Upper Gastrointestinal Bleeding During the First Month After Renal Transplantation in the Mycophenolate Mofetil Era

Upper gastrointestinal (GI) bleeding remains a significant cause of mortality and morbidity among renal transplant recipients. We retrospectively analyzed the records of patients who received renal transplantations between January 2001 and July 2007 using mycophenolate mofetil (MMF) in their immunosuppressive regimens. The following data were recorded for those subjects with upper GI bleeding during the first month after transplantation (group B, cases): age, sex, acute rejection episodes, pretransplant upper GI endoscopic findings, Helicobacter positivity, and cytomegalovirus (CMV) seropositivity. The same parameters were studied among a group of patients, who did not have a history of upper GI bleeding (group A, controls). A statistical analysis was performed to ascertain potential risk factors. Among 523 patients (311 females, 212 males) of age range 7 to 58 years, 27 (5.2%) had upper GI bleeding: 13 males and 14 females of mean age 44 ± 12 years. The most frequent endoscopic finding was erosive gastritis (n = 13; 48.1%) followed by duodenal ulcers. Binary logistic regression analysis comparing the 2 groups showed that acute rejection episodes (P = .015) and active CMV infection (P = .046) were the most prominent risk factors for upper GI bleeding during the first month after renal transplantation.     

A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.     

Protection against cyclophosphamide-induced alopecia by sulfhydryl-containing agents in the newborn rat animal model

Background Alopecia is a common side-effect of cancer chemotherapy. Although this complication has been known for many decades, little progress has been made in its prevention or treatment. Previously, we made the following observations: ( a ) treatment of 8-day-old rats with 1-0-n-arabinofuranosylcytosine (ara-C), doxorubicin, and cyclophosphamide (CYC) produced either total body alopecia (ara-C and CYC) or alopecia confined to the head and proximal part of the neck (doxorubicin); ( b ) Imuvert, a biological response modifier, and interleukin-1 protected against alopecia-induced by ara-C; and (c) neither Imuvert or interleukin-1 protected against CYC-induced alopecia. Objective Experiments were designed to test for agents to protect against CYC-induced alopecia. Methods Agents were tested in the 8-day-old rats as a model for chemotherapy-induced alopecia. Results Mesna and S-2-(3-aminopropylamino)-ethylphospnorothioic acid (WR-2721) did not offer any protection against chemotherapy-induced alopecia. N-Acetylcysterine offered very good protection against alopecia induced by CYC but not that produced by ara-C in the newborn rate animal model. Conclusion N-Acetylcysteine may prove to be important in the prevention of CYC-induced alopecia, but this needs to be tested in the clinical setting.     

Studies on the mechanism of 3-deazaguanine cytotoxicity in L1210-sensitive and -resistant cell lines

Summary 3-Deazaguanine (3-DG), a purine analogue, has unusual antitumor activity against experimental mammary tumor models and a number of other solid tumors. Others have shown that mutant CHO cells deficient in hypoxanthine guanine phosphoribosyl transferase (HGPRTase) or adenine phosphoribosyl transferase (APRTase) are resistant to 3-DG. We developed a L1210 cell line resistant to 3-DG, L1210/3-DG, by subculturing the parent L1210/0 cells in the presence of increasing concentrations of 3-DG. The IC₅₀ was 3.5 M and 620 M for L1210/0 and L1210/3-DG, respectively. Cytotoxicity studies proved the resistance to be stable. Examination of the baseline-specific activity of HGPRTase and APRTase showed that the former was 118-fold lower in L1210/3-DG than in L1210/0, and the latter demonstrated no difference. A 4-h treatment of the cell lines at IC₅₀ doses showed 48% and 23% reductions in IMP dehydrogenase in L1210/0 and L1210/3-DG, respectively. The rate of de novo purine biosynthesis was studied by using [¹⁴C]formic acid. Formate flux increased 2-fold in L1210/3DG in concert with the observed deficiency of HGPRTase in the cell line. 3-DG uptake was studied with [¹⁴C]-labelled compound. The total radioactivity was 9-fold higher in L1210/0 than in L1210/3-DG at 2 h. Subsequent chromatographic separation of radioactivity showed the 3-DG and 3-deazaguanosine pools of the drug to be equal in both lines. However, 3-DG nucleotide pools at 1 min and 2 h were 2.5-fold and 16-fold lower, respectively, in L1210/3-DG than in L1210/0. 3-DG incorporation studies with radiolabelled drug demonstrated that 3-deazaguanine is incorporated in the acid-insoluble fraction of the cell. These studies conclude that HGPRTase, and not APRTase, is required for the activation of drug. Inhibition of IMP dehydrogenase is partially responsible for antitumor activity of the drug. The incorporation of drug into nucleic acids may be a major mechanism for its antitumor activity. Further studies using a cloned cDNA probe for hypoxanthine guanine phosphoribosyltransferase (HGPRT) demonstrated no change in the DNA arrangements of the L1210/3-DG cell line, and Northern blot analysis showed approximately equal expression of mRNA in both cell lines.Abbreviations used APRTase adenine phosphoribosyltransferase - HGPRTase Hypoxanthine guanine phosphoribosyltransferase - IMPD Inosine mono-phosphate dehydrogenase - PRPP 5-Phosphorylribose-1-pyrophosphate - AOPCP , -Methyleneadenosine 5-diphosphate - NAD Nicotineamide dinucleotide - EDTA Ethylenediamine tetra acetic acid Presented at annual meeting of American Association of Cancer Research in May, 1986Supported in part by Warner-Lambert Company, Ann Arbor, Michigan