Budd-Chiari Syndrome-A Single Center Experience From the United Kingdom.

Pediatric Budd-Chiari syndrome (BCS) is a rare cause of portal hypertension and liver disease in Europe and North America. In order to understand the long-term effect of radiological intervention on BCS we performed a single center retrospective review. Fourteen cases were identified; 6 of 14 (43%) had a congenital thrombophilia with many having multiple prothrombotic mutations. Two were managed with medical anticoagulation alone and two required super-urgent transplant for acute liver failure. The remaining 10 of 14 (71%) underwent radiological intervention: 1 of 14 thrombolysis, 5 of 14 angioplasty, and 4 of 14 transjugular intrahepatic portosystemic shunt (TIPS). Six of 14 (43%) patients required repeat radiological intervention (1 angioplasty, 5 TIPS) but none required surgical shunts or liver transplantation for chronic liver disease. The time between diagnosis and treatment did not predict the need for repeat radiological intervention. These data show that radiological intervention can be highly effective, and reduces the need for surgery, though it requires specialist multidisciplinary teams for monitoring.

Validating loci associated with bovine respiratory disease complex in pre-weaned Holstein calves.

Bovine respiratory disease (BRD) is considered one of the most economically important diseases in the cattle industry. Ultimately, the selection of cattle that are less susceptible to disease will allow producers to reduce the prevalence of BRD and lessen its economic impact. The objective of this study was to validate previously identified loci associated with susceptibility to BRD in an independent population of 140 pre-weaned Holstein calves from Wisconsin (WI). Using the McGuirk health scoring system, calves were classified as either clinically affected with BRD (n = 35) or healthy (n = 105). Additive genotypic tests were performed for genomic regions previously associated with susceptibility to BRD in calves from California (CA) and New Mexico (NM). Using this method, 4 loci (P < 0.01) consisting of 10 SNP were validated in the WI population, including 2 loci from CA, 1 locus from NM, and 1 locus from a combined CA + NM population. Most of the positional candidate genes and transcription factor binding site motifs associated with these loci have functions related to innate and adaptive immune responses. The validation of loci associated with susceptibility to BRD in independent populations allows producers to more reliably select cattle that are less susceptible to BRD, improving animal welfare, decreasing the annual revenue losses, and lowering the prevalence of the disease.

Consensus recommendations on calf- and herd-level passive immunity in dairy calves in the United States.

Passive immunity in calves is evaluated or quantified by measuring serum or plasma IgG or serum total protein within the first 7 d of age. While these measurements inform about circulating concentrations of this important protein, they are also a proxy for evaluating all of the additional benefits of colostral ingestion. The current individual calf standard for categorizing dairy calves with successful passive transfer or failure of passive transfer of immunity are based on serum IgG concentrations of ≥10 and <10 g/L, respectively. This cutoff was based on higher mortality rates in calves with serum IgG <10 g/L. Mortality rates have decreased since 1991, but the percentage of calves with morbidity events has not changed over the same time period. Almost 90% of calves sampled in the USDA National Animal Health Monitoring System's Dairy 2014 study had successful passive immunity based on the dichotomous standard. Based on these observations, a group of calf experts were assembled to evaluate current data and determine if changes to the passive immunity standards were necessary to reduce morbidity and possibly mortality. In addition to the USDA National Animal Health Monitoring System's Dairy 2014 study, other peer-reviewed publications and personal experience were used to identify and evaluate potential standards. Four options were evaluated based on the observed statistical differences between categories. The proposed standard includes 4 serum IgG categories: excellent, good, fair, and poor with serum IgG levels of ≥25.0, 18.0-24.9, 10.0-17.9, and <10 g/L, respectively. At the herd level, we propose an achievable standard of >40, 30, 20, and <10% of calves in the excellent, good, fair, and poor categories, respectively. Because serum IgG concentrations are not practical for on-farm implementation, we provide corresponding serum total protein and %Brix values for use on farm. With one-third of heifer calves in 2014 already meeting the goal of ≥25 g/L serum IgG at 24 h of life, this achievable standard will require more refinement of colostrum management programs on many dairy farms. Implementation of the proposed standard should further reduce the risk of both mortality and morbidity in preweaned dairy calves, improving overall calf health and welfare.

Proposed dairy calf birth certificate data and death loss categorization scheme.

The majority of dairy heifer calves in the United States are destined to be dairy replacements. However, many dairy heifer and bull calves die before 6 mo of age. Of these calves, about 6% (more than 500,000 calves) die at birth or shortly after (i.e., currently termed "stillbirth"). An additional 6% of dairy heifers die during the preweaning period. Death loss in dairy calves is primarily due to stillbirths, failure to adapt to extrauterine life, and infectious disease processes. The reasons for preweaning heifer calf deaths caused by infectious diseases are generally categorized based on easily recognizable clinical signs such as digestive disease/scours or respiratory disease. Most causes of calf death can be mitigated by appropriate preventive care or well-tailored treatments, meaning that the typical death loss percentage could be decreased with better management. Producers could gather information on the circumstances near birth and at death if they had appropriate guidance on what details to record and monitor. This paper provides recommendations on data to collect at the time of birth (i.e., calf birth certificate data). The recording of these critical pieces of information is valuable in evaluating trends over time in morbidity and mortality events in dairy calves. Ideally, necropsy examination would substantially improve the identification of cause of death, but even without necropsy, attribution of cause of death can be improved by more carefully defining death loss categories in on-farm record systems. We propose a death loss categorization scheme that more clearly delineates causes of death. Recommendations are provided for additional data to be collected at the time of death. Recording and analyzing birth certificate and death loss data will allow producers and veterinarians to better evaluate associations between calf risk factors and death, with the goal of reducing dairy calf mortality.

Randomized clinical trial of the effect of a fixed or increasing milk allowance in the first 2 weeks of life on health and performance of dairy calves.

The objective of this study was to describe the effect of offering a fixed or increasing milk allowance in the first 1 to 2 wk of life. We hypothesized that calves offered a fixed amount of milk early in life would not experience more scours, but rather would experience improved health and growth compared with calves that had their daily milk allowance slowly increased over a period of 1 to 2 wk. This randomized controlled clinical trial was conducted on 5 dairy farms in Minnesota with both a summer (June-August 2016) and winter (December-February 2017) period of enrollment. Heifer calves were enrolled at birth, weighed, and systematically assigned by birth order to either the slowly increasing (INC) control group or fixed allowance (FIX) treatment group by farm personnel. Calves assigned to the INC group were slowly increased from 4 to 5 L/d to gradually reach the full peak milk allowance of 6 to 8 L/d over a 7- to 14-d period, whereas calves assigned to the FIX group were offered a full peak milk allowance of 6 to 8 L/d beginning on d 1 after birth. The average FIX calf consumed an extra 14 L of milk as compared with INC calves over the first 2 wk of life, corresponding to an average INC intake of 5 L/d during first 1 to 2 wk of life as compared with an average intake of 6.8 L/d in FIX calves. Study technicians visited all farms weekly to collect health and performance data. Multivariable mixed models were used to describe the effect of treatment (INC/FIX) on 3-wk average daily gain (kg/d), 3-wk weight (kg), and hip height at wk 1, 3, and 7, controlling for the effect of season, birth weight, and the random effect of calf within farm. Multivariable logistic regression models were used to describe the effect of treatment on odds of technician and producer reported health events. A total of 1,264 heifer calves were enrolled (FIX n = 641; INC n = 623) with no difference in enrollment weight or hip height between groups. By 3 wk of age, FIX calves weighed 1.4 (0.59) kg more than INC calves, though the magnitude of this difference varied depending on the period of time INC calves were slowly increased in milk allowance (7 vs. 10 vs. 14 d). Calves in the FIX group grew 0.1 kg/d faster and were taller at wk 3 (0.3 ± 0.15 cm) of life. Forty-two percent (536/1,264) of all enrolled calves had a first treatment event, with no effect of treatment on technician-reported health scores and no overall effect on producer-reported treatment or mortality events. Under the conditions of this study, offering a fixed milk allowance from d 1 of life improved calf growth during the first 3 wk as compared with a gradual increase in milk allowance, with no detrimental effect on calf health.

Health benefits of orally administered anti-IL-10 antibody in milk-fed dairy calves.

The primary objective of this randomized controlled trial was to determine whether anti-IL-10 egg yolk antibodies fed upon arrival to a calf ranch would lower the prevalence of Cryptosporidium parvum shedding in naturally challenged preweaned dairy calves. The secondary objectives included measuring the effect of anti-IL-10 antibodies on calf health, performance, and shedding of less common diarrheal pathogens. A total of 133 calves, enrolled at 24 to 72 h of age, received a daily dose of 0.96 g of egg yolk powder with anti-IL-10 antibodies (MAB, n = 71) or without anti-IL-10 antibodies (MEP, n = 62) split between 2 feedings for the first 11 d on feed at a calf ranch. Daily health evaluations were completed for 15 d after arrival and on d 56. Digital weights were collected at enrollment and d 56, and hipometer weights were collected at enrollment and d 7 and 56. Packed cell volume and serum total protein concentration were measured at enrollment and on d 7 and 14. Fecal pH was measured at enrollment and on d 5 and 14, and fecal pathogen (C. parvum, coronavirus, rotavirus, and Salmonella spp.) shedding was assessed at d 5 and 14. Continuous outcomes were compared between groups using a Student's t-test or Wilcoxon rank sum test. Fecal pathogen shedding at d 14, respiratory disease at d 56, and antibiotic usage were compared using relative risk (RR) and chi-squared test. Fecal pH (median and interquartile range) on d 14 was 6.65 (6.39-6.99) and 6.52 (5.97-6.81) for MAB and MEP, respectively. On d 56, the risk of respiratory disease was lower for MAB compared with MEP (RR = 0.40; confidence interval = 0.16-0.99). The risk for antibiotic treatment was lower for MAB- compared with MEP-treated calves (RR = 0.38; confidence interval = 0.17-0.88). The risk of shedding rotavirus was higher in MAB (RR = 1.38; confidence interval = 1.10-1.81) calves. After multivariable analyses, hipometer weights (least squares means ± standard error) were 1.7 ± 0.8 kg greater on d 56 in MAB compared with MEP; however, ADG was 0.04 ± 0.02 kg/d lower in MAB calves. Total health score, diarrhea days, average respiratory score, packed cell volume, and serum total protein were not affected by feeding anti-IL-10 egg antibodies. In summary, feeding anti-IL-10 antibodies was associated with increased fecal pH, reduced risk of respiratory disease later in the preweaning period, and decreased antibiotic usage despite higher rotavirus infection. These findings might be associated with improved mucosal immunity, enhanced host defenses, or reduced susceptibility and warrant further investigation.

Use of invasive placebos in research on local anaesthetic interventions.

Placebos play a vital role in clinical research, but their invasive use in the context of local anaesthetic blocks is controversial. We assessed whether recently published randomised controlled trials of local anaesthetic blocks risked harming control group patients in contravention of the Declaration of Helsinki. We developed the 'SHAM' (Serious Harm and Morbidity) scale to assess risk: grade 0 = no risk (no intervention); grade 1 = minimal risk (for example, skin allergy to dressing); grade 2 = minor risk (for example, subcutaneous haematoma, infection); grade 3 = moderate risk (with or without placebo injection) (for example, neuropraxia); and grade 4 = major risk (such as blindness, pneumothorax, or liver laceration). Placebo interventions of the 59 included trials were given a SHAM grade. Nine hundred and nineteen patients in 31 studies, including six studies with 183 children, received an invasive placebo assessed as SHAM grade ≥ 3. A high level of agreement (78%, κ = 0.80, p < 0.001) for SHAM grades 0-4 increased to 100% following discussion between assessors. More than half of the randomised controlled study designs subjected patients in control groups to risks of serious or irreversible harm. A debate on whether it is justifiable to expose control group patients to risks of serious harm is overdue.

Calf respiratory disease and pen microenvironments in naturally ventilated calf barns in winter.

Relationships between air quality, a variety of environmental risk factors, and calf respiratory health were studied in 13 naturally ventilated calf barns during winter. A minimum of 12 preweaned calves were randomly selected and scored for the presence of respiratory disease in each barn. An air sampling device was used to determine airborne bacteria colony-forming units per cubic meter (cfu/m3) of air in calf pens and central alleys within the barns. Airborne bacteria samples were collected on sheep blood agar (BAP) and eosin methylene blue (EMB) agar plates. Temperature and relative humidity were recorded in each calf pen, the barn alley, and outside the barn. Samples of bedding were collected in each pen and DM was measured. Pen bedding type and a calf nesting score (degree to which the calves could nestle into the bedding) was assigned to each barn. Calf numbers, barn and pen dimensions, ridge, eave, and curtain openings, and exterior wind speed and direction were determined and used to estimate building ventilation rates. Factors that were significantly associated with a reduced prevalence of respiratory disease were reduced pen bacterial counts (log10 cfu/m3) on BAP, presence of a solid barrier between each calf pen, and increased ability to nest. Individual calf pen bacterial counts were significantly different from barn alley bacterial counts on both BAP and EMB. Significant factors associated with reduced calf pen bacterial counts on BAP were increasing pen area, increasing number of open planes of the calf pen, decreasing pen temperature, and wood-particle bedding. Significant factors associated with reduced alley bacterial counts on BAP were increased ventilation changes per hour, increased barn volume per kilogram of calf, reduced pen bacterial counts, and barn type.

G-protein mediation in nociceptive signal transduction: an investigation into the excitatory action of bradykinin in a subpopulation of cultured rat sensory neurons.

Bradykinin is one of several pro-inflammatory, pain-inducing substances produced during inflammation--the body's response to injury. In previous work we have shown that bradykinin and guanosine-5'-O-3-thiotriphosphate increase excitability in a subpopulation of cultured neonatal rat dorsal root ganglion neurons. We now describe experiments in which the mechanism underlying the stimulatory action of these two substances has been examined in more detail. Using the whole-cell voltage-clamp technique, bradykinin-sensitive cells were distinguished by their response to a 1-s depolarizing voltage-pulse which evoked more than one inward current during the step command. The secondary inward currents are likely to represent action potentials generated at the poorly clamped neurites of these cells. Bradykinin- and guanosine-5'-O-3-thiotriphosphate-induced changes in excitability were measured indirectly by a change in the number of inward currents recorded during the 1-s depolarizing voltage-step. The effect of activators and inhibitors of protein kinase C, arachidonic acid metabolism, G-protein activation and release of intracellular Ca2+ were examined on this response. In the presence of extracellular staurosporine (1.0 microM) or nordihydroguaiaretic acid (10 microM), these excitatory effects were reduced but not abolished, whilst indomethacin (20 microM) had no effect. Intracellular application of guanosine-5'-O-2-thiodiphosphate (10 mM) or ryanodine (100 microM) substantially reduced the effect of bradykinin. The excitatory effect of internal guanosine-5'-O-3-thiotriphosphate (500 microM) occurred gradually over time, and this was mimicked by internal application of myo-inositol 1,4,5-trisphosphorothioate (1.0 microM). From the results, it is proposed that G-protein activation is an essential component of the bradykinin response, which may also require a Ca(2+)-activated conductance modulated by protein kinase C and lipoxygenase metabolites of arachidonic acid.

Modulation of divalent cation-activated chloride ion currents.

1. Voltage-sensitive calcium channel currents carried by Ca2+ (ICa) or Ba2+ (IBa) were followed by tail currents carried by Cl- ions in approximately 45% of cultured dorsal root ganglion neurones. 2. Extracellular application of (-)-baclofen (100 microM) inhibited IBa and ICl(Ba). Bay K 8644 (5 microM) potentiated both currents. 3. Intracellular GTP-gamma-S increased the proportion of neurones in which ICl(Ba) was recorded. In addition, the activation by GTP-gamma-S of a pertussis toxin-sensitive GTP binding (G)-protein resulted in a steady increase in the Cl- tail current with time, despite a concurrent reduction in IBa. 4. Extracellular application of 10mM caffeine selectively reduced ICl(Ba) without significant change in IBa. When Ca2+ was the charge carrier, caffeine had little effect on ICl(Ca), and increased the inactivation of ICa. 5. We conclude that, in addition to being regulated by divalent cation entry through Ca2+ channels, the Cl- current is also regulated by G-protein activation. The mechanism of activation of ICl(Ba) may involve Ca2+ release from intracellular stores.

An investigation into the mechanisms of inhibition of calcium channel currents in cultured sensory neurones of the rat by guanine nucleotide analogues and (-)-baclofen.

1. The mechanism of inhibition of calcium channel currents by the guanine nucleotide analogue guanosine 5'-O-3 thiotriphosphate (GTP-gamma-S) and by the GABAB agonist (-)-baclofen has been studied in cultured dorsal root ganglion neurones of the rat. The inhibition by GTP-gamma-S is particularly characterized by an abolition of the transient component of calcium channel currents carried either by Ba2+ (IBa) or by Ca2+ (ICa). 2. The effect of agents increasing intracellular cyclic AMP levels has been examined. Neither internal cyclic AMP nor forskolin prevented the inhibition of IBa by baclofen. Neither forskolin nor pretreatment of cells with cholera toxin prevented the inhibition of the transient component of IBa by GTP-gamma-S. However, both these treatments increased the amplitude of the sustained IBa in the presence of GTP-gamma-S. The ATP analogue adenosine imido-diphosphate which inhibits many ATP requiring enzymes did not prevent the effect of GTP-gamma-S although it reduced the amplitude of IBa. 3. Baclofen (100 microM) produced a 22 +/- 2% increase in inositol phosphate production in 30 s, whereas the increase produced by bradykinin (1 microM) was 70 +/- 14%. However, unlike baclofen, bradykinin did not inhibit IBa or ICa in these cells. 4. The effect of protein kinase C inhibitors was examined. Polymixin B (20 microM in patch pipette) had no effect on the inhibition of IBa by baclofen or GTP-gamma-S. A higher concentration (100 microM) alone inhibited IBa and no further inhibition by baclofen was observed. Neither H7 (50 microM) nor staurosporine (100 nM), applied extracellularly, prevented the response to GTP-gamma-S. 5. The protein kinase C activator di-octanoyl glycerol (20 microM) did not inhibit IBa. Arachidonic acid (100 microM) also produced no inhibition of IBa. 6. In conclusion we have obtained no evidence that a second messenger system mediates the inhibition of calcium channel currents by GTP-gamma-S or baclofen in dorsal root ganglion neurones. These results support the hypothesis that GABAB receptors are directly coupled to calcium channels by G proteins.

Increased spinal monoamine concentrations after chronic thoracic dorsal rhizotomy in goats.

In goats, bilateral thoracic dorsal rhizotomy (TDR) causes severe ventilatory failure during exercise, followed by progressive functional recovery. We investigated spinal neurochemical changes associated with TDR and/or functional recovery by measuring spinal concentrations of the monoamines serotonin (5-HT), norepinephrine, and dopamine via HPLC. Changes in 5-HT and calcitonin gene-related peptide were visualized with immunohistochemistry. Goat spinal cords were compared 4-15 mo after TDR from T(2) to T(12) (n = 7) with sham-operated (n = 4) or unoperated controls (n = 4). TDR increased the concentration of cervical 5-HT (C(5)-C(6); 122% change), caudal thoracic norepinephrine (T(7)-T(11); 53% change), and rostral thoracic dopamine (T(3)-T(6); 234% change). TDR increased 5-HT-immunoreactive terminal density (dorsal and ventral horns) and nearly eliminated calcitonin gene-related peptide immunoreactivity in the superficial laminae of the dorsal horn in rostral thoracic segments; both effects became less pronounced in caudal thoracic segments. Thus TDR elevates monoamine concentrations in discrete spinal regions, including possible compensatory changes in descending serotonergic inputs to spinal segments not directly affected by TDR (i.e., cervical) but associated with functionally related motor nuclei (i.e., phrenic nucleus).

Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir.

BACKGROUND: Hypersensitivity reactions consist of a variable group of clinical findings and have been described for a wide variety of chemical compounds. OBJECTIVE: This review characterizes the clinical profile of hypersensitivity to the nucleoside reverse transcriptase inhibitor abacavir sulfate. METHODS: We performed a retrospective medical review of pooled adverse events data from approximately 200,000 patients who received abacavir in clinical trials, through expanded-access programs, or by prescription from 1996 through 2000. Screened cases of hypersensitivity were classified as either definitive or probable. Definitive cases were identified when initial symptoms resolved on interruption of abacavir therapy and returned on reintroduction of abacavir therapy. RESULTS: A total of 1803 cases were identified, 1302 in the 30,595 patients participating in clinical trials or the expanded-access program and 501 in patients from the post-marketing experience. On review, 176 (9.8%) of these cases were considered definitive and the remainder probable. Based on the 1302 cases identified in clinical trials or the expanded-access program, the calculated incidence of hypersensitivity was 4.3%. Symptoms reported in > or = 20% of cases of this multiorgan reaction included fever, rash, malaise/fatigue, and gastrointestinal symptoms such as nausea, vomiting, and diarrhea, among others. Respiratory symptoms occurred in 30% of cases and included dyspnea (12%), cough (10%), and pharyngitis (6%). In 90% of cases, hypersensitivity reactions occurred within the first 6 weeks after initiation of abacavir (median time, 11 days); after an initial reaction, rechallenge with abacavir resulted in the reappearance of symptoms within hours of reexposure. Hypotension was present in 25% of these rechallenge reactions. Among patients who received abacavir in clinical trials, the mortality rate was 0.03% (3 per 10,000 patients). CONCLUSIONS: Hypersensitivity to abacavir is an idiosyncratic reaction and a distinct clinical syndrome characterized predominantly by systemic involvement. It can be expected to appear as a treatment-limiting event in approximately 5% of patients. The appearance of clinical symptoms consistent with this syndrome mandates immediate discontinuation of abacavir. Hypersensitivity to abacavir is an absolute contraindication to subsequent treatment with any formulation that includes this agent.

Bradykinin enhances excitability in cultured rat sensory neurones by a GTP-dependent mechanism.

The excitatory action of bradykinin (Bk; 0.1-1.0 microM) on cultured rat dorsal root ganglion neurones (DRGs) was studied using the whole cell clamp technique. In a subpopulation of DRGs, a 1 s depolarising voltage pulse from -70 to +20 mV evoked more than one inward current. In these neurones, local application of Bk increased the inward current frequency from 7.0 +/- 0.7 s-1 to 14.9 +/- 1.0 s-1 (mean +/- S.E.M., n = 53). Intracellular application of the GTP analogue, guanosine 5'O-3-thiotriphosphate (GTP gamma S) mimicked this excitatory action of Bk: the frequency of inward currents increased from 5.0 +/- 0.8 s-1, 30 s after the start of recording to 6.9 +/- 1.1 s-1 at 5 min to a maximum of 18.5 +/- 2.2 s-1 at 15 min (n = 16). In control cells, the frequency decreased from 4.6 +/- 0.8 s-1 to 2.5 +/- 0.5 s-1 at 5 min (n = 12). Bk also increased excitability in 4/11 Herpes Simplex Virus I (HSV-I)-infected DRGs. Thus, we demonstrate an excitatory action of Bk in DRGs, which may involve G-protein activation.

Twenty-year follow-up of aortic valve replacement with antibiotic sterilized homografts in 200 patients.

The aim of this study was to determine long-term results from one unit of subcoronary homograft aortic valve replacement (AVR) using the same sterilization and preservation techniques in each case. Between 1973 and 1983, 200 patients underwent AVR using an unstented homograft previously sterilized in antibiotics and preserved at 4 degrees C. Surviving patients were monitored for a minimum of 15 years to the end of 1998. Mean age was 50.0+/-14 (1 standard deviation) years; 121 patients were men (60.5%). Mean patient follow-up time was 15.6+/-6.7 years, with a total follow-up time of 3,115 patient years. Follow-up was 95.6% complete. There were three early deaths (1.5%). At autopsy, the homograft was anatomically normal and in a satisfactory position. Kaplan-Meier survival, including early death, was 81.2%+/-2.8% (1 standard error) at 10 years, 68.1%+/-3.4% at 15 years, and 58.0%+/-3.7% at 20 years. Repeat AVR was undertaken in 74 patients, giving a freedom from reoperation for any reason of 86.5%+/-2.6%, 69.6%+/-3.8%, and 38.8%+/-5.3% at 10, 15, and 20 years, respectively. Freedom from structural valve degeneration at 10, 15, and 20 years was 81.1%+/-2.9%, 61.7%+/-3.9%, and 31.2%+/-4.7%, respectively. Freedom from endocarditis at 10, 15, and 20 years was 98.7%+/-0.9%, 96.0%+/-1.8%, and 94.6%,+/-2.3%, respectively. Homograft AVR with an antibiotic-sterilized valve stored at 4 degrees C and implanted in the subcoronary position offers low operative mortality and good long-term outcome for patients.

Effect of colostral ingestion on immunoglobulin-positive cells in calves.

The importance of colostrum for passive transfer of maternal immunoglobulin in calves is well established. Colostrum is thought to have additional generalized and antigen-specific immunomodulatory activities, of which the downregulation of endogenous immunoglobulin production is best documented. The objective of this study was to examine whether ingestion of colostrum altered the B cell subpopulations in the lymph nodes of newborn calves. Calves were fed one gallon of either fresh colostrum (Group A, n = 5), milk replacer (Group B, n = 5) or treated (frozen or irradiated) colostrum (Group D, n = 4) and were euthanized at 36-48 h. An additional 5 calves (Group C, 3 newborn and 2 mid-term fetuses) did not receive any feedings; the neonatal calves were euthanized immediately following birth. Mesenteric and regional lymph nodes from all calves were analyzed by immunocytochemistry using monoclonal antibodies recognizing bovine IgA, IgG1, IgG2, and IgM. Calves from Groups B and C (colostrum deprived, neonates, and fetuses) showed a consistent pattern of IgG1 and IgG2 positive cells scattered individually and in clusters throughout lymph node cortex, paracortex, and cortico-medullary junction. In sharp contrast, no IgG1 and IgG2 positive cells were present in the lymphoid tissues of colostrum fed calves (Groups A or D). Numbers of IgM and IgA positive cells were similarly distributed in all calf groups. These findings demonstrate that colostrum feeding reduces the number of immunoglobulin positive cells in the lymphoid tissues of newborn calves in an isotype-specific manner. This results in the elimination of IgG1 and IgG2 positive cells that are present in both fetuses and newborn calves. This effect is not eliminated by freezing or irradiation, indicating that a non-cellular, cold-stable colostral factor is responsible. Systemically distributed colostral proteins such as immunoglobulin or cytokines are the most likely mediators. The significance of this phenomenon in terms of colostral modulation of calf endogenous antibody production is discussed.

Investigation of caval syndrome in dogs experimentally infected with Dirofilaria immitis.

Nine of 16 dogs inoculated with 200 infective heartworm larvae developed caval syndrome (CS) of heartworm disease (HWD). There was no difference between dogs that did and did not develop CS with regard to total heartworm burden, burden relative to body weight, or female heartworm burden, indicating that factors other than worm mass are involved in the pathogenesis of CS. Male dogs were twice as frequently affected as females, although this finding was not statistically significant. Dogs afflicted with CS exhibited radiographic, pathologic, and hemodynamic evidence of chronic HWD. In a model of single heartworm exposure, these findings strongly support the theory that CS develops due to retrograde migration of adult worms from the pulmonary arteries and right ventricle to the right atrium and venae cavae. Pulmonary artery pressures were dramatically and significantly greater in dogs with CS (60 +/- 18 torr) as compared to non-CS (30 +/- 4 torr) dogs with equal worm burdens.

Pathophysiologic mechanism of cardiac dysfunction in experimentally induced heartworm caval syndrome in dogs: an echocardiographic study.

In dogs with experimentally induced heartworm infection, the onset of caval syndrome (CS) was characterized by a murmur, loudest over the tricuspid valve, and a large worm mass in the right ventricular lumen detectable during diastole by use of M-mode echocardiography. Two-dimensional echocardiography indicated that the worm mass was located in the right atrium and venae cavae and was "flowing" into the right ventricle during rapid diastolic filling. Paradoxical septal motion and vigorous right ventricular cranial wall motion also were observed. Other echocardiographic changes included decreased size of the left atrium and ventricle, aortic root, and ratio of left-to-right ventricular diastolic luminal diameter, compared with values obtained 6 months after experimentally induced heartworm infection. Right ventricular end diastolic diameter increased considerably. Most echocardiographic indices of left ventricular function (fractional shortening, velocity of circumferential fiber shortening, ejection fraction, and preejection period) were not altered appreciably, but estimates of cardiac index and stroke volume were markedly decreased. Electrocardiography revealed ventricular and supraventricular premature complexes in 7 of the 8 dogs studied, evidence of right ventricular enlargement in 6 of the 8 dogs studied, and increased mean heart rate, compared with that measured 6 months after inoculation of infective larvae, before the onset of CS. Cardiac catheterization was performed in 3 days at the onset of CS. Severe pulmonary arterial and right ventricular hypertension and decreased cardiac index (compared with values obtained before inoculation) were observed. Evidence of right ventricular inflow obstruction was not detected. Mean aortic blood pressure decreased with the onset of CS, but right ventricular end diastolic pressure increased.(ABSTRACT TRUNCATED AT 250 WORDS)