Kawasaki disease: a dangerous acute childhood illness

Kawasaki disease is an acute febrile illness most commonly seen in children under the age of 5. It is characterized by fever, rash, cervical lymphadenopathy, bilateral nonexudative conjunctivitis, oropharyngeal mucosal changes, and erythema of the hands and feet followed by desquamation. However, a child with Kawasaki disease may not exhibit all of these symptoms. The disease resembles many other childhood illnesses, such as measles and scarlet fever, and misdiagnosis is common. Left untreated, Kawasaki disease has potential life-threatening consequences; 20% to 25% of children develop coronary artery aneurysms as a result. Although no specific laboratory tests exist that identify Kawasaki disease definitively, there are clinical and laboratory findings that guide diagnosis and treatment. Treatment includes the hospitalization of the child and subsequent administration of high doses of aspirin and intravenous immunoglobulin. With recovery, aspirin doses are reduced and the child may be monitored at home with outpatient follow-up. It is imperative that the health care provider be aware of the symptoms of Kawasaki disease in order to make the diagnosis and treat the child before cardiac sequelae ensue.     

Leukocyte counts in patients with Kawasaki disease: from the results of nationwide surveys of Kawasaki disease in Japan

In the latest survey of Kawasaki disease in Japan, questionnaires on maximal leukocyte counts of the patients were included to clarify whether leukocyte counts could be of value for the diagnosis and prediction of outcome. A questionnaire form and diagnostic guidelines for Kawasaki disease were sent to all pediatric departments of hospitals with > or = 100 beds throughout Japan, and information including maximal leukocyte counts was obtained on patients with Kawasaki disease diagnosed during the 2-y period from January 1993 to December 1994. Of the 11,458 patients diagnosed during the 2-y period, maximal leukocyte counts were reported in 11,062 patients (96.5%). The mean value and the distribution of maximal leukocyte counts were lower in the age group under 1 y. The mean values and the distribution of leukocyte counts were lowest in suspected cases among three diagnostic categories: typical cases of Kawasaki disease, atypical cases, and suspected cases. The mean values of maximal leukocyte counts of the patients with cardiac sequelae were significantly higher than those without cardiac sequelae in each age group. The proportion of patients with cardiac sequelae increased with leukocyte counts in each age group. The Receiver/Response Operating Characteristic (ROC) curve for maximal leukocyte counts in Kawasaki disease revealed that the accuracy of maximal leukocyte counts for prediction of cardiac sequelae was highest in the age group < 6 months, and the most accurate cut-off point was 16 x 10(9)/l. The strongest association between higher leukocyte counts (> or = 16 x 10(9)/l) and cardiac sequelae was observed in the age group < 6 M. A large-scale analysis of leukocyte counts in patients with Kawasaki disease revealed age-dependent relationship between maximal leukocyte counts, diagnostic categories and outcome. Maximal leukocyte counts may be helpful for the prediction of outcome with the consideration of age.     

Hospital facilities available to patients with Kawasaki disease: results of a national survey of Kawasaki disease in Japan

Since 1970, thirteen nationwide epidemiologic surveys of Kawasaki disease have been conducted, and questions on the current situation of hospitals and their facilities have been included in the survey form to assess the care available to patients with Kawasaki disease. To clarify the characteristics of medical care for Kawasaki disease, this paper summarizes the present condition of hospital facilities available to patients with Kawasaki disease. A questionnaire form including questions about the situation of hospital facilities was sent to all pediatric departments of hospitals with 100 or more beds throughout Japan. The proportion of hospitals in which successive observations with echocardiography (UCG) is available (UCG available hospital) was significantly increased compared with the ninth survey (1985-86), whereas that of the hospitals in which coronary angiography (CAG) is available (CAG available hospital) was significantly decreased. Almost all (96.2%) of the patients were reported from the UCG available hospitals. The proportion of patients reported from hospitals with a set policy for intravenous gamma globulin (IVGG) therapy was 74.5%. The proportion of UCG available and CAG available hospitals and that of hospitals with a set policy for IVGG therapy correlated with the increase in the number of patients. In conclusion, hospital facilities available to patients with Kawasaki disease in Japan have satisfactory capability for diagnosis and management of Kawasaki disease.     

The endothelium in Kawasaki disease: the next frontier

A 24-mo study of the laboratory life cycle of the tick Ixodes woodi Bishopp was conducted. No other such study of any species in the subgenus Ixodiopsis Filippova has been reported. Three generations of I. woodi were examined. Larvae and nymphs fed for an average of 4 d; approximately 8-9 d were required for females to engorge. Females laid approximately 900 eggs that required an average of 37.33 d to hatch.     

Male gonadal function in Hodgkin's disease before and after treatment

Twenty eight histologically confirmed cases of Hodgkin's disease were evaluates with regard to libido, sperm count, FSH, LH and urinary ketosteroid levels, before and during different stages of chemotherapy along with testicular biopsy on 16 cases. Decrease in libido during therapy improved following treatment, 50% cases who were oligospermic before treatment became azospermic, Serum FSH levels increased significantly (p 0.001) during the course of treatment. There was no significant change in LH and urinary ketosteroid levels (p 0.05). Testicular biopsy, normal initially, showed germ cell aplasia and absence of spermatogenesis after therapy. Drug induced testicular change leads to sterility.     

The immunologic effects of IVIG in Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness of early childhood that is associated with the development of coronary artery aneurysms in 15-25% of the cases. The acute phase of KD is characterized by a deficiency of suppressor T cells, marked activation of the immune system and increased secretion of cytokines by immune effector cells. Evidence that this immune activation contributes to the vascular endothelial cell damage in KD is suggested by the observation that patients in the acute phase of KD have circulating antibodies lytic for vascular endothelial cells activated with gamma interferon, IL-1 or tumor necrosis factor. In contrast, sera from these patients do not lyse unstimulated endothelial cells. High dose intravenous gammaglobulin (IVGG) treatment is effective in preventing the occurrence of coronary artery abnormalities in KD. Patients treated with IVGG have a significant increase in T suppressor cells, a decrease in circulating activated T helper cells, and a decrease in spontaneous IgG and IgM synthesis. These observations suggest that IVGG reduces the vasculitis in KD by suppressing the marked immune activation associated with this disease.     

Evaluation and treatment of uncompensated unilateral vestibular disease

Polar auxin transport plays a key role in the regulation of plant growth and development. To identify genes involved in this process, we have developed a genetic procedure to screen for mutants of Arabidopsis that are altered in their response to auxin transport inhibitors. We recovered a total of 16 independent mutants that defined seven genes, called TRANSPORT INHIBITOR RESPONSE (TIR) genes. Recessive mutations in one of these genes, TIR3, result in altered responses to transport inhibitors, a reduction in polar auxin transport, and a variety of morphological defects that can be ascribed to changes in indole-3-acetic acid distribution. Most dramatically, tir3 seedlings are strongly deficient in lateral root production, a process that is known to depend on polar auxin transport from the shoot into the root. In addition, tir3 plants display a reduction in apical dominance as well as decreased elongation of siliques, pedicels, roots, and the inflorescence. Biochemical studies indicate that tir3 plants have a reduced number of N-1-naphthylphthalamic (NPA) binding sites, suggesting that the TIR3 gene is required for expression, localization, or stabilization of the NPA binding protein (NBP). Alternatively, the TIR3 gene may encode the NBP. Because the tir3 mutants have a substantial defect in NPA binding, their phenotype provides genetic evidence for a role for the NBP in plant growth and development.     

Beyond lithium in the treatment of bipolar illness

Primary non-Hodgkin lymphoma of the stomach is a rare disorder for which clinical management has not yet been settled completely. Faced with the many uncertainties associated with the selection of a treatment for a patient with this disorder, it is difficult to determine the treatment that is optimal for the patient, as well as the prognosis to be expected. The development of a decision-theoretic model of non-Hodgkin lymphoma of the stomach is described. The model aims to assist the clinician in exploring various clinical questions, among others questions concerning prognosis and optimal treatment. Central to the model is a probabilistic network that offers an explicit representation of the uncertainties underlying the decision-making process. The model has been incorporated in a decision-support system. Preliminary evaluation results indicate that the performance of the model in its present form matches the performance of experienced clinicians.     

Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy

Our purpose in this study was to determine the effects of cheilectomy on the mechanics of dorsiflexion of the first metatarsophalangeal (MTP) joint. Ten fresh-frozen cadaver feet were utilized, of which two demonstrated radiographic evidence of hallux rigidus. Each specimen was rigidly mounted on a custom-made slide tray that was articulated with a hinge mechanism designed to dorsiflex the first MTP joint. Range-of-motion measurements were made on the first MTP joint. Cheilectomy of 30% of the metatarsal head diameter was performed. Lateral radiographs with the beam centered on the MTP joint were taken with the joint at neutral, 20 degrees, 40 degrees, and at the limits of dorsiflexion. This process was repeated after a 50% cheilectomy was performed. The radiographs were examined for changes in joint congruence and in patterns of surface motion as the hallux moved from neutral to full dorsiflexion. Instant centers of rotation were determined by a method first described by Rouleaux. We constructed surface velocity vectors to describe patterns of motion of the first MTP joint. The mean dorsiflexion of the first MTP joint was 67.9 degrees and increased to 78.3 degrees after 30% cheilectomy. The increase in dorsiflexion was significantly greater in the two specimens with hallux rigidus (33%) than in the other specimens (12.1%). After both levels of cheilectomy, the proximal phalanx demonstrated pivoting at the resection site on the metatarsal head. This pivoting resulted in abnormal motion patterns across the MTP joint. Normal sliding motion predominated in early dorsiflexion, with compression peaking at the end stage of dorsiflexion, producing jamming of the articular surfaces. Cheilectomy significantly increased dorsiflexion of the MTP joint, but resulted in abnormal motion patterns. The increase in dorsiflexion resulted from pivoting of the proximal phalanx on the metatarsal head, resulting in anomalous velocity vectors and compression across the MTP joint.     

Changes in epidemic patterns of Kawasaki disease in Japan

Cholangiocarcinoma is the second most common primary tumor of the liver after hepatocellular carcinoma and accounts for 5 to 25% of primary hepatic malignancies. Patients with intrahepatic or peripheral cholangiocarcinoma (ICC) most often present at an advanced stage leading to a poor prognosis. A review of the literature has produced only 10 patients who have survived over five years. We review the case of a young woman with a large cholangiocarcinoma, who has been disease free for eight years. The patient was treated with a right hepatic lobectomy, and received 4 cycles of 5-fluorouracil and levamisole postoperatively. Known factors associated with longer survival in patients with ICC include lack of evidence of local invasion (i.e. capsular, lymphatic, or vascular), negative margins, mucoblia, and well differentiation of the tumor, as well as the absence of lymph node metastases. Our patient had negative margins and lymph nodes, and showed no local invasion. However, no mucobilia was noted, and the tumor was only moderately differentiated. Young age has never been associated with increased survival. ICC remains a relatively uncommon tumor with an insidious onset and late presentation contributing to poor survival. Surgical resection remains the only therapeutic option. Since few patients are potentially resectable at the time of presentation, efforts at early diagnosis and options for adjuvant therapy are imperative.     

Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease

Kawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial aneurysms and myocardial infarction in young children. Prominent thrombocytosis with increased megakaryocytes develops during the convalescent period. To clarify the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (TPO) and other thrombopoietic cytokines in 40 patients with KD (149 samples) and 106 age-matched controls using ELISA. TPO values in the controls were 1.94 +/- 0.69 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85 to 3.27 fmol/ml. In the first week of KD, platelet counts were normal but TPO values increased (approximately 15.5 fmol/ml). TPO levels peaked on day 6 +/- 2 at 5.94 +/- 2.64 fmol/ml and then fell gradually. When platelet counts peaked in the second to third weeks, TPO levels were still high or comparable with the controls. TPO levels in KD patients with normal platelet counts were significantly higher than control levels. Interleukin (IL)-6 levels in the first week rose, but neither IL-11 nor leukemia inhibitory factor was detectable. These results suggest that TPO contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production may be enhanced during the acute phase.     

The efficacy of guanidine hydrochloride in the treatment of Werdnig-Hoffmann disease (author's transl)

The use of guanidine hydrochloride is reported in the treatment of 4 cases of Werdnig-Hoffmann disease. Improvement was achieved in two cases. Amelioration was initially observed in the third patient, but a relapse occurred during temporary discontinuation of therapy and the disease progressed, albeit at a slower rate, after resumption of therapy. The final case was a terminal one in which, however, slight temporary improvement occurred in response to therapy. A maximum dosage of 0.4 g (based on the assumption of an average body weight of 15 kg in these children) was reached by gradual increments. Side effects like shortlasting vomiting were observed only in case 1. The pharmacological action of guanidine hydrochloride is discussed. According to Otsuka and Endon the mechanism of action may be based on an increase in the end-plate potential amplitude. However, an augmented supply of spinal transmitters may also play a role in the mediation to the pharmacological action.     

Evaluation of surgical treatment of renal hyperparathyroidism by measuring intact parathormone blood levels on first postoperative day

In order to further investigate the paternal-age effect on meiotic non-disjunction rates for the chromosomes 14 and 21, we examined spermatozoa from three men aged > 60, using multicolour fluorescent in-situ hybridization (FISH). More than 10,000 sperm cells were analysed for each of the three subjects (A, B and C), by simultaneously hybridizing two YAC probes specific for chromosomes 14 and 21 respectively using two-colour FISH. The results show that the disomy 21 rates observed in the spermatozoa of two out of the three men aged > 60 years were higher (1.02 and 1.17% respectively) than the rates observed in eight control adults aged < 30 years (mean frequency 0.48%) analysed under similar conditions. These results suggest that there may be a small effect of age on male non-disjunction rates for chromosome 21. However, before any firm conclusions could be drawn, a much bigger sample of older men would have to be compared with a paired control population using the same FISH experimental approach.