Pediatric intracranial pressure monitoring in hypoxic and nonhypoxic brain injury

We reviewed the results of all pediatric patients undergoing intracranial pressure (ICP) monitoring in a 2-year period at our institution. The outcome of patients suffering hypoxia or ischemic injuries (HII) is compared to those suffering non-hypoxic or non-ischemic injuries (NHII). Thirty-four patients had ICP monitors placed during the study period. Inconplete patient information led to the exclusion of 5 patients. An additional 5 patients were excluded because no measures to control ICP were taken after the monitor was placed. Twenty-four patients required treatment for raised ICP (hyperventilation, 24; mannitol, 19; barbiturate coma, 6). Admission Glasgow Coma Score in patients suffering HII (median score 5) and NHII (median score 6) were not significantly different (Mann-Whitney U Test). Only 2 of 8 patients with HII were near-drowning vietims. The remaining 6 had HII from other causes (5 survivors of various forms of asphyxia and 1 of cardiac arrest). All 8 patients had poor outcomes (1 severely disabled; 7 died). The 16 patients with NHII had a variety of diagnoses (6 trauma, 5 encephalitis, 4 bacterial meningitis, 1 diabetic ketoacidosis). Among these, 6 had good outcomes and 10 poor outcomes (2 severely disabled, 2 vegetative, and 6 died). The difference in outcome between patients with NHII and HII is significant at P=0.059 (Fischer Exact test). Patients with NHII may benefit from ICP monitoring. Patients with HII from near-drowning and other causes did not appear to benefit from ICP monitoring and interventions directed at controlling ICP.     

Evaluation of Tenidap (CP-66,248) on human neutrophil arachidonic acid metabolism, chemotactic potential and clinical efficacy in the treatment of rheumatoid arthritis

Ten patients with rheumatoid arthritis (RA) were evaluated in a placebo-controlled, double-blind study examining the clinical efficacy of a novel nonsteroidal anti-inflammatory agent: Tenidap (CP-66,248). RA patients receiving active drug therapy (n = 6) demonstrated clinically significant improvements in observer assessment of pain (p less than 0.025), painful joint count (p less than 0.010), and overall clinical assessment as based on a modified rheumatoid activity index, MRAI (p less than 0.025). In parallel laboratory assays, Tenidap was found to exhibit a significant in vitro dose-dependent inhibition of ionophore-stimulated neutrophil production of the 5-lipoxygenase product: [3H]leukotriene B4 (LTB4). Although more importantly, Tenidap was also found to exhibit an in vitro dose-dependent inhibition (IC50 20 microM) of the ionophore-stimulated release (deacylation) of the precursor [3H]arachidonic acid (AA) from membrane phospholipids. In further studies, Tenidap did not have any effect on fMLP-induced neutrophil chemotactic response. These results suggest that one of the possible mechanisms for the clinical effectiveness of this agent, may be through its effect at inhibiting the release of free AA from membrane phospholipids and therefore limiting its further metabolism into certain biologically-active inflammatory lipids.     

Induction of light hydrocarbon nephropathy by p-dichlorobenzene

In order to clarify the etiology of a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidney in male rats, the nephrotoxicity of p-dichlorobenzene (p-DCB) was investigated in a subchronic study. Groups of ten male and ten female Fischer 344 rats were dosed by gavage with 0 (controls), 75, 150, 300 or 600 mg p-DCB/kg/day in corn oil. Half of the animals were sacrificed after 4 weeks and the remainder after 13 weeks. Increased urinary LDH and epithelial cell excretion and exacerbation of hyaline droplet accumulation in the cytoplasm of renal cortical cells were observed in male rats over the entire dose range investigated. Tubular single cell necrosis, dilated tubules with granular cast formation in the outer zone of the medulla, were evident in male rats after 4 and 13 weeks of treatment with doses of 150–600 mg/kg/day. In female rats there was no indication of a nephrotoxic action of p-DCB. The effects on the kidney, both in their morphological characteristics and the fact that they occur exclusively in male animals, correspond to the light hydrocarbon nephropathy observed as a result of short-term treatment with a number of aliphatic and cyclic hydrocarbons. The development of cortical renal tumors seems to be associated with this kind of kidney damage which is unique to male rats. The literature on this subject generally regards these renal effects as not predictive for man.     

维生素D_3对报告载体荧光素酶表达的作用

目的：　研究１,２５－二羟维生素Ｄ３ 对结肠癌细胞系Ｃａｃｏ－２ 细胞中报告基因表达的作用,并探讨在报告载体ｐＧＬ２ 序列中存在潜在的抑制性维生素Ｄ应答元件（ＶＤＲＥ）的可能性。方法：　采用磷酸钙沉淀法将报告载体转染入Ｃａｃｏ－２ 细胞。Ｃａｃｏ－２细胞经不同浓度１,２５－二羟维生素Ｄ３ 处理后测定细胞裂解液中表达的荧光素酶活性。结果：　应用ｐＧＬ２ 报告载体时,当用ｐＳＧ５－ＶＤＲ表达载体共转染后,１,２５－二羟维生素Ｄ３显著地抑制Ｃａｃｏ－２ 细胞荧光素酶的表达（Ｐ＜ ０．０５）;而未使用该表达载体共转染则无抑制作用（Ｐ＞ ０．０５）。应用ｐＧＬ３ 报告载体时,不同浓度的１,２５－二羟维生素Ｄ３ 对ｐＬＧ３转染后Ｃａｃｏ－２ 细胞表达的荧光素酶活性均无显著抑制作用（Ｐ＞ ０．０５）,该作用不依赖是否存在有ｐＳＧ５－ＶＤＲ表达载体共转染。结论：１,２５－二羟维生素Ｄ３ 对报告载体ＰＧＬ２ 荧光素酶表达具有抑制作用,而对ｐＧＬ３ 则否;类似人类ＰＴＨ基因中的潜在抑制性ＶＤＲＥ存在于报告载体ｐＧＬ２,在ｐＧＬ３ 中该ＶＤＲＥ业已改变。     

The organization and evaluation of a computer-assisted, centralized immunization registry

The rationale for, and establishment of, a computer-assisted, centralized immunization registry are described. This registry was created to improve the quality and quantity of information regarding immunization status for a defined population receiving primary care from a variety of providers, principally public clinics and private practitioners. An evaluation of the feasibility of the registry after one year's function shows that 93 per cent of eligible providers initially agreed to participate and 73 per cent continue to do so. Their reports have resulted in the creation of 17,500 individual patient files. Of a prospective cohort of newborns, 23 per cent were identified as "high-risk" for overdue immunizations. After one year, the immunization rates in audited groups improved significantly. The direct cost of this registry is less than 65 cents per currently registered child per year.     

A quality assessment tool to evaluate tocolytic studies

Over the past 15 years, the use of β-agonists has declined worldwide. Following the Royal College of Obstetricians and Gynaecologists guidelines in 2002, clinicians in the UK and beyond were faced with the dilemma of continuing to use β-agonists, desist from using tocolytic therapy completely or choosing to change to atosiban or calcium channel blockers (CCBs). While grade A level 1 evidence exists to show that atosiban is significantly more efficacious than placebo and significantly safer than β-agonists for the treatment of spontaneous preterm labour, the evidence for CCBs, such as nifedipine, is much less robust and no placebo-controlled trials have been performed. Published studies on nifedipine are largely investigator-led studies of small sample size, which lack sufficient power. As a result, most of the evidence has been based on meta-analyses of these studies, which look retrospectively at pooled data and are only as good as the quality of the studies included. In light of this, a tool was developed to produce a systematic review of studies on tocolytic effectiveness, which can and should be applied to all tocolytics and which considered both method- and topic-specific markers of quality. In the process of applying this tool to nifedipine, an extensive literature search identified 31 studies for a systematic review of the quality of nifedipine studies assessed by eight paired reviewers with wide experience in the subject of spontaneous preterm labour and preterm birth. Forty topic- and method-specific items of quality were assessed. The paucity of good quality studies of nifedipine used for the treatment of spontaneous preterm labour should be highlighted in meta-analyses or systematic reviews, which measure efficacy and should limit and influence the degree to which recommendations and guidelines are made on the basis of such studies.     

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