Comparison of Simulated and in-Vivo Plasma Levels of Cilastatin Following Intravenous in-Line Drug Administration

The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data.     

Osmotic mini-pumps: A convenient program for weight-adjusted filling concentrations

A BASIC computer program is described which is useful for calculating filling concentrations for ALZET osmotic mini-pumps employed in studies of chronic drug and hormone administration. After the user has entered the required daily dose, the pump parameters and the animals' weights, the program gives the following information: The total quantity of the drug or hormone required for the experiment; the minimum volume and concentration of solution, allowing a 10% margin for error, to serve as a standard that, when diluted, will fill all pumps in the experiment; individual volumes of this solution that, when diluted to a constant volume will yield the required concentrations to fill each of the respective pumps. Use of this program will ensure reliably accurate and very rapid preparations of solutions for mini-pump use.     

The effects of intermittent administration of human parathyroid hormone (1–34) on streptozotocin-induced diabetic rats

Intermittent administration of low doses of human parathyroid hormone (h-PTH) has been reported to exhibit an anabolic effect on bone, increasing its mass. We investigated the effects of intermittent administration of h-PTH on bone changes in streptozotocin- (STZ-) induced diabetes mellitus (DM) rats by measuring bone mineral density and bone mineral contents and by bone histomorphometry. Wistar rats, 7–8 months old, were used. Osteoporosis was induced by diabetes mellitus, which was established by an intraperitoneal injection of STZ. Rats were separated into five groups: sham-injected, baseline control, vehicle-only-administered, and low-dose (6.0μg/kg) or high-dose (60.0μg/kg) h-PTH-administered groups. h-PTH or vehicle was injected subcutaneously six times a week for 4 weeks beginning 9 weeks after STZ administration. Bone mineral density and mineral contents were significantly lower in the baseline control and vehicle groups than in the control group. The PTH-administered groups showed higher values compared with both vehicle and baseline control groups. In bone histomorphometry, both bone volume and bone formation in the STZ group were markedly reduced. The h-PTH-administered rats showed increase in both bone volume and bone formation, which are related parameters, but administration of h-PTH did not alter the extent of eroded surface. Our results suggest that intermittent administration of h-PTH is effective in activating bone formation and in preventing further bone loss in osteoporosis developed by STZ-induced DM.     

Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis

BACKGROUND: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion. OBJECTIVE: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR. METHODS: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis. RESULTS: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.     

A study of some current methods for assessment of nasal histamine reactivity

The aim of this study was to investigate the reactivity of the nasal mucosa of patients with pollen allergy compared to healthy controls, when challenged with histamine outside the pollen season. Assessments were made with symptom score, acoustic rhinometry, nasal peak expiratory and inspiratory flow (NPEF and NPIF) and rhinomanometry in order to find the most sensitive method for the purpose. Twenty-one patients with seasonal allergic rhinitis and 20 healthy controls were challenged with histamine dihydrochloride in increasing concentrations (0.01, 0.1, 1.0 mg/ml) locally in the nose. Our results show no difference in mucosal reactivity between the patients and controls regardless of the method used. When comparing the methods we find that NPIF and NPEF are more sensitive to mucosal changes than the other methods we have studied.     

Techniques of nasotracheal intubation with the fiberoptic bronchoscope

When nasotracheal intubation with a fiberoptic bronchoscope is performed, the tube may be blocked in the nasal cavity or larynx, resulting in several complications including epistaxis and hoarseness. We review the causes and complications of tube blockage and discuss optimal techniques for minimizing it.     

鞘内注射两性霉素B治疗隐球菌性脑膜炎的临床观察

目的观察鞘内注射两性霉素B（amphotericin B，AMB）治疗隐球菌性脑膜炎的疗效和不良反应。方法回顾性分析1995-2006年作者医院治疗的8例隐球菌性脑膜炎患者的临床资料，8例患者均采用同时鞘内注射和静脉注射AMB并联合应用氟康唑或氟胞嘧啶治疗。结果痊愈4例，好转3例，死亡1例；鞘内注射后均有头疼、恶心呕吐及下肢麻痛等症状，并出现短暂性双下肢截瘫2例，尿潴留1例，意识障碍2例。结论反复行腰穿放脑脊液控制颅压并联合鞘内注射AMB治疗隐球菌性脑膜炎疗效肯定，但患者有不同程度不良反应。     

Nasal septum lesions caused by chromium exposure among chromium electroplating workers

A chromium electroplating worker, suffering from epistaxis during work, was found to have nasal septum perforation. To determine the etiology and prevalence of nasal septum lesions, we conducted a survey of seven chromium electroplating factories and examined 79 workers. Forty workers from three aluminum electroplating factories were also enrolled as the reference group. Subjects were thoroughly examined by an otolaryngologist and each of them provided a blood and urine sample. A questionnaire interview regarding symptoms of the upper respiratory tract, past medical history, life style, and work history was also conducted. Air chromium concentrations were measured by taking area samples for 4–6 hours. Based on field observation and chromium measurements, we divided chromium electroplating into three different exposure zones: workers directly dealing with electroplating tanks (n = 31), other process workers (n = 29), and office workers and drivers (n = 19). Among the 79 chromium electroplating workers, there were 16 cases of nasal septum perforation, and 42 with either scar formation or ulceration; 10 chromium electroplating workers developed skin ulcers after performing chrome plating. No workers from aluminum electroplating factories had any nasal septum or skin abnormalities. There was a consistent trend between the degree of chromium exposure and the signs and symptoms related to the nose, throat, and skin. Immediate improvement of occupational hygiene is warranted.     

5-HT1A receptor agonists: recent developments and controversial issues

During the last decade, serotonin (5-HT)_1A receptors have been a major target for neurobiological research and drug development. 5-HT_1A receptors have been cloned and a variety of selective agonists, such as the aminotetraline 8-OH-DPAT and the pyrimidinylpiperazine ipsapirone, have become available. Demonstrations of apparent intrinsic activity of these ligands at 5-HT_1A receptors, however, depend highly on the particular assay system. This may be due to the possible existence of receptor subtypes and to assay (or brain region)-dependent differences in receptor reserve and the nature of receptor-effector coupling. Nevertheless, the apparent intrinsic activity of 8-OH-DPAT seems to be higher (although possibly not yet maximal) than that of the pyrimidinylpiperazines. In the brain, 5-HT_1A receptors are located presynaptically as somatodendritic receptors on 5-HT neurons and postsynaptically in particular limbic and cortical regions. Although it is generally accepted that presynaptic 5-HT_1A receptors control 5-HT neuronal activity, recent evidence suggests an additional role of postsynaptic 5-HT_1A receptors in cortex as part of a negative feedback loop. Anxiolytic and antidepressive properties of selective 5-HT_1A receptor agonists have now been confirmed by clinical studies. Although it is well established that the latter properties depend on theagonistic activity of these compounds, theoptimal level of intrinsic activity is still a matter of debate and may be dependent on the clinical indication. Such compounds may also have antiaggressive effects, and possibly anticraving effects (manifested by their alcohol intake-reducing effects in dependent animals), but the specificity of these so-called anti-impulsivity effects is still controversial and not yet tested clinically. Anticataleptic, antiemetic and neuroprotective properties have been demonstrated in different species. Behavioral studies on the mechanisms underlying the anxiolytic and antidepressive effects have examined the relative contribution of pre-and postsynaptic 5-HT_1A receptors by means of local cerebral application and lesion techniques. Most evidence points towards a critical involvement of presynaptic receptors in the anxiolytic effects of 5-HT_1A receptor agonists (although a possible contribution of postsynaptic receptors cannot be excluded). With regard to the antidepressive properties, a case can be made for the reverse; i.e., a strong involvement of postsynaptic receptors and a questionable contribution of presynaptic receptors. However, as the therapeutic effects of those 5-HT_1A receptor (partial) agonists which have been tested clinically require repeated administration, attention has been directed increasingly towards chronic studies. These studies have shown that a number of electrophysiological, biochemical, behavioral and endocrinological 5-HT_1A receptor-related events adapt differentially to repeated or sustained administration. Thus, several hypotheses accounting for the delayed onset of action have been advanced. Among these, time-dependent downregulation /desensitization of eitherpre- orpostsynaptic 5-HT_1A receptors, or cortical 5-HT₂ receptors have received much attention. However, these hypotheses have their weaknesses, and it is argued thatfunctional sensitization of particular postsynaptic 5-HT_1A receptor-mediated events remains a valuable alternate hypothesis. Basic research on the role of 5-HT_1A receptors in psychopathology and in the therapeutic effects of clinically effective therapeutics, as well as on the mechanism of action of 5-HT_1A receptor ligands, will enable rational design of ligands with particular profiles of intrinsic activity at different 5-HT_1A receptor populations, and may contribute to a more efficient treatment of a multiplicity of brain disorders.     

护理管理自选课题中常见的问题及对策

通过归纳护理管理论文自选课题中常见的错误,即选题重复、过大、偏离、有悖伦理、缺乏实用性和可行性等,提出立题前检索、选择贴近护理管理领域的课题、认真筛选专家进行论证、选择易于操作的课题等改进措施。