The concept of hepatorenal syndrome is well recognized, although incompletely understood. The converse clinical problem of hepatic dysfunction in patients with acute kidney injury (AKI) is less well recognized yet may be a contributor to the high patient morbidity and mortality seen in this group. This review draws together the available evidence for AKI's effect on the liver from animal models, pharmacological studies and recent clinical data. It examines liver function beyond clinically used blood tests, to determine the effect of AKI on hepatic synthetic function, acute phase response and drug metabolism. Parallels are drawn with other organ crosstalk in AKI and with liver-kidney interactions in chronic kidney disease. Definition of the pathophysiology of renohepatic crosstalk may lead to improved management strategies for this vulnerable patient group.
A novel point mutation in the ND6 subunit of complex I at position 14,459 of the mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for the highly tissue-specific disease. Leber's hereditary optic neuropathy plus dystonia. Since the MTND6*LDYT14459A mutation was identified in a single family, other pedigrees with the mutation are needed to confirm its association with the disease. Clinical, biochemical, and genetic characterization is reported in two additional pedigrees. Leber's hereditary optic neuropathy developed in two family members in one pedigree. The daughter had clinically silent basal ganglia lesions. In a second pedigree, a single individual presented with childhood-onset generalized dystonia and bilateral basal ganglia lesions. Patient groups that included individuals with Leigh's disease, dystonia plus complex neurodegeneration, and Leber's hereditary optic neuropathy did not harbor the MTND6*LDYT14459A mutation, suggesting that this mutation displays a high degree of tissue specificity, thus producing a narrow phenotypic range. These results confirm the association of the MTND6*LDYT14459A mutation with Leber's hereditary optic neuropathy and/or dystonia. As the first genetic abnormality that has been identified to cause generalized dystonia, this mutation suggests that nuclear DNA or mitochondrial DNA mutations in oxidative phosphorylation genes are important considerations in the pathogenesis of dystonia.
Background: Three-dimensional computed tomographic (CT) evaluation of the cervical vertebral column enables more accurate identification of osseous and soft tissue lesions than traditional latero-lateral radiography. However, examination of the complete cervical vertebral column has been limited by horse size, preventing evaluation of the caudal cervical vertebrae. Objectives: To describe a technique to enable CT myelography of the complete cervical spine and describe the findings in 51 horses. Animals: Records of 51 horses presented for evaluation of cervical vertebral lesions. Methods: A retrospective review of clinical records from all horses presented for CT myelography to further investigate possible cervical vertebral lesions was performed. A description of a novel approach to CT myelography in horses and retrospective review of the findings in clinical cases has been included. Results: Degenerative joint disease was identified at 1 or more dorsal articular process joint in 50/51 horses, of which 44/51 had a site of grade 2 or greater. Spinal cord compression was observed on CT myelography in 31/51 horses, whereas attenuation of the dorsal contrast column was identified radiographically in 11/50 horses. Thirty-three horses showed narrowing or obliteration of the intervertebral foramina at 1 or more site and osteochondral fragments were seen in 11/51 horses. Conclusions and Clinical Importance: Computed tomography myelography is relatively safe and an easily performed technique with the correct equipment, enabling evaluation of the cervical vertebral structures of horses in all planes and volumetrically. It is possible that lesion extent might be underestimated with this diagnostic modality, hence interpretation should be complimented with flexed and extended views radiographically.
Summary A yearling Thoroughbred colt was presented for investigation of neck stiffness and episodes of intermittent neck pain without neurological signs. Osteochondrosis (OCD) of the cervical articular process joints (APJs) was diagnosed with the aid of radiography and computed tomography. An articular osteochondral fragment of the left fourth caudal cervical articular process was removed arthroscopically following a cut down approach to the joint capsule of the affected APJ. Surgical removal resulted in resolution of clinical signs at 4 weeks. However, subsequently the horse was markedly ataxic 6 weeks post surgery after being found cast in its stable. Cervical stenotic myelopathy was considered the most likely cause based on clinical and radiographic signs and the horse was subjected to euthanasia due to a poor prognosis for racing. Post‐mortem examination identified atypical cartilage within several cervical APJs with histological changes consistent with OCD. This case report supports OCD of the APJs as a cause of neck pain and confirms the clinical practicality and short‐term effectiveness of arthroscopic fragment removal. Surgical treatment for cervical OCD should be considered in horses without neurological signs, although case selection is important and the underlying pathology remains a risk factor for the development of subsequent neurological signs.
Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.