Pathological changes in human retinal ganglion cells associated with diabetic and hypertensive retinopathy.

BACKGROUND: To examine whether systemic diseases like diabetes and arterial hypertension, which frequently cause retinopathies leading to blindness effect the morphology of retinal ganglion cells (RGC). METHODS: Histological retina material with a history of being untreated, or laser-coagulated (LC) diabetic retinopathy (DR), or arterial hypertensive retinopathy (AHR) was used. The RGC were labeled by introducing crystals of the fluorescent carbocyanine dye DiI into the nerve fiber layer, which contains ganglion cell axons. RESULTS: The typical silhouettes of both major types of RGC, parasol and midget cells, were identified. The axons in DR and AHR retinas showed morphology changes such as irregular swelling and beading. Dendritic field sizes were significantly reduced in RGC of both the hypertonic and diabetic retinas. A significant reduction in branching frequency was evident in both the diabetic and hypertonic retinas, in both the midget and the parasol cells. In LC retinas, both parasol and midget RGC were observed within the LC spots, although their numbers were dramatically decreased compared with normal retinas. CONCLUSIONS: The data suggest that diabetes and arterial hypertonia have similar effects on the morphology of RGC, in addition to causing microvascular alterations and bleeding. Therefore, therapeutic measures and prognostic outcomes in diabetic and hypertensive retinopathy should also consider regressive changes in retinal neurons.     

Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture

PURPOSE: To examine and quantify neuroprotective and neurite-promoting activity on retinal ganglion cells (RGCs) after injury of the lens. METHODS: In adult albino rats, penetrating lens injury was performed by intraocular injection. To test for injury-induced neuroprotective effects in vivo, fluorescence-prelabeled RGCs were axotomized by subsequent crush of the optic nerve (ON) with concomitant lens injury to cause cataract. The numbers of surviving RGCs were determined in retinal wholemounts and compared between the different experimental and control groups. To examine axonal regeneration in vivo, the ON was cut and replaced with an autologous piece of sciatic nerve (SN). Retinal ganglion cells with axons that had regenerated within the SN under lens injury or control conditions were retrogradely labeled with a fluorescent dye and counted on retinal wholemounts. Neurite regeneration was also studied in adult retinal explants obtained either after lens injury or without injury. The numbers of axons were determined after 1 and 2 days in culture. Putative neurotrophins (NTs) were studied within immunohistochemistry and Western blot analysis. RESULTS: Cataractogenic lens injury performed at the same time as ON crush resulted in highly significant rescue of 746 +/- 126 RGCs/mm(2) (mean +/- SD; approximately 39% of total RGCs) 14 days after injury compared with controls without injury or with injection of buffer into the vitreous body (30 +/- 18 RGCs/mm(2)). When lens injury was performed with a delay of 3 days after ON crush, 49% of RGCs survived, whereas delay of 5 days still rescued 45% of all RGCs. In the grafting paradigm virtually all surviving RGCs after lens injury appeared to have regenerated an axon within the SN graft (763 +/- 114 RGCs/mm(2) versus 79 +/- 17 RGCs/mm(2) in controls). This rate of regeneration corresponds to approximately 40% of all RGCs. In the regeneration paradigm in vitro preceding lens injury and ON crush 5 days previous resulted in a maximum of regeneration of 273 +/- 39 fibers/explant after 1 day and 574 +/- 38 fibers/explant after 2 days in vitro. In comparison, in control retinal pieces without lens injury 28 +/- 13 fibers/explant grew out at 1 day, and 97 +/- 37 fibers/explant grew out at 2 days in culture. Immunohistochemical and Western blot analysis of potential NTs in the injured lens revealed no expression of ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), NT-4, nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). CONCLUSIONS: The findings indicate that the lens contains high neuroprotective and neuritogenic activity, which is not caused by NT. Compared with the data available in the literature, this neuroprotection is quantitatively among the highest ever reported within the adult rat visual system.     

Aorto-right atrial fistula associated with native tricuspid valve endocarditis

Abnormal connections between the ascending aorta and the cardiac chambers are rare. Most are due to ruptured aneurysms of the sinus of Valsalva. Congenital fistulae between the aorta and left atrium are described. We report a case of native tricuspid valve endocarditis associated with a fistula between the right atrium and the aorta.     

Microglia promote glioma migration

Diffuse astrocytic gliomas extensively infiltrate brain tissue and contain numerous microglial cells, but it is unknown whether these two characteristic features are pathogenetically related. We therefore studied the effects of murine microglial cells on motility of GL261 mouse glioma cells using Boyden chamber assays. In the presence of microglia, glioma cell migration occurred earlier, and after 48 h it was threefold higher as compared to incubations without microglia. This effect was mediated by substances released from microglia, because similar effects were observed by microglia-conditioned medium, and it was specific to microglia, because oligodendroglia and endothelial cells only weakly stimulated glioma cell migration. Microglia activating substances (GM-CSF, LPS) led to a further increase of motility. These data support the notion that microglia accumulation in diffuse glial tumors does not merely represent a nonspecific reaction to tissue injury, but reflects participation of these cells in supporting and promoting the invasive phenotype of astrocytoma cells.     

A biomechanical study of two postoperative prostheses for transtibial amputees: a custom-molded and a prefabricated adjustable pneumatic prosthesis

We evaluated an adjustable pneumatic prefabricated prosthesis and a rigid custom-molded prosthesis for immediate postoperative use. Twelve transtibial amputations were performed on cadaver limbs. Differential variable reluctance transducers were placed subcutaneously across the wound edge medially and laterally. The limbs were then placed in either the pneumatic prosthesis (five limbs) or the rigid prosthesis (seven limbs). The specimens underwent static and cyclic loading to simulate weight bearing. The strain readings for static and cyclic loading were greater in the rigid prosthetic group. Only the mean medial strain measurement after cyclic loading was statistically significant. The results demonstrate that the pneumatic prosthesis places less strain across the wound than a rigid prosthesis.     

Reduced Fhit protein expression and loss of heterozygosity at FHIT gene in tumours from smoking and asbestos-exposed lung cancer patients.

The FHIT gene, at 3p14.2, has been suggested to form a molecular target to damage induced by human lung carcinogens. We examined aberrant expression of the Fhit protein and allele loss at the FHIT gene in a series of lung cancer cases, mainly of non-small cell carcinoma (NSCLC) histology. We had detailed data on tobacco smoke exposure and occupational asbestos exposure available for the cases. The principal aim of the present study was to investigate whether absent or reduced Fhit expression or FHIT allele loss was associated with exposure to these pulmonary carcinogens. We detected reduced Fhit expression in 62% (33/53) of the cases analysed. Prevalence of allele loss at the FHIT locus was 22% (20/89). Reduced protein expression was common both in the asbestos-exposed (67%) and non-exposed cases (59%); [odds ratio (OR) 1.4, 95% confidence interval (CI) 0.4-4.9]. LOH frequencies differed somewhat between the two groups and were 25% vs. 16%, respectively (OR 1.8; 95% CI 0.5-5.9). Absent or reduced expression was common in smokers, with no significant difference found between current smokers and non-smokers (mainly former smokers) (OR 1.4, 95% CI 0.5-4.5). NSCLCs with squamous cell histology exhibited both aberrant expression (OR 3.1, 95% CI 0.9-10.3) and allele loss (OR 3.3, 95% CI 0.9-12.7) more frequently than adenocarcinoma. Finally, we found that FHIT allele loss was increased in stage II or more advanced disease (OR 2.5, 95% CI 0.9-7.4), and in poorly differentiated tumours (grade 3, OR 2.6, 95% CI 0.8-8.1). In conclusion, our present data support significance of FHIT inactivation in development of lung cancer.     

Emergency thoracotomy in the pre-hospital setting: a procedure requiring clarification.

OBJECTIVE: The aim of this study is to investigate the influence of Emergency Thoracotomy (ET) on mortality in a group of patients suffering from severe thoracic trauma requiring Helicopter Emergency Medical Service (HEMS) transfer to hospital. This is not clearly defined especially when thoracotomy takes place in the pre-hospital setting. METHODS: A retrospective review of 670 consecutive patients with severe thoracic trauma, transferred to The Royal London Hospital by HEMS between November 1994 and December 2002. ET (on scene, in the Accident and Emergency (A&E) department or in the operating theatre) was performed in 53 patients (7.7%). Both univariate and multivariate analyses were performed to evaluate ET as an independent predictor of mortality. RESULTS: There were 510 males and 160 females with a mean Injury Severity Score (ISS) of 35.12+/-17.5. Univariate analysis identified ET to be a predictor of mortality (OR=0.15, 95% CI=0.07-0.30). However, with multivariate analysis, ET was not found to be an independent predictor of mortality (OR=1.93, 95% CI=0.61-6.1). The independent predictors of mortality identified were: age>60 years (OR 5.57, 95% CI 2.19-14.16), Glasgow Coma Score <8 at the scene (OR=7.4, 95% CI=3.15-17.46), ISS>25 (OR 5.3, 95% CI=1.64-17.11), need for intubation at the scene (OR=2.80, 95% CI=1.022-7.69), oxygen saturation in A&E (<89%) (OR=2.39, 95% CI=1.13-5.05), haemothorax (OR=3.30, 95% CI=1.53-7.13) and bilateral injury (OR=3.1, 95% CI=1.51-6.61). CONCLUSIONS: Our study has shown that when confounding variables are accounted for, ET is not a predictor of mortality following severe chest trauma. This implies that in a well-selected group of patients it may be a significant and life-saving procedure.     

Is virtual bronchoscopy an efficient diagnostic tool for the thoracic surgeon?

Virtual bronchoscopy has emerged over the past decade as a potentially complementary investigation to conventional bronchoscopy in the diagnosis, grading, and monitoring of pulmonary disease. A meta-analysis reporting on the use of virtual bronchoscopy has not yet been performed. The primary aim of this study is to evaluate its diagnostic accuracy compared to the gold standard investigation of conventional bronchoscopy (fiberoptic or rigid). Quantitative data synthesis included the calculation of independent sensitivity and specificity, construction of summary receiver operating characteristic curves, pooled analysis, and sensitivity analysis. Seventeen studies were identified comprising 459 patients. The calculated pooled sensitivity was 84% (95% CI, 78% to 89%), specificity 75% (95% CI, 62% to 85%) and area under the curve was 0.92, which shows good diagnostic performance. Meta-analysis confirms virtual bronchoscopy is very discriminating in the evaluation of patients with significant airway stenosis that is due to a wide spectrum of pathologic conditions. It can potentially have a beneficial role in selected thoracic patients (with bronchoesophageal fistulas, postlung transplantation, anastomoses, and suspected foreign body aspiration).     

Unilateral optic nerve crush induces bilateral retinal glial cell proliferation

The post-injury responses of retinal ganglion cells elicit a number of glial reactions which have not been completely understood. The bilateral pattern of non-neuronal retinal cell proliferation was examined in association with the differential fates of unilaterally injured adult retinal ganglion cells by means of bromodeoxyuridine (BrdU) immunocytochemistry. Lateralization of the glioproliferative events was studied by analysing both the experimental and the uninjured contralateral as well as matched retinas of sham-operated animals. Control adult rat retina included very few BrdU-positive cells within the nerve fibre and ganglion cell layers; however, experimental retinas of degenerating groups exhibited statistically significantly higher densities of newborn cells in most layers. Clusters of labelled cells were found in the inner plexiform layer related to OX-42 staining, indicating their microglial nature. Indeed, double-labelling experiments, after short-term unilateral optic nerve crushing, identified proliferating retinal glial cells in vivo. Both types of glia, astroglial and microglial cells, exhibited BrdU-positive labelling in injured as well as uninjured experimental rat retinas. Moreover, microglial proliferating cells were also identified in explanted retinal pieces after 2 days in culture. Affected and contralateral retinas responded similarly to the unilateral experimental manipulations applied with respect to BrdU labelling. The acute glial responses observed suggest that bilateral glial proliferation might represent a common response related to degeneration events in both retinas, i.e. ipsi- and contralateral to the experimental injury.