High prevalence of human papillomavirus infections in urine samples from human immunodeficiency virus-infected men

Infection with human immunodeficiency virus (HIV) and the resulting immunosuppression are associated with an increased risk for human papillomavirus (HPV) persistence and related malignancies. In the present study we investigated the prevalence of HPV in urine samples from 104 HIV-infected men with low CD4+ cell counts (<100 per mm(3)) and 115 urine samples from HIV-negative men. A high prevalence of HPV DNA (39.4%) was found in the HIV patients. Most of the HPV types were high risk (81.4%), with HPV 52 as the most prevalent type (12.5%), followed by HPV 18 (6.7%), HPV 35 (5.8%), and HPV 70 (4.8%). Multiple HPV genotypes were observed in 17 (41%) of the 41 HPV- and HIV-positive men. In contrast, only 11 (9.6%) HPV DNA-positive cases were observed among the 115 HIV-uninfected men, and 3 (27.3%) contained multiple genotypes. Quantitative analyses indicated that the HPV viral load, as measured in urine samples, is significantly higher in HIV-positive men compared to HIV-negative men. In the present study we show that urine samples are useful for detecting HPV DNA, there is a high prevalence of HPV in HIV-positive men, and the HPV viral load is substantially higher in HIV-positive than in HIV-negative men. More studies are needed to evaluate the risk and natural development of HPV-related malignancies in HIV-positive men.     

Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction.

Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response.     

Skeletal tissue engineering-from in vitro studies to large animal models

Bone is a tissue with a strong regenerative potential. New strategies for tissue engineering of bone should therefore only focus on defects with a certain size that will not heal spontaneously. In the development of tissue-engineered constructs many variables may play a role, e.g. the source of the cells used, the design and mechanical properties of the scaffold and the concentration and mode of application of growth factor(s).Models for studying new strategies for tissue engineering of bone should be based on the target tissue to be restored. However, in light of the many potential variables, which may also interact if used in combination(s), there is also a large need for relatively simple models in which variables can be tested in a limited number of animals. Moreover, in compromised bone there may be a problem with the load-bearing capacity of the remaining healthy bone. In this light, an important prerequisite for tissue-engineering constructs is that they can be tested in loaded conditions. Particularly, this latter prerequisite is very difficult to achieve. Therefore, in vitro tests for mechanical stability are very useful for evaluating the mechanical consequences of a particular reconstruction procedure prior to the animal experiment. Before a tissue-engineered construct can be introduced into a clinical trial, a final test should be available in a large animal model that is as close and relevant to a particular problematic clinical situation as possible.In the past, a series of models were developed in our laboratory that are very useful for testing tissue-engineered constructs. In this paper, we focus on the use of relatively new simple in vitro and in vivo models for hip revision surgery, segmental bone defect restoration and tumour surgery.     

Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole

A case of Scedosporium apiospermum keratitis was successfully treated with oral voriconazole and penetrating keratoplasty. Voriconazole levels in the aqueous humor were 53% of the levels in plasma and exceeded the MIC for the isolate by sevenfold.     

Isolated aorta setup for hemodynamic studies

A setup consisting of a high-performance hydraulic pump connected to the ascending part of an isolated aorta, including all major distal branches, each loaded with calibrated artificial resistors, was developed. The system was used to study total aortic compliance of the baboon as a function of mean aortic pressure (n=5). The aorta loaded with the resistors was mounted in a custom-designed sink table, such that it was submersed in physiological saline maintained at 37°C. Mean distending pressure in the entire aortic compliance from pressure and flow waves generated by the pump. Total aortic compliance as a function of mean pressure was fitted with a logarithmic function: Ln (Compliance)=A+B * P. The value of A(±SE) was: 1.565±0.319 and B: −0.020±0.003 (P<0.001). The results were compared with previously published results (also using the same three-element Windkessel fit) obtained in three of the same animalsin vivo. Thein vivo data were A: 1.095±0.235 and B: −0.019±0.003.In vitro data had a significantly higher value of A thanin vivo (P=0.017), implying a significantly higher aortic compliancein vitro thanin vivo. Occlusion of the proximal descending aorta was performed at a low distending pressure (55 mm Hg) to determine the proximal complicance. It was found (n=4) that 46±11% (SD) of the total arterial compliance is to be attributed to the ascending and proximal descending aorta. This work was supported in part by Grant RG 86/0066 from the scientific affairs division of Nato.     

Integration of target and effector information in human posterior parietal cortex for the planning of action

Recently, using event-related functional MRI (fMRI), we located a bilateral region in the human posterior parietal cortex (retIPS) that topographically represents and updates targets for saccades and pointing movements in eye-centered coordinates. To generate movements, this spatial information must be integrated with the selected effector. We now tested whether the activation in retIPS is dependent on the hand selected. Using 4-T fMRI, we compared the activation produced by movements, using either eyes or the left or right hand, to targets presented either leftward or rightward of central fixation. The majority of the regions activated during saccades were also activated during pointing movements, including occipital, posterior parietal, and premotor cortex. The topographic retIPS region was activated more strongly for saccades than for pointing. The activation associated with pointing was significantly greater when pointing with the unseen hand to targets ipsilateral to the hand. For example, although there was activation in the left retIPS when pointing to targets on the right with the left hand, the activation was significantly greater when using the right hand. The mirror symmetric effect was observed in the right retIPS. Similar hand preferences were observed in a nearby anterior occipital region. This effector specificity is consistent with previous clinical and behavioral studies showing that each hand is more effective in directing movements to targets in ipsilateral visual space. We conclude that not only do these regions code target location, but they also appear to integrate target selection with effector selection.     

Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression

We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value.