The efficacy of pulsed ultraviolet light processing for table and hatching eggs.

In the United States, every year an average of 287.1 eggs are consumed per person, and over 14.1 billion eggs are set in hatchery incubators to produce chicks destined for the egg and meat bird industries. By reducing the microbial load on eggs, food-borne-associated outbreaks can be reduced while good chick health is maintained. Pulsed ultraviolet (PUV) light system delivers an energy-intense broad spectrum (100-1,100 nm) pulse derived from a xenon flashlamp. In recent years, PUV light has been shown to reduce microbial pathogens on the surface of shell eggs by using a static PUV light system. In this study, shell eggs were surface inoculated with Escherichia coli or Enterococcus faecium and treated with PUV light using a modified egg candling conveyor that provided complete rotation of eggs under a flashlamp. Pulsed UV light treatment inactivated both microbial strains, with greater energy resulting in a greater germicidal response (P < 0.05). Treatments of 1.0, 2.4, 3.1, and 4.9 J/cm2 resulted in microbial reductions (Log10 CFU/cm2) of 3.83, 4.26, 4.28, and 4.62 for E. coli and 2.04, 3.12, 3.11, and 3.82 for E. faecium, respectively. This study also evaluated the effects of PUV light treatment of hatching eggs (commercial Leghorn hybrids) on both embryo and chick growth parameters. Using the same system, 4 replicates of 125 fertile eggs per rep were treated with 0 (control), 4.9, 24.4, or 48.8 J/cm2 of PUV light. After processing, eggs were placed in a commercial incubator under normal incubation conditions. There was no significant effect of the PUV light treatment on percent fertility, hatchability, or hatch (P > 0.05). Furthermore, there were no significant effects on posthatch observations, including livability and average bird weight at hatch or at 42 d of age (P > 0.05). In conclusion, this study supports the application of PUV light as an effective antimicrobial intervention for both table and hatching eggs.

Treatment for life for severe haemophilia A- A cost-utility model for prophylaxis vs. on-demand treatment.

Prophylaxis has been established as the treatment of choice in children with haemophilia and its continuation into the adult years has been shown to decrease morbidity throughout life. The cost of factor therapy has made the option questionable in cost-effectiveness studies. The role of prophylaxis in pharmacokinetic dosage and tolerization against inhibitor formation were used to model the cost utility of prophylaxis vs. on-demand (OD) therapy over a lifetime horizon in severe haemophilia A. The model was applied to a single provider national health system exemplified by the United Kingdom's National Health Service and a third party provider in the United States. The incremental cost-effectiveness ratio (ICER) was estimated and compared to threshold values used by payer agencies to guide reimbursement decisions. A cost per quality-adjusted life year (QALY) was also estimated for Sweden. Prophylaxis was dominant over OD treatment in the UK. The model resulted in an ICER - $68 000 - within the range of treatments reimbursed in the USA. In Sweden, a cost/QALY of SEK 1.1 million was also within the range of reimbursed treatments in that country. Dosage- and treatment-induced inhibitor incidence were the most important variables in the model. Subject to continuing clinical evidence of the effectiveness of pharmacokinetic dosage and the role of prophylaxis in decreasing inhibitor incidence, treatment for life with prophylaxis is a cost-effective therapy, using current criteria for the reimbursement of health care technologies in a number of countries.

Health technology assessment and haemophilia.

Although the funding of rare diseases such as haemophilia in developing countries remains a low priority, pressures on the funding of haemophilia treatment are also emerging in developed economies affected by the global economic downturn and the other demands on health care budgets. This is leading advisory bodies and payers alike to explore the tools of Health Technology Assessment (HTAs) in deriving recommendations for reimbursement policies. In particular, the use of cost utility analysis (CUA) in deriving costs per quality adjusted life year (QALY) for different interventions is being used to rank interventions in order of priorities relative to a threshold cost per QALY. In these exercises, rare chronic disorders such as haemophilia emerge as particularly unattractive propositions for reimbursement, as the accepted methodology of deriving a CUA. For e.g. the use of prophylaxis in haemophilia leads to a range of costs/QALY which exceed the willingness to pay thresholds of most payers. In this commentary, we review the principles utilized in a recent systematic review of the use of haemophilia products carried out in Sweden as part of an HTA. We suggest that ranking haemophilia related interventions with the standard interventions of therapeutics and public health in CUA comparisons is inappropriate. Given that haemophilia treatment is a form of blood replacement therapy, we propose that such comparisons should be made with the interventions of mainstream blood transfusion. We suggest that unequivocally effective treatments such as haemophilia therapies should be assessed differently from mainstream interventions, that new methodologies are required for these kinds of diseases and that evidence of a societal willingness to support people with rare disorders needs to be recognized when reimbursement policies are developed.

Setting up and modelling of overflowing fed-batch cultures of Bacillus subtilis for the production and continuous removal of lipopeptides.

This work is related to the set-up of overflowing exponential fed-batch cultures (O-EFBC) derived from carbon limited EFBC dedicated to the production of mycosubtilin, an antifungal lipopeptide belonging to the iturin family. O-EFBC permits the continuous removal of the product from the bioreactor achieving a complete extraction of mycosubtilin. This paper also provides a dynamical Monod-based growth model of this process that is accurate enough to simulate the evolution of the specific growth rate and to correlate it to the mycosubtilin specific productivity. Two particular and dependant phenomena related to the foam overflow are taken into account by the model: the outgoing flow rate of a broth volume and the loss of biomass. Interestingly, the biomass concentration in the foam was found to be lower than the biomass concentration in the bioreactor relating this process to a recycling one. Parameters of this model are the growth yield on substrate and the maximal specific growth rate estimated from experiments led at feed rates of 0.062, 0.071 and 0.086h(-1). The model was extrapolated to five additional experiments carried out at feed rates of 0.008, 0.022, 0.040, 0.042 and 0.062h(-1) enabling the correlation of the mean specific growth rates with productivity results. Finally, a feed rate of 0.086h(-1) corresponding to a mean specific growth rate of 0.070h(-1) allowed a specific productivity of 1.27mg of mycosubtiling(-1) of dried biomassh(-1).

Real time in situ microscopy for animal cell-concentration monitoring during high density culture in bioreactor.

An in situ microscope (ISM) device is utilised in this study to monitor hybridoma cells concentration in a stirred bioreactor. It generates images by using pulsed illumination of the liquid broth synchronised with the camera frame generation to avoid blur from the cell's motion. An appropriate image processing isolates the sharp objects from the blurred ones that are far from the focal plane. As image processing involves several parameters, this paper focuses on the robustness of the results of the cells counting. This stage determines the applicability of the measuring device and has seldom been tackled in the presentations of ISM devices. Calibration is secondly performed for assessing the cell-concentration from the cell automated numeration provided by the ISM. Flow cytometry and hemacytometer chamber were used as reference analytical methods. These measures and the output of the image processing allow estimating a single calibration parameter: the reference volume per image equal to 1.08 x 10(-6) mL. In these conditions, the correlation coefficient between both reference and ISM data sets becomes equal to 0.99. A saturation of this system during an ultrasonic wave perfusion phase that deeply changes the culture conditions is observed and discussed. Principal component analysis (PCA) is used to undergo the robustness study and the ISM calibration step.

From zero to one hundred million in six months: the treatment of azoospermia in congenital adrenal hyperplasia.

In the majority of the 25% of couples in which a male factor is responsible for their infertility, no identifiable pathology is found. It is unusual to be faced with an etiology that is readily amenable to successful treatment without the eventual dependence on assisted reproductive techniques for pregnancy. The diagnosis of congenital adrenal hyperplasia has variable implications on fertility. A case is presented of azoospermia in a man diagnosed with classical non-salt-losing congenital adrenal hyperplasia. Within 9 months of treatment with dexamethasone, his sperm count had risen to above 100 million per milliliter, enough to overcome very poor morphology and a naturally conceived pregnancy ensued. The pregnancy is ongoing. Although an increase in sperm count has been shown in such cases, the degree of improvement in semen parameters is unique, especially in an azoospermic patient.

Cardiac illustrations.

Pictures of congenital heart lesions are very useful for patient and parent understanding of underlying problems, and the actual physical mechanics of treatment/s, both past and proposed. In this article, we have produced scanned pictures by Heartline from their book 'Heart Children'. We have also added some new graphics that depict heart lesions not originally in this book, and in addition, some postoperative situations. Heartline.

Retinal blood flow changes during pregnancy in women with diabetes.

PURPOSE: To study retinal blood flow (RBF) during pregnancy in subjects with and without diabetes and to relate the changes to progression in diabetic retinopathy. METHODS: RBF in a major temporal retinal vein was measured, where possible, during all three trimesters (T1 to T3) and the postpartum period (PP) using laser Doppler velocimetry (measuring velocity [V]) and monochromatic fundus photographs (measuring diameter [D]). RESULTS: In the subjects without diabetes (n = 19), no significant change in RBF was demonstrated. V was significantly greater in T3 than in PP (P = 0.01). D was significantly smaller in T1 to T3 than in PP (P < or = 0.01). RBF in the subjects with diabetes was significantly higher in T2 and T3 than in PP (P < 0.05). V increased from T1 to T2 (P = 0.04) and decreased from T2 to PP (P = 0.001) and from T3 to PP (P = 0.002). The only significant change in D was a smaller value in T1 than in PP (P = 0.003). However, it was only those subjects whose DR progressed (n = 11) who had a significant increase in RBF during pregnancy (P = 0.0001). CONCLUSIONS: These data suggest that the hyperdynamic circulation present in pregnancy led to compensatory retinal vessel constriction (autoregulation) in the group without diabetes; this was largely absent in the patients with diabetes, with resultant increase in retinal blood flow associated with worsening retinopathy. This finding lends further support to the hypothesis that increased retinal blood flow is a pathogenic mechanism for diabetic retinopathy.

Bilateral adrenal infarction, hypoadrenalism and splinter haemorrhages in the 'primary' antiphospholipid syndrome.

We describe a patient with a 3-year history of recurrent deep vein thromboses (DVT) of the lower limbs, who developed adrenal insufficiency following withdrawal of warfarin therapy. Multiple splinter haemorrhages of the nail beds were evident, simultaneous with the development of adrenal infarction in the absence of infective endocarditis. CT scans of the adrenal glands were consistent with bilateral adrenal infarctions. The patient had persistently high titres of IgG anticardiolipin antibodies (aCL) over the previous 4 years in the absence of antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA) or extractable nuclear antigens (ENA). Thrombocytopenia and an intermittently positive Coombs' test had been noted. Previous episodes of DVT were associated with inadequate warfarin control and a period of warfarin resistance. He conforms to a diagnosis of a 'primary' antiphospholipid syndrome.

Herbal medicine as a cause of combined lead and arsenic poisoning.

1. Combined chronic lead and arsenic poisoning was diagnosed in a 33-year-old Korean woman following consumption of a Korean herbal medicine prescribed for haemorrhoids. 2. The patient had malaise, severe difficulty walking, arthralgia, oedema and abdominal pain with diarrhoea. 3. Investigation showed anaemia with basophilic stippling, fragmentation and a raised reticulocyte count. 4. Raised blood and urine lead levels and urine arsenic levels were found. 5. Analysis of the herbal medicine revealed a high lead and arsenic content. 6. Treatment with the newer chelating agent 2,3-dimercaptosuccinic acid was successful, with no detectable side-effects.

Thyroid function tests in amyloid goitre.

We present two patients with amyloid goitre due to primary systemic amyloidosis which was confirmed at post-mortem. Both were clinically euthyroid but had hyperthyroxinaemia and other thyroid function tests suggestive of thyrotoxicosis.