Risk factors for severe hand foot and mouth disease

Background: Hand foot and mouth disease (HFMD) and herpangina are enteroviral infectious diseases caused mainly by Coxsackie virus A (CA) or enterovirus 71 (EV71). From 2000 to 2002, many complicated cases were reported in Japan, therefore a nationwide questionnaire survey was carried out to assess the situation. The subjects were patients with HFMD or herpangina, or other enterovirus infection from 2000 to 2002, who were either hospitalized over 24 h or who died. The response rates were 41.3% in 2000 and 2001 and 31.6% in 2002. The survey period included the year 2000, when HFMD epidemics due to EV71 occurred. To examine risk factors causing complications of enterovirus infection, severe cases of HFMD were focused on. Methods: HFMD cases in 2000 were divided into two groups according to severity: ‘more severe’ and ‘less severe’. ‘More severe’ was defined as ‘fatal, involving sequelae, or involving hospitalization for 7 days or longer’. Statistical analyses were conducted with Epi info version 3.3 and the association between risk factors and severity was estimated. Results: The number of patients with more severe and less severe cases was 96 and 103, respectively. There was no difference in sex, age, having siblings and family history between the two groups. There was a significant association between attending child care center and severe HFMD. Conclusions: It is not clear why attending child care centers was associated with HFMD severity. Further study is needed.     

Effects of 3-methyl-4-nitrophenol on the suppression of adrenocortical function in immature male rats

In previous studies, we found that 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) isolated from diesel exhaust particles, and also a degradation product of the insecticide fenitrothion, exhibited testicular toxicity in the male of both immature rat and adult Japanese quail. It is well established that a functional relationship exists between the gonads and adrenals. The present study investigates the effect of PNMC on the adrenocortical functions of immature male rats. We subcutaneously injected 28-d-old rats with PNMC (1, 10 or 100 mg/kg) daily for 5 d. The adrenal glands weights significantly decreased in rats treated with 10 or 100 mg/kg PNMC. Plasma concentrations of adrenocorticotropic hormone (ACTH) were significantly increased in animals treated with 100 mg/kg PNMC. In contrast, plasma concentrations of corticosterone were significantly decreased in all PNMC-treated groups, and plasma concentrations of progesterone were significantly decreased in rats treated with 10 or 100 mg/kg PNMC. To investigate the direct effects of PNMC on the secretion of ACTH from the anterior pituitary gland, and on the secretion of corticosterone from the adrenal, we exposed cultured primary anterior pituitary and adrenal cells to PNMC (10(-8), 10(-7), 10(-6), or 10(-5 m)) for 24 h. PNMC did not change basal levels of ACTH released from cultured anterior pituitary cells. However, PNMC significantly inhibited ACTH-stimulated production of corticosterone and progesterone from cultured adrenal cells. These results clearly show that PNMC has a direct effect on the adrenal gland to reduce corticosterone secretion, and the associated increase in plasma ACTH is probably due decreased negative feedback regulation by corticosterone.     

Prostaglandin E1, lidocaine, and prostaglandin E1-lidocaine combination for attenuating cardiovascular responses to extubation

Purpose

Tracheal extubation produces haemodynamic changes that may cause myocardial ischaemia in patients with coronary arterial disease. Intravenous infusion of prostaglandin El (PGE₁) attenuated the hypertensive response to tracheal extubation but failed to blunt the tachycardia, which was attenuated by intravenous lidocaine. Thus, we investigated whether a combination of PGE, and lidocaine can overcome the drawbacks of treatment with PGE₁, alone.

Methods

One hundred adult patients (ASA 1) undergoing elective minor surgery were randomly assigned to receive one of four treatments: saline (as a control), I mg·kg^?1 lidocaine, infusion of 0.1 μg^?1·kg^?1·min^?1 PGE₁, or infusion of 0.1 μg^?1·kg^?1 min^?1 PGE₁ plus injection of I mg^?1·kg/^?1 lidocaine. Lidocaine was injected two minutes before tracheal extubation. The PGE, was infused from completion of surgery until five minutes after tracheal extubation. Anaesthesia was maintained with sevoflurane 1.0%–2.5% and nitrous oxide 60%. Heart rate (HR) and blood pressure (BP) were measured before and after tracheal extubation.

Results

Lidocaine alone and PGE₁-lidocaine combination attenuated the increases in BP and HR observed in the control group: PGE₁ alone was effective in attenuating hypertensive response but ineffective for tachycardia. The suppressive effect of the PGE₁ -lidocaine combination on BP increase was superior to that of each drug alone, and the combined effect on HR increase was similar to that of lidocaine alone.

Conclusion

The combination of PGE₁ infusion and lidocaine is a more effective method of attenuating hypertension and tachycardia associated with tracheal extubation than either drug alone.     

Effects of Exogenous Surfactant on Acute Lung Injury Induced by Intratracheal Instillation of Infant Formula or Human Breast Milk in Rabbits

Background: An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products.

Methods: The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured.

Results: The acidified milk products increased A-aDO(2) (550 +/- 52 and 156 +/- 28 mmHg; mean +/- SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6 +/- 0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84 +/- 4% and 8 +/- 2%), and decreased compliance (0.76 +/- 0.09 and 1.90 +/- 0.11 ml/cm H2 O). Surfactant improved these variables in a dose-dependent manner (A-aDO(2) = 363 +/- 50 and 237 +/- 55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it.     

Neuro-regulational therapy for neuropsychiatric diseases using Ca++ antagonists

It is possible to discuss the role that Ca⁺⁺ antagonists might provide as a therapeutic means of treating various types of cerebral dysfunction, by maintaining a dynamic homeostasis of Ca⁺⁺ in brain neurons. In this paper, we will review the results of Ca⁺⁺ antagonist treatments of subarachnoid haemorrhage (SAH), traumatic subarachnoid haemorrhage, stroke, migraine, dementia, psychiatric disorders, substance abusers, Menière's disease, and amyotrophic lateral sclerosis, and discuss the future of Ca⁺⁺ antagonists and problems in their development. Ca⁺⁺ antagonists have been established as a standard therapy for SAH in the USA, but their efficacy for traumatic SAH has not been confirmed because of the pathological variability of this disease. The data on strokes have not always indicated improved outcomes. Dementia may be a disease for which Ca⁺⁺ antagonists should be indicated. Many clinical studies have also suggested some effectiveness of Ca⁺⁺ antagonists, but the number of patients examined was too small to draw any firm conclusions. Thus, the development of Ca⁺⁺ antagonists to treat cerebral dysfunction is not as greatly advanced as would be expected. This is probably due to the fact that most of the currently used Ca⁺⁺ antagonists were selected on the basis of their cardiovascular effects, but not their effects on the central nervous system. © 1998 John Wiley & Sons, Ltd.     

Induction of different types of uterine adenocarcinomas in Donryu rats due to neonatal exposure to high-dose p-t-octylphenol for different periods

Inappropriate exposure to estrogens in the fetal and/or newborn period can exert irreversible influence, including carcinogenesis on the reproductive system in mammals. The present study was conducted to investigate uterine carcinogenesis in Donryu rats treated neonatally with a high-dose estrogenic compound, p-t-octylphenol (OP) for different exposure periods. Female Donryu rats were subcutaneously administered 100 mg/kg/day OP every other day for the first 5 postnatal days (PNDs 1-5) or the first 2 weeks (PNDs 1-15). They received a single injection of 20 mg/kg N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) into a uterine horn at 11 weeks of age and were examined until 15 months of age. PNDs 1-5 OP-treated rats showed normal development of the female reproductive system, including uterine gland genesis and normal estrous cycling after vaginal opening. The treatment, however, accelerated an earlier occurrence of persistent estrus and increased the number of well differentiated uterine adenocarcinomas as compared with controls. This indicated that PNDs 1-5 OP treatment acts as a delayed modulator of the hypothalamus-pituitary-ovarian hormonal control system and the modulation increased the serum estrogen:progesterone ratio, resulting in induction of uterine tumors. On the contrary, PNDs 1-15 OP treatment demonstrated immediate and irreversible influences on the control system, called 'androgenization', and induced abnormal uterine development manifested by prolonged persistent estrus immediately after vaginal opening and also suppression of uterine gland genesis. In addition, uterine tumor malignancy in morphological and biological property clearly increased in this group although the total number of adenocarcinomas was not increased. The present study provides evidence that neonatal exposure to a high-dose OP enhances uterine carcinogenesis in rats, and the type of uterine tumors is changed by the periods of neonatal exposure to OP, suggesting that the mechanism of uterine tumor development is dependent upon neonatal exposure periods.     

An ovarian interstitial cell hamartoma in a newborn foal.

A case of congenital ovarian interstitial cell hamartoma in a thoroughbred foal that died of apparent nutritional myopathy (white-muscle disease) 14 h after birth is described. An incidental finding at necropsy was a pale brown, mushroom-shaped, pedunculated mass (6 x 4 x 3 cm) attached to the left ovary. On the cut surface, the mass had a peripheral rim of dense parenchyma (3-5 mm wide), surrounding a pale gelatinous core. Histologically, the mass consisted of a peripheral zone of densely packed large cells that were quite similar, morphologically, to fetal ovarian interstitial cells, and a central area of small nests of similar cells scattered within an extremely loose connective tissue matrix. Immunohistochemically, intracytoplasmic positive labelling for inhibin was detected in these cells. These observations suggest that the lesion was an ovarian interstitial cell hamartoma.