Ductal Plate Malformation in the Liver of Boxer Dogs: Clinical and Histological Features.

Ductal plate malformations (DPMs) represent developmental biliary disorders with a wide phenotypic spectrum. This study characterizes DPM in 30 Boxer dogs. Median age was 1.5 (range, 0.3-10.0) years, with 12 dogs <1 year. Clinical features included increased serum levels of liver enzymes (28), gastrointestinal signs (16), poor body condition (14), abdominal effusion (9), and hepatic encephalopathy (2). Additional malformations included gallbladder atresia (8), atrophied left liver (2), absent quadrate lobe with left-displaced gallbladder (1), portal vasculature atresia (left liver, 1), intrahepatic portosystemic shunt (1), and complex intrahepatic arteriovenous malformation (1). All dogs had portal tracts dimensionally expanded by a moderate-to-severe multiple small bile duct phenotype embedded in abundant extracellular matrix; 80% displayed variable portal-to-portal bridging. Quantitative analysis confirmed significantly increased fibrillar collagen and a 3-fold increased portal tract area relative to 6 Boxer and 10 non-Boxer controls. Biliary phenotype was dominated by tightly formed CK19-positive ductules, typically 10 to 15 µm in diameter, with 3 to >30 profiles per portal tract, reduced luminal apertures, and negative Ki-67 immunoreactivity. CK19-positive biliary epithelium intersected directly with zone 1 hepatocytes as a signature feature when considered with other DPM characteristics. Phenotypic variation included a multiple small bile duct phenotype (all dogs), predominantly thin-walled sacculated ducts (4), well-formed saccular ducts (4), and sacculated segmental, interlobular, and intralobular ducts (Caroli malformation, 2 dogs, one with bridging portal fibrosis). Histologic evidence of portal venous hypoperfusion accompanied increased biliary profiles in every case. We propose that this spectrum of disorders be referred to as DPM with appropriate modifiers to characterize the unique phenotypes.

Viral-like brain inflammation during development causes increased seizure susceptibility in adult rats.

Viral infections of the CNS and their accompanying inflammation can cause long-term neurological effects, including increased risk for seizures. To examine the effects of CNS inflammation, we infused polyinosinic:polycytidylic acid, intracerebroventricularly to mimic a viral CNS infection in 14 day-old rats. This caused fever and an increase in the pro-inflammatory cytokine, interleukin (IL)-1beta in the brain. As young adults, these animals were more susceptible to lithium-pilocarpine and pentylenetetrazol-induced seizures and showed memory deficits in fear conditioning. Whereas there was no alteration in adult hippocampal cytokine levels, we found a marked increase in NMDA (NR2A and C) and AMPA (GluR1) glutamate receptor subunit mRNA expression. The increase in seizure susceptibility, glutamate receptor subunits, and hippocampal IL-1beta levels were suppressed by neonatal systemic minocycline. Thus, a novel model of viral CNS inflammation reveals pathophysiological relationships between brain cytokines, glutamate receptors, behaviour and seizures, which can be attenuated by anti-inflammatory agents like minocycline.

Abdominal Ultrasound Examination Findings in 534 Hyperthyroid Cats Referred for Radioiodine Treatment Between 2007-2010.

BACKGROUND: The prevalence of concurrent disease in hyperthyroid cats is unknown. OBJECTIVES: To identify the prevalence of concurrent intra-abdominal disease using abdominal ultrasound examination (AUS) in hyperthyroid cats referred for radioactive iodine treatment (RIT) and to determine whether the requirement for pretreatment AUS is justified. ANIMALS: Five hundred and thirty-four client-owned cats diagnosed with hyperthyroidism and referred for RIT. METHODS: Retrospective study. Age, breed, sex, body weight, clinical signs, total serum T4 concentration, blood urea nitrogen (BUN) concentration, serum creatinine concentration, urine specific gravity (USG), AUS results, and biopsy or cytology results, or both (if obtained) were collected from the medical records. RESULTS: The prevalence of concurrent disease identified using AUS in hyperthyroid cats referred for RIT was 36.1%; 22.8% of the cats in the study had renal disease and 2.4% had confirmed neoplasia. Significant differences in median USG (P value 0.032) and median BUN (P value 0.028) were found between cats that had abnormal kidneys on AUS compared to those with normal-appearing kidneys. Only 2.2% of the cats were not treated with RIT as a result of changes identified on AUS and subsequently obtained cytology or biopsy results. CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that pretreatment AUS in hyperthyroid cats referred for RIT is unnecessary in most patients.

Blood lead levels of primary school children in Dhaka, Bangladesh.

Dhaka, Bangladesh, has one of the highest air lead levels in the world. In February 2000, we evaluated children at five primary schools in Dhaka to determine blood lead (BPb) levels, sources of environmental exposure, and potential risk factors for lead poisoning. Selected schools represented a range of geographic and socioeconomic strata. A total of 779 students 4-12 years of age participated. The mean BPb level was 15.0 microg/dL (range 4.2-63.1 microg/dL). Most students (87.4%) had BPb levels above the Centers for Disease Control and Prevention's level of concern (10 microg/dL). Elevated BPb levels correlated with soil eating [odds ratio (OR) = 3.31; 95% confidence interval (CI), 1.30-8.39], low parental education (OR = 2.72; 95% CI, 1.97-3.75), living close to major roads (OR = 2.30; 95% CI, 1.23-4.29), and increasing age (OR = 1.11; 95% CI, 1.06-1.16). BPb levels measured were similar to those in other countries that use leaded gasoline. No other potential sources of lead exposure were consistently identified. Combustion of leaded gasoline is the main source of lead exposure in Dhaka, resulting in ubiquitous contamination of the environment. The increase in BPb levels with age, a finding contrary to observations in the United States and Australia, may be related to increased outdoor activities. The Bangladeshi government recently announced a plan to eliminate leaded gasoline. Baseline BPb surveys are critical to develop and evaluate intervention policies. Strategies to reduce BPb levels need to address variations in socioeconomic status, construction type and location of housing, and levels of hygiene.

Breast-feeding among women exposed to polybrominated biphenyls in Michigan.

In the early 1970s, the largest industrial accident in the United States resulted in widespread contamination of the food supply in Michigan with polybrominated biphenyls (PBBs). The chemical similarity of PBBs to compounds implicated as endocrine disruptors has raised the question of whether PBBs could affect the reproductive system. In the present analysis we examine the relation between serum measurements of PBBs and the frequency and duration of lactation. Persons who lived on or received food from farms exposed to PBBs were enrolled in a registry by the Michigan Department of Public Health. Female members of the cohort were invited to participate in a telephone survey of reproductive outcomes. The three outcomes of interest in the present analysis were a) the decision to breast-feed (yes/no); b) the duration, in months, of breast-feeding as the main source of nutrition; and c) the total duration, in months, of breast-feeding. None of the three outcomes was significantly associated with serum PBB levels, even after controlling for maternal age, previous history of breast-feeding, body mass index, maternal education, household income, history of smoking in the year before pregnancy, consumption of alcohol during the first trimester of pregnancy, history of thyroid disorder, gestational age of the infant in weeks, time to pregnancy, and year of birth.

Determinants of polybrominated biphenyl serum decay among women in the Michigan PBB cohort.

Accidental contamination of the food chain in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. Serum was collected and analyzed for PBB at the time of enrollment and for targeted studies in the following years. We used the archived PBB data to study the elimination of PBB and to identify factors associated with elimination. A total of 380 women >= 16 years of age who had an initial PBB level of 2 ppb and at least two serum samples drawn when they were not pregnant were included in the analysis. The mean initial PBB level was 20.9 ppb (median 4) and mean time between the first and last measurement was 4.2 years (range 0.5-11.1). PBB was assumed to reach equilibrium in the body before substantial amounts were eliminated and before the first serum measurements were taken; therefore, the entire body was modeled as a single compartment for PBB with exponential decay. Subject-specific decay rate estimates were regressed on predictor variables including initial age, body mass index (BMI), smoking history, breast-feeding duration, and parity. In women with an initial PBB level < 10 ppb, the median half-life was 12.9 years; in those with > 10 ppb, the median half-life was 28.7 years. Decay was significantly slower among women with an initial BMI at or above the median (BMI >= 23). The calculated half-life values are estimates of decay and can be used to estimate body burden of PBB at various points in time other than at the time of serum collection.

Neurokinin A receptors are coupled to calcium mobilization in transfected fibroblasts.

Neurokinin A (NKA) mediated a concentration dependent increase in the intracellular free Ca2+ concentration, [Ca2+]i, in B82 fibroblasts transfected with the neurokinin 2 (NK2) receptor. The EC50 value of this response was 24 nM. A selective NK2 antagonist, MEN 10207, at a concentration of 1 microM completely inhibited the [Ca2+]i rise to 0.1 microM NKA. These results suggest that activation of NK2 receptors expressed in the transfected fibroblasts are functionally coupled to intracellular calcium mobilization.

Desensitization of neurokinin A receptors expressed by B82 fibroblasts.

After chronic exposure to neurokinin A, a time-dependent and recoverable desensitization of inositol monophosphate accumulation occurred in B82 fibroblasts transfected with cDNAs encoding for the bovine stomach NK2 receptor. Desensitized cells also showed decreased Ca2+ mobilization. While NK2 receptor antagonists had no effect on inositol monophosphate accumulation, substance P and senktide both produced a small degree of desensitization.

Demonstration of a neurokinin A receptor subtype in transfected fibroblasts.

In competitive radioligand binding assays, the NK2 receptor antagonists [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10) (MEN 10207) and [Tyr5,D-Trp6,8,9,Arg10]NKA(3-10) (MEN 10208) had high and low affinity, respectively, in bovine stomach membranes and SKLKB82#3 cells, a murine fibroblast cell line transfected with a cDNA encoding for the bovine NK2 receptor. These antagonists also had different affinities when inhibiting neurokinin A-induced polyphosphoinositide hydrolysis in SKLKB82#3 murine fibroblasts. Thus, the de novo protein expressed by the SKLKB82#3 murine fibroblasts may represent a distinct NK2 receptor subtype.

Occupational burns in Washington State, 1989-1993.

Occupational burns cause significant morbidity in the United States each year; however, there are few studies that report industries or workplaces where workers are at an increased risk of burn injuries. Washington State's Department of Labor and Industries (L and I) computerized workers' compensation database was used to describe work-related burns over 5 years. From 1989 to 1993, L and I accepted 27,323 claims for occupational burns, 71.4% of them thermal burns and 26.8% chemical burns. The most common sources of injury were cooking oils (14%) and hot water/steam (13%). Workers involved in food preparation or food handling accounted for the highest proportion of injured workers (30%). Industries involved in the smelting, sintering, or refining of ore had the highest rate for thermal burns, with a rate of 15.0 burn injuries per 100 full-time equivalent workers per year, followed by paper, pulp, or wood fiber manufacturing, with a rate of 5.8, then roof work, with a rate of 4.3. Industries involved in hazardous waste landfill clean-up had the highest rate for chemical burns, with a rate of 4.9, followed by portable cleaning and washing, with a rate of 3.5, and paper, pulp, and wood fiber manufacturing, with a rate of 2.6. Further study is needed to identify work practices that result in burn injuries in order to decrease the incidence of this preventable occupational injury.

Surveillance of occupational diseases in the United States. A survey of activities and determinants of success.

Managers of state-based occupational disease surveillance programs were interviewed for information on their program's characteristics and factors that contributed to their success. There were 68 programs in 52 jurisdictions (50 states, the District of Columbia and New York City). Reportable conditions ranged from a specific disease to "all occupational diseases". Of these programs, 56% met at least one of their objectives. Conditions associated with successful programs usually had short latency periods, were easily diagnosed, and were related to a workplace hazard. They included agricultural injuries, burns, respiratory diseases, cumulative trauma disorders, and poisonings due to lead, pesticides, or carbon monoxide. Successful programs had larger budgets and more staff than did unsuccessful programs, and also took actions after notification of a condition.

An unusual case of wegener's granulomatosis.

A 58-year-old male developed extensive multisystem Wegener's granulomatosis eight years after pneumonectomy for a large solitary granuloma of the lung. Follow up following pneumonectomy had indicated a very prolonged disease free interval.

Pulmonary hypersensitivity in the alginate industry.

Salts of alginic acid are complex polymerised polysaccharides which are chemically extracted from seaweed. Workers in the alginate industry are exposed to dust from dried milled seaweed and pure alginate compounds. In this survey of one of the two factories in Britain producing alginates, we found evidence of pulmonary hypersensitivity to seaweed dust in seven per cent of the total work force, and evidence of precipitating antibody to sodium alginate and seaweed extracts in the serum of 4.5 per cent of the work force. Challenge testing of a number of employees with symptoms showed a dual response with immediate airways obstruction, and a later loss of lung volume, with associated impairment of transfer factor.

High frequency stimulation alters motor maps, impairs skilled reaching performance and is accompanied by an upregulation of specific GABA, glutamate and NMDA receptor subunits.

High frequency stimulation (HFS) has the potential to interfere with learning and memory. HFS and motor skill training both lead to potentiation of the stimulated network and alter motor map expression. However, the extent to which HFS can interfere with the learning and performance of a skilled motor task and the resulting effect on the representation of movement has not been examined. Moreover, the molecular mechanisms associated with HFS and skilled motor training on the motor cortex are not known. We hypothesized that HFS would impair performance on a skilled reaching task, and would be associated with alterations in motor map expression and protein levels compared to non-stimulated and untrained controls. Long Evans Hooded rats were chronically implanted with stimulating and recording electrodes in the corpus callosum and frontal neocortex, respectively. High frequency theta burst stimulation or sham stimulation was applied once daily for 20 sessions. The rats were divided into five groups: control, HFS and assessed at 1 week post stimulation, HFS and assessed 3 weeks post stimulation, reach trained, and HFS and reach trained. A subset of rats from each group was assessed with either intracortical microstimulation (ICMS) to examine motor map expression or Western blot techniques to determine protein expression of several excitatory and inhibitory receptor subunits. Firstly, we found that HFS resulted in larger and reorganized motor maps, and lower movement thresholds compared to controls. This was associated with an up-regulation of the GABA(A)α1 and NR1 receptor subunits 3 weeks after the last stimulation session only. Stimulation affected skilled reaching performance in a subset of all stimulated rats. Rats that were poor performers had larger rostral forelimb areas, higher proximal and lower distal movement thresholds compared to rats that were good performers after stimulation. Reach training alone was associated with an up-regulation of GABA(A)α1, α2, GluR2, NR1 and NR2A compared to controls. HFS and reach-trained rats showed an up-regulation of GABA(A)α2 compared to stimulated rats that were not reach-trained. Therefore, we have shown that HFS induces significant plasticity in the motor cortex, and has the potential to disrupt performance on a skilled motor task.

Injuries and deaths at a pub fire in Bangkok, Thailand on New Year's Eve 2009.

This investigation describes the 67 people who died and the 153 who were hospitalized from a New Years' Eve fire in a Bangkok pub. We interviewed survivors and reviewed medical charts and forensic reports of decedents. Survivors were young (median age 27 years), single (84.7%) and lived in Thailand (93.6%). Most were on the concert floor when the fire started (74.0%), became aware of danger when they saw flames (61.5%) and escaped through the main entry door (42.9%). Common injuries were burns (75.6%), smoke inhalation (47.4%) and open wounds (32.1%). The decedents' median age was 27 years and 88.1% lived in Thailand. Most of the dead bodies were found at or near the main entrance. The main causes of death were asphyxia (88.1%) or burn (10.4%). Soot was present in the trachea of 95.5% of the decedents. Carboxyhemoglobin level in 37.5% was in the toxic range. The average percent of body surface burned was 75.0%. Loss of consciousness in the pub (RR 3.5, 95% CI 1.7-7.3) was a risk factor for severe injury and smoke inhalation (RR 9.3, 95% CI 3.1-28.0) was a risk factor for death.

Training-induced and electrically induced potentiation in the neocortex.

Long-term potentiation (LTP) shares many properties with memory and is currently the most popular laboratory model of memory. Although it has not been proven that memory is based on an LTP-like mechanism, there is evidence that learning a motor skill can induce LTP-like effects. This evidence was obtained in a slice-preparation experiment, which precluded within-animal comparisons before and after training. In the present experiments, Long-Evans rats were unilaterally trained to acquire a forelimb reaching and grasping skill. Evoked potentials were found to be larger in motor cortex layer II/III in the trained, compared to the untrained, hemisphere in slice, acute, and chronic preparations. Consistent with previous research, the trained hemisphere was less amenable to subsequent LTP induction. Furthermore, the application of either LTP- or LTD-inducing stimulation during the training phase of the reaching task disrupted the acquisition of the skill, providing further evidence that memory may be based on an LTP mechanism.

Cardiogenic oscillations of nitrogen and argon concentration in expired gas in man.

1. The cardiogenic oscillations in the concentration of nitrogen and argon in expired gas, which are seen after the inspiration from residual volume of pure oxygen or a bolus of argon, have been studied in normal subjects and in patients with atrial fibrillation. 2. In the upright position of the subject, the peaks of nitrogen and argon concentration coincide with ventricular systole, although there is a transit delay along the tracheobronchial tree before any change of concentration occurs at the mouth. 3. Studies in different postures demonstrated that the effect of the heart is predominantly due to a reduction in cardiac volume during systole with a decrease in airflow from regions adjacent to the heart. These areas contain a different concentration of nitrogen and argon in the alveolar air from the more apical regions. 4. It has been shown that the results are consistent with the present concepts of the influence of gravity on the distribution of inspired air.

Heat-related death and mental illness during the 1999 Cincinnati heat wave.

During a 1999 heat wave in Cincinnati, Ohio, the Hamilton County Coroner reported 18 heat-related deaths. The Centers for Disease Control and Prevention and the Cincinnati Department of Health conducted a case-control study using surrogate case information and first-person control information to identify risk factors for mortality during the heat wave. Surrogate data were supplemented by systematic death scene investigation reports and comprehensive toxicologic screens, important sources of data that are routinely collected by the Hamilton County Coroner's Office. The study included 17 case subjects and 34 controls from the decedents' neighborhood. Among 17 case subjects, 8 (47.1%) had mental illness (odds ratio [OR], 14.0; 95% confidence interval [CI], 1.8-633). There was a suggestion of an interaction between age and mental health. A working air-conditioner was the strongest protective factor (OR, 0.03; 95% CI, 0-0.2). Toxicologic screening indicated that case subjects with reported mental illness and a prescription for psychotropic drugs may not have been medication compliant. Three decedents lived in group homes for people with mental illness, indicating that opportunities for prevention may have been missed. Systematic death investigations, including toxicologic screening, provide valuable information about the circumstances of heat-related death, particularly the role of medication compliance as a risk factor. Prevention programs during heat waves should target people with mental illness, especially those who take psychotropic medication.

Disaster medical assistance teams: providing health care to a community struck by Hurricane Iniki.

STUDY OBJECTIVE: To describe the type of medical care that disaster medical assistance teams (DMATs) provided to a community struck by a major hurricane. STUDY DESIGN: A prospective study describing the use of DMAT field clinics by a population affected by a major hurricane. Data regarding the type of medical care provided to disaster victims and the acuity of each patient's medical condition were abstracted from medical charts at each field clinic. SETTING: Three DMAT field clinics that provided medical care to residents of Kauai, Hawaii, after Hurricane Iniki struck the island on September 11, 1992. RESULTS: From September 16 to 19, 1992, three DMATs provided medical care to 614 people. The patients' average age was 34 years, and 60% were male. The largest treatment categories were injury (40.4%), illness (38.6%), and preventive services (9.0%). Most illnesses and injuries were minor, and 99% of the patients were ambulatory. Only 33 patients (5.4%) were referred to another medical provider. Referrals were generally for procedures not available in DMAT field clinics rather than for life-threatening conditions. CONCLUSION: DMATs sent to assist with the medical needs of a US community struck by a major hurricane should be prepared to deliver basic medical services and primary health care. The need for these medical services will continue beyond the impact phase of a hurricane disaster.