Changes in serum and intestinal diamine oxidase (DAO) activity after proximal enterectomy in rats

To determine whether serum and mucosal DAO activity reflects quantitative changes in the small bowel mucosal mass, we have chosen an experimental model of mucosal hyperplasia which is known to occur in the rat after enterectomy. A 50% proximal enterectomy or a single transection was performed in 20 growing rats weighing 145–160 g. Ten days following surgery, we determined mucosal mass parameters (weight, protein, and DNA content), sucrase activity, and DAO activity in the duodenum (segment A), proximal ileum (segment B), and distal ileum (segment C) of the remaining small intestine. Mucosal hyperplasia was demonstrated by the finding that in each segment, mucosal weight, protein, and DNA content per centimeter of gut length were significantly (P<0.01) higher (+38 to+78%) in the resected group than in transected controls. In segments B and C of resected rats, the changes in DAO activity expressed per gram of mucosa paralleled the changes in mucosal mass, the activity being increased by +69% and +49% (P<0.05) compared to the values recorded in transected controls. Expressed per centimeter of gut length, total DAO activity was also enhanced by +141% in segment B (P<0.05 vs controls) and by +87% in segment C(P>0.01 vs controls) of resected rats. In the duodenum, the changes in DAO activity were small (+36%) and not significant. In the ileum (segment C), significant correlations were established between total DAO activity and either mucosal weight (r=0.75,N=20,P<0.01) or mucosal DNA concentration (r=0.78, N=20, P<0.01) per centimeter of gut length, but there was no correlation between DAO activity and sucrase activity. Compared to control rats with transection, proximal enterectomy produced marked changes in the serum activity of DAO. Ten days following surgery, the mean value of serum DAO was fivefold higher (P< it0.005) in the resected group than in the transected group. These data indicate that after jejunectomy (1) the intestinal activity of DAO reflects accurately quantitative changes of the mucosal mass in the remaining ileum but not in the duodenum, and (2) circulating levels of DAO could be used as a marker of ileal mucosal adaptation after proximal enterectomy.     

Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88^−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b⁻Gr-1⁺ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88^−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88^−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88^−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection.     

Rectal puncture complicating caudal blockade in a child with severe rectal distension

We describe a case of unrecognized rectal puncture following unsuccessful caudal blockade in a patient later found to have marked rectal distension on MRI. This may have contributed to the rectal injury.     

The Olfactory Strip and Its Preservation in Endoscopic Pituitary Surgery Maintains Smell and Sinonasal Function

Background The return of olfaction and of sinonasal function are important end points after pituitary surgery. Opinions differ on the impact of surgery because techniques vary greatly. A modified preservation of the so-called olfactory strip is described that utilizes a small nasoseptal flap and wide exposure. Methods A cohort of patients undergoing pituitary surgery and endoscopic sinonasal tumor surgery were assessed. Patient-reported outcomes (Sino-Nasal Outcome Test [SNOT22] and Nasal Symptom Score [NSS]) were recorded. A global score of sinonasal function and the impact on smell and taste were obtained. Objective smell discrimination testing was performed in the pituitary group with the Smell Identification Test. Outcomes were assessed at baseline and at 6 months. Results Ninety-eight patients, n = 40 pituitary (50.95 ± 15.31 years; 47.5% female) and n = 58 tumor (52.35 ± 18.51 years; 52.5% female) were assessed. For pituitary patients, NSSs were not significantly different pre- and postsurgery (2.75 ± 3.40 versus 3.05 ± 3.03; p = 0.53). SNOT22 scores improved postsurgery (1.02 ± 0.80 versus 0.83 ± 0.70; p = 0.046). Objective smell discrimination scores between baseline and 6 months were similar (31.63 ± 3.49 versus 31.35 ± 4.61; p = 0.68). No difference in change of olfaction was seen compared with controls (Kendall tau-b p = 0.46). Conclusions Preservation of the olfactory strip can provide a low morbidity approach without adversely affecting olfaction and maintaining reconstruction options.     

The effects of household wealth on HIV prevalence in Manicaland,Zimbabwe – a prospective household census and population-based open cohort study

Introduction

Intensified poverty arising from economic decline and crisis may have contributed to reductions in HIV prevalence in Zimbabwe.

Objectives

To assess the impact of the economic decline on household wealth and prevalent HIV infection using data from a population-based open cohort.

Methods

Household wealth was estimated using data from a prospective household census in Manicaland Province (1998 to 2011). Temporal trends in summed asset ownership indices for sellable, non-sellable and all assets combined were compared for households in four socio-economic strata (small towns, agricultural estates, roadside settlements and subsistence farming areas). Multivariate logistic random-effects models were used to measure differences in individual-level associations between prevalent HIV infection and place of residence, absolute wealth group and occupation.

Results

Household mean asset scores remained similar at around 0.37 (on a scale of 0 to 1) up to 2007 but decreased to below 0.35 thereafter. Sellable assets fell substantially from 2004 while non-sellable assets continued increasing until 2008. Small-town households had the highest wealth scores but the gap to other locations decreased over time, especially for sellable assets. Concurrently, adult HIV prevalence fell from 22.3 to 14.3%. HIV prevalence was highest in better-off locations (small towns) but differed little by household wealth or occupation. Initially, HIV prevalence was elevated in women from poorer households and lower in men in professional occupations. However, most recently (2009 to 2011), men and women in the poorest households had lower HIV prevalence and men in professional occupations had similar prevalence to unemployed men.

Conclusions

The economic crisis drove more households into extreme poverty. However, HIV prevalence fell in all socio-economic locations and sub-groups, and there was limited evidence that increased poverty contributed to HIV prevalence decline.     

Comparison of structural genetics of non-schistosoma-associated squamous cell carcinoma of the urinary bladder

Little is known about genetic changes in squamous differentiation of non-schistosomiasis-associated bladder cancer. Therefore, we investigated pure squamous cell carcinomas (SqCC), squamous parts of mixed urothelial carcinomas with squamous differentiation (MIX) and mere urothelial cancers (UC) for structural genetic differences. Tissue microarray slides (n = 29 SqCC, n = 35 MIX and n = 23 UC) were analyzed by ZytoLight SPEC p16/CEN3/7/17 Quadruple Color Probe fluorescence-in-situ-hybridization (FISH) and DNA was investigated by comparative genomic hybridization (CGH) (n = 35 SqCCs, n = 40 MIX and n = 36 UC). By FISH the mean number of polysomic cells was lowest in SqCC (CEN3 P = 0.0498, CEN17 P = 0.0009). A slight tendency of lower copy numbers of chromosomes 3, 7 and 17 and higher numbers of the p16-locus in SqCC (P = 0.45) indicated less aneuploid tumor cells in SqCC compared to MIX and UC. In CGH SqCC showed the lowest mean number of aberrations per tumor (SqCC 5.37 changes, MIX 6.75 and UC 7.64; P = 0.1754). Significant differences between the three groups were found for loss of chromosome 3p (P = 0.004), 6q (P = 0.028), 11p (P = 0.024) and gains of 5p (P = 0.020). Loss of 3p was more frequent in SqCC (51.4%) than in MIX (37.5%) or UC (13.9%). To conclude, SqCCs show less polysomy and genetic alterations than MIX and UC. Loss of 3p is more frequent in SqCC but there are no absolute specific alterations for each tumor group. Squamous parts of mixed tumors show similar alterations than UC and should be considered as further development of UC, while pure SqCC seem to be a separate tumor group.     

Web-Based Immersive Virtual Patient Simulators: Positive Effect on Clinical Reasoning in Medical Education

Background

Clinical reasoning is based on the declarative and procedural knowledge of workflows in clinical medicine. Educational approaches such as problem-based learning or mannequin simulators support learning of procedural knowledge. Immersive patient simulators (IPSs) go one step further as they allow an illusionary immersion into a synthetic world. Students can freely navigate an avatar through a three-dimensional environment, interact with the virtual surroundings, and treat virtual patients. By playful learning with IPS, medical workflows can be repetitively trained and internalized. As there are only a few university-driven IPS with a profound amount of medical knowledge available, we developed a university-based IPS framework. Our simulator is free to use and combines a high degree of immersion with in-depth medical content. By adding disease-specific content modules, the simulator framework can be expanded depending on the curricular demands. However, these new educational tools compete with the traditional teaching

Objective

It was our aim to develop an educational content module that teaches clinical and therapeutic workflows in surgical oncology. Furthermore, we wanted to examine how the use of this module affects student performance.

Methods

The new module was based on the declarative and procedural learning targets of the official German medical examination regulations. The module was added to our custom-made IPS named ALICE (Artificial Learning Interface for Clinical Education). ALICE was evaluated on 62 third-year students.

Results

Students showed a high degree of motivation when using the simulator as most of them had fun using it. ALICE showed positive impact on clinical reasoning as there was a significant improvement in determining the correct therapy after using the simulator. ALICE positively impacted the rise in declarative knowledge as there was improvement in answering multiple-choice questions before and after simulator use.

Conclusions

ALICE has a positive effect on knowledge gain and raises students’ motivation. It is a suitable tool for supporting clinical education in the blended learning context.