Renal peripelvic multicystic lymphangiectasia

Renal peripelvic multicystic lymphangiectasia is an unusual benign peripelvic fluid collection. The sonographic appearance, etiology, and differential diagnosis of peripelvic fluid collections are reviewed.     

The association of neuropsychiatric symptoms and environment with quality of life in assisted living residents with dementia

PURPOSE: We conducted this study to determine whether neuropsychiatric symptoms and environmental characteristics are associated with quality of life in assisted living residents with dementia. DESIGN AND METHODS: We used a cross-sectional study of 134 residents from 22 facilities and employed the Alzheimer's Disease-Related Quality of Life Scale and the Neuropsychiatric Inventory. A scale was developed to capture the homelike climate of each facility. Linear regression analyses were used to estimate the relationship of neuropsychiatric symptoms and homelike climate with quality of life, controlling for sociodemographics, cognition, functional dependence, and physical health. Exploratory analyses and graphical techniques were employed to test for environmental-level moderating effects. RESULTS: Agitation, depression, apathy, and irritability were significant predictors of quality of life, explaining 29% of the variance. Neither facility size nor homelike environment was significantly associated with quality of life in univariate analyses. Size of facility moderated the relationship between agitation and quality of life. IMPLICATIONS: Neuropsychiatric symptoms impair quality of life in residents with dementia. Further research should investigate the role of other environmental aspects.     

Sequential infusion of donor‐derived dendritic cells with donor lymphocyte infusion for relapsed hematologic cancers after allogeneic hematopoietic stem cell transplantation

Donor lymphocyte infusion (DLI) is often given to induce a graft‐versus‐leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT). However, efficacy of DLI is limited in most hematologic cancers. As antigen presenting cells, dendritic cells (DC) bolster immune responses. We conducted a Phase I trial testing the coinfusion of DC followed by DLI. DC were generated by culturing peripheral blood mononuclear cells from HLA matched‐related donors in GM‐CSF and IL‐4 for 7 days, followed by TNF‐α for 3 days. DC were administered intravenously on 3 dose levels (5 × 10⁶; 1 × 10⁷; 5 × 10⁷ cells). DLI (3 × 10⁷ CD3+ cells/kg) was administered intravenously 1 day after the DC. Sixteen patients with hematologic cancers relapsed after HSCT were treated. A maximum tolerated dose for DC was not reached. Two of 16 patients met criteria for DLT within 10 weeks of the infusion: 1 idiopathic respiratory failure, 1 ventricular cardiac arrest. None developed grade III/IV GVHD. One patient developed grade II acute intestinal graft‐vs.‐host disease (GVHD) and 1 chronic GVHD within 6 months of the infusion. Both resolved with corticosteroids. Four of 14 patients evaluable for disease response achieved durable remissions and are alive and cancer free 6.7, 8.4, 8.8, and 10.1 years from infusion. Sequential infusion of donor‐derived DC with DLI is feasible in patients with relapsed hematologic cancers after allogeneic HSCT. Future studies may consider donor DC preloaded with tumor antigens to investigate whether DC infusion could augment the GVL effect. Am. J. Hematol. 89:1092–1096, 2014. © 2014 Wiley Periodicals, Inc.     

A multiresponse parathyroid hormone assay: an inhibitor has agonist properties in vivo

Vitamin D-deficient rats subjected to thyroparathyroidectomy (TPTX) were used to evaluate in vivo the biological properties of native bovine parathyroid hormone (bPTH) and chemically synthesized fragments and analogues of the hormone on several parameters of hormone action: calcium and phosphorus fluxes, generation of cyclic adenosine 3',5'-monophosphate (cAMP), and the metabolism of 25-hydroxyvitamin D3 [25(OH)D3]. Vitamin D-deficient rats, after TPTX or sham operation, were intravenously infused with a nutrient containing 7.5 mM CaCl2 for 30 h. During the last 7 h, PTH or one of its analogues was infused intravenously at rates between 0.04 and 20 nmol/h. One hour after the start of the peptide infusion, tritiated 25(OH)D3 was injected. Urine was collected hourly for phosphate and cAMP determinations and, at the end of the experiment, blood was obtained to determine the relative accumulation of tritiated 1,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3). Infusion of bPTH-(1--84), bPTH-(1--34), human (h)PTH-(1--34), or [Nle8, Nle18, Tyr34]bPTH-(1--34) amide was accompanied by a comparable dose-dependent decrease in plasma phosphate and a dose-dependent increase in plasma calcium and [3H]-1,25(OH)2D3, and urinary excretion of phosphate and cAMP. An evaluation of [Nle8, Nle18, Tyr34]bPTH-(3--34) amide, a potent inhibitor of PTH action in vitro in the renal adenylate cyclase assay, revealed that the analogue possessed weak agonist properties in vivo. The analogue increased excretion of both cAMP and phosphate in the urine, decreased plasma phosphate levels, and increased the accumulation of [3H]-1,25(OH)2D3 in the plasma. This multiparameter model system should aid in the elucidation of the in vivo biological effects of PTH and its analogues.     

Corticosteroidogenesis and adenosine 3', 5'- monophosphate production by the amino-terminal (1-34) fragment of human parathyroid hormone in rat adrenocortical cells

Several studies have revealed a variety of interactions between PTH and ACTH. The existence of a significant area of homology in the bioactive regions of the two molecules has been proposed as a possible reason for such interactions. To clarify the relationship, corticosteroidogenic and cAMP accumulative effects of bovine PTH (bPTH 1-84), its amino-terminal fragment (bPTH 1-34), and the amino terminal fragment of human PTH (hPTH 1-34) were compared with ACTH 1-39 by determining their dose-response characteristics in collagenase-dissociated adrenocortical cells from rats. bPTH 1-84 and bPTH 1-34 (10(-8)-10(-5)M) did not alter steroid production of the cells nor did 10(-6)M bPTH 1-34 affect the steroid response curve to ACTH 1-39. However, the degree of steroidogenesis elicited by hPTH 1-34 over the dose range 3.3 X 10(-7)-3.3 X 10(-5)M was the same as that elicited by ACTH 1-39 over the range 10(-11)-10(-9) M. cAMP generation with hPTH 1-34 was maximal at 10(-4) M but the correlation between the steroid and cAMP responses with ACTH 1-39 was noticeably different from that with hPTH 1-34. In experiments with ACTH 6-24 (a competitive inhibitor of ACTH 1-39), both steroid and cAMP responses to hPTH 1-34 were greatly reduced. Oxidized hPTH 1-34 did not elicit any steroid production nor did several other peptide hormones (arginine vasopressin, angiotensin II, calcitonin, insulin, GH) at 10(-5) M. These observations indicate that hPTH 1-34 can exert a direct and specific effect on rat adrenocortical cells revealing the peptide as a full agonist for steroid production in this system. We suggest that it is a combination of sequence homology and conformational structure which permits hPTH 1-34 to interact with, and elicit its response through, the receptor for ACTH 1-39.     

Narratives of grieving African-Americans about racism in the lives of deceased family members

As part of a comprehensive interview study on African-American grief, the authors explored how racism is incorporated into narratives about a deceased family member. To the extent that experiences of racism are pervasive in African-American life and to the extent that narratives about a person who has died generally account for the life experiences, achievements, character, and challenges faced by the deceased, the authors expected narratives about a deceased African-American to deal with the person's encounters with racism. In fact, most of the 26 African-Americans who were interviewed spoke about racism in the life of the deceased. Many talked about racism blocking the deceased from getting ahead occupationally and in other ways and about how the deceased resisted or stood up to racism. Some people spoke about the ways the deceased taught them to deal with racism. The narratives that indicated that the deceased had rarely or ever talked about racism still made clear that the deceased lived in a racist world but chose not to bring racism into family conversation. The findings suggest that a view of African-American grieving that is insensitive to racism in African-American experience may lead to unhelpful grief support or counseling.     

Matchmaking facilitates the diagnosis of an autosomal‐recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene

Deleterious variants in the same gene present in two or more families with overlapping clinical features provide convincing evidence of a disease–gene association; this can be a challenge in the study of ultrarare diseases. To facilitate the identification of additional families, several groups have created “matching” platforms. We describe four individuals from three unrelated families “matched” by GeneMatcher and MatchMakerExchange. Individuals had microcephaly, developmental delay, epilepsy, and recessive mutations in TRIT1. A single homozygous mutation in TRIT1 associated with similar features had previously been reported in one family. The identification of these individuals provides additional evidence to support TRIT1 as the disease‐causing gene and interprets the variants as “pathogenic.” TRIT1 functions to modify mitochondrial tRNAs and is necessary for protein translation. We show that dysfunctional TRIT1 results in decreased levels of select mitochondrial proteins. Our findings confirm the TRIT1 disease association and advance the phenotypic and molecular understanding of this disorder.     

Rest Myocardial Perfusion Imaging in a Patient with Atypical Chest Pain and a Nondiagnostic Electrocardiogram

ACC/AHA guidelines assign a class I indication for use of myocardial perfusion imaging (MPI) for the evaluation of chest pain in patients with acute coronary syndromes and a nondiagnostic ECG. However, MPI is not a widely used modality for the evaluation of patients who present to the ER with chest pain and an intermediate pretest probability for coronary artery disease. We report a case in which resting MPI was pivotal in diagnosing acute myocardial infarction and expedited the appropriate reperfusion strategy. Copyright © 2010 Wiley Periodicals, Inc.     

CD-20 expression in post-transplant lymphoproliferative disorders: treatment with rituximab

B-cell lymphoproliferative disorders are rare but serious complications of solid organ and bone marrow transplantation. We report that these tumors frequently express the CD-20 antigen, and immunotherapy directed at this antigen may be a well-tolerated and effective treatment.