Study on the clinical value of Vitamin D in recurrent spontaneous abortion: Revisiting the Importance of Vitamin D.

OBJECTIVE: This study explores the possible pathogenesis of recurrent spontaneous abortion (RSA) caused by vitamin D (VD), provides evidence-based bases for prevention and treatment of RSA, improves female reproductive health. METHODS: This study randomly selected 305 patients without spontaneous abortion (SA0), 216 patients with a spontaneous abortion (SA1) and 200 patients with RSA from 1421 women of childbearing age who visited the RSA specialty clinic of Hangzhou First People's Hospital from January 2021 to June 2023 to conduct a prospective clinical study. Then, we collected the data of clinical diagnosis and treatment, conducted intervention and follow-up, and finally executed statistical analysis. RESULTS: (1) RSA patients were significantly older than the other two groups. (2) The rates of VD deficiency in SA1 and RSA patients were significantly higher than those in SA0. (3) When BMI < 20  or > 24 kg/m2 , there were abnormal increase in VD and increased number of spontaneous abortions. (4) The bilateral S/D of the VD-sufficient, VD-insufficient and VD-deficient groups gradually increased with statistical significance (p ≤ .018). (5) Among the 65 cases undergoing embryo chromosome examinations, chromosomal abnormalities accounted for 55.38% and 69.05% in RSA patients. (6) Among 186 patients with abnormal ACA, there was a certain negative correlation between ACA and VD, which was stronger among RSA patients. Moreover, ACA significantly decreased (p < .001) after effectively supplementing VD, and the miscarriage rate of re-pregnancy also decreased. CONCLUSION: The rate of VD deficiency is higher in RSA patients. VD deficiency may be related to the age of women of childbearing age and too low or high BMI, and may cause abnormal plasma antiphospholipid antibodies, increased uterine artery resistance and abnormal chromosomal division during fertilization, leading to spontaneous abortion and even RSA. The improvement of VD deficiency may reduce the risk of RSA occurrence.

Umbilical artery thrombosis diagnosed at different gestational ages and fetal outcomes: a case series.

BACKGROUND: Umbilical artery thrombosis is a rare complication of pregnancy strongly associated with poor fetal and perinatal outcomes, such as intrauterine asphyxia, fetal growth restriction, and stillbirth. Its pathogenesis remains unclear, and there is the added challenge of selecting an appropriate delivery time to achieve excellent neonatal outcomes. METHODS: Our Hospital is a critical maternal rescue center with approximately 7000 births annually. We present a series of 8 cases of umbilical artery thrombosis diagnosed at the hospital between Apr 1, 2018, and Jan 31, 2020. We identified the cases through a keyword search of the maternity and pathology information management systems. RESULTS: Three patients were diagnosed with a transabdominal ultrasound scan and hypoxia on fetal heart monitoring. All three patients had emergency cesarean section delivery. Four patients were observed closely for 5 to 13 weeks from initial detection by an ultrasound scan to delivery. Only one patient was diagnosed after vaginal delivery by Hematoxylin-eosin staining of umbilical cord sections. Seven patients had deliveries by cesarean section, and one patient had a vaginal delivery. All infants were born alive. CONCLUSIONS: Umbilical artery thrombosis is a challenging and rare condition that can occur at different gestational ages, especially when diagnosed in the third trimester and accompanied by fetal growth restriction. Consequently, these patients require close monitoring of umbilical blood flow and fetal growth and intervention at the appropriate time to achieve an optimal outcome.

[Prenatal diagnosis and genetic analysis of 17 fetuses with skeletal dysplasia].

OBJECTIVE: To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development. METHODS: Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed. RESULTS: For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes. CONCLUSION: For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.

Exacerbation of primary intestinal lymphangiectasia during late pregnancy and recovery after delivery: A case report and literature review.

RATIONALE: Primary intestinal lymphangiectasia (PIL) is a rare disease characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen. Main clinical features include intermittent diarrhea, hypoproteinemia. Scattered case reports suggested that PIL is compatible to pregnancy, but with increased complications. PATIENT CONCERNS: A 34-year-old woman with endoscopically diagnosed PIL presented to antenatal our clinic at 10 weeks into gestation. She reported strict adherence to low-fat/high-protein diet with medium-chain triglycerides (MCTs) supplementation. She was general well except for moderate edema and hypoalbuminemia. At 33 weeks, she developed diarrhea, nausea, and vomiting, with decreased fetal movements. One week later, she had an asthma attack. Nonstress test showed frequent variable deceleration. DIAGNOSES: The diagnosis of PIL was established endoscopically 8 years earlier. INTERVENTIONS: Hypoalbuminemia was corrected with intravenous albumin administration. She also received corticosteroid therapy to promote fetal lung maturation in anticipation to early termination of the pregnancy. OUTCOMES: A cesarean section was carried out at 34 weeks due to fetal distress. The baby girl was apparently healthy: weighing 2160 g, with an Apgar score of 9 at both 1 and 5 minutes. Symptoms dissipated rapidly after the delivery. The last follow-up visit at 15 months was unremarkable for both the mother and infant. LESSONS: PIL could be compatible with pregnancy, but requires strict adherence to dietary treatment, proper management of the symptoms (e.g., hypoalbuminemia), particularly during late gestation.

Bioequivalence in keratolytic activity of formulations vs its vehicle and comparator formulation: randomized, double-blind clinical trial.

This study assessed the bioequivalence, using keratolytic efficacy, of topical preparations studied in humans using adhesive tape stripping and biophysical methods. Ten healthy patients (3 men and 7 women [7 Caucasians and 3 Asians] mean age, 47 years) completed the study. Each coded product was randomly applied to the back according to the designated time of each sample. In addition, an untreated site (normal skin), and an untreated occluded site (chamber only) served as controls. At the end of the application time, each site was rinsed with tap water and then covered with a plastic chamber for 6 hours. Following removal of the chamber, the site was stripped for protein assay and squamometry analysis. This extends previous observations discerning bioequivalence resulting from different active materials with varying mechanism of action and potency on the skin. Results showed no significant difference between tested products. The novel formulations were of equal keratolytic activity to the "standard" (comparator) and hence bioequivalent in keratolytic activity.

Skin decontamination: principles and perspectives.

Skin decontamination is the primary intervention needed in chemical, biological and radiological exposures, involving immediate removal of the contaminant from the skin performed in the most efficient way. The most readily available decontamination system on a practical basis is washing with soap and water or water only. Timely use of flushing with copious amounts of water may physically remove the contaminant. However, this traditional method may not be completely effective, and contaminants left on the skin after traditional washing procedures can have toxic consequences. This article focuses on the principles and practices of skin decontamination.

Anti-irritants agents for the treatment of irritant contact dermatitis: clinical and patent perspective.

This overview defines whether anti-irritant agents, in fact, inhibit, prevent or treat irritant contact dermatitis (ICD) in man. We performed a literature search using PubMed, EMBASE, and Scopus via the library at University of California San Francisco, and a hand search of relevant text books to investigate chemicals that can be considered anti-irritants in either prevention or treatment. Emphasis was placed on data that included quantitative and qualitative results and that followed evidence-based dermatological guidelines. Related patents were summarized. Conflicting observations summarized here suggest well controlled, but often arduous, field type studies are required for confirmation.

Irritant contact dermatitis: effect of age.

Knowledge on age-relationship to irritant contact dermatitis (ICD) remains of interest. We searched for articles and textbooks on age-relationship to ICD and evaluated relevant data. Irritant response may be enhanced in children and decline with increasing age. In general, older skin reacts more slowly and with less intensity to irritants when compared with young skin. Such age-related changes may depend: (i) on differences in percutaneous penetration in old and young skin, and/or on (ii) differences in the microcirculatory efficiency, which serves as the route by which inflammatory cells make their way to the site of inflammation. Additionally, stratum corneum turnover time increases with age which means that an irritant remains longer on the skin; a compromised cutaneous blood vessel network with ageing may lead to a decreased inflammatory response, decreased absorption and decreased clearance. In conclusion, age-related differences of ICD are present despite some conflicting data. Investigations elucidating this interesting subject may benefit in prevention and intervention strategies.

Reactions of non-immunologic contact urticaria on scalp, face, and back.

BACKGROUND: This study compared the reactivity of scalp, face, and back to nonimmunologic contact urticants (NICU) to ascertain relative responsiveness. METHODS: Model urticants, benzoic acid (BA) and hexyl nicotinate (HN) with 3 concentrations of each were applied to marked skin of 10 bald males during 6 weeks. One urticant was applied to one side of nasolabial fold, back, and scalp and the other applied to the contralateral side. Reactivity was assessed by visual scores (VS) and biophysical instruments. Subjects ranked skin sensation with a 10-point visual analogue scale. RESULTS: With 0.25% HN application, upper back VS significantly (p<0.05) exceeded scalp and back VS also showed significantly (p<0.05) stronger reaction than face at 60 min post-application; however, at 2.5% BA site, VS of face exhibited significantly (p<0.05) higher than back at 15 min post-application but with 0.625% BA site, VS of back was significantly (p<0.05) higher than face. The a* value was significantly (p<0.05) higher on back than scalp with 0.625% BA treatment. CONCLUSION: Thus symptoms and measurements vary among sites. Differences may be related to solubility related percutaneous penetration. We encourage investigation into this relatively neglected but clinically important arena, to help explain difference in consumer/patient acceptance of topical formulations.

Allergic contact dermatitis: effect of age.

The relationship between allergic contact dermatitis (ACD) and age has not been well documented. We searched for articles and textbooks based on age-ACD relationship and evaluated relevant data. The frequency of skin reactions to allergens increased with age in some studies, whereas others showed no definite effect. This might be caused by variations in study design, genetic factors or by external influences such as from different regions and environmental exposure. In general, investigators agree that elderly patients were more likely to have multiple contact allergies than younger persons. This may be because of the frequent use of topical medicaments and having a longer time for potential allergen exposure. However, a review of marketed transdermal products for ACD shows a very low incidence, and no age-related effects were reported. One exception to this low incidence of ACD is the transdermal product, Catapres-TTS(®) (clonidine), which has a reported incidence rate of ~16%. The generally low incidence of ACD in marketed products and the conflicting findings in the prevalence of specific age-related ACD indicate the need for further investigation as to the proclivity for developing new sensitivities with age.

Measuring human skin buffering capacity: an in vitro model.

BACKGROUND/PURPOSE: It has been thought that skin possesses buffering capacity. This study measured the skin buffering capacity against two model solutions of acid and base at three concentrations with an in vitro system. METHODS: Ten microliters of model base (sodium hydroxide--NaOH) and acid (hydrochloric acid--HCl) solutions at concentrations of 0.025, 0.05, and 0.1 N was applied to human cadaver skin (3.18 microL/cm(2)) placed onto glass diffusion cells. Phosphate-buffered saline (PBS) was used as a standard buffer solution. Deionized water served as the negative control, whereas untreated skin served as the blank control. Skin pH was read and recorded immediately following dosing (0 time), and at 10 and 30 min of post-dosing. After the 30 min of dosing, each skin, except untreated skin (blank control), was then washed by applying 1 cm(3) of deionized water. The pH on each washed skin was measured immediately following washing, and the pH measurement was repeated at 10 and 30 min of post-washing. Six replicates were conducted. RESULTS: The pH values sharply significantly increased (P<0.05) immediately following dosing with NaOH at all concentrations (the highest concentration, caused the highest pH), and then decreased closely to baselines within 30 min post-application but still remained at significantly (P<0.05) higher values when compared with the blank control (untreated skin). HCl (acid) significantly (P<0.05) decreased skin pH immediately following dosing with all concentrations (the highest concentration, caused the lowest pH) and then restored rapidly to baseline. There was no significant difference in post-washing procedures on the skins that were pre-treated with the acid (HCI) solutions. However, with all base solutions (NaOH) pre-treated skin, pH values were significantly higher (P<0.05) at all time points post-washing. Furthermore, both PBS and water controls significantly elevated (P<0.05) the pH values following washing. CONCLUSION: Skin pH and its buffering capacity can be measured on human cadaver skin in vitro, which may partially replicate the response of in vivo skin. Dose-response was noted; i.e. the higher concentration caused larger changes in skin pH. In addition, the restoration of skin pH is relatively faster with acid when compared with base treatment. Clinical implications are offered.

Cutaneous bioengineering instrumentation standardization: the Tissue Viability Imager.

BACKGROUND: Tissue Viability Imaging (TiVi) is a new bioengineering technology intended for remote two-dimensional mapping of skin red blood cell concentration (RBC(conc)). Before use in the laboratory, work-site and dermatology clinic, critical performance parameters of this emerging technology require careful evaluation. OBJECTIVE: To assess short- and long-term stability, image uniformity, distance and image size dependence, ambient light and curvature influence in a production batch of Tissue Viability Imagers. METHODS: Four Tissue Viability Imagers from the same production batch were evaluated at two laboratories (one industrial and one dermatological) with respect to critical parameter performance. RESULTS: The average systematic drift in sensitivity over time was 0.27% and <1.02% for all four units tested. Difference in sensitivity between units was limited to 4.1% and was due to offset rather than gain deviation. Spatial variation in image uniformity was below 3.08% and 1.93% in the corners and centre of an individual image, respectively. This spatial variation could be further reduced to 0.25% and 0.13%, respectively by image normalization. Ambient light from a 40 W bulb or a 11 W fluorescent light source at a distance of 50-60 cm above the object, reduced the recorded values by about 10%, while the camera to object distance and image size had no detectable influence on sensitivity. Curved objects, such as human forearm, demonstrated an edge effect limited to below 10%. CONCLUSION: The critical TiVi performance parameters evaluated proved stable in relation to expected variations in skin RBC(conc) over time. Calibration by way of a two-point method may reduce differences in sensitivity between instruments to further facilitate inter-laboratory comparison of results.

Tissue viability imaging: mapping skin erythema.

BACKGROUND: Tissue Viability Imaging (TiVi) is an emerging bioengineering technology intended for two-dimensional mapping of skin erythema and blanching. Before TiVi can be effectively used in studies of diseased or damaged skin, the variability in normal skin red blood cell concentration (RBC(conc)) requires evaluation. OBJECTIVE: To demonstrate how TiVi maps spatial and temporal variations in normal skin RBC(conc) at the dorsal side of the hand at rest and during post-occlusive hyperemia. METHODS: Short-term and day-to-day variations in skin RBC(conc) were quantified at the dorsal side of the hand in four healthy volunteers at rest. In a separate study, the increase in skin RBC(conc) was recorded during post-occlusive hyperemia. RESULTS: A lower skin RBC(conc) (179-184 TiVi units) was observed at the back of the hand and base of the thumb compared with areas adjacent to the nailfoldfold region of the fingers (190-213 TiVi units). The short-term variation (within 70 s) was <2% in all areas of the dorsal side of the hand, while day-to-day variations were in the range 5-7% in the back of the hand and up to 10% in areas adjacent to the nailfold region. In the post-occlusive hyperemia phase, up to a 60% increase in skin RBC(conc) was observed in the early part of the reactive hyperemia phase. This increase in skin RBC(conc) successively decreased but remained about 18% above the pre-occlusion level after 30 min. CONCLUSION: Establishment of healthy skin RBC(conc) reference values is important for the design of versatile test procedures for assessment of skin damage caused by vibration tools, chemical exposure or peripheral vascular disease.

Comparison of tissue viability imaging and colorimetry: skin blanching.

BACKGROUND: Operator-independent assessment of skin blanching is important in the development and evaluation of topically applied steroids. Spectroscopic instruments based on hand-held probes, however, include elements of operator dependence such as difference in applied pressure and probe misalignment, while laser Doppler-based methods are better suited for demonstration of skin vasodilatation than for vasoconstriction. OBJECTIVE: To demonstrate the potential of the emerging technology of Tissue Viability Imaging (TiVi) in the objective and operator-independent assessment of skin blanching. METHODS: The WheelsBridge TiVi600 Tissue Viability Imager was used for quantification of human skin blanching with the Minolta chromameter CR 200 as an independent colorimeter reference method. Desoximetasone gel 0.05% was applied topically on the volar side of the forearm under occlusion for 6 h in four healthy adults. In a separate study, the induction of blanching in the occlusion phase was mapped using a transparent occlusion cover. RESULTS: The relative uncertainty in the blanching estimate produced by the Tissue Viability Imager was about 5% and similar to that of the chromameter operated by a single user and taking the a(*) parameter as a measure of blanching. Estimation of skin blanching could also be performed in the presence of a transient paradoxical erythema, using the integrated TiVi software. The successive induction of skin blanching during the occlusion phase could readily be mapped by the Tissue Viability Imager. CONCLUSION: TiVi seems to be suitable for operator-independent and remote mapping of human skin blanching, eliminating the main disadvantages of methods based on hand-held probes.

Determination of the antioxidative capacity of an antioxidant complex and idebenone: an in vitro rapid and sensitive method.

BACKGROUND/AIMS: The goal of this study was to determine the ability of two putative antioxidant solutions to suppress the formation of superoxide anion radicals created by optical excitation of a photosensitizer and measured by highly sensitive luminometric detection. METHODS/RESULTS: Solutions containing 3% antioxidant complex and 1% idebenone were tested. The antioxidant complex is an aqueous combination of botanical extracts rich in ferulic acid, caffeic acid, and other polyphenols. Idebenone is a lower molecular weight analog of coenzyme Q(10) (a potent antioxidant). Each was dissolved in lipid soluble reagents (solutions) and run through a Photochem (photochemiluminometer system) device. Their antioxidant capacity was expressed as nmol equivalents of synthetic vitamin E. Nine aliquots of each compound were measured. The mean antioxidant capacities for the 3% antioxidant complex and 1% idebenone were 525 +/- 23 and 213 +/- 14 nmol, respectively, with a statistically significant difference between the two compounds (P < 0.001). CONCLUSION: The 3% antioxidant solution possesses a significant antioxidative capacity, which was 2.5 times greater than the known antioxidant idebenone in a 1% solution as shown by the quenching of superoxide anion radicals measured by photochemiluminescence. This method provides rapid, accurate, and sensitive measurement of the antioxidant properties of lipid-soluble compounds.

Tape-stripping method in man: comparison of evaporimetric methods.

BACKGROUND/PURPOSE: If the occlusion time of a closed chamber evaporimeter on the skin is too long, saturation might occur. We previously compared an open chamber and a closed chamber device on healthy volunteers. Comparable data on stripped skin with higher evaporation rates are not available. This study compares the sensitivity and correlation of open and closed chamber devices in a tape-stripping human model. The amount of tape removed SC was also quantified with a protein assay method. METHODS: Ten healthy volunteers (six male and four female; seven Caucasians and three Asian; mean age 38+/-16) were enrolled. In a randomized manner, one forearm was measured by an open chamber device and the opposite by a closed chamber device. After recording baseline measurements, 20 strippings were taken on each test site with tape disks. Transepidermal water loss (TEWL) was measured at the end of 10 and 20 tape strippings at each test site. Stratum corneum (SC) aggregates in the strips was assayed. RESULTS: The mean values obtained from two devices were similar after 10 trips and 20 strips. There was no statistically significant difference. The closed chamber device showed a slightly higher (but not significant) inter-individual coefficient of variation. SC aggregates in the strips were similar and without a statistically significant difference. CONCLUSION: The study suggests that both devices might yield similar TEWL values on stripped human skin in vivo.

Protection from irritants.

Contact dermatitis is a common skin disease in the workplace and at home. The theoretically optimal way to minimize this problem is to use skin protection products such as barrier creams and moisturizers. Numerous ingredients have been formulated into the skin protection products in the marketplace. However, the US Food and Drug Administration only issued 13 skin protectants for over-the-counter products. Definition, reasons, mechanism of action and duration, application methods as well as efficacy of using skin protection products are extensively reviewed in this article. We conclude that the use of skin protection products may help people to reduce the intensity of skin irritations caused by irritants at home and at the workplace. We should remind the public not to use them as a primary protection against high-risk substances such as corrosive agents. Additionally, careful selection of appropriate skin protection products in the specific situations/environments is suggested.

Effect of Occlusion and Semi-occlusion on Experimental Skin Wound Healing: A Reevaluation.

UNLABELLED: The benefits of occlusive and/or semi-occlusive dressings to accelerate epidermal wound healing have been documented in experiments on human and animal models, as well as in clinical settings. Their benefits have been generally accepted. However, reports either from experimental or clinical observations suggest that occlusive dressings may occasionally delay wound healing. METHODS: Data presented here were reevaluated from experimental models conducted on controlled wounds. CONCLUSION: Although most human studies document that occlusive dressings facilitate epidermal wound healing, sufficient observations suggest that some experiment factors (latex rather than plastic and species) were not investigated in the earlier occlusive dressing observations, mandating the need for clarification. The differences between the earlier and more recent, significantly different, observations may relate to species (largely mouse rather than human), occlusive materials (latex rather than plastic), and type of wound (split-thickness versus stripping).

Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study.

Skin may adapt to topical irritants through accommodation. This study focuses on long-term exposure to irritants and attempts to demonstrate accommodation. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as controls. Experimental compounds were applied to forearms of 7 healthy volunteers for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over 103 days. Possible accommodation was quantified by visual scoring (erythema and dryness) and by bioengineering parameters: transepidermal water loss (TEWL), capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema, dryness, elevated TEWL, skin colour reflectance and LDF values occurred during the exposure periods. Upon repeat exposure, an immediate and augmented response in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant skin changes were not sustained. Irritation parameters return to baseline after cessation of exposure. There was no evidence of sustained irritation or accommodation after the last exposure. Study findings do not document sustained accommodation or adaptive hyposensitivity after long-term repetitive irritant exposure under these test conditions. Alternative models should be developed to prove or disprove the accommodation hypothesis.