Prevention of biochemical changes in gamma-irradiated rats by some metal complexes.

The formation of superoxide partially accounts for the well-known oxygen enhancement of radiation-induced biochemical changes and cell damage. Radioprotective effects of copper (II), manganese (IV) or vanadium (IV) complexes, of superoxide dismutase-mimetic activity, on body weight, survival rate and some biochemical parameters in pre-treated irradiated, untreated irradiated and treated non-irradiated female albino rats have been studied 24 h after whole body gamma-irradiation at a dose level of 6 Gy. Survival time, body weight, red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin (Hb) concentration, percentage of hematocrit (Hct%), reduced glutathione (GSH), serum total protein, albumin, globulin (G), blood urea, creatinine and cholesterol were estimated, as well as the activities of blood superoxide dismutase (SOD), glutamate-oxaloacetic (GOT) and glutamate-pyruvic (GPT) transaminases, and alkaline phosphatase were assessed. A significant decline was shown in body weight, survival rate, the mean values of RBC and WBC counts, Hb and Hct percentages, and GSH concentration, as well as blood SOD activity, in whole body gamma-irradiated rats compared with the control non-irradiated rat group. The mean activity values of alkaline phosphatase, GOT and GPT, as well as the average values of blood urea, creatinine, total cholesterol, total protein and globulin were significantly elevated, while the average values of albumin and the albumin/globulin ratio were decreased in gamma-irradiated rats compared with the corresponding values of the normal control rat group. Pretreatment of rats with either manganese or vanadium complexes resulted in a significant increase in survival rate and body weight over that of the non-treated irradiated rat group. Pretreatment of rats with copper (II), manganese (IV) or vanadium (IV) complexes caused a significant increase in RBC and WBC counts, Hb concentration, HCt (%), GSH content and SOD activity in blood when compared to the irradiated rat group without treatment. The administration of copper (II), manganese (IV) or vanadium (IV) complexes prior to irradiation exposure resulted in a significant decrease in GOT and GPT activities in addition to blood urea, creatinine, cholesterol, globulin and total protein contents, while each complex exhibited a significant increase in plasma alkaline phosphatase, albumin, and the albumin/globulin ratio compared to the untreated irradiated rat group. Administration of vanadium (IV), manganese (IV) or copper (II) complexes in non-irradiated rats caused a significant increase in SOD activity without changing other biochemical parameters compared with the corresponding values of the normal control rat group. We conclude that these metallo-elements, particularly manganese (IV) and vanadium (IV) complexes of 2-methylaminopyridine, have radiation protection and radiation recovery. Furthermore, these metal complexes offer a new approach to overcome the pathological effects of ionizing radiation and suggest their use as a physiological approach to preventing or perhaps predominantly facilitating recovery from radiation injury.     

Interaction of the leucine-rich repeats of polycystin-1 with extracellular matrix proteins: possible role in cell proliferation.

Polycystin-1, the product of the PKD1 gene, is a membrane-bound multidomain protein with a unique structure and a molecular weight of approximately 460 kD. The purpose of this study is to investigate the binding of the cystein-flanked leucine-rich repeats (LRR) of polycystin-1 to extracellular matrix (ECM) components. These interactions may play a role in normal renal development as well as the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). In vitro assays were used to assess the binding of a fusion protein containing the LRR of polycystin-1 and that of affinity purified polycystin-1 to a number of ECM components. The results showed that the LRR modulate the binding of polycystin-1 to collagen I, fibronectin, laminin, and cyst fluid-derived laminin fragments. The addition of the LRR fusion protein to cells in culture resulted in a significant dose-dependent reduction in the rate of proliferation. Cyst fluid-derived laminin fragments had a stimulatory effect on cell proliferation, which was reversed by the LRR fusion protein. These results suggest that the LRR of polycystin-1 act as mediators of the polycystin-1 interaction with the ECM. The observed suppression effect of the LRR on cell proliferation suggests a functional role of the LRR-mediated polycystin-1 involvement in cell-matrix and cell-cell interactions. These interactions may result in the enhanced cell proliferation that is a characteristic feature of ADPKD.     

Characteristics of patients with congenital clasped thumb: a prospective study of 40 patients with the results of treatment

Purpose  Congenital clasped thumb is a deformity that is associated with heterogeneous congenital anomalies and it has been addressed in many congenital syndromes. The aim of this study was to diagnose and evaluate cases of clasped thumb as regards the associated congenital anomalies and syndromes, and evaluation of the results of treatment of such cases. Methods  A prospective study on 40 patients with 73 clasped thumbs was done. All the patients’ data regarding their personal, family, pregnancy and developmental histories were recorded. All the patients were exposed to thorough clinical and radiological examination and genetic assessment. The cases were classified using the Tsuyuguchi et al. (J Hand Surg [Am] 10:613–618, 1985) classification into three types. Conservative treatment was adopted in ten hands, and surgical treatment was performed for 28 hands in 17 patients, with an average follow-up of 26 months. Results  Positive consanguinity was recorded in 57.5% of cases. Associated anomalies were recorded in 77.5% of cases. Type I was the most common one, followed by type III and then type II. Conservative treatment is effective in type I cases when presented early, and all patients were satisfied with the results of surgical treatment. Conclusions  We reported associated anomalies which are to our knowledge have not mentioned before in the literature which include; congenital blindness, radial deviation of the index finger and ventricular septal defect. We found that 68% of the patients had associated syndromes, and this has not been mentioned before. In this study, we found that there were no difference between type II and type III clasped thumb as regards the pathological findings, severity, the operative procedures, the treatment protocol and the operative results. Properly planned treatment gives satisfactory results.     

Tracheostomal stenosis revision with simultaneous tracheoesophageal puncture

Objectives/Hypothesis: Vocal rehabilitation of patients who have undergone laryngectomy is best accomplished by a tracheoesophageal puncture. Optimal function of the prosthesis requires an adequate stoma. Patients with tracheostomal stenosis require revision of the stoma if vocal rehabilitation is to take place. Revision and tracheoesophageal placement are usually done as two separate procedures. Creating a tracheoesophageal fistula at the time of stomal revision has not been addressed in the literature. Study Design: Prospective analysis and follow-up of 10 patients undergoing simultaneous tracheoesophageal puncture and stomal revision for tracheostomal stenosis between 1991 and 1996. Methods: Ten patients were reviewed. An inferiorly based V-Y advancement flap was used so as not to interfere with the tracheoesophageal puncture. All patients had received radiation prior to revision and tracheoesophageal puncture. Patients were followed for a minimum of 2 years (range, 2–6 y; median, 3 y). Results: All patients maintained an adequate stoma without stenting. Eight of ten patients (80%) developed and maintained good tracheoesophageal speech. Two patients had their speech fistulas removed. There were no intraoperative or postoperative complications. Conclusions: Creation of a tracheoesophageal fistula at the time of stomal revision allows for vocal rehabilitation with a single visit to the operating room. Laryngoscope, 108:1509-1513, 1998     

Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1). METHODS: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion. RESULTS: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated. CONCLUSIONS: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.     

Transcranial Doppler to evaluate the effects of antihypertensive medication on cerebral blood flow velocity.

The effect of oral nifedipine on cerebral blood flow velocity was studied in six elderly hypertensive patients using transcranial Doppler. Serial measurements of blood pressure (BP), middle cerebral artery (MCA) flow velocity and nifedipine serum concentrations were obtained over an 8-hour period. The authors found a significant inverse relationship between MCA velocities and nifedipine concentrations, independent of BP changes. These results are consistent with a direct vasodilatory effect of nifedipine on cerebral vessels and support the use of TCD in pharmacodynamic investigations of the cerebral vasculature.     

Adenocarcinoma with simultaneous squamous carcinomas of the larynx

Background. Primary adenocarcinoma of the larynx is a rare neoplasm. The incidence is reported as less than 1% of all laryngeal neoplasms in multiple series. Simultaneous primary adenocarcinoma and a solitary squamous cell carcinoma of the larynx is even rarer and only one case has been found on review of the literature. Methods. A case report of a 74-year-old man with a history of right-sided throat pain, odynophagia, and progressive hoarseness is presented with a review of the literature pertaining to this unusual case. Results. The patient was found to have three distinctly separate laryngeal lesions on direct laryngoscopy. Histopathologic diagnosis of adenocarcinoma was made on one of the three biopsied sites with the other sites being squamous cell carcinoma. Following Combined radiotherapy and surgical treatment, the patient has remained free of disease. Conclusions. Adenocarcinoma of the larynx is an infrequent and lethal disease. This case report and a review of the literature demonstrate that aggressive surgical management is indicated, although still may not result in improved survival. © 1994 John Wiley & Sons, Inc.