Inheritance, mode of inheritance, and candidate genes for primary hyperparathyroidism in Keeshonden

BACKGROUND: Primary hyperparathyroidism (PHPT) is caused by inappropriate secretion of parathyroid hormone (PTH) by autonomously functioning neoplastic or hyperplastic parathyroid "chief" cells. Keeshonden are thought to be over-represented in studies on canine PHPT, but no proof of heritability or mode of inheritance has been published. The canine disease clinically resembles human familial isolated hyperparathyroidism (FIHP). HYPOTHESIS: Primary hyperparathyroidism in Keeshonden is genetically transmitted and is caused by a mutation in 1 of 4 genes implicated in human FIHP: MEN1, CASR, HRPT2, or RET. ANIMALS: Pedigrees consisting of 1647 Keeshonden were created including 219 Keeshonden with known PHPT phenotypes (69 positive). DNA samples were obtained from 176 of the 219 Keeshonden (34 positive). METHODS: Heritability and mode of inheritance were determined by segregation analysis. Canine homologs to the human genes were identified. Exons and surrounding intron regions were sequenced and scanned for sense-altering polymorphisms or polymorphisms that segregated with the disease. Messenger RNA from a parathyroid tumor of an affected Keeshond was analyzed for polymorphisms and splice alterations. RESULTS: PHPT follows an autosomal dominant mode of inheritance in Keeshonden with possible age-dependent penetrance. No polymorphisms identified in the genes analyzed were associated with a change in predicted protein or in hypothesized splice sites. CONCLUSIONS AND CLINICAL IMPORTANCE: PHPT is an autosomal dominant, genetically transmitted disease in Keeshonden. Once the mutation locus is identified, genetic testing should quickly decrease the incidence of PHPT in this breed. It is unlikely that mutations in MEN1, CASR, HRPT2, or RET cause PHPT in Keeshonden.     

Chloramphenicol 3. Clinical pharmacology of systemic use in the horse

The use of chloramphenicol in the horse is now prohibited as horses are classified as food-producing animals. However, chloramphenicol has until recently been widely available for oral, intramuscular or intravenous administration. A critical appraisal of the published literature on the use of chloramphenicol in the horse clearly demonstrates that there are sound pharmacokinetic and microbiological reasons for concluding that chloramphenicol is not an appropriate antibiotic for systemic use. The short half-life of chloramphenicol in the horse, together with the broad range of minimum inhibitory concentrations of target pathogens, preclude the use of practical dosage regimens. It can be concluded that the withdrawal of chloramphenicol will have no adverse effects on chemotherapy in the horse.     

A tsunami about 1000 years ago in puget sound, washington

Water surged from Puget Sound sometime between 1000 and 1100 years ago, overrunning tidal marshes and mantling them with centimeters of sand. One overrun site is 10 kilometers northwest of downtown Seattle; another is on Whidbey Island, some 30 kilometers farther north. Neither site has been widely mantled with sand at any other time in the past 2000 years. Deposition of the sand coincided-to the year or less-with abrupt, probably tectonic subsidence at the Seattle site and with landsliding into nearby Lake Washington. These findings show that a tsunami was generated in Puget Sound, and they tend to confirm that a large shallow earthquake occurred in the Seattle area about 1000 years ago.     

Search for Borrelia burgdorferi in kidneys of dogs with suspected "Lyme nephritis"

BACKGROUND: "Lyme nephritis" is a poorly characterized condition associated with proteinuria and often fatal renal failure in dogs with serological evidence of infection with Borrelia burgdorferi. OBJECTIVE: The aim of this study was to determine if intact B. burgdorferi organisms were present in the kidneys of serologically Lyme-positive dogs with histopathologic features of Lyme nephritis. ANIMALS: Twenty-six affected and 10 control dogs were identified over an 8-year period (1996-2004) in databases at Cornell University's College of Veterinary Medicine. Case inclusion required serologic evidence of natural exposure to B. burgdorferi and availability of renal tissue (frozen or paraffin embedded) exhibiting pathology consistent with Lyme nephritis. METHODS: Renal tissue samples were assessed using modified Steiner (silver) (MS) staining, immunohistochemistry (IHC), polymerase chain reaction (PCR) using 4 primer sets (eubacterial, B. burgdorferi, Bartonella, and canine genomic DNA), and fluorescence in situ hybridization (FISH) using a 5'-cy3-eubacterial probe for 16S rRNA. RESULTS: MS stain was positive in 1 case; IHC was negative in all cases. None of the B. burgdorferi or Bartonella PCR reactions was positive. Two of the B. burgdorferi FISH analyses were positive. CONCLUSIONS AND CLINICAL IMPORTANCE: Minimal evidence of the presence of intact B. burgdorferi or any other bacterial organism was found in the renal tissue of dogs with suspected Lyme nephritis. Direct renal invasion by B. burgdorferi organisms does not appear to be responsible for this syndrome.     

Transient uplift after a 17th-century earthquake along the Kuril subduction zone

In eastern Hokkaido, 60 to 80 kilometers above a subducting oceanic plate, tidal mudflats changed into freshwater forests during the first decades after a 17th-century tsunami. The mudflats gradually rose by a meter, as judged from fossil diatom assemblages. Both the tsunami and the ensuing uplift exceeded any in the region's 200 years of written history, and both resulted from a shallow plate-boundary earthquake of unusually large size along the Kuril subduction zone. This earthquake probably induced more creep farther down the plate boundary than did any of the region's historical events.     

Negative refraction at visible frequencies

Nanofabricated photonic materials offer opportunities for crafting the propagation and dispersion of light in matter. We demonstrate an experimental realization of a two-dimensional negative-index material in the blue-green region of the visible spectrum, substantiated by direct geometric visualization of negative refraction. Negative indices were achieved with the use of an ultrathin Au-Si3N4-Ag waveguide sustaining a surface plasmon polariton mode with antiparallel group and phase velocities. All-angle negative refraction was observed at the interface between this bimetal waveguide and a conventional Ag-Si3N4-Ag slot waveguide. The results may enable the development of practical negative-index optical designs in the visible regime.     

Hemoglobin Lepore trait: globin synthesis in bone marrow and peripheral blood

There was decreased synthesis of the beta-globin chain in the peripheral blood, and equal synthesis of alpha- and non-alpha-chains in the bone marrow of three patients with hemoglobin Lepore trait, similar to the findings in patients with heterozygous beta-thalassemia. There is a relative instability of the synthetic mechanism for normal beta-chain in these patients.     

Pharmacokinetics of carprofen and firocoxib for medication control in racing greyhounds

Animals used in sport should be treated as required to ensure animal welfare but any such use of medication should also be controlled to ensure integrity. Pharmacokinetic studies on groups of six greyhounds were performed to measure plasma and urine levels of carprofen and firocoxib to inform medication control advice. Using the standard methodology for medication control the Irrelevant Plasma Concentration was determined as 20 and 2 ng/mL for carprofen and firocoxib, respectively. The Irrelevant Urine Concentration was also determined as 0.3 and 2 ng/mL for carprofen and firocoxib, respectively. These Irrelevant Plasma and Urine Concentrations will allow laboratory Screening Limits, Detection Times and Withdrawal Time advice to be determined and publicised by regulators of greyhound racing. The Screening Limits will also inform Recommended Limits of Detection if meat-containing residues of these medications are fed to greyhounds.     

Antagonism of detomidine with tolazoline in isoflurane-anaesthetised ponies

The effects of tolazoline (4.0 mg/kg iv) antagonism of detomidine (0.02 mg/kg iv) were evaluated in isoflurane-anaesthetised, ventilated ponies. Each of 6 ponies received both tolazoline and saline treatment during separate anaesthetic episodes only (no surgery was performed). Detomidine administration produced an increase in blood pressure, decrease in heart rate and decrease in P_aO₂ Tolazoline treatment transiently increased heart rate while blood pressure returned to baseline after both treatments. Arterial oxygenation decreased further after tolazoline treatment while oxgenation recovered towards baseline with saline treatment. No other cardiopulmonary effects were detected. Recovery from anaesthesia tended to be more rapid when detomidine was antagonized. The potential benefit of antagonizing detomidine-induced bradycardia with tolazoline, during isoflurane anaesthesia should be weighed against the potential to produce a decrease in arterial oxygenation. The mechanism for this effect is not clear.