Increased vascular density associated with lesions of canine globoid leukodystrophy

Two control dogs and 2 dogs that had globoid cell leukodystrophy (GLD) were studied to document vascular alterations associated with the leukodystrophic lesion. Spinal white matter was sampled by transverse and frontal planes of section from dorsal and ventral halves of the lateral funiculus of five spinal segments. Vessel profiles were classified as capillaries or larger vessels. GLD lesion was associated with an increase in capillary mean diameter. Vascular density, estimated by profiles per area, was compared in affected and control tissues. Capillary density was not significantly different, but the density of larger vessels was increased in proportion to the extent of GLD lesion. The increased density is presumed to be the result of lengthening or proliferation of vessels which had normal density prior to lesion formation.     

The Clustering of Risk Behaviors Among Caribbean Youth

Objective: To examine the relationships among risk behaviors for Caribbean youth; and to determine the correlations between initiation of sexual activity and other risk behaviors. Methods: The associations between cigarette smoking, alcohol and marijuana use, early initiation of sexual intercourse, involvement in violence and delinquency were examined using odds ratios on data from the Caribbean Youth Health Survey (n = 15,695). Survival analysis was then used to determine the association between initiation of sexual activity and the risk behaviors. Findings: There were statistically significant relationships between all pairs of risk behaviors for both male and female adolescents. Even though more males than females had engaged in each of the behaviors, the strengths of association were higher for females. From survival analysis, initiation of sexual activity was associated with gang involvement and weapon carrying among young adolescents and even more risk behaviors among the older adolescents. Conclusion: Health compromising behaviors cluster among Caribbean youth with associations being stronger for females. Initiating sexual activity was a predictor of other risk behaviors with the likelihood increasing among older adolescents and females.     

Megakaryocytes modulate osteoblast synthesis of type-l collagen, osteoprotegerin, and RANKL

We have previously reported evidence that megakaryocytes may play a role in bone remodeling, possibly by interactions with cells at the bone surface. To investigate the direct effects of megakaryocytes on osteoblasts, maturing megakaryocytes (CD61 positive cells) were isolated and added to cultures of human osteoblasts. Osteoblasts alone and osteoblasts treated with CD61-negative (non-megakaryocytic) cells were used as control cultures. After 48 h in culture, megakaryocytes were removed and osteoblasts immunolocalized for type-1 collagen, osteoprotegerin (OPG), and RANKL expression. Similar cultures were used for RNA extraction with mRNA for Col 1A1, OPG, and RANKL in osteoblasts measured quantitatively by RT-PCR. Osteoblasts cultured alone showed high levels of expression of collagen with 74% (+/-7) of cells staining positively. When cultured with megakaryocytes, the number of positively staining cells remained similar but the intensity of expression was increased 1.54-fold (P < 0.02). OPG was expressed by 32% (+/-6.3) of osteoblasts increasing to 51% (+/-5.5) when cultured in the presence of megakaryocytes (P < 0.01) with a 1.63-fold increase in intensity of expression (P < 0.01). In contrast, osteoblasts cultured with megakaryocytes showed suppression of RANKL expression; 35.6% (+/-5.8) of osteoblasts cultured alone stained positively decreasing to 24.3% (+/-5.3) with a 1.6-fold diminished intensity of expression (P < 0.02). Osteoblasts co-cultured with CD61-negative cells showed no differences in collagen, OPG, or RANKL expression levels compared to osteoblasts cultured alone. mRNA data supported these findings with a 3.1-fold increase in Col 1A1 expression in megakaryocyte-treated cultures compared to controls (P < 0.02). Low-level OPG mRNA expression increased 8.14-fold in osteoblasts cultured in the presence of megakaryocytes (P < 0.01), while RANKL expression was suppressed 3.3-fold (P < 0.02). These results demonstrate that in vitro, megakaryocytes have direct effects on osteoblastic production of factors affecting both bone formation and resorption. These data provide further evidence that megakaryocytes may play an important role in bone remodeling.     

Risk-adjusted predictive models of mortality after index arterial operations using a minimal data set

BACKGROUND: Reducing the data required for a national vascular database (NVD) without compromising the statistical basis of comparative audit is an important goal. This work attempted to model outcomes (mortality and morbidity) from a small and simple subset of the NVD data items, specifically urea, sodium, potassium, haemoglobin, white cell count, age and mode of admission. METHODS: Logistic regression models of risk of adverse outcome were built from the 2001 submission to the NVD using all records that contained the complete data required by the models. These models were applied prospectively against the equivalent data from the 2002 submission to the NVD. RESULTS: As had previously been found using the P-POSSUM (Portsmouth POSSUM) approach, although elective abdominal aortic aneurysm (AAA) repair and infrainguinal bypass (IIB) operations could be described by the same model, separate models were required for carotid endarterectomy (CEA) and emergency AAA repair. For CEA there were insufficient adverse events recorded to allow prospective testing of the models. The overall mean predicted risk of death in 530 patients undergoing elective AAA repair or IIB operations was 5.6 per cent, predicting 30 deaths. There were 28 reported deaths (chi(2) = 2.75, 4 d.f., P = 0.600; no evidence of lack of fit). Similarly, accurate predictions were obtained across a range of predicted risks as well as for patients undergoing repair of ruptured AAA and for morbidity. CONCLUSION: A 'data economic' model for risk stratification of national data is feasible. The ability to use a minimal data set may facilitate the process of comparative audit within the NVD.