静脉补充左卡尼汀治疗透析相关性肉碱缺乏症88例

1临床资料2004-06/12我院终末期肾衰血透治疗≥3 mo;血清肉碱水平≤50 μmol/L;存在不同程度的精神状态差,食欲差,肌肉无力,透析中低血压、痉挛,心律失常,红细胞压积(Hct)≤25%共88(男48,女40)例,年龄18～76(平均48)岁,透析时间3～168(平均69.6)mo.     

Molecular requirements for inhibition of the chemokine receptor CCR8 – probe-dependent allosteric interactions

BACKGROUND AND PURPOSE

Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative structural probes.

EXPERIMENTAL APPROACH

The compounds were tested as inverse agonists and as antagonists against CCL1-induced activity in Gα_i signalling and chemotaxis. Furthermore, they were assessed by heterologous competition binding against two radiolabelled receptor ligands: the endogenous agonist CCL1 and the virus-encoded antagonist MC148.

KEY RESULTS

All compounds were highly potent inverse agonists with EC₅₀ values from 1.7 to 23 nM. Their potencies as antagonists were more widely spread (EC₅₀ values from 5.9 to 1572 nM). Some compounds were balanced antagonists/inverse agonists whereas others were predominantly inverse agonists with >100-fold lower potency as antagonists. A correspondingly broad range of affinities, which followed the antagonist potencies, was disclosed by competition with [¹²⁵I]-CCL1 (K_i 3.4–842 nM), whereas the affinities measured against [¹²⁵I]-MC148 were less widely spread (K_i 0.37–27 nM), and matched the inverse agonist potencies.

CONCLUSION AND IMPLICATIONS

Despite highly potent and direct effects as inverse agonists, competition-binding experiments against radiolabelled agonist and tests for antagonism revealed a probe-dependent allosteric effect of these compounds. Thus, minor chemical changes affected the ability to modify chemokine binding and action, and divided the compounds into two groups: predominantly inverse agonists and balanced antagonists/inverse agonists. These studies have important implications for the design of new inverse agonists with or without antagonist properties.     

The hospital record of the injured child and the need for external cause-of-injury codes. American Academy of Pediatrics. Committee on Injury and Poison Prevention, 1998-1999

Proper record-keeping of emergency department visits and hospitalizations of injured children is vital for appropriate patient management. Determination and documentation of the circumstances surrounding the injury event are essential. This information not only is the basis for preventive counseling, but also provides clues about how similar injuries in other youth can be avoided. The hospital records have an important secondary purpose; namely, if sufficient information about the cause and mechanism of injury is documented, it can be subsequently coded, electronically compiled, and retrieved later to provide an epidemiologic profile of the injury, the first step in prevention at the population level. To be of greatest use, hospital records should indicate the "who, what, when, where, why, and how" of the injury occurrence and whether protective equipment (eg, a seat belt) was used. The pediatrician has two important roles in this area: to document fully the injury event and to advocate the use of standardized external cause-of-injury codes, which allow such data to be compiled and analyzed.     

Self-reported psychopathology in polydrug users

There is a large body of work investigating concurrent associations between polysubstance use and psychopathology, but much of this work has either pre-dated or failed to account for the complex and culturally specific patterns of contemporary drug use. In particular, attendees of dance music events report a greater drug history than their peers and engage in a unique lifestyle. To further investigate the consequences of this type of drug use, 100 subjects who regularly attended dance music events were administered a battery of self-report psychiatric symptom scales. This battery contained the Anxiety Sensitivity Index, the Beck Anxiety Inventory (BAI), the Center for Epidemiologic Studies Depression scale (CES-D), the Dissociative Experiences Scale, the Padua Inventory Revised and additional questions about substance use. Our study population included abstainers and drug users with a wide history of use. We demonstrated strong associations between use of many different drugs, suggesting that polydrug use is the norm in this type of population. We found weak, but statistically significant, correlations between use of alcohol (p < 0.05), amphetamine (p < 0.01) and ecstasy (p < 0.01) with self-reported score on the BAI. There were also positive associations between dissociative symptomatology and the use of amphetamine (p < 0.05) and cocaine (p < 0.05). Furthermore, weekly unit intake of alcohol positively correlated with score on the CES-D (p < 0.05). As polydrug use was the norm in this sample, we performed regression analysis to investigate the contribution of multiple drug use on self-report. This showed that weekly use of alcohol, and frequency of use of amyl nitrate and cigarettes were significant predictors of BAI score. However, the majority of subjects reported being unworried by these symptoms, which may represent a lack of self-awareness, or acceptance of them as the subacute effects of substance use. It remains to be determined at what point adverse effects of drug use begin to interfere with day-to-day life.     

Radiological assessment of constipation

A scoring system for faecal loading was constructed by two experienced observers using the abdominal radiographs of 20 children. Four other observers independently graded the radiographs using this system and there was a high degree of agreement between all six observers (p < 0.001), suggesting that radiological assessment of constipation can be standardised.     

Two‐Year Results of a Randomized Placebo‐Controlled Trial of Vertebroplasty for Acute Osteoporotic Vertebral Fractures

We previously reported the results of a randomized controlled trial that found no benefit of vertebroplasty over a sham procedure for acute osteoporotic vertebral fractures up to 6 months. We report here the 12‐month and 24‐month clinical outcomes of this trial. Eligible participants (n = 78) were randomly assigned to receive either vertebroplasty (n = 38) or a sham procedure (n = 40). Randomization was stratified by treatment center, sex, and symptom duration (<6 weeks or ≥6 weeks). Participants, investigators (except the treating radiologists), and outcome assessors were blinded to group assignments. Enrolment occurred between April 2004 and October 2008 with follow‐up completed October 2010. The primary outcome was overall pain measured on a scale of 0 (no pain) to 10 (maximal imaginable pain). Secondary outcomes included pain at rest and at night, disability, quality of life, perceived recovery, and adverse events, including incident clinically apparent vertebral fractures. At 12 and 24 months, complete data were available for 67 (86%) and 57 (73%) participants, respectively. At 12 months participants in the active group improved by 2.4 ± 2.7 (mean ± SD) units in overall pain compared with 1.9 ± 2.8 units in the sham group, adjusted between‐group mean difference (MD) 0.3 (95% confidence interval [CI], –0.9 to 1.5), whereas at 24 months participants in the active group had improved by 3.0 ± 3.1 units compared with 1.9 ± 3.0 units in the sham group, MD 1.1 (95% CI, –0.3 to 2.4). No significant between‐group differences were observed for any of the secondary efficacy outcomes at 12 or 24 months. There were no between‐group differences in incident clinical vertebral fractures up to 24 months (active: n = 14, sham: n = 13), although the study had inadequate power for this outcome. These results provide further evidence that the use of this treatment in routine care is unsupported. © 2014 American Society for Bone and Mineral Research.     

Comparison of inhibitory and binding characteristics of an antibody causing acquired von Willebrand syndrome: an assay for von Willebrand factor binding by antibody

An acquired inhibitor of von Willebrand factor (vWF) activity occurring in a patient with benign gammopathy and von Willebrand syndrome (vWS) has been partially characterized. The inhibitor-induced syndrome resulted in low to undetectable plasma levels of vWF/ristocetin, vWF/botrocetin, FVIIIR:Ag, and FVIII:C with a normal to slightly prolonged bleeding time. Platelet vWF was normal. Intensive and continuous infusion of a heat-treated factor VIII concentrate (Hemofil- T, Hyland, Glendale, Calif) elevated the FVIII:C plasma levels to about 100%, with an increase in FVIIIR:Ag levels to about 340% and vWF/ristocetin levels to about 40%, much lower than expected based on the dose of Hemofil-T and its content of vWF and FVIII:C activities. The inhibitor bound to staphylococcal protein A (SpA) with high affinity, indicating an IgG antibody (Ab). An assay for the vWF-binding capacity was developed on the basis of absorption of the Ab from serially diluted plasma by SpA and removal of vWF and FVIII:C activities from normal plasma by the SpA-Ab complex. The Ab-binding site was on the vWF component of the factor VIII complex. The Ab was unable to bind isolated FVIII:C. The combined use of the new vWF- binding assay and a battery of tests for inhibition of vWF-dependent platelet aggregation with ristocetin (which detects high molecular weight vWF), with botrocetin (which detects high and low molecular weight vWF), and with platelet-aggregating factor (which detects high molecular weight vWF) provided a means of analysis of Ab effect on in vitro vWF function. Using these tests, a comparison was made of the effects of the vWS Ab with those of an Ab inhibitor occurring in homozygous von Willebrand's disease. The Ab of the vWS patient had weak inhibitory action on vWF/ristocetin without having an effect on vWF/botrocetin and platelet-aggregating factor, a high titer vWF- binding capacity, and no anamnestic response following concentrate therapy. These findings contrasted with those of the Ab occurring in inhibitor von Willebrand's disease in which vWF inhibitor and binding values were similar, with a strong anamnestic response. The findings indicate that the vWS Ab binds to an epitope on the molecular vWF in such a way that causes only limited inhibition of vWF/ristocetin function and no inhibition of vWF/botrocetin function, suggesting that these two functional domains are at separate sites.     

An Initial Experience of Continuous Peritoneal Dialysis in Children in the Armed Forces

Background

Continuous peritoneal dialysis (CPD) is a modality of renal replacement therapy in children with renal failure. A retrospective study analysis of CPD data over four years at our center was carried out.

Methods

Ten children with renal failure on CPD were included. Depending on the supply, peritoneal dialysis (PD) fluids of two different brands were used in the same patients over time. The patient months of CPD were divided into two groups based on the brand of PD fluid used. The rates of complications with the two different fluid brands were compared.

Results

The mean age of our patients was 8.8 ± 2.51 years (range 4 – 13), with a total of 141 patient months of CPD. The mean follow up period was 13.6 months (range 1- 48). The commonest underlying renal pathology was focal segmental glomerulosclerosis in 30%, followed by cresentric glomerulonephritis in 20%. Peritonitis rate was 0.48 episodes per patient year. Patients in Group I had one episode of peritonitis per 53.5 patient months and Group II had one episode per 7.25 patient months (p= 0.021, relative risk of 7.3). Patients in Group I had one episode of hypertensive encephalopathy per 107 patient months and Group II had one episode per 4.8 patient months (p= 0.001, relative risk of 21.9). On analyzing the outcome, four patients were eventually transplanted, three continued on CPD awaiting a renal transplant, two died and one recovered spontaneously.

Conclusion

CPD is an effective bridge to renal transplant in children with end stage renal disease. The risk of developing peritonitis and hypertensive encephalopathy varied with the brand of fluid used over time in the same set of patients.Key Words: Continuous peritoneal dialysis, Peritonitis