HLA-DRB1*04 subtypes are associated with increased inflammatory activity in early rheumatoid arthritis

The sequence polymorphism of HLA-DRB1 molecules in 84 rheumatoid arthritis (RA) patients with early RA has been analysed to evaluate whether particular HLA-DR alleles influence disease progression in the early stage of the disease. Clinical data were analysed by grouping the patients according to disease-associated haplotype combinations (DRB1*04,04/DRB1*04,01/DRB1*04,X/DRB1*01,X) in comparison to patients who did not carry these haplotypes (DRB1*X,X). Our results indicate that patients with early RA who are homozygous for DRB1*04 exhibit an elevated inflammatory activity and an increase of joint affections. In addition, the amino acid polymorphism (QR/KRAA) at position 70-74 seems to affect the production of rheumatoid factors. These results support the role of HLA-DRB1 alleles in the pathogenesis of RA and indicate that patients with particular HLA-DRB1*04 haplotype combinations may require intensified therapeutic interventions in the early stage of the disease to prevent disease progression.      

双波长一元线性回归分光光度法同时测定复方氨基比林注射液中三组分含量

本文依据一组含有不同比例待测和干扰组分的标准混合液的吸收值,采用一元线性回归方法,在选择最佳测定波长对的同时建立标准工作曲线方程,使其更符合实际作品测定时的情况,提高了结果的精度和可靠性,并使计算量和实验工作量得以降低。应用于复方氨基比林注射液中三组分氨基比林、安替比林和巴比妥的同时测定,其平均回收率分别为99.8%,100.4%和99.8%,变异系数分别为0.59,1.48和1.05,结果优于卡尔曼滤波法、偏最小二乘法和目标因子分析法。     

Effects of pretreatment with clonidine, lithium and quinine on the activities of antidepressant drugs in the mouse tail suspension test

Summary— The aim of the present study was the investigation of pretreatment effects with clonidine (0.06 mg/kg, intraperitoneal [ip]), lithium (1 mEq, ip) or quinine (0.5 mg/kg, ip) on the activities of various drugs acting on noradrenergic and/or serotonergic systems in the mouse tail suspension test. Drugs used in the present study included: the tricyclic antidepressants imipramine and dothiepin, the heterocyclic antidepressant trazodone, the 5-HT reuptake inhibitor (SSRI) fluoxetine, the atypical antidepressants mianserin and iprindole, the 5-HT_1A receptor agonist ipsapirone, the 5-HT_2A/2C receptor antagonist ritanserin, and the 5-HT₃ receptor antagonist ondansetron. Clonidine, lithium and quinine differentially enhanced the effects of several psychotropic drugs administered at sub-active doses. The activity of iprindole (32 mg/kg, ip) was not potentiated by pretreatment with clonidine, lithium or quinine. Our results suggest that lithium exerted additive effects via postsynaptic 5-HT_1A receptor activation, quinine via potassium ion channel blockade of 5-HT₃ receptors, while clonidine did so primarily via action at 5-HT₂ receptors.     

Dual energy X-ray absorptiometry of the hand and wrist–a possible technique to assess skeletal maturation: methodology and data in normal youths

Ninety five normal Caucasian subjects (51F, 44 M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA™) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 ± 0.007 g/cm to 0.365 ± 0.035 g/cm in females and 0.425 ± 0.040 g/cm in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1–5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively ( r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age ( r > 0.85).     

Breast MR imaging with loop-gap resonators

Breast images obtained at 1.5 T using a loop-gap resonator pair as both the excitation and detection device are presented. The efficiency of this approach is high, as judged by the low level of radio frequency (RF) power required to obtain a 90 degree pulse and the uniformity of the RF field within the resonator pair. A modification of the pair geometry provides for reasonable observation of the tissues through the chest wall and laterally to the axillae.     

Specificity of the phase I trial for cytotoxic drugs in oncology

Summary— The phase I trial in oncology follows a very different methodology than in other areas of medicine. Its main objective is the identification of the maximal tolerated dose with short and middle range toxicity limits. In general the therapeutic index of anticancer drugs is narrow and the efficacy of drugs is closely associated with their toxic range: specially hematologic. This toxicity has to be well defined within its nature, its gravity, its dose relationship and its reversibility. It is usually correlated with pharmacokinetic. The cytotoxic agents have as their main target DNA and therefore the long term toxicity is poorly defined and seldom wellknown. The oncology phase I trial is always done in advanced cancer patients and in the great majority of cases after several therapeutic tentative having failed. It is never done in healthy volunteers. Patients have to be informed of the nature of the trial with the possibility of a therapeutic response as an associated objective.     

An open-label study of alefacept plus ultraviolet B light as combination therapy for chronic plaque psoriasis

BACKGROUND: Alefacept, a fully human LFA-3/IgG(1) fusion protein, is a selective biological agent approved in the United States for the treatment of chronic plaque psoriasis. In phase 3 trials, clinical improvement and prolonged off-treatment remission of psoriasis correlated with reductions in circulating memory T cells. Reductions in pathogenic epidermal T cells in psoriatic lesions also have been noted following phototherapy with ultraviolet B (UVB) light. Because alefacept and UVB target T cells in different ways, combination therapy with these two agents may lead to greater efficacy. OBJECTIVES: To determine the safety, tolerability, and efficacy trends of combination therapy with alefacept plus UVB light in patients with chronic plaque psoriasis. METHODS: In an open-label, parallel-group study conducted at two sites, one in France and one in the United States, patients with chronic plaque psoriasis who were candidates for phototherapy received 12-weekly intramuscular injections of alefacept, 15 mg. In addition, patients were randomized to one of three treatment arms: no UVB treatment, 6-week UVB treatment, and 12-week UVB treatment. UVB treatment consisted of narrowband (NB) UVB at the site in France and broadband (BB) UVB at the site in the United States. The 12-week treatment period was followed by a 12-week follow-up period. Clinic visits occurred weekly during treatment and every 2-4 weeks during follow-up. RESULTS: A total of 60 patients (n = 30/site) were enrolled in the study. Alefacept was well tolerated when administered in combination with UVB treatment and as monotherapy. There was no evidence of increased phototoxicity or photosensitivity with the combination. At each study site, alefacept/UVB provided a higher overall response rate and led to a more rapid onset of response compared with alefacept monotherapy. Of patients who achieved > or = 50% reduction from baseline Psoriasis Area Severity Index (PASI 50) at 2 weeks after the last dose of alefacept, 75-100% in the combination therapy groups maintained this response throughout follow-up in the absence of further psoriasis therapy. CONCLUSIONS: In patients with chronic plaque psoriasis, combination therapy with alefacept plus short-term (6-12 weeks) UVB treatment is well tolerated with a trend toward greater and more rapid efficacy than alefacept alone.     

三种抗癫痫药对癫痫患者脑电图的背景影响比较研究

目的 :观察比较苯妥因钠 (PHT)、丙戊酸钠 (SVP)和卡马西平 (CBZ)三种抗癫痫药物在治疗癫痫过程中对脑电图(EEG)的背景影响。方法 :对 76例临床确诊为癫痫、EEG检查有痫样波放电的病人按照用药分成 PHT组 2 6例 ,SVP组 2 7例 ,CBZ组 2 3例 ,动态观察各组在服药期间痫样波放电的频度和 EEG背景的变化。结果 :SVP组对 EEG痫样波放电的抑制率明显优于 PHT和 CBZ,对 EEG背景活动影响最明显的是 CBZ,服用 CBZ两周后α波即开始变慢 ,三周后慢波明显增多 ,这种变化与临床疗效不呈一致。结论 :三种药物对 EEG背景活动影响的程度顺序是 CBZ>PHT>SVP,开始时间是服药后 2周 ,而对痫样波放电的抑制率是 SVP>PHT>CBZ     

Early tracheostomy in closed head injuries: experience at a tertiary center in a developing country – a prospective study

Background

An important factor contributing to the high mortality in patients with severe head trauma is cerebral hypoxia. The mechanical ventilation helps both by reduction in the intracranial pressure and hypoxia. Ventilatory support is also required in these patients because of patient's inability to protect the airway, persistence of excessive secretions, and inadequacy of spontaneous ventilation. Prolonged endotracheal intubation is however associated with trauma to the larynx, trachea, and patient discomfort in addition to requirement of sedatives. Tracheostomy has been found to play an integral role in the airway management of such patients, but its timing remains subject to considerable practice variation. In a developing country like India where the intensive care facilities are scarce and rarely available, these critical patients have to be managed in high dependency cubicles in the ward, often with inadequately trained nursing staff and equipment to monitor them. An early tracheostomy in the selected group of patients based on Glasgow Coma Score(GCS) may prove to be life saving.Against this background a prospective study was contemplated to assess the role of early tracheostomy in patients with isolated closed head injury.

Methods

The series consisted of a cohort of 50 patients admitted to the surgical emergency with isolated closed head injury, that were not considered for surgery by the neuro-surgeon or shifted to ICU, but had GCS score of less than 8 and SAPS II score of more than 50. First 50 case records from January 2001 that fulfilled the criteria constituted the control group. The patients were managed as per ATLS protocol and intubated if required at any time before decision to perform tracheostomy was taken. These patients were serially assessed for GCS (worst score of the day as calculated by senior surgical resident) and SAPS scores till day 15 to chart any changes in their status of head injuries and predictive mortality. Those patients who continued to have a GCS score of <8 and SAPS score of >50 for more than 24 hours (to rule out concussion or recovery) underwent tracheostomy. All these patients were finally assessed for mortality rate and hospital stay, the statistical analysis was carried out using SPSS10 version. The final outcome (in terms of mortality) was analyzed utilizing chi-square test and p value <0.05 was considered significant.

Results

At admission both tracheostomy and non-tracheostomy groups were matched with respect to GCS score and SAPS score. The average day of tracheostomy was 2.18 ± 1.0038 days. The GCS scores on days 1, 2, 3, 4, 5, 10 between tracheostomy and non-tracheostomized group were comparable. However the difference in the GCS scores was statistically significant on day 15 being higher in the tracheostomy group.Thus early tracheostomy was observed to improve the mortality rate significantly in patients with isolated closed head injury

Conclusion

It may be concluded that early tracheostomy is beneficial in patients with isolated closed head injury which is severe enough to affect systemic physiological parameters, in terms of decreased mortality and intubation associated complications in centers where ICU care is not readily available. Also, in a selected group of patients, early tracheostomy may do away with the need for prolonged mechanical ventilation.