Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

A profile of invasive cutaneous malignant melanoma in Malta: 1993–2002

BACKGROUND: The incidence of malignant melanoma of the skin has risen in every part of the world where reliable cancer registration data are found. OBJECTIVE: Our study aims to describe the changing incidence of and survival from invasive cutaneous malignant melanoma in Malta, by analysing the data from the 211 cases that were registered at the Malta National Cancer Registry between 1993 and 2002. RESULTS: The age standardized incidence rates for invasive cutaneous malignant melanoma rose from 3.7 per 100,000 population per year for males and 5.1 for females in the first 5-year period, to 8.0 per 100,000 population per year for males and 5.9 for females in the second 5-year period. In both sexes, numbers of thin (< or = 1.0 mm) invasive melanomas increased significantly between 1993 and 2002; males also registered a significant increase in intermediate-thickness (1.01-4.0 mm) melanomas. The increase in numbers of thin and intermediate-thickness melanomas between the two 5-year periods was greatest in patients aged 60 years and over. The overall absolute 5-year survival rate for the first period was 74% and for the second period 92%. CONCLUSION: Numbers of reported cases of invasive cutaneous malignant melanoma in Malta have more than doubled during the 10-year study period. This is mostly due to a marked rise in the diagnosis of thin melanomas in both sexes, occurring mainly in patients aged 60 years and over. As thin melanomas are of low metastasizing potential, this has resulted in an increase in survival between the two 5-year study periods.     

A survey: conscious sedation with epidural and zygapophyseal injections: is it necessary?

BACKGROUND CONTEXT: Substantial variation exists regarding the use of sedation before interventional spine techniques. Patient preference should play an important role in decision making regarding the need for sedation. However, little is known about patients' anxiety levels before spinal injections and their perceptions about the necessity of sedation. PURPOSE: To determine patient perception for need for sedation before epidural steroid injections and zygapophyseal joint injections. STUDY DESIGN/SETTING: Survey of consecutive spinal injection patients in an outpatient spine center. PATIENT SAMPLE: 500 consecutive lumbar, thoracic, and cervical patients receiving spinal injections. OUTCOME MEASURES: A 12-item questionnaire assessing patients' perceived anxiety before to a spinal injection. METHODS: Subjects were given the questionnaire after their spinal injection. Percentages requesting sedation for a first and potential second procedure were assessed. Additionally, anxiety level and pain rating, location of injection, age, sex, and other medication use were analyzed to determine the effect on the request for sedation. RESULTS: 17% of patients questioned requested sedation before an injection, and 28% would request sedation if they were to have a second injection. CONCLUSIONS: Routine sedation before diagnostic and therapeutic injections is not necessary as the majority of patients would not request sedation before the procedure when given the option. However, in some patients sedation is indicated, and all patients would benefit from educational material on sedation before the injection.     

Advanced thyroid carcinoma: an experience of 385 cases.

AIMS: To report clinical outcomes of a large series of cases with advanced thyroid cancer. STUDY DESIGN: Three hundred and eighty-five patients at the UICC stages III and IV were selected for the study with thyroid cancer. RESULTS: Papillary carcinoma and sclerosing carcinoma have better survival than the Hürthle cell and insular types. Lymphatic metastasis does not appear to worsen the prognosis. All the tumour forms offer the chance of long survival. CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma. The combined treatments of surgery, metabolic beam therapy, suppressive hormone therapy, radiotherapy and chemotherapy cure a high percentage of patients with the tumour at an advanced stage.     

Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion.

The new treatment strategy for Peritoneal Surface Malignancy combines a cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cytoreduction removes all macroscopic tumor. Intraperitoneal chemotherapy avoids implantation of microscopic residual tumor cells on intra-abdominal surfaces when it is administered intraoperatively and/or early in the postoperative period. Delivering cytotoxic drugs directly into the peritoneal cavity maximizes dose intensity and minimizes systemic toxicity. Hyperthermia is selectively cytotoxic for malignant cells and potentiates the effect of chemotherapy. Implementation of this procedure makes the perioperative personnel to face a risk of exposure to cytotoxic agents. Furthermore, peritonectomies and electro-evaporation of tumor nodules are performed with high voltage electrocautery, generating a large amount of surgical smoke during several hours. Inhalation of these fumes may be also a risk for healthcare workers. In this article, we analyse in depth these new risks of the operating room personnel, we review the literature, and we give guidelines for secure performance of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy, as well as for early postoperative intraperitoneal chemotherapy administration. These new procedures are safe techniques for patients and healthcare workers provided adequate policies are adopted to avoid occupational exposure.     

灾难的时代错误:灾害医学的过去、现在和将来(一)

灾难,特别是地震、火山、洪水以及与战争有关的事件如饥饿和流行性传染病,是人类有记录的经历的一部分。从意大利庞贝的火山爆发,到约翰斯顿的洪水、第二次世界大战和黑色瘟疫,到西班牙流感,都发生了灾难,这不会被传说和历史书籍长期忘却。不过,在20世纪中叶以前,那些灾难的发生相对较少,且相距时间较长。从20世纪中叶以来,灾难的本质发生了变化。从恐怖分子使用“新技术”,到与气候有关的导致亿万美元经济损失的事件,表明这个世界正在发生变化。仅仅在最近的50~60年间,造成多种多样的伤亡事件,其危险性和频率的增加引人注目,并且注定要在接…     

Combined transbronchial needle aspiration and positron emission tomography for mediastinal staging of NSCLC.

There are no data available combining transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and positron emission tomography (PET) in the staging of nonsmall cell lung cancer (NSCLC). The aim of the current study was to determine if these two methods can enhance the negative predictive value of the individual modality alone, for a specific lymph node station, and if this integrated approach can reduce the number of mediastinoscopies. A total of 113 patients with enlarged mediastinal lymph nodes (> or = 1 cm), who underwent both TBNA and PET scanning, were included. In 51 patients, histopathology, confirmed by surgical lymph node dissection, was compared with PET results and TBNA. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect malignant lymphadenopathy was 68 (13/19), 89 (119/134), 46 (13/28), 95 (119/125) and 86% (132/152) for PET, respectively; 54% (6/11), 100 (53/53), 100 (6/6), 91 (53/58) and 92% (59/64), respectively for TBNA; and 100 (11/11), 94 (50/53), 79 (11/14), 100 (50/50) and 95 (61/64) for combined TBNA and PET, respectively. Combination of transbronchial needle aspiration and positron emission tomography has the potential to allow adequate mediastinal staging of nonsmall cell lung cancer with enlarged lymph nodes in most patients without the need for mediastinoscopy.