Application of iodinated starch powder using an atomizer spray gun - a new and effective tool to evaluate hypohidrosis.

BACKGROUND: Hypohidrosis is defined as diminished sweating in response to an appropriate thermal or sympathetic stimulus. When encountered in a clinical setting, it necessitates an accurate documentation of its pattern and extent to prognosticate the risk of associated heat-related illnesses. This can be achieved by thermoregulatory sweat testing which includes a starch-iodine sweat test that can be administered via various methods. OBJECTIVE: To describe and evaluate the effectiveness and safety of a novel method of using an atomizer spray gun in administering the starch-iodine test. METHODS: We describe the administration of the starch-iodine test via an atomizer spray gun (Series 700 Lab Model; Mitsuba Systems, Mumbai, India). The method was utilized for the evaluation of 30 individuals who presented with symptoms of hypohidrosis. RESULTS: Application of iodinated starch powder prepared in-house with the atomizer spray gun achieved a lightweight and homogeneous coat on our patients' skin which allowed for clear visualization of the sweating pattern in areas of anhidrosis. The sharp demarcation of the pathological regions enabled the precise calculation of the affected body surface area of impaired sweating. Unlike the starch-iodine tests using the Minor and Wada methods, neither staining of the skin nor irritation was detected in this method. CONCLUSION: We report a novel method of using an atomizer spray gun to perform the starch-iodine test in a rapid, reproducible, effective, and safe manner suitable for use in the clinical evaluation of hypohidrosis.

A study of topical methyl-aminolaevulinate red-light photodynamic therapy in the treatment of actinic keratosis in Chinese patients: a Singaporean experience.

BACKGROUND: The incidence of skin cancers has been increasing in Singapore, owing to the country's location near the equator and its ageing population. Topical photodynamic therapy (PDT) is a treatment method employing light and a topical photosensitizer to treat actinic keratosis (AK). Most published data to date on PDT have been drawn from studies of patient with Fitzpatrick skin phototypes I and II. AIM: To evaluate the effectiveness of PDT in the treatment of AK in patients with skin phototype IV in Singapore. METHODS: This was a retrospective analysis of 13 East Asian patients with AK treated with PDT at the National Skin Centre, Singapore, from 2006 to 2013. RESULTS: The overall clearance rate of AK at 3 months was 81.8% (9 of 11 patients; the other 2 were lost to follow-up). Mild to moderate pain during therapy was a common adverse event. CONCLUSIONS: PDT is a useful treatment method for AK in East Asian patients with skin phototype IV. Further larger prospective studies will be needed to evaluate its overall efficacy in East Asian patients.

Narrow-band ultraviolet B phototherapy for mycosis fungoides in children.

BACKGROUND: Mycosis fungoides (MF), the commonest form of cutaneous T-cell lymphoma, is uncommon in childhood. Phototherapy is a common treatment for MF. AIM: To retrospectively evaluate the efficacy and safety of narrow band ultraviolet B (NB-UVB) phototherapy for the treatment of MF n children. METHODS: We performed a retrospective analysis of children of East Asian descent with a clinical and histological diagnosis of MF, who were treated with NB-UVB phototherapy at the National Skin Centre, Singapore over the 5-year period 2004-2008. RESULTS: We identified nine suitable patients (eight boys, one girl; age range 5-12 years). Mean time from disease onset to diagnosis was 21 months (range 4 months to 3 years). There were two patients with stage 1A disease, six with stage 1B disease and one with stage 2A disease. Body surface area involvement ranged from 10% to 60%, and none of the patients had systemic involvement. Eight patients attained complete response after phototherapy, but only three had sustained remission after a follow-up of 1-3 years. Five patients had recurrence of lesions after an mean of 13.8 months (range 4-36). Treatment was well tolerated. CONCLUSION: Phototherapy using NB-UVB in the treatment of MF is efficacious and safe. We recommend it as first-line treatment in the management of early-stage MF in children.

Efficacy of iontophoresis with glycopyrronium bromide for treatment of primary palmar hyperhidrosis.

BACKGROUND: There is limited data on the efficacy of iontophoretic treatment of primary palmar hyperhidrosis using glycopyrronium bromide. The first line treatment for primary palmar hyperhidrosis is usually topical aluminium chloride, but clinical experience indicates that it is not effective for more severe disease. OBJECTIVE: To evaluate the efficacy of using glycopyrronium bromide iontophoresis in the treatment of primary palmar hyperhidrosis, and to evaluate if the benefit of treatment varies with the severity of disease. METHODS: This is an open-label study involving patients undergoing weekly treatment of iontophoresis with glycopyrronium bromide for 4 weeks. Gravimetric measurements of sweat production and subjective scores of palmar sweatiness were recorded prior to starting treatment and 1 week after the last treatment. Side-effects were monitored weekly. RESULTS: Twenty two of the 25 patients recruited completed the 4-week treatment. There was a significant mean improvement of 23.4 mg/min (P = 0.001) between baseline and post-treatment gravimetric measurements. Patients with a higher baseline sweat output demonstrated a trend towards a greater reduction in sweat production (Pearson's correlation correlation coefficient, r = 0.41). The patients experienced dryness of the palms for a mean duration of 5 days after iontophoresis. All patients reported an improvement in satisfaction scores and 81.8% reported an improvement in subjective severity scores. No serious side-effects were encountered during the study. CONCLUSIONS: Iontophoresis using glycopyrronium bromide is an effective and well-tolerated treatment for primary palmar hyperhidrosis. The possibility of its greater benefit in patients with more severe baseline disease requires verification.

Nasal-type extranodal natural killer/T-cell lymphoma presenting with extensive leg ulcers.

Primary cutaneous T-cell lymphomas are rare and can be difficult to classify precisely. We present a case of extranodal natural killer (NK)/T-cell lymphoma in a previously healthy, immunocompetent man who presented with extensive necrotic leg ulcers and disseminated skin nodules. Immunohistochemical studies revealed that the tumour cells were positive for CD3, CD30, granzyme B and T-cell intracellular antigen-1, and negative for CD5 and CD56, with positive staining for Epstein-Barr virus (EBV) RNA on in situ hybridization. A diagnosis of extranodal NK/T-cell lymphoma was made, based on the presence of cytotoxic granules and positive EBV RNA staining. The patient was treated with a regimen of chemotherapy comprising corticosteroids, intravenous methotrexate, ifosphamide, L-asparaginase and etoposide with initial response.

Endothelial potentiation of relaxation response to ascorbic acid in rat and guinea pig thoracic aorta.

The role of the endothelium was evaluated in the relaxation of rat and guinea pig aortic rings induced by ascorbic acid. Ascorbic acid relaxed rat and guinea pig aortic rings that were previously contracted with submaximal dose of phenylephrine (PE), in a concentration dependent manner. Removal of the endothelium significantly reduced the sensitivity but not the magnitude of the response to ascorbic acid. Methylene blue, but not propranolol, blocked the endothelial augmentation of vascular relaxation to ascorbic acid. Vessels precontracted with potassium chloride (high K+) were also relaxed by ascorbic acid. Methylene blue also inhibited the response to ascorbic acid in the intact vessels precontracted with high K+. A23187 and acetylcholine, but not ADP, variably caused endothelium dependent component relaxation in guinea pigs, whereas all of these three probes constantly caused it. In Ca(2+)-free medium, Ca(2+)-induced contraction of high K(+)-depolarized rat aorta was inhibited by the presence of ascorbate, which was more pronounced in endothelium intact rings than in endothelium denuded ones. PE-induced contraction in the presence of different concentrations of ascorbate reduced both the sensitivity and the maximal contractile force in rat aorta. Ascorbic acid (0.125-32 mM) did not change the pH in the medium. From these findings, it is speculated that 1) receptor- and potential-operated Ca2+ channels may be modulated by ascorbate, 2) endothelium has a significant role in promoting relaxation induced by ascorbic acid.

Viral warts in children seen at a tertiary referral centre.

INTRODUCTION: This study aims to determine the epidemiology of viral warts in children seen at a tertiary referral centre and the treatments used. MATERIALS AND METHODS: This is a retrospective study of viral warts in children aged 12 years and below seen at the National Skin Centre in the year 2000. RESULTS: There were 302 cases of viral warts, 187 (61.9%) in boys and 115 (38.1%) in girls. The greatest number was seen at age 12 and none were noted in those below 1 year of age. The racial breakdown was as follows: 69.9% Chinese, 13.9% Malays, 11.3% Indians and 4.9% of other ethnic groups. Treatment with liquid nitrogen was used most commonly in 267 (88.4%) cases, with a clearance rate of 48.3%. Electrocautery was used in 11 cases with complete clearance in 8 cases. CONCLUSION: Viral warts are common in children, but uncommon in infants. There is no difference in distribution of warts among the races in Singapore. Liquid nitrogen and electrocautery are effective treatments of viral warts in children.

Leprosy-associated eccrine syringofibroadenoma of Mascaro.

Eccrine syringofibroadenoma of Mascaro is a rare benign tumour. There are five subtypes, one of which is known to occur in reaction to inflammatory and neoplastic dermatoses. We describe a patient with previous lepromatous leprosy presenting with multiple flesh-coloured verrucous plaques over the right foot. Histology was consistent with eccrine syringofibroadenoma. To our knowledge, this is the first reported case of multiple eccrine syringofibroadenomata occurring in association with leprosy. The tumours in this case are most likely reactive in nature, subsequent to multiple traumatic events with tissue remodelling in an insensate foot affected by leprosy. It is less probable that the tumours are a result of scarring from recurrent infections. We also raise the possibility of a neuroeccrine interaction, with sympathetic neuropathy in leprosy as a contributing factor in the pathogenesis.

Cutaneous sarcoidosis in Asians: a report of 25 patients from Singapore.

Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin involving multiple organ systems. There has been no report so far to describe the epidemiological pattern of cutaneous involvement in sarcoidosis in South-East Asia with diverse ethnic groups. A retrospective study examining the clinicopathological features of all patients diagnosed with sarcoidosis at a tertiary dermatology centre in Singapore from 1980 to 2003 was conducted. Cutaneous sarcoidosis was diagnosed in 25 patients: 13 were Indian, 11 were Chinese and one was Eurasian. Cutaneous manifestations included papules, nodules, plaques and scarring alopecia. Extracutaneous involvement of lymph nodes (four patients), lungs (eight patients) and eyes (two patients) was seen. Eight patients had abnormal chest radiographic findings. Histopathological examination of skin lesions revealed noncaseating, epithelioid granulomatous infiltration in the dermis without evidence of mycobacterial infection, deep fungal infection or polarizable birefringent material. Treatment modalities included corticosteroids, hydroxychloroquine, isotretinoin, methotrexate and surgical excision. Five patients had complete resolution of the cutaneous lesions. Cutaneous sarcoidosis is rare in Asia and indeed in Singapore. Extracutaneous involvement is not uncommon and a thorough clinical evaluation should be undertaken.

Expression of divalent metal transporter 1 (DMT1) isoforms in first trimester human placenta and embryonic tissues.

BACKGROUND: Divalent metal transporter 1 (DMT1) is a transmembrane glycoprotein which mediates the proton-coupled transport of a variety of divalent metal ions. Two isoforms, which differ by the presence (DMT1-IRE) or absence (DMT1-nonIRE) of an iron-responsive element (IRE) in their 3' untranslated region, are implicated in apical iron transport and endosomal iron transport respectively. Although the expression pattern of DMT1 isoforms is tissue specific in adult, data regarding its expression in embryonic tissues are lacking. METHODS: Semiquantitative RT-PCR and immunohistochemistry were used to study the mRNA and protein expression of both DMT1 isoforms in embryonic tissues between 8 and 14 weeks gestational age. RESULTS: DMT1-IRE and DMT1-nonIRE expressions were ubiquitous in embryonic tissues examined. In the lung, statistically significant correlations were found between the levels of DMT1 isoform expression and gestational age. In the placenta, DMT1-IRE was the predominantly expressed isoform. Both isoform proteins were localized in embryonic epithelial cellular membrane. CONCLUSION: Both DMT1 isoforms are ubiquitously expressed in embryonic tissues in the first trimester. Predominant DMT1-IRE isoform expression in placenta suggests an iron-regulatory mechanism reminiscent of that in the adult duodenum. Epithelial distributions of both DMT1 isoforms are associated with the absorptive or excretory functions of the expressed tissues.

Different pharmacological characteristics of structurally similar benzylisoquinoline analogs, papaverine, higenamine, and GS 389, on isolated rat aorta and heart.

In the present study, we compared the pharmacological properties of structurally similar benzylisoquinoline compounds, papaverine, higenamine, and GS 389, using isolated rat aorta and atrial preparations. The three benzylisoquinoline compounds, concentration dependently, relaxed phenylephrine (3 microM) induced contraction of rat aortic rings, with the rank order of potency being higenamine > papaverine > GS 389. They also relaxed high K+ (60 mM) induced contraction, with the rank order of potency being papaverine > GS 389 >> higenamine. The relaxation was not modified by the presence of endothelium. To assess whether these compounds directly interfere with Ca2+ influx, the effects of these compounds on Ca(2+)-induced contraction in Ca(2+)-free media were examined. Among the three compounds, papaverine most strongly inhibited Ca(2+)-induced contraction of both K+ stimulated and phenylephrine-stimulated aorta. Higenamine was least potent in inhibition of Ca(2+)-induced contraction in high K+ depolarized aorta. In atrial tissues, lower concentrations of papaverine increased spontaneous beats and isometric tension, whereas above 30 microM its action was reversed. GS 389 decreased heart rate without affecting the contractility. On the other hand, higenamine concentration dependently increased both heart rate and isometric tension, as well as cyclic AMP levels in atrial tissues as a result of beta-receptor activation. Cyclic AMP and cyclic GMP dependent phosphodiesterases from rat atrial and ventricular tissue homogenates were inhibited by papaverine and GS 389, but not by higenamine. These results suggest that calcium antagonistic action of these compounds is at least in part responsible for vasodilation action, but not for cardiac action.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic comparison of two valproic acid formulations--a plain and a controlled release enteric-coated tablets.

We investigated the single- and multiple dose pharmacokinetics of a new controlled-release formulation (Orfil retard enteric coated tablet) of valproic acid in comparison with those of the plain tablet as a reference. Twelve healthy volunteers were given each formulation of 300 mg in the single-dose study. In the steady-state multiple-dose study, twelve epileptic patients received 1200 mg/day of the reference drug (300 mg 9 AM, 300 mg 3 PM, 600 mg 9 PM) and the test formulation (600 mg 9 AM, 600 mg 9 PM) with at least one week interval in cross-over manner. The AUC values of the test controlled release formulation were 91.7% (95% confidence interval: 78.4-100.4%) of the reference drug in the single-dose study and 98.2% (95% confidence interval: 86.2%-109.9%) in the steady-state study. The AUC's of the two formulations were not significantly different by ANOVA test. The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158.4%, Cmax: 52.5% of the reference) and multiple-dose study (Tmax: 153.5% of the reference). The MRT values of the test formulation were also significantly greater (129.4% of the reference) in the single-dose study. Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet. Area deviation was even smaller in the test regimen of the controlled release formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin.

We have investigated changes in the pharmacokinetics of prednisolone caused by co-administration or discontinuation of rifampin. Serial IV pharmacokinetic studies of prednisolone (1 mg/kg) in groups of 3 patients over a 1 month period of rifampin co-treatment or after its withdrawal, revealed significant changes in the area under the curve, the total clearance, the non-renal clearance and the half-life. The changes in the pharmacokinetic parameters reached a 1.5 to 2-fold plateau after 2 weeks and the half maximal effect was attained within 5 days. Neither the volume of distribution nor the protein binding of prednisolone were significantly altered.

NO- and NO2-carrying molecules potentiate photorelaxation in rat trachea and aorta.

Photorelaxation elicited by ultraviolet light (366 nm) was investigated on isolated rat thoracic aorta and trachealis. Rat tracheal smooth muscle but not aorta did not show UV-induced photorelaxation. Both streptozotocin, NO-carrying molecule and N omega-nitro-L-arginine, NO2-carrying molecule significantly enhanced photorelaxation, concentration-dependently, in rat trachealis and aorta. Methylene blue (10 microM) inhibited the potentiation action of streptozotocin and N omega-nitro-L-arginine in both tissues. Superoxide dismutase (300 U/ml) enhanced streptozotocin- and N omega-nitro-L-arginine-potentiated photorelaxation in rat trachealis, while pyrogallol (0.1 mM), a potent O2- generating agent, inhibited streptozotocin-potentiated photorelaxation in trachealis. Streptozotocin was much more effective than N omega-nitro-L-Arginine in potentiating of photorelaxation elicited by UV light in both tissues. From these findings, we conclude that streptozotocin and N omega-nitro-L-arginine produce EDRF like labile substance(s) by UV irradiation.

Possible superoxide radical-induced alteration of vascular reactivity in aortas from streptozotocin-treated rats.

We investigated the possible involvement of the superoxide (.O2-) radical in alterations of vascular reactivity and phosphoinositide (PI) turnover in aortas from streptozotocin (STZ)-induced diabetic (4 week) rats. STZ treatment increased the maximal contractile response of the aorta to norepinephrine (NE), phenylephrine (PE) and high K+, whereas the sensitivity remained unaltered. Ca(++)-induced contractions in the presence of maximally effective concentrations of PE and K+ were also augmented after STZ treatment. The increased maximal response was associated with both decreased endothelium-dependent relaxation and increased NE-induced PI turnover. Pyrogallol (PYR), a potent .O2- generating agent, did not affect basal tone or PI turnover but, depending on concentrations, it significantly increased or decreased both the contractile response to PE and NE-induced PI turnover in control aorta. In contrast, PYR decreased NE-induced PI turnover in diabetic aorta. The malondialdehyde content of liver, serum and aorta, and of .O2- from aorta of diabetic rats, were increased significantly. Copper catalyzed oxidation of ascorbic acid resulted in contraction followed by relaxation, depending upon the ascorbic acid concentration in both control and diabetic aorta. Pretreatment with superoxide dismutase (300 U/ml) prevented the PYR-induced potentiation of the PE contraction, but not of NE+PYR-induced PI turnover in control aorta and decreased further NE+PYR-induced PI turnover in diabetic aorta. The present findings indicate that .O2- may be responsible, at least in part, for the impaired endothelial integrity, enhanced alpha adrenergic receptor-mediated PI turnover and augmented contractility, possibly through modification of calcium channels in STZ-induced short-term (4 week) diabetic rat aorta.