Pulse methylprednisolone with gammaglobulin as an initial treatment for acute Kawasaki disease.

Approximately 15-20% of patients with Kawasaki disease (KD) are not responsive to high-dose intravenous gammaglobulin (IVIG). We have previously reported a predictive method for identifying IVIG-non-responsive patients (high-risk KD patients). We determined the safety and effectiveness of pulse methylprednisolone with high-dose IVIG (mPSL+IVIG) as a primary treatment for high-risk KD patients. Sixty-two high-risk KD patients were treated with pulse methylprednisolone 30 mg/kg over 2 h, followed by IVIG 2 g/kg over 24 h (mPSL+IVIG group) and were compared with a historical control group of 32 high-risk patients treated with IVIG 2 g/kg alone at the participating hospitals before this study was opened (IVIG group). High-risk patients were identified with at least two of three predictors (C-reactive protein >or=7 mg/dL, total bilirubin >or=0.9 mg/dL or aspartate aminotransferase >or=200 IU/L). Sixty-six percent (95% confidence interval [CI] 54-78%) of patients had a prompt defervescence in the mPSL+IVIG group compared with 44% (95% CI 26-62%) for the IVIG group (p=0.048). Coronary artery lesions were observed in 24.2% (95% CI 13.2-35.2%) and 46.9% (95% CI 28.6-65.2%) of patients in the mPSL+IVIG and IVIG groups, respectively (p=0.025). This is the first report showing that mPSL+IVIG is effective and safe as a primary treatment for high-risk KD patients.

Necrotizing fasciitis in the head and neck region: an analysis of standard treatment effectiveness.

A standard treatment procedure for necrotizing fasciitis in the head and neck region was introduced in 1999 at Rigshospitalet (National Hospital of Denmark) Copenhagen. The new procedure introduced more drastic surgical debridement than before, combined with a set antibiotic regime and intravenous gamma globulin and adjunctive hyperbaric oxygen treatment (HBO). To evaluate the effect of this, a retrospective study was undertaken, involving 19 patients treated for NF at the ENT department from 1996-2004. Between 1996 and 1999 eight patients were treated (non-HBO) from 1999-2004 eleven patients were treated (HBO group). Length of antibiotic treatment was very similar in the two groups (mean 22.5 days) as was bacteriology. Aetiological focus differed marginally with the HBO group showing a clear tendency towards odontogen focus. The HBO group was found to undergo significantly more debridement procedures (3.36). The most drastic difference in the two groups however, was the reduction in mortality. The non-HBO group had a mortality of 75% and in the HBO group they all survived. This obviously resulted in a prolonged hospital stay for the HBO group (mean 30.8 days). The study concluded that the reduction in mortality was due to the combined effects of the different entities in the new treatment guidelines. It was not possible to isolate a specific factor responsible for the change.

Long-term changes in coronary artery aneurysms in patients with Kawasaki disease: comparison of therapeutic regimens.

BACKGROUND: There are few studies of the therapeutic regimens for the prevention of stenotic transformation of aneurysms in Kawasaki disease (KD). The aim of this study was to assess the prophylactic effect of combined therapy in the acute stage and convalescent- to chronic-stage against the formation of stenotic lesions. METHODS AND RESULTS: In 85 patients, 103 giant aneurysms (ANl), 46 medium-sized aneurysms (ANm), and 13 small aneurysms (ANs) were analyzed. With respect to therapy in the acute stage, no localized stenosis of ANl in the left coronary artery was noted in patients who received high-dose gamma globulin therapy (G). For ANm, the group (G) showed a significantly higher regression rate than the aspirin group and steroids group. Furthermore, no coronary artery occlusion/recanalization of ANl occurred with the prophylactic regimen of aspirin and warfarin {aw}. Prophylaxis {aw} and the prophylactic regimen of aspirin alone {a} significantly lowered the incidence compared with either the prophylactic regimen of warfarin {w} or no prophylaxis {n}. However, no significant differences were noted between prophylaxis {w} and {n}. CONCLUSIONS: High-dose gamma globulin therapy in the acute stage of KD is the first choice for the prevention of stenotic transformation. Prophylaxis {aw} is recommended for ANl.

Impaired endothelial function in the brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C.

BACKGROUND: Previous studies in patients with a history of Kawasaki disease have focused on vascular endothelial function in coronary arteries, and the endothelial function of systemic arteries is not fully understood. Furthermore the effect of vitamin C on systemic endothelial function after Kawasaki disease has not been elucidated. OBJECTIVES: We attempted to analyze endothelium-dependent vasodilatation in the brachial artery after Kawasaki disease by using high resolution ultrasonography and to investigate whether the acute administration of vitamin C could restore such systemic endothelial dysfunction. METHODS: We compared 39 patients (7.1 +/- 2.7 years) 1.0 to 9.6 years after acute Kawasaki disease with 17 matched healthy subjects (7.0 +/- 3.1 years) as controls. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilatation) and sublingual nitroglycerin (causing endothelium-independent dilatation). RESULTS: The percent change in diameter of the brachial artery induced by reactive hyperemia in the patients with a history of Kawasaki disease (6.2 +/- 3.9%) was significantly lower than that in the control group (14.1 +/- 6.8%; P < 0.0001). No significant difference could be found in percent change in diameter induced by sublingual administration of nitroglycerin between the control (33.2 +/- 13.7%) and the patients with a history of Kawasaki disease (30.6 +/- 9.2%; P = 0.49). There was no significant difference in percent change in diameter of the brachial artery induced by reactive hyperemia between the patients who received gamma-globulin (6.0 +/- 4.0%) and those who did not receive gamma-globulin (7.9 +/- 3.3%; P = 0.33). Intravenous infusion of vitamin C significantly increased the percent change in diameter of brachial artery induced by reactive hyperemia in 19 patients with history of Kawasaki disease (6.6 +/- 3.5 to 13.0 +/- 5.5%; P < 0.0001), whereas no significant increase was seen in the percent change in diameter of brachial artery induced by reactive hyperemia in 20 patients with history of Kawasaki disease after placebo administration (6.5 +/- 4.5 to 7.3 +/- 4.9%; P = 0.20). CONCLUSIONS: Our study showed decreased percent change in diameter of the brachial artery induced by reactive hyperemia in patients with history of Kawasaki disease compared with the healthy children, indicating that systemic endothelial dysfunction exits after Kawasaki disease. Although such systemic endothelial dysfunction after Kawasaki disease is not influenced by early treatment with high dose gamma-globulin in the acute stage of Kawasaki disease, it can be restored by the acute intravenous administration of vitamin C.

Enfermedad de Kawasaki / Kawasaki disease

La enfermedad de Kawasaki es un cuadro de descripción reciente con una etiopatogenia confusa y con un diagnóstico fundamentalmente clínico. Existen formas muy típicas de la enfermedad que son fáciles de diagnosticar, pero cada vez se presentan más casos atípicos o incompletos que pueden pasar inadvertidos o que se diagnostican tardíamente. Es un síndrome que puede tener graves alteraciones cardiovasculares, por lo que es imprescindible realizar un diagnóstico y un tratamiento precoces para intentar evitar su morbimortalidad (AU)

[A case of severe adult measles pneumonia--efficacy of combination of steroid pulse therapy, high-dose vitamin A and gamma globulins].

A 33 year-old female was admitted with facial, trunk and limb eruptions, conjunctiva intrahemorrhage, Koplik's spots in the pharynx and severe hypoxemia after fever and upper respiratory tract symptom. Infiltrative shadow of the whole right lung was seen on chest radiography. Fine crackles were seen in the lower left lung and in the whole right lung. Severe inflammation and liver dysfunction were indicated by blood test. Measles antibody IgM was high. The abnormal interstitial shadows were confirmed in greater detail by chest computed tomography. Her condition was diagnosed as measles pneumonia. A combination therapy with steroid pulse, high dose vitamin A, and gamma globulin was started, after which the patient gradually improved, indicating the effectiveness of this combination therapy for severe adult measles pneumonia.

Enfermedad de Kawasaki de presentación incompleta / Kawasaki disease of atypical presentation

Presentamos el caso de una niña de 7 años con un cuadro de fiebre elevada de larga evolución, sin respuesta a distintos trata-mientos antibióticos, acompañada de exantema generalizado. Durante su evolución padeció una hepatosplenomegalia de aparición y resolución recortadas en el tiempo y una trombocitosis progresiva, junto con descamación laminar de los dedos de manos y pies, por lo que se instauró tratamiento con gammaglobulina intravenosa, con la consiguiente remisión de la fiebre y el exantema. A pesar de que los sucesivos controles ecocardiográficos practicados fueron normales, pensamos que se trata de una forma incompleta de enfermedad de Kawasaki. Queremos incidir en la importancia de sospechar este cuadro clínico ante todo niño con fiebre de origen desconocido, aunque no se cumplan todos los criterios diagnósticos, por la existencia de numerosas referencias en la literatura acerca de casos de presentación incompleta que desarrollan aneurismas coronarios (AU)

[Human herpesvirus-6 and -7 infection and bone marrow transplantation (BMT)].

In our all patients, the antibodies to HHV-6 and -7 were positive before BMT. HHV -6 and -7 DNA were sometimes detected after BMT, and HHV-6 infection after BMT caused fever, interstitial peumonitis, diarrhea, and myelosuppression. However, HHV -7 didn't induce any clinical symptoms. For the diagnosis of the HHV-6 or -7 infection, we used the virus isolation, semiquantitative PCR, and 4-hold elevation of the antibodies to HHV-6 or -7. Ganciclovir, foscarnet, high dose gamma-globulin and high dose acyclovir were useful for the treatment of HHV-6 infection after BMT. HHV-6 is an important agent for the fever of unknown origin, interstitial peumonitis, diarrhea, and myelosuppression after BMT.

Acetoside, a component of Stachys sieboldii MIQ, may be a promising antinephritic agent: effect of acteoside on crescentic-type anti-GBM nephritis in rats.

Effects of acetoside (ACT) on crescentic-type anti-GBM nephritis in rats were investigated. When rats were treated with ACT from the 1st day after i.v. injection of anti-GBM serum, ACT inhibited the elevation of protein excretion into urine. In the ACT-treated rats, cholesterol and creatinine contents and antibody production against rabbit gamma-globulin in the plasmas were lower than those of the nephritic control rats. Histological observation demonstrated that this agent suppressed hypercellularity and the incidence of crescent formation, adhesion of capillary wall to Bowman's capsule and fibrinoid necrosis in the glomeruli. Furthermore, rat-IgG and C3 deposits on the GBM were significantly less in the ACT-treated group than in the control nephritic group. When the treatment was started from the 20th day after i.v. injection of anti-GBM serum, by which the disease had been established, ACT resulted in a similar effect on the nephritic rats as stated above. These results suggest that ACT may be a useful medicine against rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesions with diffuse crescents.

High-dose intravenous gammaglobulin therapy for neonatal immune haemolytic jaundice due to blood group incompatibility.

Three newborn infants who developed hyperbilirubinemia due to blood group incompatibility were treated with high-dose gammaglobulin. Hyperbilirubinemia was caused by Rhesus (Rh) incompatibility (anti-E + anti-c) in Infant 1 and ABO incompatibility (anti-B) in Infants 2 and 3. Hyperbilirubinemia was refractory to conventional phototherapy but responded well to intravenous gammaglobulin (IVGG) at a dose of 1 g/kg in all infants. No adverse effects were observed. These findings suggest that high-dose IVGG may be useful in the treatment of hyperbilirubinemia due to isoimmune haemolytic disease resistant to phototherapy.

Early and late phases of ocular anaphylaxis in actively immunized guinea pigs.

A model of ocular anaphylaxis with distinct early- and late-phase components was studied in actively immunized guinea pigs. Twenty guinea pigs were injected with dinitrophenylated (DNP) bovine gamma globulin emulsified in Freund's complete adjuvant and challenged topically with di-DNP-lysine. Clinical signs were monitored over a 48 h period. An early-phase reaction (EPR) characterized by conjunctival edema, conjunctival erythema, lid swelling, and lid redness was observed. This reaction peaked at 0.5 h after challenge and subsided to a low point at 3-4 h. Subsequently, a second episode of lid swelling and lid redness was observed at 4-8 h. All animals in both groups exhibited an EPR. In addition, 75% of the animals underwent an EPR and an LPR. No animals exhibited an isolated LPR. Of the animals that underwent a dual response, 47% were biphasic, 6% were prolonged and 47% were multiphasic. The development of an active model of ocular anaphylaxis exhibiting both EPR and LPR components will enable studies of mechanisms which regulate the frequency and magnitude of these ocular allergic responses.

Autoimmune thrombocytopenia in pediatric systemic lupus erythematosus: alternative therapeutic modalities.

Three patients with pediatric systemic lupus erythematosus (PSLE) and autoimmune thrombocytopenia (AT), who developed unacceptable side effects (pseudotumor cerebri, hypertension, excessive weight gain) from treatment with steroids, were treated successfully with vincristine (2 patients) or intravenous immunoglobulin (1 patient). All patients remained off steroids without any complications for 11 to 23 months.

Stress-induced secretion of alpha-melanocyte-stimulating hormone and its physiological role in modulating the secretion of prolactin and luteinizing hormone in the female rat.

The pattern of alpha MSH release during immobilization stress in ovariectomized rats was determined and correlated with that of plasma PRL and LH. Stress induced a marked elevation in plasma immunoreactive alpha MSH, with a time course identical to that of plasma PRL. The increment in plasma PRL was greater than that in plasma alpha MSH. Plasma LH was markedly lowered by stress. Analysis of pituitary and hypothalamic alpha MSH indicated a significant (P less than 0.05) increase in the neurointermediate lobe and anterior lobe content of alpha MSH. The alpha MSH content in the hypothalamus was lowered by stress when expressed as tissue content (P less than 0.025), although no significant differences in content in this area were detected when the results were expressed in terms of tissue protein. Stress induced a marked increase (P less than 0.01) in the median eminence levels of alpha MSH. Intraventricular (third ventricle) injection of the gamma-globulin fraction of a specific antiserum raised against alpha MSH increased basal PRL levels (P less than 0.025) and prevented the decline in plasma PRL that occurred 60 min after the onset of stress in the normal rabbit serum-injected rats. The stress-induced suppression of plasma LH was attenuated and delayed by the administration of alpha MSH antibodies. In conclusion, alpha MSH of brain origin is released during stress and is involved in lowering plasma PRL to basal levels and producing a partial suppression of plasma LH.

Synthesis of a coupled tumor antigen with specificity against transplanted tumors in C3H/HeJ mice.

A spontaneous mammary adenocarcinoma from a female C3H/HeJ mouse was excised, dissected into 2 mm3 pieces, and transplanted into 20 4-month-old C3H/HeJ female mice. After each tumor developed to approximately 1 cm3, they were excised, and their proteins were solubilized and extracted with hypertonic potassium chloride. The extract was purified and subsequently fractionated through a Sephadex G-200 column. The different fractions were read for absorbance on a Beckman spectrophotometer, and those fractions which represented a peak were pooled and tested for cutaneous delayed hypersensitivity on preimmunized guinea pigs. The two fractions which gave maximum hypersensitivity reactions were then coupled to human gamma-globulin. The conjugate was emulsified in Freund's complete adjuvant and used as a treatment against the proliferation of tumors transplanted in C3H/HeJ mice. 70 mice were used in this study. Animals treated with the coupled antigen had significantly smaller tumors when compared with nontreated animals.

Delayed hypersensitivity and granulomatous response after immunization with protein antigens associated with a mycobacterial glycolipid and oil droplets.

A myocardial glycolipid (P3) mixed with protein antigens in oil-in-water emulsion induced lasting delayed hypersensitivity (DH) and granulomatous inflammation after intradermal injection into guinea pigs. This did not occur when P3 and bovine serum albumin (BSA) were given in Freund's incomplete adjuvant. The oil-in-water emulsions consisted of microscopic oil droplets suspended in aqueous medium. By separating oil and aqueous phases from BSA + P3 emulsion it was shown that antigen retained with oil droplets led to DH and granuloma formation. The association of antigen with oil droplets was P3 dependent and was quantitated with 125I-labeled BSA. The same phenomenon occurred with 125I-labeled rabbit gamma-globulin (RGG) + P3 emulsion. Fluorescein-conjugated RGG was observed in a particulate state within or on oil droplets in emulsion containing P3. These physical characteristics of antigen + P3 emulsion appeared to be important for immunogenicity.

Ancillary measures in treatment of myeloma. Use of immune serum globulin, fluoride, or androgen.

We reviewed the efficacy of three agents advocated as ancillary therapy in myeloma patients. Intramuscularly administered immune serum globulin (gamma globulin) was ineffective in preventing infection. Hemoglobin level was improved in some myeloma patients receiving androgens. However, the response rate and the degree of leukopenia or thrombocytopenia were not superior with androgen-melphalan-prenisone combination therapy, as compared with those resulting from the two-drug combination without androgen. A controlled study evaluating androgen plus melphalan has not been done. The long-term administration of fluoride, supplemented by calcium and androgen, induced radiologically apparent bone fluorosis, but strengthening of lytic bone was not observed. Neither objective nor subjective benefit was demonstrated in a controlled study comparing the effects of fluoride (without calcium supplement) with those of the placebo.