Simultaneous expression of CD4 and CD8 antigens by a substantial proportion of resting porcine T lymphocytes

The existence of four subpopulations in resting porcine T lymphocytes is documented. In addition to the two known subpopulations which are typified by a mutually exclusive expression of either the CD8 or the CD4 differentiation antigen, CD4-CD8+ and CD4+CD8- T lymphocytes, respectively, two unusual subpopulations were prominent not only in peripheral blood, but also in lymphoid tissues: CD4-CD8- T lymphocytes expressing neither of these antigens and CD4+CD8+ T lymphocytes coexpressing both antigens. While CD4+CD8+ lymphoblasts have been found also in other species, resting T lymphocytes with that phenotype are without precedent among all species analyzed to date. This unique composition of the porcine T lymphocyte population has to be taken into consideration when the swine is used as a large animal model in experimental medicine

Relationship Between Calcium Consumption from Dairy and Non-Dairy Sources on Bone Mineral Density of College Students

Dairy product consumption has been on the decline for decades in the US and worldwide, and the increase in plant-based substitutes has grown substantially. Osteoporosis and the risk of bone fractures are serious public health issues. To date, little scientific-based studies have compared the relationship between calcium intake from dairy sources vs non-dairy sources and bone mineral density. The purpose of this study is to compare the relationships between calcium consumption from dairy vs. non-dairy sources and bone mineral density among college students. There was a total of 66 participants in the study including 15 (23%) males and 51 (77%) females. The participants’ ages ranged from 17 to 43 years with 48 (74%) being white, 16 (25%) African American, and 1 (1%) Hispanic. There was a significant difference found between males (M =.00, SD = .00) and females (M =.62, SD = 1.21) for z-scores, t(37), p \u3c.01. There was a significant difference found between males (M = 126.27, SD = 22.44) and females (M = 110.21, SD = 21.55) for stiffness index scores, t(60), p \u3c 02. There was a significant difference found between whites (M = 109.60, SD = 20.67) and non-whites (M = 129.27, SD = 22.86) in stiffness index scores t(58), p \u3c .01. There was a significant difference in dairy calcium intake between participants who did not meet the RDA (M = 293.43, SD = 249.36) and participants who did meet the RDA (M = 940.98, SD = 618.89) t(15.54), p \u3c .01. This study confirmed that not only were participants who didn’t consume dairy calcium not meeting the RDA, but they weren’t making up for the difference in non-dairy sources

Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients

M.D. Pescovitz, R.B. Ettenger, C.F. Strife, J.R. Sherbotie, S.E. Thomas, S. McDiarmid, S. Bartosh, J. Ives, M.R. Bouw, J. Bucuvalas. Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients. Transpl Infect Dis 2010: 12: 195–203. All rights reservedIn an open-label, prospective, pharmacokinetic assessment, we evaluated total drug exposure (area under the curve [AUC]) of intravenous (IV) ganciclovir (GCV) and oral (p.o.) valganciclovir when normalized for body surface area (BSA) in pediatric liver ( n =20) and renal ( n =26) transplant patients Reference doses for IV GCV (200 mg/m 2 ) and p.o. valganciclovir (520 mg/m 2 ) were based on adult doses, and adjusted for BSA initially, and BSA and renal function (estimated via creatinine clearance [CrCL]) thereafter. Renal transplant patients received GCV on days 1–2, valganciclovir 260 mg/m 2 on day 3, and valganciclovir 520 mg/m 2 on day 4. Liver transplant patients received twice daily GCV from enrollment to day 12, and then valganciclovir twice daily on days 13–14. GCV pharmacokinetics were described using a population pharmacokinetic approach. Type of solid organ transplant (kidney or liver) had no effect on GCV pharmacokinetics. Median GCV exposure following valganciclovir 520 mg/m 2 was similar to that with IV GCV, and to that reported in adults. Patients <5 years of age had AUC values approximately 50% of those compared with older age ranges; dosing based on both BSA and CrCL increased drug exposure in younger patients. A dosing algorithm based on BSA and CrCL should be tested in future studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78598/1/j.1399-3062.2009.00478.x.pd

High cut-off haemodialysis induces remission of recurrent idiopathic focal segmental glomerulosclerosis after renal transplantation but is no alternative to plasmapheresis

A 26-year-old male experienced a recurrence of idiopathic focal segmental glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of proteinuria was rapidly induced by plasmapheresis (PP) and the patient has remained in remission with a once-weekly PP regimen, which has now been continued for >3½ years. We were also able to induce remission of iFSGS in this patient by treatment with high cut-off haemodialysis using the Theralite™ dialyser. This observation lends support for the pathophysiological role of an as yet unknown, circulating glomerular filtration barrier permeability factor with an estimated weight of between 30 and 50 kDa

A national survey of valganciclovir dosing strategies in pediatric organ transplant recipients

PurposeData remain limited on the most appropriate valganciclovir (VGCV) dosing strategy for cytomegalovirus (CMV) prophylaxis and treatment in pediatric organ transplant recipients. Therefore, the objective of this study was to describe methods used to calculate VGCV dosing among pediatric transplant centers.MethodsA survey of pharmacists was conducted to assess VGCV dosing strategies for CMV prophylaxis and treatment among pediatric organ transplant centers in the U.S.FindingsOf 54 centers that perform pediatric organ transplants, 22 (40.7%) centers responded to the survey. Fourteen centers (53.8%) utilize the Food and Drug Administration (FDA) recommended VGCV dosing strategy of 7 à  body surface area (BSA) à  creatinine clearance (CrCl) for CMV prophylaxis. Other dosing strategies reported included weight based and 520 mg/m2 à  BSA per day. Dosing strategies of VGCV for the treatment of CMV also differed across centers, with a majority (43.5%) using 7 à  BSA à  CrCl twice daily.ConclusionLess than twoâ thirds of centers utilize the FDAâ approved daily dosing regimen with various methods of CrCl calculation and serum creatinine assay measurements used. More retrospective and prospective studies with clinical outcomes associated with VCGV dosing strategies are warranted to determine the most appropriate prophylaxis and treatment strategies for CMV.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146489/1/ctr13369.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146489/2/ctr13369_am.pd

Sample Size Requirements for Studies of Treatment Effects on Beta-Cell Function in Newly Diagnosed Type 1 Diabetes

Preservation of -cell function as measured by stimulated C-peptide has recently been accepted as a therapeutic target for subjects with newly diagnosed type 1 diabetes. In recently completed studies conducted by the Type 1 Diabetes Trial Network (TrialNet), repeated 2-hour Mixed Meal Tolerance Tests (MMTT) were obtained for up to 24 months from 156 subjects with up to 3 months duration of type 1 diabetes at the time of study enrollment. These data provide the information needed to more accurately determine the sample size needed for future studies of the effects of new agents on the 2-hour area under the curve (AUC) of the C-peptide values. The natural log(), log(+1) and square-root transformations of the AUC were assessed. In general, a transformation of the data is needed to better satisfy the normality assumptions for commonly used statistical tests. Statistical analysis of the raw and transformed data are provided to estimate the mean levels over time and the residual variation in untreated subjects that allow sample size calculations for future studies at either 12 or 24 months of follow-up and among children 8–12 years of age, adolescents (13–17 years) and adults (18+ years). The sample size needed to detect a given relative (percentage) difference with treatment versus control is greater at 24 months than at 12 months of follow-up, and differs among age categories. Owing to greater residual variation among those 13–17 years of age, a larger sample size is required for this age group. Methods are also described for assessment of sample size for mixtures of subjects among the age categories. Statistical expressions are presented for the presentation of analyses of log(+1) and transformed values in terms of the original units of measurement (pmol/ml). Analyses using different transformations are described for the TrialNet study of masked anti-CD20 (rituximab) versus masked placebo. These results provide the information needed to accurately evaluate the sample size for studies of new agents to preserve C-peptide levels in newly diagnosed type 1 diabetes

Hepatocellular Carcinoma with Immature T-Cell (T-lymphoblastic) Proliferation

Indolent T-lymphoblastic proliferation has been rarely reported in the upper aerodigestive tract. The lymphoid cells associated with this condition have the morphological and phenotypical features of immature thymocytes. However, their pathogenesis and biology are unknown. We present an unusual type of tumor infiltrating lymphocytes in a case with hepatocellular carcinoma, presumed to be a T-lymphoblastic proliferation. A 58-yr-old female patient presented with indigestion and a palpable epigastric mass. The abdominal computed tomography revealed a mass in the S6 region of the liver. A hepatic segmentectomy was performed. Microscopic examination showed dense isolated nests of monomorphic lymphoid cells within the tumor. Immunohistochemically, the lymphoid cells were positive for CD3, terminal deoxymucleotide transferase (TdT) and CD1a. In addition, they showed dual expression of CD4 and CD8. The polymerase chain reaction used to examine the T-cell antigen receptor gamma gene rearrangement showed polyclonal T-cell proliferation. This is the second case of hepatocellular carcinoma combined with indolent T-lymphoblastic proliferation identified by an unusual tumor infiltrating lymphocytes

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future