Systemic arterial blood pressure and urine protein/creatinine ratio in dogs with hyperadrenocorticism

OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease. DESIGN: Case series and cohort study. ANIMALS: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment. RESULTS: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease. CLINICAL IMPLICATIONS: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.     

Perceptual errors and negligence

Radiologic errors continue to be made at a rate that has changed little over the past 50 years, despite a variety of methods that have been proposed to reduce such errors. Many of these methods, as well as other steps that can be taken to decrease errors, are described elsewhere [6, 31, 32]. However, the question of whether a missed radiographic diagnosis constitutes malpractice has confounded radiologists, patients, referring physicians, attorneys, jurors, and judges for decades, and it is not likely that the question will be resolved to the satisfaction of any of these parties in the foreseeable future. Against this backdrop, radiologists continue to be subjected to malpractice litigation more for missing radiographic diagnoses than for any other reason. Moreover, radiologists who are sued for missing diagnoses are likely to have more indemnification paid on their behalf to satisfy a settlement or adverse jury verdict than for any other malpractice allegation. Assuredly, it is difficult to defend a radiologist who has failed to perceive a radiographic abnormality that in retrospect can be readily perceived by medical and nonmedical observers alike. Nonetheless, solid defense-supporting data are available that, at times, can be presented to a jury successfully to achieve vindication for a defendant radiologist. These data include statistics regarding the frequency of errors committed by radiologists and other physicians during the course of ordinary everyday practice, the factors that cause varying conspicuity of radiographic densities, the limitations of normal human visual perception, and evidence that the process by which the radiologist originally rendered the interpretation was free of deficiency.     

Apoptosis after traumatic human spinal cord injury

OBJECT: Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. METHODS: The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. CONCLUSIONS: These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.     

A probabilistic method for leak-before-break analysis of CANDU reactor pressure tubes

In modern CANDU nuclear generating stations, pressure tubes of cold-worked Zr-2.5Nb material are used in the reactor core to contain the fuel bundles and the heavy water (D₂O) coolant. The pressure tubes operate at an internal pressure of 10 MPa and temperatures ranging from 250°C at the inlet to 310°C at the outlet. Over the expected 30 year lifetime of these tubes, they would be subjected to a total fluence of 3×10²⁶ n m⁻². In addition, these tubes gradually pick up deuterium as a result of a slow corrosion process. When the hydrogen plus deuterium concentration in the tubes exceeds the hydrogen/deuterium solvus, the tubes are susceptible to a crack initiation and propagation process called delayed hydride cracking (DHC). If undetected, such a cracking mechanism could lead to unstable rupture of the pressure tube. The service life of the pressure tubes is determined, in part, by changes in the probability for the rupture of a tube. This probability is made up of the probability for crack initiation by DHC multiplied by the sum of the probabilities of break-before-leak and leak-before-break (LBB). A probabilistic model, BLOOM, is described which makes it possible to estimate the cumulative probabilities of break-before-leak and LBB. The probability of break-before-leak depends on the crack length at first leak detection and the critical crack length. The probability of a LBB depends on the shut-down scenario used. The probabilistic approach is described in relation to an example of a possible shut-down scenario. Key physical input parameters into this analysis are pressure tube mechanical properties, such as the crack length at first coolant leakage, the DHC velocity and the critical crack length. Since none of these parameters are known precisely, either because they depend on material properties, which vary within and between pressure tubes, and/or because of measurement errors, they are given in terms of their means and standard deviations at the different temperatures and pressures defined by the shut-down scenario.     

Pre- and postoperative nutritional care in liver transplantation in children

Orthotopic liver transplantation (OLT) is now a definitive treatment option for most cases of endstage liver disease (ESLD) in children. Efforts now focus on active supportive treatment to maintain, if not improve, the patient's clinical status before OLT and to ensure normal patterns of growth and development after OLT. Malnutrition adversely affects the outcome of OLT and is probably the single area in pre-operative management where the largest potential improvement can be made. Our studies indicate significant abnormalities of protein energy metabolism and body composition in children referred for OLT. We have shown that the use of enteral formulae, enriched with branched-chain amino acids, have significant advantages. Other adjunctive therapy, such as growth hormone, is the subject of current investigation. Following transplantation, catch-up weight and growth does occur with the advent of normal liver function, but patients at continuing risk for undernutrition, such as those with rejection and/or chronic infection, need to be targeted for specific nutritional therapy.     

Identification of potential ferric binding residues in the iron-binding protein of pathogenic Neisseria meningitidis through structure-based multiple sequence alignments

Toxic effects of hyperglycemia-induced advanced glycosylated end products (AGEs) may explain some vasculopathic complications of diabetes. Aminoguanidine, a known inhibitor of AGE formation, was administered by gavage to Sprague-Dawley streptozotocin-induced diabetic rats made azotemic by surgical reduction of renal mass. All rats became hyperglycemic. Renal ablation caused renal insufficiency, as evidenced by markedly reduced endogenous creatinine clearances at days 7 and 14. Aminoguanidine-treated rats had significantly (P < 0.04) superior survival to that of untreated azotemic diabetic rats. We infer from the extended life in a rat model of uremia in diabetic nephropathy that aminoguanidine may prove beneficial in human diabetes.     

Age-related differences in the temporal and spatial regulation of matrix metalloproteinases (MMPs) in normal skin and acute cutaneous wounds of healthy humans

Despite the association of increasing age with chronic wound-healing disorders and an impaired rate of healing of acute cutaneous wounds, the role of matrix metalloproteinases (MMPs) is unknown. To determine the spatial and temporal patterns and activities of MMP-1, -2, -3 and -9, 132 healthy humans aged between 19 and 96 years underwent 4-mm punch biopsies followed by wound excision between day 1 and day 180 post-wounding. Wounds showed an age-related increase in MMP-2 and MMP-9 immunostaining from day 3; this was associated with degradation of gelatin as shown by zymograms and with increased proteinase activity as shown by azocoll assays. Distinct spatial localisations for each MMP were observed: MMP-2 was found in epidermal structures; MMP-9 was observed in inflammatory cells up to day 21; MMP-1 was localised to keratinocytes at the wound margin. Normal old skin showed pro-MMP-2 bands on zymography and increased MMP-2 immunostaining. These results indicate that: (1) intrinsic ageing is associated with the up-regulation of MMPs previously associated with chronic wound healing; (2) wound-tissue proteinases are essentially active up to day 21 postwounding; and (3) intrinsic ageing may predispose to tissue breakdown disorders because of MMP-2 up-regulation in normal skin.