Involvement of the Mitochondrial Pathway in Cold Storage and Rewarming-Associated Apoptosis of Human Renal Proximal Tubular Cells

The cellular and molecular mechanisms of cold storage-ATN are not well characterized. In our earlier studies, cold storage caused necrosis of human proximal tubular epithelial (RPTE) cells, whereas apoptosis was prominent during rewarming. An intriguing finding was the pronounced swelling of the mitochondria in the cold, which promoted us to further characterize its role in rewarming-associated apoptosis. Human proximal tubular epithelial cells were cold stored in University of Wisconsin (UW) solution for 48 h followed by 24 h of rewarming in regular cell culture medium. During the cold storage, there was no significant change in the Bcl-2 to Bax protein ratio, mitochondrial location of cytochrome C or caspse-3 activity. However, during rewarming, the Bcl-2 to Bax ratio increased, cytochrome C was translocated to cytosol, and caspase-3 was activated: events and timing were consistent with the occurrence of apoptosis during rewarming. In a time-course experiment, mitochondrial swelling was discernable by electron microscopy as early as at 2 h. Cold storage of isolated-mitochondria for 2 h was attended by an increase in the opening of the permeability transition pores (PTP), suggesting PTP opening as an early mechanism for mitochondrial swelling. Addition of antioxidants (deferoxamine or 2-methyaminochroman) to the storage solution suppressed mitochondrial pore opening and swelling, Bcl-2 to Bax ratio increase, cytochrome C translocation, caspase-3 activation as well as rewarming-induced apoptosis. Our data demonstrate for the first time that apoptosis following cold storage and rewarming of human renal tubular cells is accompanied by specific mitochondrial events, and that these events and apoptosis can be suppressed by adding antioxidants to the cold storage solution.     

Orbital tumors in children. Characterization by computed tomography

CT characteristics of orbital masses in 39 children were reviewed. Histological types and their relative frequencies differed considerably from reported adult cases. Analysis of seven separate CT characteristics for each type of mass indicated certain trends which may aid in the differential diagnosis.     

Comorbidity between ADDH and learning disability: a review and report in a clinically referred sample.

A widely variable overlap ranging from 10 to 92% has been reported in the literature between attention deficit disorder with hyperactivity (ADDH) and learning disability (LD), most likely a result of inconsistencies in the criteria used to define LD in different studies. The following study seeks to more accurately determine rates of LD in clinically referred children. Using a psychometrically reliable methodological approach, it was expected that the rate of LD in ADDH children would be far more modest than previously reported. Subjects were referred children with ADDH (N = 60), children with academic problems (N = 30), and normal controls (N = 36) of both sexes with available psychological and achievement testing. Using a liberal definition of LD, significant differences were found between the groups (ADDH = 38% versus academic problems = 43% versus normals = 8%; p = 0.002). In contrast, more modest rates were found using two more stringent methods of assessment (23 and 17%; 10 and 3%; 2 and 0%, respectively; p = 0.02). Arithmetic-based LD appears to be equally identified by both stringent methods, whereas the liberal definition overidentified children in all three groups. These findings show that a liberal definition of LD overidentifies LD not only in ADDH children but also in normal children.     

Serum bilirubin subfractions in patients with alcohol abuse during detoxication

Sera were obtained from 41 alcohol abusers consecutively admitted for detoxication. Blood samples were withdrawn on the second, fourth and seventh days of abstention. Initial bilirubin values were moderately elevated in 10 patients. Determination of the bilirubin subfractions by high performance liquid chromatography showed elevated values of unconjugated (alpha), monoconjugated (beta), diconjugated (gamma) and albumin-bound (delta) bilirubin, in 8, 15, 4 and 15 patients, respectively. During abstention, the total bilirubin value normalized rapidly, only three patients still had values above the upper reference limit after 7 days. In patients with initially elevated values of bilirubin subfractions, only a few had elevated beta and gamma levels on the seventh day, whereas delta levels decreased at a slower rate and remained virtually unchanged. On admission, 27 patients exhibited elevated levels of serum bile acids; these values decreased during abstention and after 7 days only six patients had slightly elevated values. Only five patients had initially elevated levels of alkaline phosphatase (ALP). These became normalized in all but two patients during abstention. The results suggest that mild cholestasis is common among alcohol-abusers without clinically evident liver disease and that these changes are reversible on abstention.     

Infections in elderly persons. An altered clinical presentation.

The high prevalence, morbidity, and mortality of infectious diseases in the geriatric population mandates that clinicians caring for older patients become better acquainted and familiar with the special and unique characteristics and features of this common clinical problem. Only through such awareness and understanding will clinical outcomes, functional capacity, and quality of life be improved in the elderly population.     

Pre-operative evaluation of patients with low rectal carcinoma

Advances in surgical technique and adjuvant therapy have broadened the spectrum of treatment available for patients with low rectal cancer. Combination of careful pre-operative clinical examination with newer, more sophisticated techniques, particularly in the field of imaging, can stage the extent of disease more accurately then previously. Adoption of an extended pre-operative evaluation allows a more rational approach to treatment in the individual, and standardizes criteria for entry into, and interpretation of, future clinical trials.

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Resumen Los avances en la técnica quirúrgica y en las terapias adyuvantes han ampliado la perspectiva terapéutica en los pacientes con cáncer del recto distal. La combinación de un meticuloso examen clínico preoperatorio con las nuevas y sofisticadas técnicas de diagnóstico, especialmente en el campo de la imagenología, ha logrado realizar la estadificación de la enfermedad en forma más certera. La adopción de una extensa valoración preoperatoria permite un aproche más racional al tratamiento en cada caso individual y la mejor estandarización de criterios para iniciar e interpretar ensayos clínicos futuros. Son cuatro los parámetros de importancia en cuanto a pronóstico en un paciente con carcinoma rectal: el grado de invasión local intrapélvica, el estado de los ganglios locales, el grado de diferenciación tumoral y la presencia de metástasis distantes. Las técnicas imagenológicas más usadas para determinar el grado de extensión intrapélvica son la tomografía computadorizada (TC) y la ultrasonografía endoluminal transanal. La resonancia magnética ha demostrado ser menos precisa. La ultrasonografía endoluminal es más precisa que la TC en cuanto a detectar invasión linfática, y la linfoescintigrafía y linfografía carecen de utilidad. El grado de diferenciación histológica del tumor se logra con la toma de múltiples biopsias mediante el sigmoidoscopio; el estudio de citometría de flujo permite establecer el contenido nuclear de DNA y la ploidia celular; esta técnica puede lograr creciente aceptación en el futuro. La valoración de metástasis distantes se obtiene mediante tres téchnicas principales de imagenología: la ultrasonografía, la escanografía con isótopos y la TC, siendo la TC el método de elección. Niveles elevados de antígeno carcinoembriónico permiten predecir la existencia de enfermedad metastásica.Entre 2% y 9% de los pacientes con carcinoma rectal distal presentan un segundo carcinoma en el colon, y un porcentaje mucho mayor exhibe pólipos sincrónicos, por lo cual todo paciente con carcinoma rectal debe ser sometido a examen de la totalidad del colon, idealmente mediante colonoscopia.

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Résumé Les progrès enregistrés en matière de technique chirurgicale et de traitement adjuvant ont élargi la panoplie thérapeutique pour les patients ayant un cancer du rectum. La combinaison d'un examen clinique préopératoire soigneux et de techniques plus sophistiquées, telle l'imagerie moderne, conribue à un bilan d'extension plus précis qu'avant. Un tel bilan préopératoire permet une approche rationnelle de chaque patient, et le recueil d'informations importantes pouvant guider la conduite et l'interprétation d'essais thérapeutiques futurs.

     

Long-term effects of radiotherapy administered in childhood for the treatment of malignant diseases

Background: The use of radiotherapy for the treatment of childhood malignancy has improved long-term survival significantly, and many treated children now survive well into adulthood. As a consequence, long-term effects of childhood irradiation are being seen with increasing frequency. Methods: The medical records of 236 patients who had been treated for malignant disease with radiotherapy during childhood were examined to determine the long-term effect of the radiation on their growth and development. Results: Mean treatment dose was 35.5 Gy; mean age at treatment was 7.2 years; and mean follow-up was 14.5 years. Adjuvant chemotherapy was given to 82%. Some degree of bone deformity (usually with overlying soft-tissue hypoplasia) was seen in 40%; 21% developed some type of endocrine deficiency; 30% developed atrophic skin changes; and 7% developed second malignancies. The incidence of bone deformity and hormonal deficiency increased with the radiation dose; the incidence of second malignancy was independent of dose. Bone deformities were more common when radiation was administered before the age of 2 years. Conclusions: The consequences of radiotherapy in childhood are significant and must be considered when planning treatment. Even when treatment is essential, families should be informed of the possibility of growth disturbance to prevent subsequent misunderstanding.