Where does the Albumin go? Human Albumin Solution usage following the implementation of a demand management programme.

OBJECTIVE: To outline the Guy's and St Thomas' NHS Foundation Trust (GSTFT) and Evelina London Children's Hospital (ELCH) demand management plan for human albumin solution (HAS) and usage. BACKGROUND: There is no UK-wide guidance governing the use of HAS. A severe shortage in 2015 prompted a Trust demand management programme. Indications were categorised according to locally agreed colour code and ASFA categories. METHODS: Following the implementation of the demand management programme, a 6-month audit of HAS usage was completed. RESULTS: A total of 1303.1 L of HAS was used in 1139 infusions; 737 infusions were 20% HAS, accounting for 175.7 L (13.5%) in 181 patients. Indications for 20% HAS were red in 53.9% (94.7 L), blue in 26.5% (46.5 L) and grey in 19.6% (34.5 L). The remaining 1127.4 L (86.5%) infused were of 4.5 and 5 % HAS. A total of 1102.3 L (97.8%) was used for plasma exchange, 941.4 L (85.4%) ASFA category I, 93.7 L (8.5%) category II, 25.5 L (2.3%) category IV and 41.7 L (3.8%) for indications not specified according to ASFA; 25.1 L (2.2%) were used for a grey indication (volume resuscitation for hypovolaemia). CONCLUSIONS: The demand management programme provides surveillance of indications and retrospective verification of appropriate use. The majority of HAS indications were appropriate. Plasma exchange accounted for 84.6% of HAS usage and will be the focus of further demand management strategies. The demand management programme whilst aiming to promote best transfusion practice also ensures a tool to manage future shortages according to indication and available supply.

Risk of clinical deterioration in patients with lupus nephritis receiving rituximab.

Rituximab is a chimeric anti-CD20 monoclonal antibody that is used as an immunosuppressive agent in cyclophosphamide refractory lupus nephritis to induce remission. Although uncontrolled case series suggest efficacy, this is not yet supported by evidence from prospective randomized controlled trials. The objective of this retrospective case series is to report the clinical outcome of seven patients who received rituximab for lupus nephritis in a single centre between 2011 and 2014. One patient had clinical evidence of an uncomplicated response to therapy. A second patient responded well with the first rituximab course, but had transient worsening of renal function and nephrotic syndrome with a second course. The other five patients all had evidence of a clinical deterioration following rituximab. Two had transient worsening of both renal function and nephrotic syndrome, with subsequent evidence of response in one of these. A fifth patient showed evidence of worsening nephrotic syndrome and renal function which then improved but with renal function remaining below the level present before rituximab. A sixth developed rapidly progressive renal failure following rituximab with active nephritis on renal biopsy and required rescue therapy with high dose steroids and cyclophosphamide. A seventh developed a transient worsening of her nephrotic syndrome and an exacerbation of extrarenal symptoms following rituximab. The two patients showing a good response had complete B cell depletion and incomplete depletion may be a factor in the deterioration seen in the other patients. Our experience suggests that rituximab therapy in lupus nephritis is not without risk and patients should be informed of this beforehand. This is particularly important in view of the uncertainty that rituximab will offer a therapeutic benefit.

Green Tobacco Sickness among Thai Traditional Tobacco Farmers, Thailand.

BACKGROUND: Traditional Thai tobacco (Nicotiana abacus L.) is known as a non-Virginia type whose mature leaf contains three to four times more nicotine than that of a Virginia type. As such, the process of Thai traditional tobacco production may lead to adverse health effects such as green tobacco sickness (GTS). OBJECTIVE: To investigate the prevalence of GTS and risk factors related to GTS among Thai traditional tobacco farmers in Nan province, northern Thailand. METHODS: 473 Thai traditional tobacco farmers from rural areas in Nan province were randomly selected and interviewed in person by means of questionnaires and environmental survey. Statistical analyses were used to identify potential risk factors for GTS. RESULTS: The prevalence of GTS was 22.6% (95% CI 19.1% to 26.6%). Multivariate analysis showed various risk factors associated with GTS including gender of the farmer (ORadj 0.44, 95% CI 0.26 to 0.73), smoking (ORadj 4.36, 95% CI 1.41 to 13.47), skin rash (ORadj 0.36, 95% CI 0.19 to 0.68), wearing a wet suit (ORadj 1.91, 95% CI 1.12 to 3.23), process of curing tobacco leaves (ORadj 0.06, 95% CI 0.02 to 0.16), and watering tobacco plants (ORadj 0.42, 95% CI 0.25 to 0.72). CONCLUSION: The process of traditional Thai tobacco production can result in increased dermal exposure and can be considered a major risk factor for GTS. Body soaking during watering may further increase adverse health effects related to GTS.

Animal models of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Antibodies against neutrophil proteins myeloperoxidase (MPO) and proteinase 3 are thought to cause disease in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. There have been a number of recent developments in the animal models of ANCA vasculitis in both mice and rats. These include models based on an immune response to MPO generated in MPO-deficient mice, with other models using MPO-sufficient mice and rats. In addition, there is a report of the use of humanized mice where immunodeficient mice have been engrafted with human haematopoietic stem cells and injected with patient ANCA. Antibodies to another protein lysosomal-associated protein-2 have been found in patients with ANCA vasculitis, and evidence from a rat model suggests that they are also pathogenic. These models all have advantages and disadvantages, which are discussed. We also consider what these models have taught us about the pathogenesis of ANCA vasculitis. Experiments using genetically modified mice and pharmacological inhibition have given insights into disease mechanisms and have identified potential therapeutic targets. Toll-like receptor stimulation modifies disease by acting both at the level of tissue injury and in the generation of the autoimmune response. Complement is also potentially important with data to support the role of the alternative pathway and C5a in particular. Intracellular pathways have been examined, with a role showing p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase γ. Serine proteases are now known to contribute to disease by release of interleukin-1ß in ANCA-activated neutrophils and monocytes. Other potential therapies studied in these models include the use of bortezemib and strategies to modify antibody glycosylation.

Antibody-mediated glomerulonephritis in mice: the role of endotoxin, complement and genetic background.

Antibody-mediated glomerulonephritis in man may be exacerbated by infection and this effect may be mediated by bacterial endotoxin. There is evidence supporting a role for endotoxin in heterologous nephrotoxic nephritis in rats, but the role of endotoxin in this model in mice has not previously been explored. Previous data in mice on the role of complement in this model are conflicting and this may be due to the mixed genetic background of mice used in these studies. We used the model of heterologous nephrotoxic nephritis in mice and explored the role of endotoxin, complement and genetic background. In this study we show a synergy between antibody and endotoxin in causing a neutrophil influx. We also show that C1q-deficient mice have an increased susceptibility to glomerular inflammation but this is seen only on a mixed 129/Sv x C57BL/6 genetic background. On a C57BL/6 background we did not find any differences in disease susceptibility when wildtype, C1q, factor B or factor B/C2 deficient mice were compared. We also demonstrate that C57BL/6 mice are more susceptible to glomerular inflammation than 129/Sv mice. These results show that endotoxin is required in this model in mice, and that complement does not play a major role in glomerular inflammation in C57BL/6 mice. C1q may play a protective role in mixed-strain 129/Sv x C57BL/6 mice, but the data may also be explained by systematic bias in background genes, as there is a large difference in disease susceptibility between C57BL/6 and 129/Sv mice.

Outdoor exposure to airborne polycyclic organic matter and adverse reproductive outcomes: a pilot study.

BACKGROUND: To investigate the association between outdoor airborne polycyclic organic matter (POM) and adverse reproductive outcomes in New Jersey, we used a cross-sectional design combining air quality data from the USA EPA Cumulative Exposure Project and individual data on pregnancy outcomes from birth and fetal death certificates at the census tract level. METHODS: After excluding plural births and chromosomal anomalies, 221,406 live births and 1,591 fetal deaths registered in New Jersey during the years of 1990 and 1991 were included. The exposure estimates were derived from modeled average POM concentrations for each census tract in the state. RESULTS: After adjustment for potential confounders, the odds ratios (OR) for very low birth weight for the highest exposure compared to the lowest exposure group was 1.31 (95% CI 1.15-1.51); among term births, high POM exposure was associated with low birth weight OR = 1.31 (95% CI 1.21-1.43), with fetal death OR = 1.19 (95% CI 1.02-1.39) and with premature birth OR = 1.25 (95% CI 1.19-1.31). The univariate stratified analyses suggested effect modification of all observed associations by maternal alcohol consumption. CONCLUSIONS: This study found associations between outdoor exposure to modeled average airborne POM and several adverse pregnancy outcomes. The data and methods utilized in this pilot study may be useful for identifying hazardous air pollutants requiring in-depth investigation.

Accelerated nephrotoxic nephritis is exacerbated in C1q-deficient mice.

C1q deficiency strongly predisposes to the development of systemic lupus erythematosus in humans and mice. We used the model of accelerated nephrotoxic nephritis in C1q-deficient mice to explore the mechanisms behind these associations. C1q-deficient mice developed severe glomerular thrombosis within 4 days of induction of disease, whereas wild-type mice developed mild injury. These findings suggest that C1q protects from immune-mediated glomerular injury. This exacerbated thrombosis was also seen in mice triply deficient in C1q, factor B, and C2, excluding a major pathogenic role for the alternative pathway of complement in this phenomenon. However, these mice did not develop elevated creatinine levels. No exacerbation of accelerated nephrotoxic nephritis was observed in mice doubly deficient in factor B and C2, suggesting a protective role for C1q against renal inflammation that is proximal to C2 activation. There were increased murine IgG deposits, neutrophil numbers, and apoptotic cells in the glomeruli of C1q-deficient mice compared with wild-type mice. Renal expression of genes encoding procoagulant proteins was also enhanced in C1q-deficient mice. The increased IgG deposits and apoptotic cells in the glomeruli of C1q-deficient mice suggest that the exacerbation of disease may be due to a defect in the clearance of immune complexes and/or apoptotic cells from their kidneys.

Case study on chronic organophosphate poisoning.

Ernest and Leslie Rea, two farmers in their mid-fifties, contacted their local County Agricultural Extension Office in Cape May, New Jersey, regarding health problems associated with their use of pesticides. They were referred to Dr. Hamilton and the Environmental and Occupational Health Sciences Institute (EOHSI) clinic for consultation and evaluations. They were diagnosed with chronic intoxication of organophosphate pesticides. Recommendations were made to decrease health risks in the farming operations. These included the usage of personal protective equipment while handling or applying pesticides, transportation of pesticides in a separate trailer behind the farm truck, and construction of separate storage areas for herbicides, insecticides and fungicides. A separate wash site was also constructed for use at the end of the work day. Compliance with these strategies resulted in improvements in health for both farmers.

Associations of polycyclic organic matter in outdoor air with decreased birth weight: a pilot cross-sectional analysis.

The association between births that are small for gestational age and outdoor airborne polycyclic organic matter (POM) was examined in New Jersey, a highly urban state. This pilot study utilizes a cross-sectional investigation combining maternal and pregnancy outcome information from birth certificates with air toxics data from the U.S. Environmental Protection Agency Cumulative Exposure Project and census data at the census tract level. The exposure categories were based on tertiles of modeled average POM concentrations for each census tract in New Jersey. High POM exposure was positively associated with delivery of "small for gestational age" (SGA) births. After adjustment for potential individual-level confounding factors, the odds ratios for term, preterm, and all SGA were 1.22 (1.16-1.27), 1.26 (1.07-1.49), and 1.22 (1.17-1.27), respectively, for the highest exposure tertile in the urban population of the state (89% of the state's birth population). For group-level variables, the corresponding ORs were 1.12 (1.07-1.18), 1.23 (1.02-1.47), and 1.13 (1.07-1.18). The results of this study suggest that residential exposure to airborne polycyclic organic matter (POM) is associated with increased prevalence of "small for gestational age" births among urban population. Cross-sectional investigations combining air dispersion models with routinely collected population-based health and census data could be a useful approach for identifying the hazardous air pollutants of greatest public health concern.

Microbiological contamination of compressed air used in dentistry: an investigation.

The purpose of this preliminary investigation was twofold: 1) to examine the possibility of cross-contamination between a dental-evacuation system and the compressed air used in dental operatories and 2) to capture and identify the most common microflora in the compressed-air supply. The investigation used swab, water, and air sampling that was designed to track microorganisms from the evacuation system, through the air of the mechanical room, into the compressed-air system, and back to the patient. Samples taken in the vacuum system, the air space in the mechanical room, and the compressed-air storage tank had significantly higher total concentrations of bacteria than the outside air sampled. Samples of the compressed air returning to the operatory were found to match the outside air sample in total bacteria. It was concluded that the air dryer may have played a significant role in the elimination of microorganisms from the dental compressed-air supply.

Size characteristics of larger academic human environmental health programs in the United States.

We have performed a benchmark exercise evaluating larger academic programs in human environmental health sciences. These programs are located at schools of public health and at other institutions that have NIEHS Centers of Excellence. The largest programs were those in which there was both an NIEHS center and a public health graduate education program. This suggests that there is synergy between environmental health sciences research and involvement in public and community health.

Atheroembolic disease.

Atheroembolism is becoming an increasingly common cause of renal failure in people with widespread atheromatous disease. It remains a diagnosis that is often missed, or made only at postmortem. An awareness of risk factors and a high index of suspicion will allow it to be recognized more often.

Systemic lupus erythematosus and acute demyelinating polyneuropathy.

Guillain-Barré syndrome has been described only rarely in patients with SLE. In this Grand Round we describe a 33-yr-old patient who presented with features of central nervous system lupus, thrombocytopenia, and a severe haemolytic anaemia. Within a few days of her admission, following the commencement of steroid therapy, and a grand mal seizure, the patient developed paralysis of her lower limbs, due to an acute demyelinating polyneuropathy, and subsequently a retinal vasculitis. We discuss the epidemiological and possible immunopathological links between SLE and Guillain-Barré syndrome, and possible treatment strategies.

Disbudding of red deer stag calves to prevent antler growth.

Red deer stag calves aged five to seven months were disbudded with a standard cattle disbudding iron as a means of preventing antler growth and development. Two sizes of iron, one 2.2 cm in diameter and one 1.5 cm in diameter, were compared at disbudding in November or January. Disbudding in November and January with the 2.2 cm iron had success rates of 97 per cent and 92 per cent, respectively. Treatment with the 1.5 cm iron was less effective at both times. There was no significant difference between the liveweights of the treated groups and a non-disbudded control group at turnout in the spring or at slaughter in November when the stags were 16 months of age.

Inappropriate use of antibiotics in croup at three types of hospital.

Despite recent suggestions that bacterial infection is an increasingly important cause of serious croup, most authorities still consider croup a viral disease in which antibiotic therapy is unnecessary. To assess the frequency of antibiotic use in croup among children in hospital, we reviewed the records at three types of hospital in Ontario. Children with evidence of a concurrent infection that might be bacterial were considered to have received antibiotics appropriately. Whereas only 6% of cases at a university-affiliated children's hospital were inappropriately treated with antibiotics, the proportions at a small rural community hospital staffed by general practitioners and a general hospital staffed by both pediatricians and general practitioners in a medium-sized city were 63% and 38%. Possible reasons for these differences are discussed.