Clinical and histologic outcome in a dog surviving massive hepatic necrosis.
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ABSTRACT:
SUBMITTER: Kook PH
PROVIDER: S-EPMC6430912 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background & aimsClinical manifestation of hepatic involvement in sarcoidosis can vary from asymptomatic disease to severe complications such as cirrhosis and portal hypertension. However, data on hepatic sarcoidosis are limited, and evidence-based recommendations are lacking. Our study aimed to assess the features and clinical course of hepatic sarcoidosis in a predominantly Caucasian cohort.MethodsWe performed a retrospective study including all patients with hepatic sarcoidosis between 2004 and 2020 in 5 German centres. The median follow-up time was 36 months (range 0.0-195). Data on demographic parameters, clinical manifestations, diagnostic test results, treatment, and outcome were collected.ResultsA total of 1,476 patients with sarcoidosis and 62 patients with hepatic involvement (4.2%) were identified. Of the patients, 51.6% were female, and 80.6% were Caucasian. Most patients were asymptomatic and were observed to have a cholestatic pattern of liver enzyme elevations. Cirrhosis was detected in 9 patients (14.5%), of whom 6 developed clinical manifestations of portal hypertension. Fifty-four patients were medically treated, most commonly with glucocorticoids (69.4%) or ursodeoxycholic acid (UDCA) (40.3%). Levels of alkaline phosphatase (ALP) decreased by 60.8% on average from baseline in patients treated with glucocorticoids and by 59.9% in patients treated with UDCA. Seventeen patients received treatment augmentation with a second line agent, of whom 8 patients normalised ALP levels during follow-up. None of the patients underwent liver transplantation or developed hepatocellular carcinoma (HCC). Three of the patients died during follow-up owing to liver-related complications.ConclusionsHepatic involvement in sarcoidosis was found in 4.2% of patients with sarcoidosis and was clinically significant in 14.5% of those. These findings highlight the importance of early identifying, monitoring, and treating hepatic sarcoidosis, given its increased mortality when associated with end-stage liver disease.Lay summaryClinical diagnostic and surveillance of hepatic involvement in sarcoidosis has not been standardised, and management of hepatic involvement is a clinical challenge, since it remains poorly characterised in many ways. Our results show that one-third of patients with hepatic sarcoidosis presented with clinically significant portal hypertension, 14.5% suffered from cirrhosis, and 3 patients died owing to liver-related complications. Regarding pharmacological treatment options, corticosteroids and UDCA were the medical agents most frequently used, and both of them have been shown to induce biochemical response in the majority of patients. These findings highlight the importance of correctly and early identifying hepatic involvement in sarcoidosis, because of the potentially progressive course of disease.
| S-EPMC8571721 | biostudies-literature
Project description:To date, no published reports (human or animal) have examined the impact of acute liver failure on global gene expression profiles in remote organ systems like the kidney. In this study, we have characterized a model of acute kidney injury (AKI) using two highly-accurate techniques for assessing renal function in a mouse. In this model, mice developed massive hepatocyte necrosis, disordered hepatosplanchnic hemodynamics, and alterations consistent with ALF. Simultaneously, acute renal insufficiency developed, manifesting as oliguria, azotemia, and decreased glomerular filtration. In this paper, renal function is corroborated using two independent methodologies. These techniques are used in addition to hemodynamic, biochemical, and histologic analyses to demonstrate that acute hepatic injury promulgates renal dysfunction in a mouse. Similar to network-based analyses conducted in other models of human disease, we present a comprehensive, genome-wide assessment of the differentially-regulated, renal transcriptome in the setting of massive hepatic necrosis. Using this approach, mice receiving the select hepatotoxin D-(+)-Galactosamine HCl (GalN) were found to have significant perturbations in renal pathways related to lipid metabolism, small molecule biochemistry, the cell cycle, molecular transport, and amino acid metabolism, despite normal renal histology. By combining data obtained from clinical, physiologic, and molecular investigations, our findings have direct implications for exploring potential pharmacological approaches to the prevention of AKI in this setting.
2012-01-01 | GSE24971 | GEO
Project description:To date, no published reports (human or animal) have examined the impact of acute liver failure on global gene expression profiles in remote organ systems like the kidney. In this study, we have characterized a model of acute kidney injury (AKI) using two highly-accurate techniques for assessing renal function in a mouse. In this model, mice developed massive hepatocyte necrosis, disordered hepatosplanchnic hemodynamics, and alterations consistent with ALF. Simultaneously, acute renal insufficiency developed, manifesting as oliguria, azotemia, and decreased glomerular filtration. In this paper, renal function is corroborated using two independent methodologies. These techniques are used in addition to hemodynamic, biochemical, and histologic analyses to demonstrate that acute hepatic injury promulgates renal dysfunction in a mouse. Similar to network-based analyses conducted in other models of human disease, we present a comprehensive, genome-wide assessment of the differentially-regulated, renal transcriptome in the setting of massive hepatic necrosis. Using this approach, mice receiving the select hepatotoxin D-(+)-Galactosamine HCl (GalN) were found to have significant perturbations in renal pathways related to lipid metabolism, small molecule biochemistry, the cell cycle, molecular transport, and amino acid metabolism, despite normal renal histology. By combining data obtained from clinical, physiologic, and molecular investigations, our findings have direct implications for exploring potential pharmacological approaches to the prevention of AKI in this setting. Male C57BL6 mice weighing 20 grams were given i.p. injections of the select hepatotoxin D-(+)-Galactosamine HCl (GalN). Animals were divided into 3 groups (n =3 per group): 1) Saline control injection (necropsy at 24 hours), 2) 4.5 g / kg GalN injection (necropsy at 24 hours), and 3) 4.5 g / kg i.p. injection (necropsy at 48 hours). At necropsy, liver and kidney were harvested after in situ perfusion with 10 ml of ribonuclease (RNAse)-free PBS and 10 ml of RNA Later reagent (Qiagen, Valencia, CA). Total cellular RNA was isolated from morcellated whole kidneys and liver using a commercial kit (RNA Easy, Qiagen). To extract RNA, 30 mg of tissue was processed according to the manufacturer’s instructions. RNA integrity was monitored using an Agilent Bioanalyzer (Agilent Technologies, Palo Alto, CA). One microgram of denatured RNA was used for cDNA synthesis, with reverse transcription carried out using random hexamer primers (Invitrogen, Carlsbad, CA). For quantitative real-time PCR (RT-PCR), 100 ng of cDNA template, 20 μL of SYBR green master mix and pre-optimized and validated mouse primer sets (Qiagen, Valencia, CA) were used and analyzed in an ABI Prism 7000 Thermocycler or a Roche LightCycler. Relative expression of gene targets was determined by the ΔΔCt method first normalizing to expression of the housekeeping gene, GAPDH, and then to expression in the sham treated control. Expression of RPLP0 was included in the analysis to verify the “housekeeping” status of GAPDH. Efficiencies for each primer pair were determined using the REST program and verified to be comparable to efficiencies for housekeeping gene primer pairs Equal amounts of total RNA from the three individual mice for each treatment condition were prepared for Affymetrix array hybridization according to the Affymetrix GeneChip Expression Analysis Technical Manual (www.affymetrix.com). A total of 18 array measurements were made (sham, 24 hr., and 48 hr. for each animal, liver and kidney, respectively). These correspond to the various CEL files and are labeled 1-18. All samples were hybridized to the GeneChip Mouse Genome 430 2.0 Array (Affymetrix, Santa Clara, CA) and preprocessed using R packages affy and gcRMA from the Bioconducter project. Greater than 45,000 transcripts and variants on the mouse genome 430 2.0 gene chip array were analyzed. Probe sets significantly perturbed after GalN administration were identified using rank product analysis. False discovery rate was used to control for multiple comparisons using the method of Benjamini and Hochberg. Adjusted p-values <0.05 were considered significant.
2012-01-01 | E-GEOD-24971 | biostudies-arrayexpress
Project description:Renal interstitial cell tumors are benign tumors of renomedullary origin; however, malignant features have not been reported in dogs, to our knowledge. A 17-y-old spayed female Maltese dog was presented to a local animal hospital with a mass in the right abdomen. Clinicopathologic findings prior to surgery revealed renal insufficiency and anemia. Imaging revealed that the right kidney was enlarged by an amorphous mass with opaque areas, indicative of mineralization. Upon histologic examination, the mass was comprised of malignant mesenchymal cells that produced mucinous matrix. The tumor cells were positive for vimentin and COX-2, but negative for pancytokeratin; the matrix stained positively with alcian blue. Therefore, the mass was diagnosed as a renal interstitial cell tumor, with malignant features. COX-2 may be useful in the diagnosis of canine renal interstitial cell tumors, similar to its diagnostic role in humans.
| S-EPMC7003225 | biostudies-literature
Project description:Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass (P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases (P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.
| S-EPMC10722206 | biostudies-literature
Project description:OBJECTIVE: This study investigated the prevalence and nature of physical and neurocognitive sequelae in pediatric intensive care unit (PICU) survivors. DESIGN AND SETTING: Prospective follow-up study 3 months after discharge from a 14-bed tertiary PICU in The Netherlands. PATIENTS AND PARTICIPANTS: The families of 250 previously healthy children unexpectedly admitted to the PICU were invited to visit the outpatient follow-up clinic for structured medical examination of the child 3 months after discharge; 186 patients were evaluated. MEASUREMENTS AND RESULTS: Pediatric Cerebral Performance Category (PCPC) and Pediatric Overall Performance Category (POPC) values were determined at PICU discharge, at the outpatient follow-up clinic, and retrospectively before admission to the PICU. We found that 69% of children had physical sequelae. In 30% of cases these were caused by a previously unknown illness and in 39% by acquired morbidity. In 8% of the children the acquired morbidity was related to complications from PICU procedures. Three months after discharge 77% of the children had normal PCPC scores and 31% had normal POPC scores. CONCLUSIONS: Our results indicate that PICU survival may be associated with substantial physical sequelae. Structured follow-up research, preferably by multicenter studies, is warranted in PICU survivors.
| S-EPMC2480486 | biostudies-other
Project description:ObjectiveTo describe options for vitreoretinal surgery in the management of massive suprachoroidal hemorrhage (SCH).MethodsVisual acuity (VA), ocular findings, timing of surgical intervention, surgical procedures, and outcomes of four patients diagnosed with massive SCH and admitted to the University Eye Clinic Essen were reviewed retrospectively.ResultsFour eyes of four patients (mean age, 82 years; range, 74-89 years) were studied. In three cases the occurrence of SCH was related to cataract surgery and occurred intra- or postoperatively. One patient developed spontaneous SCH of unclear origin. Three patients had a history of arterial hypertension; one eye had high myopia, two patients suffered from cardiovascular diseases, and two patients had glaucoma. Postoperative follow up of the patients ranged from 5 to 29.5 months (mean, 19.6 months). Transscleral drainage of SCH was in all cases combined with pars plana vitrectomy, use of heavy liquids (perfluorodecalin) and silicone oil tamponade. The mean time interval from hemorrhage to surgical intervention was 16.5 days (range 5-29 days). Preoperative VA of all eyes was light perception. Two patients achieved a final postoperative visual acuity of 20/20 and 20/320, respectively, one patient improved to hand motion, and one patient resulted in no light perception.ConclusionsSurgical interventions including transscleral drainage of SCH, vitrectomy, and silicone oil tamponade are valuable options in the management of massive SCH to save the eye and possibly improve the otherwise extreme poor prognosis.
| S-EPMC5015633 | biostudies-literature
Project description:Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus that produces an acute, lethal infection in rainbow trout (Oncorhynchus mykiss). Fish that survive infection cease to produce detectable infectious virus at approximately 46 days after infection, yet there is evidence that survivor fish continue to harbor virus particles (B. S. Drolet, P. P. Chiou, J. Heidel, and J. C. Leong, J. Virol. 69:2140-2147, 1995). In an effort to determine the biological function of these particles, the kidneys and livers from IHNV survivors were harvested and divided into samples for nested reverse transcriptase PCR analysis and explant culture. Sequences for the IHNV nucleoprotein and polymerase genes were detected in 50 and 89%, respectively, of the organs from survivor fish. When explant tissue cultures were infected with purified standard IHNV, the liver tissues from survivor fish produced up to 10-fold less virus than naive control fish liver tissues. In addition, immunosorbent electron microscopy analysis of the supernatant media from the cultured explants of survivor fish revealed truncated particles, whereas the control tissue supernatants contained only standard viral particles. These results suggest that the truncated IHNV particles observed in persistently infected fish are defective interfering particles that may mediate virus persistence.
| S-EPMC103901 | biostudies-literature
Project description:Massive tears in the rotator cuff are debilitating pathologies normally associated with loss of function and pain. Tendon reconstruction is seen as the standard treatment in order to preserve shoulder function and to inhibit cuff associated osteoarthritis. However, the effect on longer-term shoulder function and patient satisfaction is unknown.165 consecutive patients with massive tears were included. 57 debridement (mean age 61.9±8.7 years (range 43-77)) and 108 reconstruction (mean age 57.5±8.9 years (range 45-74)) cases could be followed up 2-4 (short-term), 5-6 (mid-term) and 8-10 (long-term) years after surgery. Evaluation was performed with the Constant, a modified ASES and the DASH score. Statistical analysis was done using Sigma-Stat Version 3.5 with a p-value<0.05 indicating statistical significant differences.All three scoring systems showed no significant differences in the short-term follow-up for the two groups (mean values: Constant debridement/repair: 70±11.9/66±13.6; ASES debridement/repair: 22.3±3.3/ 23.3±3.3; DASH debridement/repair: 22.3±11.0/ 24.3±10.1). In the mid-term (Constant debridement/repair: 51±2.9/68.3±5.2; ASES debridement/repair: 20.3±1.3/24.3±1.7; DASH debridement/repair: 31.0±6.5/20.3±5.4) and long-term follow-up (Constant debridement/repair: 42.3±3.8 /60.7±2.6, ASES debridement/repair: 17.3±0.5/21.7±0.5, DASH debridement/repair: 41.3±6.2/25.0±1.4), rotator cuff reconstruction revealed better objective results and better patients' satisfaction.Rotator cuff tendon repair leads to better long-term clinical outcome and subjective satisfaction compared to debridement. Tendon reconstruction should be considered as a treatment for patients suffering from massive rotator cuff tears, thus preserving shoulder function and by that means delay indication for reverse arthroplasty.
| S-EPMC5543680 | biostudies-other
Project description:The novel coronavirus SARS-CoV-2 (coronavirus disease 19, or COVID-19) primarily causes pulmonary injury, but has been implicated to cause hepatic injury, both by serum markers and histologic evaluation. The histologic pattern of injury has not been completely described. Studies quantifying viral load in the liver are lacking. Here we report the clinical and histologic findings related to the liver in 40 patients who died of complications of COVID-19. A subset of liver tissue blocks were subjected to polymerase chain reaction (PCR) for viral ribonucleic acid (RNA). Peak levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated; median ALT peak 68 U/l (normal up to 46 U/l) and median AST peak 102 U/l (normal up to 37 U/l). Macrovesicular steatosis was the most common finding, involving 30 patients (75%). Mild lobular necroinflammation and portal inflammation were present in 20 cases each (50%). Vascular pathology, including sinusoidal microthrombi, was infrequent, seen in six cases (15%). PCR of liver tissue was positive in 11 of 20 patients tested (55%). In conclusion, we found patients dying of COVID-19 had biochemical evidence of hepatitis (of variable severity) and demonstrated histologic findings of macrovesicular steatosis and mild acute hepatitis (lobular necroinflammation) and mild portal inflammation. We also identified viral RNA in a sizeable subset of liver tissue samples.
| S-EPMC7424245 | biostudies-literature