A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.     

Management of late-onset bleb leaks

PURPOSE OF REVIEW: This paper reviews various methods of both medical and surgical management of late bleb leaks. RECENT FINDINGS: The hood procedure without bleb removal may be preferred for small leaking blebs and autologous conjunctival bleb resurfacing for large leaking blebs. If hypotony is present preleak, revision of the underlying scleral flap may also be required. SUMMARY: Blebs with late leaks are a major problem after glaucoma filtration surgery and can result in hypotony or endophthalmitis. Conservative treatment and laser therapy both have limited success in sealing the leaks and are not as effective as surgical management. Many surgical techniques are used, but none is universally successful.     

Determination of certain drugs in binary mixtures formulations by second derivative ratio spectrophotometry and LC

Spectrophotometric and high-performance liquid chromatographic (HPLC) methods are developed for simultaneous determination of three binary mixtures with overlapping spectra. The spectrophotometric method is based on the use of second derivative of the ratio spectra (2DD) for resolution of three binary mixtures of indapamide with captopril (mixture 1), cinnarizine with heptaminol acefylline (mixture 2) and amoxycillin trihydrate with flucloxacillin sodium (mixture 3). The HPLC method depends on the separation of components of binary mixtures using ODS column with mobile phase consisting of acetonitrile and 5 mM aqueous heptane sulphonic acid sodium salt in ratios of (60:40, v/v, pH 5.5) for mixture 1, (50:50, v/v, pH 3.0) for mixture 2 and (35:65, v/v, pH 4.2) for mixture 3. The proposed methods are accurate, non-destructive and successfully applied for the determination of the three binary combinations in synthetic mixtures and commercial pharmaceutical products.     

Single photon emission tomography (SPECT) study of regional cerebral blood flow in normoalbuminuric children and adolescents with type 1 diabetes

Abstract: Cerebral damage in diabetes can be related to chronic hyperglycemia and recurrent severe hypoglycemia as well as due to the associated vasculopathy. The pattern of regional cerebral blood flow using cerebral single photon emission tomography (SPECT) was evaluated in normoalbuminuric type 1 diabetic children and adolescents and its relation to the metabolic control and cognitive functions. Thirty-one type 1 diabetics aged 10–18 yr (mean 14.7 ± 3.4) were included, 16 males and 15 females, divided into four groups: group I (n = 8) with history of recurrent severe hypoglycemia (≥ 3); group II (n = 8) with history of severe diabetic ketoacidosis (≥ 3); group III (n = 7) with recurrent minor hypoglycemia (≥ 3/week); and group IV (n = 8) with controlled diabetes. The control group (V) comprised seven healthy children, aged 10–18 yr (mean 14.2 ± 3.1). SPECT was done using technetium-99m hexamethyl propylene amine oxime. There was significant brain hypoperfusion in diabetics compared with controls, mainly in the basal ganglia (p < 0.01) and frontal regions (p < 0.01), with less changes in parietal and temporal regions. These changes were not related to the age, sex, diabetes duration, mean blood glucose or HbA1C. Basal ganglia hypoperfusion was significant in groups I (p < 0.01) and II (p < 0.01) compared with controlled diabetics. There was no correlation between cerebral SPECT changes and cognitive scores in type 1 diabetics.
Conclusion: Subclinical alterations in cerebral blood flow (hypoperfusion) are present in children and adolescents with type 1 diabetes mainly affecting the basal ganglia and frontal regions, usually not associated with measurable alterations of the cognitive functions     

Oxygen radical production in neutrophils interacting with platelets and surface-immobilized plasma proteins: role of tyrosine phosphorylation

The interaction between neutrophil granulocytes and platelets is considered to play an important role in the inflammatory process induced by an implanted foreign material. However, the cellular mechanisms involved remain incompletely understood. We used a luminol-dependent chemiluminescence (CL) technique to analyze the generation of reactive oxygen species (ROS) in human neutrophils interacting with different plasma protein-coated surfaces in the presence or absence of unstimulated or stimulated platelets. The role of tyrosine phosphorylation in the regulation of NADPH oxidase activity was evaluated with quantitative fluorescence microscopy and the specific tyrosine kinase inhibitor genistein. We found that the ROS-production is 2 to 3 times higher in neutrophils on immunoglobulin G (IgG)-coated surfaces than in cells interacting with albumin- or fibrinogen-coated surfaces. Incubation with superoxide dismutase and catalase revealed that about 45% of the ROS was released extracellularly on IgG surfaces whereas corresponding values were 90% and 85% in neutrophils interacting with albumin and fibrinogen, respectively. The presence of platelets markedly increased the extracellular generation of ROS, mainly in neutrophils interacting with IgG- or fibrinogen-coated surfaces whereas the intracellular production was only modestly affected. Quantitative fluorescence microscopy of neutrophils stained with FITC-conjugated anti-phosphotyrosine antibodies showed a correlation between tyrosine phosphorylation, cell spreading, and ROS production. Platelets markedly amplified the anti-phosphotyrosine staining on both fibrinogen- and IgG-coated surfaces whereas the low level of tyrosine phosphorylation in neutrophils on albumin-coated surfaces was not further elevated by platelets. Furthermore, the tyrosine kinase inhibitor genistein inhibited both extra- and intracellular ROS production in neutrophils regardless of the presence of platelets. We demonstrate that plasma protein coating and the presence of platelets are crucial for the inflammatory response of adhering neutrophils and that the oxidative response correlates with the extent of tyrosine phosphorylation of proteins in focal contacts.     

Alterations of the Cell Cycle Regulators Cyclin D1, Cyclin A, p27, p21, p16, and pRb in Apocrine Metaplasia of the Breast

Abstract:  G1/S transition defects have been a proposed requirement for tumor development. Apocrine metaplasia (APM) in the breast has been held as a sign of benignity. Yet, a number of studies have reported the presence of molecular abnormalities in some forms of APM suggesting a possible oncogenic potential for some of these lesions. We currently investigate the role of some of the cell cycle proteins, previously reported to be de-regulated in breast cancer, in an attempt to assess their significance in APM. Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki-67 was examined in 93 cases of APM. The cases were divided into nonpapillary (NAPM) (30 cases) and papillary metaplasia (PAPM) (63 cases). PAPM was further subdivided into simple papillary (SPAPM) (29 cases), complex papillary (28 cases) and highly complex papillary (six cases). For statistical analysis, the last two groups were merged together (CPAPM). The results showed that increased histological complexity was associated with significant increase of proliferative capacity and alterations of the cell cycle control. The median Ki-67 index was 1.5% in SPAPM and 4.8% in the CPAPM. Also, alterations of the cell cycle regulators were significantly higher in the CPAPM than in the SPAPM. NAPM was generally similar to normal breast epithelium. Apocrine cells were negative for p16 while pRb was expressed in all cases. These findings suggest that in complex forms of APM, there is a considerable degree of cellular unrest. This may contribute to increased susceptibility to carcinogenesis.     

Limitations of the Heidelberg Retina Tomograph.

Glaucoma is a progressive optic neuropathy where damages that occur at the optic nerve head and the retinal never fiber layer are associated with changes in the visual field. The Heidelberg Retina Tomograph (Heidelberg Engineering, Carlsbad, CA), a scanning laser ophthalmoscope, performs a three-dimensional topographic analysis of the optic nerve head and the retinal never fiber layer. The Heidelberg Retina Tomograph has been reported to be a reliable and objective method of identifying structural changes prior to the occurrence of visual field defects. In our series of patients, all had significant visual field defects but normal Heidelberg Retina Tomograph results, including rim area and Moorfield regression analysis. It is important to recognize that interpreting the Heidelberg Retina Tomograph results alone may be misleading; however, when combined with careful clinical evaluation of the optic nerve head and the visual field, the Heidelberg Retina Tomograph may provide valuable information in assisting the clinician with the diagnosis and management of glaucoma.