Identification of a putative haplotype associated with recumbency in Holstein calves.

Thirty-four Holstein calves from multiple farms were found recumbent during the neonatal period with no detectable neurologic, infectious, or metabolic abnormalities. Most calves did not survive beyond 6 wk of age. The objective of this study was to conduct a genome-wide association and pedigree analysis to determine if a genetic origin was plausible. There were 101,917 DNA markers for 18 affected calves and 26 unaffected family controls available for analysis. Genome-wide association, homozygosity screening, and a parental based transmission disequilibrium test were conducted in PLINK. A genomic region on the end of chromosome 16 that contained 78 markers based on a recessive inheritance model and that spanned 5.1 million bp was considered the most probable region for a genetic defect; the region was narrowed to 2.1 million bp following homozygosity screening and the transmission disequilibrium test with all affected calves homozygous in the candidate region and 1 homozygous control. A genotyped sire and 2 dams with imputed genotypes were heterozygous in the candidate region. A common sire born in 2008 was identified that was present for both paternal and maternal lineages of all affected calves; nearly all lineages traced through a prolific son born in 2010 who was genotyped and was heterozygous for the candidate region. Therefore, a possible genetic defect with incomplete penetrance on chromosome 16 that results in recumbency has been identified. Further efforts with an increase in families represented are needed to confirm a genetic basis, and identify the mutation and mode of inheritance.

Role of the Maillard reaction in aging of tissue proteins. Advanced glycation end product-dependent increase in imidazolium cross-links in human lens proteins.

Dicarbonyl compounds such as glyoxal and methylglyoxal are reactive dicarbonyl intermediates in the nonenzymatic browning and cross-linking of proteins during the Maillard reaction. We describe here the quantification of glyoxal and methylglyoxal-derived imidazolium cross-links in tissue proteins. The imidazolium salt cross-links, glyoxal-lysine dimer (GOLD) and methylglyoxal-lysine dimer (MOLD), were measured by liquid chromatography/mass spectrometry and were present in lens protein at concentrations of 0. 02-0.2 and 0.1-0.8 mmol/mol of lysine, respectively. The lens concentrations of GOLD and MOLD correlated significantly with one another and also increased with lens age. GOLD and MOLD were present at significantly higher concentrations than the fluorescent cross-links pentosidine and dityrosine, identifying them as major Maillard reaction cross-links in lens proteins. Like the N-carboxy-alkyllysines Nepsilon-(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine, these cross-links were also detected at lower concentrations in human skin collagen and increased with age in collagen. The presence of GOLD and MOLD in tissue proteins implicates methylglyoxal and glyoxal, either free or protein-bound, as important precursors of protein cross-links formed during Maillard reactions in vivo during aging and in disease.

Imidazolium crosslinks derived from reaction of lysine with glyoxal and methylglyoxal are increased in serum proteins of uremic patients: evidence for increased oxidative stress in uremia.

Glyoxal (GO) and methylglyoxal (MGO) are reactive dicarbonyl compounds formed during autoxidation of both carbohydrates and lipids. They may react with lysine and arginine residues of proteins in Maillard or browning reactions, yielding advanced glycation or lipoxidation end products. Among these are the imidazolium crosslinks, N,N(-di(N(epsilon)-lysino))imidazolium (glyoxal-lysine dimer, GOLD) and N,N(-di(N(epsilon)-lysino))-4-methyl-imidazolium (methylglyoxal-lysine dimer, MOLD). We have detected and measured GOLD and MOLD in human serum by electrospray ionization/mass spectrometry/mass spectrometry (ESI/MS/MS), using 15N4-GOLD and 15N4-MOLD as internal standards. In this report we show that levels of GOLD and MOLD are significantly elevated (3-4-fold, P< 0.01) in sera of non-diabetic uremic patients, compared to age-matched controls, and represent a major class of non-enzymatic, Maillard reaction crosslinks in plasma proteins. These results provide strong evidence for increased non-enzymatic crosslinking of tissue proteins by GO and MGO in uremia, implicating oxidative stress and resultant advanced glycation and lipoxidation reactions in tissue damage in uremia.

N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins.

Advanced glycation end-products and glycoxidation products, such as Nepsilon-(carboxymethyl)lysine (CML) and pentosidine, accumulate in long-lived tissue proteins with age and are implicated in the aging of tissue proteins and in the development of pathology in diabetes, atherosclerosis and other diseases. In this paper we describe a new advanced glycation end-product, Nepsilon-(carboxyethyl)lysine (CEL), which is formed during the reaction of methylglyoxal with lysine residues in model compounds and in the proteins RNase and collagen. CEL was also detected in human lens proteins at a concentration similar to that of CML, and increased with age in parallel with the concentration of CML. Although CEL was formed in highest yields during the reaction of methylglyoxal and triose phosphates with lysine and protein, it was also formed in reactions of pentoses, ascorbate and other sugars with lysine and RNase. We propose that levels of CML and CEL and their ratio to one another in tissue proteins and in urine will provide an index of glyoxal and methylglyoxal concentrations in tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and disease.

A simple modification in operative technique can reduce the incidence of nonanastomotic biliary strictures after orthotopic liver transplantation.

Nonanastomotic strictures after liver transplantations are a source of significant morbidity, often necessitating retransplantation. The purpose of this study was twofold: first to identify features associated with the development of this lesion; second, to make technical modifications that will decrease the incidence of this problem. In the first part of this study, 15 of 131 patients were diagnosed with nonanastomotic biliary stricture. A stepwise logistic-regression analysis associated donor cold ischemic time and dopamine dose with the development of nonanastomotic biliary strictures. All these patients had arterial reconstruction after partial revascularization of the liver with portal venous blood. Because the bile duct receives its blood supply from only the hepatic artery, we hypothesized that the prolonged period of warm ischemia from staged reconstruction of the vascular supply would promote the development of this lesion. In a second part of this study, the stricture rate in 45 patients with simultaneous revascularization using both the hepatic artery and portal vein was compared with that in 83 patients from the first part of this study initially revascularized with portal venous blood. All patients in the second study had grafts preserved using UW solution. Only 1 patient with simultaneous revascularization developed a nonanastomotic biliary stricture. Because we were unable to identify any significant complications related to this method of revascularization, we propose that the hepatic artery and portal vein should be released simultaneously, especially in patients receiving a graft with prolonged storage time.

Admission hyponatremia in the elderly: factors influencing prognosis.

The authors studied the occurrence of admission hyponatremia and its association with selected patient and hospitalization characteristics and in-hospital mortality in a geriatric patient cohort (n = 4,123). Prevalence of admission hyponatremia was 3.5% and higher among women (4.6% vs 2.6%). In-hospital mortality was 16% for patients with admission hyponatremia versus 8.0% for patients without admission, hyponatremia. Adjusting for patient and hospitalization characteristics with a logistic regression analysis, admission hyponatremia was a significant independent predictor of mortality (RR = 1.95). Admission hyponatremia is associated with poor prognosis in the elderly hospitalized population.

Effect of sequential early burn wound excision and closure on postburn oxygen consumption.

OBJECTIVE: To determine the effect of early excision and closure of burns on postburn hypermetabolism, measured as oxygen consumption (VO2). METHODS: Twelve patients with deep burns of 30% to 50% of total body surface underwent sequential excisions and wound coverage, beginning 1 to 3 days after burn. The majority of the deep burn was removed by day 7, but with the addition of a donor site area of 20% to 25% of total body surface. RESULTS: No decrease in VO2 was noted in relation to the percent removal of burn tissue. In addition, a transient further increase in VO2 was noted early after excision, especially with surgical procedures performed after 5 days. This response could not be attributed to wound manipulation-induced bacteremias. CONCLUSION: We conclude that early surgical excision and closure of burns in excess of 30% to 50% of total body surface do not decrease postburn hypermetabolism in proportion to the area closed. It is possible that remaining open wounds in the form of donor sites and nonexcised burn are sufficient to perpetuate the hypermetabolic process, once established.

Routine admission laboratory testing for general medical patients.

We evaluated the usefulness of commonly ordered routine admission laboratory tests in 301 patients admitted consecutively to the internal medicine wards of a university teaching hospital. Using a consensus analysis approach, three Department of Medicine faculty members reviewed the charts of admitted patients to determine the impact of the test results on patient care. The evaluated tests were the urinalysis, hematocrit, white blood cell count, platelet count, six-factor automated multiple analysis (serum sodium, potassium, chloride, bicarbonate, glucose, and blood urea nitrogen), prothrombin time, partial thromboplastin time, chest x-ray, and electrocardiogram. Forty-five percent of the 3,684 tests were ordered for patients without recognizable medical indications. Twelve percent of these routine tests were abnormal, 5% led to additional laboratory testing, but only 0.5% led to change in the treatment of patients. We conclude that the impact of routine admission laboratory testing on patient care is very small and that there is little justification for ordering tests solely because of hospital admission.

Usefulness of routine admission complete blood cell counts on a general medical service.

The usefulness of three components of the routine admission complete blood cell count (leukocyte count, hematocrit, and platelet count) was evaluated in 301 patients consecutively admitted to the internal medicine wards of a university teaching hospital. Using a consensus analysis approach, three faculty members reviewed the patients' charts to determine which tests were performed routinely, which tests were abnormal, and which routine tests led to diagnostic or therapeutic changes. Overall, 55.3% of the tests were considered routine admission tests. Abnormalities were detected in 13.6% of the routine leukocyte counts, in 8.2% of the routine hematocrit levels, and in 12.4% of the routine platelet counts. However, treatment was changed for only three patients, all of whom had low hematocrits; this amounted to 0.6% of all tests. Furthermore, only one of the three patients received appropriate treatment that might have been withheld if a routine hematocrit determination had not been ordered. The authors conclude that the impact of routine admission complete blood cell counts on patient management is small and that the practice of ordering this test for all hospitalized patients could be eliminated with little adverse effect on patient care.

Electrolyte, blood urea nitrogen and glucose level screening in medical admissions. Impact on patient management.

Investigators have failed to show the usefulness of screening electrolyte-sodium, potassium, chloride and bicarbonate-blood urea nitrogen and glucose levels. In spite of this, we observed that that practice continues to be widely used at our university medical center. Using a form of consensus analysis, we examined the records of 301 admissions to the medicine service to determine whether laboratory tests were done for diagnostic or screening purposes and whether screening test results led to changes in patient management. Of the 1,764 tests done, 716 (40.6%) were for screening purposes. Only 2 (0.3%) screening test abnormalities led to any therapeutic changes, and many false-positive tests led to unnecessary diagnostic retesting.

Efficacy of the routine admission urinalysis.

The clinical efficacy of routine admission urinalyses was evaluated in 301 patients admitted to the internal medicine wards of a university teaching hospital. Using a consensus analysis approach, three Department of Medicine faculty members reviewed the patients' charts to determine which tests were performed routinely and which test results led to diagnostic or therapeutic management changes. Of the 243 urinalyses performed, 123 (51 percent) were ordered routinely for patients without recognizable medical indications. Results of the routine urinalyses were abnormal in 42 (34 percent) of the patients and led to additional laboratory testing in 20 (16 percent) of the cases. However, the test results led to therapeutic changes in only three (2.4 percent) of the patients, and in two of these patients, the treatment instituted probably was unnecessary. It is concluded that the impact of routine admission urinalysis on patient care is very small and that there is little justification for ordering this test for all patients admitted to the hospital.

Cardiovascular pathology in renal transplant recipients.

Various cardiovascular complications are among the major causes of mortality in renal transplant recipients. The authors examined the cardiovascular findings from necropsy of 18 renal transplant patients. All but three of the patients showed one or more pathological abnormalities. Five patients exhibited severe coronary arteriosclerosis with acute myocardial infarction with a history of myocardial infarction noted in four patients. In addition, one patient showed moderate and two showed mild coronary arteriosclerosis. Also prevalent were left ventricular (LV) hypertrophy (10/18), right ventricular (RV) hypertrophy (7/18), LV dilatation (4/18), RV dilatation (8/18), left atrial dilatation (3/18), and right atrial dilatation (6/18). Valvular abnormalities consisted of dilatations of mitral ring (1/18), pulmonic valve (2/18), and tricuspid valve (3/18). Pericarditis was found in two patients and aortic atherosclerosis in ten patients. Findings on routine chest roentgenograms and electrocardiograms did not always correspond with the anatomical findings noted on necropsy examination. The results demonstrate a marked increase in the incidence of various cardiac abnormalities in renal transplant recipients.

Feasibility and usefulness of depression screening in medical outpatients.

Depression is common in medical outpatients, but the diagnosis is frequently missed. We introduced the Beck Depression Index into our clinic as a screening tool to determine the feasibility of depression screening, the prevalence of depression in our patients, and the clinical usefulness of the depression index. The questionnaire was easily implemented and well accepted by the 375 patients screened. Moderate or severe depression was identified in 32% of our patients. By several measures, the Beck Depression Index proved to be a highly useful clinical tool. It provided information significant enough to change the plan in 20% of the entire population of patients screened. The severity or presence of depression would probably have been missed without the screening. Depression screening should be considered in all primary care settings.

Usefulness of screening chest roentgenograms in preoperative patients.

We proposed that clinical criteria could define a group of patients very unlikely to have abnormal preoperative chest roentgenograms. Nine hundred five surgical admissions were screened for the presence of clinical factors we thought would make those patients more likely to have abnormal preoperative chest roentgenograms. Of these, 368 had no risk factors. One patient (0.3%) of the 368 had an abnormal x-ray film, which did not affect the surgery. No material abnormalities were found in the remainder of the group without risk factors. Five hundred four patients had identifiable risk factors. Of these, 114 (22%) were found to have serious abnormalities on preoperative chest roentgenogram.