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Berlin C.M.,Milton rshey Medical Center | van den Anker J.N.,Michigan Science Center
Seminars in Fetal and Neonatal Medicine | Year: 2013

The two ultimate goals of using maternal medications during breastfeeding are (i) to provide definitive therapy for maternal conditions for which the drugs have been prescribed, and (ii) to assure protection of the nursing infant from any adverse event related to his/her mother's treatment. Fortunately there are only a few drugs that have been identified as potentially causing harm to the infant. Analytic techniques exist to measure compounds in concentrations as small as nanograms per liter of milk. For nearly all compounds these very small amounts would not be able to exert pharmacological activity, even if absorbed by the infant via the oral route. For environmental chemicals, this ability to measure very small amounts exceeds our knowledge of any biological activity. Concern over any possible adverse event to the nursing infant should take into account the drug, its dose, the age of the infant, recognition of the interindividual variation in drug response and the role of pharmacogenetics. The latter two variables are closely linked. © 2012. Source


Green J.,Novartis | Lipton A.,Milton rshey Medical Center
Cancer Investigation | Year: 2010

Zoledronic acid effectively reduces/delays skeletal-related events in patients with metastatic disease or skeletal-related cancers. Emerging data suggest that zoledronic acid may also exhibit anticancer properties. Zoledronic acid ± anticancer therapies in animal models inhibits soft-tissue tumor growth, decreases tumor cell proliferation, increases apoptosis, inhibits angiogenesis, alters tumor-associated macrophage function, and enhances immune surveillance. Data from in vitro and pilot studies suggest that zoledronic acid inhibits tumor cell dissemination in bone marrow, and early clinical data show that it may improve disease-related outcomes. Ongoing studies will further elucidate the role of zoledronic acid in cancer patients. © 2010 Informa Healthcare USA, Inc. Source


Cui J.,Penn State College of Medicine | Boehmer J.P.,Penn State College of Medicine | Blaha C.,Penn State College of Medicine | Lucking R.,Penn State College of Medicine | And 2 more authors.
Circulation: Heart Failure | Year: 2013

Background.Previous studies show that the rise in skin blood flow and cutaneous vascular conductance during heat stress is substantially attenuated in chronic heart failure (CHF) patients. The mechanisms responsible for this finding are not clear. In particular, little is known regarding the responses of skin sympathetic nerve activity (SSNA) that control the skin blood flow during heat stress in CHF patients. We examined the effects of a modest heat stress to test the hypothesis that SSNA responses could be attenuated in CHF. Methods and Results.We assessed SSNA (microneurography) from the peroneal nerve and skin blood flow (forearm laser Doppler) in 9 patients with stable class II.III CHF and in matched healthy subjects during passive whole-body heating with a water-perfused suit. Whole-body heating induced similar increases in internal temperature (.0.6-C) in both groups. Whole-body heat stress evoked similar SSNA activation in CHF patients (δ891±110 U/min) and the control subjects (δ787±84 U/min; P=0.66), whereas the elevation in forearm cutaneous vascular conductance in patients with CHF was significantly lower than that in healthy control subjects (δ131±29% vs δ623± 131%; P=0.001). Conclusions.The present data show that SSNA activation during a modest whole-body heat stress is not attenuated in CHF. Thus, the attenuated skin vasodilator response in CHF patients is not attributable to a reduction in total activity of sympathetic outflow to skin. © 2013 American Heart Association, Inc. Source


Connelly T.M.,Penn State College of Medicine | Berg A.S.,Milton rshey Medical Center | Hegarty J.P.,Penn State College of Medicine | Deiling S.,Penn State College of Medicine | And 3 more authors.
Annals of Surgery | Year: 2014

OBJECTIVE:: To determine if single nuclear polymorphisms (SNPs) in the TFNSF15 gene play a role in patients requiring surgery for diverticulitis. BACKGROUND:: A role for a genetic predisposition in diverticulitis is suggested by its association with hereditary connective tissue disorders, youthful onset in some patients, and the observation of families with multiple affected individuals. The TNFSF15 gene has been associated with other inflammatory diseases affecting the colon such as medically refractory ulcerative colitis (UC), aggressive Crohn's disease (CD), and pouchitis after restorative proctocolectomy. METHODS:: In the discovery phase of this study, 21 sporadic surgical diverticulitis (SD) patients (9 female, mean age = 52 ± 5) and 5 individuals from a single family with surgically managed diverticulitis [familial diverticulitis (FD), 4 female, mean age = 51.1 ± 7] were studied. SD patients were age and sex matched with 3 separate groups of healthy, CD and UC control patients. All patients were genotyped for 5 known TNFSF15-associated SNPs. The SNP discovered to be associated with diverticulitis (rs7848647) was then confirmed in a separate test group composed of 34 additional patients (20 female, mean age 57.7 ± 2) who also underwent surgical treatment for diverticulitis. These patients were age matched to a new control cohort of patients having no history of diverticulitis (26 female). Patients were genotyped using a TaqMan assay. In the discovery phase, logistical regression on matched subjects was performed to determine an association of TNFSF SNP with diverticulitis versus the control groups. In the test phase, significance for the rs7848647 SNP was assessed by the Fischer's exact test. RESULTS:: In the discovery phase, the TNFSF15 SNP rs7848647 was significantly associated with SD (p = 0.0003) versus all control groups studied. The risk allele for this SNP (G substituted for A) was found in all SD patients. The homozygous GG allele was found in 62% (13/21) of SD patients versus only 5% (1/21) of healthy controls (p = 0.001) and 24% (10/42) of all UC + CD controls (p = 0.002). All 5 members of the FD cohort were homozygous for the at-risk "G" allele. In the test group, the homozygous GG genotype was found in 56% of SD patients compared with 17% of healthy controls (p = 0.006). Risk of SD seemed to increase with number of the G alleles with 8% of SD patients having AA homozygosity, 35% of SD patients having AG heterozygosity, and 56% of SD patients having GG homozygosity. CONCLUSIONS:: The SNP rs7848647 associated with the TNFSF15 gene is associated with surgical diverticulitis. This finding suggests a fundamental role for TNFSF15, a T-cell receptor gene involved in T-cell maturation, in the pathophysiology of diverticulitis requiring surgery. This SNP may be a marker of diverticular disease severity that might assist in surgical decision making. © 2013 Lippincott Williams & Wilkins. Source


Dallon J.C.,Brigham Young University | Ehrlich H.P.,Milton rshey Medical Center
Journal of Cellular Biochemistry | Year: 2010

Both rat derived vascular smooth muscle cells (SMC) and human myofibroblasts contain a smooth muscle actin (SMA), but they utilize different mechanisms to contract populated collagen lattices (PCLs). The difference is in how the cells generate the force that contracts the lattices. Human dermal fibroblasts transform into myofibroblasts, expressing α-SMA within stress fibers, when cultured in lattices that remain attached to the surface of a tissue culture dish. When attached lattices are populated with rat derived vascular SMC, the cells retain their vascular SMC phenotype. Comparing the contraction of attached PCLs when they are released from the culture dish on day 4 shows that lattices populated with rat vascular SMC contract less than those populated with human myofibroblast. PCL contraction was evaluated in the presence of vanadate and genistein, which modify protein tyrosine phosphorylation, and ML-7 and Y-27632, which modify myosin ATPase activity. Genistein and ML-7 had no affect upon either myofibroblast or vascular SMC-PCL contraction, demonstrating that neither protein tyrosine kinase nor myosin light chain kinase was involved. Vanadate inhibited myofibroblast-PCL contraction, consistent with a role for protein tyrosine phosphatase activity with myofibroblast-generated forces. Y-27632 inhibited both SMC and myofibroblast PCL contraction, consistent with a central role of myosin light chain phosphatase. © 2010 Wiley-Liss, Inc. Source

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