The Nephropathy of Experimental Hepatosplenic Schistosomiasis

The glomerular lesions induced in 10 chimpanzees infected with variable numbers of Schistosoma japonicum cercariae were studied by means of light and electron microscopy and fluorescent antibody technic. Ten animals served as controls; 5 were uninfected and 5 were only lightly infected. The animals were observed for periods ranging from 3 to 17 months, and by the time of sacrifice, all had developed advanced liver fibrosis. In general, the degree of glomerular injury was related to infection intensity and degree and duration of portal liver fibrosis. Some animals had terminal BUN elevation and slight proteinuria. By light and electron microscopy, in the initial stages, only part of the glomeruli were involved and exhibited mesangial matrix expansion and mesangial cell proliferation with intracellular hyaline droplets. At later stages, a larger number of glomeruli were affected and exhibited diffuse hypercellularity, glomerular basement thickening, mesangial sclerosis and less often, focal necrosis, crescent formation, synechiae and global hyalinization. In addition, there were discrete electron-dense deposits localized in the mesangial area in some glomeruli. Immunofluorescent studies utilizing antisera to chimpanzee γ-globulin and complement (C3) and to human properdin disclosed only faint deposits of C3, apparently in mesangial areas. The association of hepatosplenic schistosomiasis and nephropathy, the possible role of schistosomal antigen and the mechanism(s) of such glomerular injuries are reviewed and compared with the disease in humans and other host species infected with Schistosoma.     

Isolation and genetic characterization of human KB cell lines resistant to multiple drugs

Human KB cell lines resistant to high levels of colchicine were isolated by several successive single-step selections. Most of these selection steps resulted in cross-resistance to vincristine, vinblastine, adriamycin, actinomycin D, and puromycin; however, at the highest levels of colchicine resistance, increased cross-resistance to other drugs was not observed. There was no major change in protein synthesis or alteration in protein phosphorylation or [^14C]glucosamine labeling patterns accompanying the development of multiple drug resistance as measured by analysis of metabolically labeled proteins on SDS gels. Cell-cell hybridization experiments showed that the colchicine-resistant and multiple drug-resistant phenotypes were incompletely dominant. In addition, colchicine resistance was found to segregate independently from resistance to other drugs in one somatic cell hybrid, suggesting that complex genetic loci are involved in the development of the multiple drug-resistant phenotype. These mutants should be useful for the study of the clinically important problem of multiple drug resistance in human cancer.     

Intralesional ethanol in the treatment of unresectable liver cancer

Percutaneous ethanol injection (PEI) under ultrasonography guidance has been widely tried in not advanced hepatocellular carcinoma (HCC). Ten years after the introduction of PEI, some conclusions of its indications can be drawn. In our series, 210 cirrhotic patients were treated; 141 with multisession PEI in an outpatient clinic, 57 with single session PEI under general anesthesia, and 12 with both. The 1-, 3-, and 5-year survival rates (by Kaplan-Meier method) were 93%, 65%, and 41% for Child class A patients with single HCC 5 cm, and 88%, 47%, and 33% for patients with multiple HCC up to five lesions 5 cm. In these patients the local recurrence rate was 15% and the new lesion rate at the 5-year follow-up was 74%. One death due to hemorrhage from esophageal varices in a Child class C patient treated by single session PEI occurred. The large number of cirrhotic patients enrolled in ultrasonography screening programs has created a large demand for effective, safe, repeatable, low-cost treatment that can be offered at many centers. PEI meets all these requirements. PEI is proposed as the treatment of choice for the mentioned patients, excluding candidates for liver transplantation and surgical resection according to the predictive adverse factors currently in use. Single session technique widened the indications of traditional PEI to larger lesions.

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Resumen La inyección percutánea de etanol (IPE) bajo guía ultrasonográfica ha sido ampliamente ensayada en carcinoma hepatocelular (CHC) no avanzado. Transcurridos diez años luego luego de la introducción de la IPE, se pueden sacar conclusiones pertinentes a su indicación: En nuestra serie, se trataron 200 pacientes cirróticos, 141 de ellos con IPE en múltiples sesiones en forma ambulatoria, 57 con una sesión única de IPE bajo anestesia generaly y 12 con ambas modalidades. Las tasas de sobrevida a 1, 3 y 5 años (por el método de Kaplan-Meier) fueron 93%, 65%, 41% en los pacientes en clase Child-A con CHC único de 5 cm, y 88%, 47% 33% en CHC múltiple de hasta 5 lesiones de 5 cm. En estos pacientes la tasa de recurrencia local fue 15% y la tasa de nuevas lesiones a los 5 años de seguimiento fue de 54%. Se presentó una muerte por hemorragia de várices esofágicas en un paciente en clase Child-C tratado con una sesión única de IPE. El gran número de pacientes cirróticos incorporados a programas de tamizaje con ultrasonido ha creado una gran demanda por tratamientos eficaces, seguros, reproducibles y de bajo costo. El IPE llena todos estos requerimientos. Se propone el IPE como el tratamiento de escogencia para los pacientes arriba mencionados, haciendo exclusión de los candidatos para transplante hepático y para resección quirúrgica de acuerdo con los factores adversos de pronóstico actualmente en uso. La técnica de une sesión única ha ampliado las significaciones tradicionales del IPE para ser aplicada a lesiones de mayor tamaño.

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Résumé L'alcoolisation par injection percutanée (APC) sous échographie est utilisée pour traiter des carcinomes hépatocellulaires (CHC) peu volumineux. Dix ans après l'introduction de la technique d'APC, on peut tirer des conclusions quant à es indications. Dans notre expérience, 210 patients cirrhotiques ont été traités: 141 ont été traités par APC en ambulatoire, 57 en «séance unique» sous anesthésie et 12 par les deux. La survie à 1, 3 et 5 ans (méthode de Kaplan-Meier) était respectivement de 93, de 65 et de 41 % pour les patients ayant une lésion unique 5 cm, classés Child A, et de 88, de 47 et de 33% chez les patients ayant des lésions multiples mais inférieures au nombre de 5, toujours 5 cm. Chez ces patients, le taux de récidive locale était de 15% et le taux de nouvelles lésions à 5 ans, de 74%. Il y a eu un décès par hémorragie en rapport avec une rupture de varices oesophagiennes chez un patient Child C traité en une seule séance d'APC. Le nombre croissant de patients actuellement soumis, à une surveillance par échographie va de paire avec un traitement efficace, sûr, de coût réduit, et facilement disponible dans de nombreux centres. L'APC répond à toutes ces conditions. L'APC peut être proposée comme traitement de choix pour des patients répondant aux critères suscités, en excluant les candidats à la transplantation ou ceux qui peuvent être traités chirurgicalement. Les indications de la technique préconisée ici, en une seule séance, s'élargissent actuellement à des lésions plus volumineuses.

     

Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days.

PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting.     

Dedifferentiated endometrial cancer: an atypical case diagnosed from cerebellar and adrenal metastasis: case presentation and review of literature

Dedifferentiated endometrial cancer (DEC) is microscopically characterized by the presence of high-grade areas emerging from low-grade tumour. DEC is an aggressive tumour even when the dedifferentiated component represents only 20% of the entire neoplasm. A proper histological diagnosis is essential to define the most appropriate therapeutic approach for these tumors, since they are characterized by a particularly aggressive trend and by an extremely poor prognosis. We report a single case of DEC associated with dedifferentiated and adrenal metastasis, for which the patient underwent both abdominal-pelvic and cerebellar surgery. Dedifferentiated carcinoma of the endometrium is a poorly recognized neoplasm since they have not been clearly defined the histological features discriminating this neoplasm from high-grade endometrioid adenocarcinoma. Revising existing literature we found 79 described cases of central nervous system secondary involvement and 13 cases where the onset of the disease was characterized by neurological signs and symptoms. We could only find two reported cases of adrenal metastases originating from endometrial neoplasia but in no case of dedifferentiated endometrial carcinoma previously described has been reported the concomitant adrenal-cerebellar involvement.     

Usefulness of a state-legislated,comparative database to evaluate quality in colorectal surgery

PURPOSE: Colorectal surgery, a high-volume procedure, has been targeted for performance improvement to reduce length of stay. Specific postoperative quality indicators and readmission rates should be analyzed concomitantly to assure that adverse events are not associated with earlier discharge. METHODS: From July 1, 1990, to June 30, 1997, 1,218 consecutive patients who underwent transabdominal colorectal surgery were analyzed for length of stay, mortality, morbidity, and discharge disposition. Each patient was assigned an Admission Severity Group rating 0 to 4 using a hospital-based state-legislated software system (Atlas) to validate comparative performance internally and externally. Readmission data within 120 days of discharge were available for the last 678 consecutive patients from July 1, 1993, to June 30, 1997, using Lastword (computerized medical records). RESULTS: The annual frequencies of the 1,218 procedures were 173, 183, 175, 146, 167, 189, and 185, respectively, from July 1990 through June 1997. Severity distribution was 32 for Admission Severity Group 0, 517 for Admission Severity Group 1, 540 for Admission Severity Group 2, 128 for Admission Severity Group 3, and 1 for Admission Severity Group 4, with no annual difference (P=0.012). There was a significant reduction in total length of stay of 3.1 (12.9–9.8) days during the seven years (P=0.001). The overall operative mortality rate was 1.4 percent, and the morbidity was 2.6 percent, with no annual differences (P=0.655 andP=0.033, respectively). The disposition to home did not change (P=0.21). Of the 678 patients followed up for readmission, 100 (14.7 percent) were readmitted within 120 days, with no annual difference (P=0.302). CONCLUSION: Mortality, morbidity, disposition, and readmission rates were not affected by a decreased length of stay after colorectal surgery.Presented at the Research Forum at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Use of N-Butyl-2-Cyanoacrylate (Glubran2?) in Fractures of Orbital-Maxillo-Zygomatic Complex

Introduction

Fractures of the orbital-maxillo-zygomatic complex are among the most common fractures affecting the facial skeleton. Goal of surgical treatment is the realignment of fracture lines for a complete functional and aesthetic rehabilitation.

Materials and Methods

From January 2008 to January 2011 in the Department of Maxillofacial Surgery of Complesso Integrato Columbus of the Università Cattolica del Sacro Cuore in Rome, 25 patients, affected by comminute fractures of the anterior wall of the maxillary sinus associated with fractures of the orbital-maxillary complex were selected. The synthesis of the larger fracture fragments was performed by plates and screws (1.5 mm) while a biocompatible glue (N-Butyl-2-Cyanoacrylate–Glubran2^®) was applied to treat the comminute fractures of the anterior wall of the maxillary sinus.

Results and Conclusion

The aim of our article is to report our experience and a review of the literature on application of–Butyl-2-Cyanoacrylate for treatment of comminute fractures of the anterior wall of the maxillary sinus. According to the results achieved in our study the N-Butyl-2-Cyanoacrylate can be indicated to treat comminuted fractures of the anterior wall of the maxillary sinus which could not easily be treated with internal rigid fixation.     

Central nervous mechanisms of cough

Cough is an airway defensive reflex substantially consisting in a modified respiratory act. Transection experiments have shown that the fundamental structures responsible for this reflex are located within the medulla oblongata. Electrical stimulation applied to the medulla failed to provide convincing evidence of a cough centre distinct from the brainstem respiratory network. In fact, electrical stimuli affect not only neuronal somata, but also intramedullary cough-related pathways. Studies on the behaviour of medullary respiratory neurones have led to the conclusion that the same respiratory neurones involved in the generation of the eupnoeic pattern of breathing also participate in the production of the cough motor pattern. These findings support the existence of multifunctional neural networks in the mammal brainstem. B?tzinger complex expiratory neurones with augmenting discharge patterns have been suggested to convey an excitatory drive to the expiratory bulbospinal neurones of the caudal ventral respiratory group and, hence, to expiratory motoneurones. The excitatory drive to caudal medullary expiratory neurones is mediated by ionotropic glutamate receptors. Recent lines of evidence indicate that the B?tzinger complex and the caudal ventral respiratory group have a crucial role in determining both the inspiratory and the expiratory components of the cough motor pattern.