食管癌的诊断和治疗

1诊断 1.1普查由于食管早期癌的疗效明显好于进展期癌,加之,内镜下食管粘膜切除术用于无淋巴结转移的表浅食管癌的根治已取得良好疗效,并已逐渐被医患双方所接受,因而普查仍是目前改善食管癌(EC)疗效的肯定手段.我国北方尤其是太行山地区及伊朗里海沿岸居民、有头颈癌肿史者是EC的高发人群.     

Conjunctival-Limbal Autograft for Primary and Recurrent Pterygium

Background

It has been postulated that pterygium results from hypo function of limbal stem cells. Therefore conjunctival-limbal autograft has been advocated for the treatment of this condition. This study was undertaken to evaluate the results of conjunctival-limbal autograft procedure in primary and recurrent pterygia.

Methods

32 eyes of 28 individuals with primary and recurrent pterygium (24 primary, 8 recurrent) were undertaken for conjunctival-limbal autograft procedure under peribulbar anaesthesia followed by topical antibiotic- steroid drops for two weeks. The cases were reviewed as per protocol for 6 to 18 months.

Result

There was no recurrence of pterygium in these cases and they were free from any major postoperative complications. Conclusion: Conjunctival-limbal autograft is the procedure of choice for primary and recurrent pterygia.Key Words: Conjunctival-limbal autograft, Pterygium     

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 CASE survey: Patient and physician perceptions regarding asthma medication use and associated oropharyngeal symptoms

BACKGROUND:

Oropharyngeal (OP) symptoms are common in asthma patients using inhaled corticosteroids (ICSs) alone and in combination with a long-acting beta₂-agonist (LABA). Patterns of medication use, level of asthma control and association with OP symptoms are not often reported in a nonstudy setting.

OBJECTIVES:

To determine the prevalence of OP symptoms among adult asthma patients using ICSs alone and an ICS plus a LABA; to investigate the relationships between medication use, asthma control and OP symptoms; and to assess family physicians’ (FPs’) perceptions of the prevalence and management of OP symptoms.

METHODS:

A random telephone survey of 1003 asthma patients and 250 FPs treating asthma patients was conducted from February to March 2005 across Canada.

RESULTS:

Twenty-four per cent of patients experienced OP symptoms; 67% of them spoke to their FPs about the OP symptoms. Thirty-one per cent of patients who experienced OP symptoms stopped or reduced their dose of medication. OP symptoms were reported by 25% of patients using ICSs and 22% using an ICS plus a LABA. The incidence of OP symptoms was not affected by the choice of inhalation device (metered-dose inhaler versus dry powder inhaler) or the use of a spacer. Fifty-eight per cent of patients had uncontrolled asthma; patients achieving a lower level of general education were more likely to have poor control. Patients with uncontrolled asthma were more likely than those with controlled asthma to report OP symptoms (28% versus 18%, respectively; P<0.05). Eighty-nine per cent of FPs had patients who had reported OP symptoms to them. FPs estimated that 15% of their patients experienced OP symptoms and that compliance to treatment worsened in approximately 20% of them.

CONCLUSIONS:

The prevalence of OP symptoms in asthma patients using ICSs and an ICS plus a LABA is significant. OP symptoms were found to be associated with a reduced patient education level, with a likelihood of reducing or stopping medication, and with a less well-controlled asthma patient. While FPs recognized that a significant proportion of their asthma patients experience OP symptoms and that OP symptoms may affect compliance, they underestimated the prevalence of this problem.