Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.      

Post-phototherapy neonatal bilirubin rebound: a potential cause of significant hyperbilirubinaemia.

AIM: To determine the incidence of post-phototherapy neonatal plasma total bilirubin (PTB) rebound. METHODS: A prospective clinical survey was performed on 226 term and near-term neonates treated with phototherapy in the well baby nursery of the Shaare Zedek Medical Center from January 2001 to September 2002. Neonates were tested for PTB 24 hours (between 12 and 36 hours) after discontinuation of phototherapy, with additional testing as clinically indicated. The main outcome measure, significant bilirubin rebound, was defined as a post-phototherapy PTB > or =256 micromol/l. Phototherapy was not reinstituted in all cases of rebound, but rather according to clinical indications. RESULTS: A total of 30 (13.3%) neonates developed significant rebound (mean (SD) PTB 287 (27) micromol/l, upper range 351 micromol/l). Twenty two of these (73%) were retreated with phototherapy at mean PTB 296 (29) micromol/l. Multiple logistic regression analysis showed significant risk for aetiological risk factors including positive direct Coombs test (odds ratio 2.44, 95% CI 1.25 to 4.74) and gestational age <37 weeks (odds ratio 3.21, 95% CI 1.29 to 7.96). A greater number of neonates rebounded among those in whom phototherapy was commenced < or =72 hours (26/152, 17%) compared with >72 hours (4/74, 5.4%) (odds ratio 3.61, 95% CI 1.21 to 10.77). CONCLUSION: Post-phototherapy neonatal bilirubin rebound to clinically significant levels may occur, especially in cases of prematurity, direct Coombs test positivity, and those treated < or =72 hours. These risk factors should be taken into account when planning post-phototherapy follow up.     

Risperidone in the treatment of acute stress disorder in physically traumatized in-patients

Although symptoms of acute stress disorder or PTSD in the aftermath of physical trauma may be a reason for psychiatric referral, little has been written on the management of patients in this context. We report the possible benefit of risperidone, an atypical antipsychotic, in 4 cases where flashbacks were reported in patients hospitalized for the treatment of physical trauma.     

尖叶清风藤化学成分的研究

从尖叶清风藤(Sabia swinhoei Hmsl.exForb.etHemsl.)的地上部分分离出8个化合物,经理化常数测定和光谱解析,证明其中2个为新成分,分别命名为清风藤内酯(I)和清风藤酮(II),另外6个为已知化合物,即没药烯(III)、三十烷醇(IV)、β-谷甾醇(V)、二十八烷酸(VI)、齐墩果酸(VII)和胡萝卜甙(VIII)。     

Human erythrocyte protein 4.2 deficiency associated with hemolytic anemia and a homozygous 40glutamic acid-->lysine substitution in the cytoplasmic domain of band 3 (band 3Montefiore)

Red blood cell (RBC) protein 4.2 deficiency is often associated with a moderate nonimmune hemolytic anemia, splenomegaly, and osmotically fragile RBCs resembling, but not identical to, hereditary spherocytosis (HS). In the Japanese type of protein 4.2 deficiency (protein 4.2Nippon), the anemia is associated with a point mutation in the protein 4.2 cDNA. In this report, we describe a patient with moderate and apparently episodic nonimmune hemolytic anemia with splenomegaly, spherocytosis, osmotically fragile RBCs, reduced whole cell deformability, and abnormally dense cells. Sodium dodecyl sulfate- polyacrylamide gel electrophoresis analysis of the proposita's RBC membrane proteins showed an 88% deficiency of protein 4.2 and a 30% deficiency of glyceraldehyde-3-phosphate dehydrogenase (band 6). Structural and molecular analyses of the proposita's protein 4.2 were normal. In contrast, limited tryptic digestion of the proposita's band 3 showed a homozygous abnormality in the cytoplasmic domain. Analysis of the pedigree disclosed six members who were heterozygotes for the band 3 structural abnormality and one member who was a normal homozygote. Direct sequence analysis of the abnormal band 3 tryptic peptide suggested that the structural abnormality resided at or near residue 40. Sequence analysis of the proposita's band 3 cDNA showed a 232G-->A mutation resulting in a 40glutamic acid-->lysine substitution (band 3Montefiore). Allele-specific oligonucleotide hybridization was used to probe for the mutation in the pedigree, showing that the proposita was homozygous, and the pedigree members who were heterozygous for the band 3 structural abnormality were also heterozygous for the band 3Montefiore mutation. The band 3Montefiore mutation was absent in 26 chromosomes from race-matched controls and in one pedigree member who did not express the band 3 structural abnormality. In coincidence with splenectomy, the proposita's anemia was largely corrected along with the disappearance of most spherocytes and considerable improvements of RBC osmotic fragility, whole cell deformability, and cell density. We conclude that this hereditary hemolytic anemia is associated with the homozygous state for band 3Montefiore (40glutamic acid-->lysine) and a decreased RBC membrane content of protein 4.2. We speculate that band 3 structural abnormalities can result in defective interactions with protein 4.2 and band 6, and in particular, that the region of band 3 containing 40glutamic acid is involved directly or indirectly in interactions with these proteins.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Gholestatic jaundice associated with chlordiazepoxide hydrochloride (librium) therapy

Summary and conclusions A case is described of cholestasis associated with chlordiazepoxide therapy, and 3 previously reported cases are reveiwed. Chlordiazepoxide should be included in the ever-growing list of commonly used medications that are considered in the differential diagnosis of cholestasis.Supported by Gastroenterology Training Grant 5T1 AM 5099 (Drs. Lo and Eidelman) from the National Institute of Arthritis and Metabolic Diseases, U. S. Public Health Service.     

Successful lung transplantation following lung volume reduction surgery

BACKGROUND: Lung volume reduction surgery (LVRS) is an accepted treatment modality for patients with advanced emphysema. Recently, successful lung transplantation (LTX) has been reported following LVRS. We assess the pulmonary functions in lung transplant recipients after LVRS. METHODS: 8 patients - 5 males and 3 women--aged 53-66 years with advanced emphysema underwent LVRS. Following clinical deterioration and decline of pulmonary function, patients underwent single LTX. Post transplantation follow-up included pulmonary function, 6 minute walk distance (6 MWD) and recording perioperative complications. RESULTS: Median forced expiratory in one second (FEV 1) before and after LVRS were 24 % with 31 % predicted, respectively. All but one showed improvement in lung function and 6 MWD following LVRS. Median maximal 6 MWD before and after LVRS was 222 and 316 meters, respectively. Median time from LVRS to LTX was 46 months (range 10-83). All patients survived and were discharged after LTX. Median FEV1 before and after LTX was 23 % with 57 % predicted, respectively. Median 6MWD before and after LTX was 240 and 462 meters, respectively. NYHA classes improved from 3-4 to 1-2 in 7 surviving patients. At transplantation, bleeding due to pleural adhesions was observed in 4 patients; two required blood transfusions. One patient developed acute respiratory distress syndrome and one had unilateral vocal cord paralysis. At nine-month follow-up, 7 patients are doing remarkably well, while one patient died 6 months after LTX due to bronchiolitis obliterans syndrome (BOS). CONCLUSIONS: LVRS is a therapeutic option in patients with end-stage emphysema. When emphysema deteriorates, LTX can be successfully performed with significant improvement of quality of life without significant additional risk.