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.     

Complications of liver donation for living related liver transplantation

Living related liver transplantation (LRLT) has gained popularity, especially in Asian countries as the primary mode of liver transplantation. LRLT, however, carries the inherent problem of potential donor harm. In view of reports of donor deaths and significant donor morbidity (as high as 67%), we examined donor complication rates in our LRLT program. All sixteen LRLT donors between February 2000 and January 2003 were retrospectively analyzed. The 16 donors (13 men, 3 women) of mean age 30 years (range, 18-49 years) included 5 donations from siblings, 2 from parents, and 9 from offsprings. The portion of liver donated was L hepatectomy (n = 4) R hepatectomy (n = 7), and Modified Extended R hepatectomy (n = 5) with the weight of resected liver being 618.9 g (range, 380-1000). The mean blood loss was 936 mL (range, 400-1900 mL), but only 2 donors required transfusion of banked blood. The mean intensive care unitstay was 1.06 days (range, 1-2 days) and the mean hospital stay was 9.12 days (range, 7-14 days). There was no case of reoperation and no mortality. There was no biliary or vascular complication. Four of 16 (25%) donors had a minor morbidity; 2 of 16 (12.5%) had a morbidity requiring intervention. In conclusion, with meticulous preoperative, intraoperative, and postoperative management, successful LRLT can be performed with minimal donor morbidities.     

Evaluation of four DNA extraction methods for the detection of Mycobacterium avium subsp. paratuberculosis by polymerase chain reaction

Polymerase chain reaction (PCR) has been widely used due to its high specificity, sensitivity, and rapid turn-around time. However, inhibitory factors may be co-extracted with the target nucleic acid that will hinder the performance of PCR. In this study, DNA extraction methods for Mycobacterium avium subsp. paratuberculosis were evaluated including rapid lysis, organic extraction, silica-based and magnetic particle-based (MagaZorb) technologies on bacterial cells, and spiked bovine feces. Efficiency of the extraction was determined by PCR end point titration with primers targeting the insertion sequence, IS900. Results of the end point titrations are identical for bacterial cells and spiked feces. Inhibition was observed in PCR with DNA isolated from spiked feces, and a 1/100 dilution was able to alleviate this problem with DNA extracted by MagaZorb. A 1/1000 dilution was required for the other three methods. MagaZorb proved to be more efficient at removing inhibitory factors and required the least labor and completion time. Further evaluation is required for its utilization in other clinical specimens.     

Trends in accessibility to medicines for children in New Zealand: 1998-2002

BACKGROUND: Reported rates of unlicensed and off-label use of medicines in children raise concerns regarding overall access of children to medicines OBJECTIVE: To assess changes in availability of proprietary formulations suitable for infants and young children; licensing of medicines; and subsidization of medicines for children in New Zealand. METHODS: Review of the New Ethicals Catalogue, New Ethicals Compendium, product data sheets and the New Zealand Pharmaceutical Schedule covering the years 1998-2002 inclusive. RESULTS: There was a decrease in the total number of medicines licensed in New Zealand from 2014 to 1840; but there was an increase in the number and percentage of suitable formulations that were licensed for paediatric use from 616[31%] to 642[35%]. The number of suitable paediatric formulations that were subsidized decreased from 281[13.9%] to 260[14.1%]. The number of orally available chemical entities with suitable formulations, licensed and subsidized for paediatric use declined from 101[5.0%] to 94[5.1%], but all of these chemical entities that were withdrawn had therapeutic alternatives that were licensed and subsidized. Only 36% of new medicines that had licensing for children were licensed for the 0-23 month age group. CONCLUSION: There have been modest improvements in licensing of medicines for children in New Zealand from 1998 to 2002.     

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.     

Spontaneous multiloculated multiseptated pneumomediastinum in a newborn baby: the spinnaker sail is rigged—CT features with pathologic correlation

The CT appearance of a pathologically proven spontaneous multiloculated multiseptated pneumomediastinum in a newborn baby has not been reported in the English literature. Our baby was delivered vaginally at term and developed mild respiratory distress after birth. The antenatal history was unremarkable apart from borderline oligohydramnios. The multiple septa seen within the pneumomediastinum on CT on day 3 may simulate an underlying 'bubbly' lung lesion like congenital cystadenomatoid malformation or congenital lobar emphysema, but actually represent anatomically known fascia surrounding the thymus. Furthermore, in neonates, air in the mediastinum often loculates locally and tends not to dissect widely as in adults.     

The effects of intra-fraction organ motion on the delivery of intensity-modulated field with a multileaf collimator

Intensity-modulated radiation therapy can be conveniently delivered with a multileaf collimator. With this method, the entire field is not delivered at once, but rather it is composed of many subfields defined by the leaf positions as a function of beam on time. At any given instant, only these subfields are delivered. During treatment, if the organ moves, part of the volume may move in or out of these subfields. Due to this interplay between organ motion and leaf motion the delivered dose may be different from what was planned. In this work, we present a method that calculates the effects of organ motion on delivered dose. The direction of organ motion may be parallel or perpendicular to the leaf motion, and the effect can be calculated for a single fraction or for multiple fractions. Three breast patients and four lung patients were included in this study,with the amplitude of the organ motion varying from +/- 3.5 mm to +/- 10 mm, and the period varying from 4 to 8 seconds. Calculations were made for these patients with and without organ motion, and results were examined in terms of isodose distribution and dose volume histograms. Each calculation was repeated ten times in order to estimate the statistical uncertainties. For selected patients, calculations were also made with conventional treatment technique. The effects of organ motion on conventional techniques were compared relative to that on IMRT techniques. For breast treatment, the effect of organ motion primarily broadened the penumbra at the posterior field edge. The dose in the rest of the treatment volume was not significantly affected. For lung treatment, the effect also broadened the penumbra and degraded the coverage of the planning target volume (PTV). However, the coverage of the clinical target volume (CTV) was not much affected, provided the PTV margin was adequate. The same effects were observed for both IMRT and conventional treatment techniques. For the IMRT technique, the standard deviations of ten samples of a 30-fraction calculation were very small for all patients, implying that over a typical treatment course of 30 fractions, the delivered dose was very close to the expected value. Hence, under typical clinical conditions, the effect of organ motion on delivered dose can be calculated without considering the interplay between the organ motion and the leaf motion. It can be calculated as the weighted average of the dose distribution without organ motion with the distribution of organ motion. Since the effects of organ motion on dose were comparable for both IMRT and conventional techniques, the PTV margin should remain the same for both techniques.