Prepartum antibiotic treatment of heifers: milk production, milk quality and economic benefit.

Prepartum intramammary antibiotic infusion of heifer mammary glands at 7 or 14 d before expected parturition is an effective procedure for eliminating many infections in heifers during late gestation and for reducing the prevalence of mastitis in heifers during early lactation and throughout lactation. Mastitis pathogens were isolated from 76% of samples obtained from untreated control quarters 7 d before expected calving, from 47% of samples obtained 3 d after calving, and from 29% of samples obtained 10 d postpartum. Mastitis pathogens were isolated from about 30% of control quarters through 240 d of lactation. A similar percentage of samples (70%) was positive for mastitis pathogens at C-7 before antibiotic treatment. However, only 8% of samples obtained at 3 d after calving and 4% of samples obtained at 10 d postpartum from quarters of antibiotic-treated heifers contained mastitis pathogens. Throughout the remainder of lactation, mastitis pathogens were isolated from an average of about 11% of quarters. The percentage of samples with mastitis pathogens was higher in untreated controls than in antibiotic-treated quarters at all sampling intervals during lactation. A similar response was observed in heifers that were treated with antibiotics at 14 d before expected parturition. Prepartum antibiotic-treated heifers produced significantly more milk than control heifers and had significantly lower somatic cell count scores than untreated control heifers. These observations are likely associated with or due to the lower prevalence of mastitis pathogen isolation in prepartum antibiotic-treated heifers throughout lactation. Prepartum antibiotic-treated heifers produced 531 kg more milk than heifers in the untreated control group. Multiplying this increase by a milk price of 0.407 dollars/kg yielded a 216.24 dollars per-heifer increase in gross revenue. The cost of treatment, including the cost of testing for antibiotic residues, was estimated at 15.60 dollars for a net revenue of 200.64 dollars per heifer. Prepartum antibiotic treatment to reduce the rate of mastitis in heifers during lactation was highly effective and economically beneficial.

Supplemental low flow oxygen prevents hypoxia during endoscopic cholangiopancreatography.

Administration of continuous oxygen during ERCP may prevent hypoxia. Oxygen saturation was recorded using pulse oximetry in 50 consecutive patients undergoing ERCP. Patients were randomly allocated to receive no oxygen or low flow oxygen (2 liters/min) via nasal prongs or nasopharyngeal cannula. Oxygen saturation fell below 90% in 47% of patients not receiving oxygen compared with 0% in those administered oxygen (p less than 0.001). No difference existed in oxygen saturations between those groups receiving supplemental oxygen via nasal prongs or nasopharyngeal cannula. Continuous administration of low flow oxygen is recommended during ERCP.

Metabolic fate of [3H]deoxycorticosterone and [14C]progesterone--I. Early tissue metabolites and analysis of 21-hydroxysteroids by high pressure liquid chromatography.

Rabbits injected with mixtures of [3H]deoxycorticosterone and [14C]progesterone had significant levels of both 3H and 14C in several tissues and fluids extracted 10-45 min later. The distribution of radioactivity between 21-deoxysteroid, 21-hydroxysteroid, steroid acid and steroid glucuronide fractions was determined by alumina adsorption chromatography. Steroid acids derived from both steroids accumulated in the liver, kidney and urine, but were quantitatively less significant in the bile, duodenum, uterus, spleen and lung and were detected in the blood for the first time. Different 21-hydroxysteroid profiles were detected in the tissue and fluid extracts by reverse and straight phase high pressure liquid chromatography. [3H]Deoxycorticosterone accumulated in the kidney, lung, spleen and uterus, whereas tetra and hexahydro reduced metabolites predominated in the liver, bile and duodenum. By contrast, [14C]progesterone was metabolised to more polar 21-hydroxylated metabolites which were detected in the liver, kidney and urine. These results show the influence of a steroid 21-hydroxyl function, when administered, as opposed to being formed in in vivo, on the metabolic fate and excretory pathways of 21-hydroxysteroids by the rabbit.

Effect of aging on hepatic elimination of cimetidine and subsequent interaction of aging and cimetidine on aminopyrine metabolism.

Aging and cimetidine may each impair hepatic microsomal drug metabolism. To test if and by what mechanisms advanced age may increase sensitivity to the inhibitory effects of cimetidine, the interaction of these two factors with aminopyrine metabolism in the rat was studied using a correlative approach. Initial studies using the aminopyrine breath test indicated that a 40 mg/kg dose of cimetidine, i.p., impaired the 14CO2 exhaled by up to 76% more in aged (26-month) than in young (3- to 4-month-old) rats. Using an isolated liver perfusion to dissect out hepatic components of this phenomenon, it was found that various doses of cimetidine impaired aminopyrine clearance to a greater degree (P less than 0.05) in aged than in young livers. However, cimetidine metabolism in this system ranged from 36 to 78% less in aged versus young livers (P less than 0.05). Subsequent in vitro studies indicated that microsomes isolated from aged livers also averaged a 76% lower rate of cimetidine metabolism (P less than 0.05). A fixed cimetidine concentration, however, inhibited aminopyrine demethylation to the same degree in aged versus young rats (P less than 0.05). In vivo pharmacokinetics showed an age-related decrease in both aminopyrine and cimetidine systemic clearance. In the young rat the liver contributed about 30% to total systemic clearance of cimetidine. In the aged rat, all clearance was renal. Despite a decrease in glomerular filtration rate, net tubular cimetidine secretion was well-maintained. Despite this, absence of the hepatic component resulted in decreased overall systemic clearance of the drug in aged rats. It is concluded that (1) the aged rat liver exhibits impaired cimetidine metabolism, resulting in decreased overall systemic clearance of the drug despite normal net renal tubular secretion, (2) there is no age-related enhanced sensitivity to cimetidine of the hepatic microsomal oxidizing system using aminopyrine as the probe drug, and (3) the larger inhibition of aminopyrine metabolism in aged rats following various doses of cimetidine is due to decreased overall cimetidine clearance, resulting in higher concentrations of the inhibitor in the liver of aged rats.

Effect of H2-receptor antagonists on steady-state extraction of indocyanine green and lidocaine by the perfused rat liver.

Variable effects of cimetidine on the clearance in humans of the high-clearance compounds lidocaine and indocyanine green have been reported, some investigators finding a reduction and others no change. We measured the extraction of indocyanine green, which is not metabolized and of lidocaine, which is metabolized by the perfused rat liver, in an open system with a fixed flow rate. The extraction ratios of both indocyanine green (ERICG) and lidocaine (ERL) were determined under control conditions and during continuous infusion of cimetidine and other H2-receptor antagonists (ranitidine, nizatidine, and ICI 125,211) on separate occasions. The effects of increasing concentrations of cimetidine and ranitidine were measured, and single concentrations of nizatidine and ICI 125,211 were used. Indocyanine green was measured spectrophotometrically or by high-performance liquid chromatography (HPLC). Lidocaine concentrations in perfusate were measured by gas chromatography, and H2-receptor antagonist levels in perfusate and in liver by HPLC. The perfused rat liver extracted indocyanine green (ERICG = 0.43 +/- 0.04) and lidocaine (ERL = 0.78 +/- 0.01) with steady state being reached within 5 minutes. Neither cimetidine nor ranitidine altered steady-state indocyanine green extraction. In contrast, ERL was decreased by all four H2-receptor antagonists but with differing potencies. In this system, cimetidine was the most potent agent, reducing ERL by 28.5% at a cimetidine concentration of 56 mumol/L. The other H2-receptor antagonists also decreased ERL:ICI 125,211 by 20% (49 mumol/L), ranitidine by 13% (38 mumol/L), and nizatidine by 9% (43 mumol/L). A dose-response relationship for cimetidine and ranitidine was developed, confirming the greater potency of cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cimetidine-theophylline interaction in patients with chronic obstructive airways disease.

The effect of cimetidine on the elimination of theophylline was studied in six patients with chronic obstructive airways disease, who were receiving maintenance therapy with theophylline. The administration of cimetidine resulted in a decrease of 25% in the interdose clearance of theophylline, which led to an increase in "steady-state" theophylline levels in five of the patients. Prescribers should be aware of this potential interaction and reduce theophylline dosage where appropriate.

Oral contraceptive steroids impair the elimination of theophylline.

The influence of OCS and sex differences on the disposition of theophylline has been studied in 12 healthy young men (29 +/- 4 years old), 13 healthy young women (29 +/- 12), and 10 healthy young women (24 +/- 3) receiving OCS for a period greater than 6 months. The elimination t1/2 was longer in women taking oral contraceptives (523 +/- 110 min) than in women not on oral contraceptives (386 +/- 157). Weight-normalized plasma clearance of theophylline was less in women taking oral contraceptive steroids (0.70 +/- 0.15 ml X min-1 X kg-1) than in women not on oral contraceptive steroids (0.98 +/- 0.32). Plasma binding and volume of distribution were not different between the two groups of women. Weight-normalized clearance, weight-normalized volume of distribution, plasma t1/2, and plasma binding were not different between men and women not taking OCS.

PIP: The influence of oral contraceptives (OCs) and sex differences on the disposition of theophylline has been studied in 12 healthy young men (29 +or- 4 years old), 13 healthy young women (29 +or- 12), and 10 healthy young women (24 +or- 3) receiving OCs for a period greater than 6 months. The elimination 1/2-life was longer in women taking OCs (523 +or- 110 minutes) than in women not taking OCs (386 +or- 157). Weight-normalized plasma clearance of theophylline was less in women taking OCs than in women not on OCs. Plasma binding and volume distribution were not different between the 2 groups of women. Weight-normalized clearance, weight-normalized volume of distribution, plasma 1/2-life, and plasma binding were not different between men and women not taking OCs.

Contamination and crossinfection with Clostridium difficile in an intensive care unit.

An outbreak of pseudomembranous colitis in an intensive care unit is described. This resulted in environmental contamination by Clostridium difficile. The outbreak could be traced to one patient who received several antibiotics over the preceding three months. A search was conducted for asymptomatic carriers among patient and staff but none were found. Aquisition of C. difficile from inanimate environmental sources was the most probable means of transmission of the organism. Its persistence in the hospital environment for several weeks, most likely as spores, suggests that patients who develop pseudomembranous colitis should be isolated, especially in areas of high antibiotic usage.

Liver disease induced by perhexiline maleate.

This paper reports a case of fatal perhexiline maleate liver injury. A 62-year-old man had received perhexiline maleate for 18 months before death. Hepatic failure developed after a routine surgical procedure. The clinical course and histological findings are presented.

Cimetidine impairs the elimination of theophylline and antipyrine.

In 7 healthy subjects theophylline and antipyrine elimination were determined before and during a course of oral cimetidine in a dose of 1 g/day. Plasma clearance of theophylline was reduced from 71.2 +/- 10.1 ml/min to 56.0 +/- 18.5 ml/min and the plasma clearance of antipyrine from 53.7 +/- 14.2 ml/min to 48.1 +/- 11.7 ml/min. Elimination half-life of theophylline was prolonged from 5.1 +/- 1.6 to 8.1 +/- 1.4 h. All these changes were statistically significant. Volume of distribution of theophylline (31.7 +/- 8.4 L before and 39.2 +/- 5.6 L during cimetidine administration) and plasma binding of theophylline (44.7 +/- 3.8% before and 44.3 +/- 3.1% during cimetidine administration) were not significantly different. Similarly, volume of distribution of antipyrine (45.8 +/- 14.0 vs. 47.6 +/- 17.9) was not significantly affected by cimetidine administration. We conclude that cimetidine impairs the elimination of theophylline and antipyrine in healthy subjects.

Effect of heparin administration on plasma binding of benzodiazepines.

1 The effect of intravenous administration of 100 units of heparin on plasma of diazepam, chlordiazepoxide, oxazepam and lorazepam was examined in fourteen normal subjects and five patients with cirrhosis. 2 In normal non-fasted subjects heparin caused a rapid 150--250% rise in the free fraction of diazepam, chlordiazepoxide and oxazepam but no change of lorazepam. The changes in free fraction were slightly smaller, but still significant, when the subjects were fasted. 3 These change in free fraction occurred within 90 s of administration of heparin and binding had returned to baseline by 30 to 45 min. 4 In the cirrhotic subjects the response to heparin was variable. 5 The use of heparin during drug disposition studies may affect the estimation of pharmacokinetic parameters and possibly pharmacological effects which are dependent on the circulating unbound drug level.