硫酸奈替米星注射液与硫酸丁胺卡那注射液临床疗效及安全性的比较

为评价硫酸奈替米星的临床疗效及安全性,在１７０例急性细菌感染性病人中作多中心临床研究。结果显示：硫酸奈替米星的有效率（９５．３％）显著高于对照药硫酸丁胺卡那的有效率（８４．１％）,试验组病人咳痰和腰痛症状的平均下降显著高于对照组;硫酸奈替米星治疗后细菌清除率达９７．２％;２组病人不良反应发生率均为４．８％,对照组中有２例（３．２％）出现耳鸣、１例（１．６％）听力减退,但试验组病人用药后未发现听力异常。结论：硫酸奈替米星临床疗效优于硫酸丁胺卡那且较少耳毒性。     

乳腺癌（改良）根治术住院流程与平均住院日

参照业务流程重组的理论与方法研究了乳腺癌根治术的住院流程。结果显示,该病种住院流程存在的主要问题有：诊疗服务的随意性过大,等待诊疗服务的时间过长,患者入院标准的掌握过松,对该病种往院注程进行重组,将在不影响医疗服务质量的前提下有效缩短平均住院日。     

Indocyanine green guided laser photocoagulation in patients with occult choroidal neovascularisation

AIMS: To determine whether indocyanine green (ICG) guided laser photocoagulation of occult choroidal neovascularisations (OCNV) is beneficial for patients with occult choroidal neovascularisation secondary to age related macular degeneration (AMD). METHODS: A prospective pilot study was performed in 21 eyes with OCNV secondary to AMD that could be identified extrafoveolarly or juxtafoveolarly in an early ICG angiographic study. Laser photocoagulation was applied to the neovascular membrane identified in the early ICG angiographic study. RESULTS: Visual acuity ranged from 20/400 to 20/20 (logMAR 0.54 (SD 0.29) before and hand movements and 20/30 (logMAR 0.81 (0.69)) at the last follow up after laser photocoagulation. During the follow up (30 (13) months) vision improved in four eyes (two lines), in seven eyes the initial visual acuity could be stabilised (two lines), in five eyes vision dropped moderately (three to five lines), and in five eyes vision decreased severely (six or more lines). Recurrences (seven patients) or persistent CNV (six patients) was observed in 13 patients. CONCLUSION: This preliminary study of ICG guided laser photocoagulation of occult extrafoveal and juxtafoveal choroidal neovascularisations suggests that this technique may improve the visual prognosis of these patients. Further prospective controlled studies are necessary to confirm these data.     

Inhibition of cardiac inward-rectifier K current by terodiline

The antispasmodic agent terodiline has cardiotoxic effects that include QT lengthening. To determine whether inhibition of inwardly-rectifying K⁺ current (I_K1) might be a factor in the cardiotoxicity, we measured I_K1 in guinea pig ventricular myocytes. Terodiline reduced outward I_K1 with an IC₅₀ of 7 μM; maximal reduction was 60% with 100–300 μM concentration. Inhibition was independent of current direction, and persisted after removal of the drug. Terodiline (3–5 μM) lengthened action potentials in guinea pig papillary muscles by ca. 10%, primarily by slowing phase 3 repolarization; higher concentrations abbreviated the plateau and markedly slowed late repolarization. Terodiline washout provoked an extra lengthening, consistent with persistent inhibition of I_K1 and rapid recovery of net inward plateau current. The results suggest that inhibition of I_K1 is a likely factor in the cardiotoxicity of the drug.     

Effects of acute and chronic administration of olanzapine in comparison to clozapine and haloperidol on extracellular recordings of substantia nigra reticulata neurons in the rat brain

Rationale: Previously, we have shown that the atypical antipsychotics clozapine and risperidone, unlike haloperidol, decreased the firing rate of substantia nigra reticulata (SNR) neurons. As the SNR receives substantial input from the striatum, an area where motoric side-effects of antipsychotics are thought to be mediated, the SNR might be an interesting brain structure with regard to motor side-effects. Objective: The newly developed atypical antipsychotic olanzapine was studied for its effects on the firing rate of SNR cells. In addition, to gain insight in the implications of our experimental setup for clinical use, responses upon clozapine, olanzapine and haloperidol were studied after chronic treatment. Methods: In chloralhydrate-anaesthetized male Wistar rats, extracellular recordings were made from SNR neurons upon intravenously (IV) administered cumulative doses of the antipsychotics. Naive rats and rats that were subcutaneously (SC) injected for 21 days with an antipsychotic were used. Results: Olanzapine (50–1600 mg/kg; IV), significantly inhibited the firing rate of the SNR neurons. Upon 21 days of treatment with a daily SC injection of 20 mg/kg clozapine, the challenge on day 22 with cumulative injections of clozapine (200–6400 mg/kg; IV) significantly inhibited the firing rate of the SNR neurons. Olanzapine (50–1600 mg/kg; IV) also significantly inhibited the SNR activity when pretreated with olanzapine in an SC administered dose of 1 mg/kg, but not 5 mg/kg. Haloperidol (12.5–800 μg/kg; IV) did not significantly affect the SNR activity in rats pretreated with SC administered 0.5 mg/kg haloperidol. Conclusions: Upon acute and chronic administration of clozapine and olanzapine versus haloperidol, differential effects on SNR neuronal firing could be obtained. The experimental setup seem to be valid for further studies into the mechanism of action of typical versus (relatively low doses of) atypical antipsychotics. The implications of the inhibitory effect of atypical antipsychotics on the SNR firing rate are presently unknown, but could be associated with the lower propensity to induced motoric side-effects. On the other hand, the SNR activity might also reflect non-motoric activity possibly related to negative symptoms. Received: 11 December 1998/Final version: 20 January 1999     

Characterizing withdrawal in rats following repeated drug administration using an amphetamine-vehicle-haloperidol drug discrimination

Rationale: Previous research using an amphetamine (AM)-haloperidol (HA) drug- drug discrimination task has shown that predominant responding on the HA-appropriate lever occurs 24 h after a single or multiple administrations of 10 mg/kg AM. Conversely, rebound responding on the AM-appropriate lever occurs following single or multiple administrations of 1 mg/kg HA. HA-appropriate responding was also observed 24 h following a single injection of AM using a three-lever, AM-vehicle-HA discrimination task. However, a single administration of HA did not produce robust rebound responding on the AM-appropriate lever. The present studies seek to clarify the discrepancy between responding following HA in the two- and three-choice tasks. Objective: Experiment 1 examined the extent of rebound responding that could be achieved following ten daily administrations of either 10 mg/kg AM or 1 mg/kg HA. Experiment 2 explored potential differences between the two- and three-choice tasks in characterizing the post-HA cue. Methods: Animals were trained to discriminate 0.35 mg/kg AM, vehicle, and 0.033 mg/kg HA. In experiment 1, animals received ten daily injections of 10 mg/kg AM, vehicle, or 1 mg/kg HA, and were tested 24 h after the final injection, and again 8, 15, and 22 days post-treatment. In experiment 2, animals were retrained and then treated daily with either vehicle or 1.0 mg/kg HA for 10 days, and then tested 24 h after the final injection, and again 5 and 11 days post-treatment, with either all three levers or with only the AM- and HA-appropriate levers available. Results: In experiment 1, multiple injections of AM produced robust HA lever responding, which is consistent with results from previous studies that used the two-choice, AM-HA discrimination task. However, multiple injections of HA did not produce predominant responding on the AM-appropriate lever. In experiment 2, animals treated with either vehicle or HA responded predominantly on the vehicle-appropriate lever when tested with all three levers present. When tested with the vehicle lever removed, however, animals treated with vehicle responded predominantly on the HA-appropriate lever, whereas those treated with HA responded predominantly on the AM-appropriate lever. Conclusions: These results suggest that the two-choice and three-choice task used here differ in how the post-HA withdrawal cue is characterized. This finding emphasizes the importance of knowing the relative locations of the agonist-, vehicle-, and antagonist-produced cues on the interoceptive stimulus continuum established by discrimination training. Received: 3 December 1997/Final version: 16 November 1998     

国产生长激素治疗生长激素缺乏症的疗效观察

了解国产人生长激素（ｈＧＨ）的治疗效果。方法：对１５例未经生长激素治疗的生长激素缺乏症（ＧＨＤ）病人（均经精氨酸和可乐宁两项生长激素激发试验明确诊断,生长激素峰值均小于 １０ μｇ／Ｌ）应用国产分泌型基因重组人生长激素（ｒｈＧＨ）进行治疗,剂量为０．１ｕ／（ｋｇ·ｄ）睡前脐周皮下注射,治疗时间６个月。结果：１５例ＧＨＤ病人６个月身高平均增长（６．３４±０．９４）ｃｍ,生长速度由治疗前的（３．３３±０．４９）ｃｍ／年增加到治疗后的（１２．６８±１．８６）ｃｍ／年。结论：国产人生长激素治疗效果达到国外同类产品水平,而价格仅为进口产品的１／６左右。可安全有效地用于治疗ＧＨＤ身材矮小病人。     

Dose-dependent alteration of rat cardiac sodium current by isoproterenol: Results from direct measurements on multicellular preparations

Conflicting results have been reported in literature about the influence of-adrenergic stimulation on the fast cardiac sodium current (I _Na ⁺). To elucidate these mechanisms in multicellular preparations we used the loose-patch-clamp technique to evaluate the effect of the-adrenergic agonist isoproterenol 1–1000 nmol/l. Isoproterenol enhancedI _Na+ at all membrane potentials by elevation of the maximal availableI _Na ⁺. Only at the high concentration of 1 mol/l wasI _Na ⁺ slightly depressed after depolarizing conditioning clamps. The most marked increase of the maximal availableI _Na ⁺ was 30 ± 9 % after application of 100 nmol/l isoproterenol. To learn about the mechanisms in view of sodium channel modulation we combined isoproterenol with the sodium channel blocker lidocaine (47 mol/l). Under these circumstances the effects of both drugs were completely independent. This investigation shows clearly that low concentrations of isoproterenol increaseI _Na+ in multicellular preparations by a gating-independent mechanism.     

Acyclovir treatment of relapsing-remitting multiple sclerosis

Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on intent-to-treat data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0–2), medium (3–5) and high (6–8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.     

How long is too long? Determining the early management ofmeningococcal disease in Birmingham

Objective:

To determine the length of time cases of meningococcal disease wait before receiving parenteral antibiotic therapy in hospital.

Method:

The hospital case notes of residents of Birmingham who were admitted to local hospitals in 1993 anddischarged with a diagnosis of meningitis or meningococcal disease were reviewed. This information was combined with that held by the West Midlands Ambulance Service.

Results:

Forty out of the 82 patients (49%) who met the case definition had meningococcal infection. Twentyone patients (26%) were admitted by ambulance, 11 of whom had meningococcal infection. The mean time from a request for an ambulance to the patient reaching hospital was 52 min for those with meningococcal infection compared to 55 min for those without. Nineteen patients (47.5%) with meningococcal infection waited more than one hour after admission for antibiotic treatment. Seven had an initial diagnosis of meningitis or meningococcal infection. Ten out of 27 patients with a meningococcal rash (37%), 13 out of 22 patients aged under five years (59%) and 13 out of 24 patients with microbiologically confirmed meningococcal infection (54%) waited more than one hour for treatment. Seven patients with meningococcal infection received benzyl penicillin before admission. Six received hospital antibiotic treatment within the hour.

Conclusion:

The assumption that patients suspected of having meningitis or meningococcal disease are treated promptly once in hospital is not always correct. The results of this study reinforce the need for all doctors to give benzyl penicillin promptly to patients they suspect have meningococcal disease.