Spinal 2-chloroprocaine: a comparison with lidocaine in volunteers

Subarachnoid lidocaine has been the anesthetic of choice for outpatient spinal anesthesia. However, its use is associated with transient neurologic symptoms (TNS). Preservative-free formulations of 2-chloroprocaine are now available and may compare favorably with lidocaine for spinal anesthesia. In this double-blinded, randomized, crossover study, we compared spinal chloroprocaine and lidocaine in 8 volunteers, each receiving 2 spinal anesthetics: 1 with 40 mg 2% lidocaine and the other with 40 mg 2% preservative-free 2-chloroprocaine. Pinprick anesthesia, tolerance to transcutaneous electrical stimulation and thigh tourniquet, motor strength, and a simulated discharge pathway were assessed. Chloroprocaine produced anesthetic efficacy similar to lidocaine, including peak block height (T8 [T5-11] versus T8 [T6-12], P = 0.8183) and tourniquet tolerance (46 +/- 6 min versus 38 +/- 24 min, P = 0.4897). Chloroprocaine anesthesia resulted in faster resolution of sensory (103 +/- 13 min versus 126 +/- 16 min, P = 0.0045) and more rapid attainment of simulated discharge criteria (104 +/- 12 min versus 134 +/- 14 min, P = 0.0007). Lidocaine was associated with mild to moderate TNS in 7 of 8 subjects; no subject complained of TNS with chloroprocaine (P = 0.0004). We conclude that the anesthetic profile of chloroprocaine compares favorably with lidocaine. Reliable sensory and motor blockade with predictable duration and minimal side effects make chloroprocaine an attractive choice for outpatient spinal anesthesia. IMPLICATIONS: The spinal anesthetic profile of chloroprocaine (40 mg) compares favorably with the same dose of spinal lidocaine. Reliable sensory and motor blockade with predictable duration and minimal side effects and without signs of transient neurological symptoms make chloroprocaine an attractive choice for outpatient spinal anesthesia.     

Nicotine alters some of cocaine's subjective effects in the absence of physiological or pharmacokinetic changes.

Tobacco smoking and cocaine use often co-occurs and the frequency of smoking has been positively correlated with the likelihood of cocaine use. In addition, nicotine pretreatment has been shown to increase the rate of cocaine self-administration in rats and to enhance cue-induced cocaine craving in humans. The present study was conducted to investigate whether nicotine pretreatment via a transdermal patch alters the behavioral, physiological, and pharmacokinetic effects of an acute dose of cocaine in nondependent human volunteers. Seven male tobacco smokers who used cocaine occasionally provided informed consent and participated in this placebo-controlled, four-visit study. Following pretreatment with a transdermal nicotine patch (placebo, 14 mg), subjects were challenged with an acute dose of intranasal cocaine (placebo, 0.9 mg/kg). Nicotine pretreatment attenuated cocaine-induced increases in reports of "high" and "stimulated" and increased the latency to detect cocaine effects and cocaine-induced euphoria. Nicotine did not alter cocaine's effects on heart rate, skin temperature, and blood pressure or plasma cocaine, benzoylecgonine (BE), or ecgonine methylester (EME) concentrations. Our findings indicate that nicotine pretreatment alters some of the positive subjective effects of cocaine in humans without affecting cocaine's effects on physiologic responses or pharmacokinetic profiles.     

Abstinence symptoms during withdrawal from chronic marijuana use

Although marijuana is the most commonly used illicit drug in the United States, it is not established whether withdrawal from chronic use results in a clinically significant abstinence syndrome. The present study was conducted to characterize symptoms associated with marijuana withdrawal following chronic use during a supervised 28-day abstinence period. Three groups of participants were studied: (a) current chronic marijuana users, (b) former chronic marijuana users who had not used marijuana for at least 6 months prior to the study, and (c) marijuana nonusers. Current users experienced significant increases in anxiety, irritability, physical tension, and physical symptoms and decreases in mood and appetite during marijuana withdrawal. These symptoms were most pronounced during the initial 10 days of abstinence, but some were present for the entire 28-day withdrawal period. These findings support the notion of a marijuana withdrawal syndrome in humans.     

Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam

Background  

Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics.     

A method for the amplification of chemically induced transformation in C3H/10T1/2 clone 8 cells: its use as a potential screening assay

A method has been developed by which to amplify expression of phenotypic transformation of C3H/10T1/2 clone 8 mouse embryo cells not otherwise observed in the standard transformation assay. The expression of transformed foci was amplified by subcultivating chemically treated target cells after they had reached confluence and replating them at subconfluent cell densities. Conditions leading to the expression of the highest numbers of transformed foci include a) a cell seeding density for chemical treatment of 1 X 10(4) cells/dish, b) subculture 4 weeks after treatment, and c) replating cells at a density of 2 X 10(5) cells/-dish. Agents capable of inducing transformation in the standard assay (e.g., 4,4'-bis(dimethylamino)benzophenone, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and others) also yielded transformation in the replating assay. The more marginal transforming activities of chemicals such as ethyl methanesulfonate, 7-(bromomethyl)-12-methylbenz[a]anthracene, and N-methyl-N'-nitro-N-nitrosoguanidine were enhanced by the amplification procedure. Compounds that failed to elicit focal transformation in the standard assay (e.g., dibenz[a,h]anthracene, Tris(2,3-dibromopropyl) phosphate, lead acetate, benzidine, propyleneimine, N-hydroxy-2-fluorenylacetamide, and numerous other compounds of various chemical classes) induced significant levels of phenotypic transformation upon amplification. Noncarcinogens (e.g., phenanthrene, anthracene, 2-aminobiphenyl, cycloheximide, and others) failed to cause significant phenotypic transformation even when cells were replated. To further enhance the applicability of this new replating system, an exogenous source of metabolic activation was added: a 9,000 X g supernatant from Aroclor 1254-induced rat hepatic S-9. This activation system was found a) to be only minimally cytotoxic by itself and b) to be able to mediate NADPH-dependent, dose-dependent toxicity, and transformation by activating the procarcinogens dimethylnitrosamine, 2-naphthylamine, 2-aminoanthracene, and aflatoxin B1. With the use of this revised assay, 14 coded and 23 model compounds were tested. Agreement with in vivo results was observed to be over 85%. The marked sensitivity and discriminatory ability of this revised assay procedure suggest its usefulness as a screen for potential carcinogens of diverse chemical structure.     

Diploid predominance in hereditary nonpolyposis colorectal carcinoma evaluated by flow cytometry

Fifty-nine colorectal carcinomas of patients with verified cancer family syndrome (CFS) were analyzed for DNA ploidy using flow cytometry. Sixty-eight percent of the tumors were diploid, and 32% were aneuploid. The aneuploid tumors had a median DNA index of 1.24 (range, 1.12-1.97). In 90% of all tumors the DNA index was less than 1.27. This predominance of diploid/near-diploid tumors was seen both in primary and in metachronous carcinomas. In 21 cases a cell cycle analysis was possible. Tumors with the S-phase fraction (SPF) greater than or equal to 9.8% had a worse prognosis than tumors with the SPF of less than 9.8%. These findings suggest that the predominance of diploid/near diploid DNA values is one of the characteristics of colorectal carcinomas in CFS. This might signify the existence of two or more pathogenetically different subgroups of colorectal carcinoma and explain the proposed better prognosis of colorectal carcinoma in CFS compared with other colorectal carcinomas.     

Microalbuminuria. Invalidity of simple concentration-based screening tests for early nephropathy due to urinary volumes of diabetic patients

OBJECTIVE: To evaluate the possibility of replacing quantitative albumin excretion rate (AER) measurements with rapid screening tests for microalbuminuria. RESEARCH DESIGN AND METHODS: Dipstick-negative specimens from 363 consecutive insulin-dependent diabetes mellitus (IDDM) and 46 non-insulin-dependent diabetes mellitus (NIDDM) patients from primary-care and hospital clinics (11% inpatients) within the district of Turku University Hospital were studied. Albumin concentrations and 12-h nightly excretion rates (N-AER) were measured by nephelometry (sensitivity 2 mg/L). RESULTS: An increased N-AER (greater than 15 micrograms/min) was seen in 99 IDDM (27%) and 15 NIDDM (33%) patients. The median urinary volume was 900 ml/12 h, with a maximum of 3000 ml. At the level of 20 mg albumin/L, the sensitivity to detect elevated N-AER was 70% among IDDM patients and 60% among NIDDM patients. At a lower albumin concentration of 10 mg/L, the sensitivities were increased to 91 and 87% in IDDM and NIDDM patients, respectively, but the specificities were reduced to 77 and 71%, respectively. CONCLUSIONS: To evaluate incipient nephropathy, we recommend quantitative measurements of N-AER from timed urine collections only. Dipstick tests are either insensitive or nonspecific.     

The role of automated urine particle flow cytometry in clinical practice

Urine particle flow cytometers (UFC) have improved count precision and accuracy compared to visual microscopy and offer significant labor saving. The absence of an internationally recognized reference measurement procedure, however, is a serious drawback to their validation. Chamber counting by phase contrast microscopy of supravitally-stained uncentrifuged urine is considered the best candidate for reference. The UF-100 (Sysmex Corporation, Japan) identifies RBC, WBC, squamous epithelial cells, transitional epithelial and renal tubular cells (SRC), bacteria, hyaline and inclusional casts, yeast-like cells, crystals and spermatozoa, using argon laser flow cytometry. Evaluations have established acceptable linearity over useful working ranges, with an imprecision that is consistently and significantly less than microscopy, and with negligible carry-over. Comparisons of UFC with chamber counts, quantitative urine microscopy, sediment counts, test strips, bacterial culture and urine density are reviewed. Clinical studies include diagnosis and monitoring of urinary tract infection; localization of the sites of hematuria; and diagnosis, monitoring and exclusion of renal disease. The most popular approach is to combine test strips with UFC for primary screening either always by both methods or by using test strips for analytes unrelated to particles analyzed by UFC. Expert systems now exist combining both test modalities based on user definable decision rules. The implementation of such a strategy significantly reduces microscopy review and saves time and expense without diminishing clinical utility.     

In vitro susceptibility of 50 non-beta-lactamase-producing Neisseria gonorrhoeae strains to 12 antimicrobial agents

The in vitro activities of six commonly used antibiotics and six newer β-lactam agents were determined in 50 consecutive clinical isolates of β-lactamase-negative Neisseria gonorrhoeae. The gonococci isolated were notably resistant to penicillin, ampicillin, erythromycin, and tetracycline, whereas all of the strains were susceptible to the newer β-lactam agents cefoxitin and spectinomycin.     

白细胞介素1及白细胞介素8在心肌缺血再灌注损伤中的动态演变及药物干预效果

目的:在心肌缺血再灌注损伤中,炎症细胞因子参与其过程的多个环节。实验拟验证白细胞介素1、白细胞介素8因子在此过程中的动态变化,并分析其与药物干预的关系。方法:实验于2005-10/2006-11在新乡医学院形态学实验室完成。①实验分组:选择健康Wistar成年大鼠70只,按随机数字表法分为3组:对照组(n=10)、模型组(n=30)和药物组(n=30)。后两组又分为缺血0.5h,再灌注2,4,8,12,24h6个时相点,每个时相点5只。对照组只设12h一个时相点作为总体对照。②实验方法:大鼠麻醉后,药物组在右股静脉注入甲泼尼龙(30mg/kg),对照组及模型组注入生理盐水(0.75mg/kg)。采用夹闭左冠状动脉前降支建立大鼠心肌缺血再灌注损伤模型。对照组只开胸不夹闭。③实验评估:在各时相点观察各组大鼠缺血再灌注后的心肌细胞改变;血清学检测白细胞介素1、白细胞介素8因子的动态表达。结果:①模型组缺血再灌注12h炎细胞浸润最显著,药物组炎细胞呈散在浸润。②模型组和药物组白细胞介素1、白细胞介素8因子质量浓度明显高于对照组[缺血再灌注8h为例,白细胞介素1分别为(99.21±14.37),(85.77±11.31),(21.87±10.32)ng/L;白细胞介素8分别为(794.85±24.07),(536.95±19.72),(103.94±11.59)ng/L,P<0.05],峰值分别在缺血再灌注4,8h;同时相点药物组白细胞介素1、白细胞介素8因子质量浓度明显低于模型组(P<0.05)。结论:白细胞介素1和白细胞介素8因子在心肌缺血再灌注损伤的炎症反应中发挥着重要作用;甲泼尼龙对缺血再灌注损伤心肌有保护作用。