Diagnostic error due to vicarious excretion of rectal iodinated contrast

Introduction of iodinated contrast into the intact colon is not expected to result in imaging‐visible renal excretion of this contrast and is a phenomenon that has only rarely been described. We present a case in which such vicarious renal excretion was misinterpreted as a recto‐vesical fistula which resulted in unnecessary delay in the patient’s management.     

Precision of genotyping of Epstein-Barr virus by polymerase chain reaction using three gene loci (EBNA-2, EBNA-3C, and EBER): predominance of type A virus associated with Hodgkin's disease [published erratum appears in Blood 1993 Oct 1;82(7):2268]

To precisely determine the genotype of Epstein-Barr virus (EBV) in Hodgkin's disease (HD), we simultaneously analyzed three divergent gene loci (EBNA-2, EBNA-3C, and EBER) that distinguish type A and B viruses. The primers designed to amplify these three gene loci encompass either type-specific deletion sequences (EBNA-2 and EBNA-3C) or type-specific point mutations (EBER) that identify the virus strain based on the sizes of the polymerase chain reaction (PCR)-amplified products or the mobility shifts in single-strand conformation polymorphism analysis. The locations of point mutations were identified by direct sequencing of the PCR-amplified DNA. We analyzed 15 EBV-infected cell lines and found a good correlation between EBNA-2 and EBNA-3C typing results. In contrast, approximately 33% of the cell lines analyzed maintained type A sequences in EBNA-2 and EBNA-3C genes while carrying type B sequences in the EBER region. Data obtained from analysis of cell lines served as a reference for studying HD samples. EBV DNA was detected in about 70% of HD. Among the EBV-positive samples, 56% were associated with type A virus, 13% with type B, and 31% with dual viral sequences. Thus, type A virus is predominant in HD. Based on the histology, the frequencies of EBV positivity were 83%, 71%, and 33% for mixed cellularity, nodular sclerosis, and lymphocyte predominance, respectively. The detection of high frequency of both type A and B sequences in HD may provide a lead in investigating the role of dual viral infection in EBV pathogenesis.     

Production and characterization of a bispecific IgG capable of inducing T-cell-mediated lysis of malignant B cells

Bispecific monoclonal antibodies (bsabs) recognizing both CD3 and a tumor antigen can redirect T-cell-mediated cytotoxicity toward cells bearing that antigen. Such bsabs have been shown to be more effective than monospecific monoclonal antibodies (MoAbs) at preventing tumor growth in animal models of B-cell malignancy. The current studies describe the production and preliminary evaluation of a bsab designed to induce the lysis of malignant human B cells by human T cells. The bsab was obtained from a hybrid-hybridoma cell line produced by fusing OKT3-secreting hybridoma cells with hybridoma cells that secrete 1D10. 1D10 is an MoAb that recognizes an antigen found on a majority of malignant human B cells that has not been detected to a significant degree on normal resting or activated lymphocytes. High performance liquid chromatography (HPLC) was used to separate bsab from monospecific antibodies that were also present in the hybrid-hybridoma antibody product. The bsab was then evaluated in vitro for its ability to induce lysis of malignant B cells by activated T cells. The bsab consistently induced extensive lysis in vitro of 1D10 (+) cells, including both cell lines and cells obtained from patients with a variety of B-cell malignancies. No such effect was seen with activated T cells alone or activated T cells with monospecific antibody. No increased lysis was seen with 1D10 (-) cell lines. The bsab also mediated lysis of malignant B cells by autologous T cells. We conclude bsab containing an OKT3 arm and a 1D10 arm can induce T-cell-mediated lysis in a manner that is both potent and specific. This supports further evaluation of this bsab as a potential immunotherapy of B-cell malignancy.     

Profile of Live-born Infants of In-vitro Fertilisation

Introduction

The Army Hospital (R&R) is the only service hospital providing in-vitro fertilisation (IVF) facility. Neonatal characteristics of live-born infants at this centre over a two-year period are analyzed in this study.

Methods

Data on 504 consecutive live-born IVF infants over a two-year period (01 Feb 2007 to 31 Jan 2009) were analysed.

Result

Of the 504 neonates, 190 (37.7%) were born by vaginal delivery, 156 (30.9%) by elective lower segment cesarean section (LSCS) and 127 (25.19%) following emergency LSCS. Maternal illness posing specific risk to the neonate was present in 165 out of 504 (32.7%). There were 239 (47.4%) preterm neonates. Males formed 51.8% of the cohort. Singletons accounted for 51.2%, while the rest (48.8%) were products of twin pregnancies. Small for gestational age neonates formed 22.6% (n = 114). A total of 20 (3.9%) infants had congenital malformations. There were 242 (48.1%) low birth weight neonates. A total of 128 (25.4%) neonates needed neonatal intensive care. Of the 504, there were 474 (94.1%) survivors while 30 (5.9%) did not survive. Twenty-nine (6.1%) neonates required readmission during the neonatal period.

Conclusion

In our setting, neonates born following IVF appeared to be at increased risk of prematurity, multiple births and low birth weight. Proper obstetric and neonatal management can result in good neonatal outcomes.Key Words: In-vitro fertilisation, Live-births, Low birth weight     

Results of definitive radiotherapy in T1 and T2 glottic carcinoma: Institute of Rotary Cancer Hospital experience

Early glottic carcinomas (T₁ and T₂) constitute only 2% of all laryngeal cancers in our data. Seventy patients were seen between 1985 and 1992. All patients were treated by cobalt-60 small field radiotherapy using a beam directed shell. The total dose delivered was 60–65 Gy in 31 patients and 66–70 Gy in 39 patients. The follow-up period ranged from 5 to 126 months, with a mean follow up of 37 months overall and 55 months in the surgical salvage group. Radiation therapy controlled disease in 71% (50 of 70) of patients overall; 75% with T₁ and 67% with T₂ lesions. Total laryngectomy as salvage surgery was performed in 70% (14 of 20) of patients whose disease recurred. Ultimate control including surgical salvage occurred in 64 (91%) of 70 patients in the present study. The actuarial 5 year survival was 83 and 80% in T₁ and T₂ tumours, respectively (statistically insignificant). This report supports the policy of definitive irradiation, reserving surgical salvage for radiation failures in early laryngeal cancers.     

Localized folate and vitamin B-12 deficiency in squamous cell lung cancer is associated with global DNA hypomethylation

We measured the concentrations of folate and vitamin B-12 in paired tissue samples of squamous cell cancer (SCC) and adjacent grossly normal-appearing uninvolved bronchial mucosa (from which SCC developed and also "at risk" of developing SCC) of the lung in 12 subjects to determine the involvement of these vitamins in 1) lung carcinogenesis and 2) global DNA methylation. The folate concentrations were significantly lower in SCCs than in uninvolved tissues (p = 0.03). The vitamin B-12 concentrations were also significantly lower in SCCs than in uninvolved tissues (p = 0.02). The radiolabeled methyl incorporation (inversely related to the degree of in vivo DNA methylation) was significantly higher in SCCs than in uninvolved tissues (p < 0.0001). The correlation between folate and radiolabeled methyl incorporation was inverse and statistically significant in SCCs (p = 0.03). The correlation between vitamin B-12 and radiolabeled methyl incorporation also was inverse and statistically significant in SCCs (p = 0.009). The relationship between tissue vitamin B-12 and DNA methylation was minimal in uninvolved tissues. The relationship between folate and DNA methylation, however, was inverse in uninvolved tissues. In the multiple regression models that included both vitamins, only folate was inversely associated with radiolabeled methyl incorporation in uninvolved and cancerous tissues. These results suggested that folate might be the limiting vitamin for proper DNA methylation in SCC as well as in tissues at risk of developing SCC. Several possible mechanisms of folate deficiency, including inactivation of the vitamin by exposure to carcinogens of cigarette smoke and underexpression or absence of folate receptor in SCCs and associated premalignant lesions, are discussed in light of these findings.     

Changes in cyclin dependent kinase inhibitors p21 and p27 during the castration induced regression of the CWR22 model of prostatic adenocarcinoma

PURPOSE: The expression of the cyclin dependent kinase inhibitors p21 and p27 was examined in prostatic adenocarcinomas following castration. MATERIALS AND METHODS: Male nude mice inoculated with the androgen dependent human prostatic tumor CWR22 were castrated when the tumors reached a volume of 0.8 to 1.1 cm.3 and were sacrificed at 3, 7, 21, 28 and 42 days post-castration. An additional group of mice received a subcutaneous testosterone pellet at 21 days post-castration and was sacrificed at 28 days post-castration. The expression of the Ki-67 antigen, p21 and p27 was examined by immunohistochemistry. RESULTS: The mitotic rate as well as the number of Ki-67 antigen positive cells decreased to 3% of intact control values by 7 days post-castration and were less than 0.01% of intact control values at 21, 28 and 42 days post-castration. The percentage of p21 expressing cells decreased from 15+/-2% in intact controls to less than 1% by 42 days post-castration. In contrast, the percentage of cells that expressed p27 increased from 25+/-3% in intact controls to 51+/-8% at 3 days post-castration and to 80 to 95% at days 7, 21, 28 and 42 days post-castration. Testosterone treatment from 21 to 28 days post-castration resulted in an increase in Ki-67 antigen positive cells to 200% of intact controls and a concomitant reduction in p27 expressing cells to about 50% of intact controls. Castration-induced changes in p27 expression were not observed in the CWR22R tumor, a transplantable relapsed derivative of the CWR22 tumor. CONCLUSION: These findings suggest that p27 expression is regulated negatively by androgens and that increased expression of p27 in CWR22 xenografts may be involved in the suppression of proliferation following castration.