A Simple Formula to Estimate Parathyroid Weight on 4D-CT, Predict Pathologic Weight, and Diagnose Parathyroid Adenoma in Patients with Primary Hyperparathyroidism.

BACKGROUND AND PURPOSE: Parathyroid gland weight is a clinically relevant parameter used to diagnose parathyroid adenomas intraoperatively. We evaluated the accuracy of a formula to estimate parathyroid weight on preoperative 4D-CT. MATERIALS AND METHODS: A single-institution retrospective study was performed in patients with primary hyperparathyroidism who underwent 4D-CT between January 2013 and December 2014 with subsequent parathyroidectomy and surgical cure. All patients had correct localization of a solitary parathyroid adenoma. The longest 3 dimensions of all identified parathyroid glands were measured on CT, and weight was estimated using the formula: weight4D-CT (mg) = 1 mg/mm3 × Length (mm) × Width (mm) × Height (mm) × π/6. We correlated weight4D-CT with pathology specimen weight (weightpathology). Using receiver operating characteristic analysis, we estimated the performance of weight4D-CT to discriminate a parathyroid adenoma from normal glands on 4D-CT and determined the optimal threshold based on the Youden index. RESULTS: One hundred sixteen patients (85 women, 31 men) were evaluated. Weight4D-CT was shown to be strongly correlated with weightpathology as demonstrated by Spearman ρ = 0.73 (P < .01), concordance correlation coefficient = 0.92 (95% CI, 0.89-0.94), and Cronbach α = 0.96. The performance of weight4D-CT for the diagnosis of parathyroid adenoma was excellent, with an area under the curve of 0.955 (95% CI, 0.925-0.985; P < .001). Based on the Youden index, the optimal threshold was >50 mg, with a sensitivity of 96.7% and a specificity of 95.7%. CONCLUSIONS: Radiologists can accurately estimate parathyroid adenoma weight on 4D-CT. This metric is highly correlated with pathologic weight, and a threshold cutoff of >50 mg can be used to distinguish parathyroid adenoma from normal glands.

Increased risk of strontium ranelate-related SJS/TEN is associated with HLA.

UNLABELLED: Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN. INTRODUCTION: In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant. METHODS: Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles. RESULTS: Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n = 76). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3 months (range 3 months to 8 years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12 weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n = 5). The majority of the accrued samples were of Han Chinese descent: controls (n = 72) and cases (n = 4). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA-A*33:03 (p = 0.002) and HLA-B*58:01 (p = 0.023). There was no significant association with any HLA-C or HLA-DRB1 alleles. CONCLUSIONS: This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate.

Danazol-induced Stevens-Johnson syndrome in a patient with systemic lupus erythematosus.

A patient with Stevens-Johnson syndrome related to danazol is presented.

Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study.

To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7-3785, P=6.9 × 10(-8)). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.

AFOMP POLICY STATEMENT No. 2: recommended clinical radiation oncology medical physicist staffing levels in AFOMP countries.

This document is the second of a series of policy statements being issued by the Asia-Oceania Federation of Organizations for Medical Physics (AFOMP). The document was developed by the AFOMP Professional Development Committee (PDC) and was released by the AFOMP Council in 2009. The main purpose of the document is to give guidance as to how many medical physicists are required to staff a radiation oncology department. Strict guidelines are difficult to define as work practices vary from country-to-country and from hospital-to-hospital. A calculation scheme is presented to aid in estimating medical physics staffing requirements that is primarily based on equipment levels and patient numbers but also with allowances for staff training, professional development and leave requirements.

Stevens-Johnson syndrome and toxic epidermal necrolysis: efficacy of intravenous immunoglobulin and a review of treatment options.

Toxic epidermal necrolysis (TEN) is a rare, severe adverse drug reaction. Steven-Johnson syndrome (SJS) represents the milder end of the spectrum. The exact pathogenesis of TEN and SJS is still unknown and many drugs, including prednisolone, cyclosporin and intravenous immunoglobulin (IVIG), have been used in an attempt to halt the disease process. The use of IVIG in particular is controversial. We share our experience with the use of IVIG in six patients with TEN. We will also review the various proposed mechanisms underlying TEN, the mechanism of action of IVIG in TEN and summarise useful treatment options.

Pustular pyoderma gangrenosum: an uncommon variant which is easily misdiagnosed.

Pustular pyoderma gangrenosum is a relatively uncommon clinical form of pyoderma gangrenosum; it presents with vesiculo-pustular lesions that do not develop into frank ulceration. We report a case of a 44-year-old man with associated ulcerative colitis, who was misdiagnosed as having necrotizing fasciitis. He underwent multiple debridements and a subsequent skin grafting procedure, but without improvement. The diagnosis of pyoderma gangrenosum is often challenging because there is no defining diagnostic clinical, laboratory, or histopathological feature. A high index of suspicion is, therefore, essential to diagnose pyoderma gangrenosum clinically because failure to do so in the early stages of the disease can lead to disfigurement and even unnecessary and detrimental surgery.

A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma.

BACKGROUND: Melasma is an acquired, chronic hypermelanosis for which therapy remains a challenge. OBJECTIVES: To compare the efficacy and safety of a triple combination [TC: fluocinolone acetonide 0.01%, hydroquinone (HQ) 4%, tretinoin 0.05%] vs. HQ 4% after 8 weeks of treatment of moderate to severe facial melasma in Asian patients. METHODS: This was a multicentre, randomized, controlled, investigator-blinded, parallel comparison study. East and South-East Asian patients aged 18 years or older, with a clinical diagnosis of moderate to severe melasma, were enrolled in this study. Patients were enrolled at baseline and treated daily for 8 weeks with TC cream (one application at bedtime) or HQ cream (twice daily). There were four study visits: at baseline and weeks 2, 4 and 8. The primary efficacy variable was the melasma global severity score (GSS). Other outcome measures included Melasma Area and Severity Index, global improvement and patient satisfaction. Safety was assessed through the reporting of adverse events. RESULTS: TC had superior efficacy to HQ for the primary variable: 77/120 patients (64.2%) on TC had GSS 'none' or 'mild' at week 8 vs. 48/122 patients (39.4%) on HQ (P < 0.001). The secondary efficacy variables confirmed these results. Patient satisfaction was in favour of TC (90/127, 70.8%, vs. 64/129, 49.6%; P = 0.005). More patients had related adverse events on TC (63/129, 48.8%) than on HQ (18/131, 13.7%) but most were mild and none was severe. CONCLUSIONS: Efficacy in Asians and patient satisfaction were superior with the fixed TC than with HQ 4%.

Phrynoderma: a forgotten entity in a developed country.

Phrynoderma is a type of follicular hyperkeratosis attributed to various nutritional deficiencies, most notably vitamin A. We report a case of a 31-year-old mentally-deficient man who was a resident of a voluntary welfare nursing home. He presented with characteristic hyperkeratotic follicular papules on his trunk in a setting of low serum level of vitamin A and malnutrition. Although commonly seen in South and East Asia, it is rarely reported in Singapore. However, there is still a population at risk here--patients with malabsorption and eating disorders, and institutionalised persons. Phrynoderma should, therefore, be considered in the differential diagnosis in patients with hyperkeratotic folliculitis, especially when malnutrition is also present.

Delaying acute graft-versus-host disease in mouse bone marrow transplantation by treating donor cells with antibodies directed at l-selectin and alpha4-integrin prior to infusion.

Acute graft-versus-host disease (GVHD) is still a major hurdle for successful bone marrow transplantation (BMT). Although many immunosuppressive drugs are available, none of them alone or in combination are able to completely abolish acute GVHD. The lifelong immunosuppression profoundly reduces the quality of life of BMT recipients. Therefore, new therapeutic approaches are needed. We previously reported that, in an acute GVHD model using SCID mice as recipient, incubating donor spleen cells with antibodies directed at CD49d and CD62L could significantly delay the occurrence of acute GVHD. To test the potential usefulness of this treatment in BMT, we examined this therapeutic protocol in a mouse BMT model. The present mouse BMT study confirmed our previous results that incubation of donor cells with antibodies directed at CD49d and CD62L prior to infusion into the recipient can effectively delay acute GVHD, allowing the recipients to recover from the side effects of total body irradiation. This one-time treatment is easy and simple and may be modified for clinical usage.

Topical calcipotriol ointment in the treatment of morphea.

A 5-year-old girl presented with a 2-month history of an indurated hypopigmented, atrophic plaque of biopsy-documented morphea over the right hip area. Previous treatment with 0,1% betamethasone valerate cream twice a day for 3 months failed to improve the lesion. She was treated with calcipotriol ointment twice daily, with nightly occlusion to the plaque for 9 months, and this resulted in resolution. No side effects were noted.

Thermosensory abnormalities and blood flow dysfunction in psoriatic skin.

BACKGROUND: Accumulating data have shown evidence of involvement of cutaneous nerve fibres and neuropeptides in psoriasis. Although ample evidence of structural and biochemical data exist no studies have been done on assessing the function of small nerve fibres in this disease. OBJECTIVES: To investigate the function of small nerve fibres in patients with psoriasis between psoriatic plaques and non-involved skin and in comparison with healthy controls. METHODS: We performed computerized psychophysical thermal sensory testing of warmth, cold and heat pain thresholds and skin blood flow using laser Doppler imaging in psoriatic lesions vs. non-involved skin and healthy skin. We evaluated these parameters before and immediately after barrier perturbation, and 1 week after as a measure of barrier repair. RESULTS: There is a significantly elevated warm and decreased cold sensation threshold in psoriatic skin compared with non-involved skin and skin of healthy controls in the same sites. These differences were particularly abnormal 1 week poststripping. The warm sensation threshold was significantly elevated in non-involved skin in psoriatics vs. skin of healthy controls after tape stripping. These findings suggest there is an abnormal function of cutaneous nerve fibres in response to trauma to the stratum corneum, which is not limited to the visible plaque but could be generalized and aggravated by stressful events. Skin blood flow was significantly elevated in psoriatic plaques and inversely correlated to warm sensation thresholds while in healthy controls a direct correlation was noted. CONCLUSIONS: Our data demonstrate an abnormal thermosensory response in psoriasis.

Screening for childhood obesity: international vs population-specific definitions. Which is more appropriate?

AIM: The objectives of this study are: (1) to study the relation between body mass index (BMI), percentage-weight-for-height (PWH) and percentage body fat (PBF) in Singaporean Chinese children; (2) to assess the applicability of an international definition of obesity (the International Obesity Task Force (IOTF) BMI) as a screening tool to detect childhood obesity, as compared with the current Singapore population-specific definition using PWH. METHODS: A total of 623 Chinese children aged 6-11 y (321 males, 302 females) were recruited from a school by proportionate (40%) stratified random sampling. BMI and PWH were calculated from weight and height, while PBF was derived using leg-to-leg bioelectrical impedance analysis. The strength of association among the three indices of obesity was assessed using Spearman's correlation coefficient. Obese children were defined as those above the 95th percentile of PBF in each age-gender-specific group. Sensitivity and specificity of IOTF-BMI cutoff values and PWH cutoff values were compared by testing their ability to correctly identify obese children. RESULTS: All three indices correlated well with one another (BMI:PWH r=0.83, BMI:PBF r=0.87, PWH:PBF r=0.76). Prevalence of obesity was lower using IOTF-BMI cutoffs (6.9%) than using PWH cutoffs (16.4%). The sensitivity and specificity of IOTF-BMI cutoff values were 75.0 and 96.0%, respectively, with sensitivity differing between boys (83.3%) and girls (66.6%) (P=0.35). In comparison, PWH cutoff values had higher sensitivity (91.6%) but lower specificity (86.6%), with no significant difference between the genders. CONCLUSION: IOTF-recommended BMI cutoff values had low sensitivity and may underestimate the local prevalence of childhood obesity. For screening purposes, we recommend that population-specific measures rather than international cutoff values be used.

Allopurinol hypersensitivity syndrome and acute myocardial infarction--two case reports.

INTRODUCTION: Allopurinol hypersensitivity syndrome is an idiosyncratic drug reaction characterised by an acute and severe multiorgan disease. It usually begins 2 to 6 weeks after starting allopurinol. The most important and critical characteristics are the presence of visceral involvement and haematological abnormalities; hepatitis, interstitial nephritis and eosinophilia are most frequently seen. However, cardiac involvement has not been previously reported. CLINICAL PICTURE: Two previously well young Chinese men presented with fever, rash and hepatitis 3 weeks after taking allopurinol. The clinicopathological presentation was typical of allopurinol hypersensitivity syndrome. TREATMENT AND OUTCOME: Both men received systemic corticosteroid therapy and had full recovery. A few months later, they each had an acute myocardial infarction with a fatal outcome, despite minimal cardiac risk factors and no family history of coronary artery disease. CONCLUSION: The immunologic process in allopurinol hypersensitivity syndrome may have caused coronary vasculitis and subsequent myocardial infarct. Alternatively, the idiosyncratic reaction may have damaged myocardium, with the resultant myocarditis masquerading as coronary artery disease. Patients with allopurinol hypersensitivity syndrome should be followed up for cardiac involvement.

The prevalence and descriptive epidemiology of atopic dermatitis in Singapore school children.

BACKGROUND: Atopic dermatitis is a common disease that appears to be increasing in frequency during recent decades. Most of the studies are based on the Western population, and there are few data in the Asian population. OBJECTIVES: To determine the prevalence and descriptive epidemiology of atopic dermatitis among school children in the general community in Singapore. METHODS: This is a questionnaire study of 12 323 students done over a 1-year period, comprising 7 year olds (4605), 12 year olds (3940) and 16 year olds (3778) from 19 primary and 17 secondary schools randomly selected in Singapore. All children had a complete cutaneous examination. The diagnosis of atopic dermatitis was based on the U.K. Working Party diagnostic criteria. The questionnaire was translated into Chinese and both the English and Chinese versions were issued simultaneously to the students. RESULTS: The 1-year period prevalence of atopic dermatitis was 20.8%. Atopic dermatitis was present in 22.7% of 7 year olds, 17.9% of 12 year olds and 21.5% of 16 year olds. The overall sex ratio was equal. There were slightly more boys with atopic dermatitis among the younger children (6 and 12 year olds, 1.18 : 1 and 1.19 : 1, respectively) but more girls were affected (1.57 : 1) among the 16 year olds. Atopic dermatitis was more common among the Chinese (21.6%) and Malays (19.8%) compared with the Indians (16%) and other races (14%). The onset of the disease occurred before the age of 10 years in 49.5% of the 16 year olds. "Pure" atopic dermatitis without concomitant respiratory allergies was noted in 788 respondents (30.7%); 1775 (69.3%) suffered from a "mixed" type, with 34.3% having allergic rhinitis, 9.5% having asthma and 25.5% having both asthma and allergic rhinitis. More boys had atopic dermatitis and concomitant respiratory allergies whereas more girls were affected with "pure" atopic dermatitis alone (1.4 : 1). At least one first-degree family member with atopy was noted in 1435 children (56%): atopic dermatitis (70%), asthma (62%) and allergic rhinitis (68%). Among siblings with one parent with atopic dermatitis, 37% had either a father or a mother with atopic dermatitis. Common aggravating factors reported included exercise, heat and sweating, grass intolerance, thick clothing and stress. Pityriasis alba was noted in 25% of the study population, keratosis pilaris in 13% and ichthyosis vulgaris in 8%. Most respondents had mild to moderate atopic dermatitis that could be controlled with a fairly simple regimen of moisturizers, topical steroids, antihistamines and antibiotics. CONCLUSIONS: The high prevalence of atopic dermatitis in Singapore is similar to that observed in developed countries, suggesting that environmental factors may be important in determining the expression of the disease.

Pemphigus vulgaris following varicella infection.

We describe a 26-year-old Indian man who presented with chickenpox and subsequently developed pemphigus vulgaris 17 days after initial resolution of lesions. The mechanism of progression from one disease to the other is postulated to be that of epitope spreading or molecular mimicry.