The effects of myasthenic immunoglobulins on neuromuscular transmission and thymus histology in mice.

An autoimmune reaction to the endplate acetylcholine receptor (AChR) is thought to be responsible for the muscular weakness of myasthenia gravis (MG). However, the significance of antithymic antibodies and the thymic AChR-like protein is still uncertain. We transferred immunoglobulins (Igs) from patients with MG to mice. Thymitis was observed in 12 of 14 mice, and miniature endplate potential amplitudes were reduced in 8. Control mice showed none of these abnormalities. Immunofluorescence examination failed to reveal the binding of human IgG, IgM, or IgA to the thymic tissue. Our findings support the hypothesis that antithymic antibodies may alter thymic histology.

Association of tumor washout rates and accumulation of technetium-99m-MIBI with expression of P-glycoprotein in lung cancer.

UNLABELLED: In a prospective study, we correlated the washout rates of 99mTc-sestamibi (MIBI) and the degree of MIBI accumulation with the expression of P-glycoprotein (Pgp) in tumor tissues in a total of 46 patients with lung cancer. METHODS: All patients underwent early (30 min) and delayed (3 hr) MIBI imaging and bronchoscopic biopsy before initiation of chemo- or radiotherapy. The interval between biopsy and imaging varied between 2 and 10 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of Pgp. Normal tissue and tumor washout rates and tumor-to-background ratios were correlated with the level of Pgp expression. RESULTS: There was an inverse correlation between tumor-to-background ratios and the density of Pgp (p = 0.001), whereas there was no appreciable correlation between tumor washout rates of MIBI and the level of Pgp expression (p = 0.414). CONCLUSION: The current data strongly suggest that, although the reduced ability for the tumors to accumulate MIBI correlates well with the increased levels of Pgp expression, tumor washout rates of MIBI do not correlate with the density of Pgp in tumor tissues. Our results also warrant additional research for correlating immunohistological and imaging findings with messenger RNA levels determined by polymerase chain reaction and flow cytometry.

Influence of the heterogeneity of P-glycoprotein expression on technetium-99m-MIBI uptake in breast cancer.

UNLABELLED: We prospectively studied a total of 30 patients with breast cancer to evaluate the relationship between the degree of accumulation of 99mTc-sestamibi (MIBI) and the heterogeneity of p-glycoprotein expression in tumor tissues. METHODS: Twenty patients during initial presentation and 10 patients during post-therapy evaluation underwent contemporaneous 99mTc-MIBI imaging and surgery or biopsy. Immunohistochemical studies were performed on multiple nonconsecutive sections of the same tumor using a p-glycoprotein-specific monoclonal antibody, JSB-1. Tumor-to-background (T/B) ratios were correlated with the level and heterogeneity of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: The T/B ratios were lower for those tumors with strong p-glycoprotein expression (Group 1) than those with strong-to-weak expression (Group 2) or those with weak-to-no expression (Group 3) (1.32 +/- 0.19 and 1.85 +/- 0.56 and 2.86 +/- 1.06, respectively). There was statistically significant difference in T/B ratios between all 3 groups (p < 0.005). Although T/B ratios for Group 1 and Group 3 were clearly distinct from one another with no overlapping values, the values for Group 2 overlapped with those of Group 1 and Group 3. When we evaluated the entire patient group with excluding those with strong-to-weak expression, although the p value remained the same (p < 0.001), we obtained a stronger correlation between T/B ratios and p-glycoprotein expression (r = 0.808 versus 0.735). CONCLUSION: Due to the heterogeneous expression of p-glycoprotein, both immunohistochemistry and 99mTc-MIBI scintigraphy may yield confounding results by contrasting with one another if the presence or absence of p-glycoprotein is not extensively explored. Although our data confirmed that 99mTc-MIBI imaging is useful in the determination of the presence of multidrug resistance in patients with breast cancer, the issue of heterogeneous expression of the antigen should be further investigated when unexpected results are obtained.

Clinical validation of the influence of P-glycoprotein on technetium-99m-sestamibi uptake in malignant tumors.

UNLABELLED: We prospectively studied 48 patients with either breast cancer (30 patients) or lung cancer (18 patients) to ascertain the relationship between the degree of accumulation of 99mTc-sestamibi and the expression of p-glycoprotein in tumor tissues. METHODS: During initial presentation (37 patients) or post-therapy evaluation (11 patients), the patients underwent contemporaneous 99mTc-sestamibi imaging and biopsy (30 patients) or surgery (18 patients). The interval between surgery/biopsy and imaging varied between 3 and 15 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of p-glycoprotein. Tumor-to-background ratios were correlated with the level of p-glycoprotein expression determined by immunohistochemical studies. RESULTS: Our results showed an inverse correlation between the tumor-to-background ratios of 99mTc-sestamibi and the density of p-glycoprotein expression in tumor tissues. The values for the tumor-to-background ratios were significantly lower for those tumors expressing p-glycoprotein at high levels than those with scattered and no expression (p < 0.01 and p < 0.001, respectively). CONCLUSION: Although our results warrant further studies at the molecular level using PCR techniques after the extraction of mRNA, our data strongly suggest that 99mTc-sestamibi imaging is useful to noninvasively determine the presence of multidrug resistance in patients with malignant tumors.

Incidence of aplastic anemia in Turkey: a hospital-based prospective multicentre study.

The incidence of aplastic anemia among hospitalized adult patients was prospectively determined in this first study in Turkey. New cases of aplastic anemia among patients 14 years and older who were admitted to the study centers were included in a 3 year survey. Seventy-three patients fulfilled the diagnostic criteria, yielding a mean annual incidence rate of 1.14 cases in 10(3) admissions. The male-to-female ratio of the cases (1.6:1) differed from the almost equal ratio of the larger population of Turkey. The median age was 30 years and females were younger at diagnosis. The age distribution of the cases was different from that of the population; showing two incidence peaks in both sexes. The majority of the patients (89%) had severe disease.

Gastritis cystica polyposa.

Gastritis cystica polyposa was diagnosed in five patients between ages 29 and 61 years. All five had been operated on for peptic ulcer disease three to 26 years earlier, when gastroenteric anastomoses had been made. The presenting complaint was abdominal pain, nausea and vomiting, or gastrointestinal bleeding. The lesions, located on the gastric side of the anastomosis, consisted of polypoid mucosal changes associated with hyperplasia and cystic dilatation of glands. Radiologic and endoscopic findings were often nondiagnostic, and surgical intervention was necessary to relieve obstruction and to rule out carcinoma. Resection of the gastrojejunostomy site and choosing anastomotic techniques to minimize bile reflux into the stomach appear to be the preferred methods of treatment.

Myasthenia gravis and lymphoblastic lymphoma involving the thymus: a rare association.

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disease. An association between thymic epithelial neoplasms and MG is well known. However, it is rarely associated with hematologic malignancies. In particular, very few cases of lymphoblastic lymphoma involving the thymus and MG have been reported. Here we report a case T-cell lymphoblastic lymphoma involving the thymus who developed MG after the initial diagnosis. The patient initially presented with a mediastinal mass which was diagnosed as lymphoblastic lymphoma. MG was diagnosed during leukemic relapse in this patient and was based on clinical presentation and neurophysiologic studies including single fiber electromyography (EMG) and repetitive nerve stimulation tests. In contrast to the other cases with such an association, the myasthenic symptoms presented nine months after the diagnosis of lymphoma by thymectomy. The patient had a highly aggressive clinical course and was resistant to various chemotherapy regimens.

Posterior deviation of left ventricular outflow tract septal components without ventricular septal defect.

OBJECTIVE: To describe 11 patients with narrowing of the left ventricular outflow tract caused by angular posterior deviation of both the outlet septum and the upper part of trabecular septum, which was diagnosed by cross sectional echocardiography in all and confirmed by angiocardiography in seven. RESULTS: Four patients had a subaortic systolic pressure gradient ranging from 23 to 70 mm Hg by Doppler echocardiography; cardiac catheterisation showed a significant (60 and 104 mm Hg) systolic pressure gradient in two. In four cases aortic regurgitation and two tricuspid pouches were shown by Doppler echocardiography, angiocardiography, or both. Four cases had a ridge at the angulation point on echocardiographic examination. Three patients were operated on for systolic pressure gradients of the left ventricular outflow tract and one for severe aortic regurgitation. There was proliferation of collagen-rich fibrous tissue in the subendocardial region on histopathological examination of the myectomy material. A ventricular septal defect had been diagnosed previously by contrast echocardiography in one patient; thus ventricular septal defects may close spontaneously over a period of time including fetal life. A subaortic ridge was detected in one patient at follow up. CONCLUSIONS: Deviation of the outlet and trabecular septa should be considered as a cause of ventricular outflow tract obstruction even when no ventricular septal defect is present.

Malignant teratoma of the cerebellopontine angle: case report.

A case of malignant teratoma of the cerebellopontine angle is presented. Preoperative findings suggested an acoustic neurinoma or a meningioma. Particularly in adulthood, malignant teratomas arising in unusual locations can simulate common intracranial tumors.

Cystic cavernous hemangioma of the cerebellopontine angle: case report.

A case of cystic cavernous hemangioma of the cerebellopontine angle is described. The clinical findings, location of the tumor, and computed tomographic findings were unusual. This rare lesion must be considered in the differential diagnosis of cystic infratentorial masses.

Familial atrial myxoma.

Familial and biatrial myxomas of the heart have rarely been described. We describe a familial atrial myxoma involving a parent with biatrial and a child with a left atrial myxoma. Atrial myxomas were diagnosed preoperatively by echocardiography and successfully removed at operation. Echocardiography can be used in the diagnosis of cardiac myxoma, detection of its possible recurrence and for screening other members of the family.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with prostatic carcinoma.

Inappropriate antidiuretic hormone secretion (SIADH) may occur in a variety of diseases, including malignancies, and can be induced by drugs. We report a case of SIADH associated with prostatic carcinoma. A 50-year-old man was admitted to hospital with severe flank pain and weight loss. The diagnosis of SIADH syndrome and prostatic carcinoma was established, and hormonal therapy was instituted. However, the patient died in a month without any response to therapy. We conclude that prostatic carcinoma may cause SIADH and should therefore be considered in the differential diagnosis.

Factors influencing the distribution of metastases and survival in metastatic breast carcinoma.

A total of 370 patients with metastatic breast, carcinoma who had been followed at Hacettepe Oncology Department between 1980 and 1991 were retrospectively analyzed for the factors influencing the distribution of metastases and survival. Median age was 47 years. Radical or modified radical mastectomies were performed in 199 (53.8%). Infiltrative ductal carcinoma was the most common pathologic subtype (69.4%). In 191 patients who were evaluated for estrogen receptor (ER) status, 101 (52.9%) were positive and 90 (47.1%) were negative. The distribution of first metastases did not differ between the soft tissue, bone, and visceral sites. The second, third, and fourth metastases were more common in visceral sites (p < 0.05). ER and menopausal status did not affect distribution. Mortality rate was significantly lower in the group having the first metastasis to the bone (p < 0.05). Of interest, first metastases were predominantly found in visceral sites in patients having radical or modified radical mastectomies (p < 0.05). Response to therapy, presence of initial metastases, axillary status, and age were the important factors influencing the overall survival in univariate analysis, whereas response to therapy, ER status, age, and presence of initial metastases were the important factors according to the multivariate analysis.

In situ characterization of gingival mononuclear cells in rapidly progressive periodontitis.

Rapidly progressive periodontitis (RPP) has been suggested as a distinct clinical entity within the spectrum of early onset periodontitis. Immunological mechanisms have been considered in the pathogenesis of RPP. This study was designed to evaluate the distribution and phenotypic properties of the lymphocyte populations within the affected gingival tissue of patients with RPP. Biopsies were obtained from 16 patients between 22 and 33 years of age. The tissue samples were processed for both histopathological and immunohistochemical examinations. Gingival tissue T lymphocytes (CD3+), helper T cells (CD4+), suppressor-cytotoxic T cells (CD8+), and cells positive for HLA-DR antigen were identified using monoclonal antibodies with an immunoperoxidase technique. Intracytoplasmic immunoglobulin-containing cells were also stained immunohistochemically with polyclonal antibodies. CD3+ cells were mainly located beneath the pocket epithelium. CD4+ and CD8+ cells were evenly distributed within this T-cell infiltrate with a CD4+/CD8+ ratio of 1:12. Numerous HLA-DR+ cells were also observed in the lymphocytic infiltrates. The majority of mononuclear cells located throughout the stroma were IgG+ plasma cells. Our results indicate that RPP patients present an IgG-bearing plasma cell dominated lesion with equal participation of both T-cell subpopulations. These findings suggest that activation and proliferation of B-cells play an important role in the pathogenesis of periodontal diseases.

The effect of age on proliferating cell nuclear antigen expression in oral gingival epithelium of healthy and inflamed human gingiva.

BACKGROUND: Age-related changes in proliferative activity in human gingival epithelium are uncertain. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. The aims of this study were to investigate the localization of PCNA expression in oral gingival epithelium (OGE) and to define the age-related changes as to PCNA-proliferative index (PI) in inflamed as well as healthy gingiva. Mitotic index (MI) was also used as a conventional marker of cell proliferation. Additionally, the effect of aging upon the maximum epithelial thickness (MET) was determined. METHODS: Twenty older (65 to 85 years) (study) and 20 middle-aged (35 to 45 years) (controls) subjects were included in the study. Biopsies were obtained both from healthy and inflamed gingiva. The expression of PCNA was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and PC 10 monoclonal antibody to PCNA. Hematoxylin and eosin stained sections were used for the quantitative measurement of MI and MET. RESULTS: All the tissue sections contained positive staining cells for PCNA in the gingival epithelium. Although PCNA expression was observed both in the basal and suprabasal layers, it was more prominent in the suprabasal layers. PI in inflamed gingiva was significantly higher in the older group. However, no significant difference was observed between the study and control groups with respect to PI in healthy gingiva. When all the subjects taken into the study were analyzed as a single group, PI in the inflamed gingival samples were found to be increased with aging. Nevertheless, no age-related change was noted in MI and MET. In both the study and the control groups, PI, MI, and MET were found to be increased due to inflammation. CONCLUSIONS: Our data indicate that PCNA expression in inflamed gingiva is higher in older subjects. Furthermore, a significant correlation was noted between aging and PCNA expression in inflamed gingiva. As there is no increase in mucosal epithelial thickness despite increased proliferation, we speculate that the duration of the PCNA+ phase in cell cycle may be longer in older subjects. This study also implies that PCNA immunolocalization can be used as an index of the state of cell proliferation in both biological and pathological events of the gingiva and/or other mucosal tissues.

Epidermolysis bullosa acquisita: clinical manifestations, microscopic findings, and surgical periodontal therapy. A case report.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an uncommon, acquired, chronic subepidermal bullous disease. This report describes a case of EBA with gingival involvement. A 43-year-old woman with EBA was referred to our clinic for periodontal therapy because of gingival tenderness and bleeding. She has been on cyclosporin A therapy for the last 2 years. METHODS: Clinical findings were analyzed. Anterior gingivectomy operations were performed in 2 stages. The samples obtained during the surgery were examined using histopathologic, immunohistologic, and electronmicroscopic methods. Long-term effects of the surgical periodontal treatment on gingiva were evaluated both clinically and microscopically. RESULTS: The dentition displayed minimal enamel hypoplasia. Decayed, missing, and filled surfaces score was found to be elevated. Periodontal examination showed generalized diffuse gingival inflammation and gingival enlargement localized mainly to the anterior region. Nikolsky's sign was positive. However, wound healing was uneventful after the operations. Microscopic findings were similar to those obtained from the skin. Twenty-one months after the operations, Nikolsky's sign was negative and no remarkable gingival inflammation was noted. Microscopic examination revealed that the blisters were fewer in number and smaller in size. CONCLUSIONS: These results indicate that gingival tissues may also be involved in EBA. Uneventful wound healing after periodontal surgery in this case suggests that periodontal surgery can be performed in patients with EBA. Moreover, both our clinical and histopathologic findings imply that gingivectomy proves useful in maintaining gingival integrity in these patients. Our data may also suggest that the patients with EBA are highly likely to develop dental caries.

Hypereosinophilia and metastatic anaplastic carcinoma of unknown primary.

The differential diagnosis of eosinophilia may sometimes be difficult. Eosinophilia may occur in a diverse array of conditions from parasitic infestations to malignacies. Idiopathic hypereosinophilic syndrome has also been described. A 65-year-old male patient presenting with eosinophilia of obscure etiology is described in the present report. Three years after the diagnosis of eosinophilia, metastatic anaplastic carcinoma of unknown primary was detected. Differential diagnosis is disscussed briefly. It is stressed that patients with hypereosinophilia of unknown etiology must be screened for malignancy regularly during follow up.

Subependymal giant cell astrocytoma associated with tuberous sclerosis: diagnostic and surgical characteristics of five cases with unusual features.

Five children with tuberous sclerosis and intracranial tumors were surgically treated at Neurosurgery Department of Hacettepe University School of Medicine. Two of the five patients presented with the giant cell astrocytoma filling the third ventricle. Direct surgical intervention and tumor removal was carried out in all four patients (three with a total surgical resection and one with a subtotal resection) and cerebrospinal fluid shunting procedure in one. Histopathological examination revealed giant cell astrocytomas in four patients. Postoperatively, one died and the rest four patients survived with minor focal neurologic difficulties. The surgical results and the changing concepts in the treatment of tuberous sclerosis are discussed and the literature is reviewed.

Myasthenia gravis and primary squamous cell carcinoma of the thymus.

Occurrence of primary squamous cell carcinoma of the thymus gland in a 65-year-old man with myasthenia gravis is reported. Histologic and immunohistochemical studies confirmed the diagnosis of a differentiated squamous cell carcinoma. Extensive clinical investigations ruled out another primary site for the tumor. The patient made a full recovery postoperatively. Only three cases of primary squamous cell carcinoma of the thymus gland in association with myasthenia gravis have been reported in the literature.

Correlation of flow cytometric parameters and transferrin receptors with gallium-67 scintigraphic images in lymphoma patients.

The purpose of this study was to determine the correlation of flow cytometric parameters and transferrin receptors with gallium-67 scintigraphic imaging results in Hodgkin's and non-Hodgkin's lymphoma patients. DNA content and cell cycle analyses were performed using flow cytometry and transferrin receptor analysis was carried out by the immunohistochemistry technique in 24 patients aged between 16 and 62 years. All patients underwent gallium-67 scintigraphy, and tumour to background ratios were calculated. The findings were correlated with computed tomography and/or magnetic resonance imaging. A strong relationship was observed between flow cytometry and transferrin receptor expression with gallium-67 tumour scintigraphy [P = 0.005, r = 0.054 and P = 0.038, r = 0.54 (Spearman test), respectively]. The results of this study show that there is a close correlation between each of these modalities and, as they reflect the biological activity of the tumour, together they have a major role in treatment and follow-up.