Vulval acne: a case series describing clinical features and management.

Intermittent inflammation of the vulval pilosebaceous units is common and usually self-limiting, but some patients experience recurrent and more troublesome symptoms. There is a scarcity of information on this problem. We describe the clinical and histological features in these patients and the response to treatment. A retrospective, observational study of 16 patients with this phenomenon of recurrent, protracted folliculocentric inflammation of the vulval pilosebaceous unit was performed. Details on the clinical features, histology and response to treatment were collected. Mean age at presentation was 32 years (range 21-45). All patients reported recurrent painful papules and pustules on the labia majora and labia minora. Nine patients reported a cyclical pattern to the development of lesions, with premenstrual exacerbation being most common. Histological examination of these lesions showed a folliculocentric microabscess formation surrounded by an acute and chronic inflammatory cell infiltrate, with a focal foreign-body granulomatous reaction. All our patients responded well to tetracycline, antiandrogenic or retinoid therapy. We propose the term 'vulval acne' for this condition and propose a stepwise approach to its management. We hope to highlight this as a common but underreported entity.

The impact and indications for Oncotype DX on adjuvant treatment recommendations when third-party funding is unavailable.

OBJECTIVES: Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs. METHODS: Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. RESULTS: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. CONCLUSION: Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.

A 10-year longitudinal follow-up study of a U.K. paediatric transplant population to assess for skin cancer.

BACKGROUND: Our earlier study, published in 2004,found no skin cancer in a cohort of paediatric organ transplant recipients (POTRs) 5-16 years post-transplantation. We re-evaluated the same cohort 10 years later. OBJECTIVES: To determine the prevalence of premalignant and malignant skin lesions and identify known risk factors associated with melanocytic naevi in a U.K. paediatric transplant population. METHODS: Ninety-eight POTRs from the original 2004 study were invited to participate in this longitudinal follow-up study. History of sun exposure, demographics and transplantation details were collected using face-to-face interviews, questionnaires and case note reviews. Skin examination was performed for regional count of malignant lesions, benign and atypical naevi. RESULTS: Of the 98 patients involved in the initial study, 45 POTRs (eight kidney, 37 liver), with a median follow-up of 19 years (range 15-26 years), agreed to participate. Neither skin cancer nor premalignant lesions were detected in these patients. When compared with the 2004 cohort, 41 patients in our current cohort had increased numbers of benign naevi (P < 0·001) with 11 patients having ≥ 50 benign naevi. Seventy-one per cent of benign naevi in our 2014 cohort occurred on sun-exposed sites (13% head/neck, 35% arms and 23% legs). Patients who regularly used sunscreen had more benign naevi on their arms (P = 0·008). CONCLUSIONS: Although skin cancer was not observed in our cohort, we identified a significant increase in the number of benign naevi, particularly in those reporting frequent sunburn and sunscreen use.

Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.

Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-nuclear factor of activated T cells (NFAT) pathway, including cyclosporine A or tacrolimus, is commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threatening conditions. A component of the A. fumigatus cell wall, ß-glucan, is recognized by dendritic cells (DCs) via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important antifungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.

Intra-articular nodular fasciitis: an unexpected diagnosis for a joint lesion: a case report.

UNLABELLED: Pathological lesions in and around a joint can arise from underlying dermis, subcutis, deep muscle, bone or synovium. Clinical presentation can include joint pain, joint swelling, palpable masses and mechanical restriction. Whilst giant cell tumour of tendon sheath, pigmented villonodular synovitis, synovial chondromatosis, lipoma arborescens, juxta articular myxomas and inflammatory arthritis are the better-known conditions of the joint. Intra-articular nodular fasciitis, on the other hand, is less well recognized both clinically and radiologically. It is rarely seen in routine practice and is only described in case reports in the literature. Due to the non-specific clinical and radiological findings as well as the unfamiliarity with the entity, the diagnosis of intra-articular nodular fasciitis is usually clinched only after histological examination. We present a case of intra-articular nodular fasciitis arising in the knee joint which was not suspected clinically or radiologically. KEY WORDS: Intra-articular, nodular fasciitis, joint, knee, MRI.

Sequestrated meningocoele within a naevus sebaceous of Jadassohn on the scalp of a child.

Sequestrated meningocoele is an uncommon developmental anomaly in which meningothelial elements are found in the skin or subcutaneous tissue without underlying bony defect. By contrast, naevus sebaceous of Jadassohn (NSJ) is a circumscribed hamartomatous lesion occurring in about 0.3% of newborns. We report a child with a histologically confirmed sequestrated meningocoele within an NSJ on his scalp vertex. Such an occurrence has not been reported previously.

Nox4-dependent ROS modulation by amino endoperoxides to induce apoptosis in cancer cells.

Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance is one critical malefactor of metastatic cancer cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few have been clinically employed due to their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy to synthesize novel amino endoperoxides and their derivatives with good yields and stabilities. In vitro cell-based assays revealed that 4 out of the 14 amino endoperoxides selectively induce metastatic breast carcinoma cells but not normal breast cells to undergo apoptosis, in a dose-dependent manner. Mechanistic studies showed that the most potent amino endoperoxide, 4-Me, is selective for cancer cells expressing a high level of Nox4. The anticancer effects are further shown to be associated with reduced O2(-):H2O2 ratio and increased ·OH level in the cancerous cells. Animal study showed that 4-Me impairs orthotopic breast tumor growth as well as tumor cell metastasis to lymph nodes. Altogether, our study suggests that anticancer strategies that focus on redox-based apoptosis induction in tumors are clinically viable.

Regulation of inducible BALT formation and contribution to immunity and pathology.

Inducible bronchus-associated lymphoid tissue (iBALT) is an organized tertiary lymphoid structure that is not pre-programmed but develops in response to infection or under chronic inflammatory conditions. Emerging research has shown that iBALT provides a niche for T-cell priming and B-cell education to assist in the clearance of infectious agents, highlighting the prospect that iBALT may be engineered and harnessed to enhance protective immunity against respiratory pathogens. Although iBALT formation is associated with several canonical factors of secondary lymphoid organogenesis such as lymphotoxin-α and the homeostatic chemokines, CXCL13, CCL19, and CCL21, these cytokines are not mandatory for its formation, even though they influence its organization and function. Similarly, lymphoid tissue-inducer cells are not a requisite of iBALT formation. In contrast, dendritic cells are emerging as pivotal players required to form and sustain the presence of iBALT. Regulatory T cells appear to be able to attenuate the development of iBALT, although the underlying mechanisms remain ill-defined. In this review, we discuss facets unique to iBALT induction, the cellular subsets, and molecular cues that govern this process, and the contribution of this ectopic structure toward the generation of immune responses in the pulmonary compartment.

Dopamine-secreting phaeochromocytomas and paragangliomas: clinical features and management.

Most functional phaeochromocytomas/paragangliomas produce noradrenaline and/or adrenaline. Those that produce dopamine are rare. We describe the distinguishing clinical features of dopamine-secreting phaeochromocytomas and paragangliomas from those that secrete noradrenaline/adrenaline and the impact on their management. We present a case of a dopamine-secreting paraganglioma from our institution and review 14 case reports of dopamine-secreting phaeochromocytomas/paragangliomas published between 1984 and 2008. As observed in the literature, 80% of the tumours were extra-adrenal. Most patients presented with non-specific symptoms or mass effect without the classical presentation of catecholamine excess. The majority were diagnosed with urinary or plasma dopamine. Five patients had malignant tumours and 12 patients underwent surgical resection of the primary tumours. Unlike noradrenaline/adrenaline-secreting phaeochromocytomas/paragangliomas, dopamine-secreting tumours lack a classical presentation, are extra-adrenal and have a higher malignant potential. A routine inclusion of urinary or plasma dopamine as part of catecholamine screening in all suspected phaeochromocytomas and paragangliomas is recommended.

Acute stroke patients with high BMI are less likely to have severe disability at initial presentation.

This is a prospective study to determine the severity of disability and prognosis of acute stroke patients related to their Body Mass index (BMI). A total of 79 consecutive CT-scan-proven acute stroke patients who were admitted to Hospital Tuanku Ja'afar, Seremban between November 2006 and April 2007 were recruited (male:female 49:30; mean age 62.7 years; ischemic stroke 70, intracerebral bleed 9). The patients were divided according to BMI less than 25 (Group A) and equal or greater than 25 (Group B). Severity of disability was measured between 24-48 hours by modified Rankin's score. Patients were followed up after one month. Thirty-seven patients had severe disability (Rankin Score 5). Twenty-nine patients had adverse outcomes including 11 deaths and 18 rehospitalizations or prolonged hospital/nursing home stay. 34.3% of Group B had severe disability compared to 56.8% of Group A (chi2 P = 0.046). Conversely 42.9% of Group B had adverse events at one month compared to 31.8% of Group A (chi2 P = 0.312). There were no statistical differences between high- and low-BMI groups for gender ratio, smoking, hypertension, diabetes, prior cardiovascular disease, mean age, mean lipid profile and blood pressure. When comparing patients with Rankin Score 1-4 versus 5, age and BMI were statistically significant between the two groups. By multivariate analysis only age is independent predictor for severe disability (P < 0.05). The results of this pilot study should be confirmed in larger prospective multicentre trial.

Unusual cause of seizures in Singapore: neurocysticercosis.

Neurocysticercosis is the commonest cause for adult onset of seizures in developing countries, and is relatively uncommon in Singapore. However, with the influx of foreign workers from developing countries, we need to consider it as a differential diagnosis in our approach to adult-onset seizures in this group of patients. We describe a neurocysticercosis occurring in a 22-year-old Indian man who presented with a single episode of generalised tonic-clonic seizures. Magnetic resonance imaging of the brain showed a well-defined, hypointense lesion in the cortical and subcortical regions of the left frontal lobe with adjacent vasogenic oedema. Following contrast administration, a well-defined ring enhancement was noted, with suggestion of some internal enhancement. Imaging findings were suggestive of neurocysticercosis. Follow-up magnetic resonance imaging of the brain two weeks after treatment showed lesion resolution.

The comparison of discomfort level between upper arm and forearm tourniquet.

The conventional upper arm tourniquet used for hand and wrist operations may cause significant discomfort to patient when the procedure is performed under local anaesthesia. Forearm tourniquet causes less muscle ischeamia and pain. The discomfort experienced while using a forearm and upper arm tourniquet was assessed in 96 healthy subjects. Tourniquet placed on both sides was inflated sequentially to 250mmhg for five minutes on different hand. The discomfort level was assessed using a small visual analogue scale and complications were recorded. In the upper arm tourniquet, 24.9% had mild, 60.5% had moderate and 14.6% had severe pain whereas with forearm tourniquet, 99% had mild pain and only 1% had moderate pain. Seventy-nine percent of the subjects tested with forearm tourniquet had no discomfort at all. The average discomfort level for upper arm and forearm tourniquet was 4.72 and 0.39 respectively, which is statistically significant. Complications that were observed only in upper arm tourniquet included prolonged tingling, burning sensation and discomfort and stiffness of the upper limb. We concluded that forearm tourniquet was safe and well tolerated and should be used more often when indicated.

Positron emission tomography scanning in the assessment of patients with lymphoma.

BACKGROUND: The detection of lymphoma by computed tomography (CT) scanning is known to be improved by positron emission tomography (PET) and/or gallium scanning, although the direct comparative accuracy of these imaging modalities remains a subject of ongoing review. AIMS: The aim of the present study was to compare PET scanning with conventional imaging (CT and/or gallium scanning) in patients with lymphoma. METHODS: A retrospective study of 38 patients (25 men; 13 women; median age 39.5 years; range 18.0-81.0 years) who had had PET scans (24 scans at initial staging and 46 scans at restaging, including suspected disease relapse) was carried out. Thirty-one concurrent gallium scans had been performed. Disease was validated with clinical follow up or biopsy. RESULTS: The sensitivities of PET and CT at initial staging were 96 and 71%, respectively. PET identified additional sites of disease compared with CT in 29% of patients. Of the 15 patients who had had all three imaging modalities, the sensitivities of PET, CT and gallium were 93, 67 and 87%, respectively. At treatment completion, the positive predictive values of PET, CT and gallium scans for relapse given a residual mass were 100, 33 and 0%, respectively (P = 0.006 for PET and CT comparison). The negative predictive values of PET, CT and gallium were 76, 0 and 70%, respectively (P-value not significant). In suspected disease relapse, PET results changed management in 50% of patients. CONCLUSION: Compared with CT and gallium scans, PET has superior accuracy in staging and restaging, and its greatest value lies in its positive predictive value for relapse in patients with residual masses.

Nitrogen dioxide exposure from domestic gas cooking and airway response in asthmatic women.

BACKGROUND: Previous studies have not found a consistent association between exposure to domestic cooking using gas appliances and exacerbation of asthma. We investigated the immediate airflow response to acute exposure from single episodes of gas cooking, and peak airflow variability from continued exposure to repeated episodes of gas cooking in a group of non-smoking asthmatic women. METHODS: Sixteen adult non-smoking women with mild to severe persistent asthma were studied. The acute short term level of nitrogen dioxide (NO2) during gas cooking episodes and the mean exposure to NO2 from repeated gas cooking episodes were measured over a 2 week period, as well as proxy measures of frequency of cooking on each day and the length of time spent cooking each day. Their asthma status was monitored using peak expiratory flow rates (PEFR) before and after cooking, 2 week self-recorded serial readings of PEFR, respiratory symptom severity score, and use of rescue bronchodilators for acute asthma attacks. RESULTS: Cooking was significantly associated with an immediate mean fall in PEFR of 3.4% (p=0.015, paired t test). The acute short term NO2 level during cooking was significantly correlated with the fall in PEFR (r=-0.579; p=0.019). The frequency of cooking over a 2 week period was positively correlated with the mean exposure to NO2 (r=0.529; p=0.042). Continued exposure to NO2 over a 2 week period was associated significantly with increased frequency of rescue bronchodilator usage for asthma attacks (r=0.597; p=0.031). However, it was negatively associated with PEFR variability (r=-0.512; p=0.051) and respiratory symptom severity score (r= -0.567; p=0.043), probably due to the masking effects of bronchodilator treatment. CONCLUSIONS: Acute short term exposure to NO2 from single episodes of gas cooking is associated with immediate airflow limitation. Continued exposure from repeated episodes of gas cooking in asthmatic women is associated with greater use of rescue bronchodilators.

An epidemiological survey of methicillin-resistant Staphylococcus aureus in a tertiary referral hospital.

Over a 30-month period from July 1995 to December 1997, new detections of methicillin-resistant Staphylococcus aureus (MRSA) were prospectively studied in a tertiary referral hospital. The aims of the study were to determine the incidence of colonization of patients admitted to each of the hospital's 39 clinical units and ascertain where each patient had become colonized. Epidemiological information (time to detection, ward movement, admission to other hospitals, data on MRSA isolations in hospital wards) and phage typing were used by the hospital's infection control unit to make this determination. Routine containment procedures included cohorting, flagging and triclosan body washes. Surveillance cultures were collected infrequently. Patients known to be colonized with MRSA were excluded from orthopaedic and haematology wards. During the study period, 995 patients were found to be newly colonized. The incidence of colonization varied from nil to 72 per 1000 admissions, being highest in the main intensive care unit and in services which frequently used that unit. The incidence of colonization in elective orthopaedic surgery (< 1 per 1000) and haematology (3 per 1000) was very low. Determining the place where patients acquired MRSA was made difficult by the high frequency of endemic phage types and frequent patient transfer between wards. Epidemiological data suggested that the main intensive care unit and surgical wards nursing patients with colorectal, urological and vascular diseases were the places where most patients became colonized. MRSA was never acquired by patients nursed in wards which practised an exclusion policy towards patients known to be colonized with MRSA. Our data suggest that in tertiary referral hospitals, where MRSA is not only endemic but frequently imported from other hospitals, it is possible to establish areas where MRSA is never acquired.

NF-kappaB to the rescue: RELs, apoptosis and cellular transformation.

The REL/NF-kappaB/IkappaB superfamily of signal transducers and transcription factors are paradigmatic of molecular mechanisms by which rapid responses in the immune system can be achieved. NF-kappaB proteins have been implicated in diverse processes such as the ontogeny of the immune system, immune responses to pathogens and, importantly, in contributions to the multistage processes of oncogenesis, as described in this review. NF-kappaB and its regulators, the IkappaBs, are linked to pro- and anti-apoptotic events as well as signaling systems contributing to cellular transformation. How are these disparate events controlled to effect normal and abnormal processes in cells? Here we explore a few of the many events in which NF-kappaB appears to participate and processes that integrate signals to control important stages of oncogenesis.

Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast cancer risk.

Metabolism of estradiol occurs via two mutually exclusive hydroxylative pathways, yielding metabolites of divergent biological properties. 2-hydroxyestrone (2OHE1) is anti-estrogenic while 16 alpha-hydroxyestrone (16 alpha OHE1) is a potent estrogen. The ratio of 2OHE1 to 16 alpha OHE1 (2/16 alpha-OHE1 ratio) represents the net in vivo estrogenic activity. In this study, we sought to determine if the urinary 2/16 alpha-OHE1 ratio could be a predictor of breast cancer risk and the factors which influence this ratio. Variables analysed included age at diagnosis, menopausal status, parity, use of oral contraceptives, body mass index, serum levels of insulin-like growth factor-I (IGF-I), IGF binding proteins (BPs) and the presence of breast cancer. Serum and urine were collected from 65 breast cancer patients and 36 controls after an overnight fast. Urinary estrogen metabolites were measured by enzyme immunoassays while serum levels of IGF-I, BP-1 and BP-3 were determined by immunoradiometric assays. 2OHE1 levels and 2/16 alpha-OHE1 ratios were significantly lower (P < 0.05) while 16 alpha OHE1 levels were higher (P < 0.01) in cancer patients. Multiple linear regression analysis showed that levels of urinary metabolites were influenced by parity and breast carcinoma. 2/16 alpha-OHE1 ratio correlated positively with serum BP-3 level (P = 0.03). By multiple logistic regression, 2/16 alpha-OHE1 ratio was the most significant factor predictive of breast cancer. The odds ratio for women with higher 2/16 alpha-OHE1 ratios was 0.10 (0.03-0.38, 95% confidence interval). In conclusion, the profile of urinary estradiol metabolites was distinctly altered in breast cancer patients. In addition, BP-3 may be a potential mechanism by which estradiol metabolites influence breast cancer progression. As 16 alpha OHE1 has been shown to initiate neoplastic transformation of mammary epithelial cells, the 2/16 alpha-OHE1 ratio may serve as a biomarker of increased risk of breast cancer.