Fabry disease (FD) is an X-linked monogenic disorder caused by mutations in the GLA gene which leads to a deficiency of the functionally active lysosomal α-galactosidase A enzyme. Here, we report on a family of five members: unaffected parents, one unaffected son, and another son and daughter both carrying the same mutation (p.G138E) in the GLA gene. Genotype analysis using intragenic GLA markers confirmed the maternal origin of the mutation. The affected son and daughter carried the same mutation; however, it was not detected in the peripheral blood, buccal cells, and urinary sediment cells of their mother. Moreover, the unaffected son without the alteration in the GLA gene carried the same maternal chromosome X (disease-associated) haplotype. To the best of our knowledge, this study represents the first case of maternal germline mosaicism in FD.
In previous studies, data deriving from Google Trends showed promising correlation with disease incidence trends assessed with public health control systems. The aim of this work is to use search engine query data to investigate seasonal dynamics in Guillain-Barré syndrome (GBS) in the USA.
Methods
Average Google monthly search volumes for GBS from 2008 to 2017 were analysed for the USA overall and on regional base with generalized estimating equation models. Association with monthly historical temperature variations was tested.
Results
Monthly search volume for GBS displayed the greatest positive anomaly for October, clustering with September and November. Region-wide analysis confirmed this pattern and showed secondary spring (Feb/Apr) subpeaks in Pacific and Midwest. Association of GBS search volume with month-to-month temperature variations showed J-shaped relationship, with the highest peak occurring in months with greatest temperature falls, and subpeak in months with sharpest temperature rises.
Conclusions
This study represents the first approach in investigating digital epidemiology of GBS and establishing possible links with traditional epidemiology. Cold season GBS peak has been observed by some traditional studies; hypothetical pathogenic relationship with infectious antecedents is supported from finding GBS peaks clustering with greatest temperature change. Further studies are needed to compare these findings to traditional public health approaches.
The effect of doubling the immersion fluid (eluate) volume on antibiotic concentrations and on mechanical stability from vancomycin and gentamicin loaded bone cements was investigated in vitro. Antibiotic loaded bone cements containing premixed 1.34% gentamicin antibiotic concentration in the cement powder (wt), premixed 1.19% gentamicin wt and 4.76% vancomycin wt and premixed 1.17% wt gentamicin additionally manually blended with 4.68% wt vancomycin were tested. Six specimens per group were immersed in 4 ml and 8 ml for 6 weeks while the eluate was exchanged every 24 h. The antibiotic concentrations were repeatedly measured. Then the specimens were tested for compressive strength. Doubling the eluate volume significantly decreased gentamicin and vancomycin concentrations from 6 h and 24 h on, except for the gentamicin concentration of the additionally manually blended formulation after 3 weeks. The additionally manually blended vancomycin formulation produced significantly higher gentamicin concentrations in 8 ml compared to the other formulations. The reduction ratios of the vancomycin concentrations were significantly smaller than the reduction ratios of the gentamicin concentrations for the manually blended vancomycin formulation. Vancomycin containing formulations showed significantly lower compressive strengths than the vancomycin free formulation after immersion. Doubling the eluate volume lead to significant compressive strength reduction of the vancomycin containing formulations. Eluate volume change influences antibiotic elution dependent on the antibiotic combination and loading technique. The reducing effect is higher on vancomycin than on gentamicin elution. Compressive strength of gentamicin/vancomycin loaded bone cements after immersion is eluate volume dependent.
To analyze the feasibility, surgical outcomes and possible risks and complications encountered during transoral robotic surgery (TORS) for approaching parapharyngeal space (PPS) tumours, a retrospective cohort study was conducted. Out of 108 TORS procedures performed, 5 PPS tumours were identified from May 2011- November 2017. This study included 2 retrostyloid (benign nerve sheath tumour) and 3 prestyloid tumours (pleomorphic adenoma), of which one patient had previously undergone a transcervical approach for deep lobe of parotid pleomorphic adenoma. Average tumour dimensions were 4.56 × 4.5 × 3.64 cm, with largest antero-posterior, medial—lateral and craniocaudal dimensions being, 5.1 cm, 7.1 cm and 6.5 cm, respectively. Adverse peri-operative events encountered were tumour fragmentation (n = 1), Secondary hemorrhage (n = 1) and Horner's syndrome (n = 1). Oral feeds could be initiated after 7.6 days. No recurrences were noted during a mean follow up of 21.6 months. Therefore, in properly selected cases, excellent results in terms of extracapsular resection and low morbidity can be obtained with TORS without resorting to mandibulotomy or transcervical incision.
The thymus is a primary lymphoid organ where T lymphocyte proliferation and selection takes place. The different subsets of lymphocytes leave the thymus as recent thymic emigrants. Peripheral dendritic cells migrate to the thymus. In addition to the homing of hematopoietic progenitor cells to the thymus, there is evidence for lymphocyte entry from peripheral lymphoid tissues mainly into the medulla. The entry sites are the venules in the medullary part near to the cortex with a higher endothelium. Furthermore, there are also B lymphocytes in the thymus. The thymus is not only a primary lymphoid organ but is well integrated in lymphocyte traffic as shown in several different species.
To review the current state of the use of ultrasound in hepatocellular carcinoma (HCC) surveillance.
Findings
Despite limitations in the evidence supporting the use of ultrasound in HCC surveillance, it has been formally recommended by a number of guidelines based on the best available evidence showing that it improves survival and is cost effective. However, ultrasound surveillance is inconsistently adopted and is prone to a number of practical and technical challenges. The recent introduction of ultrasound LI-RADS aims to standardize performance and reporting of these surveillance studies.
Summary
Despite remaining a controversial topic, semi-annual ultrasound screening for HCC is still supported by multiple hepatology societies. Ongoing evaluation of its performance and cost-effectiveness is required as new standards such as US LI-RADS, as well as evolving therapies and technologies emerge.
It is important to monitor the safety profile of drugs, and mining for strong associations between drugs and adverse events is an effective and inexpensive method of post-marketing safety surveillance.
Objective
The objective of our work was to compare the accuracy of both common and innovative methods of data mining for pharmacovigilance purposes.
Methods
We used the reference standard provided by the Observational Medical Outcomes Partnership, which contains 398 drug–adverse event pairs (165 positive controls, 233 negative controls). Ten methods and algorithms were applied to the US FDA Adverse Event Reporting System data to investigate the 398 pairs. The ten methods include popular methods in the pharmacovigilance literature, newly developed pharmacovigilance methods as at 2018, and popular methods in the genome-wide association study literature. We compared their performance using the receiver operating characteristic (ROC) plot, area under the curve (AUC), and Youden's index.
Results
The Bayesian confidence propagation neural network had the highest AUC overall. Monte Carlo expectation maximization, a method developed in 2018, had the second highest AUC and the highest Youden's index, and performed very well in terms of high specificity. The regression-adjusted gamma Poisson shrinkage model performed best under high-sensitivity requirements.
Conclusion
Our results will be useful to help choose a method for a given desired level of specificity. Methods popular in the genome-wide association study literature did not perform well because of the sparsity of data and will need modification before their properties can be used in the drug–adverse event association problem.
Drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH) are two of several types of drug-induced liver injury (DILI). They can be caused by various drugs and may present as acute, potentially lethal disorders or as chronic slowly progressive liver injury. Despite the fact that they are distinct disorders, the slow progressive forms of DIS and DISH are often confused with or misdiagnosed as non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), which are much more common and, by definition, not caused by drugs. Currently the only way to identify DIS is via imaging studies or a liver biopsy, while DISH can be identified only through liver biopsy. In addition, diagnosis of either DIS or DISH requires an exhaustive clinical evaluation and comprehensive causality assessment to rule out other possible causes and determine the association with the suspected drug. Furthermore, it is difficult, using existing methods, to monitor the progression of DIS and DISH and to determine the underlying mechanism. Therefore, there is a great unmet need for non-invasive biomarkers that will be able to identify the development of DIS or DISH during drug development and to monitor for progression or regression of the disorder during treatment or following drug discontinuation. Recent developments in the fields of NAFLD and NASH have introduced several novel biomarkers that show promise for the diagnosis, monitoring, and severity assessment of these common diseases. Given the significant overlap in possible underlying mechanisms and histological pattern between NAFLD/NASH and DIS/DISH, these postulated NAFLD and NASH biomarkers may have a potential application to DIS and DISH. This article reviews the existing medical literature and other publically available information pertaining to novel serum biomarkers for NAFLD and NASH, and explores the concurrent identification of these biomarkers for DIS and DISH.
Autistic-undisciplined thinking in the practice of medical trichology
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Ralph Michel Trueb, Hudson Dutra, Maria Fernanda Reis Gavazzoni Dias DOI:10.4103/ijt.ijt_79_18
Medical trichology is the branch of dermatology that deals with the scientific study of the hair and scalp in health and disease. As any discipline, the practice of medical trichology is not immune to malpractice, either deliberately or carelessly. In his publication "Autistic Undisciplined Thinking in Medicine and How to Overcome It," Swiss psychiatrist Eugen Bleuler describes yet another form of malpractice in medicine reflecting autistic-undisciplined thinking. Autism is not limited to psychopathology, but inherent to the thinking of man throughout history in his drive for knowledge, with thousands of theories lacking any basis in reality. Bleuler recognized the drive character of autistic thinking and how it leads to conclusions that are unshakable because they are determined by, and fulfill, emotional needs, rather than rational argumentation. Even with correct questions, the complexity and incalculability of some problems are often so great that it cannot do justice to realistic thinking and the boundaries between inadequately substantiated hypothesis and autistic sham explanation disappear. Statistics, careful research design, and the attempt to impose stringent methods on our thinking are to be commended. The habituation of the public to useless medicine, to misconceptions, is not hygiene, but negligent endangerment. It has created an industry that largely lives on the autistic thinking of patients and doctors and because it is prosperous, makes propaganda among lay people as well as among doctors that necessarily leads to abuses. This article aims at exposing the most prevalent among abuses in trichological practice due to autistic-undisciplined thinking, specifically: iron supplementation, antiandrogenic treatment, and individualized cell-based therapy in female androgenetic alopecia, treatment of folliculitis decalvans with retinoids, and the value of nutritional therapies.
Light microscopic morphology of indigenous Ghanaian African hair from scalp, eyebrow, axilla, and pubic regions
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Yusra Kalmoni, Frederick Kwaku Addai, Saviour Kweku Adjenti, Kevin Kofi Adutwum-Ofosu, John Ahenkorah, Bismarck Afedo Hottor, Richard Michael Blay DOI:10.4103/ijt.ijt_70_18
Context: Relatively scanty literature on autochthonic African Negroid hair morphology provokes research interest for anthropological, forensic, and cosmetic purposes. Aims: This study aimed to contribute basic morphological information on Ghanaian African hairs. Settings and Design: The study was done in selected second-cycle schools in Accra, Ghana, using convenient sampling. Subjects and Methods: Hairs were obtained by pluck method, from 30 males and 30 females aged 15–20 years. Ghanaian African autochthony was established if individuals had two generations of indigenous Ghanaian parentage. Scalp, eyebrow, axilla, and pubic hairs were image captured using a digital light microscope eyepiece connected to a computer. Diameters of hair strands were measured; types of the medulla and the form and shape of the hair roots were studied. Statistical Analysis Used: ANOVA test (SPSS Version 17.0) was used to compare the means of quantitative hair features among the sexes and the four regions of the body studied. Results: Pubic hair shaft was thickest (respective male and female diameters were 100.21 μm, 88.40 μm) and eyebrow hair was thinnest (53.97 and 46.69-μm diameters in males and females, respectively). Axillary and scalp hairs were the closest in diameters with 76.21 and 72.02 μm, respectively, in males and 73.07 and 71.15 μm, respectively, in females. Continuous type medulla was predominant in all hairs, with a trend of percentage occurrence in descending order from the pubic, axilla, eyebrow, and scalp in both sexes. Conclusions: Bodily regional differences in diameter of hair shaft and medullary presence were affirmed.
Introduction: Hair casts have been reported in a variety of hair and scalp disorders. Trichoscopy allows a quick and noninvasive method for the evaluation of hair and scalp disorders in high magnification. However, the study of hair casts seen in trichoscopy is lacking. Objective: The main objective is to study the occurrence and patterns of tubular hair cast (THC) in different hair and scalp disorders. Patients and Methods: The patients with hair and scalp disorders presenting at the dermatology department of our hospital were evaluated using trichoscopy. Cases of primary parakeratotic disorders and behavioral disorders were excluded. After a detailed history and evaluation of the hair and scalp, histopathology, light microscopic examination, potassium hydroxide examination, and fungal culture were done when necessary. Results: THC was seen in total 21 cases of seven different hair and scalp disorders. Of these, the majority of cases were of discoid lupus erythematosus (DLE) (5/21) and maximum frequency of THCs within a disorder was seen in cases of pemphigus foliaceus (PF) (50%). Proximal casts occurred in 90.47% of cases. Single cast involving two shafts was seen in a case of PF, and two casts within a single shaft were seen in two cases of DLE and one case of alopecia areata. Conclusions: THCs in trichoscopy can be seen in various hair and scalp disorders and their study may help during the diagnosis of those disorders when combined with other trichoscopic features.
Research on the balance of thiol-disulfide in blood serum in women with telogen effluvium
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Ayşe Akbas, Fadime Kılınç, Sertaç Sener, Akta Akınş, Cemile Bıçer, Orhan Şen DOI:10.4103/ijt.ijt_78_17
Backgrounds: Telogen effluvium (TE) is the most common reason for hair loss in humans. Although the exact etiopathogenesis of TE has not been revealed clearly and completely, multifactorial etiologies are to be blamed. In recent years, since oxidative stress (OS) has been shown to play an important role in the etiopathogenesis of so many diseases, the effects of OS on several skin diseases are researched and analyzed. Thiols are antioxidant components that include sulfur group, and the balance of thiol-disulfide has an important role in the formation and prevention of OS. This balance is destroyed in many diseases and its effect on TE is not clearly understood yet. Objectives: In this study, we aimed to search the thiol–disulfide balance that could reveal OS in patients with TE. Materials and Methods: Fifty-two patients with TE and control group of 46 persons were included in the study. Native thiol, disulfide, and total thiol levels were evaluated by a new, automatic spectrophotometric method. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol rates were calculated. Results: There was no statistical difference between TE patients and control group in terms of native thiol, disulfide, and total thiol levels. Thiol–disulfide balance was fixed and not affected in TE patients.
Serum interleukin-15 is a marker of alopecia areata severity
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Adel Ali Ebrahim, Rehab Mohammed Salem, Asmaa Adel El Fallah, Esraa Taha Younis DOI:10.4103/ijt.ijt_80_18
Background: Interleukin-15 (IL-15) is a cytokine that is involved in many inflammatory and autoimmune diseases. Although alopecia areata (AA) is an autoimmune disease, serum levels of IL-15 have not been studied well in AA patients. Aim of the Work: We aims at evaluating the serum levels of IL-15 in active AA. Subject and Methods:This case-control study included 40 AA patients and 40 apparently healthy matched controls. Written informed consents were obtained from all the participants. The scalp was examined to assess sites, number, and size of alopecia patches, and the severity of AA lesions was assessed using the Severity of Alopecia Tool score (SALT score) which determine the percentage of hair loss in the scalp. The body was carefully examined to detect any alopecia patches in any hairy area. Nail examination was carried out to detect any nail involvement. Serum IL-15 levels were measured using an ELISA kits. Results: Serum levels of IL-15 in patients were significantly higher than those in the control group (P < 0.001). Serum levels in alopecia totalis were significantly higher than those with one or two patches, and serum levels in patients with both scalp and body involvement were significantly elevated than the levels of patients with either scalp or body involvement. There was a statistically significant positive correlation between SALT score and serum levels of IL-15 (P < 0.001). Conclusion: Serum IL-15 may be a marker of AA severity.
Luisa Groba Bandeira, Maria Cláudia Alves Luce, Bruno De Castro E Souza, Priscila Kakizaki, Neusa Yuriko Sakai Valente DOI:10.4103/ijt.ijt_16_18
We report a case of trigeminal trophic syndrome (TTS) on the scalp of a 69-year-old woman. Initially, the diagnosis of pityriasis amiantacea was considered. The review of pathological antecedents and knowledge of TTS were fundamental for the diagnosis of this illness. We performed a brief review on TTS and differential diagnoses.
Nerve sheath myxoma, a superficial myxoid tumor, was first described in 1969 by Harkin and Reed. Tumor has cytological and histological resemblance with neurothekeoma, another cutaneous myxoid lesion. Nerve sheath myxoma affects individuals of all age groups and equal predilection for both genders with most favored sites being the fingers and knee. Here, we present a case report of nerve sheath myxoma of the scalp, diagnosed and confirmed with histopathology and immunohistochemistry.
Woolly hair nevus is a rare non hereditary disorder of scalp characterized by curling and kinking of hair. It can present in childhood or adolescent age. Dermoscopy is a useful noninvasive technique to help in the diagnosis of wolly hair nevus. We report a case of woolly hair nevus associated with linear epidermal nevus.
