Fatal donor-derived Kaposi sarcoma following liver transplantation.

Human herpesvirus-8 (HHV8) is a recognised precursor for a number of neoplastic and non-neoplastic processes. Immunosuppressed recipients of both solid organ and haematopoietic stem cell transplants are at risk of life-threatening lytic reactivations of HHV8-infected B-lymphocytes, primary infections after receiving grafts from HHV8-seropositive donors and more rarely by the direct transplantation of malignant Kaposi sarcoma cells seeded within graft tissue. We describe the case of an HHV8-seronegative patient with confirmed, post-orthotopic liver transplant transmission of HHV8 from a seropositive donor with quantitative evidence of viraemia and subsequent development of disseminated visceral and cutaneous Kaposi sarcoma with a rapidly fatal outcome.

Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement.

PURPOSE: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. METHODS AND MATERIALS: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. RESULTS: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse-free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse-free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. CONCLUSIONS: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

Comparison of allergic reactions to intravenous and intramuscular pegaspargase in children with acute lymphoblastic leukemia.

Pegaspargase (PEG) is a standard component of therapy for pediatric acute lymphoblastic leukemia (ALL). Because PEG preparations are bacterially derived, they are highly immunogenic. PEG has traditionally been delivered intramuscularly (IM), but over the last several years, more PEG has been given intravenously (IV) in order to provide a less painful and more convenient means of delivery. However, there are limited data comparing allergic reactions between IV and IM PEG recipients, especially in a large cohort of patients. We reviewed the charts of pediatric ALL patients diagnosed from 2006 to 2011 who received PEG at our institution and compared the incidence, time to onset of symptoms, reaction grade, and hospitalization rate for patients who had allergic reactions to PEG. Of 318 evaluable patients, 159 received IV and 159 received IM PEG. Thirty-one (19.5%) IV patients had an allergic reaction, compared to 17 (10.7%) IM patients (P = .028). Time to onset of symptoms was ≤ 30 minutes for 26 of 27 evaluable IV patients (96.3%) versus only two of 11 evaluable IM patients (18.2%; P < .001). Four of 31 IV patients (12.9%) and six of 17 IM patients (35.5%) required hospitalization (P = .134). There is increased incidence of allergy in patients who received IV PEG compared to IM. Grade of reaction was similar between IV and IM, but allergic reactions to IV PEG had a more rapid onset. While the risk of allergy may be increased, IV delivery appears to have an acceptable safety profile for administration in ALL patients.

Disordered vascular compliance in haemochromatosis.

BACKGROUND: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk. AIMS: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls. METHODS: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured. RESULTS: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 µmol/L, p = 0.011), retinol (1.17 vs. 1.81 µmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 µmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32). CONCLUSIONS: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.

Paracetamol overdose: the liver unit perspective.

Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres. Severe hepatic dysfunction often appears 72-96 h after overdose. Liver injury can be prevented by timely administration of the specific antidote, N-acetylcysteine. Unfortunately, administration of N-acetylcysteine is frequently delayed due to late presentation or late administration. While N-acetylcysteine works best if given within 8 h of overdose, it is beneficial at any time period and should always be given if there is concern about significant overdose, irrespective of interval from time of ingestion. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure.

Successful pregnancy after liver transplantation in progressive familial intrahepatic cholestasis, type 1.

A woman who had undergone liver transplantation for genetically documented ATP8B1 disease/progressive familial intrahepatic cholestasis, type 1, successfully conceived, carried, and was delivered of a healthy child. The pregnancy and its management are described; implications are discussed.

Concurrent avian malaria and avipox virus infection in translocated South Island saddlebacks (Philesturnus carunculatus carunculatus).

CASE HISTORY: Outbreaks of mortality in South Island saddlebacks (Philesturnus carunculatus carunculatus) that had been translocated to two offshore islands in the Marlborough Sounds of New Zealand were investigated during the summers of 2002 and 2007. Both outbreaks were associated with a severe decrease in numbers of saddlebacks of up to 60% of approximately 200 birds. CLINICAL AND PATHOLOGICAL FINDINGS: Many of the surviving birds were in poor condition, and had skin lesions on the legs and head. Necropsy showed pale liver and lungs, and a swollen spleen. Histopathology revealed schizonts resembling Plasmodium spp. within the cytoplasm of many hepatocytes and splenic histiocytes. The skin lesions consisted of epithelial proliferations containing numerous Bollinger bodies typical of avipox virus (APV) infection. Two different APV were isolated, using PCR, from two different birds exhibiting skin lesions. Each isolate had 100% sequence homology with APV members from either Clade A or Clade B. In addition, PCR analysis revealed that the Plasmodium elongatum present in infected birds belonged to a strain that was endemic in the population of North Island saddlebacks (Philesturnus carunculatus rufusater). DIAGNOSIS: Concurrent infections with Plasmodium spp. haemoparasites and APV were identified as the likely cause of death in the birds examined. CONCLUSIONS AND CLINICAL RELEVANCE: Although the Plasmodium spp. identified is thought to be endemic to saddlebacks in New Zealand, the affected birds were likely to be immunocompromised by concurrent APV infection or through lack of genetic diversity. Both the introduced mosquito Culex quinquefasicatus and the native mosquito Culex pervigilans are likely vectors for both these diseases, and the provision of water supplies less favourable to mosquito-breeding is recommended.

Current concepts in the assessment and treatment of hepatic encephalopathy.

Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain that may occur in acute or chronic liver disease. Standardized nomenclature has been proposed but a standardized approach to the treatment, particularly of persistent, episodic and recurrent encephalopathy associated with liver cirrhosis has not been proposed. This review focuses on the pathogenesis and treatment of HE in patients with cirrhosis. The pathogenesis and treatment of hepatic encephalopathy in fulminant hepatic failure is quite different and is reviewed elsewhere.

Adjuvant therapy used in conjunction with combination therapy for chronic hepatitis C improves sustained virus response rates in genotype 1 patients.

Combination treatment with pegylated interferon (Peg-IFN) and ribavirin remains the gold standard in the treatment of chronic hepatitis C. This therapy is limited by many side-effects including anaemia, neutropenia and reduced quality of life. The use of adjuvant agents to reduce the frequency of dose reductions because of haematological side-effects has been proven to be effective but there are few reports of what effect the use of these adjuvant therapies is having on sustained virological response (SVR). The aim of the study was to assess the clinical impact on sustained virological response of adjuvant therapies during combination therapy with Peg-IFN and ribavirin for chronic hepatitis C. A total of 132 patients, 96 males, were included in the study. The overall SVR was 66.7%, with 50% of genotype 1/4/6 (n = 27/54) patients achieving SVR and 78.2% of genotypes 2/3. The overall SVR of the treatment naïve patients (83/121) was 68.6%. Fifty-one of these patients were genotype 1 with 49.0% (25/51) of this group achieving SVR. The genotype 2/3 group of treatment naïve patients reached an SVR of 82.9% (58/70). Adjuvant therapy was used in 57 patients (43.8%). With the use of supportive adjuvant therapy, we achieved an overall SVR of 66.7% and in treatment naïve patients 68.6%. In genotype 1 patients, SVR rates of up to 46% have been reported in previous studies without the use of erythropoietin and granulocyte colony stimulating factor. We have demonstrated the SVR for genotype 1 can be improved to 50% overall.

A landmark contribution to poultry science--a bioassay for true metabolizable energy in feedingstuffs.

Research by Ian Sibbald resulted in the development of a practical method of measuring the TME content of feed ingredients. The method was expanded to include measuring the true digestibility of several nutrients, most importantly amino acids.

The role of corticosterone in supporting migratory lipogenesis in the dark-eyed Junco, Junco hyemalis: a model for central and peripheral regulation.

The functional role of corticosterone (CORT) in regulating migratory hyperphagia and lipogenesis was investigated in an annual migrant, the dark-eyed junco (Junco hyemalis). Intraperitoneal injections of either dexamethasone (9 microg DXM/500 microL of 5% EtOH in saline, n=10) to inhibit an increase in baseline CORT or saline (5% EtOH, n=9) were given every 48 h for 15 d after transfer from short (10.5L:13.5D) to long (15.5L:8.5D) days. Food intake, body mass, furcular fat deposition scores, and nocturnal migratory activity were recorded for 29 d after photostimulation. Both groups showed the same increase in daily food intake over the study period (DXM=52%, control=41%). Controls began to increase baseline CORT and mass about 2 wk after photostimulation. DXM-treated birds maintained low CORT and did not increase mass or CORT until injections ceased, at which time they gained mass at the same rate shown earlier by controls. DXM-treated birds did not show greater levels of migratory activity despite experiencing an increase in energy intake during the CORT-inhibited period. Collectively, the results support the migration modulation hypothesis, illustrating how an increase in baseline CORT is needed to support the development of migratory condition. We address the apparent conflict with earlier studies on CORT and migratory food intake and propose a model in which migratory hyperphagia is supported by changes in centrally regulated responses to CORT that can occur even if CORT remains low and lipogenesis is regulated predominantly by peripheral mechanisms that require an increase in baseline CORT.

Endocrine and behavioral response to a decline in habitat quality: effects of pond drying on the slider turtle, Trachemys scripta.

The effect of the simulated drying of a pond on the behavior and corticosterone secretion of Trachemys scripta was measured in a field situation. Slider turtles were held in experimental and control ponds (12 x 15 m) enclosed with a drift fence integrated with spring-triggered livetraps. The experimental pond water level was dropped 10 cm per day for 8 d, until water was completely drained. Slider turtles responded to the draining of the pond by the emigration of the majority (75%) of the experimental population. Emigrating turtles had significantly elevated corticosterone at Time 0 (blood sample within 10 min of handling=4.48 ng/mL+/-0.503SE) when compared with turtles captured in a control pond (Time 0=0.954 ng/mL+/-0.121SE), where conditions were held constant. Turtles emigrated during the final 72 hr of pond draining when ponds reached 30 cm depth and lower and water temperature was at least 30.8 degrees C or higher. Additionally, the effect of trapping using spring-activated livetraps was tested. Turtles held in livetraps (n=6) for 45-110 min showed a characteristic corticosterone response (Time 0=0.957 ng/mL+/-0.091SE; Time 30=2.85 ng/mL+/-0.131SE), indicating that this trapping technique alone does not stimulate corticosterone secretion. The findings of the study met our predictions that turtles would respond to the draining of the pond behaviorally by emigrating from the habitat concurrent with an elevated corticosterone concentration. This supports the view that corticosterone is involved in stress avoidance mechanisms that allow organisms to respond to environmental perturbations.

A novel method for preparing histology slides without a microtome.

A study was undertaken to determine if it might be possible to prepare tissue sections on slides without the use of paraffin embedding, microtome sectioning, or cryostat sectioning which involve equipment and training not always available to scholars or professionals wishing to examine tissue microscopically. After evaluating many different reagents, cutting instruments and solid supports, we developed a method involving application of super glue to a slide, adhering a section of tissue to it, cutting the tissue with a disposable microtome blade, staining the tissue and removing the superglue with a commercially available product. The sections are similar to those sectioned on a microtome, but do not at this time equal their quality. However, histoarchitecture is preserved and individual cell morphology is usually good. We conclude that this is a viable method for preparing histology sections without the use of a microtome or cryostat, something long thought impossible. We have dubbed the method 'RAMP' (Rapid Adhesive-Mediated Procedure).

Severe complication after administration of formalin for treatment of progressive ethmoidal hematoma in a horse.

Formalin was injected into an ethmoidal hematoma in an 18-year-old Arabian gelding. Abnormal neurologic signs were observed within minutes of the injection. The horse did not respond favorably to medical treatment of the neurologic signs and was euthanatized. Postmortem examination revealed erosion and necrosis of the ventral cribriform plate, which appeared to have allowed the injected formalin to reach the rostral portion of the frontal lobe of the brain. Endoscopy and radiography had been performed prior to euthanasia, but neither delineated the cribriform lesion. Before treating large progressive ethmoidal hematomas with formalin, it may be beneficial to perform computed tomography to assess the extent of damage caused by the lesion.

Laboratory detection of X-ray fringes with a grazing-incidence interferometer

Starting with Galileo's observations of the Solar System, improvements of an order of magnitude in either the sensitivity or resolution of astronomical instruments have always brought revolutionary discoveries. The X-ray band of the spectrum, where exotic objects can have extremely high surface brightness, is ideally suited for significant improvements in imaging, but progress has been impeded by a lack of optics of sufficiently high sensitivity and quality. Here we present an X-ray interferometer design that is practical for adaptation to astronomical observatories. Our prototype interferometer, having just under one millimetre of baseline, creates fringes at 1.25 keV with an angular resolution of 100 milliarcseconds. With a larger version in orbit it will be possible to resolve X-ray sources at 10(-7) arcseconds, three orders of magnitude better than the finest-resolution images ever achieved on the sky (in the radio part of the spectrum) and over one million times better than the current best X-ray images. With such resolutions, we can study the environments of pulsars, resolve and then model relativistic blast waves, image material falling into a black hole, watch the physical formation of astrophysical jets, and study the dynamos of stellar coronae.

Hypertrophic muscular dystrophy in a young dog.

Hypertrophic muscular dystrophy was diagnosed in a 10-month-old male Rat Terrier with hypersalivation, dysphagia, gait abnormalities, and generalized weakness. Serum creatine kinase activity was high, and electromyography revealed myotonic discharges. Histologic examination of a muscle biopsy specimen revealed muscle fiber degeneration, clusters of basophilic regenerating fibers, and endomysial fibrosis. Staining for dystrophin, a sarcolemmal protein, was decreased, compared with that in muscle specimens from clinically normal dogs. Treatment with mexiletene hydrochloride and procainamide hydrochloride resulted in temporary improvement in clinical signs, but the disease became refractory to treatment, and the dog was euthanatized. Clinical and histologic characteristics of this dystrophin deficiency-related muscular dystrophy were similar to those of X-linked muscular dystrophy in dogs, hypertrophic muscular dystrophy in cats, and Duchenne muscular dystrophy in humans.

Effects of exogenous corticosterone on locomotor activity in the red-eared slider turtle, Trachemys scripta elegans.

We investigated the effects of exogenous corticosterone on the locomotor activity of captive red-eared slider turtles, Trachemys scripta elegans. An increase in plasma corticosterone often increases locomotor activity in mammals and birds, but there are no reported findings for turtles. In this study turtles implanted with corticosterone-filled Silastic((R)) implants showed a significant increase in caged locomotor activity when compared to control animals with empty implants. Corticosterone-treated turtles also showed a significant increase in plasma corticosterone concentration when pre-trial plasma samples were compared to post-trial plasma samples, while control turtles exhibited no such increase, validating the effectiveness of our implants to deliver corticosterone. Although corticosterone remained high at the end of the activity trials, the increase in activity was ephemeral in nature, peaking within 48 hr after the implant was in place. This suggests that the effects of corticosterone on behavior may be context-dependent (i.e., whether the turtles can find food) and concentration-dependent, and that there are underlying physiological mechanisms, perhaps mediated at the receptor level in the brain, involved in locomotor activity behavior in slider turtles. Environmental perturbations that cause a reduction in available food resources may cause the organism to increase its level of locomotor activity to increase food encounter rate but later reduce activity to conserve energy reserves. These data are important when considering behavioral and physiological mechanisms involved in a turtle's response to changing conditions in habitat quality. J. Exp. Zool. 284:637-644, 1999.

Characterization of anatomic communications of the fetlock in cattle, using intra-articular latex injection and positive-contrast arthrography.

OBJECTIVE: To evaluate the frequency and sites of communication between the lateral and medial synovial sacs of the metatarsophalangeal or metacarpophalangeal joints in cattle. ANIMALS: 188 limbs were obtained from 55 fresh bovine cadavers submitted for necropsy because of problems unrelated to the fetlocks. PROCEDURE: In each ox, lateral or medial synovial sacs of each fetlock were randomly assigned. Joints were injected with a mixture of latex and barium sulfate. Communication between 2 joints was determined by presence of latex and contrast material in a joint adjacent to the injected joint by examining frozen sections and use of positive-contrast arthrography. RESULTS: Communication between the 2 synovial sacs existed in 186 of 188 (98.9%) specimens. The communication site between lateral and medial synovial sacs was located at the level of the proximal sesamoid bones, between the distal aspect of the interdigital band of the axial branch of the interosseus muscle and the metacarpal or metatarsal bone. CONCLUSIONS AND CLINICAL RELEVANCE: Although communication between the lateral and medial synovial sacs did not exist in 2 specimens, the fetlock in cattle can be treated as 1 compartment.

Characterization of anatomic communications among the antebrachiocarpal, middle carpal, and carpometacarpal joints in cattle, using intra-articular latex, positive-contrast arthrography, and fluoroscopy.

OBJECTIVE: To evaluate the frequency and sites of communication among the antebrachiocarpal, middle carpal, and carpometacarpal joints in cattle. ANIMALS: 137 limbs were obtained from 72 fresh bovine cadavers submitted for necropsy because of problems unrelated to the carpus. PROCEDURE: 1 of the 3 injection sites was randomly assigned to both carpi of each ox, and a mixture of latex and barium sulfate was injected into the joint. Communication between 2 or more joints was determined by the presence of latex and contrast material in a joint adjacent to the injected joint by examination of frozen sections, positive-contrast arthrography, and fluoroscopy. RESULTS: Communication existed among the 3 joints in 18 specimens (13.1%). The middle carpal joint and the carpometacarpal joint always communicated. The antebrachiocarpal joint communicated with the middle carpal joint between the ulnar and intermediate carpal bones. The middle carpal and carpometacarpal joints always communicated between the fourth and fused second and third carpal bones. In a few specimens, additional sites of communication were identified at the palmar aspect of the fourth carpal bone and the fused second and third carpal bones. CONCLUSIONS AND CLINICAL RELEVANCE: Individual anatomic variation of the carpus in cattle should be considered when diagnostic or treatment protocols are established.