Rectal prolapse secondary to antibiotic-associated colitis in a dog

Many animals with rectal prolapse have an antecedent history of dyschezia and tenesmus associated with colonic inflammatory disease. However, it seems that there are no reports of rectal prolapse concurrent with antibiotic-associated colitis in the veterinary literature. A 3-month-old male cross-bred dog presented with a history of recurrent episodes of rectal prolapse following the administration of oral cephalexin. The rectal prolapse was corrected surgically. Based on the dog's recent history of antibiotic use, the sudden onset of bloody diarrhoea, tenesmus and subsequent rectal prolapse, antibiotic-associated diarrhoea was considered as the primary cause of rectal prolapse in this case. Clostridium perfringens were isolated from a bacteriological stool culture. The dog was treated with amoxicillin for three consecutive weeks. There were no detectable signs of diarrhoea or a recurrence of rectal prolapse during the 2-month follow-up period.     

Managing Philadelphia chromosome-positive acute lymphoblastic leukemia: role of tyrosine kinase inhibitors

Before the introduction of tyrosine kinase inhibitors, the prognosis for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia was poor. The treatment of choice, stem cell transplantation, is a potentially curative option, but it is available only for a minority of patients and is associated with significant risk of morbidity and mortality. Although imatinib is largely effective, a substantial proportion of patients become resistant or intolerant to it. The activity of imatinib may be enhanced by coadministration with chemotherapy; such treatment is effective in many patients. Dasatinib is established as a second-line treatment in patients with resistance to or intolerance of imatinib. Recent data suggest that dasatinib, either alone or in combination with chemotherapy, has utility as first-line therapy. Dasatinib is more potent than imatinib, is less susceptible to drug-resistance mechanisms, and has been shown to penetrate the blood-brain barrier, making it potentially effective for treating central nervous system disease. Patients who relapse during treatment with dasatinib frequently carry the T315I mutation of BCR-ABL. Future regimens combining dasatinib with an agent able to inhibit this mutation may further improve outcome.     

New treatments and strategies in acute myeloid leukemia

Despite considerable progress in the treatment of acute myeloid leukemia in the past several decades, the prognosis of the majority of patients with this disease remains guarded. Advances in supportive care and better characterization of disease subsets through cytogenetics and molecular analysis have led to significant success in treating specific subsets of patients, such as those with acute promyelocytic leukemia and core binding factor leukemias, particularly among the younger patients who are able to better tolerate the effects of cytotoxic chemotherapy. However, overall, only about 40% of younger patients and <10% of older patients with this disease are alive at 5 years. Current research is focusing on the identification of new cellular targets amenable to specific inhibitors, designing the best strategies for combining these novel agents with traditional chemotherapy regimens, and determining prognostic indicators that may allow us to better stratify therapy.     

High prevalence of chronic kidney disease in Iran: a large population-based study

Background  

Chronic kidney disease (CKD) is a global public health threat, associated with an alarming increase in morbidity and mortality. The importance is the worldwide increase in its incidence and prevalence.     

Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma

Glaucoma, frequently associated with high IOP (intra-ocular pressure), is a leading cause of blindness, characterized by a loss of retinal ganglion cells and the corresponding optic nerve fibres. In the present study, acutely and transiently elevated IOP, characteristic of acute angle-closure glaucoma in humans, was observed in CLR (calcitonin receptor-like receptor) transgenic mice between 1 and 3 months of age. Expression of CLR under the control of a smooth muscle alpha-actin promoter in these mice augmented signalling of the smooth-muscle-relaxing peptide adrenomedullin in the pupillary sphincter muscle and resulted in pupillary palsy. Elevated IOP was prevented in CLR transgenic mice when mated with hemizygote adrenomedullin-deficient mice with up to 50% lower plasma and organ adrenomedullin concentrations. This indicates that endogenous adrenomedullin of iris ciliary body origin causes pupillary palsy and angle closure in CLR transgenic mice overexpressing adrenomedullin receptors in the pupillary sphincter muscle. In human eyes, immunoreactive adrenomedullin has also been detected in the ciliary body. Furthermore, the CLR and RAMP2 (receptor-activity-modifying protein 2), constituting adrenomedullin receptor heterodimers, were identified in the human pupillary sphincter muscle. Thus, in humans, defective regulation of adrenomedullin action in the pupillary sphincter muscle, provoked in the present study in CLR transgenic mice, may cause acute and chronic atony and, thereby, contribute to the development of angle-closure glaucoma. The CLR transgenic mice used in the present study provide a model for acute angle-closure glaucoma.     

A novel method to localize antibody-targeted cancer deposits intraoperatively using handheld PET beta and gamma probes

Background Assessing cancer margins, lymph nodes, and small cancer deposits intraoperatively can be challenging. A new device has become available that allows the detection of positron emission tomography (PET) radiotracers through both high-energy gamma and short-range beta emissions. These PET probes are handheld, allowing for real-time evaluation of cancer using a tool that provides surgeons with better intraoperative assessment of tumor sites. Methods Within the context of two institutional review board (IRB)-approved protocols investigating new applications of antibody-labeled PET scanning, ¹²⁴I-labeled humanized monoclonal antibodies specific for colorectal cancer (huA33) and renal tumors (cG250) were constructed. Patients underwent preoperative PET scans, approximately seven days post-tracer infusion, when tumor-to-nontumor ratios were high. Suspected tumor deposits were evaluated intraoperatively with handheld beta and gamma PET probes. Results Handheld PET probes detected emissions from all tumors. Count rates from the gamma probe on tumor ranged from 48 to 306 cps, and for the beta probe ranged from 18 to 190 cps. Gamma and beta emissions exhibited a strong positive correlation. The ratio of gamma and beta counts was at least twice that of the background counts for all tumors evaluated. Conclusions This study is the first to demonstrate the utility of beta probes for the intraoperative detection of radiolabeled antibodies targeting cancer. Importantly, the recorded beta count rates from the beta probe correlate with the count rates from the high-energy gamma probe. Furthermore, the beta probe may offer superior specificity for real-time localization of small tumor deposits, compared to gamma probes. The intraoperative portable PET probe may prove a valuable bridge to combining tumor biology and PET technology to guide surgical therapy.     

Clinical Value of Immunohistochemically Detected Lymphovascular Space Invasion in Early Stage Cervical Carcinoma

Background  This study investigates the clinical significance of lymphovascular space invasion (LVSI) as detected by hematoxylin and eosin (LVSI-H&E) and immunohistochemistry (LVSI-IHC) in early stage cervical carcinoma. Methods  Single representative sections from 97 patients with early stage squamous cell cervical cancer were immunostained with pancytokeratin and CD31 endothelial cell marker antibodies. The H&E sections and their corresponding immunostained sections were reexamined to identify LVSI. Associations between LVSI with clinicopathological factors were sought. Results  Overall, LVSI was present in 29 (29.9%) and absent in 68 (70.1%) by IHC, as compared with 18 cases (18.6%) and 79 cases (81.4%), respectively, by H&E. Statistical analysis revealed a significant association between LVSI-H&E and nodal metastasis (P = .004). Follow-up data were available for 76 patients. The median follow-up period was 64 months. During follow-up, 7 of 24 patients with recurrent disease had evidence of LVSI-H&E as opposed to 3 of 52 cases with no recurrence. There was a significant association between tumor recurrence and LVSI-H&E (P = .009). The 5-year recurrence-free survival was 30% for the group with LVSI-H&E compared with 73% without. There was a significant difference in the recurrence-free survival between the two groups (P = .002). In contrast LVSI-IHC was found to be associated with no pathological factors, and survival analysis revealed no statistically significant association with recurrence or survival. Conclusion  LVSI-H&E in early stage cervical cancer remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event and seems to be of no clinical value.     

The Width:thickness Ratio of the Patella

Establishing the appropriate size of the patellar implant-bone composite is one of the important steps ensuring functional success in arthroplasty. Conventionally, the patella is measured intraoperatively and its thickness is used to guide the depth of resection. However, in a diseased joint, this may not reflect the native patellar thickness. We studied the relationship between the patellar thickness and various patellar dimensions on three-dimensional reconstructed computed tomographic scans from 37 normal adult knees. Patellar width correlated with thickness. The average patellar width:thickness ratio was 2.0 (standard deviation, 0.106; 95% confidence interval, 1.96–2.03). The cartilage thickness was on average 2.5 mm (standard deviation, 1.0). The width:thickness ratio was similar in 79 digital radiographs taken before TKA of knees without patellofemoral disease (mean, 2.1; standard deviation, 0.28). When compared with the two other methods for calculating patellar resection described in the literature, the width:thickness ratio was more reliable. The width:thickness ratio appears anatomically constant and may be a useful guide for estimating premorbid patellar thickness. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.     

Bulk collagen incorporation rates into knitted stiff fibre polymer in tissue-engineered scaffolds: the rate-limiting step

Fabrication of tissue-engineered constructs in vitro relies on sufficient synthesis of extracellular matrix (ECM) by cells to form a material suitable for normal function in vivo. Collagen synthesis by human dermal fibroblasts grown in vitro on two polymers, polyethylene terephthalate (PET) and polyglycolic acid (PGA), was measured by high-performance liquid chromatography (HPLC). Cells were either cultured in a dynamic environment, where meshes were loaded onto a pulsing tube in a bioreactor, or in a static environment without pulsing. Collagen synthesis by cells cultured on a static mesh increased by six-fold compared to monolayer culture, and increased by up to a further 5.4-fold in a pulsed bioreactor. However, little of the collagen synthesized was deposited onto the meshes, almost all being lost to the medium. The amount of collagen deposited onto meshes was highest when cells were cultured dynamically on PET meshes (17.6 microg), but deposition still represented only 1.4% of the total synthesized. Although total collagen synthesis was increased by the use of 3D culture and the introduction of pulsing, the results suggest that the limiting factor for fabrication of a tissue-engineered construct within practical timescales is not the amount of collagen synthesized but the quantity retained (i.e. deposited) within the construct during culture. This may be enhanced by systems which promote or assemble true 3D multi-layers of cells.