Drug reaction with eosinophilia and systemic symptoms syndrome is not uncommon and shows better clinical outcome than generally recognised.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare disease which can cause severe morbidity and mortality. The aim of this study is to evaluate the clinical manifestation and course of DRESS syndrome. METHODS: We conducted a retrospective analysis of prospectively collected data in 45 patients with DRESS syndrome diagnosed between September 2009 and August 2011. RESULTS: The most common causative drug group was antibiotics (n=13, 28.9%), followed by anticonvulsants (n=12, 26.7%), antituberculosis drugs (n=6, 13.3%), non-steroidal anti-inflammatory drugs (n=4, 8.9%), undetermined agents (n=4, 8.9%), allopurinol (n=3, 6.7%), and others (n=3, 6.7%). The latency period ranged from 2 to 120 days, with a mean of 20.2 ± 24.3 days. The longest latency period was noted for the antituberculosis drug group, at 46.5 ± 29.9 days. Eosinophilia in peripheral blood examination was noted in 35 subjects (77.8%). Atypical lymphocytosis was noted in 16 patients (35.6%), and thrombocytopenia in seven patients (15.6%). Hepatic involvement was noted in 39 (86.7%) study patients, kidney in eight (17.8%), lung in four (8.9%), and central nervous system in one (2.3%). Systemic corticosteroids were administered to 10 patients (22.2%). Forty-three patients (95.6%) showed complete recovery, while two patients had poor outcomes. CONCLUSIONS: DRESS syndrome was not more uncommon than generally recognised. Antibiotics were the most frequently implicated drug group, followed by anticonvulsants. Most patients with this disease showed a better clinical outcome than that which had been generally expected.

Uncertain areas in the diagnosis of allergic bronchopulmonary aspergillosis in patients with asthma.

BACKGROUND AND OBJECTIVE: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with bronchial asthma remains unknown. We evaluated the roles of various laboratory tests in the diagnosis of ABPA, including, skin prick test (SPT) for Aspergillus fumigatus (Af), and serum Af specific IgE and IgG antibody measurement. METHODS: A total of 50 asthma patients with more than 1000cell/µL of peripheral blood eosinophils were prospectively collected between January 2007 and September 2011. Evaluations using SPT for Af, serum total IgE and specific IgE antibody to Af by CAP system, IgG antibody to Af by enzyme immunoassay (EIA) or CAP system were performed according to the essential minimal criteria for the diagnosis of ABPA - asthma, immediate cutaneous reactivity to Af, elevated total IgE, and raised Af specific IgE and IgG. RESULTS: Among 50 patients, three patients (6.0%) were diagnosed as ABPA, of whom each confirmed five items of the essential minimal diagnostic criteria for the diagnosis of ABPA. Six patients (12.0%) showed negative responses to Af in SPT, but positive responses in specific IgE by CAP system. Eight patients (16.0%) showed negative responses to IgG to Af by CAP system, but positive responses by enzyme immunoassay (EIA). CONCLUSIONS: SPT and serum IgE to Af measurement by CAP system should be performed simultaneously. It is reasonable to set up cut-off values in Af specific IgE/IgG by CAP system for the differentiation of ABPA from Af sensitised asthma patients.

Clinical features of drug-induced hypersensitivity syndrome in 38 patients.

BACKGROUND: The clinical features of drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS) syndrome are complicated, and the incidence of this condition is very low. OBJECTIVE: To evaluate the clinical course of DIHS/DRESS and identify effective treatment options. METHODS: This study was a retrospective analysis of prospectively collected clinical data in 38 consecutive patients with DIHS/DRESS diagnosed between March 2004 and January 2009. We investigated the clinical features, response to treatment, and outcome of 38 patients. RESULTS: The study patients consisted of 18 men (47.4%) and 20 women (52.6%). The most common causative drugs were anticonvulsants (47.4%) and antibiotics (18.4%), followed by nonsteroidal anti-inflammatory drugs (NSAIDs) (13.2%), allopurinol (5.3%), and undetermined agents (15.8%). The latency period ranged from 3 to 105 days, with a mean (SD) of 25.2 (21.5) days. Systemic corticosteroids were administered to 16 patients (42.1%). Twenty-two (57.9%) patients were treated with topical corticosteroids and antihistamines (no systemic corticosteroids). Complete recovery was noted in 36 patients (94.8%). Two of the patients treated with systemic corticosteroids had a poor outcome: one died due to an opportunistic infection secondary to long-term systemic corticosteroid treatment; the other showed progressive deterioration of liver damage, although the final outcome is not known. CONCLUSION: The drugs associated with DIHS/DRESS were variable and most frequently included anticonvulsants, beta-lactam antibiotics, and NSAIDs. The syndrome was more common than generally recognized. Additional studies are needed to evaluate the clinical indications for systemic corticosteroids in patients with DIHS/DRESS.

Acute generalized exanthematous pustulosis as a manifestation of carbamazepine hypersensitivity syndrome.

Anticonvulsant hypersensitivity syndrome (AHS) is a multisystemic disorder involving cutaneous changes and typical blood abnormalities that can be triggered by aromatic anticonvulsant drugs.The syndrome is commonly associated with a macular or papular rash or erythroderma. Acute generalized exanthematous pustulosis is a very rare cutaneous manifestation of AHS. A 41-year-old man was referred to our hospital for evaluation of a 3-day history of fever, leukocytosis, and generalized skin eruption. The patient had been taking carbamazepine for 1 month to treat hand tremor following surgery for intracerebral hemorrhage. Physical examination revealed facial edema and a large number of variable-sized pustules covering the body. Initial laboratory testing showed peripheral blood eosinophilia and abnormal liver function.A biopsy of pustular lesions revealed intraepidermal pustules, with perivascular lymphocytic infiltration. The skin lesions and laboratory results improved after withdrawal of carbamazepine and treatment with oral corticosteroids.

Modification of radiation response in mice by Panax ginseng and diethyldithiocarbamate.

The aim of this study was to determine the effect of Panax ginseng and its fractions on jejunal crypt survival, endogenous spleen colony formation and apoptosis in jejunal crypt cells of mice irradiated with high- and low-dose of gamma-irradiation. The radioprotective effect of ginseng was compared with the effect of diethyldithiocarbamate (DDC). Ginseng administration before irradiation protected the jejunal crypts (p < 0.005), increased the formation of endogenous spleen colony (p < 0.005) and reduced the frequency of radiation-induced apoptosis (p < 0.05). The radioprotective effect on jejunal crypts and apoptosis in the DDC-treated group appeared similar to that in the ginseng--treated groups. Treatment with DDC showed no significant modifying effects on the formation of endogenous spleen colony. In the experiment on the effect of fractions of ginseng, the result indicated that the lipophilic non-polar compounds (Fraction 1), lipophilic-acidic compounds (Fraction 2), free sugars (Fraction 7) and saponin compounds (Fraction 8) might have a major radioprotective effect. Although the mechanisms of this inhibitory effect remain to be elucidated, these results indicated that ginseng might be a useful radioprotector, especially since it is a relatively nontoxic natural product. Further studies are needed to fully characterize the protective nature of ginseng extract and its components.

Establishment of the prediction table of parturition day with ultrasonography in small pet dogs.

To establish a prediction table of parturition day the real-time B-mode ultrasonographic examinations were performed in the 8 pregnant Malteses and 10 Yorkshire terriers (total pups, 25 and 38 pups, respectively) from 18 days of gestation until the parturition. Ovulation was designated the first day of gestation (day 0). Extra fetal and fetal structures were measured from all conceptues. The parameters that exhibited the best correlation to parturition were used to compile a prediction table of parturition day. To testify the precision of the prediction table of parturition day, the 15 pregnant Malteses (48 pups) and 13 pregnant Yorkshire terriers (42 pups) with unknown mating time were examined using ultrasonography. Inner chorionic cavity diameter on days 18 to 37 and fetal head diameter on day 38 to parturition that showed the best correlation to gestational age were the most pertinent to the estimation of gestational age and the prediction of parturition day. The two parameters were used to compile a prediction table of parturition with averaged regression equations. In verificational examinations, with the exception of I Yorkshire terrier (3.6%) having 1 fetus, 18 of 28 bitches (64.3%) delivered exactly on the date predicted and 9 of 28 bitches (32.1%) delivered within I day of the date predicted. Therefore, the prediction table of parturition day seems to be a useful tool of the prediction of parturition day in practice.

Establishment of a biological indicator for the radiation and safety of diagnostic ultrasound using apoptosis.

We have studied, by a nonisotopic in situ end-labeling (ISEL) technique, the frequency of apoptosis in the intestinal crypt cell of adult mice and in the external granular layer(EGL) of the cerebellum of fetuses by gamma-ray irradiation from 60Co or diagnostic ultrasound exposure. The extent of changes following 200 cGy(1090 cGy/min) was studied at 2, 4, 6, 8, 12, or 24 hours after exposure. The maximal frequency was found 4-8 hours after exposure. The mice that received 18, 36, 54, 108, 198, 396 cGy of gamma-rays or diagnostic ultrasound (7.5 MHz, 4.2 mW, ISPTA = 7.9 mW/cm2, IsppA = 114.3 W/cm2) for 10 or 30 minutes were examined 6 hours after irradiation. Measurements performed after gamma-ray irradiation showed a dose-related increase in apoptotic cells in each of the mice studied. The dose-response curves were analyzed with alpha linear-quadratic model: the frequency (number per crypt) of apoptotic cells in the intestinal crypt of adult mice was y = (0.0386 +/- 0.004204)D + (-0.0000535 +/- 0.00001120)D2 + 0.15475(r2 = 0.952, y = apoptotic cell per crypt cell, D = dose in cGy), and the frequency (percentage of apoptotic cell in the EGL) of apoptotic cell in the EGL of fetus was y = (0.1349 +/- 1.175)D + (-0.001522 +/- 0.334)D2 + 0.0477(r2 = 0.981, y = % of apoptotic cell in the EGL, D = dose in cGy). In the experiment of ultrasound exposure, the frequencies of apoptosis were 0.181 +/- 0.055(10 minutes exposure) and 0.325 +/- 0.294 (30 minutes exposure) in the crypt cells and 0.106 +/- 0.130% (10 minutes exposure) and 0.167 +/- 0.220%(30 minutes exposure) in the EGL. We estimated the relative dose of the yield from the experiment with ultrasound by substituting the yield from ultrasound exposure into the curue from the gamma-irradiation. The relative doses of ultrasound exposure compared with gamma-irradiation were 0.692 cGy(10 minutes exposure) and 1.334 cGy(30 minutes exposure) in the experiment for crypt cells and 0.432 cGy(10 minutes exposure) and 0.885 cGy(30 minutes exposure) in the experiment for EGL. Although there is presently no evidence to indicate that diagnostic ultrasound involves a significant risk, it is not wise to use diagnostic ultrasound indiscriminately.

Cell death by apoptosis in the neonatal mouse cerebellum following gamma-irradiation.

We have studied, by a nonisotopic in situ DNA end-labeling (ISEL) technique, the frequency of apoptosis in the external granular layer (EGL) of the cerebellum after whole-body irradiation of newborn mice by gamma-rays from 60Co. The total number of normal cells and cells showing morphological features of apoptosis were counted. The frequency of apoptotic cells was expressed as a percentage of the total number of cells in EGL. The extent of changes following 2 Gy (10.9 Gy/min) was studied at 2, 4, 6, 8, 12, or 24 hours after exposure. The maximal frequency was found 6-8 hours after exposure. Newborn mice that received 0.18, 0.36, 0.54, 1.08, 1.98, or 3.96 Gy were examined 6 hours after irradiation. Measurements performed after irradiation showed a dose-related increase in apoptotic cells in each of the mice studied. The dose-response curves were analyzed by a linear- quadratic model; frequency was (13.49 +/- 1.175) D + (-1.52 +/- 0.334) D2 +/- 0.048 (r2 = 0.981, D = dose in Gy). It provides the basis required for a better understanding of results which will be obtained in any further studies for biological responses of radiation using newborn orfetal mice.