Cellular and molecular studies on cisplatin-induced apoptotic cell death in rat kidney

Using morphological and molecular approaches, we characterized cisplatin-induced cell necrosis and apoptosis in rat kidney. Male Sprague-Dawley rats (n=5 per group) received a single intraperitoneal injection of either cisplatin (5 mg/kg) or saline, and were killed on day 5. Functionally, cisplatin-treated rats developed polyuric acute renal failure. Morphologically, kidneys of cisplatin-treated rats showed overt tubular necrosis associated with apoptosis in the corticomedullary junction. Cell necrosis was segment-specific and was distributed in radial fashion at the corticomedullary junction. The apoptosis was limited to discrete cells in apparently intact tubules in the vicinity of the necrosed tubules. The apoptotic changes were confirmed by TUNEL (TdT-mediated deoxyuridine triphosphate nick-end labeling) and staining for cleaved caspase-3. Analysis of outer medullary tissue for apoptosis-related molecules by RNase protection assay revealed a significant increase in the expression of pro-apoptotic mRNAs (caspases 1, 2, and 8, and Bax) in cisplatin-treated rats. On the other hand, the expression of mRNA for the anti-apoptotic Bcl-2 did not change, resulting in a decrease in relative ratio of Bcl-2/Bax, and thus favoring apoptosis. The above changes were paralleled by a marked increase in caspase-3 precursor, the executioner protease. Furthermore, these pro-apoptotic molecular changes were associated with a 3-fold increase in the activity of JNK1 in the outer medulla, but not in the cortex, of cisplatin-treated rat kidneys, localizing to the site of maximal apoptosis. Upregulation of JNK1 activity in the outer medulla was not accompanied by changes in the activities of ERK or p38 kinase. In conclusion, these data suggest that cisplatin-induced apoptotic cell death in native kidney may be mediated by cooperative activation of the JNK1 pathway and Bax in the outer medulla.     

Absence of impact of donor hepatic steatosis and posttransplantation lamivudine resistance in a patient with chronic hepatitis B

A patient with chronic hepatitis B underwent liver transplantation for end-stage cirrhosis. The donor liver graft had moderate steatosis and fibrosis. He was placed on lamivudine for hepatitis B prophylaxis but developed viral relapse due to emergence of a lamivudine-resistant mutant at week 72 posttransplantation. Results of liver biochemistry were normal liver histology revealed minimal steatosis and inflammation at weeks 151 and 128, respectively. This report illustrates that the use of a steatotic donor liver and the emergence of lamivudine resistance posttransplantation are not necessarily associated with significant graft damage. A marginal donor graft can be considered due to the donor shortage. Lamivudine monoprophylaxis for hepatitis B virus-related liver diseases post liver transplantation can be used in areas where hepatitis B immunoglobulin is not affordable.     

Multimodality tumor control and living donor transplantation for unresectable hepatocellular carcinoma

Liver transplantation (LT) is an acceptable mode of treatment for selected patients with unresectable hepatocellular carcinoma (HCC). However, due to the scarcity of cadaveric donor organs, it is considered desirable for patients to opt for living donor liver transplantation (LDLT) or, for those not being transplanted soon, to have some form of tumor control therapy. Such an approach in our program is analyzed and reported. At our institution, 42 LTs were performed between October 1999 and April 2003. Of these, 18 recipients (15 men, 3 women) had 27 HCC. The average number and size of HCC was 1.59 (1 to 4) and 2.31 (0.2 to 6.5) cm, respectively. Thirteen (72%) patients were transplanted primarily for the HCC, whereas five (28%) others were incidental HCC cases. Seven patients (5 LRLT, 2 cadaveric LT) were transplanted soon after listing, and thus did not require tumor control therapy. Six patients waited for 11 (6 to 19) months before LT. Three patients underwent microwave coagulation therapy, and one had additional alcohol injections. One patient received the novel PIAF (cisplatin, interferon, adriamycin, and 5-FU) chemotherapy regimen followed by selective internal irradiation (SIR) treatment. One patient received conformal radiation therapy and another received SIR treatment before LT. Besides 2 postoperative deaths, the remaining 16 patients have been well, with a mean follow-up of 20.4 (3.6 to 41.2) months. In conclusion, for patients with unresectable HCC, in areas with poor cadaveric donor rate, living donation should be the first option. If a suitable live donor is not available, aggressive multimodality therapy is recommended while waiting for cadaveric LT.     

Intra-abdominal and Retroperitoneal Lymphangiomas in Pediatric and Adult Patients

Intra-abdominal and retroperitoneal lymphangiomas are a rare, congenital malformations of the lymphatics, which are found predominantly in children. The aim of this study is to evaluate the clinical features of this tumor, highlighting the differences in adults and pediatric patients. We also evaluate the preoperative diagnosis, radiological features, surgical treatment, and outcome of this rare condition. Between 1990 and 2004, 14 patients who underwent surgical resection of an intra-abdominal lymphangioma were reviewed retrospectively. There were five pediatric patients between fetal age and 17 years of age and nine adults between 31 and 62 years of age. Overall, females outnumbered males in the series, with a male-to-female ratio of 3:4. However, males predominated in the pediatric age group with a male-to-female ratio of 1.5:1. The clinical presentation of children was more acute ranging from 3 days to 2 months. In adults, four patients were asymptomatic, and the remaining five had symptom duration ranging from 2 weeks to a year. The lymphangiomas occurred in the mesentery (n = 4), retroperitoneum (n = 4), omentum (n = 3), pancreas (n = 2), and spleen (n = 1). All the patients underwent total surgical resection with or without organ resection, and there were no recurrences at a median follow-up of 2 years (range; 3 months–13 years). This series demonstrates that abdominal lymphangiomas have a male preponderance and present more acutely in pediatric patients, whereas in adults, female patients predominate and the history is more chronic. Presented orally at the 19th World Congress of the International Society for Digestive Surgery (Yokohama) December 2004     

Central nervous system candidiasis in preterm infants: limited value of biochemical markers for diagnosis

Two rare cases of isolated central nervous system (CNS) candidiasis in preterm infants have been diagnosed in a tertiary neonatal centre over the past 6 years. Despite the life-threatening nature of the disease, biochemical infection markers were not useful for the early identification of localized fungal infection. Because the infection was likely to have been blood borne, we postulated that the initial fungal load was probably low and that the organisms were rapidly eliminated from the circulation after a few had been deposited in the CNS. Hence, the absence of fungaemia or systemic involvement precluded the activation of cytokines and cellular markers. Clinicians should be aware of the limitation of biochemical infection markers so that diagnosis and treatment of fungal infection will not be delayed.     

Development of a mobile pulse waveform analyzer for cardiovascular health monitoring

Noninvasive pulse waveforms contain rich pathophysiological information of cardiovascular system. It is hereby a tradition of interest to implement risk stratification by pulse waveform monitoring and analysis. In contrast to conventional computer- or network-based solutions, we attempt to accomplish pulse waveform monitoring and analysis within a self-contained mobile platform. It adopts a compact biosensor for pulse waveform acquisition. The collected signals are then submitted to a core board for pulse waveform processing and analysis. In addition, the core board coordinates user interaction and network communication too. Such compact pulse waveform analyzer is of great help for cardiovascular health monitoring at home. A carefully designed evaluation has been undertaken within our research group. The results confirmed its prospect in home healthcare.