D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.
Adolescent ; Adult ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Antibodies, Antineutrophil Cytoplasmic ; Biopsy ; Child ; Cyclophosphamide ; Diagnosis ; Dyspnea ; Emergency Service, Hospital ; Female ; Glomerulonephritis ; Hematuria ; Hemoptysis ; Hemorrhage ; Hepatolenticular Degeneration ; Humans ; Penicillamine ; Peroxidase ; Plasmapheresis ; Proteinuria ; Trientine ; Vasculitis

No abstract available.
Penicillamine*

PURPOSE: To evaluate clinical and laboratory profile of Wilson's disease (WD) in children. METHODS: This cross sectional study was conducted at Bangabandhu Sheikh Mujib Medical University Hospital. Bangladesh, over a period of 3 years. One hundred consecutive children of WD between 3 to 18 years of age were evaluated. RESULTS: Mean age was 8.5+/-1.5 years. Male female ratio was 2:1. Ninety-one percent of patients were Muslim and 9% Hindu. A total of 53% cases of hepatic WD presented between 5 to 10 years of age and most of the neurologic WD manifested in 10-15 years age group. Sixty-nine children presented only with hepatic manifestations, 6 only with neurological manifestations, 14 with both hepatic and neurological manifestation, 10 children was asymptomatic and 1 patient presented with psychiatric features. WD presented as chronic liver disease (CLD) in 42%, CLD with portal hypertension in 34%, acute hepatitis in 20% and fulminant hepatic failure in 4% cases. Stigmata of CLD were found in 18% patients. Keiser-Fleischser ring was found in 76% total patients. Elevated serum transaminase was found in 85% cases, prolonged prothrombin time in 59% cases and hypoalbuminaemia in 53% cases. A total of 73% patients had low serum ceruloplasmin, basal urinary copper of >100 microg/day was found in 81% cases and urinary copper following penicillamine challenge of >1,200 microg/day was found in 92% cases. CONCLUSION: Majority of studied WD children presented with hepatic manifestation of which 76% presented with CLD. Any child presented with jaundice after the age of 3 years should be investigated for WD.
Bangladesh ; Ceruloplasmin ; Child* ; Christianity ; Copper ; Female ; Hepatitis ; Hepatolenticular Degeneration* ; Humans ; Hypertension, Portal ; Islam ; Jaundice ; Liver Diseases ; Liver Failure, Acute ; Male ; Neurologic Manifestations ; Penicillamine ; Prothrombin Time

Toxic epidermal necrolysis (TEN) is rare but life-threatening severe cutaneous adverse reaction, which is mostly induced by drugs. It characterized by widespread epidermal necrosis, resulting in bullae with sloughing and frequent involvement of the mucous membrane. Due to high mortality, management of patients requires prompt withdrawal of the causative drug, appropriate supportive care, and consideration of immune-modulating agents, such as intravenous immunoglobulin or corticosteroids. Wilson disease is an inherited disorder of copper transport that results in excessive accumulation of copper in the body. Copper chelation with penicillamine is an effective first line therapy in most patients. We present a 20-year-old man with Wilson disease who developed TEN following administration of penicillamine. He was successfully treated with systemic corticosteroid, intravenous immunoglobulin, and supportive management.
Adrenal Cortex Hormones ; Copper ; Hepatolenticular Degeneration* ; Humans ; Immunoglobulins ; Mortality ; Mucous Membrane ; Necrosis ; Penicillamine ; Stevens-Johnson Syndrome* ; Young Adult

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.
Administration, Oral ; Adolescent ; Chelating Agents ; administration & dosage ; adverse effects ; therapeutic use ; Chelation Therapy ; adverse effects ; methods ; Child ; Copper ; urine ; Drug Administration Schedule ; Drug Hypersensitivity ; etiology ; Drug Therapy, Combination ; Hepatolenticular Degeneration ; drug therapy ; Humans ; Injections, Intravenous ; Male ; Neutropenia ; chemically induced ; Partial Thromboplastin Time ; Penicillamine ; administration & dosage ; adverse effects ; therapeutic use ; Prothrombin Time ; Thrombocytopenia ; chemically induced ; Time Factors ; Treatment Outcome ; Unithiol ; administration & dosage ; adverse effects ; therapeutic use

A 64-year-old woman was diagnosed with non-small cell lung cancer. Her disease was stage 4 (T2N2M1) with squamous cell carcinoma. She had been treated with docetaxel and carboplatin. After a completion of 11 cycle of chemotherapy, edema appeared on both feet and had spread rapidly up to the pretibial area without response to diuretics. Sclerotic changes and pigmentation followed but both knees and other parts of the body were spared. There was no evidence of vascular occlusions. On serologic tests, antinuclear, anti-centromere, and anti-topoisomerase I antibodies were all negative. A skin biopsy revealed diffuse infiltration of lymphocytes and discretely thickened collagen bundles in the superficial dermis. After discontinuing docetaxel chemotherapy, she was treated with prednisolone and D-penicillamine and sclerotic changes on the lower legs were improved.
Antibodies ; Biopsy ; Carboplatin ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Collagen ; Dermis ; Diuretics ; Edema ; Female ; Foot ; Glycogen Storage Disease Type VI ; Humans ; Knee ; Leg ; Lung Neoplasms ; Lymphocytes ; Penicillamine ; Pigmentation ; Prednisolone ; Sclerosis ; Serologic Tests ; Skin ; Taxoids

Opioid receptors have been pharmacologically classified as micro, delta, kappa and epsilon. We have recently reported that the antinociceptive effect of morphine (a micro-opioid receptor agonist), but not that of beta-endorphin (a novel micro/epsilon-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of micro-, delta-, kappa- and epsilon-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a 60Co gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water (52degrees C) tail-immersion test. Morphine and D-Ala2,N-Me-Phe4,Gly-olenkephalin(DAMGO), [D-Pen2-D-Pen5]enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U50,488H), and beta-endorphin were tested as agonists for micro, delta, kappa, and epsilon-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of beta-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on micro- and epsilon-opioid receptor agonists, we assessed pretreatment effects of beta-funaltrexamine (beta-FNA, a micro-opioid receptor antagonist) or beta-endorphin1-27 (beta-EP1-27, an epsilon-opioid receptor antagonist), and found that pretreatment with beta-FNA significantly attenuated the antinociceptive effects of morphine and beta-endorphin by WBI. beta-EP1-27 significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of beta-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for micro- and epsilon-opioid receptors.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; Animals ; beta-Endorphin ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; Enkephalin, D-Penicillamine (2,5)- ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Morphine ; Naltrexone ; Receptors, Opioid ; Water ; Whole-Body Irradiation

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents (Icap). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on Icap. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on Icap. The PKG inhibitor KT5823 prevented the inhibition of Icap by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.
Animals ; Benzoates ; Carbazoles ; Cyclic GMP-Dependent Protein Kinases ; Ganglia, Spinal ; Guanosine ; Guanylate Cyclase ; Hemoglobins ; Humans ; Imidazoles ; Neurons ; Nitric Oxide ; Nitroprusside ; Penicillamine ; Phosphotransferases ; Proteins ; Rats ; Receptors, Cytoplasmic and Nuclear ; Sensory Receptor Cells ; Spinal Nerve Roots ; Tissue Donors

A 62-year-old Korean woman was admitted to our department to evaluate a chronic cough and sputum, which had begun several weeks ago. The patient had been diagnosed with systemic sclerosis in 2004. Autoantibody screening tests were negative for the anticentromere and antitopoisomerase antibodies. She received therapy with combined cyclophosphamide, a calcium channel blocker, D-penicillamine, and low dose steroid. In 2006, a pulmonary function test (PFT) showed a restrictive pattern, and a computed tomography (CT) scan of the lungs revealed interstitial lung disease, but no symptoms were present, so we maintained her on the medication. In October 2008, a chest x-ray and CT scan of the lungs demonstrated aggravation with bilateral basal interstitial infiltrates and hilar lymphadenopathy. Cyclophosphamide pulse therapy was conducted six times during 6 months, but there was no change on her chest CT and PFT, and she had no symptoms, so we decided to follow up. On admission, no significant interval change in the reticular opacity of both lower lungs was observed, but several lymph nodes were enlarged on a chest and neck CT. The skin showed multiple large polygonal-shaped scaled lesions on her upper and lower extremities. Biopsies were taken from the skin of the lower extremities and the left cervical lymph node. Typical non-caseating granulomas corresponding to sarcoidosis were found along with systemic sclerosis findings.
Antibodies ; Biopsy ; Calcium Channels ; Cough ; Cyclophosphamide ; Female ; Follow-Up Studies ; Granuloma ; Humans ; Lower Extremity ; Lung ; Lung Diseases, Interstitial ; Lymph Nodes ; Lymphatic Diseases ; Mass Screening ; Middle Aged ; Neck ; Penicillamine ; Respiratory Function Tests ; Sarcoidosis ; Scleroderma, Systemic ; Skin ; Sputum ; Thorax

OBJECTIVETo reassess the diagnostic value of 24 hour urinary copper excretion in children with Wilson disease (WD).

METHODSFrom July 2005 to June 2007, inpatients over three years old in a pediatric liver center were assigned into WD and non-WD group.

RESULTS94 patients, including 26 cases in WD and 68 in non-WD group, were enrolled in this study. The median of 24 h urinary copper excretion was 98.5 microg in WD group and 25.8 microg in the non-WD group (Z = -6.111, P equal to 0.000). The area under receiver operator curve (ROC) was 0.909 (95% CI: 0.839-0.979, P equal to 0.000). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84.6%, 91.2%, 89.4%, 78.6% and 93.9% respectively using 52.0 ug as a cutoff value, and 50.0%, 97.1%, 84.0%, 86.7% and 83.5% using 100 microg as a cutoff value. The goodness of fitness of 52 microg criteria was significantly higher than 100 microg criteria (kappacoefficient 0.760, 0.541 respectively, P equal to 0.000).

CONCLUSIONComparing to 100, 52 microg of 24 h urinary copper excretion as a cutoff value significantly improves the sensitivity and accuracy for diagnosing WD in children.

Adolescent ; Age Factors ; Ceruloplasmin ; Child ; Child, Preschool ; Copper ; urine ; Female ; Hepatitis ; diagnosis ; pathology ; urine ; Hepatitis A ; diagnosis ; pathology ; urine ; Hepatolenticular Degeneration ; diagnosis ; pathology ; urine ; Humans ; Liver ; pathology ; Male ; Penicillamine ; Predictive Value of Tests ; ROC Curve ; Sensitivity and Specificity ; Time Factors