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Biomedical subjects

J T DiPiro

Publications and source records attributed to J T DiPiro.

87 records · Page 5Linked to original sources
PubMed1980

Spironolactone interference with digoxin radioimmunoassay in cirrhotic patients.

The effects of spironolactone and cirrhosis on the measurement of serum digoxin levels by radioimmunoassay were studied in patients not receiving cardiac glycosides. Three groups of 10 patients each were studied. Groups 1 and 2 included patients with alcoholic cirrhosis, with Group 1 patients receiving spironolactone and Group 2 receiving no spironolactone. Group 3, the control group, included patients who were not receiving spironolactone and did not have cirrhosis. Apparent digoxin serum levels were measured by radioimmunoassay, and the mean levels of each group were compared. Group 1 had significantly higher apparent digoxin levels (1.3 +/- 0.62 ng/ml, p 0.05) than Groups 2 or 3. The apparent digoxin level of Group 2 (0.74 +/- 0.44 ng/ml) did not differ significantly from that of Group 3 (0.40 +/- 0.35 ng/ml). Significant correlations were found between apparent serum digoxin levels and daily spironolactone dose (Group 1), SGOT levels (Group 1), and prothrombin time/control ratios (Group 2 and all groups combined). Spironolactone appears to increase digoxin levels measured by radioimmunoassay. The effect of cirrhosis on digoxin radioimmunoassay has not been confirmed.

Digoxin↗
PubMedDate not supplied

Investigation of mezlocillin disposition with a porcine model.

The suitability of the pig as an animal model for mezlocillin disposition was assessed. Serum, urine, and bile were collected after the administration of 50, 100 and 200 mg kg-1 mezlocillin to pigs and drug pharmacokinetics were characterized. Mezlocillin concentrations in biological fluids were determined by HPLC and free mezlocillin was determined by ultrafiltration. The pharmacokinetics of mezlocillin appeared to be independent of dose over the dosage range studied. Total clearance, renal clearance, and biliary clearance were 0.18 (0.05) 1 h-1 kg-1, 0.13 (0.03) 1 h-1 kg-1, and 0.07 (0.02) 1 h-1 kg-1, respectively. The steady-state volume of distribution was 0.29 (0.08) 1 kg-1. The pharmacokinetic parameters determined in the porcine model are similar to those reported for health human volunteers. Therefore, this model appears suitable for the study of mezlocillin disposition, and may be applied to the study of other agents that are appreciably biliary excreted.

Animals↗
PubMedDate not supplied

Oral neomycin sulfate and erythromycin base before colon surgery: a comparison of serum and tissue concentrations.

It is accepted that the use of oral neomycin sulfate and erythromycin base before colon surgery results in decreased numbers of intestinal bacteria. Intraluminal levels of these agents are reported to be very high, but systemic availability is still debated. The systemic levels were studied in 8 patients undergoing colon surgery. Each patient received neomycin sulfate and erythromycin base, 1 g each, 19, 18 and 9 hours preoperatively. Twelve samples from serum, one from wound muscle and one from the intestinal wall were obtained from each patient in the 26 hours after the initial dose. Considerable variation was observed among levels. The following means were calculated: peak serum levels were 3.4 and 0.59 micrograms/ml, muscle levels were 1.68 and 0.23 micrograms/g and intestinal wall levels were 6.4 and 12.9 micrograms/g for erythromycin and neomycin respectively. Observed times to peak levels were 19 and 12 hours after the initial dose for erythromycin and neomycin respectively. The detectable systemic concentrations that result when these agents are given orally for bowel preparation before colon surgery may contribute to the drugs' efficacy.

Adult↗
PubMedDate not supplied

Vancomycin: an update.

Vancomycin is a narrow-spectrum glycopeptide antibiotic with potent antistaphylococcal activity. It is primarily active against gram-positive organisms. Bacterial resistance rarely develops due to its numerous modes of action. The toxic potential of vancomycin is less significant than previously thought. "Red neck syndrome" seems to be the most common side effect and appears to be caused by rapid intravenous infusion. It is characterized by erythema at the base of the neck and the upper back; hypotensive episodes may also occur. Nephrotoxicity and ototoxicity are rare. Relationships between toxicities and serum concentrations have not been established. The disposition of vancomycin after intravenous administration proceeds biphasically--rapid distribution followed by elimination. The drug is excreted primarily unchanged in the urine by glomerular filtration. Vancomycin clearance is reduced and elimination half-life is prolonged in patients with renal insufficiency. Various methods have been published to aid in dosing the drug in these patients. Vancomycin is the drug of choice in the treatment of methicillin-resistant staphylococcal infections. It is also useful in the treatment of gram-positive endocarditis and has been used as alternative therapy in the treatment of prophylaxis of gram-positive infections in penicillin-allergic patients. Oral vancomycin is the preferred therapy in antibiotic-associated colitis.

Absorption↗
PubMedDate not supplied

Effects of free glycerol contained in intravenous fat emulsion on plasma triglyceride determination.

BACKGROUND: Plasma triglyceride analyses to evaluate the clearance of IV fat emulsion are necessary in patients receiving parenteral nutrition. Enzymatic kits for triglyceride analysis measure the glycerol that is hydrolyzed from triglyceride. This study investigates the effect of fat emulsion free glycerol on plasma triglyceride determination. METHODS: Venous blood from fasting volunteers (n = 10) was drawn into tubes containing EDTA and was centrifuged to separate the plasma. An IV fat emulsion containing 2.25% glycerol was added to plasma samples to create serial dilutions ranging from 0.049% to 0.245% final lipid concentration. Total triglyceride and free glycerol concentrations were determined in each dilution and control sample. The free glycerol concentration was subtracted from the total triglyceride concentration to yield a true triglyceride value. RESULTS: Increasing concentrations of fat emulsion added to donor plasma produced increases in total triglyceride and free glycerol concentrations. The increase in free glycerol concentration produced significant concentration-related differences between total and true triglyceride concentrations. CONCLUSIONS: The total triglyceride level overestimated the true triglyceride concentration due to fat emulsion free glycerol. To assure reliable triglyceride results in patients receiving fat emulsion, blanking for free glycerol should be considered.

Adult↗
PubMedDate not supplied

Whole-bowel irrigation for mechanical colon cleansing.

The physiology, solution composition, indications, efficacy, and safety of whole-bowel irrigation (WBI) for mechanical bowel cleansing are reviewed. WBI with isotonic electrolyte solutions produces diarrhea when the infusion rate exceeds the capacity of the intestine to distend and absorb the solution. A number of solutions are used for WBI, including 0.9% sodium chloride, balanced electrolyte solutions, lactated Ringer's, mannitol, and electrolyte solutions containing polyethylene glycol 3350 (PEG). WBI solution administration rates vary from 15-90 mL/min, by oral ingestion or nasogastric tube, with total volumes ranging from 1 to 20 L. The onset of diarrhea occurs as soon as 20 minutes with clearing of the effluent as early as 90 minutes. Faster administration rates appear to shorten overall cleansing time. Two PEG-electrolyte lavage solutions (ELSs) have recently gained FDA approval. The recommended dosage rate is 1.2-1.8 L/hr orally or by nasogastric tube until rectal effluent is clear. In most patients, this requires a maximum of 4-6 L. Initial data indicate that PEG-ELSs are safe for elderly patients and for patients who have an increased risk of fluid overload, but these solutions have not been evaluated in children, pregnant women, or patients with inflammatory bowel disease. WBI is an effective alternative to other regimens for removing fecal material and reducing bowel lumen bacterial counts before colonoscopy and colorectal surgery. Retention of bacterial counts before colonoscopy and colorectal surgery. Retention of excess WBI solution may interfere with the quality of barium enema radiographs; this can be minimized by completing the irrigation the evening before the examination. Gastrointestinal side effects occur in about one third of the patients following WBI, but do not generally require discontinuing the irrigation. Solutions containing PEG with sodium sulfate as the primary electrolyte result in the least net water and electrolyte movement and are preferred over other solutions.

Aged↗
PubMedDate not supplied

Intraoperative serum concentrations of cefazolin and cefoxitin administered preoperatively at different times.

The effect of administration time on the serum concentrations of cefazolin and cefoxitin achieved during surgery was studied. Patients about to undergo elective surgery were randomly selected to receive one of four antibiotic prophylaxis regimens. Two of the regimens consisted of cefazolin 20 mg/kg i.v. (as the sodium salt) administered either "on call" to the operating room or with anesthesia in the operating room. The other two regimens were identical except that cefoxitin 30 mg/kg i.v. (as the sodium salt) was substituted for cefazolin. Intraoperative blood samples for analysis of serum concentrations were obtained at the time of surgical incision, one hour after incision, and at wound closure. Forty patients completed the study (10 patients received each treatment). Mean projected cefazolin concentrations at the time of incision and at wound closure for both two-hour and three-hour operations were significantly higher after administration with anesthesia than after "on-call" administration. For cefoxitin, differences in projected concentrations for "on-call" administration versus administration with anesthesia were significant at the time of incision and at wound closure in a two-hour operation. At times corresponding to initial incision, projected free-cefoxitin concentrations were higher than those of cefazolin; however, projected free-cefazolin concentrations were higher than free-cefoxitin concentrations at wound closure for two-hour and three-hour operations. To ensure that antibiotic is present in serum throughout a two- or three-hour surgical procedure, cefoxitin should probably be administered at the induction of anesthesia. Cefazolin administered "on call" appears to be acceptable for maintaining serum concentrations throughout surgery of this duration.

Adolescent↗
PubMedDate not supplied

Evaluation of new cephalosporins for prophylaxis of surgical infection.

The appropriate use of recently marketed cephalosporins for antimicrobial prophylaxis during surgery is discussed. New cephalosporins (cefamandole, cefoxitin, cefotaxime, moxalactam, and cefoperazone) are often substituted in situations where older, "first-generation" cephalosporins or other antimicrobials traditionally have been used. Adoption of these newer agents for routine use in prophylaxis of surgical infection has led to concerns of substantially increased costs as well as development of bacterial resistance. To date, some of the newer cephalosporins have been investigated for prophylaxis of postoperative infection in cesarean section, vaginal hysterectomy, gastrointestinal surgery, open-heart surgery, and total-hip replacement. Assessment of new cephalosporins for surgical prophylaxis should include: (1) the nature of infection with each specific type of procedure, (2) the effect of antimicrobials on prevention of infection with specific procedures, and (3) factors related to the institutional environment. For the surgical procedures listed above, newer cephalosporins either have not been studied or studies have not demonstrated a reduction in postoperative infection rates in comparisons with "first-generation" cephalosporins. Valid prophylactic uses for the newer agents may arise if comparative studies demonstrate postoperative infection rates lower than with regimens using the older cephalosporins or with other established regimens. Currently, none of the newer cephalosporins can be recommended for routine use in the prophylaxis of surgical infection.

Cardiac Surgical Procedures↗
PubMedDate not supplied

High-performance capillary electrophoresis in the pharmaceutical sciences.

High-performance capillary electrophoresis (HPCE) is a new separation technique that is applied in the pharmaceutical sciences. Separations by HPCE occur in a narrow-bore capillary under the influence of an applied electrical field. Components of the sample matrix are separated and migrate at different rates based on physicochemical properties, including ionic charge, charge to mass ratio, lipid solubility, and spatial orientation. Detection is achieved through an on-line capillary detection window. The technique has several advantages, such as rapid analysis times, automation, and minute sample volume requirements. However, a significant disadvantage of HPCE is the high concentration limit of detection. Although HPCE will not displace traditional separation techniques, it will add another dimension to existing laboratories.

Capillary Action↗
PubMedDate not supplied

Sepsis syndrome and associated sequelae in patients at high risk for gram-negative sepsis.

We conducted a prospective surveillance study of 80 hospitals across the United States to determine the incidence of sepsis syndrome and its associated sequelae in hospitalized patients over age 18 years who were administered antibiotics for suspected or documented gram-negative infection. A sample of 1754 hospitalized patients were followed from onset of antimicrobial therapy to discharge or death. Mortality rates (MR) varied depending on the suspected source of sepsis syndrome. For patients in whom the syndrome was associated with community-acquired urinary tract infections, mortality was 20% (relative risk [RR] = 0.51, p < 0.05), for those with trauma 20.6% (RR = 0.51, p < 0.05), and patients with nosocomial respiratory tract infections 57.1% (RR = 1.66, p < 0.05). More than two complications occurred in 65.2% of patients under age 60 years (MR 31%), 40.8% of those age 60-80 (MR 42%), and 35.6% of patients older than 80 years (MR 33.3%, p > 0.05). Various patient populations had significant differences in both the incidence of the syndrome and its complications, and consequent mortality. Perhaps morbidity as well as mortality should be used as outcomes when testing the efficacy of innovative therapies for sepsis.

Adolescent↗
PubMedDate not supplied

Considerations for therapy of mixed infections: focus on intraabdominal infection.

Intraabdominal infections are a wide range of diseases that include penetrating abdominal trauma, appendicitis, peritonitis, and abscess. Most are polymicrobic, involving aerobic and anaerobic bacteria. The primary treatment is surgery, but important issues regarding administration of antimicrobials may affect patient outcome. Evaluation of an antimicrobial regimen must include consideration of outcomes--survival, organ failure, adverse drug effects, and superinfection. Single-agent regimens have demonstrated benefit in patients with acute intraabdominal contamination and established infections. Guidelines for selecting antimicrobial agents are available from the Surgical Infection Society. Regimens are effective when active against most bacteria isolated from the focus of abdominal infection. The patient's clinical response, not culture results independent of clinical findings, is the primary guide for directing changes in therapy.

Abdomen↗
PubMedDate not supplied

Single-agent versus combination antibiotic therapy in the management of intraabdominal infections.

For the treatment of intraabdominal infection, single-agent antimicrobial regimens such as beta-lactams with good antianaerobic activity are frequent alternatives to combination regimens such as aminoglycosides or aztreonam plus an antianaerobic agent such as clindamycin or metronidazole. The major issues in selecting a regimen are relative efficacy, potential for adverse drug effects, and cost. Single agents are clearly equivalent to combinations in preventing infectious complications after penetrating abdominal trauma and in treating established intraabdominal infections of mild to moderate severity or in relatively low-risk patients. A few trials demonstrated their equivalency in patients at high risk of mortality, although experience is limited. Single-agent regimens may reduce the risks of adverse drug effects compared with combination regimens, but they are not always less expensive.

Abdomen↗
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Cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis.

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram-negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL-1, tumor necrosis factor-alpha, interferon-gamma) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.

Animals↗