Validation of a new in vitro Sun Protection Factor method to include a wide range of sunscreen product emulsion types.

In 2017, Cosmetics Europe performed a double-blinded ring test of 24 emulsion-type sunscreen products, across 3 in vivo test laboratories and 3 in vitro test laboratories, using a new candidate in vitro SPF test method. Based on the results of this work, an article was published showing how data derived from a new lead candidate method conform to new International Standards (ISO) acceptance criteria for alternative SPF test methods (Any alternative method should consider the matrix effect and if required, specify the matrix applicability of the method; Criterion 1a: Systematic differences between methods should be negligible: 95% of all individual results of an alternative method are within the range of ±2× reproducibility standard deviation of the in vivo method, that is overall bias must be below 0.5× reproducibility standard deviation of the in vivo method; Criterion 1b: Measurement uncertainty of an alternative method should be below the measurement uncertainty of the in vivo method. Candidate method predicted values must fall within the full 'funnel' (SPF 6-50+) limits proposed by Cosmetics Europe (derived from the same minimum test design, that is using the ISO24444 Method to measure at least 24 products across at least 3 laboratories using at least 5 test subjects/laboratory, in a blinded fashion).). Of the 24 sunscreen products tested, the majority of emulsions were of the oil-in-water (O/W) type, whereas only one was water-in-oil (W/O) and there were no products with a mineral-only sun filter system. In order to confirm the scope of this method, therefore, a new study was conducted that included 73 W/O (12 mineral + organic, 44 mineral only and 17 organic only) and 3 O/W mineral-only, emulsion-type sunscreen products (a total of 76 new sunscreen products). When combined with the previous 24 products (tested in 3 different laboratories), this yielded a new data set comprising a total of 100 emulsion-type sunscreen products, with SPF values ranging from 6 to 50+ (with a total of 148 data points). These products were tested using the double-plate in vitro SPF test method and compared with the ISO TC217/WG7 acceptance criteria for alternative SPF test methods. Over 95% of paired in vitro: in vivo SPF values lay within the upper and lower limits of the ISO acceptance criteria funnel, with no bias. This new in vitro SPF test method, therefore, meets the minimum requirements for an alternative SPF test method to ISO24444:2010, for emulsion-type sunscreen products (which make up the majority of marketed sunscreen products).

En 2017, Cosmetics Europe a réalisé un ring test en double aveugle de 24 produits de protection solaire de type émulsion, dans 3 laboratoires de test in vivo et 3 laboratoires de test in vitro, en utilisant une nouvelle méthode de test SPF in vitro. Sur la base des résultats de ces travaux, un article a été publié montrant comment les données dérivées de cette nouvelle méthode sont conformes aux nouveaux critères d'acceptation des normes internationales (ISO) pour les méthodes de test SPF alternatives. Sur les 24 produits de protection solaire testés, la majorité des émulsions étaient du type huile dans l'eau (H / E), tandis qu'un seul était de l'eau dans l'huile (E / H) et il n'y avait aucun produit contenant uniquement des minéraux. Afin de confirmer cette méthode, une nouvelle étude a donc été menée comprenant 73 produits E/ H (12 produits contenant des filtres minéraux + organiques, 44 produits contenant des filtres minéraux uniquement et 17 produits contenant des filtres organiques uniquement) et 3 produits H / E contenant des filtres minéraux uniquement, tous de type émulsion (donc un un total de 76 nouveaux produits de protection solaire). Combiné aux 24 produits précédents (testés dans 3 laboratoires différents), cela a donné un nouvel ensemble de données comprenant un total de 100 produits de protection solaire de type émulsion, avec des valeurs SPF allant de 6 à 50+ (avec un total de 148 points de données) . Ces produits ont été testés à l'aide de la méthode de test SPF in vitro double approche et comparés aux critères d'acceptation de l'ISO TC217 / WG7 pour les méthodes alternatives du SPF in vivo. Plus de 95% des valeurs de SPF appariées in vitro: in vivo se situent dans les limites supérieure et inférieure de l'entonnoir des critères d'acceptation ISO, sans biais. Cette nouvelle méthode de test SPF in vitro, par conséquent, répond aux exigences minimales d'une méthode de test SPF alternative à ISO24444: 2010, pour les produits de protection solaire de type émulsion (qui constituent la majorité des produits de protection solaire commercialisés).

Validation of an in vitro sun protection factor (SPF) method in blinded ring-testing.

OBJECTIVE: The objective of this work was to investigate the utility of a new in vitro SPF test method in blinded ring-testing, against new ISO acceptance criteria. METHODS: Twenty four blinded, commercial, emulsion-type, primary sunscreen products, covering the full range of labelled SPF in Europe (SPF6 - 50+), were tested by three test institutes using the current ISO24444:2010 In Vivo SPF Test Method and simultaneously by three separate test laboratories using a new candidate in vitro SPF test method, developed under the leadership of Cosmetics Europe (CE). The resulting relationship between in vitro SPF and in vivo SPF values was then compared with acceptance criteria developed recently by the International Standards (ISO) TC217/WG7 Sun Protection Test Methods Working Group. RESULTS: Analysis of the mean inter-laboratory in vitro and mean inter-institute in vivo SPF values revealed a strong correlation between in vitro and in vivo values, with a Pearson correlation coefficient of r2  = 0.88 (P < 0.0001), a slope of 1.01 and a non-significant intercept (-1.48; P = 0.62). When these data were compared to the new ISO WG7 acceptance criteria, method bias was found to be extremely low and over 95% of the coupled data lay within the model 'funnel' (defined by upper and lower confidence intervals). CONCLUSION: In conclusion, the results of blinded ring testing and comparison to new ISO WG7 acceptance criteria indicate that a new in vitro SPF test method meets (and exceeds) these minimum criteria and is an interesting candidate for possible deployment as an industry test methodology.

Cryosurgery of breast cancer.

OBJECTIVE: To determine the feasibility and efficacy of cryosurgery of breast cancer. DESIGN: In phase 1, carcinogen-induced mammary adenocarcinomas in 13 Sprague-Dawley rats were treated by cryosurgery and were then examined for histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50 DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor temperatures, and duration and number of freeze-thaw cycles on tumor viability. In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the breasts of 4 dogs and 4 sheep. These animals were followed up for procedure-related complications; the histopathologic necrosis of the cryolesions were correlated with the ultrasound images. Based on the results of these experiments, ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical trial. RESULTS: In phase 1, a single, short-term (< 7 minutes) freeze killed only tumors smaller than 1.5 cm in diameter, despite an apparent decrease to -40 degrees C at the periphery of each tumor. In phase 2, varying the peripheral tumor temperature to as low as -70 degrees C, using a single, short-term (< 7 minutes) freeze did not alter the results from phase 1. If the ice ball fully encompassed the tumor, however, maintaining it for at least 15 minutes achieved 100% tumor kill independent of tumor size. In phase 3, creation of a reproducible ultrasound-monitored cryolesion was facilitated when 2 freeze-thaw cycles were performed. No procedure-related complications were noted. In the human trial, 2 invasive lobular carcinomas from 1 patient were treated by cryosurgery and were negative for persistent tumor by core needle biopsy performed 4 and 12 weeks after a well-tolerated procedure. CONCLUSIONS: In situ breast cryosurgery has been proved to be feasible and efficacious in small and large animal studies and has been successfully performed in 1 patient with breast cancer. The results of this study suggest that ultrasound-guided cryosurgery of breast cancer warrants further investigation.

Reduced tissue thyroid hormone levels in fatal illness.

Patients with severe nonthyroidal illnesses (NTIs) frequently have decreased serum concentrations of triiodothyronine (T3) and less often of thyroxine (T4) without clear evidence of hypothyroidism. To determine whether T3 and T4 levels are also reduced in the tissues, we analyzed autopsy samples from 12 patients dying of NTI and 10 previously healthy individuals dying suddenly from trauma. Mean serum T3, T4, and free T4 index values were lower by 79%, 71%, and 49%, respectively, in the NTI group than in controls, but serum thyrotropin (TSH) values did not differ significantly. Mean T3 concentrations in cerebral cortex, hypothalamus, pituitary, liver, kidney, and lung were lower in the NTI group than in controls by 43% to 76%, but mean values in heart and skeletal muscle did not differ significantly between the groups. The mean liver T4 concentration was 66% lower in the NTI group, but mean T4 concentrations in the cerebral cortex were similar in the two groups. These results indicate that many tissues may be deficient in thyroid hormones in patients with fatal NTI, although the severity of the reduction in thyroid hormone concentrations may vary from one organ to another.

Chronic hoarseness secondary to gastroesophageal reflux disease: documentation with 24-h ambulatory pH monitoring.

Gastroesophageal reflux (GER) has been implicated in otolaryngologic problems, particularly chronic hoarseness that cannot be attributed to other causes. To study this relationship, we used 24-h ambulatory intraesophageal or dual pharyngoesophageal pH monitoring in 33 patients with chronic hoarseness and laryngeal lesions suggestive of acid irritation. Twenty-six of the patients (78.8%) had pH evidence of severe GER, being at least three times greater than the upper limit of normal. In contrast to 19 patients with proven esophagitis, this GER was worse in the upright position. Of 15 patients with both pharyngeal and esophageal probes, three had esophagopharyngeal reflux, and two had atypical unexplained pharyngeal decreases in pH to below 4.0. Less than half of the 33 patients had the typical symptoms of GER, and standard esophageal tests usually yielded normal findings. Occult GER, predominantly in the upright position, appears to be common and severe in patients with chronic hoarseness, who have laryngeal lesions suggestive of GER. The causative mechanisms are not clear. The 24-h esophageal pH monitor is useful in screening this potentially treatable problem.

Ambulatory 24-hour esophageal pH monitoring. Reproducibility and variability of pH parameters.

If 24-hour esophageal pH monitoring is to be a useful diagnostic tool, it must reliably discriminate gastroesophageal reflux patients despite daily variations in distal esophageal acid exposure. To address this issue, we studied 53 subjects (14 healthy normals, 14 esophagitis patients, and 25 patients with atypical symptoms) with two ambulatory pH tests performed within 10 days of each other. Intrasubject reproducibility of 12 pH parameters to discriminate the presence of abnormal acid reflux was determined. As a group, the parameters of percent time with pH less than 4 (total, upright, recumbent) were most reproducible (80%). Therefore, a subject was defined as having gastroesophageal reflux disease if at least one of these three values were abnormal. Intrasubject reproducibility for the diagnosis of reflux disease was 89% for the entire sample. Among subsets, the reproducibility was 93% for the normals and esophagitis patients and 84% for the atypical symptom patients. Total percent time with pH less than 4 was the single most discriminate pH parameter (85%) and nearly equaled that of the three combined parameters (89%). The intrasubject variability of this parameter was determined by the mean +/- 2 SD of the relative differences between the two test results for all 53 subjects. Total percent time with pH less than 4 may vary between tests by a factor of 3.2-fold or less (218% higher to 69% lower). We conclude: (1) ambulatory 24-hr esophageal monitoring is a reproducible test for the diagnosis of gastroesophageal reflux disease; and (2) the large intrastudy variability in 24-hr total acid exposure may limit this test's usefulness as a measurement of therapeutic improvement.

The symptom index: a clinically important parameter of ambulatory 24-hour esophageal pH monitoring.

Ambulatory 24-h esophageal pH monitoring is an accurate quantitative test of gastroesophageal reflux (GER). However, it does not answer the question: are the patients' symptoms due to GER? We developed a numerical scale to quantify the percent association between symptoms and pH less than 4--the symptom index (SI). In 100 consecutive patients with heartburn or chest pain, the SI for the chief complaint was either high (greater than 75%) or low (less than 25%) in 77% of cases. A similar bimodal distribution was seen when heartburn or chest pain symptoms were individually evaluated. There was a good association between high SI and the presence of GER (97.5%), as well as low SI and a normal 24-h pH study (81.1%). Endoscopy was normal in 89.5% of patients with low SI, but patients with high SI had esophagitis in only 69.7% of cases. The Bernstein test showed a poor association with the SI. Therefore, the SI gives clinically relevant information regarding the role of acid reflux and patient's symptoms. We believe this simple calculated index should be included in the analysis of 24-h esophageal pH studies.

Diffuse hepatocellular dysplasia and carcinoma associated with the Mmalton variant of alpha 1-antitrypsin.

The cirrhosis and hepatocellular carcinoma associated with alpha 1-antitrypsin deficiency has been exclusively reported with the PI Z allele. We present a 63-yr-old white man with emphysema, cirrhosis, and hepatocellular carcinoma. The latter occurred on a background of diffusely distributed hepatocellular dysplasia. Serum protein electrophoresis suggested a deficiency of alpha 1-antitrypsin quantitated at 13% of normal. PI phenotyping showed that he had only the rare PI Mmalton allele, previously associated only with severe lung disease. Family studies demonstrated the distribution of this rare allele. The liver at autopsy displayed well-differentiated hepatocellular carcinoma in addition to alpha 1-antitrypsin deposits in normal, dysplastic, and malignant cells.

Reye's syndrome in adults. A case report and review of the literature.

Adult Reye's syndrome (ARS) is an infrequently diagnosed condition that typically affects patients younger than age 35 years. We describe a 61-year-old man with ARS occurring after influenza B-USSR infection and aspirin use. The diagnosis of ARS was confirmed by oil-red-O stain of liver biopsy tissue and subsequent electron microscopy. We review the literature on ARS and compare the clinical features and management of ARS with pediatric Rye's syndrome. This case is of interest to practitioners treating adult patients because it demonstrates that the patient population at risk for Reye's syndrome is broader than generally believed.

Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep.

Activities of the enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were examined in the blood of 364 ewes of a lowland grazing flock comprising Scottish Blackface ewes and crosses of that breed with Border Leicester, Cambridge, East Friesland, Oldenburg and Texel rams. Half were bled at 16 months old and again two years later, and half at 28 months old. Variation attributable to breed of sire was not statistically significant (P less than 0.1) for GSH-Px, but was significant for whole blood copper concentration (P less than 0.01) and for SOD activity (P less than 0.05) although the latter was complicated by a large breed by age interaction involving two of the breeds. The correlation of SOD activity (per g haemoglobin) and whole blood copper concentration was 0.5, and the intraclass correlation between the estimates of SOD activities two years apart was 0.7.

Selenium concentration in the blood and wool and glutathione peroxidase activity in the blood of three breeds of sheep.

The activity of the enzyme glutathione peroxidase (GSH-Px) in whole blood and the selenium concentrations in whole blood and wool were measured in samples taken from 15 Scottish Blackface, 16 Welsh Mountain and 16 Finnish landrace sheep. Blood selenium sheep had almost twice the GSH-Px activity and blood selenium concentration of the other two breeds (P less than 0.001). Wool selenium concentrations of the three breeds were not significantly different. Blood selenium concentration and GSH-Px activity were highly correlated (r = 0.8, P less than 0.01) but wool selenium concentration was not significantly correlated with either of these measurements.

Deaths from copper toxicity of sheep at pasture and the use of fresh seaweed.

A number of sheep of the Orkney breed died of suspected copper poisoning while at pasture under circumstances which left sheep of other breeds apparently unaffected. Fresh seaweed offered to sheep with symptoms of copper toxicity appeared to be therapeutic and to lead to a reduction in plasma Cu level.