Accumulation of Mercury in Ovaries of Mice After the Application of Skin-lightening Creams

Skin-lightening creams are being increasingly used by women in particular, worldwide in an attempt to whiten their skin. Men and older people use these creams to remove age spots or other pigmentation disorders. Several studies have reported the presence of high mercury levels in skin-lightening cream. Women, especially pregnant and nursing mothers, who use these creams are at risk of mercury toxicity because long-term exposure can cause permanent neurological damage, nephrological disorders, fertility problems, and birth defects. Early exposure usually has no clinical symptoms. Mercury levels were measured in a total of 49 ovary tissue samples. The mean mercury contents in the ovaries of non-treated mice (11.70 ± 13.38 ng/g) were compared to mice treated with Rose skin-lightening cream samples (2,471.92 ± 1,336.31 ng/g) and those treated with Fair & Lovely skin-lightening creams (58.47 ± 39.51 ng/g). The mercury content in the ovary tissues increased with number of cream applications and were highest in the ovaries of mice treated twice a day with Fair & Lovely (87.79 ± 26.20 ng/g) and once a day with Rose (3,515.61 ± 1,099.78 ng/g). Our data indicate that dermal exposure to mercury can result in a significant accumulation in the ovaries of mice following the application of skin-lightening cream. This may cause alterations in reproductive behavior and contribute to infertility or ovarian failure. Of course, these results need to be confirmed by further research. Imported or locally made skin-lightening creams are widely available in Saudi market. It would be ideal to ban the sale of these creams but unfortunately, advertisements in the mass media presenting celebrities and beauty specialists make these products more popular. Alternatively, public health authorities should encourage more reliance on prescribed creams for the treatment of skin pigmentation problems.     

Comparison of mercury levels in various tissues of albino and pigmented mice treated with two different brands of mercury skin-lightening creams

The use of mercury containing skin-lightening creams are becoming increasingly popular among dark-skinned women. The long-term use of certain brands may cause serious health effects over the years. In the present study, we investigated the dermal absorption of mercury and its accumulation in the tissues of albino and pigmented mice treated with two brands of mercury containing skin-lightening creams for a period of one months at different intervals. The mean +/- SD of mercury in the selected brands were: (1) Fair & Lovely (0.304 +/- 0.316 microg/g); and (2) Rose (77513.0 +/- 71063.0 microg/g). Mercury levels were measured in a total of 133 and 144 liver, kidney and brain tissue samples of albino and pigmented mice respectively by the Atomic Absorption Spectrophotometer coupled to Vapour Generator Accessory. In both strains, we found that the mercury concentration in the tissues of mice treated with Rose skin-lightening cream samples was significantly higher than those treated with Fair & Lovely skin lightening cream. Looking at the mercury concentration in the tissue samples with respect to the application of skin lightening creams at different intervals, the highest mercury concentrations were found in the tissues of albino and pigmented mice treated three times a day. On the other hand, the lowest mercury concentrations were found in the tissues of mice treated once a week. Despite the brand of skin-lightening cream that was applied, the study indicated that mercury was readily absorbed through the skin of both albino and pigmented mice as evidenced with its accumulation in the brain, kidney and liver tissues where the kidney had the highest mercury content and brain had the lowest (it P < 0.0001). Significant differences in the mercury levels were observed between the albino and pigmented mice. This emphasizes the protective role of melanin against mercury toxicity. Results of this study stresses the potential harm of these mercury containing skin-lightening creams regardless of their mercury contents especially for women who apply these creams frequently or for extended periods. Permanent nephrological or/and neurological deficits may occur if the damage is severe and diagnosis and treatment are delayed.     

Histological Reassessment of Three Kidneys Originally Described by Richard Bright in 1827-36

Portions of kidney from three patients with renal disease that were originally described by Richard Bright between 1827 and 1836 have been preserved in the Gordon Museum at Guy''s Hospital. Histological study has shown that two cases fall into the current diagnostic category of mesangiocapillary (membranoproliferative) glomerulonephritis. One of these patients had a five-year clinical history and died with chronic renal failure and uraemia. The other patient died after three to four months with a severe nephrotic syndrome. The third patient was a young woman with chronic “phthisis pulmonalis” and renal amyloidosis.     

The Association between the Use of Proton Pump Inhibitors and the Risk of Hypomagnesemia: A Systematic Review and Meta-Analysis

Background

Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis.

Methods

We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords “proton pump,” “dexlansoprazole,” “esomeprazole,” “ilaprazole,” “lansoprazole,” “omeprazole,” “pantoprazole,” “rabeprazole,” “hypomagnesemia,” “hypomagnesaemia,” and “magnesium.” Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran’s Q test and I ² statistics.

Results

Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6–9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3–55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3–52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077–2.924). Significant heterogeneity was identified using Cochran’s Q test (df = 7, P<0.001, I ² = 98.0%).

Conclusions

PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.     

Erythropoietic Protoporphyria IV. Protection from Sunlight

Dihydroxyacetone and lawsone, in a vanishing cream base, applied to the skin was found to protect patients with erythropoietic protoporphyria against sunlight. The use of the same ingredients in a 50% isopropyl alcohol/water solution did not induce adequate light protection. The chemically induced ultraviolet light filter in the stratum corneum allowed these patients to change their lives from an “indoor” to an “outdoor” environment.     

Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules

“The incidence of thyroid cancer, the most common endocrine malignancy, is rising. The two most common types of thyroid cancer are papillary and follicular” thyroid carcinomas. “Fine-needle aspiration (FNA) of thyroid nodules” can permit to detect many genetic mutations and other molecular alterations, including RAS and BRAF point mutations, PAX8/peroxisome proliferator-activated receptor (PPAR)γ and “RET/PTC rearrangements, occurring in thyroid papillary and follicular carcinomas” (more than 70% of cases), which can be used successfully to improve the diagnosis “and the management of patients with thyroid nodules”. The most extensive experience has been accumulated with “the diagnostic use of BRAF mutation”, which is highly specific for malignancy. “Testing FNA samples for a panel of mutations” that typically includes RAS, BRAF, PAX8/PPARγ and RET/PTC could permit to achieve the biggest diagnostic impact. “The accuracy of cancer diagnosis in thyroid nodules could be improved significantly using these and other emerging molecular markers”.     

Bubble Stability Test Compared with Lecithin Assay in Prediction of Respiratory Distress Syndrome

A simple test for surfactant, utilizing bubble stability in ethanol, was performed in 106 samples of amniotic fluid obtained from 94 patients. Of these patients 80 delivered within 48 hours of the collection of the sample. The results were compared with the lecithin concentration in the same amniotic fluid samples and with the quality of respiration in the neonate. The test was “positive,” indicating fetal pulmonary maturity, in 37 cases and none of these infants developed respiratory distress syndrome (R.D.S.). In only one of these cases, however, was gestation less than 37 weeks. The test was “intermediate” or “negative” in 43 cases but in 35 of these infants respiration at birth was perfectly normal.Performed by the method described by its originators, this simple test gives too many false negative results to be of value in routine clinical practice, although a positive result is helpful. The concept of the test is ingenious, however, and further developments may be expected.     

Framingham Risk Score with Cardiovascular Events in Chronic Kidney Disease

The Framingham Risk Score (FRS) was developed to predict coronary heart disease in various populations, and it tended to under-estimate the risk in chronic kidney disease (CKD) patients. Our objectives were to determine whether FRS was associated with cardiovascular events, and to evaluate the role of new risk markers and echocardiographic parameters when they were added to a FRS model. This study enrolled 439 CKD patients. The FRS is used to identify individuals categorically as “low” (<10% of 10-year risk), “intermediate” (10–20% risk) or “high” risk (≧ 20% risk). A significant improvement in model prediction was based on the −2 log likelihood ratio statistic and c-statistic. “High” risk (v.s. “low” risk) predicts cardiovascular events either without (hazard ratios [HR] 2.090, 95% confidence interval [CI] 1.144 to 3.818) or with adjustment for clinical, biochemical and echocardiographic parameters (HR 1.924, 95% CI 1.008 to 3.673). Besides, the addition of albumin, hemoglobin, estimated glomerular filtration rate, proteinuria, left atrial diameter >4.7 cm, left ventricular hypertrophy or left ventricular ejection fraction<50% to the FRS model significantly improves the predictive values for cardiovascular events. In CKD patients, “high” risk categorized by FRS predicts cardiovascular events. Novel biomarkers and echocardiographic parameters provide additional predictive values for cardiovascular events. Future study is needed to assess whether risk assessment enhanced by using these biomarkers and echocardiographic parameters might contribute to more effective prediction and better care for patients.     

Determining the Variability of Lesion Size Measurements from CT Patient Data Sets Acquired under “No Change” Conditions

PURPOSE: To determine the variability of lesion size measurements in computed tomography data sets of patients imaged under a “no change” (“coffee break”) condition and to determine the impact of two reading paradigms on measurement variability. METHOD AND MATERIALS: Using data sets from 32 non-small cell lung cancer patients scanned twice within 15 minutes (“no change”), measurements were performed by five radiologists in two phases: (1) independent reading of each computed tomography dataset (timepoint): (2) a locked, sequential reading of datasets. Readers performed measurements using several sizing methods, including one-dimensional (1D) longest in-slice dimension and 3D semi-automated segmented volume. Change in size was estimated by comparing measurements performed on both timepoints for the same lesion, for each reader and each measurement method. For each reading paradigm, results were pooled across lesions, across readers, and across both readers and lesions, for each measurement method. RESULTS: The mean percent difference (± SD) when pooled across both readers and lesions for 1D and 3D measurements extracted from contours was 2.8 ± 22.2% and 23.4 ± 105.0%, respectively, for the independent reads. For the locked, sequential reads, the mean percent differences (± SD) reduced to 2.52 ± 14.2% and 7.4 ± 44.2% for the 1D and 3D measurements, respectively. CONCLUSION: Even under a “no change” condition between scans, there is variation in lesion size measurements due to repeat scans and variations in reader, lesion, and measurement method. This variation is reduced when using a locked, sequential reading paradigm compared to an independent reading paradigm.     

Identification of Two Missense Mutations of ERCC6 in Three Chinese Sisters with Cockayne Syndrome by Whole Exome Sequencing

Cockayne syndrome (CS) is a rare autosomal recessive disorder, the primary manifestations of which are poor growth and neurologic abnormality. Mutations of the ERCC6 and ERCC8 genes are the predominant cause of Cockayne syndrome, and the ERCC6 gene mutation is present in approximately 65% of cases. The present report describes a case of Cockayne syndrome in a Chinese family, with the patients carrying two missense mutations (c.1595A>G, p.Asp532Gly and c.1607T>G, p.Leu536Trp) in the ERCC6 gene in an apparently compound heterozygote status, especially, p.Asp532Gly has never been reported. The compound heterozygote mutation was found in three patients in the family using whole exome sequencing. The patients’ father and mother carried a heterozygous allele at different locations of the ERCC6 gene, which was confirmed by Sanger DNA sequencing. The two mutations are both located in the highly conserved motif I of ATP-binding helicase and are considered “Damaging,” “Probably Damaging,” “Disease Causing,” and “Conserved”, indicating the role of DNA damage in the pathogenetic process of the disease. The results not only enrich the ERCC6 mutations database, but also indicate that whole exome sequencing will be a powerful tool for discovering the disease causing mutations in clinical diagnosis.     

LEUKOCYTES IN “VIRUS X” INFECTION

Study of blood taken from patients with the recent “Virus X” “flu” syndrome showed slight leukopenia and the presence of abnormal lymphocytes, the most characteristic of which were those showing basophilic cytoplasm. These cells, often called Turk cells, and which the authors have termed “toxic” lymphocytes, are similar to those found in other virus infections.     

Nephrotic Syndrome Due to Primary Renal Disease in Adults: I. Survey of Incidence in South-east England

In a prospective survey of the nephritic syndrome due to primary renal disease in adult patients in the South-east Metropolitan Region of England 50 patients were seen in a two-year period—a minimum annual incidence of 9·0 new cases per million adult population. The frequency distribution of the three main histological groups was “minimal change” 30%, membranous nephropathy 12%, and proliferative glomerulonephritis 58%. The higher proportion of patients with minimal histological change compared with that found in most previously published series may be explained by the avoidance of selection of patients for inclusion. The much lower incidence of membranous nephropathy probably reflects the use of stricter histological criteria for this diagnosis.     

Membranoproliferative Glomerulonephritis and Persistent Hypocomplementaemia

The clinical, laboratory, and histological findings of 50 patients with membranoproliferative glomerulonephritis are described. Three-quarters of the patients, who were mostly older children and young adults, presented clinically with a mixture of “nephritic” and “nephrotic” symptoms; the remaining quarter had no symptoms and were diagnosed after the discovery of proteinuria and microscopic haematuria.Though this clinical picture may occur in other forms of glomerulonephritis, the patients described here were unified as a group by their glomerular morphological appearance—namely, a combination of mesangial proliferation and capillary wall thickening, mainly due to subendothelial accumulations of mesangial matrix.In 68% serum C3 (β10-globulin) levels were reduced initially, while a further 16% subsequently showed a fall to abnormally low levels. All patients had substantial proteinuria, usually of moderately impaired selectivity, and all but one had haematuria in addition. Children frequently presented with an illness resembling acute nephritis, whereas adults usually had a nephrotic syndrome from the start.In 31 patients, followed for periods of one to eight and a half years, serial measurements of glomerular filtration rate were made. Sixteen have experienced no deterioration of renal function, though their proteinuria continues unchanged. Fifteen have shown progressive deterioration; six of them are still well, six are on regular dialysis treatment, and three have died. Treatment with corticosteroids, azathioprine, or cyclophosphamide, alone or in combination, did not seem to influence the course of the disease, and another two patients died from complications of steroid therapy. The disease usually runs a chronic course and appears to be progressive.     

Unusual Non-Occupational Exposure to Metals

Exposure to metals at workplaces is well known and in many cases occupational studies led to an adoption of limit values. For airborne concentrations of substances as metals refer to the “Maximaleo Arbeitsplatz-Konzentration” (MAK) in Germany or the “Threshold Limit Value” (TLV) in USA. Biological monitoring consists of an assessment of overall exposure to chemicals at the workplace and in the environment. The “Biologischer Arbeitsstoff Toleranzwert” (BAT) in Germany and the “Biological Exposure Index” in the USA serve as reference values. Besides these occupational limit values, reference values exist in Germany for the background exposure of the non occupationally exposed general population. In some cases the reference values are exceeded without any occupational exposure. Several cases of unusual environmental exposure to cobalt, mercury and manganese are reported. In such cases, it is often difficult to evaluate the measured concentration. In Germany, therefore, the “Human-Biomonitoring-Werte” (HBMValues) have been adopted in order to evaluate such high background exposures. The HBM-concept is presented. Environmental exposure to metals is usual within some limits. Reference values are helpful for an assessment. Unusual exposure occurs and the physician should be alert to symptoms of poisoning.     

Beneficial Effect of Isoniazid Preventive Therapy and Antiretroviral Therapy on the Incidence of Tuberculosis in People Living with HIV in Ethiopia

Background

IPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.

Objectives

To measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.

Methods

A retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, “IPT-only,” “IPT-before-ART,” “IPT-and-ART started simultaneously,” “ART-only,” and “IPT-after-ART” on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.

Results

Of 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of “IPT-only” (aHR = 0.36, 95% CI = 0.19–0.66) and “ART-only” (aHR = 0.32, 95% CI = 0.24–0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08–0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10–0.42) provided further reduction of TB at ∼80%.

Conclusions

IPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.     

Psychiatric Illness in General Practice: A Detailed Study Using a New Method of Case Identification

A self-administered questionary (the General Health Questionnaire) aimed at detecting current psychiatric disturbance was given to 553 consecutive attenders to a general practitioner''s surgery. A sample of 200 of these patients was given an independent assessment of their mental state by a psychiatrist using a standardized psychiatric interview. Over 90% of the patients were correctly classified as “well” or “ill” by the questionary, and the correlation between questionary score and the clinical assessment of severity of disturbance was found to be +0·80.The “conspicuous psychiatric morbidity” of a suburban general practice assessed by a general practitioner who was himself a psychiatrist and validated against independent psychiatric assessment was found to be 20%. “Hidden psychiatric morbidity” was found to account for one-third of all disturbed patients. These patients were similar to patients with “conspicuous illnesses” in terms both of degree of disturbance and the course of their illnesses at six-month follow-up, but were distinguished by their attitude to their illness and by usually presenting a physical symptom to the general practitioner.When 87 patients who had been assessed as psychiatric cases at the index consultation were called back for follow-up six months later, two-thirds of them were functioning in the normal range. Frequency of attendance at the surgery in the six months following index consultation was found to have only a modest relationship to severity of psychiatric disturbance.It is argued that minor affective illnesses and physical complaints often accompany each other and usually have a good prognosis.     

Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review

The aim of this review was to assess recent progress in targeted radionuclide tumor therapy, focusing on the best delivery strategies. A literature search was conducted in PubMed, Web of Science, and Scopus using the terms “radionuclides”, “liposomes”, “avidin–biotin interaction”, “theranostic”, and “molecular docking”. The 10 year filter was applied, except for the avidin–biotin interaction. Data were retrieved from both preclinical and clinical settings. Three targeting strategies were considered: pretargeting, liposomes, and ligands. Pretargeting can be achieved by exploiting the avidin–biotin interaction. This strategy seems very promising, although it has been investigated mainly in resectable tumors. Radiolabeled liposomes have attracted new interest as probes to identify the most suitable patients for treatment with liposomal formulations of common chemotherapeutics. The use of ligands for the delivery of radiotherapeutics to a specific target is still the most appealing strategy for treating tumors. The most appropriate ligand can be identified by virtually simulating its interaction with the receptor. All strategies showed great potential for use in targeted radionuclide therapy, but they also have numerous drawbacks. The most promising option is probably the one based on the use of new ligands.     

Human Quadrupeds,Primate Quadrupedalism,and Uner Tan Syndrome

Since 2005, an extensive literature documents individuals from several families afflicted with “Uner Tan Syndrome (UTS),” a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or “devolution.” In support of this idea, individuals with “UTS” are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary “reversal,” no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with “UTS”, we found that these humans almost exclusively used lateral sequence–not diagonal sequence–quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the “devolution” hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.