Zoster paresis

Herpes zoster (HZ) is essentially a viral disease of the posterior root ganglia and sensory nerve fibers, which presents clinically with vesicular eruption of the skin, radicular pain and sensory changes in the distribution of the affected ganglion. However, motor involvement can be seen as well. If classic cutaneous lesions are present, HZ-related motor paresis is easily diagnosed. Otherwise, the diagnosis may be suspicious, especially if the weakness occurs before the cutaneous lesions have appeared, or weeks after they have subsided. We present a patient with HZ-related motor paresis due to radiculopathy in the cervical segments whose motor symptoms and signs appear as major clinical features.     

A prospective clinical and immunologic analysis of patients with serum sickness

We prospectively evaluated the clinical and immunologic features of serum sickness in 12 patients with bone-marrow failure treated for 10 days with intravenous infusions of horse antithymocyte globulin. Eleven of the 12 patients had signs and symptoms of serum sickness 8 to 13 days after beginning therapy with antithymocyte globulin. Eleven patients (including 10 of 11 with signs and symptoms of serum sickness) acquired circulating immune complexes, with peak levels occurring at 10 to 12 days. Serum C4 and C3 levels fell precipitously, with nadirs on the 10th day. Plasma levels of C3a anaphylatoxin were elevated in the four patients in whom it was measured. Eight of the 11 patients with signs and symptoms of serum sickness had a characteristic serpiginous erythematous and purpuric eruption on the hands and feet at the junction of palmar and plantar skin. Direct immunofluorescence of skin lesions revealed immune deposits (IgM, IgE, IgA, or C3) in the blood vessels of three of five patients. This study documents the immunopathology of serum sickness in human beings and describes a cutaneous marker for the disease.     

Oral iron cutaneous adverse reaction and successful desensitization.

BACKGROUND: The oral administering of iron preparations sometimes produces adverse gastrointestinal effects. In contrast, cutaneous reactions are extremely rare. OBJECTIVE: We report a patient with several episodes of generalized pruritus and erythematous maculopapular eruption after receiving oral compounds of iron and on whom desensitization with oral iron was attempted. METHODS: We studied a female with microcytic anemia due to gynecologic blood loss who presented several episodes of cutaneous eruption after receiving oral compounds of iron. Skin prick-test and two simple-blind, placebo-controlled oral challenges were performed with various iron compounds, and finally desensitization with oral iron was carried out. RESULTS: Skin prick-test and patch-test with iron preparations were negative. Two simple-blind, placebo-controlled oral challenges were performed and the patient began experiencing similar cutaneous symptoms. We started a slow desensitization protocol using increasing doses until the target amount of the drug was tolerated without adverse effects. The chronic administration of oral iron therapy once a day for 9 months sustained the desensitized state and the anemia disappeared. CONCLUSION: We present methods to effectively manage iron supply for a microcytic anemia patient with cutaneous reactions due to oral iron compounds, to avoid repeated transfusions, slow desensitization with oral iron was successfully attempted.     

Chronic granulomatous disease carrier geno-dermatosis (CGDCGD)

A persistent eruption in light-exposed areas in two related carriers of X-linked chronic granulomatous disease is described. This eruption appears to be a separate entity, rather than a variant of cutaneous lupus erythematosus or Jessner's disease. Recognition may enable detection of carrier females prior to the birth of an affected son, so that genetic counselling and antenatal diagnosis can be instituted.     

Temporal evolution of epithelial, vascular and interstitial lung injury in an experimental model of idiopathic pulmonary fibrosis induced by butyl-hydroxytoluene

This study was undertaken to test whether the structural remodelling of pulmonary parenchyma can be sequentially altered in a model and method that demonstrate the progression of the disease and result in remodelling within the lungs that is typical of idiopathic pulmonary fibrosis. Three groups of mice were studied: (i) animals that received 3-5-di-tert-butyl-4-hydroxytoluene (BHT) and were killed after 2 weeks (early BHT = 9); (ii) animals that received BHT and were killed after 4 weeks (late BHT = 11); (iii) animals that received corn oil solution (control = 10). The mice were placed in a ventilated Plexiglas chamber with a mixture of pure humidified oxygen and compressed air. Lung histological sections underwent haematoxylin-eosin, immunohistochemistry (epithelial, endothelial and immune cells) and specific staining (collagen/elastic fibres) methods for morphometric analysis. When compared with the control group, early BHT and late BHT groups showed significant decrease of type II pneumocytes, lower vascular density in both and higher endothelial activity. CD4 was increased in late BHT compared with early and control groups, while CD8, macrophage and neutrophil cells were more prominent only in early BHT. The collagenous fibre density were significantly higher only in late BHT, whereas elastic fibre content in late BHT was lower than that in control group. We conclude that the BHT experimental model is pathologically very similar to human usual interstitial pneumonia. This feature is important in the identification of animal models of idiopathic pulmonary fibrosis that can accurately reflect the pathogenesis and progression of the human disease.     

Murine model of atopic dermatitis associated with food hypersensitivity

BACKGROUND: Atopic dermatitis (AD) is an eczematous skin eruption that generally begins in early infancy and affects up to 12% of the population. The cause of this disorder is not fully understood, although it is frequently the first sign of atopic disease and is characterized by an elevated serum IgE level, eosinophilia, and histologic tissue changes characterized early by spongiosis and a CD4(+) T(H)2 cellular infiltrate. Hypersensitivity to foods has been implicated as one causative factor in up to 40% of children with moderate-to-severe AD. OBJECTIVE: The purpose of this study was to establish a murine model of food-induced AD. METHODS: Female C3H/HeJ mice were sensitized orally to cow's milk or peanut with a cholera toxin adjuvant and then subjected to low-grade allergen exposure. Histologic examination of skin lesions, allergen-specific serum Ig levels, and allergen-induced T-cell proliferation and cytokine production were examined. RESULTS: An eczematous eruption developed in approximately one third of mice after low-grade exposure to milk or peanut proteins. Peripheral blood eosinophilia and elevated serum IgE levels were noted. Histologic examination of the lesional skin revealed spongiosis and a cellular infiltrate consisting of CD4(+) lymphocytes, eosinophils, and mast cells. IL-5 and IL-13 mRNA expression was elevated only in the skin of mice with the eczematous eruption. Treatment of the eruption with topical corticosteroids led to decreased pruritus and resolution of the cutaneous eruption. CONCLUSION: This eczematous eruption resembles AD in human subjects and should provide a useful model for studying immunopathogenic mechanisms of food hypersensitivity in AD.     

Elastin gene expression is upregulated during pulmonary fibrosis

Elastin is a chief component of lung interstitium, and it is central to lung morphology and function. Efforts to understand the pathogenesis of pulmonary fibrosis have focused primarily upon collagen turnover in the lung; few studies have focused on elastin. In this study, we examined steady-state elastin mRNA levels after lung injury in the mouse induced by (1) butylated hydroxytoluene (BHT) which causes acute lung injury with recovery, (2) BHT + 70% O2 (fibrosis), or (3) 70% O2. Total lung elastin mRNA increased 70-80-fold on d10-14 after BHT/O2, but was unchanged after BHT or O2 alone. In situ hybridization studies localized elastin mRNA to cells in the muscularis of conducting airways and to scattered interstitial cells in fibrotic foci. Elastic fiber morphology was markedly distorted after BHT/O2. Thus, marked upregulation of elastin gene expression is correlated with the histopathology of fibrotic lung disease.     

Delayed hypersensitivity to 6-methyl-prednisolone in Henoch Schoenlein syndrome

We report a case of allergic reaction to oral 6-methyl-prednisolone in a patient with Henoch Schoenlein syndrome. When this syndrome was first diagnosed the patient was started on 6-methyl-prednisolone orally and after 4 days he developed a pruriginous generalized maculo-papular eruption. The rash disappeared 1 week after withdrawal of 6-methyl-prednisolone. The skin tests performed 1 month after with main food allergens were negative. Patch test with 0.10 ml of solution containing 6-methyl-prednisolone 40 mg/ml was positive after 48 and 72 h. The cutaneous biopsy on the patch tested skin revealed a perivaseular infiltrate of lymphocytes, histiocytes and eosinophils.     

The relationship between unmyelinated afferent type and neurogenic plasma extravasation in normal and reinnervated rat skin.

Electrophysiological experiments have been carried out on rats to examine the relationship between plasma extravasation into skin and antidromic activation of individual unmyelinated afferent fibres supplying cutaneous receptors, particularly polymodal nociceptors. Normal animals and ones in which the skin had been reinnervated after peripheral nerve transection 26-52 weeks before were studied. In the normal animals 12 of 18 (66%) polymodal nociceptor afferents showed evidence of plasma extravasation after antidromic stimulation of the nerve filament from which they were initially recorded. Antidromic stimulation of other types of unmyelinated unit gave no detectable signs of plasma extravasation. The results from the animals with regenerated nerves were similar with 15 of 21 (71%) of the polymodal nociceptor afferents showing clear signs of plasma extravasation after antidromic activation and the other types of unit giving no signs of such a response. These results show that while antidromic stimulation of a cutaneous nerve after intravascular administration of Evans Blue dye can be used to get a general view of the extent of innervation by polymodal nociceptors, it does not necessarily show the entire distribution of these receptors. It is likely that the ability or lack of ability of a polymodal nociceptor afferent to enhance vascular permeability, and so bring about plasma extravasation, is related to its neuropeptide content, and thus it follows that this might be a useful criterion for separating this broad class of cutaneous receptor into sub-groups.     

The effect of butylated hydroxytoluene (BHT) on bull spermatozoa frozen in two different extenders

This study evaluated the protective effect of butylated hydroxytoluene (BHT), a lipid-soluble antioxidant against cryopreservation damage on bull spermatozoa. Four BHT concentrations (0.5, 1, 2 and 4?mM) were evaluated. Sperm characteristics were evaluated when BHT was added to a post-thaw–freezing extender by measuring the degree of sperm lipid peroxidation (using malondialdehyde, MDA) and by measuring parameters such as motility and viability of spermatozoa. Production of MDA as an indicator of lipid peroxidation was obtained when BHT ranged from 0.5 to 1?mM in both extenders (P?<?0.0001). Sperm motility and viability evaluated immediately after thawing was higher in BHT-treated spermatozoa, this was significant (P?<?0.001) when the freezing egg yolk–citrate extender was supplemented with 0.5 and 1?mM BHT and when egg yolk–Tris extender was supplemented with 0.5?mM BHT. The addition of 0.5 and 1?mM BHT to semen egg yolk–citrate extender increased the viability of frozen semen after thawing (P?<?0.007). The addition of 0.5 and 1?mM BHT to both extenders resulted in a significant (P?<?0.0001) decrease in MDA production. In conclusion, the addition of BHT to freezing egg yolk–citrate extender improved the overall efficiency of thawed bull spermatozoa, but the addition of BHT to the freezing egg yolk–Tris extender did not.     

Review: putative mutagens and carcinogens in foods. III. Butylated hydroxytoluene (BHT)

Although the average American's daily consumption of BHT can be measured in milligrams, there are numerous reports that BHT causes organ damage in laboratory animals. Only a few genotoxic effects of BHT have been reported, however, including mutagenicity in the abnormal sperm assay and ambiguous results regarding its teratogenicity. More dramatic are the modulatory effects of BHT on the actions of established mutagens and carcinogens. BHT can either enhance or inhibit mutagenic potency, depending on the substance tested. For example, in the Ames test, BHT is antimutagenic towards benzo(a)pyrene, but increases the number of Salmonella revertants induced by aflatoxin B1. BHT is one of the few compounds to have both tumor prophylactic and tumor promoting capacities. It is the temporal sequence in which BHT and carcinogens are administered to test animals which determines how BHT affects the response to these carcinogens. In common with other antioxidants, BHT inhibits the ability of carcinogens to induce tumors in various rodent organs when the animal is given BHT prior to carcinogen treatment. Unlike other antioxidants, however, the number of tumors increase when BHT is administered after carcinogen exposure. The comutagenic and cocarcinogenic properties of BHT have been demonstrated in tests ranging from the Ames test to cell transformation procedures to in vivo assays. These effects are probably mediated by metabolites of BHT, rather than by BHT itself.     

Review: Putative mutagens and carcinogens in foods III. Butylated hydroxytoluene (BHT)

Although the average American's daily consumption of BHT can be measured in milligrams, there are numerous reports that BHT causes organ damage in laboratory animals. Only a few genotoxic effects of BHT have been reported, however, including mutagenicity in the abnormal sperm assay and ambiguous results regarding its teratogenicity. More dramatic are the modulatory effects of BHT on the actions of established mutagens and carcinogens. BHT can either enhance or inhibit mutagenic potency, depending on the substance tested. For example, in the Ames test, BHT is antimutagenic towards benzo(a)pyrene, but increases the number of Salmonella revenants induced by aflatoxin B₁. BHT is one of the few compounds to have both tumor prophylactic and tumor promoting capacities. It is the temporal sequence in which BHT and carcinogens are administered to test animals which determines how BHT affects the response to these carcinogens. In common with other antioxidants, BHT inhibits the ability of carcinogens to induce tumors in various rodent organs when the animal is given BHT prior to carcinogen treatment. Unlike other antioxidants, however, the number of tumors increase when BHT is administered after carcinogen exposure. The comutagenic and cocarcinogenic properties of BHT have been demonstrated in tests ranging from the Ames test to cell transformation procedures to in vivo assays. These effects are probably mediated by metabolites of BHT, rather than by BHT itself.     

A control study of the cutaneous side effects of chronic lithium therapy

BACKGROUND: To assess the nature and prevalence of skin disorders among psychiatric patients on chronic lithium therapy and to compare them with patients on other psychotropic medications. METHOD: 51 patients on lithium and 57 patients on other psychotropics were recruited. Dermatological assessment included a semi-structured questionnaire and clinical examination of the subjects by two dermatologists who were blind to the psychiatric diagnosis and treatment. Secondary cutaneous reaction was defined as skin eruption that developed or deteriorated after commencement of psychiatric medication. RESULTS: Lithium treated patients developed significantly more secondary cutaneous reactions than the control group. This applied particularly to acne and psoriasis. Male patients on lithium were more likely to be affected than female patients. CONCLUSION: Lithium aggravates or triggers cutaneous conditions that are characterized by the pathological findings of neutrophilic infiltration. Since these cutaneous problem can be distressing to patients and may affect medication compliance, there should be heightened attention to skin problems in patients receiving lithium treatment.     

Brain Hypothermic Therapy Dramatically Decreases Elevated Blood Concentrations of High Mobility Group Box 1 in Neonates with Hypoxic-Ischemic Encephalopathy

Background. According to the Consensus 2010 of the International Liaison Committee on Resuscitation (ILCOR), children with moderate to severe hypoxic-ischemic encephalopathy (HIE) should receive brain hypothermic therapy (BHT) after successful resuscitation. Elevated high mobility group box 1 (HMGB1) in the blood at the early stage of brain ischemia-reperfusion injury has been suggested to be involved in the release of various inflammatory cytokines. Methods. In total, 21 neonates plasma HMGB1 concentration was measured. These neonates included 8 with HIE in whom BHT was indicated, 5 controls diagnosed as having HIE but who were not suitable candidates for BHT, and 8 normal controls. Results. The umbilical artery HMGB1 (UA-HMGB1) level before undergoing BHT significantly exceeded reference values. The UA-HMGB1 level in the BHT (−) group did not differ significantly from reference values, but was significantly increased 24 hours after birth. Repeated measure ANOVA showed a significant difference in time course changes between the BHT (+) and BHT (−) groups (P = 0.0002). Conclusions. This study demonstrated hypothermic therapy to significantly decrease HMGB1. Furthermore, HMGB1 is a useful index of the inhibition of early stage inflammation.     

Inhibition of expression of P-selectin by antioxidant in cholesterol-fed rats

Butylated hydroxytoluene (BHT) can inhibit experimental atherosclerosis in animals. Although the agent is an antioxidant, the exact mechanism of the reaction in atherosclerosis is still unknown. To investigate the effects of BHT on expression of P-selectin (PADGEM, GMP-140), intercellular adhesion molecule-1 (ICAM-1) and class II MHC (Ia) antigen, we proposed an experiment on rats. Male rats (n=18 per group) were fed either a normal cholesterol control diet, a normal cholesterol diet containing 0.5% BHT (BD), a high cholesterol diet containing 1.5% cholesterol and 0.1% sodium cholate (CD), or the CD diet containing 0.5% BHT (BCD). Rats were sacrificed after 3 days, and after 1, 2, 4, 10, and 17 weeks of dietary treatment. Although there was no gross or light microscopic atherosclerotic lesions, scanning electron microscopy revealed monocytic adhesion to aortic endothelium and mild endothelial injuries in CD and BCD groups. Immunohistochemically, the addition of BHT to a high cholesterol diet inhibited P-selectin expression but not in ICAM-1 and Ia antigen. These findings suggest that in rats, high cholesterol diets induce expression of ICAM-1, P-selectin and Ia antigen. In addition, the antiatherogenic effect of BHT may play a role in the inhibition of P-selectin.     

Butylated hydroxytoluene does not protect Chinese hamster ovary cells from chromosomal damage induced by high-dose rate 192Ir irradiation

Previous reports showed the protective effect of the synthetic antioxidant butylated hydroxytoluene (BHT) against the chromosomal damage induced by bleomycin (BLM), cadmium chloride and potassium dichromate. To test the hypothesis that this effect was exerted by inhibition and/or scavenging of reactive oxygen species (ROS), the effect of BHT on the chromosomal damage induced by a high dose-rate gamma rays (HDR (192)Ir). Experiments were carried out by irradiating G(1) CHO cells with nominal doses of 1, 2 or 3 Gy. BHT (doses of 1.0, 2.5 or 5.0 microg/ml) was added to the culture immediately before or immediately after irradiation. Cells were then incubated in the presence of BHT for 13 h until harvesting and fixation. Results obtained showed that BHT did not decrease the chromosomal damage induced by radiation in any consistent fashion. On the contrary, in cells post-treated with 5.0 microg/ml of BHT the yield of chromosomal aberrations increased in several experimental points. These results with ionizing radiation suggest that the previous observed protective effects of BHT on the chromosomal damage induced by chemical genotoxicants may not be mediated solely through the scavenging or inactivating reactive oxidative species. The decrease of the yield of chromosomal damage induced by BLM could be due to the union of BHT with a metallic ion, in this case Fe (II), required for the activation of BLM. In the same way, the protective effect of BHT on the chromosomal damage induced by cadmium chloride and potassium dichromate could be due to the decrease of the effective dose of both salts in the cell through the chelation of the cations by BHT.     

Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines

BACKGROUND: Systemic allergic reactions to Japanese encephalitis (JE) vaccine that include urticaria, angioedema, and rash have been reported. In Japan, children who suffered from allergic immediate-type reactions to JE vaccine had antigelatin IgE in their sera. However, the immunologic mechanism of allergic nonimmediate-type reactions that consist of cutaneous signs appearing several hours or more after JE vaccination has not been defined. METHODS: Serum samples were taken from 28 children who showed allergic nonimmediate-type cutaneous reactions to JE vaccine. Furthermore, serum samples were taken from 10 children who showed allergic immediate-type reactions with cutaneous signs and/or respiratory symptoms to JE vaccine. We have defined an immediate-type reaction as one occurring within 1 h after vaccination. RESULTS: Of 10 children who showed immediate-type reactions, all had antigelatin IgE and IgG. Of 28 children who showed systemic nonimmediate-type reactions, one had antigelatin IgE and nine (32%) had antigelatin IgG. The child who had antigelatin IgE showed urticaria 2 h after JE vaccination. CONCLUSION: These results suggest that some children who showed allergic nonimmediate-type reactions to JE vaccine were sensitized to gelatin.     

Cytomegalovirus infection involving the skin in immunocompromised hosts. A clinicopathologic study

Cytomegalovirus (CMV) infection involving the skin in three transplant patients is presented. Patient 1, whose infection apparently was localized only to a cutaneous wound induced by extravasated ionotropic solution, survived. Mixed CMV and Candida infections developed in patient 2 in the cutaneous ulcer. He died of disseminated herpes simplex virus infection in two weeks. Patient 3 had CMV pneumonia and purpuric maculopapular eruption. He died of Pseudomonas sepsis 17 weeks later. Eighteen cases with CMV skin lesions are reported in the English literature. The clinical findings and the outcome of the current and the reported cases are analyzed. All patients were immunocompromised. CMV infection, when detected in the skin, appears to be associated with grave prognosis. Seventeen of 20 patients whose final outcome was recorded died within six months after the onset of CMV skin lesions. The outcome of one case is unknown. The mortality was 85%. The fatal cases had either concurrent disseminated CMV infection or mixed cutaneous or systemic infections. When the infection is localized in the skin wounds, the prognosis seems fairly good. All three such patients survived.     

Herpes simplex virus antibodies in 18 patients submitted to immunosuppressive agents after renal transplantation]

The titer of circulating antibodies to herpes simplex virus type 1 was tested in 18 patients for a few months before and after renal transplantation. No clinical illness was observed in the group of patients lacking antibodies. On the contrary, half of those with antibodies developed cutaneous eruption within 2 to 4 weeks following treatment with immunosuppressive drugs. No relationship could be found between the appearance of clinical illness and the rise in antibody titer. This lack of correlation could be explained by the multiple modifications occurring in the immune system of the host submitted to immunosuppressive drugs.