20†Simultaneous development of acute acquired concomitant esotropia in two siblings during the COVID-19 pandemic: a case report.

A 5-year-old boy (sibling one) and his 11-year-old sister (sibling two) were presented to the hospital eye service in early 2021, having both developed acute-onset large angle esotropia within three months of each other. Neither had any significant past medical, ophthalmic, or family history. The siblings lived in the same household, and both experienced lifestyle changes as a result of the UK lockdown in response to COVID-19.Sibling one had a moderate right esotropia, initially maintained straight by corneal light reflex. He measured 45/50 prism dioptres (Δ) base out at near and 45Δ base out at distance. Sibling two had esophoria which broke down into a right esotropia immediately on dissociation. The esotropia measured 30Δ base out at near and 20Δ base out at distance. At four month follow up, both siblings demonstrated a constant large angle esotropia (sibling one: 54Δ base out at near and 45Δ base out at distance, sibling two: 45Δ base out at near and 40/45Δ base out at distance).Each sibling was treated with right medial rectus recession (5.5 mm) and right lateral rectus resection (7 mm), and at a three-month follow-up, both were minimally esophoric with restored binocularity.The unusual and abrupt changes in lifestyle imposed by the COVID-19 pandemic highlight the likelihood of an environmental aetiology for some forms of esotropia and raise the possibility that extended screen time may be a contributory factor.

Determining health-related quality of life and health state utility values of recurrent urinary tract infections in women.

INTRODUCTION AND HYPOTHESIS: Health state utility values estimate an individual's valuation of their health-related quality of life. Despite prevalence of recurrent urinary tract infections (rUTIs), the health state utility value of rUTIs is unknown. The primary aim was to determine the utility value of rUTIs using the standard gamble (SG). The secondary aim was to compare the SG utility value with that derived from the EuroQol 5 dimensions (EQ-5D) and visual analog scale (VAS). We hypothesized that a utility value would be successfully derived from the SG and would differ from that derived using the EQ-5D and VAS. METHODS: Nonpregnant, adult English-speaking female patients with a diagnosis of rUTI were recruited and completed the EQ-5D, VAS, and SG (n = 25). Utility values were evaluated using Wilcoxon signed-rank tests and Spearman's rho correlation. RESULTS: Health state utility values varied depending on the assessment tool used: EQ-5D 0.76 (IQR 0.52), VAS 0.70 (IQR 0.30), and SG 0.85 (IQR 0.25). There were differences between VAS and the other two assessment methods (p<0.001), as well as between EQ-5D and SG (p=0.013). Spearman correlation demonstrated a moderately positive correlation between EQ-5D and VAS values (r(25) = 0.59, p=0.0019). CONCLUSIONS: Our data suggest that 0.85 reflects the true health state utility value of rUTIs among nonpregnant adult English-speaking women. The utility value for recurrent UTIs is worse (lower) than that previously published for nonrecurrent UTIs, reflecting the ability of the SG to convey the compounding impact of recurrent disease. In this study, neither the EQ-5D nor the VAS produced results consistent with those found using the SG, which suggests limited validity in this population.

A case of incidental endometrial adenocarcinoma diagnosed in early pregnancy and managed conservatively.

We report a 29-year old nulliparous woman diagnosed with a grade 1 endometrioid adenocarcinoma of the endometrium arising from an atypical polypoid adenomyoma, while being investigated for a suspected threatened miscarriage at 7 weeks gestation. She presented complaining of vaginal bleeding and a small amount of soft tissue in the cervical os was found and sent for histology. An ultrasound scan was performed, which confirmed an intrauterine ongoing pregnancy. The patient had no further episodes of unscheduled bleeding. After the confirmed histological diagnosis an MRI scan was requested, and there were no evidence of myometrial invasion or distant metastasis. The patient was seen at each trimester, remained asymptomatic throughout the pregnancy and had a normal delivery at term. There was no evidence of any residual endometrioid adenocarcinoma in the post-delivery specimen. Six weeks post-natally an endometrial biopsy was performed, which was normal. She is still in remission over a period of 8 years follow-up. Endometrial adenocarcinoma in young pregnant women is a rare clinical circumstance. This case shows that conservative management in young women is possible including in a case of an incidental diagnosis in pregnancy.

Less radical surgery for women with early stage cervical cancer: Our experience on radical vaginal trachelectomy and laparoscopic pelvic lymphadenectomy.

We report the use of radical vaginal trachelectomy (RVT) with pelvic laparoscopic lymphadenectomy (LPL) in patients with early stages cervical cancer (FIGO stage IA2-IB1). This is a case series prospectively collected over a 6-year period (2011-2017) at the Ipswich hospital, UK. Cases were compared to a group of women with a similar stage of cervical cancer, but treated with radical hysterectomy (RH) and pelvic lymphadenectomy (PL). A total of 19 patients (group 1) underwent RVT and LPL, and 51 (group 2) had RH and PL. We included: 5/19 (26%) stage IA2 and 14/19 (74%) stage IB1. Among those, we had: 12/19 (63%) cases of squamous cell carcinoma (SCC), 7/19(37%) of adenocarcinoma. Mean hospital stay was 2.7 days (range 2-4) in group 1 versus 4.8 days (range 3-8) group 2 (p-value = 0.173). The complication rate was not statistically different between the two groups 4/19(21%) and 7/51(14%) (p-value 0.169). The mean follow-up period was 47.3 months (range 7-78) in both groups. There were no cases of recurrence in group 1 and 2/51(4%) cases in group 2, but the difference was not significant (p-value = 0.497). In our experience RVT in well-selected patients is a safe treatment option with similar oncological outcomes when compared to patients undergoing more extensive surgery for the same early stage cervical cancer.

Water immobilization by glass microspheres affects biological activity.

We recently reported that the water holding capacity of myofibrillar protein hydrogels could be increased upon addition of small amounts of microparticles, particularly glass microspheres. Glass microspheres were found to decrease the spin-spin relaxation time (T2) of water protons in the gels, which was interpreted as enhanced water binding by the glass. We were thus interested in determining whether the observed effects on water proton relaxation were a direct consequence of water-glass interactions. Here we show how glass microspheres reduce the mobility of pure water, reflected in large decreases in the T2 of water protons, decreases in the self-diffusion coefficient of water molecules, a lower water activity, and strengthening of O-H bonds. Even though glass is considered an inert material, glass microspheres were shown to inhibit the growth of human embryonic kidney cells, and stimulate or inhibit the growth of leukemia and monocytic lymphoma cells in vitro, depending on dose and time. The germination of alfalfa seeds and the growth of E.coli cells were also inhibited upon exposure to glass microspheres. This work indicates that the properties and behavior of materials, even ones considered inert, can be affected by their size. These observations suggest possible toxicological consequences of exposure to microparticles, but also open us possibilities to affect cellular/organism function via modulation of macromolecular hydration.

Anterior approach white line advancement: technique and long-term outcomes in the correction of blepharoptosis.

PurposeAnterior approach white line advancement presents a novel surgical option for correction of blepharoptosis. The technique draws on several advantages of other approaches. The aim of this study was to present outcomes using this technique at a minimum follow-up of 18 months.Patients and methodsParticipants having undergone anterior approach white line advancement ptosis correction at a single institution were retrospectively recruited at a minimum of 18 months' follow-up. A total of 18 independent eyelid measurements were recorded at final review. Outcomes included long-term rate of surgical success, upper eyelid margin-reflex distance (MRD1) at both early and late post-operative follow-up, inter-eyelid asymmetry, complications, re-operation rate, patient satisfaction, and quality-of-life improvement using the Glasgow Benefit Inventory (GBI). Pre- and post-operative MRD1, as well as inter-eyelid asymmetry, were compared using a two-tailed t-test.ResultsIn total, 82 eyelids of 47 participants were included with a mean follow-up of 2.3 years (range 1.5-3.7). Surgical success was achieved in 91.5%, with a final mean MRD1 of 3.5 mm (95% confidence 3.2-3.7). An increase of 2.4 mm (2.1-2.8) in eyelid height was observed between baseline and long-term follow-up (P<0.0001). No significant change was observed between early and late post-operative follow-up. Pre-operative asymmetry was reduced from 1.0 mm (0.7-1.3) to 0.4 mm (0.3-0.5; P<0.0001). Patient satisfaction was 95.7% with a mean GBI score of +21.8 (13.2-30.3).ConclusionsAnterior approach white line advancement presents an excellent option for patients undergoing ptosis correction with favourable long-term results. Comparisons are made with other techniques with respect to anatomical, functional, and surgical factors.

Farm characteristics and farmer perceptions associated with bovine tuberculosis incidents in areas of emerging endemic spread.

While much is known about the risk factors for bovine tuberculosis (bTB) in herds located in high incidence areas, the drivers of bTB spread in areas of emerging endemicity are less well established. Epidemiological analysis and intensive social research identified natural and social risk factors that may prevent or encourage the spread of disease. These were investigated using a case-control study design to survey farmers in areas defined as recently having become endemic for bTB (from or after 2006). Telephone surveys were conducted for 113 farms with a recent history of a bTB incident where their officially tuberculosis free status had been withdrawn (OTFW) (cases) and 224 controls with no history of a bTB incident, matched on location, production type and the rate of endemic bTB spread. Farmers were questioned about a range of farm management strategies, farm characteristics, herd health, wildlife and biosecurity measures with a focus on farmer attitudes and behaviours such as farmers' perception of endemicity and feelings of control, openness and social cohesion. Data generated in the telephone surveys was supplemented with existing herd-level data and analysed using conditional logistic regression. Overall, herd size (OR 1.07), purchasing an animal at a cattle market compared to purchasing outside of markets (OR 2.6), the number of contiguous bTB incidents (2.30) and the number of inconclusive reactors detected in the 2 years prior to the case incident (OR 1.95) significantly increased the odds of a bTB incident. Beef herds using a field parcel more than 3.2km away from the main farm and dairy herds reporting Johne's disease in the previous 12 months were 3.0 and 4.7 times more likely to have a recent history of a bTB incident, respectively. Beef herds reporting maize growing near, but not on, their farm were less likely to be case herds. Operating a closed farm in the two years prior to the case breakdown did not reduce the odds of a bTB incident. Farmers that had recently experienced a bTB incident were more likely to have implemented badger biosecurity in the previous year, but no more likely than control farms to have implemented cattle biosecurity. Case farmers felt significantly less likely to be influenced by government, vets or other farmers compared to those with no history of bTB. This suggests that alternative methods of engaging with farmers who have recently had a breakdown may need to be developed.

Farming on the edge: farmer attitudes to bovine tuberculosis in newly endemic areas.

Defra's recent strategy to eradicate bovine tuberculosis (bTB) establishes three spatial zones: high-risk areas (HRAs) and low-risk areas, and an area referred to as 'the edge', which marks the areas where infection is spreading outwards from the HRA. Little is known about farmers in the edge area, their attitudes towards bTB and their farming practices. This paper examines farmers' practices and attitudes towards bTB in standardised epidemiologically defined areas. A survey was developed to collect data on farmer attitudes, behaviours, practices and environmental conditions as part of an interdisciplinary analysis of bTB risk factors. Survey items were developed from a literature review and focus groups with vets and farmers in different locations within the edge area. A case-control sampling framework was adopted with farms sampled from areas identified as recently endemic for bTB. 347 farmers participated in the survey including 117 with bTB, representing a 70per cent response rate. Results show that farmers believe they are unable to do anything about bTB but are keen for the government intervention to help control the spread of bTB.

A novel approach to mapping and calculating the rate of spread of endemic bovine tuberculosis in England and Wales.

A mathematical method for estimating the endemic status of bovine tuberculosis (bTB) in cattle in England and Wales has been developed. 6.25km(2) hexagonal cells were used as the base resolution. Maps were produced for overlapping two-year periods spanning 2001/03 to 2009/11. Distance from a farm to the ten nearest 'Officially Tuberculosis Free status - Withdrawn' incidents within the same time period was measured. Endemic areas were defined as those hexagons containing farms where the 3rd nearest incident occurred within 7km. Temporal spread of endemic bTB was estimated by creating a contour map displaying the spread of endemic bTB over the two-year periods, and using boundary displacement to calculate the rate of spread across each hexagon. A rate was obtained for ∼2300 cells and varied between 0.04km and 15.9km per year (median=3.3km per year). This work will enable further analysis of the factors associated with this expansion.

Method transfer, partial validation, and cross validation: recommendations for best practices and harmonization from the global bioanalysis consortium harmonization team.

This paper presents the recommendations of the Global Bioanalytical Consortium Harmonization Team on method transfer, partial validation, and cross validation. These aspects of bioanalytical method validation, while important, have received little detailed attention in recent years. The team has attempted to define, separate, and describe these related activities, and present practical guidance in how to apply these techniques.

Review of laboratory submissions from New World camelids in England and Wales (2000-2011).

Sample submissions to the Animal Health and Veterinary Laboratories Agency's (AHVLA's) diagnostic laboratory network in England and Wales were reviewed for diseases affecting New World camelids (NWCs). In the years 2000-2011, 6757 submissions were analysed, including 5154/6757 (76.3%) for diagnosing a disease problem and 1603/6757 (23.7%) for monitoring (no clinical disease). Wasting (weight loss, ill-thrift) was the most commonly reported clinical sign across all age groups. A diagnosis was reached for 1765/5154 (34.2%) diagnostic submissions. The proportion of submissions with diagnoses was higher for carcasses than non-carcass samples and multiple diagnoses were more likely to be reached from carcasses. Parasitic diseases were collectively the most common problem, including parasitic gastroenteritis (319/1765, 18.2%), coccidiosis (187/1765, 10.6%), fascioliasis (151/1765, 8.6%), ectoparasitic infestations (86/1765, 4.9%) and cryptosporidiosis (24/1765, 1.4%). The most frequently diagnosed non-parasitic problems included nutritional diseases (182/1765, 10.3%), septicaemia (104/1765, 5.9%, including 45 cases of colisepticaemia), gastric ulceration (79/1765, 4.5%), tumours/neoplastic diseases (65/1765, 3.7%), tuberculosis (57/1765, 3.2%), clostridial diseases (44/1765, 2.5%), congenital anomalies (41/1765, 2.3%), peritonitis (39/1765, 2.2%) and Johne's disease (20/1765, 1.1%).

Role of endoplasmic reticulum stress induction by the plant toxin, persin, in overcoming resistance to the apoptotic effects of tamoxifen in human breast cancer cells.

BACKGROUND: Persin is a plant toxin that displays synergistic cytotoxicity with tamoxifen in human breast cancer cell lines. Here, we examined the ability of persin to circumvent tamoxifen resistance and delineated the intracellular signalling pathways involved. METHODS: The induction of apoptosis in tamoxifen-resistant and -sensitive breast cancer cells was measured by flow cytometry following treatment with persin±tamoxifen. Markers of endoplasmic reticulum stress (ERS) were analysed following treatment, and their causal role in mediating persin-induced apoptosis was determined using chemical inhibitors and RNA interference. RESULTS: Cells that were resistant to an apoptotic concentration of tamoxifen maintained an apoptotic response to persin. Persin-induced apoptosis was associated with an increase in markers of ERS, that is, CHOP expression and XBP-1 splicing and was decreased by CHOP siRNA. The CASP-4 inhibitor Z-YVAD-FMK markedly inhibited persin-induced apoptosis in both tamoxifen-sensitive and -resistant cells. CONCLUSION: The cytotoxic effects of persin are CASP-4 dependent and mediated by CHOP-dependent and -independent ERS signalling cascades. Increased ERS signalling contributes to persin-induced reversal of tamoxifen resistance.

Evaluation of methods for measuring coverage and representativeness of an early-warning disease surveillance system.

Early-warning surveillance provides an essential component of the evidence required to protect animal health. Assessing the proportion of the population included in surveillance systems (coverage) provides a measure of the effectiveness of early-warning surveillance, and contributes to ensuring that these systems are efficient. This paper describes an investigation of methods used for assessing the coverage and representativeness of the 'FarmFile' early-warning surveillance system. This system uses information collected with samples submitted to diagnostic laboratories by private veterinary practitioners in England and Wales. Available data on pig holdings and veterinary practices in four English counties, selected to represent a range of diverse population characteristics, were supplemented using surveys of veterinary practices. Coverage assessments were based on submissions made to FarmFile in 2009. The proportion of holdings covered varied from 5-62 per cent in Devon and Cumbria, and 16-97 per cent in Norfolk and East Riding of Yorkshire. The results suggest that while the proportion of individual pigs covered by the current early-warning surveillance system is high, small and breeding-only holdings in some regions may be poorly covered. Coverage assessments vary depending on the methods used for their assessment, and multiple assessment methods can provide a 'range' within which coverage lies.

London 2012: prescribing for athletes in ophthalmology.

AIMS: Prescribing for athletes requires an up-to-date knowledge of the World Anti-Doping Agency's list of prohibited substances. As the London 2012 Olympic Games attract athletes from around the world, we review the current guidelines with respect to all medications licensed for ophthalmic use in the United Kingdom. We describe the process that an ophthalmologist can use to check for permissible medications and also highlight treatments that are contraindicated. METHODS: We systematically reviewed all 77 drugs listed in Section 11 of the British National Formulary (Issue 63) for use in the treatment of ophthalmic conditions, and referenced these against the 2012 Prohibited List published by the World Anti-Doping Agency. RESULTS: The majority of ophthalmic preparations are suitable for use in- and out-of-competition. Some preparations, such as glucocorticoids, are prohibited when administered systemically but permitted for topical administration. Beta-blockers are prohibited in-competition and oral carbonic anhydrase inhibitors are prohibited in- and out-of competition. CONCLUSION: The 2012 Prohibited List has important implications for the pharmacological treatment of ophthalmic conditions in athletes. Clinicians prescribing for athletes have a duty to familiarize themselves with the list in order to avoid causing significant damage to their patient's career and reputation.

"These boots were made for walking": the isotopic analysis of a C(4) Roman inhumation from Gravesend, Kent, UK.

As part of the road widening scheme between London and Dover, Oxford Archaeology South uncovered a large boundary ditch of Iron Age origin that contained Iron Age and Roman inhumations, adjacent to which was a small mid-late Roman cemetery, interpreted as a rural cemetery for Romano-British farmers. Grave goods in the cemetery were restricted to a few individuals with hobnailed boots. Bulk bone collagen isotopic analysis of 11 skeletons of Iron Age and Roman date gave a typical C(3) terrestrial signal (average δ(13) C = -19.8‰, δ(15) N = 9.3‰), but also revealed one (SK12671) with a diet which included a substantial C(4) component (δ(13) C = -15.2‰, δ(15) N = 11.2‰). This is only the second such diet reported in Roman Britain. Subsequent δ(18) O(c) and (87) Sr/(86) Sr measurements on the dental enamel in this individual were, however, consistent with a "local" origin, indicating that either C(4) protein was consumed in Late Roman Britain, or that he came from somewhere else, but where conditions gave rise to similar isotopic values. If we accept the latter, then it indicates that using oxygen and strontium isotopes alone to identify "incomers" may be problematic. The provision of hobnailed boots for the dead appears to have had a strong symbolic element in Late Roman Britain. We suggest that in this case the boots may be significant, in that he was being equipped for the long march home.

Chromosome microarray analysis in a clinical environment: new perspective and new challenge.

The analysis of the human genome has largely been undertaken in a research environment, but recent developments in technology and associated workflow have allowed diagnostic laboratories to interrogate DNA at significantly improved levels of resolution. Principally, whole genome-based analysis of copy number changes using microarrays has led to this method replacing conventional karyotyping as a routine diagnostic workhorse. The resolution offered by microarrays is an improvement of at least an order of magnitude compared to karyotyping, but it comes at a cost in terms of the time spent in data interpretation. Overall, however, the die has been cast and cytogeneticists need to become familiar with the tools use by molecular geneticists and bioinformaticists. The following review provides a brief background to array technology, but uses a series of case studies to illustrate the usefulness and challenges of interpreting array data.

Factors affecting cytotrophoblast cell viability and differentiation: Evidence of a link between syncytialisation and apoptosis.

A relationship between cytotrophoblast differentiation (syncytialisation) and apoptosis is hypothesised to exist, but has not been clearly determined. To address this, we explored the effects of cAMP, an inducer of syncytialisation, on human choriocarcinoma cell differentiation and viability under three different culture conditions related to diverse survival status: no serum, 10% fetal calf serum or 10% charcoal-stripped fetal calf serum. 8-Br-cAMP increased BeWo cell viability in culture media without serum, but viability was decreased in a dose- and time-dependent manner when serum was present. The appearance of apoptotic nuclei fragments were only observed when BeWo cells were cultured in media containing serum combined with 8-Br-cAMP treatment. In addition, the ratio of FasL to Fas expression following treatment with 8-Br-cAMP increased by 20-fold in 10% charcoal-stripped fetal calf serum media and 65-fold 10% fetal calf serum media, and activation of caspase-3 also required media with serum. The markers of syncytialisation (syncytin 1 expression and human chorionic gonadotropin secretion) were induced significantly by 8-Br-cAMP, and were higher in 10% fetal calf serum media than in 10% charcoal-stripped fetal calf serum media, than in the absence of serum. Syncytia formation was stimulated by 8-Br-cAMP and this required serum in the media. We now show that factors contained within serum are necessary for cAMP-stimulated cytotrophoblast differentiation, that syncytialisation involves apoptotic events, and that a lack of serum based factors could switch the cellular program away from differentiation.

Citrullinemia type I: molecular screening of the ASS1 gene by exonic sequencing and targeted mutation analysis.

We developed a mutation-screening protocol for the ASS1 gene in order to guide clinical management of neonates with elevated citrulline detected during routine newborn screening. An exon-based amplification and sequencing method was designed and successfully applied to patients to identify disease-associated mutations. The sequencing-based method was applied to three patients with mild or asymptomatic clinical courses. Identification of a homozygous mutation in these patients, c.787G>A (p.Val263Met), led to the development of a tetra-primer ARMS-PCR method that successfully detected the mutation in DNA extracted from blood or from Guthrie card spots.

ONCOPOOL - a European database for 16,944 cases of breast cancer.

ONCOPOOL is a retrospectively compiled database of primary operable invasive breast cancers treated in the 1990s in 10 European breast cancer Units. Sixteen thousand and nine hundred and forty four cases were entered, with tumours less than 5 cm diameter in women aged 70 or less (mean age 55). DATA: Data were date of birth, mode of diagnosis, pathology (size, lymph node status, grade, type, lympho-vascular invasion and hormone receptor) and therapies and outcome measures: first local, regional or distant recurrences, contralateral primary, date and cause of death. TUMOUR CHARACTERISTICS: Mean diameter 1.8 cm, 66% lymph node negative, 24% 1-3 lymph nodes involved and 10% had 4 or more involved. Grade 1, 29%; Grade 2, 41%; and Grade 3, 30%. Polynomial relationships were established between grade, stage and size. Seventy-five percent were oestrogen receptor (ER) positive. ER closely related to grade. OUTCOMES: Overall Survival was 89% at 5 years from diagnosis, 80% 10 years and 73% 15 years; Breast Cancer-Specific survivals were 91%, 84% and 79%. Survival strongly related to the Nottingham Prognostic Index (NPI). Cases detected at screening had 84% 10-year survival, those presenting symptomatically 76%. ER positive cases treated with adjuvant hormone therapy had a reduction in risk of death of 13% over those not receiving adjuvant therapy (p=0.000). ER negative cases treated with chemotherapy showed a risk reduction of 23% over those not receiving chemotherapy (p=0.000).

Control of microbial contamination of Franz diffusion cell receptor phase in the development of transcutaneous breast cancer therapeutics.

AIMS: To determine the micro-organism contamination of excised porcine (pig) ear, and evaluate the use of Cyclopore track-etched membranes (CTEM) for preventing ingress into Franz-type diffusion cells. METHODS: Swabs were taken from four locations and used to inoculate Tryptone Soya Agar (TSA) and Sabouraud Dextrose Agar (SDA) plates. Diffusion cells were assembled to include porcine skin with and without CTEM, and the receptor phase sampled periodically and spread onto plates. RESULTS: Five distinct colony types were isolated after incubation of all swabs on TSA plates at 37 degrees C; on SDA plates, one fungal colony was found at 30 degrees C and one at 37 degrees C. The SDA agar plate incubated at 30 degrees C resulted in the growth of a large diffused white fungal colony. No regional differences were observed. Without the CTEM, the receptor phase became contaminated within 6 h. With the CTEM present, microbial ingress was substantially retarded with visible presumptive fungal growth occurring at 24 h and detectable contamination on both microbiological media at 48 h. CONCLUSIONS: As expected, the native porcine ears were considerably contaminated. The ingress of contamination into the diffusion cell receptor phases can be largely, but not entirely, eliminated using CTEM. The addition of antimicrobial agents was necessary to eliminate micro-organisms that were observed at later time points. SIGNIFICANCE AND IMPACT OF THE STUDY: This article, while highlighting the presence of a high number of micro-organisms on native porcine skin, presents a practical means to reduce the risk of microbial contamination in transdermal/transcutaneous permeation studies, particularly in the study of cell cultures grown within Franz diffusion cell receptor compartments.