Early imaging in heart failure: Exploring novel molecular targets

Conclusions  Noninvasive imaging of neurohumoral upregulation in remodeled myocardium suggests that an imaging strategy can be developed for predicting the rate of remodeling and likelihood of HF development. This should allow a more judicious use of neurohumoral antagonists especially in subjects who do not have manifest HF.⁷⁴ In others specific targeted imaging may allow timely selection of individualized treatment strategies and ensure optimization of therapeutic intervention. Similar to ACE and AII receptors, multiple other targets in the hormonal cascades can identify the likelihood of adverse and favorable remodeling.⁷⁴     

Inhibition of Tuberoinfundibular Dopaminergic Neural Activity During Suckling: Involvement of μ and κ Opiate Receptor Subtypes

Previous studies have shown that mu (μ) and kappa ( κ ) opioid antagonists inhibit suckling-induced prolactin release. Prolactin responses elicited by pup suckling or opioid administration are mediated, at least in part, by suppression of dopamine (DA) release from tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus. We examined the effects of the μ opiate receptor antagonist, β -funaltrexamine ( β -FNA), and the κ opiate receptor antagonist, nor-binaltorphimine (nor-BNI) on the activity of TIDA neurons in lactating rats. TIDA neuronal activity was determined by measuring DOPA accumulation in the caudate putamen (CP) and median eminence (ME). The effects of opioid antagonist treatment were determined in pup-deprived (low circulating prolactin levels) or pup-suckled rats (high circulating prolactin levels). The accumulation of 5-hydroxytryptophan (5-HTP) in the medial preoptic area (MPOA), the anterior hypothalamus (AH) and the median eminence (ME) was quantified as an index of serotonergic activity in the same animals for comparative purposes.     

Relationships between material properties and CT scan data of cortical bone with and without metastatic lesions

Breast, prostate, lung, and other cancers can metastasize to bone and lead to pathological fracture. To lay the groundwork for new clinical techniques for assessing the risk of pathological fracture, we identified relationships between density measured using quantitative computed tomography (rhoQCT), longitudinal mechanical properties, and ash density (rhoAsh) of cortical bone from femoral diaphyses with and without metastatic lesions from breast, prostate, and lung cancer (bone with metastases from six donors; bone without metastases from one donor with cancer and two donors without cancer). Moderately strong linear relationships between rhoQCT and elastic modulus, strength, and rhoAsh were found for bone with metastases (0.73相似文献   

Selection by phage display of llama conventional V(H) fragments with heavy chain antibody V(H)H properties

A llama single domain antibody (dAb) library designed and constructed to contain only heavy chain antibody variable domains (V(H)Hs) also contained a substantial number of typical conventional antibody heavy chain variable sequences (V(H)s). Panning the library against two carbohydrate-specific antibodies yielded anti-idiotypic dAbs and enriched solely for sequences from the V(H) subpopulation of the library. The conventional antibody origin of these V(H)s was confirmed by using oligonucleotide probes, specific for the enriched V(H)s, to identify the parental sequences in the message employed in library construction. Surprisingly, these V(H) dAbs, which are produced in high yield in Escherichia coli, are highly soluble, have excellent temperature stability profiles and do not display any aggregation tendencies. The very close similarity of these molecules to human V(H)s makes them potentially very useful as therapeutic dAbs.     

Antenatal corticosteroid therapy and risk of osteoporosis

Objective To assess the risk of maternal osteoporosis associated with antenatal corticosterioid administration for neonatal respiratory distress syndrome prophylaxis.
Design Prospective longitudinal study.
Setting Maternity unit of Chelsea and Westminster Hospital, London.
Population Fourteen pregnant women who received dexamethasone therapy for fetal lung maturation in anticipation of delivery before 34 completed weeks of gestation.
Methods Blood samples were collected before dexamethasone administration, 24 hours and 48 hours after the course of dexamethasone, and within 24 hours of delivery. Serum levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) were measured to monitor the rate of bone formation, and serum levels of cross-linked carboxy terminal telopeptide (ICTP) were measured as a marker of bone resorption.
Main outcome measures Changes in the markers of bone turnover following dexamethasone administration.
Results Serum PICP levels dropped 24 hours after dexamethasone therapy (   P = 0.001  ), but partially recovered by 48 hours (   P = 0.014  ) to reach higher than pre-therapy levels at delivery (   P = 0.044  ). Although there were no corresponding changes in the serum levels of ICTP after 24 and 48 hours of therapy, levels increased from pretherapy to delivery (   P = 0.006  ).
Conclusion Antenatal corticosteroid therapy leads to a transient suppression of, followed by an increase in, bone formation without any significant alteration in the pattern of bone resorption expected during pregnancy.     

Bilateral renal lymphangiomatosis: sonographic findings

Renal lymphangiomatosis is an exceedingly rare disorder characterized by developmental malformation of the lymphatic system surrounding the kidneys. We report a case of bilateral renal lymphangiomatosis in a 21-year-old man who underwent abdominal sonographic examination that revealed numerous cystic areas of various sizes around both kidneys with extension along the renal hilum. Subsequent abdominal CT examination demonstrated bilateral, multilocular, fluid-filled cystic masses with thin walls in the perirenal and peripelvic region. MRI of the patient revealed bilaterally enlarged kidneys with multiple hyperintense lesions in both perirenal spaces and the peripelvic area on T2-weighted images. These cystic spaces appeared hypointense on T1-weighted images with no enhancement in postcontrast images. The diagnosis of renal lymphangiomatosis was made based on typical imaging findings.     

Deficits in predictive smooth pursuit after mild traumatic brain injury

Given that even mild traumatic brain injury (TBI) may produce extensive diffuse axonal injury (DAI), we hypothesized that mild TBI patients would show deficits in predictive smooth pursuit eye movements (SPEM), associated with impaired cognitive functions, as these processes are dependent on common white matter connectivity between multiple cerebral and cerebellar regions. The ability to predict target trajectories during SPEM was investigated in 21 mild TBI patients using a periodic sinusoidal paradigm. Compared to 26 control subjects, TBI patients demonstrated decreased target prediction. TBI patients also showed increased eye position error and variability of eye position, which correlated with decreased target prediction. In all subjects, average target prediction, eye position error and eye position variability correlated with scores related to attention and executive function on the California Verbal Learning Test (CVLT-II). However, there were no differences between TBI and control groups in average eye gain or intra-individual eye gain variability, or in performance on the Wechsler Abbreviated Scale of Intelligence (WASI), suggesting that the observed deficits did not result from general oculomotor impairment or reduced IQ. The correlation between SPEM performance and CVLT-II scores suggests that predictive SPEM may be a sensitive assay of cognitive functioning, including attention and executive function. This is the first report to our knowledge that TBI patients show impaired predictive SPEM and eye position variability, and that these impairments correlate with cognitive deficits.     

Computed tomographic colonography: assessment of radiologist performance with and without computer-aided detection

BACKGROUND & AIMS: In isolation, computer-aided detection (CAD) for computed tomographic (CT) colonography is as effective as optical colonoscopy for detection of significant adenomas. However, the unavoidable interaction between CAD and the reader has not been addressed. METHODS: Ten readers trained in CT but without special expertise in colonography interpreted CT colonography images of 107 patients (60 with 142 polyps), first without CAD and then with CAD after temporal separation of 2 months. Per-patient and per-polyp detection were determined by comparing responses with known patient status. RESULTS: With CAD, 41 (68%; 95% confidence interval [CI], 55%-80%) of the 60 patients with polyps were identified more frequently by readers. Per-patient sensitivity increased significantly in 70% of readers, while specificity dropped significantly in only one. Polyp detection increased significantly with CAD; on average, 12 more polyps were detected by each reader (9.1%, 95% CI, 5.2%-12.8%). Small- (< or =5 mm) and medium-sized (6-9 mm) polyps were significantly more likely to be detected when prompted correctly by CAD. However, overall performance was relatively poor; even with CAD, on average readers detected only 10 polyps (51.0%) > or =10 mm and 24 (38.2%) > or =6 mm. Interpretation time was shortened significantly with CAD: by 1.9 minutes (95% CI, 1.4-2.4 minutes) for patients with polyps and by 2.9 minutes (95% CI, 2.5-3.3 minutes) for patients without. Overall, 9 readers (90%) benefited significantly from CAD, either by increased sensitivity and/or by reduced interpretation time. CONCLUSIONS: CAD for CT colonography significantly increases per-patient and per-polyp detection and significantly reduces interpretation times but cannot substitute for adequate training.