Epidemiology and economic impact of varicella in immunocompetent children in Spain. A nation-wide study.

The epidemiology and burden of varicella was assessed through the prospective study of 683 children under 15 years, by 58 primary care paediatricians working on seven autonomous communities of Spain. The mean age was 4.5+/-2.7 years, and 566 (83%) were secondary cases. There were 111 complications in 101 children (14.8%), skin superinfection being the most frequent (8.9%), followed by respiratory tract (4.5%) and eye (2.2%) infections. The mean number of visits to the paediatric clinic was 1.42 (95% C.I. 1.37-1.47), and 5.6% of the children were attended in the emergency department of a hospital previously. All children had at least one prescription, being antihistamines and antipyretics the most prescribed. Thirteen percent received systemic antibiotics and 11% acyclovir. Children were mainly cared by grandparents, and parents were off work for a mean of 0.97 days (1.61 if children under 5 years attended day-care facilities; 0.51 if they did not). Costs derived from medical attention totalled 32.5, and social indirect costs were 63.77.

A double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of mupirocin calcium ointment for eliminating nasal carriage of Staphylococcus aureus among hospital personnel.

Sixty-eight health care workers were enrolled in a double-blind clinical trial and randomized to receive either mupirocin calcium ointment or placebo, intranasally bid for 5 days. Nasal cultures were taken immediately before starting treatment, 1 and 2 during treatment, at the end of treatment, 3 days later, weekly for 1-5 weeks and then monthly for 2-6 months after treatment. Mupirocin eliminated nasal carriage with Staphylococcus aureus in 58% of subjects within two days and 86.7% subjects by the end of therapy compared to 9.4% subjects at the end of treatment with placebo (P < 0.001). Post-treatment colonization rates of 43%, 56% and 67% were attained after 1 month, 2-4 and 6 months treatment with mupirocin respectively and recolonisation with the same strain of S. aureus that had been isolated before treatment was noted in 32%, 40% and 48%. No resistance to mupirocin developed and the drug was well tolerated. Mupirocin is safe and effective in suppressing nasal carriage of S. aureus.

Ticarcillin/clavulanate in severe infections in patients with varying renal function.

The therapeutic efficacy of ticarcillin/clavulanate was assessed in 71 patients with severe infections: 38 acute pyelonephritis, 16 septicaemia and 19 miscellaneous infections. The patients were classified according to their renal function in: Group A, normal (16 cases); B, mild renal impairment (RI) with creatinine clearance (Clcr) between 80 and 40 ml/min (18 cases); C, moderate RI with Clcr between 40 and 15 ml/min (12 cases); D, severe RI with (Clcr) between 15 and 5 ml/min (13 cases) and E, terminal with (Clcr) less than 5 ml/min (12 cases). A total of 105 microorganisms (48.6% resistant to ticarcillin): 31 Pseudomonas aeruginosa, 18 Escherichia coli, 21 other Enterobacteriaceae, 2 Haemophilus influenzae, 10 Bacteroides spp., 14 enterococci, 8 staphylococci and 1 streptococcus, were isolated. All except six Ps. aeruginosa were sensitive to ticarcillin/clavulanate, using 75:10 microgram discs. Bacteriological eradication was obtained in 97% of the cases on the third day and at the end of treatment, and in 82% of the cases after one month. In all the assessable cases, the clinical symptoms disappeared on the third day except in one patient who developed a resistant strain (Klebsiella oxytoca). The wide range of bacteria assessed and the clinical-bacteriological success rates demonstrated that the ticarcillin/clavulanate combination had an efficacy/safety profile that could be considered excellent. Tolerance was good and side effects were not observed. This study confirms the practical efficacy of the recommended dosages derived from our previous kinetic studies in RI.

The susceptibility to amoxycillin/clavulanate of Enterobacteriaceae with plasmid-mediated ampicillin resistance: a twelve-year study of strains in one Spanish hospital.

We studied the antibacterial activity of amoxycillin, clavulanic acid and the combination, against 1210 clinical isolates with plasmid-mediated ampicillin resistance, isolated at the Zaragoza Clinical University Hospital during 12 years. MICs were determined by an agar dilution technique with an inoculum of 10(4) cfu per spot. MIC50 values of amoxycillin/clavulanate ranged from 8 to 16 mg/l. The antibacterial activity of amoxycillin/clavulanate did not show any statistically significant variation during the 12-year period.

Activity of amoxycillin/clavulanate against beta-lactamase-producing Escherichia coli and Klebsiella spp.

We studied the susceptibility to the amoxycillin/clavulanate combination (2:1), and the characteristics of the beta-lactamases, of 1410 amoxycillin-resistant strains of Enterobacteriaceae (785 of Escherichia coli and 625 of Klebsiella spp.). Of the E. coli strains, 97.07% were susceptible to the combination and 98.85% produced plasmid-mediated beta-lactamases. Of the Klebsiella spp. strains, 87.84% were susceptible to the combination and 75.36% produced plasmid-mediated beta-lactamases. In both cases, the differences in MIC values, according to the characteristics of the beta-lactamases of the strains, were statistically significant. Of the 99 strains of E. coli and Klebsiella spp. that were not inhibited by amoxycillin 16 mg/l with clavulanate 8 mg/l, 19 hyperproduced chromosomal beta-lactamase; five produced a plasmid-type beta-lactamase as well. Fifty-seven strains produced two plasmid-type beta-lactamases.

Recovery of the hypothalamo-pituitary-adrenocortical axis in the rat after long-term dexamethasone treatment.

Male rats were treated for 14 days with dexamethasone (2.6 mumol/l in the drinking water) and killed at various times after withdrawal of the drug. Some animals were subjected to stress (ether or sham adrenalectomy) just before killing. The recovery of responsiveness of the components of the hypothalamo-pituitary-adrenocortical axis was assessed by measuring plasma and tissue concentrations of hormones, and the response of the tissue in vitro to appropriate stimuli. In vitro, bioactive corticotrophin-releasing factor (CRF) release in response to acetylcholine and adrenal corticosterone release in response to adrenocorticotrophin (ACTH) were significantly suppressed until 3 days after withdrawal. However, release of immunoreactive or bioactive ACTH in response to ovine CRF or hypothalamic extract did not return to normal until day 5. This was correlated with a reduction in pituitary immunoreactive ACTH content and bioactive plasma ACTH, which were suppressed until days 5 and 4, respectively. No change in hypothalamic immunoreactive CRF content could be detected after treatment, or after stress (ether or sham adrenalectomy) in either treated or control animals. Stress (ether) had no effect on the subsequent response of the anterior pituitary gland in vitro to ovine CRF. The large rises in plasma ACTH and adrenal corticosterone measured after stress (ether) in control animals were completely abolished after dexamethasone treatment and did not return to control values until 5 days after withdrawal. Therefore, it appears that after cessation of chronic dexamethasone treatment in the rat, the responsiveness of the hypothalamus and adrenal gland return to normal before that of the pituitary gland.

Adrenocortical response to acute and chronic ethanol administration in rats.

Acute ethanol administration (2 g/kg IP) induced a significant rise in serum corticosterone levels which seemed to be related to blood ethanol concentration. Chronic ethanol administration, in the form of a liquid diet for 16 or 30 days, did not alter the levels of serum corticosterone. Chronic treatment of rats with a liquid diet containing ethanol resulted in the development of tolerance.

Pituitary-adrenal responses to sub-chronic treatment with phenobarbital and/or phenytoin (diphenylhydantoin) in rats.

The response of the pituitary-adrenal axis of the male rat to sub-chronic dose treatment with phenobarbital and/or phenytoin under basal and stress conditions was investigated. Plasma corticosterone levels were measured in rats sacrificed either in the morning or in the afternoon, subjected or not to 2 hours of immobilization stress. Phenobarbital did not seem to significantly affect the pituitary-adrenal activity under basal conditions or in the response to stress. Phenytoin induced a disruption of the corticosterone diurnal variation present in the rat under basal conditions and seemed to partially inhibit the pituitary-adrenal response to stress when applied in the morning. The combined treatment with phenobarbital and phenytoin affected the afternoon rise in corticosterone levels present under basal conditions, as well as stress response at the same time of the day. The reported results agree with the hypothesis about the existence of mechanisms controlling ACTH release under basal conditions, dissociable from those controlling ACTH release in response to stress situations, and that phenytoin could influence some or others differently, depending on the animal's endocrine situation.

Sound stimulation and its effects on the pituitary-adrenocortical function and brain catecholamines in rats.

The purpose of the present study was to investigate in rats, the effects of sound stimulation upon both the pituitary-adrenal activity (evaluated by the levels of serum corticosterone (B)) and brain dopamine (DA) and noradrenaline (NA). Serum B in rats placed inside the experimental chamber without any sound stimulation was increased and brain DA decreased. For this reason, prior to any sound application, animals were kept in the experimental chamber for 115--120 min, when values had returned to basal levels. The results obtained on the effects of sound frequencies between 500 and 4,000 cps indicated a greater response in the rat pituitary-adrenal system to the lowest frequency (500 cps) we studied. Adrenal cortex hyperactivity occurred in the initial stage of daily repeated 500 cps sound stimulation. During extended periods of daily exposure, the activity of the pituitary-adrenal axis gradually diminished. Changes in the pituitary-adrenal activity, induced by sound stimulation, are closely related to changes in brain NA. The results obtained suggest that at least some of the effects of sound stimulation might be mediated by brain noradrenergic pathways and agree with the hypothesis concerning the existence of a central noradrenergic nervous component which could participate in the control of ACTH secretion.

The effects of acute and chronic administration of morphine on the turnover of brain and adrenal catecholamines in rats.

Brain and adrenal catecholamine turnover in adult female rats treated with morphine was investigated. A different time course response of brain and adrenal catecholamines to alpha-methyl-p-tyrosine methyl-ester (AMT) administration in normal rats was observed; the catecholamine turnover rate in adrenal glands appeared to be much slower than in the brain. Acute morphine increased the turnover of brain dopamine and noradrenaline as well as of adrenal catecholamines, whereas chronic morphine treatment induced a decrease in the turnover of brain noradrenaline. Withdrawal induced by nalorphine produced an increase in the utilization of brain noradrenaline and adrenal catecholamines; this effect could be related to the withdrawl stress situation induced by the opiate antagonist. Although the mechanism of morphine action may implicate other neurotransmitters besides catecholamines, our results contribute to evidence that brain and adrenal catecholamines could be involved in the mechanism of morphine tolerance and/or dependence.

Effects of morphine upon the pituitary-adrenal system and adrenal catecholamines: a comparative study in cats and rats.

The aim of the present study was to investigate the effects of acute and chronic administration of morphine upon the pituitary-adrenal activity and adrenal catecholamines in rats and cats, two animal species with very different behavioural patterns of response to the opiate. Acute administration of the drug induced in both animal species an activation of the pituitary-adrenal system. Chronic administration of morphine to cats and rats induced a depression in the pituitary-adrenal function. No significant changes in the adrenal levels of catecholamines were observed in rats treated chronically with the drug. However, in the cat, the effects of morphine on adrenomedullary function seemed to depend on the stage of morphine treatment. The behavioural patterns of response in both animal species during chronic administration of the opiate, as well as the effects of induced withdrawal with nalorphine (an antagonist of morphine), indicated that dependence on morphine had developed, not only in the rats, but also in the cats. Acute morphine administration had a sedative effect, while in the cats the opiate produced a species-specific manic response characterized by hyperexcitement and aggressive behavior.