Increased bladder apoptosis with alpha-1 adrenoceptor antagonists in benign prostatic hyperplasia.

OBJECTIVE: To determine whether preoperative usage of alpha-1 adrenoceptor antagonists (alpha-1ARA) prevents the alterations in bladder wall components due to obstruction via changing apoptotic and/or proliferative activity and provides an advantage for improvement of irritative symptoms following removal of bladder outlet obstruction. MATERIAL AND METHODS: A total of 39 patients were enrolled to the present study. According to preoperative medical treatment, patients were divided into 2 groups as preoperative untreated (n = 15) and medically treated patients with alpha-1ARA (n = 24). Apoptotic and proliferative indices of bladder wall were determined with TUNEL assay and proliferating cell nuclear antigen immunoreactivity, respectively. RESULTS: While the mean apoptotic indexes (AI) of lamina propria were 0.293 +/- 0.163 vs 0.978 +/- 0.194 in untreated and treated patients, the mean AI of myofibroblast cells were 0.10 +/- 0.06 and 0.90 +/- 0.23 in untreated and treated patients, respectively. There were statistically significant differences between lamina propria (p = 0.0067) and myofibroblast cells (p = 0.0280) AI in the two groups. However, there were no significant differences between postoperative symptom indices in preoperatively treated and untreated groups. CONCLUSIONS: alpha 1-ARA treatment might have an effect on hypertrophy and supersensitivity of bladder wall due to increased outlet obstruction via prevention of the imbalance between cell proliferation and apoptosis, providing normal homeostatic control mechanisms, through the interval between the onset of the lower urinary tract symptoms and time surgical intervention. However, further studies should be organized to demonstrate the impact of long-term alpha 1-ARA medication for post-operative significant improvement on irritative symptom index.

The role of expression of extracellular matrix proteins and epidermal growth factor receptor activity on fertilization capacity of testicular harvested spermatozoa.

It has been suggested that multiple growth factors are crucial for spermatogenesis. We analyzed whether alterations on epidermal growth factor receptor activity and different expression pattern of extracellular matrix proteins had an impact on the fertilization capacity of spermatozoa and pregnancy rate after testicular sperm extraction and intracytoplasmic injection. Extracellular matrix proteins and epidermal growth factor receptor were immunohistochemically evaluated in testis of 88 patients with nonobstructive azoospermia. Testicular sperm extraction and intracytoplasmic injection procedure was also performed in 32 of the patients for whom mature sperm could be harvested from the testicular tissue. While collagen Type-IV and laminin activity percentages were 33.1% and 86.4% in motile sperm harvested testicular tissue, these activities were 23.3% and 89.3% in immotile sperm harvested testicular tissue, respectively. In addition, the mean epidermal growth factor receptor expression was higher in immotile than motile sperm obtained tissue (56.4% vs. 51.1%, P=0.4928). There was no statistically significant relationship between the extracellular matrix protein and epidermal growth factor receptor expression patterns and sperm motility, fertilization and pregnancy rates in testicular sperm extraction and intracytoplasmic injection. However, further studies are required to investigate the relationship between other growth factors and sperm fertilization capacity.

Detection of LOH of the RB1 gene in bladder cancers by PCR-RFLP.

OBJECTIVES: Retinoblastoma (RB1) gene involves in retinoblastoma, osteosarcoma, bladder, prostate, lung, breast carcinomas, and soft tissue sarcomas. Loss of heterozygosity (LOH) is the most common mutation of the gene. METHODS: Xba I polymorphism in intron 17 of the gene was used to detect LOH in 20 bladder cancer patients. A cystitis and an osteosarcoma were used as control. LOH was investigated in three different kinds of samples (blood, paraffin-embedded tissue and fresh tissue) belonging to the same patients, and 20 blood samples, 20 paraffin-embedded tissue samples and 16 fresh tissue samples were obtained from 20 cancer patients. RESULTS: None of the 20 blood samples showed LOH. Eleven out of 20 paraffin-embedded bladder tissues were amplified, 3 of them homozygous and all 8 informative paraffin-embedded tissues showed LOH. Five out of 16 fresh tumor tissues obtained were amplified, in 1 the fresh tissue was normal, 1 fresh tissue showed LOH and 3 were not digested by Xba I. CONCLUSION: The results of the study have suggested that detection of LOH of the RB1 gene by PCR-RFLP can be a good adjunctive test for evaluation of the bladder cancer.

Persistent hyperinsulinaemic hypoglycaemia of infancy: case report.

Hyperinsulinism, although rare, is the most common cause of persistent hyperinsulinaemic hypoglycaemia in infancy. Because of persistent hypoglycaemia, serious difficulties are encountered in the long term management of this condition. A male neonate, after an uncomplicated full-term pregnancy, had been admitted to another hospital with convulsions on the third post-natal day. Meningitis had been suspected at that time and treated with phenobarbital and he had been discharged from the hospital. At three-months old he was referred to our department for persistent convulsions and lethargy. His parents were of 1st degree consanguinity. His blood glucose level was found to be 24 mg/dl (1.33 mmol/L). Because of the dangerously high insulin level during hypoglycaemia (insulin/glucose > 0.3), the absence of ketonuria, and the need for a high dose of glucose infusion (> 15 mg/kg/min) to achieve normoglycaemia and a glycaemic response to glucagon despite the hypoglycaemia, a diagnosis of persistent hyperinsulinaemic hypoglycaemia of infancy was made. Since maximal doses of prednisone, glucagon, diazoxide, octreotide and high infusion of glucose were ineffective in achieving normoglycaemia, a subtotal (80%) pancreatectomy was done. Postoperatively intermittent hypoglycaemic episodes continued. These were controlled with low doses of octreotide. Histology revealed diffuse adenomatous hyperplasia (nesidoblastosis). The boy is now in the sixth post-operative month and developing normally.

Bcl-2 and p53 expression in insular and in well-differentiated thyroid carcinomas with an insular pattern.

Expression of p53 and bcl-2 oncogenes was investigated in poorly differentiated, so-called insular carcinomas of the thyroid gland and also in the follicular and papillary carcinomas with an insular component. Hematoxylin-eosin sections of 217 thyroid carcinomas were reevaluated for insular carcinoma and also for thyroid carcinomas with an insular component. Immunohistochemical staining method was used for detecting p53 and bcl-2 expression on paraffin blocks of three pure insular, five follicular or papillary thyroid carcinomas with a major insular component (more than 50%) and six with a minor insular component (20-50%). Flow cytometry was also performed in these cases. None of the cases showed p53 immunoreactivity. Bcl-2 expression was observed in all cases and the most intense staining was seen in insular areas. All the cases were diploid. We suggest that bcl-2 plays a role in loss of differentiation of thyroid carcinomas.

Clinicopathologic evaluation of CDw75 antigen expression in patients with gastric carcinoma.

Situated on mature B lymphocytes, CDw75 antigen is a sialylated carbohydrate epitope generated by the enzyme beta-galactosyl alpha-2,6-sialyltransferase. Although CDw75 antigen expression was found to be correlated with aggressive behaviour of tumour cells in gastric adenocarcinomas, its prognostic role still remains unknown. The objective of this study was to determine the value of CDw75 antigen expression as a marker of the metastatic potential and prognosis of gastric adenocarcinomas. CDw75 antigen expression was evaluated immunohistochemically in 64 tumours and their nodal metastases. The correlation was analysed between CDw75 antigen expression and selected clinicopathological variables, including survival. Positive staining was detected in 31 cases. Non-neoplastic gastric mucosa was consistently negative. CDw75 expression was correlated with larger tumour size (p<0.006), infiltrative growth pattern (p<0.044), advanced stage (p<0.0006), and positive lymph nodes (p<0.0003). The overall survival rate of patients with CDw75 expression was 28%, which was significantly worse than that of patients without CDw75 expression (53%) (p<0.0005). Multivariate analysis showed that CDw75 expression was an independent prognostic indicator, together with the growth pattern of the tumour. These results indicate that immunohistochemical detection of CDw75 antigen expression may be a good indicator of metastatic potential and of prognosis in patients with gastric carcinomas.

EGFR and p53 expression and proliferative activity in parathyroid adenomas; an immunohistochemical study.

EGFR (epidermal growth factor receptor), p53, and proliferative markers provide some clues as to the formation of several tumours. In this study the mechanism of the genesis of parathyroid adenomas was investigated using immunohistochemistry. Sections of parathyroid adenomas from 12 cases were stained using PCNA (proliferating cell nuclear antigen), EGFR, and p53 immunohistochemistry. Correlations between PCNA LI (labelling index), EGFR expression, p53 expression, age, serum parathormone, Ca and P levels, and tumour diameter were investigated. PCNA LI was 45.8+/-33.1 (mean+/-standard deviation) and all the cases were somewhat positive. Five cases (41.67 %) were EGFR positive. Maximum 10 % of the cells were positive in these cases. All the cases were p53 negative. There was a correlation between PCNA LI and serum parathormone level (r=0.607, p=0.036). According to these results, parathormone synthesis is high when the proliferative activity of parathyroid adenoma is high. Four of the five EGFR-positive patients were below 35 years of age. These data may indicate that formation of parathyroid adenoma in young patients is related to a mechanism involving EGFR. Absence of p53 expression suggests that p53 mutation is not a common component of parathyroid adenomas.

Epithelial membrane antigen and S-100 protein expression in benign and malignant papillary thyroid neoplasms.

Papillary carcinoma of the thyroid is mainly diagnosed with histopathologic features. Classical papillary architectures are important but nuclear change is the essential diagnostic element. Papillary architecture may be seen in benign lesions such as in hyperplastic areas of the follicular neoplasms, multinodular goiter and Grave's disease. Differential diagnosis of papillary carcinoma and papillary hyperplasia is very important for clinical management. Some authors have reported that Epithelial Membrane Antigen (EMA) and S-100 protein expression would be valuable and helpful in identifying papillary neoplasia and distinguishing it from papillary hyperplasia. In this study, EMA and S-100 protein expression of 14 papillary thyroid carcinomas and 13 papillary hyperplasias were studied by using immunohistochemical methods. In 14 papillary carcinomas, 9 showed diffuse and 3 revealed focal S-100 protein nuclear and cytoplasmic immunostaining. Two cases were not stained. All of the 13 papillary hyperplasias were negative for S-100 protein. EMA expression was observed in the apical cytoplasmic location of 11 papillary carcinomas except one case that showed diffuse cytoplasmic staining and one which was negative. In the papillary hyperplasias, 7 revealed both cytoplasmic and apical cytoplasmic staining. One case showed only cytoplasmic staining. Five cases were negative for EMA. The difference in the S-100 protein expression is significant, however immunostaining of EMA is similar in both lesions. We concluded that differential diagnosis of papillary structures in carcinomas and hyperplasias was mainly diagnosed on the histopathologic features but S-100 protein expression could be helpful in difficult cases.

Multidrug resistant malignant melanoma with intracranial metastasis responding to immunotherapy.

Metastatic malignant melanoma (MM) is well known for its poor response to chemotherapy, radiotherapy, and its remarkable susceptibility to interleukin-2 (IL-2) based immunotherapies. MM with brain metastatis in particular, has 4-5 months life expectancy from metastasis to death. Drug efflux pumps such as P-glycoprotein (P-gp), or drug detoxifying mechanisms e.g. glutathion epsilon S-transferase-pi (GST) are some of the possible multidrug resistance (MDR) mechanisms in MM. Here we report the first P-gp+ MDR MM with brain metastasis in the literature, demonstrating a remarkable response to IL-2, interferon-alpha (IFN), 5-fluorouracil (5FU) regimen. A 41-year old man was admitted with multiple inoperable brain lesions. Biopsies from intracranial and dermal lesions revealed MM. Cisplatin, carmustine, dacarbazine, tamoxifen (CCDT) together with external cranial radiotherapy were administered, and partial response in lesions and symptoms was achieved. However, after the third course of CCDT treatment, he was admitted to the emergency ward with dramatically increased intracranial lesions, and recurring dermal lesions. A biopsy from the recurred lesions revealed that MM cells were P-gp+, but GST. Administration of a IL-2, IFN and 5FU regimen achieved a remarkable decline in the brain lesions with almost total disappearance of symptoms. He was well and capable of doing work for 18 months. Dermal lesions had not recurred since the beginning of immunotherapy. In contrast, another 34-year old man who developed brain metastases after CCDT for MM, was negative for P-gp and GST. Cranial radiotherapy was started and the above mentioned IL-2 based regimen was administered. However, no response was observed. These two cases together with previous studies demonstrating the susceptibility of P-gp+ MDR cancer cell lines to IL-2 activated killer (LAK) cells in this report suggest that P-gp+ MDR MM is probably a good candidate for IL-2 based treatments.

Tuberculosis-associated haemophagocytic syndrome: a report of two cases and a review of the literature.

The haemophagocytic syndrome (HS) is an uncommon reactive proliferation of mature histiocytes, and is more frequently but not exclusively associated with infections in individuals with pre-existing immunologic abnormalities. As far as we know, only 13 cases of tuberculosis-associated HS have previously been reported. We present here two cases of disseminated tuberculosis-associated HS. Both of the cases recovered with antituberculosis therapy. High-dose methylprednisolone and intravenous immunoglobulin were added in one case because of the extremely severe clinical presentation. This therapy seemed to contribute to the favourable outcome of the patient. The similarities in HLA phenotypes of this patient and others reported in the literature may provide evidence for an underlying immune dysregulation in some cases of infection-associated HS.

Cutaneous histoplasmosis in a child with hyper-IgM.

Immunodeficiency with hyperimmunoglobulinemia M is a rare disease characterized by very low levels of IgG and IgA and normal or high levels of serum IgM and IgD. Recurrent and severe systemic infections with pathogenic bacteria are frequent if immunoglobulin replacement therapy is not given. Histoplasmosis is a systemic granulomatous mycosis due to Histoplasma capsulatum and characterized by a particular affinity for the reticuloendothelial system. Glabrous skin involvement in histoplasmosis is highly unusual except in patients with advanced human immunodeficiency viral disease. Cutaneous histoplasmosis and granulomatous reaction were diagnosed in a 5-year-old boy with hyper-IgM disease. The lesion improved after oral ketoconazole therapy. To our knowledge, this is the first case of cutaneous histoplasmosis associated with hyper-IgM to be reported.

Myelodysplastic syndrome in a patient with Werner's syndrome.

Werner's syndrome is a relatively rare autosomal recessive disorder characterized by several features generally associated with aging. This syndrome is classified in the group of chromosome instability syndromes and there is an increased incidence of neoplasia. Hematologic malignancies associated with this syndrome are, however, unusual. Herein we report a case of Werner's syndrome with myelodysplastic syndrome, a clonal preleukemic disorder of hemopoietic stem cells. Such an association, to the best of our knowledge, has not been reported in the English literature so far.