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.     

Use of a symblepharon ring for treatment of over-filtration and leaking blebs after glaucoma filtration surgery

We report the use of a symblepharon ring in the treatment of seven cases of flat anterior chamber (six cases of total iridocorneal touch, and one of corneallens touch) secondary to overfiltration or to bleb leak. In all cases, the anterior chamber reformed within 24 hours after the symblepharon ring was used. Advantages of using the ring are: (a) it permits testing of visual acuity, tonometry, and intraocular examination without removing it; (b) it does not require suturing to the conjunctiva; (c) it does not disturb the corneal epithelium; (d) it may be available at institutions lacking other shells; and (e) it is cost-effective.     

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     

Biochemical mechanisms for the scheduled synergism of (αS, 5S)-2 amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid and 5-fluorouracil in P388 leukemia

Summary A study was made of the in vivo effects of equitoxic doses of AT-125 and 5-FU combination, being administered either simultaneously (% ILS 152) or with a 6-h pretreatment with AT-125 (% ILS 184). To examine the biochemical basis for the scheduled synergism, measurements were made of the concentration of PRPP, the specific activities of CPS II, cytidine, thymidine, uridine, deoxyuridine kinases, and fluorinated nucleotide formation in P388 tumors and the small intestine. Two hours after in vivo simultaneous treatment of mice bearing tumors the concentration of PRPP increased 9- and 6-fold above baseline in the tumor and the small intestine, respectively. In the AT-125 pretreatment arm the concentration of PRPP increased 18- and 7-fold above baseline in the tumor and the small intestine, respectively. CPS II activity was reduced to 28%–18% of control in the tumors in the simultaneous and pretreatment groups, respectively, whereas it remained unchanged in the small intestine. Specific activities of cytidine kinase (5.5±1), thymidine kinase (4.0±1.6), uridine kinase (35.6±6.5), and deoxyuridine kinase (2.4±1.1) nmol/mg protein/h remained unchanged with treatment. In concert with the increased intratumor concentration of PRPP, fluorinated nucleotide formation was proportionally increased in the treatment arms. These results indicate the importance of drug scheduling of the above two agents in treating P388 leukemia.Abbreviation AT 125 - S,5S -amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid - 5-FU 5-fluorouracil - 5-FdUMP 5-fluorodeoxyuridine monophosphate - PRPP phosphoribosyl pyrophosphate - 5-FUMP 5-fluorouridine monophosphate - 5-FUDP 5-fluorouridine diphosphate - 5-FUTP 5-fluorouridine triphosphate - UMP uridine monophosphate - UDP uridine diphosphate - UTP uridine triphosphate - ATP adenosine triphosphate - CPS II carbamylphosphate synthetase II - PCA perchloric acid Presented in part at the Seventy-fourth Annual Meeting of the American Association for Cancer Research, San Diego, California, May 1983     

Effects of stretching exercise training and ergonomic modifications on musculoskeletal discomforts of office workers: a randomized controlled trial

Objective

To evaluate the effectiveness of exercise, ergonomic modification, and a combination of training exercise and ergonomic modification on the scores of pain in office workers with neck, shoulders, and lower back pain.

Reflex ImmunoCyt Testing for the Diagnosis of Bladder Cancer in Patients with Atypical Urine Cytology

Background

ImmunoCyt/uCyt (Scimedx, Denville, NJ, USA) is a well-established urinary marker assay with high sensitivity for the diagnosis of urothelial carcinoma (UC) and can function as a second-level test to arbitrate atypical reads of urine cytology.

Objective

To determine the utility of uCyt as a reflex test for atypical cytology in patients undergoing a hematuria evaluation or surveillance with a history of UC.

Design, setting, and participants

The uCyt assay was performed as a second-level reflex test on all voided urine cytology tests read as atypical between January 2007 and June 2010 in an academic medical center. Records were retrospectively reviewed. Three hundred twenty-four patients underwent a total of 506 uCyt assays.

Intervention

Reflex uCyt assay on atypical urine cytology.

Outcome measurements and statistical analysis

The uCyt test characteristics include sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).

Results and limitations

Reflex uCyt was performed on 506 atypical voided urine samples that were followed by cystoscopy within 90 d. Reflex uCyt with a history of UC showed a sensitivity of 73%, a specificity of 49%, and an NPV of 80%. In those with a history of low-grade UC, reflex uCyt had a sensitivity of 75%, a specificity of 50%, and an NPV of 82%, while in those with a history of high-grade UC, it had a sensitivity of 74%, a specificity of 44%, and an NPV of 79%. Without prior history of UC, reflex uCyt had a sensitivity of 85%, a specificity of 59%, and an NPV of 94%. This study's limitations include its retrospective design and interobserver variability inherent to cystoscopy, which was used as the reference test.

Conclusions

When used as a reflex test on atypical urine cytology, negative uCyt may predict a negative cystoscopy in select patients and modulate the urgency and further work-up in those with no prior history or low-grade disease.