% confidence interval (CI): 61, 97%) receiving IFN-alpha, in 89% of patients (76, 100%) receiving 5-FU and in 89% of patients (76, 100% receiving BOTH. Side effects were similar among the three groups. CONCLUSIONS: These results are consistent with a beneficial effect of IFN-alpha2b given either alone or in combination with 5-FU after glaucoma filtering surgery. However, the lack of a clear and substantial benefit over conventional anti-fibrotic therapy does not support the further clinical evaluation of these treatments.

Adult↗
PubMed1999

Evaluation of oculokinetic perimetry.

BACKGROUND AND METHOD: Oculokinetic perimetry (OKP) was performed on 98 patients (187 eyes) using the Damato 26-point glaucoma screening chart. Results were compared with those obtained from a 24-2 full threshold test on a Humphrey Field Analyser (HFA). RESULTS: In its ability to detect pathology in individual eyes, OKP had a sensitivity of 75.0% and a specificity of 71.4%. To detect glaucoma, OKP demonstrated a sensitivity of 86.0% and a specificity of 56.1%. The number of OKP defects detected increased with increasing HFA mean defect and corrected pattern standard deviation. Whereas moderate and severe field defects were almost always detected, smaller and shallower glaucoma defects were often missed. CONCLUSION: The fall in sensitivity and specificity of the OKP chart in identifying milder glaucomatous field defects diminishes its value as a screening test. However, its introduction into wider use in the community may increase awareness of glaucoma amongst general practitioners and members of the public, and help to detect previously undiagnosed glaucoma with moderate to severe damage. A normal OKP finding does not exclude the presence of early glaucoma. Combined with ophthalmoscopy, OKP may improve glaucoma detection rates amongst non-ophthalmologists.

Adolescent↗
PubMed1999

Can the current oculokinetic perimetry chart be improved?

BACKGROUND/METHOD: Several studies have been performed to determine the effectiveness of oculokinetic perimetry (OKP) as a glaucoma screening test. In a previous study, we noted that OKP sensitivity and specificity was lower in mildly defective fields compared with moderately or severely, defective fields. In this study, we looked at visual fields with 'glaucomatous' defects. The visual field was divided into zones and points. The frequency of glaucomatous defects and visual sensitivity levels in these areas was recorded. The sensitivity and specificity of OKP to detect these defects were analysed. RESULTS: Ninety-six glaucomatous fields from 57 subjects were assessed. An OKP chart testing the 8 to 16 degrees of eccentricity, and an extended nasal region, would cover all the defective fields present in this study. The 12-16 degree eccentricity zone has the best sensitivity (75%) and specificity (65%). Points within the nasal, inferior temporal and 8-12 degree eccentricity might be less sensitive, but 11 (11.5%) fields had defects only in these areas. Zonal and point sensitivities and specificities were very similar suggesting that fewer points could be used in each zone with similar results. Many of the eyes with false-negative OKP results had Humphrey Field Analyser visual sensitivity levels in the 10-18 dB range (i.e. associated with a mild or moderate defect). Decreasing the target stimulus might increase the detection rate of these milder defects; however, it might also increase overall false-positive rates. Our proposed experimental chart consists of two to four test points in each quadrant within the 12-16 degree of eccentricity, five within the 8-12 degree zone and two in the nasal region, and a central 1 or 1.5 mm black target. CONCLUSION: Analysis of results with modifications of the testing device may permit the OKP chart to achieve its full potential.

False Negative Reactions↗
PubMed1999

Caffeine-mediated induction of c-fos, zif-268 and arc expression through A1 receptors in the striatum: different interactions with the dopaminergic system.

Adenosine and the adenosine receptor antagonist, caffeine, modulate locomotor activity and striatal neuropeptide expression through interactions with the dopaminergic system by mechanisms which remain partially undetermined. We addressed this question by using quantitative immunocytochemistry and in situ hybridization, combined with retrograde tracing of striatal neurons, to characterize the mechanism(s) leading to the striatal increase in the immediate early genes (IEG), c-fos, zif-268 and arc, following a single injection of caffeine or the A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Caffeine and DPCPX induced c-fos, zif-268 and arc expression, both at mRNA and protein levels, in large proportions of striatonigral and striatopallidal neurons. The involvement of dopamine systems was evaluated by manipulations of the dopaminergic transmission. Quinpirole, a D2 agonist, almost completely blocked the caffeine-induced IEG increase in both striatopallidal and striatonigral neurons. Conversely, the lesion of the nigrostriatal pathway and the D1 antagonist SCH23390 abolished the caffeine effects in striatonigral neurons but had no or slight effect, respectively, on its action in striatopallidal neurons. These observations demonstrate that caffeine- and DPCPX-mediated IEG inductions involved different mechanisms in striatonigral and striatopallidal neurons through blockade of A1 receptors. Immediate early gene inductions result from a stimulation of dopamine release in striatonigral neurons and from activation of glutamate release and probably also acetylcholine release in striatopallidal neurons. These results also support the idea that, besides A2A receptors, adenosine acting at the A1 receptor plays pivotal functions in the basal ganglia physiology and that blockade of these receptors by specific or nonspecific antagonists, DPCPX and caffeine, may influence a broad range of neuronal functions in the striatum.

Adenosine↗
PubMed1999

Proliferation, apoptosis and thymic involution.

The thymus reaches its maximal size at the age of 1 month in ICR mice and thereafter, the thymic cortex undergoes an exponential decline. This study was designed to compare the proliferation and apoptosis of thymocytes in different parts of the thymus of ICR female mice at the beginning and after the rapid phase of decline of the thymic cortical cellularity. The pattern of proliferation and apoptosis of the thymus was studied in situ in 1-month-old ICR female mice (10 mice) compared to mice at 7 months of age (10 mice). Staining for argyrophylic nucleolar organizer region by histochemistry was used to determine the proportion of type 2 thymocytes, which are considered as cells at S phase of the cell cycle. The mean number of type 2 cells in four random samples of 50 cells in each part of the thymus was defined as the proliferation index of this part of the thymus. In situ detection of apoptosis of thymocytes was carried out using the Apoptag kit, which can detect a single cell apoptosis. The mean number of apoptotic cells in five randomly selected fields of each part of the thymus was defined as the apoptotic index of this part of the thymus. The proliferation index of the peripheral cortex of the 1-month-old mice was 3.6 times higher than the proliferation index of the deep cortex and 5.8 times higher than the proliferation index of the medulla (P < 0.0001). The proliferation index of the peripheral cortex of the 7-month-old mice was reduced by 45% compared to the 1-month-old mice (P < 0.005). The apoptotic index of the corticomedullary junction of the 1-month-old mice was six times higher than the apoptotic index of the cortex and 18 times higher than the apoptotic index of the medulla. The apoptotic index of the thymic cortex was elevated by 66% in the 7-month-old mice compared to the 1-month-old mice (P < 0.0001). We conclude that there is a reduction of the proliferation index and an elevation of the apoptotic index of the thymic cortex in adult mice compared to young mice. These changes might account for the reduction of thymic cortical cellularity during thymic involution.

Aging↗
PubMed1999

Multiple glomus tumor: a case report and review of the literature.

Multiple glomus tumors are extremely rare and differ from the more common solitary glomus tumors in their clinical presentation and histological features. The authors report a case of multiple glomus tumors of the right hand in a 65-year-old man, its treatment, and a review of the features of this uncommon tumor. The tumor usually presents as a painful, firm, purplish, solitary nodule of the extremities, especially in the nail bed. Multiple glomus tumors are described as softer, more compressible, bluish nodules and they occur with less frequency than solitary tumors. They are often inherited in an autosomal dominant pattern. The authors present a case of multiple glomus tumors of the right hand, in which many small, painful, red papules were grouped in the right hypothenar region. The patient was treated by wide excision of the lesion and coverage of the defect with an ulnar artery forearm flap.

Aged↗
PubMed1999

The epidermotropic mycosis fungoides associated alpha1beta1 integrin (VLA-1, CD49a/CD29) is primarily a collagen IV receptor on malignant T cells.

Several of the beta1 integrin receptors [very late antigen (VLA) molecules] for extracellular matrix (ECM) proteins are expressed by malignant T cells in cutaneous T-cell lymphoma (CTCL). We evaluated the function of VLA-1, a beta1 integrin specifically expressed in epidermotropic mycosis fungoides (MF), in CD4+ leukemic T cells Jurkat line). We found that Jurkat cells adhere significantly to collagens only after their activation with phorbol 12-myristate 13-acetate (PMA). However, the adhesion to collagen IV (but not to collagen I) of Jurkat cells selected for expressing increased levels of VLA-1 (with unchanged levels of VLA-2, the second collagen integrin receptor) was significantly enhanced relative to that of "VLA-1 low" cells. Monoclonal antibody (mAb) 1B3.1, directed against the collagen binding domain of VLA-1, inhibited adhesion to collagen IV and to collagen I by 36.67%+/-5.25% and 18%+/-4.32%, respectively (p<0.05), whereas the inhibition by anti-VLA-2 mAb PIE6 was comparable on both collagens (25%+/-7.48% and 36.3%+/-0.94%, respectively; p<0.09). Immuno-histochemical studies of skin biopsies from 10 untreated MF patients showed that in all cases at least 10% of the lymphocytes residing in the epidermis are VLA-1+VLA-2-. While not directly applicable to MF, the demonstrated functions of VLA-1 in leukemic Jurkat cells, together with its expression in MF skin, suggest a role for VLA-1 integrins in epidermotropism in a small proportion of leukemic MF cells.

Antigens, CD↗
PubMed1999

Expression of metalloproteinases endometrial stromal sarcoma: immunohistochemical study using image analysis.

AIM: To investigate the expression of matrix metalloproteinases (MMP), a group of proteolytic enzymes with a central role in extracellular matrix invasion and degradation, in stromal sarcomas. METHODS: 11 endometrial stromal sarcomas (four low grade tumours, seven high grade) were stained for MMP-2, MMP-3, and MMP-9 using immunohistochemical stains. The surgical material consisted of nine hysterectomy specimens and two pelvic recurrences. Three hysterectomy specimens, removed for leiomyomas, were studied as controls. Staining area was evaluated using image analysis. RESULTS: Age at the time of diagnosis ranged from 21 to 67 years. Four of the 11 patients (three with high grade tumours and one with a low grade tumour) died of the disease, six remained free of disease, and one was lost to follow up. Staining for MMP-2, MMP-3, and MMP-9 was more diffuse in high grade tumours than in low grade tumours and controls. Staining for MMP-3 and MMP-9 was more pronounced in high grade than in low grade tumours (p = 0.04; p = 0.05). Staining for MMP-9 was significantly greater in all stromal sarcomas than in controls (p < 0.001 for high grade tumours v controls; p < 0.01 for low grade tumours v controls). Diffuse staining for MMP-2, exceeding 90% of the tumour area, was observed in three of seven high grade tumours but in no low grade tumours. There was no apparent correlation between staining for any of the three enzymes and survival. CONCLUSIONS: Both low and high grade endometrial stromal tumours express matrix metalloproteinases. MMP-3 and MMP-9 are expressed more diffusely in high grade than in low grade tumours. In the individual case, diffuse staining for MMP-2 appears to best characterise the high grade tumours. Thus staining for MMP-2 may aid in differentiating high grade from low grade tumours, and MMP-9 in differentiating normal endometrial stroma from low and high grade endometrial stromal sarcomas. MMP expression does not appear to predict disease outcome in endometrial stromal sarcoma.

Adult↗
PubMed1999

Enhancement of atherosclerosis in beta-2-glycoprotein I-immunized apolipoprotein E-deficient mice.

We have previously shown that low density lipoprotein receptor-deficient (LDL-RD) mice immunized with beta2-glycoprotein I (beta2GPI; a target of autoimmune anticardiolipin antibodies) developed enhanced early atherosclerosis, when fed a normal chow diet. The current study was undertaken to evaluate the effect of immunization with beta2GPI and the addition of a high fat diet on the progression of atherosclerosis in the apolipoprotein E (ApoE)-deficient mouse. Six-week-old female ApoE-deficient mice (n = 10) were immunized subcutaneously with either human beta2GPI or with ovalbumin, both emulsified in complete Freund's adjuvant and fed a high fat diet for 6 weeks. The beta2GPI-immunized mice were found to develop accelerated atherosclerosis when compared with their ovalbumin-immunized littermates (aortic lesion area of 137,500 +/- 13,801 vs. 72,444 +/- 14,465 microm2, respectively; p = 0.0067). The beta2GPI-immunized mice developed high titers of anti-beta2GPI antibodies, 10 days after the procedure, which were sustained until the sacrifice. LDL extracted from both study groups displayed similar susceptibility to ex vivo oxidation. These results confirm our previous study in which we found increased atherosclerosis in beta2GPI-immunized LDL-RD mice fed a chow diet. In the current study we show that the proatherogenic effect of beta2GPI immunization is maintained despite high cholesterol levels and is not associated with increased susceptibility of LDL to ex vivo oxidation.

Animals↗
PubMed1999

Increased endothelial cell expression of alpha3beta1 integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome.

The objective of this work was to determine markers of endothelial cell activation in valves from patients with antiphospholipid syndrome (APS) and heart valve involvement, in order to establish a role for endothelial cells in the pathogenesis of the valvular disease. Sixteen valves from ten patients with APS, obtained from autopsies or removed during valve replacement, were studied. Two groups of valves were used as controls. One group included seven normal valves from patients who died from non-cardiac diseases. The other group of valves were obtained from patients with bacterial endocarditis during autopsies or valve replacement operations. Immunoperoxidase and immunofluorescence stainings with antibodies to human immunoglobulins, endothelial cells, alpha3beta1 integrin, collagen IV, laminin and fibronectin were employed. Three histopathological patterns were apparent: normal valves, valves with verrucous endocarditis and valves with fibrocalcific changes. In all the valves with verrucous endocarditis the following findings were observed: (1) increased expression of the alpha3beta1 integrin on the endothelial cells, (2) increased amount of collagen IV, laminin and fibronectin, (3) proliferation of blood vessels and (4) linear subendothelial deposition of immunoglobulins and complement. The valves with fibrocalcific changes were deformed and showed a thick layer of collagen IV, laminin and fibronectin, yet in two valves the indothelial cells showed an expression of the alpha3beta1 integrin. The control valves did not express the integrin and had only a thin subendothelial band of collagen IV. In valves from patients with APS, 1 markers of endothelial cell activation are upregulated while the inflammatory exudate is scant. There is also a prominent deposition of immunoglobulins in the valves from patients with APS, suggesting a possible association between the deposition of the antibodies and the activation of the endothelial cells in APS.

Actins↗
PubMed1999

Local complement genes expression in the mammary gland: effect of gestation and inflammation.

Complement components in breast milk may enhance the local immune response in the gut of infants. In this study, we investigated the expression of complement genes in the mammary gland and attempted to determine possible regulatory mechanisms. We have studied the expression of C3, C4, factor B, and HLA-DRalpha mRNA by in situ hybridization in gestational mammary gland specimens and compared these findings to those in breast tissue affected with an inflammatory process, lactating adenoma or idiopathic gynecomastia. In normal resting breast, only C4 mRNA was noted in some ductal epithelium. In gestational mammary gland, there was a diffuse expression of C4, C3, and factor B mRNA in the epithelial cells of the acini. A similar pattern of complement gene expression was found in localized areas of an infectious inflammatory process. In addition, in the inflammatory specimens, there was also expression of C3 mRNA in infiltrating macrophages (CD 68 positive cells). In gynecomastia, C4 mRNA was noted in ductal epithelium, and there was a marked increased expression of C3 mRNA in the proliferating epithelium of the lactating adenoma. HLA-DRalpha was observed only in macrophages involved in the inflammatory response. Our findings, which reflect the hormonal and inflammatory events in vivo, provide new insights as to in situ complement gene expression.

Adenoma↗
PubMed1999

Flexible specialist training compared with full-time training.

The educational and training quality of flexible training posts compared very well and in some instances was better than that obtained in full-time training. The hours of work were fewer, but as a proportion not as small as is sometimes recognized by the Colleges and is comparable with many full-time training programmes in other European Union countries.

Curriculum↗
PubMed1999

Antibodies to the cytoplasm, cell membrane and nuclear membrane of malignant neoplasms in pooled normal human polyspecific immunoglobulin G.

IVIg is a preparation of normal polyspecific IgG obtained from pooled plasma of a large number of healthy donors. IVIg treatment of patients with chronic lymphocytic leukemia induced a reduction in the total number of lymphocytes in the peripheral blood. Regression of Kaposi's sarcoma was also noted in an HIV patient treated with IVIg. The aim of this study was to determine whether F(ab')2 prepared from IVIg binds to cellular structures of different tumor tissues. Biotinylated F(ab')2 was prepared from 3 different preparations of IVIg and from affinity purified IgG from a patient with multiple myeloma. Direct immunohistochemistry using a streptavidin peroxidase staining method was performed on biopsy samples of 18 different tumor tissues. Positive staining of the cytoplasm, cell membrane and nuclear membrane of several types of malignant tumors by F(ab')2 from IVIg was immunohistochemically demonstrated. Nuclear staining of tumor cells by IVIg was rare. IVIg bound to different tumors of epithelial origin, especially colon carcinoma, breast carcinoma and squamous cell carcinoma of the lung. Malignant tumors of mesenchymal origin such as leiomyosarcoma have also demonstrated positive staining by IVIg. IVIg contains antibodies to the cytoplasm, nuclear membrane and cell membrane of different malignant tumors especially of epithelial origin. This binding might provide a basis for the assumption that IVIg treatment of cancer patients may induce antibody dependent cell mediated cytotoxicity response against tumors, and implies that it can be potentially beneficial as adjuvant treatment of malignant diseases.

Antibody Affinity↗