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Appendicitis is a common condition in childhood and adolescence that frequently requires urgent surgical intervention. For almost two centuries appendicitis has been recognized as a medical problem with a surgical solution. Currently the appendix can be removed with a minimally invasive approach, low anesthetic and surgical risk, and swift hospital discharge. Despite these advances, surgery and anesthesia have associated risks including postoperative infection, bleeding, hernia and organ injury among others. In addition, surgery requires time off of school and work to recover and associated healthcare costs can be significant. In both adult and pediatric populations, quality data suggesting a nonoperative approach is suggesting a change to the traditional surgical paradigm. Adults studies have demonstrated both safety and efficacy in the nonoperative management of acute appendicitis. In selected children with uncomplicated appendicitis, initial nonoperative management has been shown to be safe with fewer complications, fewer disability days and less healthcare costs while avoiding the risks inherent to surgery. Ongoing randomized controlled clinical trials in both the United States and Europe seek to further demonstrate the safety of nonoperative management and assist physicians with educating patients about the risk profile of their treatment decision. In complicated appendicitis presenting with abscess or acute appendiceal phlegmon, an initial nonoperative strategy with or without abscess drainage followed by interval appendectomy is the current state of the art though the utility of interval appendectomy is questioned., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tgh-20-191). The series “Current Topics in Pediatric General Surgery” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Gastroenterology and Hepatology. All rights reserved.)

Enhanced recovery after surgery (ERAS) is a systematic approach to optimize a patient's health and improve clinical outcomes, increase patient satisfaction and decrease healthcare costs. Enhanced recovery protocols have been used across a variety of surgical disciplines and patient groups to improve patient safety and reduce hospital length of stay without increasing return visits to the system. ERAS involves the application of clinical decision making throughout the patient experience with interventions in the preoperative, perioperative and post operative phases. In addition, ERAS is multidisciplinary and the success of an ERAS program is dependent on the effort and integration of stakeholders across the healthcare system. Utilization of ERAS systems have grown across the global adult surgical community over the last three decades and adoption in pediatric surgery has only occurred recently. Hospitals in both adult and pediatric surgery have found that implementation of ERAS systems lead to a shortened length of stay and reduced complications without increasing patient returns to the system. Importantly patients who have surgery within an ERAS program experience less pain, less opioid utilization, a quicker recovery and increased satisfaction. In pediatric surgery ERAS has successfully been employed across most all disciplines from congenital cardiac surgery to colorectal surgery. The evolution of ERAS continues as a paradigm of quality and safety., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tgh-20-188). The series “Current Topics in Pediatric General Surgery” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Gastroenterology and Hepatology. All rights reserved.)

The rationale for in utero hematopoietic cell transplantation (IUHCT) rests on exploitation of normal events during hematopoietic and immunologic ontogeny to allow allogeneic hematopoietic engraftment without myeloablative conditioning.  Host hematopoietic competition is among the primary barriers to engraftment in IUHCT. In the murine model this can be partially overcome by delivery of larger donor cell doses, but volume is limiting. Enrichment of donor hematopoietic stem cells (HSCs) would seem to offer a more efficient approach, but such enriched populations have engrafted poorly in existing models of IUHCT. To increase HSC dose while maintaining the presence of accessory cells, we used a less stringent enrichment protocol of single-step lineage depleted cells alone (lin-) or in combination with whole donor bone marrow mononuclear cells. Our results confirm that increasing doses of HSCs in combination with bone marrow accessory cells can dramatically improve engraftment after IUHCT. This represents a practical and clinically applicable strategy to maximize the engraftment potential of the donor graft without risk of treatment-associated toxicity., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

In utero hematopoietic cell transplantation (IUHCT) offers the potential to achieve allogeneic engraftment and associated donor-specific tolerance without the need for toxic conditioning, as we have previously demonstrated in the murine and canine models. This strategy holds great promise in the treatment of many hematopoietic disorders, including the hemoglobinopathies. Graft-versus-host disease (GVHD) represents the greatest theoretical risk of IUHCT and has never been characterized in the context of IUHCT. We recently described a preclinical canine model of IUHCT, allowing further study of the technique and its complications. We aimed to establish a threshold T cell dose for IUHCT-induced GVHD in the haploidentical canine model and to define the GVHD phenotype. Using a range of T cell concentrations within the donor inoculum, we were able to characterize the phenotype of IUHCT-induced GVHD and establish a clear threshold for its induction between 3% and 5% graft CD3 + cell content. Given the complete absence of GVHD at CD3 doses of 1% to 3% and the excellent engraftment with the lowest dose, there is a safe therapeutic index for a clinical trial of IUHCT., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Minimally invasive surgery (MIS) in the management of blunt and penetrating pediatric trauma has evolved in the past 30 years. Laparoscopy and thoracoscopy possess high levels of diagnostic accuracy with low associated missed injury rates. Currently available data advocate limiting the use of MIS to blunt or penetrating injuries in the hemodynamically stable child. In the pediatric trauma population, MIS offers both diagnostic and therapeutic potential, as well as reduced postoperative pain, a decreased rate of postoperative complications, shortened hospital stay, and potentially reduced cost., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pediatric thoracic trauma is relatively uncommon but results in disproportionately high levels of morbidity and mortality when compared with other traumatic injuries. These injuries are often more devastating due to differences in children׳s anatomy and physiology relative to adult patients. A high index of suspicion is of utmost importance at the time of presentation because many significant thoracic injuries will have no external signs of injury. With proper recognition and management of these injuries, there is an associated improved long-term outcome. This article reviews the current literature and discusses the initial evaluation, current management practices, and future directions in pediatric thoracic trauma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Pulmonary hypoplasia and hypertension is a leading cause of morbidity and mortality in congenital diaphragmatic hernia (CDH). The etiologic insult occurs early in gestation highlighting the potential of prenatal interventions. We evaluated prenatal pharmacologic therapies in the nitrofen CDH model., Methods: Olive oil or nitrofen were administered alone or with dexamethasone (DM), sildenafil, or DM+sildenafil to pregnant rats. Newborn pups were assessed for lung function, structure and pulmonary artery (PA) flow and resistance., Results: Prenatal DM treatment of CDH pups increased alveolar volume density (Vva), decreased interalveloar septal thickness, increased tidal volumes and improved ventilation without improving oxygenation or PA resistance. Sildenafil decreased PA resistance and improved oxygenation without improving ventilation or resulting in significant histologic changes. DM+sildenafil decreased PA resistance, improved oxygenation and ventilation while increasing Vva and decreasing interalveolar septal and pulmonary arteriole medial wall thickness. Lung and body weights were decreased in pups treated with DM and/or sildenafil., Conclusion: Prenatal DM or sildenafil treatment increased pulmonary compliance and decreased pulmonary vascular resistance respectively, and was associated with improved neonatal gas exchange but had a detrimental effect on lung and fetal growth. This study highlights the potential of individual and combined prenatal pharmacologic therapies for CDH management.

Objective: The objective of the study is to describe our initial 100 attempted infant thoracoscopic lobectomies for asymptomatic, prenatally diagnosed lung lesions, and compare the results to contemporaneous age-matched patients undergoing open lobectomy., Background: Infant thoracoscopic lobectomy is a technically challenging procedure, which has only gained acceptance worldwide in recent years., Methods: This is a retrospective review of all patients undergoing thoracoscopic or open lung lobectomy between March 2005 and January 2014. Included were all asymptomatic infants younger than 4months. Excluded were patients undergoing emergent lobectomy and patients with isolated extralobar bronchopulmonary sequestrations., Results: A total of 100 attempted thoracoscopic lobectomies were compared with 188 open lobectomies. In the thoracoscopic group, mean age and weight at surgery were 7.3weeks and 4.8kg, mean operative time was 185minutes, and mean hospital stay was 3days. Twelve cases were converted to open (12%). Ten conversions occurred within the first third of the series and none in the last third. There were no mortalities. There were no differences between the thoracoscopic and open groups in perioperative complications or hospital stay. There was a significant difference in the operative time: 111minutes vs. 185minutes (open vs. thoracoscopic; p<0.001). There was a higher mean end-tidal carbon dioxide (ETCO2) and lower mean peripheral capillary oxygen saturation (SpO2) in the thoracoscopic group versus the open group (51.7 versus 38.6mmHg and 97.5 versus 99.1%, respectively)., Conclusion: In high volume centers, the learning curve of thoracoscopic lobectomy can be overcome and the procedure can be performed with equivalent outcomes and, in our opinion, superior cosmetic results to open lobectomy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate surgical treatments and outcomes in a multi-institutional cohort of neonates with Hirschsprung's disease (HD)., Methods: Using the Pediatric Health Information System (PHIS) from 1999 to 2009, neonates diagnosed with HD were identified and classified as having a single stage pull-through (SSPT) or multi-stage pull-through (MSPT). Diagnosis and classification algorithms and clinical variables and outcomes were validated by multi-institutional chart review. Groups were compared using logistic regression modeling and propensity-score matched analysis to account for baseline differences between groups., Results: 1555 neonates with HD were identified; 77.2% underwent SSPT and 22.8% underwent MSPT. Misclassification of disease or surgical treatment was <2%. Rates of SSPT increased over time (p=0.03). Compared to SSPT, patients undergoing MSPT had significantly lower birth weights and higher rates of prematurity, non-HD gastrointestinal anomalies, enterocolitis, and preoperative mechanical ventilation. Patients undergoing MSPT had significantly higher rates of readmissions (58.5 vs. 37.9%) and additional operations (38.7 vs. 26%). Results were consistent in the propensity-score matched analysis., Conclusion: Most neonates with HD undergo SSPT. In patients with similar observed baseline characteristics, MSPT was associated with worse outcomes suggesting that some infants currently selected to undergo MSPT may have better outcomes with SSPT. However, there remains a subgroup of MSPT patients who were too ill to be adequately compared to SSPT patients; for this subgroup of severely ill infants with HD, MSPT may be the best option., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Evidence supporting the efficacy of in utero hematopoietic cell transplantation (IUHCT) in a valid large animal model is needed prior to clinical application. The objective of this study was to establish clinically relevant levels of hematopoietic chimerism in a canine model of maternal-to-fetal IUHCT. We first assessed immune and hematopoietic ontogeny relevant to IUHCT in the canine model and identified 40 days' gestation (term 63 days) as a time point at the initiation of thymic selection, and prior to bone marrow hematopoiesis, that might be optimal for IUHCT. We next determined that intravascular administration of donor cells via intracardiac injection was far more efficient and resulted in much higher levels of donor cell engraftment than intraperitoneal injection. By applying these findings, we achieved stable long-term multilineage engraftment in 21 of 24 surviving recipients with an average level of initial chimerism of 11.7% (range 3% to 39%) without conditioning or evidence of graft-versus-host disease. Donor cell chimerism remained stable for up to 2 years and was associated with donor-specific tolerance for renal transplantation. The levels of donor cell chimerism achieved in this study would be therapeutic for many hematopoietic disorders and are supportive of a clinical trial of IUHCT., (© 2014 by The American Society of Hematology.)

Acute intravascular hemolysis during extracorporeal membrane oxygenation (ECMO) leads to increased levels of cell-free hemoglobin (FHb). Our aim was to investigate whether FHb levels are associated with nitric oxide (NO) consumption and clinical outcomes. A prospective observational study was performed involving pediatric patients on ECMO. Blood samples were collected before, during, and after the ECMO run, and plasma was evaluated for FHb, oxyhemoglobin, and NO consumption. Clinical data were collected including baseline patient characteristics, indications for ECMO, circuit changes, and mortality. Correlations between laboratory measures and associations between laboratory measures and clinical observations were evaluated. Twenty-three patients (11 male, 17 neonates) were enrolled with a median weight of 3.1 kg (interquartile range, 2.8-14.0 kg) and median ECMO run of 12 days (interquartile range, 5-19 day). There was a significant increase in FHb over time on ECMO (p = .007), and significant correlations were present between NO consumption and both FHb (r = .41, p = .01) and oxyhemoglobin levels (r = .98, p < .0001). Patients on ECMO for sepsis (n = 6) had lower average levels of oxyhemoglobin (mean [standard deviation {SD}] 14.5 [4.4] versus 19.0 [5.0] μM, p = .07) and NO consumption (mean [SD] 15.8 [4.1] versus 19.8 [3.7] μM, p = .04) during ECMO than patients with other indications. In the 3 days leading up to a circuit change, there were increases in mean total cell-free hemoglobin levels (24%/day, p = .08), oxyhemoglobin (37%/day, p = .005), and NO consumption (40%/day, p = .006) (n = 5). There were no significant associations identified between peak or average plasma measures of hemolysis and type of ECMO (venovenous versus venoarterial) or mortality. For children on ECMO, we observed a strong correlation between increased levels of plasma FHb and elevations in oxyhemoglobin and NO consumption; however, these changes were not associated with increased mortality. Increased hemolysis before circuit changes may be both a marker and a contributor to circuit failure.

Background: Transanal hemorrhoidal dearterialization (THD) is a recently developed procedure to minimize postoperative pain from hemorrhoidectomy. This technique utilizes Doppler signals to aid ligation of hemorrhoidal arteries followed by mucopexy of redundant mucosa if needed. The aim of the present study was to assess patient satisfaction after THD., Methods: This is a retrospective cohort study of patients who underwent THD at three different sites from April 2007 through October 2010. All procedures were performed in ambulatory settings according to protocol. Telephone surveys were conducted after a minimum of 1-month follow-up to assess patients' satisfaction on a scale of 1-10. Patients were asked whether the procedure had alleviated their symptoms. Patients were asked to recall duration of pain and time from surgery to return to work., Results: Between April 2007 and October 2010, 216 patients with grade III-IV hemorrhoids underwent THD. There were 165 males and 61 females. Average age was 52.2 ± 14.2 years. All patients were discharged the same day after meeting ambulatory surgery center discharge criteria. Postoperative difficulty urinating occurred in 37 (17 %) patients, and six of them required temporary urinary catheterization. Transitory postoperative bleeding was reported by 38 (18 %) patients. Transitory incontinence to stool and flatus occurred in 18 (9 %) and 16 patients (8 %), respectively. Pelvic muscle spasms occurred in 21 (10 %) patients. Median follow-up was 23 months (range 1-42 months) with 143 (66 %) having at least 9 months between procedure and interview. Mean patient satisfaction was 8.5 ± 0.7 (on a scale of 1-10 with 10 being the best), and 91.5 % of patients felt the procedure had "helped" them. Average number of days with discomfort was 6.7 ± 2.1. Patients returned to work after an average of 10.3 ± 3.2 days. Our study is limited by lack of long-term follow-up and by retrospective complication assessment., Conclusions: Patient satisfaction with THD performed in ambulatory settings is high. Our data support performance of this procedure in an ambulatory setting.

The prenatal diagnosis and management of congenital disease has made significant progress over the previous decade. Currently, fetal therapy (including open surgery and fetoscopic intervention) provides therapeutic options for a range of congenital anomalies; however, it is restricted to the treatment of fetal pathophysiology. Improvements in prenatal screening and the early diagnosis of genetic disease allow for preemptive treatment of anticipated postnatal disease by stem cell or genetic therapy. While currently awaiting clinical application, in utero stem cell therapy has made significant advances in overcoming the engraftment and immunologic barriers in both murine and pre-clinical large animal models. Likewise, proof in principle for fetal gene therapy has been demonstrated in rodent and large animal systems as a method to prevent the onset of inherited genetic disease; however, safety and ethical risks still need to be addressed prior to human application. In this review, we examine the current status and future direction of stem cell and genetic therapy for the fetus., (Copyright © 2013. Published by Elsevier Inc.)

Background: After acute necrotizing pancreatitis (ANP), a pancreatic fistula may occur from disconnected pancreatic duct syndrome (DPDS) where a segment of the pancreas is no longer in continuity with the main pancreatic duct., Aim: To study the outcome of patients treated using Roux-Y pancreatic fistula tract-jejunostomy for DPDS after ANP., Methods: Between 2002 and 2011, patients treated for DPDS in the setting of endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopanreatography (MRCP) documented main pancreatic duct disruption with Roux-Y pancreatic fistula tract-jejunostomy., Results: In all, seven patients with DPDS were treated. The median age was 62 years (range 49-78) and five were men. The cause of ANP was gallstones (2), alcohol (1), ERCP (1) and idiopathic (3). Pancreatic necrosectomy was done in six patients. Time from onset of pancreatitis to fistula drainage was 270 days (164-365). Pancreatic fistulae arose from DPDS in the head/neck (4) and body/tail (3). Patients had a median fistula output of 140 ml (100-200) per day before surgery. The median operative time was 142 min (75-367) and estimated blood loss was 150 ml (25 to 500). Patients began an oral diet on post-operative day 4 (3-6) and were hospitalized for a median of 7 days (5-12). The median follow-up was 264 days (29-740). Subsequently, one patient required a distal pancreatectomy. After surgery, three patients required oral hypoglycaemics. No patient developed pancreatic exocrine insufficiency., Conclusion: Internal surgical drainage using Roux-en-Y pancreatic fistula tract-jejunostomy is a safe and definitive treatment for patients with DPDS., (© 2011 International Hepato-Pancreato-Biliary Association.)

Purpose: Strictures of the esophagus in children may have multiple etiologies including congenital, inflammatory, infectious, caustic ingestion, and gastroesophageal reflux (peptic stricture [PS]). Current literature lacks good data documenting long-term outcomes in children. This makes it difficult to counsel some patients about realistic treatment expectations. The objective of this study is to evaluate our institutional experience and define the natural history and treatment outcomes., Methods: A retrospective review of clinical data obtained from children who underwent dilation for PS was performed., Results: Over the past 30 years, 114 children and adolescents received 486 dilations. The most common indications for stricture dilation were PS (42%) and esophageal atresia (38%). Other lesser indications included congenital, foreign body, corrosive, cancer, radiation, allergic, and infectious. This review focuses on the 48 children with PS. Of the children with PS, a congenital anomaly was identified in 23 children; and 12 had neurologic impairment. Average age at presentation was 10.2 years (range, 0.5-18.3 years). Most patients had had symptoms for many months before diagnosis. Peptic stricture was most common in the lower esophagus (n = 39). However, middle (n = 8) and upper (n = 1) strictures were occasionally identified. Noncompliance with medical therapy was a challenge in 12% (n = 5) of children. Children with a PS received a median of 3 dilations, but a subset of 5 patients with severe strictures underwent up to 48 dilations (range, 1-48). Repeated dilations were required for a median of 20 months (range, 1-242 months). Among patients receiving esophageal dilation for PS, 94% required an antireflux procedure (19% required a second antireflux surgery). A subgroup of patients (n = 10) was identified who required extended dilations, multiple surgeries, and esophageal resection. This subgroup had a significantly longer period of symptomatic disease and increased risk of esophageal resection compared with those patients requiring fewer dilations. Surgical resection of the esophageal stricture was ultimately required in 3 children with PS after failure of more conservative measures., Conclusion: Children and adolescents presenting with reflux esophageal stricture (PS) frequently require antireflux surgery, redo antireflux surgery, and multiple dilations for recurrent symptoms. We hope that these data will be of use to the clinician attempting to counsel patients and parents about treatment expectations in this challenging patient population., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: Abdominal compartment syndrome (ACS) in children is an infrequently reported, rapidly progressive, and often lethal condition underappreciated in the pediatric population. This underrecognition can result in a critical delay in diagnosis causing increased morbidity and mortality. This study examines the clinical course of patients treated for ACS at our institution., Methods: A review of children requiring an emergency laparotomy (n = 264) identified 26 patients with a diagnosis of ACS. ACS was defined as sustained intraabdominal hypertension (bladder pressure >12 mm Hg) that was associated with new onset organ dysfunction or failure., Results: Patients ranged in age from 3 months to 17 years old and were cared for in the pediatric intensive care unit (PICU). Twenty-seven percent (n = 7) were transferred from referring hospitals, 50% (n = 13) were admitted directly from the emergency department, and 23% (n = 6) were inpatients before being transferred to PICU. Admission diagnoses included infectious enterocolitis (n = 12), postsurgical procedure (n = 10), and others (n = 4). Patients progressed to ACS rapidly, with most requiring decompressive laparotomy within 8 hours of PICU admission (range, <1-96 hours). Preoperatively, all patients had maximum ventilatory support and oliguria, 85% (n = 22) required vasopressors/inotropes, and 31% (n = 8) required hemodialysis. Mean bladder pressure was 25 mm Hg (range, 12-44 mm Hg). In 42% (n = 11), cardiac arrest preceeded decompressive laparotomy. All patients showed evidence of tissue ischemia before decompressive laparotomy with an average preoperative lactate of 8 (range, 1.2-20). Decompressive laparotomy was done at the bedside in the PICU in 13 patients and in the operating room in 14 patients. Abdominal wounds were managed with open vacuum pack or silastic silo dressings. Physiologic data including fluid resuscitation, oxygen index, mean airway pressure, vasopressor score, and urine output were recorded at 6-hour intervals beginning 12 hours before decompressive laparotomy and extending 12 hours after operation. The data demonstrate improvement of all physiologic parameters after decompressive laparotomy except for urine output, which continued to be minimal 12 hours post intervention. Mortality was 58% (n = 15) overall. The only significant factor related to increased mortality was bladder pressure (P = .046; odds ratio, 1.258). Cardiac arrest before decompressive laparotomy, need for hemodialysis, and transfer from referring hospital also trended toward increased mortality but did not reach significance., Conclusion: Abdominal compartment syndrome in children carries a high mortality and may be a consequence of common childhood diseases such as enterocolitis. The diagnosis of ACS and the potential need for emergent decompressive laparotomy may be infrequently discussed in the pediatric literature. Increased awareness of ACS may promote earlier diagnosis, treatment, and possibly improve outcomes., (Copyright 2010 Elsevier Inc. All rights reserved.)

Introduction: Compression of the celiac artery by the diaphragmatic crura, the median arcuate ligament, or the fibrous periaortic ganglionic tissue results in a rare constellation of symptoms known as celiac artery compression syndrome (CACS)., Anatomy: First described in 1963 by Harjola in a patient with symptoms of mesenteric ischemia, it remains an elusive diagnosis., Clinical Presentation: Patients commonly present with a wide variety of symptoms resulting in multiple diagnostic tests., Diagnosis: A firm diagnosis is difficult to establish, and treatment is equally challenging. These challenges are illustrated by the following case series, and evidence supporting current treatment modalities is reviewed., Treatment: We describe a laparoscopic approach to decompression of the celiac artery facilitated by intraoperative ultrasound.

Programmed cell death (apoptosis) signaling pathways have been implicated in seizure-induced neuronal death and the pathogenesis of human temporal lobe epilepsy (TLE). End-stage DNA fragmentation during cell death may be mediated by nucleases including caspase-activated DNase (CAD), apoptosis-inducing factor (AIF) and endonuclease G. In the present study, we investigated the subcellular localization of these nucleases in resected hippocampus from TLE patients and autopsy controls. Subcellular fractionation determined levels of CAD were significantly higher in the nuclear fraction of TLE samples compared with controls, and semiquantitative immunohistochemistry revealed cleaved caspase-3 positive cells in TLE sections but not controls. While mitochondrial levels of AIF and endonuclease G were higher in TLE samples than controls, nuclear localization of AIF was limited and restricted to cells that were negative for cleaved caspase-3. Nuclear accumulation of endonuclease G was not found in TLE samples. These data support ongoing caspase-dependent apoptosis signaling in human TLE and suggest that interventions targeting such pathways may have potential as adjunctive neuroprotective therapy in epilepsy.

The medical records of eight horses with histological evidence of myodegeneration of the masseter muscles were examined. While they were alive their most common clinical signs had included difficulty in eating or opening their mouths, weight loss, difficulty in moving, and noticeable atrophy of the masseter muscles. The serum activities of muscle enzymes were abnormally high in all of the horses. Whole blood and/or liver selenium and vitamin E concentrations were less than the reference ranges in some of the horses. The lesions varied with the stage of the disease and consisted of swelling and discoloration, or muscle atrophy and fibrosis. Histologically, the muscle changes ranged from acute to subacute degeneration, with regenerative changes accompanying ongoing degeneration, to chronic degeneration with fibrotic replacement of muscle tissue. There were changes in the masseter muscle of all the horses, but some had widespread lesions in skeletal muscle, and a few also had myocardial lesions.

The objective of this study was to compare effects of dietary polyunsaturated fatty acid supplementation (corn oil or fish oil) on selected immune responses in normal horses. Two groups of horses (n = 5) were randomly assigned a dietary supplement with either 3.0% corn oil or fish oil for a period of 14 weeks. Plasma fatty acid profiles were monitored to ensure uptake of dietary fatty acids. Cell-mediated immunity was assessed by a delayed-type hypersensitivity (DTH) skin test to keyhole limpet hemocyanin (KLH), and humoral immunity was assessed by measuring antibody titers to KLH. Production of prostaglandin E2 (PGE2), expression of tumor necrosis factor-alpha (TNF-alpha), and phagocytosis of latex beads by bronchoalveolar lavage fluid (BALF) cells were also assessed. Lipopolysaccharide (LPS)-stimulated BALF cells from horses fed corn oil showed a higher production of PGE2 compared with those from horses fed fish oil at 6 and 12 weeks. Production of TNF-alpha by LPS-stimulated BALF cells was higher in both groups of horses at 6, 8, and 12 weeks compared with pretrial values, and phagocytic activity of BALF cells was higher at 8 and 12 weeks, however, there were no differences between the 2 groups of horses. The DTH skin test and antibody titers to KLH revealed no differences between horses fed corn or fish oil. Based on these studies, dietary polyunsaturated fatty acids modulate the inflammatory response of horses. Both fatty acid supplements increased production of the proinflammatory cytokine TNF-alpha, whereas only corn oil increased production of the proinflammatory eicosanoid PGE2 by LPS-stimulated BALF cells. It is possible that fish oil, because it did not increase production of PGE2, could have value in the treatment of equine recurrent airway obstruction or other equine inflammatory diseases.

Objective: To evaluate the potential of excess dietary iron to cause hepatic lesions similar to those described in horses with suspected iron toxicosis or hemochromatosis., Design: Prospective study., Animals: 6 adult male ponies., Procedure: 4 ponies received 50 mg of iron/kg (22.7 mg/lb) of body weight each day by oral administration of ferrous sulfate, which contained 20% elemental iron; 2 ponies received only the carrier (applesauce). Complete blood counts, serum biochemical analyses, and hepatic tissue biopsies were performed, and serum iron concentrations were measured. Blood and tissue samples were obtained at days 0 and 2, and at the end of weeks 1, 3, 6, and 8 after administration of iron was initiated. Treatment was discontinued after 8 weeks, and hepatic iron concentrations were measured at 28 weeks., Results: Hepatic iron concentrations, serum iron concentrations, percentage saturation of transferrin, and serum ferritin concentrations were increased, compared with baseline and control concentrations, by week 8. Adverse clinical signs or histologic lesions in the liver were not detected in any ponies. At 28 weeks, hepatic iron concentrations had decreased., Conclusions and Clinical Relevance: Histologic lesions were not seen in the hepatic biopsy specimens obtained from the ponies treated with ferrous sulfate. It was concluded that it would be unlikely for iron toxicosis to develop in adult ponies or horses during a period of < 8 weeks when food or water contained increased amounts of iron. It is suspected that previous reports of hepatopathies in animals with hemosiderin accumulation may represent a primary hepatopathy with secondary hemosiderin accumulation, especially if the only source of iron is via oral consumption.

Objective: To determine clinical, clinicopathologic, and postmortem abnormalities in New World camelids with pancreatic necrosis., Design: Retrospective study., Animals: 10 llamas and 1 alpaca., Procedures: Medical records of animals in which a diagnosis of pancreatic necrosis had been made on the basis of histologic examination of necropsy specimens or on the basis of clinical signs and results of clinicopathologic testing were reviewed., Results: The initial owner complaint varied, and various other conditions were diagnosed. Clinical and clinicopathologic abnormalities were vague. Amylase activity was higher in abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or were euthanatized. Only 1 of the animals that died had marked inflammation of the pancreatic parenchyma. All 7 had necrosis and saponification of fat in and surrounding the pancreas., Conclusions and Clinical Relevance: Results suggest that pancreatic necrosis may develop in New World camelids, but clinical signs are vague, and the condition may easily be confused with other diseases. The only laboratory test that appeared to be helpful in the antemortem diagnosis of pancreatic necrosis was comparison of amylase and lipase activities in abdominal fluid and serum.

Fifty clinically healthy llamas, 0.5-13 years of age (22 intact males, 10 neutered males, 18 females), with no biochemical evidence of liver disease or hematologic abnormalities, were selected to establish serum bile acid reference intervals. Serum samples submitted to the clinical pathology laboratory were analyzed using a colorimetric enzymatic assay to establish bile acid reference intervals. A nonparametric distribution of llama bile acid concentrations was 1-23 micromol/liter for llamas >1 year of age and 10-44 micromol/liter for llamas < or = 1 year of age. A significant difference was found between these 2 age groups. No correlation was detected between gender and bile acid concentrations. The reference intervals were 1.1-22.9 micromol/liter for llamas >1 year of age and 1.8-49.8 micromol/liter for llamas < or = 1 year of age. Additionally, a separate group of 10 healthy adult llamas (5 males, 5 females, 5-11 years of age) without biochemical or hematologic abnormalities was selected to assess the effects of feeding and time intervals on serum bile acid concentrations. These 10 llamas were provided fresh water and hay ad libitum, and serum samples were obtained via an indwelling jugular catheter hourly for 11 hours. Llamas were then kept from food overnight (12 hours), and subsequent samples were taken prior to feeding (fasting baseline time, 23 hours after trial initiation) and postprandially at 0.5, 1, 2, 4, and 8 hours. In feeding trials, there was no consistent interaction between bile acid concentrations and time, feeding, or 12-hour fasting. Prior feeding or time of day did not result in serum bile acid concentrations outside the reference interval, but concentrations from individual llamas varied within this interval over time.

Objective: To compare the effects of a 30-week trial of cyclical etidronate therapy (starting within 6 weeks of spinal cord injury [SCI] and conventional rehabilitation without etidronate treatment on the bone density of the lumbar spine and lower extremities of SCI patients., Design: Prospective, randomized control trial., Setting: Tertiary care, inpatient rehabilitation center., Patients: Acute SCI, within 6 weeks of injury. Thirteen SCI subjects were recruited; 6 were assigned randomly to receive etidronate and 7 to receive conventional treatment., Intervention: Etidronate, 800 mg orally, once per day for 2 weeks of 15 weeks, repeated once., Main Outcome Measures: Dual X-ray absorptiometry of the spine, hip, distal femur, and proximal tibia measured at baseline, 6 months, and 12 months., Results: A significant interaction between etidronate treatment and ambulatory status over time was observed in the bone density of the patients after SCI (p = .0003). The patients who became ambulatory and received etidronate treatment had a preservation of bone density as compared to all other patients who showed a loss of bone density over time. The loss of bone density occurred in the leg bones, not the spine. Cyclical etidronate treatment was tolerated well without adverse or side effects., Conclusion: Cyclical etidronate is a feasible treatment and may prevent osteoporosis associated with SCI in patients who eventually walk.

Five healthy Equidae (4 horses and one pony) were given a single i.v. dose of ceftriaxone (50 mg/kg bwt) to determine the pharmacokinetics and concentration in cerebrospinal fluid (CSF). Blood was drawn from an i.v. jugular catheter and CSF from a pre-placed, intrathecal catheter. Serum and CSF concentrations were determined by high performance liquid chromatography. The mean serum concentration of ceftriaxone was 144.7 micrograms/ml 15 min after injection and declined to 0.3 microgram/ml 10 h after injection. The elimination rate constant (lambda 2) was 0.63 +/- s.e. 0.23/h, the elimination half-life (t 1/2) was 1.62 +/- s.e. 0.42 h and the apparent volume of distribution at steady state (Vd(ss)) was 330.8 +/- 11.8 ml/kg bwt. Clearance was 312.7 +/- 38 ml/h/kg bwt and mean residence time was 1.13 +/- 0.14 h. Mean CSF concentration was 0.60 +/- 0.14 microgram/ml at 3 h after injection and 0.4 +/- 0.31 microgram/ml at 8 h. Ceftriaxone may be useful in the treatment of bacterial infections in horses. Its ability to penetrate the CSF should make it effective in the treatment of bacterial meningitis.

A group of 6- to 8-month-old calves developed head tremors, stiff gait, and staggering after consuming ryegrass straw that contained 3,711 micrograms of lolitrem-B/ kg. Signs were consistent with ryegrass staggers syndrome. At necropsy, all calves examined had atypical interstitial pneumonia, with marked emphysema and bullae. Infectious organisms and pneumotoxins were not identified. Experimentally, feeding the same ryegrass straw to age-matched calves induced similar neurologic signs, but did not result in pneumonic lesions. The high concentration of lolitrem-B in the straw or other, undefined factors, such as feed changes, may have contributed to the atypical interstitial pneumonia in the naturally exposed calves.

Objective: To evaluate the efficacy of tests for hepatic disease in young calves., Design: Prospective case-control study., Animals: 28 clinically normal calves and 47 calves with histologically proven hepatic disease., Procedure: Liver function tests and serum activity of liver-derived enzymes were determined on 28 clinically normal calves at birth and at 2 weeks of age. These values were compared with the results from 47 calves with hepatic disease verified by histologic examination. Upper limit of confidence interval was determined for the results on the clinically normal calves, and Student's t-test was used to identify significant differences in the data from calves of various age-groups., Results: None of the results of the common tests for liver damage or function (measurement of bilirubin, gamma-glutamyltransferase, glutamate dehydrogenase [GMD], alkaline phosphatase, L-lactate dehydrogenase, aspartate transaminase, or alanine transaminase) were clinically useful when used alone for detection of hepatic disease in calves less than 6 weeks old. Sensitivity of gamma-glutamyltransferase, GMD, aspartate transaminase, and alkaline phosphatase as indicators of hepatic disease in this population of calves was 0, 59, 80, and 9%, respectively. Direct bilirubin (sensitivity, 87%) was more sensitive than total bilirubin (sensitivity, 66%). Serum enzyme activity of most enzymes (P < 0.01), total bilirubin concentration (P < 0.001), and sulfobromophthalein sodium clearance half-life were significantly higher (P < 0.001) in newborn calves than in 2-week-old calves., Clinical Implications: Clinical findings that indicate hepatic disease in calves that are less than 6 weeks old could be confirmed by measurement of serum activity of GMD or concentrations of total serum bile acids or direct bilirubin. Percutaneous liver biopsy may still be needed and may provide the most information.

Megaesophagus was diagnosed in 15 llamas on the basis of survey and contrast radiography. Age of onset ranged from 13 months to 9.5 years. Clinical signs varied, with salivation being the most common; regurgitation or dysphagia were noted in only 33% of the cases. Duration of the disorder ranged from 1 week to 5 years. Organophosphate toxicity was the cause of megaesophagus in 1 llama. While most cases were of unknown etiology, the 3 with histological abnormalities included 1 with vagal neuropathy and 2 with a degenerative myopathy of esophageal muscles. The causes in most were undetermined.

Electromyography of the esophageal musculature of a cow that had been regurgitating and losing weight after correction of an esophageal obstruction was suggestive of unilateral denervation. Radiography before and after oral administration of barium sulfate revealed a dilated terminal portion of the thoracic esophagus, suggestive of a focal motility problem. Electromyography was performed on the esophageal musculature by positioning the electrode through the rumen fistula and into the thoracic esophagus and by positioning the electrode percutaneously with the aid of a tube placed in the cervical esophagus. Numerous fibrillation potentials and sharp epsilon-positive waves were detected in the muscles of the left side of the distal portions of the cervical and thoracic esophagus. During hospitalization, the cow was given alfalfa pellets, ground corn, and sodium bicarbonate through the rumen fistula 3 times each day for several weeks to maintain body weight.

The diagnosis of third compartment ulcers in the llama and alpaca is largely one of exclusion. Clinical signs may include mild to severe colic, inappetence, decreased fecal output, bruxism, and depression. Abdominocentesis results are usually unremarkable if C3 perforation has not occurred but reflective of a generalized peritonitis if full thickness ulceration has occurred. The H-2 receptor antagonists cimetidine and ranitidine do not suppress C3 acid production for a significant period of time and are of questionable efficacy in the management of C3 ulcers.

The PCV of a llama increased from 50.8 to 74.0% during a 19-month period. The llama remained clinically normal unless stressed, when it would become dyspneic and tachypneic. Thoracic auscultation revealed sounds consistent with pneumonia, but were probably attributable to pulmonary congestion resulting from polycythemia. A diagnosis of secondary absolute polycythemia was made on the basis of high serum erythropoietin concentrations and no evidence of hypoxia. Necropsy revealed congestion of the lungs and liver. Cause of the polycythemia was not determined. Polycythemia should be considered as a differential diagnosis in a llama with exercise intolerance and harsh bronchovesicular sounds.

Hemochromatosis, an iron storage disease, was diagnosed in 3 horses with hepatic cirrhosis. Each horse had bridging portal fibrosis and abundant iron deposits in the cytoplasm of hepatocytes. Serum concentrations of liver-derived enzymes and total bile acids were high. However, serum iron concentration was not high, and iron binding capacity was only 46% saturated in the 1 horse in which it was measured. However, the concentration of iron in the liver of this horse was 20 times the reference limits. Hemochromatosis is common in mynah birds and human beings. There are several types of this iron storage disease. In human beings, there is a familial disease with iron absorption inappropriate for the level of stored iron. Hemochromatosis also occurs secondary to cirrhosis of the liver, and in certain anemia diseases. Another type of hemochromatosis is seen in association with dietary iron overload. These horses were not related, and there was not any evidence of high dietary iron intake.

Serum total bile acid concentrations were determined for various types and ages of cattle. There was extreme variability among all the cattle, but the variance was twice as large (0.50 vs 0.22 in logarithmic scale) for beef cattle than for dairy cattle. There was no significant difference in serum total bile acid concentrations between beef cattle and dairy cattle in midlactation. Values for calves < 6 weeks old and for 6-month-old heifers were significantly (P = < 0.05) lower than values for lactating dairy cows. The 5th to 95th percentile range of values (mumol/L) for beef cattle was 9 to 126; for lactating dairy cattle, 15 to 88; and for 6-month-old dairy heifers, 11 to 64.

Twelve nonlactating dairy cows, free of signs of liver disease and with normal serum activities of liver-derived enzymes and normal liver biopsy tissue, were examined over a 72-hour period for serum total bile acid concentrations. The cattle were fed hay twice daily, and blood samples were obtained every hour for 24 hours, every other hour for 24 hours, then every hour for 24 hours. After 3 weeks, the study was repeated on 6 of the cattle, thus providing data for eighteen 72-hour periods. Serum bile acid concentration varied greatly over the 72 hours, with the range being from one third to 3 times the median. There were variations by as much as 60 mumol/L from 1 hour to the next. After another 3 weeks, 8 of the cattle were deprived of hay for 48 hours and then fed hay morning and afternoon of the third (last) day of the study. There was no significant reduction in bile acid concentration after withholding the hay, but the variability was reduced (P = 0.02) during the last 20 hours of the hay-deprivation period. In 3 ancillary studies, serum bile acid concentrations were examined over a 48-hour period in 2 cows in early lactation, 3 cows in midlactation, and two 6-month-old heifers. The cows were fed hay and grain twice daily, and the heifers were fed only hay twice daily. In comparison with values for the 12 nonlactating cows fed hay twice daily, mean serum bile acid concentration in the recently freshened cows was significantly (P < 0.002) higher (62.9 vs 22.0 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive changes in serum enzyme activity and liver histologic features were monitored in calves fed tansy ragwort (Senecio jacobaea)-contaminated pellets. The experiments were designed to simulate natural intoxicant ingestion conditions in relationship to the dose and duration of exposure to the toxic plant to correlate early laboratory diagnostic changes with the natural progression of the disease, thereby facilitating early diagnosis and intervention by veterinary clinicians. Eight calves were fed tansy ragwort and 4 additional calves served as controls. In group 1, 4 calves were continuously fed dried tansy ragwort mixed in a pelleted feed at a 5% concentration by dry weight until terminal liver disease developed. Serum liver enzyme (alkaline phosphatase, glutamate dehydrogenase, and gamma-glutamyltransferase) activities were monitored at weekly intervals in these calves and in the 2 controls. In group 2, 4 calves were fed the same contaminated feed for only 60 days, with return to normal feed for the duration of the trial. Two additional calves served as controls. Their liver enzyme activities were monitored every other week in conjunction with percutaneous liver biopsies. All 8 calves fed tansy ragwort-contaminated pellets developed terminal hepatopathy in either a chronic pattern (n = 6) or a chronic-delayed pattern (n = 2), with the onset of a moribund state or sudden death at 11 to 17 weeks and 27 to 51 weeks, respectively. The calves were euthanatized when classic terminal signs of hepatic encephalopathy first became evident. The clinicopathologic patterns of chronic and chronic-delayed toxicoses were typical of over 5,000 cases of field tansy toxicosis diagnosed at the diagnostic laboratory. Serum glutamate dehydrogenase was the first enzyme to increase in most animals, with a short-term increase to peak values followed by a rapid return to normal. This enzyme change was followed by increases in alkaline phosphatase and gamma-glutamyltransferase. Serum enzyme changes preceded development of recognizable histologic lesions. Vacuolar changes in hepatocyte nuclei, biliary hyperplasia, and fibrosis sequentially developed in liver biopsy specimens from each animal, whereas megalocytosis was not a predominant feature until necropsy. On the basis of our findings, we suggest that the optimal tests for diagnosis of pyrrolizidine alkaloid intoxication should consist of liver biopsy and determination of concurrent serum liver-enzyme activities.

Of 41 equids referred to a veterinary teaching hospital in the Pacific northwest because of dyspnea and inspiratory noise, 3 ponies were diagnosed as having liver failure, most likely attributable to pyrrolizidine alkaloid toxicosis. Dyspnea appeared to be caused by laryngeal and/or pharyngeal paralysis. It is proposed that this paralysis was a manifestation of hepatic encephalopathy. Although these clinical signs are not common for pyrrolizidine toxicosis, practitioners should be aware of the possibility so that misdiagnosis of other causes of inspiratory dyspnea may not be made.

A syndrome characterized by anemia, erythrocyte dyscrasia, low body weight, and hypothyroidism was observed in 8 llamas (Lama glama). At initial examination (1 to 23 months of age; median, 7.5 months), llamas (3 males, 5 females) were markedly underweight (29 to 55 kg; median, 36 kg) and anemic (PCV, 12.9 to 25.5% [median, 19%]). Five of the llamas became progressively more anemic over time; in 2 of them, PCV decreased to less than 10%. Erythrocyte changes included severe poikilocytosis, anisocytosis, asymmetric distribution of hemoglobin within the cytoplasm, and cytoplasmic extensions from one or both poles. Six llamas had moderate to severe valgus deformities of the carpus. All llamas had low baseline serum thyroxine concentration and diminished response to thyrotropin administration. Baseline and post-thyrotropin triiodothyronine concentrations did not have consistent patterns. Five llamas were hypophosphatemic and 7 had low serum iron concentration (iron concentration was not determined in 1 llama). Orally administered iron supplementation did not induce clinical improvement. Because 3 of the affected llamas were full sisters, a genetic basis for the problem has to be considered. It was not possible to evaluate the familial relationship of the other 5 affected llamas. Although the underlying cause of the problem was not established, the prognosis for affected llamas is guarded to poor.

The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 hours. Clearance was 42.3 to 69.2 ml/hr/kg. The initial distribution phase was rapid (t1/2 approx 3.5 to 4 minutes); a 2nd distribution phase was slower (t1/2 approx 1.5 to 2 hours). Plasma concentrations of theophylline were in the assumed effective range (10 to 20 micrograms/ml) from 15 minutes until 40 minutes after time zero. The mean apparent volume of distribution was 1.02 L/kg. After bolus IV injection of dyphylline (20 mg/kg), pharmacokinetics were best described by a 2-compartment open model in 2 horses and by a 3-compartment open model in 4 horses. In the 6 horses, elimination half-life of dyphylline was 1.9 to 2.9 hours, and clearance was 200 to 320 ml/hr/kg. Plasma concentrations (approx 50 micrograms/ml) were observed at 10 minutes after injection without adverse effects. Concentrations greater than 10 micrograms/ml were observed from time zero to about 1.5 hours after injection. Theophylline induced significant increases in heart rate, but dyphylline did not affect heart rate significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized clinical trial of treatment of sole abscess in cattle was conducted to determine whether bandaging a foot after debridement of an abscess improved outcome. Sixty-six feet from 63 cows were randomly allocated to bandaged or unbandaged groups, and clinical recovery was graded by comparison of lameness at initial examination and at 2 follow-up examinations. There was no statistically significant difference between the groups at entry into the trial or at 1 month after treatment. Unbandaged feet were significantly less lame 1 week after treatment, and this difference was attributed to rapid healing of small lesions in feet of cows in stanchion and tie-stall barns. There was no group in which bandaging improved outcome.

Abomasal fluid was collected from adult cows using a specially designed tube device. The device was placed in the abomasum through a rumen fistula. A filter on the end of the tube filtered out the larger particles so the liquid could be aspirated up a smaller tube placed inside a larger one. The smaller tube reduced the amount of dead space created by the distance from the abomasum to the rumen fistula.

Fifteen clinical biochemical measurements were done on serum from 64 clinically healthy adult llamas (26 males and 38 females). Values for several of these tests were different from those reported for llamas and from reference values for other domesticated ruminants. Comparison of values between males and females revealed significant differences for several tests. Clinical biochemical values reported in the present study can serve as reference values for adult llamas.

The clinical signs of tansy ragwort poisoning are variable and in 5 cases included diarrhea, tenesmus, ascites, bloody feces, icterus, paresis, CNS involvement, rectal prolapse, poor appetite and weight loss. It is thus apparent that the disease can be confused clinically with many others, and tansy ragwort poisoning should be considered in animals exhibiting ascites, diarrhea and rectal prolapse. Several cases of tansy ragwort (Senecio jacobaea) poisoning occurring from 1969 to 1976 are reported to illustrate the numerous clinical pictures that might confront a practitioner. The disease is sporadic in this area. The poisonous principles in tansy ragwort are pyrrolizidine alkaloids, which cause gradual alteration and necrosis of liver cells with replacement by fibrous tissue. The development of signs in all of these cases could be attributed to failure of one or more liver functions.

A 4-day-old foal died with bloody diarrhea. Using a mouse neutralization test, Clostridium perfringens type C was isolated from intestinal contents, and alpha and beta toxins were identified. About 4 m of the jejunum had severe necrohemorrhagic enteritis. Microscopically, large, rod-shaped, gram-positive bacteria were seen on necrotic intestinal villi by use of Brown and Hopp's stains.

The lactations of 3,172 Holstein dairy cows were divided into intervals of 15 and 21 days. The numbers of new diagnosis of metritis, cystic ovary, miscellaneous reproductive disorders, mastitis, left displaced abomasum, and milk fever in each interval were counted. The numbers of cows at risk in each interval were also counted. A cow was at risk if she was still milking, in the herd, and a diagnosis had not already been made for that condition in that lactation. A cow was also only at risk of a reproductive diagnosis if she was not pregnant. For each interval, the incidence rate of new diagnosis was calculated by dividing the number of new diagnoses by the number of cows at risk.

Salt poisoning/water deprivation has been described under various circumstances in adult cattle. The signs and lesions in cattle are somewhat different from those in swine, which are frequently affected. This report describes several cases of salt poisoning in veal calves. The calves were fed milk replacer and were housed without access to water. Presenting signs were mostly referrable to dysfunction of the central nervous system and included hyperesthesia, opisthotonus, nystagmus, muscle twitching and intermittent convulsions. Although the serum sodium concentration in some of these calves was over 200 mEq/1, no remarkable brain lesions were noted at necropsy. The salt content of the milk replacer was 10 times the level recommended by the National Research Council. This salt may have come from the whey included in the formula. The syndrome produced in the veal calves was similar to that seen in infant children given only a nursing formula containing too much salt, and limited water.