CT evaluation of an anterior urethral tear

A retrograde urethrogram is usually performed to evaluate the urethra in patients with suspected urethral injuries. A computed tomography (CT) scan is performed after the retrograde urethrogram to evaluate for further intrabdominal injuries. We present a case in which a CT scan performed after a retrograde urethrogram in a trauma patient identified a urethral tear.     

Pre-pubertal exposure of cytarabine-induced testicular atrophy,impaired spermatogenesis and germ cell DNA damage in SD rats

Context: Cytarabine (Ara-C) is an effective chemotherapeutic drug for the treatment of acute leukaemias. It inhibits the DNA synthesis and repair, thereby causes cytotoxicity in the proliferating cells.

Objective: This study was aimed to investigate the effects of pre-pubertal exposure of Ara-C on testesticular development in juvenile SD rats and their function at puberty.

Materials and methods: Ara-C was injected at the doses of 50, 100 and 200?mg/kg/day from postnatal day (PND) 29–42 (14 days) by intraperitoneal (i.p.) route. Half of the animals were sacrificed on PND 43 and remaining on PND 70. End points of the evaluation included gross pathological examination, histomorphometric analysis, sperm count and sperm head morphology, cell proliferation and DNA damage as well as apoptosis analysis.

Results: Ara-C treatment significantly decreased food and water intake, weight gain, testes and epididymis weight and increased histological alterations in the seminiferous tubule. Furthermore, Ara-C treatment significantly decreased the PCNA-positive cells and sperm count in a dose-dependent manner. Ara-C treatment also increased the DNA damage and apoptosis in testes and sperm as evident from the comet and TUNEL assays results.

Discussion: The present study results clearly indicated that Ara-C treatment impaired spermatogenesis and adversely affects the testicular development and its function in rats by reducing the germ cell proliferation and the inducing DNA damage and apoptosis.     

Large Molecule Run Acceptance: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

The L1 Global Harmonization Team provides recommendations specifically for run acceptance of ligand binding methods used in bioanalysis of macromolecules in support of pharmacokinetics. The team focused on standard curve calibrators and quality controls for use in both pre-study validation and in-study sample analysis, including their preparation and acceptance criteria. The team also considered standard curve editing and the concept of total error.     

Topical delivery of fluorescence (6‐Cf) labeled and radiolabeled (99m‐Tc) cisplatin and imiquimod by a dual drug delivery system

The present investigation deals with the development of topical (top.) formulation for co‐delivery of cisplatin and imiquimod to enhance the antitumor efficacy of the drug for skin‐cited malignancies even in immune compromised patient. Cisplatin (CDDP) and imiquimod‐loaded protransfersome gel (CDDP‐Imi‐Pts gel) formulation was characterized for entrapment efficiency, pH, and viscosity. Further, fluorescence‐labeled (6‐carboxyfluorescin) and radiolabeled (^99mtechnetium) drug‐loaded formulations were compared with respect to biodistribution and pharmacokinetic studies. Gamma scintigraphy of mice following radiolabeled formulation administrations was performed to accomplish the localization of drugs in various organs. The percentage entrapment efficiency of cisplatin and imiquimod in the protransfersome gel formulations were found to be 36.22 ± 6.41 and 63.11 ± 3.73. The skin/blood localization ratio of 1.096, 120.13, 0.174, and 349.88 was found for intraperitoneal radiolabeled drug solution (^99m‐Tc‐CDDP‐Imi‐Sol), top. radiolabeled drug‐loaded protransfersome gel formulation (^99m‐Tc‐CDDP‐Imi‐Pts gel), intraperitoneal 6‐carboxyfluorescin labeled drug solution (6‐Cf‐CDDP‐Imi‐Sol), top. 6‐carboxyfluorescin labeled drug‐loaded protransfersome gel formulation (6‐Cf‐CDDP‐Imi‐Pts gel), respectively after 0.5h of administration. CDDP‐Imi‐Pts gel has a potential for site specific delivery and reduces the systemic toxicity of anti cancer drugs. These findings suggest that the cisplatin–imiquimod co‐delivery offers an attractive, novel approach for treatment of skin‐cited malignancies.     

Improvement in renal function following cryoballoon ablation for atrial fibrillation

Purpose

Patients with chronic kidney disease are predisposed to heart rhythm disorders including atrial fibrillation (AF). Several studies have suggested that radiofrequency catheter ablation of AF improves renal function. However, little data exists for pulmonary vein isolation with cryoballoon ablation (CBA). The purpose of this study is to assess change in renal function following CBA for AF.

Method

This is a single-center retrospective study that included patients who underwent CBA for AF between 2011 and 2016. Patients were grouped by baseline-estimated glomerular filtration rate (eGFR): ≥?90 (Stage G1), 60–89.9 (Stage G2), and 30–59.9 mL/min/1.73 m² (Stage G3). Change in eGFR was assessed >?3 months post-ablation.

Results

A total of 306 patients with both pre- and post-ablation serum creatinine measurements available were included. Baseline eGFRs for Stages G1, G2, and G3 patients were 103.5?±?12.9 (n?=?82), 74.7?±?8.2 (n?=?184), and 52.6?±?6.6 mL/min/1.73 m² (n?=?40), respectively. Renal function was assessed 310.8?±?104.2 days post-ablation. Average intra-procedural contrast use was 58.4?±?23.8 mL. There was no significant change in eGFR following CBA in Stage G1 patients (p?=?0.10). For those with Stages G2 and G3 renal function, eGFR improved by 6.1% (4.2 mL/min/1.73 m², p?<?0.01) and 13.8% (7.2 mL/min/1.73 m², p?<?0.01), respectively. This improvement was seen regardless of the presence or absence of recurrent atrial arrhythmias.

Conclusions

CBA for AF may be associated with an improvement in renal function, particularly among those with a reduced baseline eGFR despite recurrence of atrial arrhythmias and intra-procedural contrast use.

     

Location of the BCR/ABL Fusion Genes on Both Chromosomes 9 in Ph Negative Young CML Patients: An Indian Experience

The BCR/ABL gene rearrangement is cytogenetically visualized in most chronic myeloid leukemia (CML) cases. About 5–10 % of CML patients lack its cytogenetic evidence, however, shows BCR/ABL fusion by molecular methods. We describe two CML patients with Philadelphia (Ph) negative (−ve) and BCR/ABL positive by fluorescence in situ hybridization (FISH). Both the cases were in chronic phase at diagnosis. Conventional cytogenetics and different FISH assays were adopted using BCR/ABL probes. Home-brew FISH assay using bacterial artificial clone (BAC) for BAC-CTA/bk 299D3 for chromosomal region 22q13.31-q13.32 was performed in case 1. Both the patients were Ph-ve. In first case, dual color dual fusion (DCDF)-FISH studies revealed 1 Red (R) 2 Green (G) 1 Fusion (F) signal pattern in 80 % of cells indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph and 2G2F signal pattern in 20 % of cells indicating two BCR/ABL fusions on both chromosomes 9q34 on presentation. In second case, FISH studies revealed the 1R1G1F signal pattern indicating BCR/ABL fusion signals on chromosomes 9 instead of Ph in 100 % of cells at presentation. During follow-up, both the patients exhibited 2G2F signal pattern indicating two BCR/ABL fusions on both chromosomes 9q34, which indicated a clonal evolution in 100 % cells. Both the patients did not achieve therapeutic response. Relocation of BCR/ABL fusion sequence on sites other than 22q11 represents a rare type of variant Ph, the present study highlights the hot spots involved in CML pathogenesis and signifies their implications in Ph−ve BCR/ABL positive CML. This study demonstrated the genetic heterogeneity of this subgroup of CML and strongly emphasized the role of metaphase FISH, especially in Ph−ve CML cases, as it detects variations of the classical t(9;22).     

Pre-transplant co-infusion of donor-adipose tissue derived mesenchymal stem cells and hematopoietic stem cells may help in achieving tolerance in living donor renal transplantation

Transplantation tolerance is still a Utopian dream for many transplanters. Mesenchymal stem cells (MSC) have shown immuno-modulatory and tolerogenic effects in experimental models. We present a 29-year-old male with end stage renal disease (ESRD) who was transplanted with HLA 4/6 matched kidney from 51-year-old father in June 2010 preceded by co-infusion of donor-adipose tissue derived mesenchymal stem cells (AD-MSC) and bone marrow derived hematopoietic stem cells (BM-HSC) under non-myeloablative conditioning for deleting rejecting T and B-cells. He has maintained fairly stable graft function with serum creatinine (SCr) between 1.5 and 1.8?mg/dL at 3 years post-transplant with absence of donor specific antibodies (DSA), normal protocol graft biopsy, and peripheral T-regulatory cell levels (pTregs) (CD127^low/?CD25^highCD4⁺) of 4.57% on zero immunosuppression since 6 months.