PubMed Health⌕ Search

Biomedical subjects

P C Smith

Publications and source records attributed to P C Smith.

At least 19 recordsLinked to original sources
PubMed1992

Nonenzymic glycation of albumin by acyl glucuronides in vitro. Comparison of reactions with reducing sugars.

Acyl glucuronides are ubiquitous metabolites formed from acidic xenobiotics and endogenous compounds, such as bilirubin. Previous studies indicated that the covalent binding of acyl glucuronides to proteins occurs via an imine intermediate in a manner analogous to the glycation of proteins via reducing sugars. When glucuronic acid was incubated in solution with albumin, it formed 10 and 4 times more fluorescent, Maillard reaction products with albumin after 25 days than did glucose or fructose, respectively. However, radiolabeled glucuronic acid exhibited less covalent binding to albumin than either glucose or fructose. Circular dichroism measurements indicate that glucuronic acid is about 0.02% open chain form with exposure of the reactive aldehyde, whereas fructose and glucose have 2 and 0.0026% present in solution as the open chain; thus, differences in reactivity of the reducing sugars were not correlated with exposure of the free aldehyde. Methyl glucuronate formed little fluorescent product with albumin, suggesting that the C-6 carboxylate of glucuronic acid may facilitate the reactions after covalent binding that lead to the formation of fluorescent products. When acyl glucuronide metabolites of two previously marketed acidic drugs, zomepirac and suprofen, were incubated with albumin at a concentration of 2.5 mM, more fluorescent product was formed than by 500 mM glucose. Reversible binding of the acyl glucuronides to albumin was 60-90%, but almost zero for the free reducing sugars, which indicates that reversible binding may explain the enhanced reactivity of the acyl glucuronides in forming fluorescent products with albumin. These results indicate that acyl glucuronides are reactive metabolites that may cause significant glycation of proteins with glucuronic acid in vivo.

Animals↗
PubMed1992

High-performance liquid chromatographic analysis of amphotericin B in plasma, blood, urine and tissues for pharmacokinetic and tissue distribution studies.

A sensitive and reproducible high-performance liquid chromatographic method was developed to assay ampherotericin B in plasma, blood, urine and various tissue samples. Amphotericin B was isolated from each sample matrix by solid-phase extraction (Bond-Elut). The eluate from Bond-Elut containing amphotericin B was injected onto a reversed-phase C18 column (Waters, mu Bondpak, 10 microns, 300 mm x 3.9 mm I.D.) with a mobile phase of 45% acetonitrile in 2.5 mM Na2EDTA at 1 ml/min. Detection of amphotericin B was by ultraviolet absorption at 382 nm. Blood and tissues were homogenized and extracted with methanol prior to Bond-Elut extraction. The extraction efficiencies of amphotericin B from plasma, blood and tissues were approximately 90, 70 and 75%, respectively. The sensitivity of the assay was less than or equal to 5 ng/ml for plasma, less than or equal to 25 ng/ml for blood, 2.5 ng/ml for urine and 50 ng/g for tissues. The linearity of the assay method was up to 2.5 micrograms/ml for plasma, 5 micrograms/ml for blood, 500 ng/ml for urine and 500 micrograms/g for tissues. The assay was reproducible with an intra-day coefficient of variation (C.V., n = 3) of less than 5% in general for plasma, blood and tissues. The inter-day C.V. of the assay was less than 5% for plasma (n = 5), less than 10% for blood (n = 4) and less than 5% for tissues (n = 3). The overall variability in the urine assay was generally less than 10%. This method has demonstrated significant improvement in the sensitivity and reproducibility in assaying amphotericin B in plasma and especially in blood, urine and tissues. We have employed this assay to compare the pharmacokinetic and tissue distribution profiles of amphotericin B in rats and dogs following administration of Fungizone and ABCD (amphotericin B-cholesteryl sulfate colloidal dispersion), a lipid-based dosage form. In addition, the assay method for plasma and urine samples can also be applied to pharmacokinetics studies of amphotericin B in man.

Amphotericin B↗
PubMed1992

Alternative approaches to abdominal wound closure in severely injured patients with massive visceral edema.

Excessive tension in an abdominal incision line may lead to fascial necrosis and wound sepsis. We utilized two alternative approaches to wound closure in 13 patients with severe abdominal trauma (2 blunt, 11 penetrating) whose midline incision could not be closed primarily without excessive tension at the initial operation because of massive visceral edema. In five patients synthetic mesh was used to bridge the fascial defect. Four patients survived the early postoperative period but had large open midline wounds that required one or more delayed procedures to close the wound or cover the visceral mass with skin graft. Two patients currently have large abdominal wall hernias. In the other eight patients the skin was reapproximated over the visceral mass utilizing towel clips at the initial operation. Six patients survived to be reexplored within 48-96 hours. Acute hemorrhage had stopped, the edema of the bowel and retroperitoneum had largely resolved, and the fascia could be closed primarily without excessive tension. All wounds went on to heal satisfactorily. When massive edema makes fascial closure at the initial operation difficult or impossible, closure of the skin over the visceral mass promotes resolution of the edema and often allows satisfactory primary closure within 48-96 hours. Synthetic mesh should be reserved for cases of abdominal wall tissue loss or dehiscence associated with wound sepsis.

Abdominal Injuries↗
PubMed1992

Laparoscopic cholecystectomy and choledochoscopy for the treatment of cholelithiasis and choledocholithiasis.

A 33-year-old woman with symptomatic cholelithiasis underwent laparoscopic cholecystectomy. Preoperative evaluation did not suggest the presence of choledocholithiasis, but intraoperative cholangiography showed a totally obstructing stone in the distal common bile duct. Laparoscopically directed, transperitoneal choledochoscopy was performed by passing a 9.4 F flexible ureteroscope through the cystic duct into the distal common bile duct. A single calculus was visualized and removed with a basket. The patient was discharged the next day, returned to full activity within 1 week, and has done well in the subsequent postoperative interval. The management of incidentally discovered common bile duct stones during performance of laparoscopic cholecystectomy is discussed.

Adult↗
PubMed1992

Stress fractures in the lower extremities of soldiers in basic training.

In a 4-year study on stress fractures of the lower extremities in basic-training soldiers at Fort Dix, New Jersey, 1,338 stress fractures were confirmed in 1,050 soldiers from a total training population of 109,296, for an incidence of 0.96%. There were 691 men with stress fractures from a male training population of 76,237 (0.91%), and 359 women with stress fractures from a female training population of 33,059 (1.09%), with significant sexual differences in the anatomic distribution of fractures as well. Common male stress-fracture sites were the metatarsals (66%), calcaneus (20%), and lower leg (13%). Common female stress-fracture sites were the calcaneus (39%), metatarsals (31%), and lower leg (27%). Female soldiers suffered more than twice the number of bilateral stress fractures than men. The week of onset of stress fractures during basic training varied directly with the sex of the soldier. Modifications in the physical training program aimed at eliminating continuous, high-impact activities during high-risk weeks resulted in a 12.73% drop in stress-fracture incidence (decreases of 7.32% in women and 16.19% in men).

Adult↗
PubMed1991

Comparative pharmacokinetics of amphotericin B after administration of a novel colloidal delivery system, ABCD, and a conventional formulation to rats.

The pharmacokinetics and tissue distribution of two amphotericin B dosage forms were compared in rats. A novel lipid-based colloidal delivery system for amphotericin B (Amphotericin B Colloidal Dispersion [ABCD]) which reduces the toxicity of amphotericin B in animals was compared with a conventional micellar formulation. Male Sprague-Dawley rats received a single intravenous injection of 1.0 mg of ABCD, 5.0 mg of ABCD, or 1.0 mg of micellar amphotericin B per kg. Plasma and tissue samples were obtained at 0.5 to 96 h after dosing and analyzed for amphotericin B by high-pressure liquid chromatography. Animals receiving ABCD demonstrated reduced peak levels in plasma, a three- to sevenfold reduction in amphotericin B delivery to the kidneys (the major target organ for toxicity), and prolonged residence time compared with those receiving the micellar formulation. In contrast, amphotericin B concentrations in the liver were two- to threefold higher with ABCD than with the micellar formulation: nearly 100% of the amphotericin B administered as ABCD was recovered from the liver 30 min after dosing. These results suggest that the colloidal particles of ABCD are taken up by the liver, which then acts as a reservoir of amphotericin B.

Amphotericin B↗
PubMed1991

Spiritual well-being, social desirability and reasons for living: is there a connection?

In order to explore the relationship between spirituality, social desirability, and reasons for living, 100 individuals completed the Reasons for Living Inventory (RFL), the Spiritual Well-being Scale (SWBS) and the Marlowe-Crowne Social Desirability Scale (MCSDS). Positive correlations were found between religious well-being and the total RFL score and Moral Objections subscale and between existential well-being and several RFL scales. Results indicate that the RFL Moral Objections subscale taps the same type of beliefs as does the SWBS religious well-being subscale. There also appears to be a strong relationship between the adaptive cognitive beliefs which people report as reasons for not considering suicide and their existential beliefs. This emphasises the need for careful assessment of individual needs and beliefs when dealing with suicidal individuals. Areas of concern to the therapist who is working with a suicidal client were not affected by high SD scores.

Adult↗
PubMed1991

Treatment outcomes of impaired physicians in Oklahoma.

Data on one hundred twenty impaired physicians were analyzed to determine treatment outcomes from three differing types of chemical dependency treatment. The data showed that long-term (three to four months) treatment geared specifically to health care professionals was the most effective treatment modality, showing higher rates of favorable treatment outcomes measured by abstinence from alcohol and other drugs.

Combined Modality Therapy↗
PubMed1990

HTLV-I/II seropositivity and death from AIDS among HIV-1 seropositive intravenous drug users.

In a prospective study of street-recruited intravenous drug users (IVDUs) in Miami, Florida, USA, 107 (46.5%) of 230 IVDUs were infected with HIV-1. Of these HIV-1 seropositive individuals, 23 were also infected with human T-lymphotropic virus type I or II (HTLV-I/II). To test the hypothesis that HTLV-I/II infection has an effect on the survival of HIV-1 seropositive IVDUs, various baseline clinical and laboratory HIV-1 related indices in HTLV-I/II positive and negative groups were compared. Life table analysis and Cox's proportional hazards model were used to estimate the potential effect of HTLV-I/II infection on the survival patterns of people infected with HIV-1. IVDUs infected with both viruses were three times more likely to die from AIDS during follow-up than were those infected with HIV-1 only. This finding suggests that HTLV-I/II seropositivity may adversely affect the clinical outcome of HIV-1 seropositive patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Irreversible binding of tolmetin glucuronic acid esters to albumin in vitro.

Tolmetin glucuronide (TG), extracted and purified from human urine, was incubated with albumin in vitro. The degradation profile and irreversible binding to protein were investigated and kinetic parameters calculated. Standard conditions were as follows: TG, 30 micrograms/ml; human serum albumin (HSA), 3%; pH 7.45; 37 degrees C. Lower pH enhanced TG stability and reduced both the extent and the rate of irreversible binding. HSA also increased TG stability, compared to protein-free buffer, but the opposite was observed with bovine serum albumin (BSA). With BSA, irreversible binding was much less, but the rate of adduct formation was the same as with HSA. Essentially fatty acid free HSA behaved similarly to HSA. Preincubation of HSA with warfarin, or diazepam, or an excess of tolmetin, did not influence irreversible binding significantly. In buffer, acyl migration led predominantly to one isomer. This isomer bound irreversibly to HSA, although more slowly and to a lesser extent than the beta 1-isomer. Incubation of TG with poly-L-lysine also resulted in irreversible binding but to a lesser extent than with HSA. Our results suggest that there is more than one binding mechanism, with the preferential pathway a function of the isomers present and the experimental conditions.

Albumins↗
PubMed1990

Patient classification in home health care: are we ready?

This longitudinal descriptive study retrospectively profiled the acutely ill patient in home health care and explored the utility of using patient record data in predicting agency resource use and patient outcome. The findings suggest that those variables traditionally relied on for reimbursement qualification and as components of patient-classification schemes may not be wholly adequate to explain resource use and patient outcome in the home health setting. Professional nursing judgment of the patient's prognosis was found to be the most sensitive variable predicting outcome. Selected diagnoses and self-care capacity of the patient were the major predictors of resource use. Suggestions are offered for further studies that may move public health nursing more quickly toward the development of consistent and accurate home health care case mix measures.

Aged↗
PubMed1990

Necrotic oophoritis in heifers vaccinated intravenously with infectious bovine rhinotracheitis virus vaccine during estrus.

Twenty-two Hereford heifers were injected IM with prostaglandin F2 alpha a, 11 days apart to synchronize estrous cycles. Twelve of 14 heifers that had signs of estrus were inoculated IV with 1 of 3 modified-live infectious bovine rhinotracheitis virus vaccines, and 2 were assigned to a nonvaccinated control group. Also, 6 of the 8 anestrous heifers were inoculated IV with 1 of the 3 vaccines on the fourth day after the last prostaglandin injection and the other 2 were assigned to the nonvaccinated group. Vaccine virus was isolated from the blood and nasal and vaginal secretions from the vaccinated heifers on postvaccination days 4, 7, and 9. On postvaccination day 9, all heifers were ovariectomized and ovarian tissues were processed for virus isolation and histologic examination. Vaccine virus was isolation and histologic examination. Vaccine virus was isolated from ovarian tissues of some heifers in each of the vaccine groups. Necrotic oophoritis characterized by multifocal areas of ovarian tissue necrosis, hemorrhage, and mononuclear lymphocytic infiltration was observed. The corpora lutea and surrounding ovarian tissues taken from vaccinated heifers in each group had varying amounts of necrotic and inflammatory change, but the changes appeared to be more severe in 1 group than in the other 2. Virus also was isolated from 2 of the controls; these heifers apparently became infected with vaccine virus that had been excreted from the vaccinated animals.

Animals↗
PubMed1990

Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial.

The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers.

Adult↗
PubMed1990

Effect of esterase inhibition on the disposition of zomepirac glucuronide and its covalent binding to plasma proteins in the guinea pig.

The disposition of zomepirac (Z) and its acyl glucuronide metabolite were studied in rabbits and guinea pigs to determine if hydrolysis of zomepirac glucuronide (ZG) by tissue esterases occurs in vivo and what effect inhibition of esterases would have on exposure to ZG and subsequent covalent binding to plasma proteins. ZG was hydrolyzed rapidly in vivo by both guinea pigs and rabbits, liberating Z. The effect of inhibition of tissue esterases was determined by administration of phenylmethylsulfonyl fluoride (PMSF) concurrently with i.v. doses of Z or ZG to anesthetized, bile duct ligated guinea pigs. Administration of PMSF decreased the apparent plasma clearance of ZG by 86% and elevated the apparent plasma clearance of Z by 300%. Exposure of the guinea pigs to ZG as measured by the area under the plasma concentration vs. time curve (AUC) was increased substantially by PMSF treatment. Covalent binding of Z to plasma proteins in the guinea pig correlated well with AUC of ZG, but not with AUC of Z. The correlation of Z covalent binding with AUC of ZG in the guinea pig is similar to that found in humans suggesting that the degree to which acyl glucuronides form covalent adducts with proteins in humans may be predictable from studies in animals.

Anesthesia↗
PubMed1990

Effectiveness of two commercial infectious bovine keratoconjunctivitis vaccines.

Two commercially available infectious bovine keratoconjunctivitis (IBK) vaccines were evaluated for their effectiveness in protecting cattle from disease caused by experimental challenge exposure and natural transmission of Moraxella bovis infections. The study was conducted as 2 experiments, using a total of 81 cattle that were culture-negative for M bovis prior to vaccination. In each experiment, young adult cattle were randomly allotted to 4 groups. Each calf in groups 1 and 2 was vaccinated according to the vaccine manufacturer's directions. Groups 3 and 4 were unvaccinated controls. Three weeks after the last vaccination, each calf in groups 1 and 3 was experimentally challenge exposed by dropping a suspension of viable cells of a virulent strain of M bovis directly onto the corneal surface of each eye. Calves in all 4 groups were then commingled in open pastures so that calves in groups 2 and 4 could be naturally exposed to the calves with experimentally induced infections. Each calf was examined for signs of ocular disease on a regular basis by 2 experienced clinicians who scored each eye for severity of disease on the basis of a prearranged scale. Neither clinician was aware of the vaccination or exposure status of the calf nor to which experimental group they belonged. Lacrimal secretions were collected regularly to determine the number of eyes in which the virulent organism became established. Moraxella bovis with bacterial cultural characteristics similar to those of the virulent strain placed in the eyes of groups 1 and 3 was cultured from greater than or equal to 83% of the eyes of calves in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Disposition and irreversible plasma protein binding of tolmetin in humans.

The pharmacokinetics and irreversible plasma protein binding of tolmetin were studied in six healthy subjects after the administration of a single, 400 mg dose of tolmetin. With HPLC analysis, tolmetin, tolmetin glucuronide, and the isomers of tolmetin glucuronide, which result from intramolecular acyl migration in vivo, were detected in the plasma up to 4 hours after administration, whereas these conjugates were present in the urine up to 24 hours. Irreversible binding of tolmetin to plasma proteins occurred in all subjects. Irreversible binding exhibited a better correlation with exposure to tolmetin glucuronide (r = 0.5618) and the isomers of tolmetin glucuronide (r = 0.8200) than with exposure to tolmetin (-0.3635). This is consistent with the hypothesis that covalent binding occurs via the acyl glucuronide.

Adult↗
PubMed1987

High-performance liquid chromatographic determination of tolmetin, tolmetin glucuronide and its isomeric conjugates in plasma and urine.

A rapid and sensitive analytical procedure is described for the simultaneous measurement of tolmetin (T), tolmetin glucuronide (1 beta-TG) and the isomers of tolmetin glucuronide in plasma and urine. A reversed-phase liquid chromatographic system is used with an ion-pairing mobile phase of methanol-tetrabutylammonium hydrogensulfate buffered to pH 4.5 and kept at a constant temperature of 50 degrees C. Detection is by UV at 313 nm. Plasma (0.5 ml) and urine (0.1 ml) are collected in pre-cooled containers and immediately adjusted to pH 3.0 to minimize TG isomerization and hydrolysis. Samples are then deproteinated with acetonitrile, the supernatant is evaporated to dryness and reconstituted in an acetate buffer (pH 4.5), and 50 microliters are injected onto the system. Using zomepirac as the internal standard, the measurable, linear concentration ranges are 0.05-50 micrograms/ml for T in plasma and 0.025-50 micrograms/ml for T in urine. Chromatographic peaks representing T,1 beta-TG and three isomers of TG were identified, all with retention times less than 10 min. The need for special handling of biological samples is discussed.

Chromatography, High Pressure Liquid↗