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In 2008, the University of Michigan Health System (UMHS) created a Laboratory Test Utilization Program that included the establishment of a Laboratory Formulary Committee under the imprimatur of the Faculty Group Practice, the Office of Clinical Affairs, the Department of Pathology, and UMHS hospital administration. A critical component of the program is UM-CareLink, an order entry system for inpatients and inpatient-like venues. UM-CareLink allows very basic decision support comment prompts. Through the application of peer-reviewed medical evidence, input by medical content experts, excellent cooperation by medical staff, and close oversight by Pathology of the Sendout Laboratory, this program has led to a robust process of test utilization oversight, excellent communication with clinical services, and significant UMHS activity-adjusted reductions in laboratory expense.

On the basis of anecdotal instances in which atypical laboratory findings suggested the possibility of unsuspected cryoglobulinemia, we applied predetermined criteria to determine how often such findings predict the presence of clinically significant cryoglobulinemia. The laboratory criteria are smeared M-spike (paraprotein) in agarose gel serum protein electrophoresis, precipitated protein at the serum application point of agarose electrophoresis gel, greater than 50% quantitative discrepancy between the densitometrically estimated M-spike and the relevant corresponding serum immunoglobulin isotype concentration from the same specimen, and smeared protein observed on an agarose electrophoresis immunofixation gel. Cases that fulfilled any of these criteria were prospectively collected for 2 years. Brouet types and clinical findings were determined in cases where cryoglobulins were subsequently identified and clinical data available. Among 83 patients in whom any of the above laboratory findings were identified, 52 had subsequent cryoglobulin evaluations. Fourteen of these 52 patients had cryoglobulinemia. Findings indicative of clinically significant cryoglobulinemia were present in 8 of the 10 patients in whom follow-up clinical data were available.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase and a proposed cardiovascular risk factor, is elevated in chronic kidney disease (CKD). Pharmacological strategies that lower plasma concentration of ADMA may be expected to increase nitric oxide (NO.) bioavailability and potentially limit atherosclerosis. We hypothesized that the antioxidant alpha-tocopherol (vitamin E) reduces ADMA levels in CKD.An open-label pilot interventional study using 800 IU of vitamin E was undertaken in eight stable out-patients with non-diabetic CKD (creatinine clearance30 ml/min/1.73 m(2)) and six healthy controls, with the objective of measuring plasma ADMA levels at baseline and after 8 weeks of treatment. Plasma ADMA, symmetric dimethylarginine (SDMA) and alpha-tocopherol concentrations were determined at study entry and exit using high-performance liquid chromatography, while plasma total F2-isoprostanes, an index of oxidative stress, were measured using a commercially available enzyme-linked immunosorbent assay kit.ADMA and SDMA concentrations were significantly higher in the plasma of patients compared with that of controls (P/= 0.001). After treatment with vitamin E, ADMA decreased by 23% in six of eight patients (P0.001). The remaining two patients showed either an increase or no change (overall, P = 0.16). There was no significant change in plasma F2-isoprostanes with vitamin E treatment for 8 weeks.Antioxidant therapy with vitamin E has the potential to lower ADMA levels in CKD patients, implying increased NO. availability. This strategy merits further exploration in the setting of CKD prior to renal replacement.

In hypophysectomized rats, prolactin induces regression of the corpora lutea. Luteal regression is accompanied by infiltration of monocytes/macrophages, declines in luteal mass and plasma progestins, and increased staining for monocyte chemoattractant protein-1 (MCP-1). We investigated whether similar events are induced during the estrous cycle, after the proestrous prolactin surge. Rats were killed on proestrus or on estrus, and one ovary was frozen for immunohistochemical detection of MCP-1, monocytes/macrophages (ED1-positive), and differentiated macrophages (ED2-positive) and for in situ detection of apoptotic nuclei. Corpora lutea of the current (proestrus) or preceding (estrus) cycle were dissected from the ovaries of additional rats and frozen for the same analyses and for determination of total protein content. In sections of whole ovaries, intensity and distribution of MCP-1 staining were increased in corpora lutea of multiple ages on estrus as compared to proestrus, as were numbers of differentiated macrophages and apoptotic nuclei per high-power field. Sections of isolated corpora lutea showed these increases on estrus, and the number of monocytes/macrophages per high-power field was also significantly increased. Accompanying these inflammatory/immune events, the corpora lutea on estrus showed decreased weight and total protein per corpus luteum, as compared to corpora lutea on proestrus. These changes are consistent with a proposed role for prolactin in the initiation of luteal apoptosis and of a sequence of inflammatory/immune events that accompany regression of the rat corpus luteum during the normal estrous cycle.

Granulocytopenia and oral mucosal defects have been reported to be important predisposing factors to recently recognized cases of Capnocytophaga septicemia. The authors call attention to an apparent preponderance of these cases in the pediatric age group and emphasize laboratory features which they have found helpful in the diagnosis of Capnocytophaga infections. Thirteen patients with Capnocytophaga infections were seen during a seven-year period. Seven of these patients had Capnocytophaga bacteremia. Six of seven bacteremic patients were granulocytopenic, six had oral mucosal defects, and three died. Five of the seven bacteremic patients were younger than 20 years of age. This represents a disproportionate distribution of cases in the pediatric age group within the author’s institution, because 43% of blood culture specimens submitted to their microbiology laboratory are obtained from pediatric patients. This observation is supported by a review of the reported cases of Capnocytophaga septicemia in which 7 of 12 patients were younger than 20 years of age. Because Capnocytophaga may superficially resemble the more commonly isolated Fusobacterium nucleatum , distinguishing features for laboratory identification are discussed.