Faculty Bibliography

Mr. [Rudolph W. Giuliani] was given a diagnosis of prostate cancer in 2000, which led him to abandon his race for the United States Senate against Hillary Rodham Clinton. Dr. [Valentin Fuster] said that Mr. Giuliani had had a P.S.A. test, which checks for prostate cancer, within the past month, and that it was ''negligible or undetectable.'' ''I got checked out up and down, inside and out,'' he said, adding, ''I think I might have ended up being more tired from the tests afterward than I was from the headache.''

Diving Bell and the Butterfly [Motion Picture] -- Dr. David S. Liebeskind, associate neurology director at the UCLA Stroke Center points out that the most common life-threatening complications are medical and include pneumonia, urinary and wound infections, occurring mostly because of immobility and flaccidity

Laminitis is a common debilitating disease in horses that involves painful disruption of the lamellar dermo-epidermal junction within the hoof. This condition is often refractory to conventional anti-inflammatory analgesia and results in unremitting pain, which in severe cases requires euthanasia. The mechanisms underlying pain in laminitis were investigated using quantification of behavioural pain indicators in conjunction with histological studies of peripheral nerves innervating the hoof. Laminitic horses displayed consistently altered or abnormal behaviours such as increased forelimb lifting and an increased proportion of time spent at the back of the box compared to normal horses. Electron micrographic analysis of the digital nerve of laminitic horses showed peripheral nerve morphology to be abnormal, as well as having reduced numbers of unmyelinated (43.2%) and myelinated fibers (34.6%) compared to normal horses. Sensory nerve cell bodies innervating the hoof, in cervical, C8 dorsal root ganglia (DRG), showed an upregulated expression of the neuronal injury marker, activating transcription factor-3 (ATF3) in both large NF-200-immunopositive neurons and small neurons that were either peripherin- or IB4-positive. A significantly increased expression of neuropeptide Y (NPY) was also observed in myelinated afferent neurons. These changes are similar to those reported in other neuropathic pain states and were not observed in the C4 DRG of laminitic horses, which is not associated with innervation of the forelimb. This study provides novel evidence for a neuropathic component to the chronic pain state associated with equine laminitis, indicating that anti-neuropathic analgesic treatment may well have a role in the management of this condition.

Awake [Motion Picture] -- According to Peter Sebel, vice chairman of anesthesiology at Emory University in Atlanta and author of a definitive study on the subject published in 2004 in the journal Anesthesia & Analgesia, the film is correct about how common the condition of anesthesia awareness is -- it occurs in about 0.14% of cases. Recognition should be easier when a patient is also in pain, Pregler says, because there are usually changes in vital signs (such as increased heart rate and blood pressure as well as sweating, pupil dilation and tear-formation) that would be noticed by any competent anesthesiologist.

The expression of matrix metalloproteinase-13 (MMP-13), involved in bone turnover, is elevated in stretched MC3T3-E1 osteoblast-like cells. Strain-mediated forces impact bone remodeling due in large part to the movement of fluid through the canalicular-lacunar network. The resulting fluid shear stress (FSS) over the surface membranes of bone cells initiates bone remodeling. Although the nuclear events mediating putative FSS-induced changes in osteoblast MMP-13 transcription are unknown, previous studies with bone cells suggest an overlap between osteoblast FSS- and PTH-induced signal response pathways. MMP-13 PTH response is regulated by a 110 bp 5' regulatory region, conserved across the mouse, rat, and human genes, that supports the binding of numerous transcription factors including Runx2, c-fos/c-jun, Ets-1, and nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) a nucleocytoplasmic shuttling trans-acting protein that attenuates PTH-driven transcription. Nmp4/CIZ also binds p130(cas), an adaptor protein implicated in mechanotransduction. Here we sought to determine whether Nmp4/CIZ contributes to FSS-induced changes in MMP-13 transcription. FSS (12 dynes/cm(2), 3-5 h) increased MMP-13 promoter-reporter activity approximately two-fold in MC3T3-E1 osteoblast-like cells attended by a comparable increase in mRNA expression. This was accompanied by a decrease in Nmp4/CIZ binding to its cis-element within the PTH response region, the mutation of which abrogated the MMP-13 response to FSS. Interestingly, FSS enhanced Nmp4/CIZ promoter activity and induced p130(cas) nuclear translocation. We conclude that the PTH regulatory region of MMP-13 also contributes to FSS response and that Nmp4/CIZ plays similar but distinct roles in mediating hormone- and FSS-driven induction of MMP-13 in bone cells.

Our aim was to investigate whether exercise-induced increase in systolic blood pressure (BP) measured during exercise stress testing (EST) adds prognostic information to cardiovascular (CV) mortality. EST is ideally suited to evaluate the prognostic power of systolic BP; it not only measures systolic BP response to exercise but also provides information about exercise capacity and other EST variables, which may affect the peak systolic BP. The study population consisted of 6,145 consecutive patients who underwent symptom-limited EST. Using the median value of change in systolic BP from baseline, patients were grouped according to exercise-induced increases in systolic BP<or=43 mm Hg (group A, n=3,062) and >or=44 mm Hg (group B, n=3,083). Multivariate analysis was used to adjust for baseline differences between the 2 groups with CV mortality as the end point for follow-up. Six thousand one hundred forty-five men underwent EST with a mean follow-up of 6.6 years. During follow-up, 676 patients died of CV causes with an average annual CV mortality of 1.6%. CV mortality was significantly higher in group A than in group B (13.7% vs 8.2%, p<0.001). After adjusting for baseline differences in the 2 groups using multivariate analysis, an increase in systolic BP of <or=44 mm Hg was a significant predictor of mortality (hazard ratio 1.2, 95% confidence interval 1.02 to 1.44, p<0.05). In conclusion, systolic BP response to maximal EST adds prognostic information to CV mortality independent of age, ST-segment abnormalities, and exercise capacity. In our study an increment in systolic BP of >or=44 mm Hg during EST was associated with a 23% improvement in survival over a mean follow-up of >6 years

The current study evaluated Mycobacterium tuberculosis isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in approximately 30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RD(Rio). Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RD(Rio) locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS6110-based restriction fragment length polymorphism analysis cumulatively support the idea that RD(Rio) strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RD(Rio) lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RD(Rio) strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RD(Rio) strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RD(Rio) M. tuberculosis

BACKGROUND:We previously reported the efficacy of a combined treatment of active acromegaly with both long-acting somatostatin analogs (SSA) and pegvisomant (PEG-V). OBJECTIVE:Our objective was to assess long-term efficacy and safety in a larger group of acromegalic patients after a period of 138 (35-149) wk [median (range)]. DESIGN/METHODS:PEG-V was added to high-dose SSA treatment in 32 subjects (13 females) who had not shown a normalization in serum IGF-I concentrations during SSA monotherapy. PEG-V dosage was increased until IGF-I concentration normalized. The maximal dose was 80 mg twice weekly. RESULTS:After dose finding, IGF-I remained within the normal range in all subjects with PEG-V administered once (n = 24) or twice (n = 8) weekly, on a total weekly dose of 60 (40-160) mg. Baseline IGF-I levels were positively correlated with the required dosage of PEG-V (r = 0.48; P = 0.006). PEG-V-dependent liver enzyme disturbances were observed in 11 (6 diabetic) subjects, of which symptomatic gallstones explained two cases. These liver enzyme disturbances were transient in all subjects without discontinuation or dose adaptation of PEG-V. In our series, diabetic patients had a 5.1 times (odds ratio) (confidence interval, 1.02-25.54; P < 0.05) higher risk for developing liver enzyme disturbances. These liver enzyme disturbances seemed to occur earlier. Pituitary adenoma size decreased in four patients. No increase in tumor size was observed in any of the patients. CONCLUSION/CONCLUSIONS:Long-term combined treatment with long-acting SSA and (twice) weekly PEG-V for active acromegaly seems to be effective and safe. Patients with acromegaly and diabetes seem to have a higher risk of developing transient liver enzyme disturbances.

If yes, have your doctor check your blood sugar level; it could be a sign of diabetes or a kidney disorder called diabetes insipidus