Analysis of gabapentin in serum and plasma by solid-phase extraction and gas chromatography-mass spectrometry for therapeutic drug monitoring.
A simple method for the determination of gabapentin (Neurontin) is described. The method uses solid-phase extraction by disk column and derivatization followed by gas chromatographic-mass spectrometric analysis. The single-step derivatization with MTBSTFA produces a t-BDMS derivative of both the carboxylic and amine moieties of the molecule. Each step of the procedure was optimized to assure reliable performance of the method. The assay limit of detection was 0.1 microg/mL with a linear range from 1.0 to 35 microg/mL. Within-run (n = 3) and between-run (n = 40) coefficients of variation were less than 8.2 and 15.9%, respectively. The method has proven reliable in routine production for more than a year, producing clean chromatography with unique ion fragments, consistent ion mass ratios, and no interferences. Statistical analysis of the gabapentin concentrations measured in 1020 random specimens over a 2-month period showed a mean concentration of 6.07 microg/mL with a standard deviation of 5.28. (+info
Progesterone alters biliary flow dynamics.
OBJECTIVE: To test the hypothesis that progesterone alters sphincter of Oddi and gallbladder function and, therefore, bile flow dynamics. SUMMARY BACKGROUND DATA: Although the effects of progesterone on the biliary tract have been implicated in the increased incidence of gallstones among women, the specific effects of prolonged elevation of progesterone levels, such as occurs with contraceptive progesterone implants and during pregnancy, on the sphincter of Oddi and biliary flow dynamics are still incompletely understood. METHODS: Adult female prairie dogs were randomly assigned to receive subcutaneous implants containing either progesterone or inactive pellet matrix only. Hepatic bile partitioning and gallbladder emptying were determined 14 days later using 99mTc-Mebrofenin cholescintigraphy. RESULTS: Significantly less hepatic bile partitioned into the gallbladder in progesterone-treated than in control animals. The gallbladder ejection fraction was significantly reduced from 73+/-6% in controls to 59+/-3% in the progesterone-treated animals. The rate of gallbladder emptying was significantly reduced from 3.6+/-0.3%/minute to 2.9+/-0.1%/minute. CONCLUSIONS: Progesterone administered as subcutaneous implants alters partitioning of hepatic bile between gallbladder and small intestine and, therefore, gallbladder filling. Progesterone also significantly impairs gallbladder emptying in response to cholecystokinin. The effects of progesterone on the sphincter of Oddi and the gallbladder may contribute to the greater prevalence of gallstones and biliary motility disorders among women. (+info
Protective effect of bactericidal/permeability-increasing protein (rBPI21) in baboon sepsis is related to its antibacterial, not antiendotoxin, properties.
OBJECTIVE AND SUMMARY BACKGROUND DATA: The recombinant fragment of bactericidal/permeability-increasing protein, rBPI21, has potent bactericidal activity against gram-negative bacteria as well as antiendotoxin (lipopolysaccharide [LPS]) action. On the basis of these activities, the authors sought to discover whether rBPI21 would be protective in baboons with live Escherichia coli-induced sepsis and whether the potential protective effects of rBPI21 (together with antibiotics) would be more closely related to its antibacterial or LPS-neutralizing effects. METHODS: In a prospective, randomized, placebo-controlled subchronic laboratory study, the efficacy of rBPI21 or placebo was studied over 72 hours in chronically instrumented male baboons infused with live E. coli under antibiotic therapy. RESULTS: Intravenous rBPI21 attenuated sepsis-related organ failure and increased survival significantly. Bacteremia was significantly reduced in the rBPI21 group at 2 hours after the start of the E. coli infusion, whereas circulating LPS was less affected. The in vivo formation of tumor necrosis factor was significantly suppressed by the rBPI21 treatment regimen. Microcirculation and organ function were improved. CONCLUSIONS: In baboon live E. coli sepsis, the salutary effect of rBPI21 results from a more prevalent antibacterial than antiendotoxin activity. (+info
Health at work in the general practice.
BACKGROUND: Poor mental health and high stress levels have been reported in staff working in general practice. Little is known about how practices are tackling these and other issues of health at work in the absence of an established occupational healthcare service. AIM: To establish the extent of knowledge and good practice of health at work policies for staff working in general practice. METHOD: Practice managers in 450 randomly selected general practices in England were interviewed by telephone, and the general practitioner (GP) with lead responsibility for workplace health in the same practice was surveyed by postal questionnaire. We surveyed the existence and implementation of practice policies, causes and effects of stress on practice staff, and agreement between practice managers and GPs on these issues. RESULTS: Seventy-one per cent of GPs and 76% of practice managers responded, with at least one reply from 408 (91%) practices and responses from both the practice manager and GPs from 252 (56%) practices. Seventy-nine per cent of practices had a policy on monitoring risks and hazards. The proportion of practices with other workplace health policies ranged from 21% (policy to minimize stress) to 91% (policy on staff smoking). There was a tendency for practices to have policies but not to implement them. The three causes of stress for practice staff most commonly cites by both GP and practice manager responders were 'patient demands', 'too much work', and 'patient abuse/aggression'. Sixty-five per cent of GPs felt that stress had caused mistakes in their practices. Although there was general agreement between the two groups, there was a considerable lack of agreement between responders working in the same practices. CONCLUSIONS: The study revealed substantial neglect of workplace health issues with many practices falling foul of health and safety legislation. This report should help general practices identify issues to tackle to improve their workplace health, and the Health at Work in the NHS project to focus on areas where their targeted help will be most worthwhile. (+info
Effect of meat (beef, chicken, and bacon) on rat colon carcinogenesis.
High intake of red meat or processed meat is associated with increased risk of colon cancer. In contrast, consumption of white meat (chicken) is not associated with risk and might even reduce the occurrence of colorectal cancer. We speculated that a diet containing beef or bacon would increase and a diet containing chicken would decrease colon carcinogenesis in rats. One hundred female Fischer 344 rats were given a single injection of azoxymethane (20 mg/kg i.p.), then randomized to 10 different AIN-76-based diets. Five diets were adjusted to 14% fat and 23% protein and five other diets to 28% fat and 40% protein. Fat and protein were supplied by 1) lard and casein, 2) olive oil and casein, 3) beef, 4) chicken with skin, and 5) bacon. Meat diets contained 30% or 60% freeze-dried fried meat. The diets were given ad libitum for 100 days, then colon tumor promotion was assessed by the multiplicity of aberrant crypt foci [number of crypts per aberrant crypt focus (ACF)]. The ACF multiplicity was nearly the same in all groups, except bacon-fed rats, with no effect of fat and protein level or source (p = 0.7 between 8 groups by analysis of variance). In contrast, compared with lard- and casein-fed controls, the ACF multiplicity was reduced by 12% in rats fed a diet with 30% bacon and by 20% in rats fed a diet with 60% bacon (p < 0.001). The water intake was higher in bacon-fed rats than in controls (p < 0.0001). The concentrations of iron and bile acids in fecal water and total fatty acids in feces changed with diet, but there was no correlation between these concentrations and the ACF multiplicity. Thus the hypothesis that colonic iron, bile acids, or total fatty acids can promote colon tumors is not supported by this study. The results suggest that, in rats, beef does not promote the growth of ACF and chicken does not protect against colon carcinogenesis. A bacon-based diet appears to protect against carcinogenesis, perhaps because bacon contains 5% NaCl and increased the rats' water intake. (+info
Gonadotropin-releasing hormone improves reproductive performance of dairy cows with slow involution of the reproductive tract.
Eighty multiparous Holstein cows were assigned randomly at calving to receive either 100 microg of GnRH or saline 13 or 14 d postpartum (PP). From 4 to 28 d PP the cows' reproductive organs were palpated weekly per rectum, and cows were subclassified within each group as undergoing slow (delayed) cervical and uterine involution (abnormal) or as normal cows. Last milk obtained after removing the milking machine was assayed for progesterone 3 times a week for 120 d PP. Fourteen of the 80 cows were removed from the experiment because of culling or various veterinary treatments of pathologic conditions that could confound analysis of the GnRH treatment effects. As expected, the treatment of normal cows with GnRH had no significant effects on the first estrus or the first estrous cycle PP, on services per conception, days open, or any other reproductive trait measured. However, in the abnormal group of cows receiving saline, first rebreeding after calving was delayed (81 vs. 67 d), fewer were pregnant by 105 d PP (23 vs. 64%), and number of days open was greater (121 vs. 87 d) compared with those receiving GnRH; all were significant (P<.05). Treated abnormal cows were equivalent to the control normal cows. Thus, GnRH given 13 to 14 d PP to cows characterized as undergoing slow involution of the reproductive system, but with no other clinical problems, seems to assist in promoting rapid normal reproductive function. Subsequent losses due to culling were greatly reduced. (+info
An estimation of the requirement for folic acid in gestating sows: the metabolic utilization of folates as a criterion of measurement.
Sows at their second parity were randomly distributed in five groups of seven animals each to determine the dietary concentration of folic acid that optimizes the metabolic utilization of the vitamin during gestation. The groups differed by dietary supplement of folic acid: 0, 5, 10, 15, or 20 ppm. Sows were fed 2.5 kg of diet each day. The response of serum folates and folate binding capacity to treatments and the excretion of urinary folates after an i.v. injection of folic acid were measured. The total daily excretion of urinary folates was corrected according to the response to one i.v. injection of saline on the day preceding the i.v. injection of folic acid. The decrease of total serum folates throughout gestation was less pronounced in the groups fed 15 and 20 ppm of dietary folic acid (supplement x period interaction, P<.06) than it was in the other three treatments. The proportion of i.v. folic acid not recovered in sow urine (injected - excreted) decreased as the amount of dietary folic acid increased to reach a minimum, which differed according to the period (supplement x period interaction, P<.02); it was 15 ppm during wk 1 of gestation and 10 ppm for the other periods studied. The unrecovered folates increased over a dietary concentration of 15 ppm. These minimum values correspond to the most appropriate feed concentration that covered the whole body utilization (tissue and cell metabolism, catabolism, and storage) of folates by the sows and could be interpreted as a reliable index of the requirement. (+info
Risk factors for lower airway bacterial colonization in chronic bronchitis.
The aim of this study was to determine the prevalence and risk factors for lower airway bacterial colonization (LABC) in stable chronic bronchitis (CB). Forty-one outpatients with CB were enrolled in the study (age 63.8+/-9.1 yrs (mean+/-SD); forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) 62.8+/-11.2; current/former smokers 24/17). All patients had normal chest radiographs and an indication for performing fibreoptic bronchoscopy (pulmonary nodule, remote haemoptysis). The protected specimen brush (PSB) was used for bacterial sampling, and concentrations > or = 1,000 colony-forming units (cfu) x mL(-1) were considered positive for LABC. The repeatability of the procedure in CB was assessed in a random subsample of 18 subjects. A 72.2% quantitative agreement was found in the repeatability assessment of the PSB technique. Positive PSB cultures, obtained in 9 out of 41 (22%) patients, mainly yielded Haemophilus influenzae. The logistic regression model, used to determine which variables were related to colonization, showed that LABC was associated with current smoking (odds ratio (OR) 9.83, confidence interval (CI) 1.16-83.20) and low FVC (OR 0.73, CI 0.65-0.81). Age and FEV1 were not related to LABC. It was concluded that the prevalence of LABC in stable CB is high (22%), and current smoking is an important risk factor. (+info