Use of a 22-gauge Whitacre needle to reduce the incidence of side effects after lumbar myelography: a prospective randomised study comparing Whitacre and Quincke spinal needles

In a prospective study lumbar iohexol myelography was performed in 107 consecutive patients, randomised for lumbar puncture with a Quincke or Whitacre spinal needle. All patients answered a questionnaire about possible side effects. Data from 100 patients (58 men, 42 women) were evaluated. In the Quincke group (n = 53), 23 (43 %) reported no side effects. In the 30 patients who reported various side effects, post-dural puncture headache (PDPH) occurred in 22 (42 %), of whom 9 had mild, 6 moderate and 7 (13 %) severe cephalalgia, 18 (34 %) reported increased low back pain/sciatica, 5 nausea and 7 dizziness. In the Whitacre group (n = 47), 33 (70 %) had no side effects. PDPH was reported by 9 patients (19 %), of whom 2 had mild, 6 moderate and only 1 (2 %) severe cephalalgia, 4 (9 %) reported increased low back pain/sciatica, 5 nausea and 4 dizziness. The conclusion drawn from this study is that lumbar myelography performed with the Whitacre spinal needle reduces postspinal side effects.     

Randomized controlled trial comparing argon plasma coagulation tonsillectomy with conventional techniques

Argon plasma coagulation (APC) is based on the principle of ionized argon creating a conductive plasma between an activating electrode and a tissue surface. To date, its use in tonsillectomy has not been extensively examined. The purpose of this randomized controlled trial was to assess the clinical efficacy of APC as a tool for this common surgical procedure. Forty patients were randomized into two groups--treatment A (conventional tonsillectomy, n = 20) and treatment B (APC tonsillectomy, n = 20). Trial end-points included a) operative time, b) intra-operative blood loss, and c) objective assessment of post-operative pain, by completion of a visual analogue pain score chart, over a two-week period. Thirty-one patients were available for analysis. There was a statistically significant reduction in the intra-operative blood loss with treatment B (p = 0.02). There was no statistical difference between both groups for the other outcome measures. First clinical experience with this treatment modality shows that it is an attractive alternative to conventional tonsillectomy and may offer possible benefits.     

Assessment of urinary trans, trans-muconic acid as a biomarker of exposure to benzene

OBJECTIVE: To assess the use of trans, trans-muconic acid as a biomarker of occupational exposure to benzene. METHODS: Trans, trans-muconic acid in urine samples of exposed (exposed group, n=36) and non-exposed (non-exposed group, n=116) workers to benzene. Urinary levels of trans, trans-muconic acid were quantified by high-performance liquid chromatography. The study sample consisted of subjects exposed to benzene in an oil refinery in Belo Horizonte, Brazil. Non-parametric statistical analysis was carried out using Kruskall-Wallis test, Mann-Whitney test and Spearman correlation at p<0.05. RESULTS: Workers were exposed on average to benzene levels of 0.15 +/- 0.05 mg/m3 (0.05 ppm) and they showed a urinary trans, trans-muconic acid mean value of 0.19 +/- 0.04 mg/g of creatinine. The reference value range of trans, trans-muconic acid in non-exposed subjects was 0.03 to 0.26 mg/g of creatinine (mean 0.10 +/- 0.08 mg/g of creatinine). There was seen a statistical difference between trans, trans-muconic acid levels in urine samples from exposed and non-exposed groups. There was no correlation between urinary trans, trans-muconic acid and air benzene levels. There was no correlation between urinary trans, trans-muconic acid levels in the exposed group and smoking. Alcohol consumption up to 48 hours before sampling procedure showed no effect on trans, trans-muconic acid levels in both exposed and non-exposed groups. There was however a correlation between age (range 18 to 25 years) and urinary metabolite levels in the latter group. CONCLUSIONS: The results show that it is important to evaluate the effect of age and smoking habits on urinary trans, trans-muconic acid levels.     

Determination of vessel size: a putative framework to assess clinical outcome

BACKGROUND: Unknown is the predictive value of the coronary artery diameter without the administration of vasomotor stimuli. A small reference diameter of the target vessel has been demonstrated to be an adverse prognostic factor in patients undergoing revascularisation. The present study investigated the prognostic value of the proximal non-stenotic left anterior descending coronary artery (LAD) diameter in patients referred for a first diagnostic angiogram without a previous revascularisation. METHODS: A total of 277 patients (mean age 57 year, 61% male) were eligible for analysis. The proximal non-stenotic diameter of the LAD was measured by quantitative coronary angiography without prior nitrate infusion. We defined a small LAD as a diameter < or =2.5 mm. Cardiovascular events were defined as cardiac death, myocardial infarction, and hospitalizations for unstable angina. RESULTS: During a median follow-up of 47 months, 24 major cardiac events occurred. The cumulative survival for patients with a small LAD was significantly lower, than for patients with a large LAD (hazard ratio 2.51; 95% confidence interval 1.11-5.66, p=0.03). In the multivariate analysis, a LAD diameter < or =2.5 mm remained a significant predictor of cardiovascular events after adjustment for age, gender, and the presence of significant coronary artery disease (hazard ratio 2.32; 95% confidence interval 1.01-5.34, p=0.048). CONCLUSION: In patients referred for a first diagnostic angiogram without a previous revascularisation, the diameter of the proximal non-stenotic LAD is an independent predictor of cardiovascular events.     

Implication of 5-HT<Subscript>2</Subscript> receptor subtypes in the mechanism of action of antidepressants in the four plates test

Rationale The selective serotonin reuptake inhibitors (SSRIs) and the serotonin and noradrenaline reuptake inhibitors (SNRIs) increase synaptic levels of serotonin, leading to an increased activation of a multitude of specific postsynaptic 5-HT receptors. However, it is not yet known which 5-HT receptor subtypes mediate the therapeutic effects of antidepressants.Methods The effects of the SSRI, paroxetine and the SNRI, venlafaxine were evaluated in the mouse four plates test (FPT).Results Paroxetine administered intraperitoneally (IP) (0.5, 2–8 mg/kg) potently augmented the number of punished passages accepted by mice in this paradigm. The effects of paroxetine (8 mg/kg) were not reversed by the selective 5-HT_2C receptor antagonist, RS 10-2221 (0.1 mg/kg and 1 mg/kg) or the selective 5-HT_2B/2C receptor antagonist SB 206553 (0.1 mg/kg and 1 mg/kg), at doses which lack an effect when administered alone. In contrast, the selective 5-HT_2A receptor antagonist, SR 46349B (0.1 mg/kg and 1 mg/kg) completely abolished the paroxetine-induced increase in punished passages. The acute administration of venlafaxine induced an anxiolytic-like effect in the FPT at the doses of 2–16 mg/kg. This effect was reversed by the 5-HT_2B/2C receptor antagonist as did SR 46349B, for both doses administered. Our results strongly suggest that activation of 5-HT_2A receptors is critically involved in the anxiolytic activity of paroxetine, whereas the 5-HT_2A and 5-HT_2B receptors are involved in the anti-punishment action of venlafaxine in the FPT. The co-administration of selective 5-HT_{2A, 2B, 2C} receptor agonists (DOI, 0.06 mg/kg and 0.25 mg/kg; BW 723C86, 0.5 mg/kg and 2 mg/kg and RO 60-0175, 0.06 mg/kg and 0.25 mg/kg), respectively, was subsequently investigated. The effects of sub-active doses of paroxetine (0.25 mg/kg and 1 mg/kg) were augmented by BW 723C86 and RO 60-0175 receptor agonist challenge. The anti-punishment effects of venlafaxine (0.25 mg/kg and 1 mg/kg) were potentialised only by DOI co-administration.Conclusion These results indicate that the co-administration of 5-HT₂ receptor agonists with paroxetine and venlafaxine may provide a powerful tool for enhancing the clinical efficacy of these antidepressants.     

氯化钐、氯化镨对大鼠肝脏形态及LPO、SOD活性的影响

本实验采用不同途径给予断乳Ｗｉｓｔａｒ大鼠小剂量（０．０５ｍｇ／ｋｇ、０．０２５ｍｇ／ｋｇ）氯化角钐（ＳｍＣｌ３）、氯化镨（ＰｒＣｌ３）后，测定了肝脏中过氧化脂质（ＬＰＯ）和超氧化物歧化酶（ＳＯＤ）的含量，观察了肝脏的超微结构。结果表明：ＳｍＣｌ３和ＰｒＣｌ３均使肝脏中ＬＰＯ活性降低、ＳＯＤ活性升高，二者比较ＰｒＣｌ３的作用更为明显，肝脏未见明显形态学改变。     

Resting-state functional connectivity abnormalities in limbic and salience networks in social anxiety disorder without comorbidity

The neurobiology of social anxiety disorder (SAD) is not yet fully understood. Structural and functional neuroimaging studies in SAD have identified abnormalities in various brain areas, particularly the amygdala and elements of the salience network. This study is the first to examine resting-state functional brain connectivity in a drug-naive sample of SAD patients without psychiatric comorbidity and healthy controls, using seed regions of interest in bilateral amygdala, in bilateral dorsal anterior cingulate cortex for the salience network, and in bilateral posterior cingulate cortex for the default mode network. Twelve drug-naive SAD patients and pair-wise matched healthy controls, all drawn from the Netherlands Study of Depression and Anxiety sample, underwent resting-state fMRI. Group differences were assessed with voxel-wise gray matter density as nuisance regressor. All results were cluster corrected for multiple comparisons (Z>2.3, p<.05). Relative to control subjects, drug-naive SAD patients demonstrated increased negative right amygdala connectivity with the left middle temporal gyrus, left supramarginal gyrus and left lateral occipital cortex. In the salience network patients showed increased positive bilateral dorsal anterior cingulate connectivity with the left precuneus and left lateral occipital cortex. Default mode network connectivity was not different between groups. These data demonstrate that drug-naive SAD patients without comorbidity show differences in functional connectivity of the amygdala, and of areas involved in self-awareness, some of which have not been implicated in SAD before.     

Identification of amino acid residues in PEPHC1 important for binding to the tumor-specific receptor EGFRvIII

EGFRvIII is a cancer-specific epidermal growth factor tyrosine kinase receptor mutation, expressed in different kinds of cancer, in particular ovarian, glioblastomas, and breast cancer. A peptide, PEPHC1, has previously been shown to bind selectively to EGFRvIII. An alanine scan was performed to identify the amino acid residues important for binding of PEPHC1 to EGFRvIII. The results indicate that the amino acid residues at the N-terminus of PEPHC1 are essential for the binding to the mutated receptor. One analog, [Ala(12)]PEPHC1, showed higher selective binding to EGFRvIII than PEPHC1. On the basis of these results, six truncated peptide analogs derived from the N-terminus of PEPHC1, H-HFIIL-NH2, H-HFIILG-NH2, H-HFIILGF-NH2, H-HFIILGFM-NH2, H-HFLIIGFMR-NH2, and H-HFLIIGFMRR-NH2 were synthesized and tested in the same manner. We observed that H-HFIIL-NH2 and H-HFIILG-NH2 showed almost threefold lower binding to the mutated receptor than PEPHC1, whereas the remainder showed 25% lower binding. The secondary structure of the PEPHC1 analogs was investigated by far UV circular dichroism spectroscopy and their binding correlated with various structural parameters such as charge, mean hydrophobicity (), and mean hydrophobic moment (). This work provides data, which will be useful in the development of novel peptide-based ligands for EGFRvIII-targeted diagnostics and therapy. This work was in part presented at the 17th International Symposium on Radiopharmaceutical Sciences, April 2007, Aachen, Germany.