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Biomedical subjects

M A Gill

Publications and source records attributed to M A Gill.

At least 19 recordsLinked to original sources
PubMed2001

Increased frequency of pre-germinal center B cells and plasma cell precursors in the blood of children with systemic lupus erythematosus.

We have analyzed the blood B cell subpopulations of children with systemic lupus erythematosus (SLE) and healthy controls. We found that the normal recirculating mature B cell pool is composed of four subsets: conventional naive and memory B cells, a novel B cell subset with pregerminal center phenotype (IgD(+)CD38(+)centerin(+)), and a plasma cell precursor subset (CD20(-)CD19(+/low)CD27(+/++) CD38(++)). In SLE patients, naive and memory B cells (CD20(+)CD38(-)) are approximately 90% reduced, whereas oligoclonal plasma cell precursors are 3-fold expanded, independently of disease activity and modality of therapy. Pregerminal center cells in SLE are decreased to a lesser extent than conventional B cells, and therefore represent the predominant blood B cell subset in a number of patients. Thus, SLE is associated with major blood B cell subset alterations.

ADP-ribosyl Cyclase↗
PubMed2001

Population pharmacokinetics and use of Monte Carlo simulation to evaluate currently recommended dosing regimens of ciprofloxacin in adult patients with cystic fibrosis.

Pharmacodynamic data on ciprofloxacin indicate that a target area under the concentration-time curve from 0 to 24 h (AUC(0-24))/MIC ratio of >or=125 is necessary to achieve optimal bactericidal activity for the treatment of gram-negative pneumonia. The purpose of this prospective study was to (i) develop a pharmacokinetic (PK) model to be utilized for therapeutic drug monitoring (TDM) of ciprofloxacin and (ii) evaluate current ciprofloxacin dosing regimens for pneumonias in cystic fibrosis (CF) patients. Twelve adult CF patients received a single 400-mg dose of IV ciprofloxacin. Six blood samples were obtained over a 12-h interval. Serum drug concentrations were determined by high-pressure liquid chromotography and were fitted to one- and two-compartment models by using NPEM2. Ciprofloxacin MIC data for Pseudomonas aeruginosa were obtained from 1,213 CF patients enrolled in a large clinical trial. A Monte Carlo simulation was performed to estimate the fractional attainment of an AUC(0-24)/MIC ratio of >or=125. A two-compartment model best describes the serum drug concentration data. The mean fitted PK parameter values are volume of distribution in the central compartment, 0.29 liter/kg; volume of distribution at steady state, 1.1 liters/kg; total clearance, 0.34 liter/h/kg; distributional clearance, 0.89 liter/h/kg; half-life at alpha phase, 0.16 h; and half-life at beta phase, 2.9 h. The overall fractional attainment of achieving an AUC(0-24)/MIC ratio of >or=125 against P. aeruginosa isolates with ciprofloxacin (400 mg every 12 h [q12h] and 8 qh) were 10 and 30%, respectively. A clinical breakpoint MIC of <0.5 microg/ml for susceptibility is suggested, based on an examination of the fractional attainment of the AUC(0-24)/MIC target at each MIC. The recommended doses of 400 mg q8h or q12h may be inadequate to treat an acute pulmonary exacerbation when given alone. The poor and variable AUC(0-24)/MIC ratios support the use of TDM to monitor and adjust the dosage to optimize the efficacy of ciprofloxacin therapy in these patients.

Adult↗
PubMed2000

Pathophysiology and treatment of psoriasis.

The pathogenesis and treatment of psoriasis are reviewed. Psoriasis is characterized by defects in the normal cycle of epidermal development that lead to epidermal hyperproliferation, altered maturation of skin cells, and vascular changes and inflammation. The condition typically manifests as areas of thickened, flaky, silvery white and reddened skin that may hurt, itch, and bleed. Biochemical markers of psoriasis are changes in levels of keratins, keratinocyte transglutamase, migration inhibitory factor-related protein, skin-derived antileukoproteinase, involucrin, small protein rich protein 2, filaggrin, and cytokines. Types of psoriasis that may be clinically encountered include plaque psoriasis, guttate psoriasis, erythrodermic psoriasis, and pustular psoriasis. Psoriasis is believed to be genetically linked but can also be triggered by mechanical, ultraviolet, and chemical injury; various infections; prescription drug use; psychological stress; smoking; and other factors. Topical treatment of psoriasis is usually the first line of therapy. Topical treatments consist of emollients and keratolytic agents, anthralin, coal tar, corticosteroids, vitamin D3 analogues, topical retinoids, and topical psoralens plus ultraviolet A (UVA) light. In patients who do not respond adequately to topical therapy, oral or injectable therapy, such as oral retinoids, methotrexate, cyclosporine, tacrolimus, and oral psoralens plus UVA light, may be warranted. Patients receiving systemic treatments should be carefully monitored for adverse effects and drug-drug interactions. Drug therapy is the mainstay of the treatment of psoriasis. The potential adverse effects and interactions necessitate vigilant monitoring.

Administration, Topical↗
PubMed2000

Estimation of creatinine clearance in patients with metastatic ovarian cancer.

The authors evaluated the predictive performance of four methods used to estimate creatinine clearance (Cl(cr)) in patients with metastatic ovarian cancer. Methods described by Cockcroft and Gault, Jelliffe, and two equations derived from cancer patients by Robinson and Tsubaki, were evaluated. Estimated Cl(cr) values obtained by each method using actual weight (ABW), ideal weight (IBW) and lower of ABW and IBW were compared with measured values determined by a 12- or 24-hour urine collection for 14 patients enrolled in a controlled clinical trial. The mean prediction errors (ME) and mean absolute errors (MAE) were calculated to evaluate the bias and precision, respectively, of each method. The relationship between predicted and measured Cl(cr) is poor (r = 0.38 to 0.54). Cockcroft and Gault using ABW (p = 0.21), Robinson using ABW (p = 0.44), and Jelliffe (p = 0.17) were equally unbiased predictors of measured Cl(cr). All other methods significantly underestimated measured Cl(cr). All methods appeared to be equally imprecise (p<0.05). The use of standard equations for estimating Cl(cr) in patients with ovarian cancer is predictive of the measured 24-hour value. The use of oncology specific equations does not improve the accuracy or precision of these estimates.

Adult↗
PubMed1999

Citrobacter urinary tract infections in children.

BACKGROUND: Citrobacter species have been described as the etiologic agents in cases of bacteremia, meningitis, diarrhea and brain abscess, but little is known of their role as a cause of urinary tract infections in children. The purpose of this study was to define the role of Citrobacter species in pediatric urinary tract infections. METHODS: The project consisted of a retrospective chart review of microbiologic and medical records of patients younger than 18 years of age with urine cultures positive for Citrobacter species during a 3-year period. RESULTS: Thirty-four patients with 37 infections were included in the review. The average patient age was 6.9 years (range, 1 month to 18 years) and 71% were female. Fifty-six percent of the patients had urinary tract/renal anomalies or neurologic impairment and 26% represented nosocomial infections. Thirty-seven percent of patients were asymptomatic at the time of diagnosis, whereas 63% complained of at least one of the following findings: gastrointestinal symptoms; dysuria; fever; incontinence; penile/vaginal discharge; frequency; flank pain; and hematuria. Twenty-six of the isolates were Citrobacter freundii and 11 were Citrobacter koseri. Blood cultures were obtained in 9 patients and all were negative for Citrobacter isolates. CONCLUSIONS: Although it is uncommon Citrobacter can cause urinary tract infections in the pediatric population, which occur more frequently in children with underlying medical conditions. It appears that treatment similar to that of other gram-negative enteric organisms is the most prudent approach to these children until more information can be gathered.

Adolescent↗
PubMed1997

Pharmacokinetics of aztreonam in critically ill surgical patients.

The pharmacokinetics of aztreonam in critically ill surgical patients with serious gram-negative infections were studied. Blood samples were taken before and at 30 minutes, 2.5 hours, and 5 hours after a dose of aztreonam 2 g i.v. every six hours. All patients had received at least two aztreonam doses before the dosage interval being studied. Aztreonam concentrations were measured by high-performance liquid chromatography. Aztreonam's pharmacokinetics, the severity of illness, and patient outcomes were examined. A total of 28 patients with 111 serum aztreonam concentrations were included in the analysis. The patients were young (mean age, 35 years) and predominantly male. The mean APACHE II score was 19.3, and 22 patients had sepsis. Four patients died. The mean volume of distribution (V) of 0.35 L/ kg was nearly twice the previously reported steady-state value for healthy volunteers (0.18 L/kg) and was highly variable. A slightly higher than normal mean V, 0.22 L/ kg, was seen in a subset of six patients whose infection occurred earlier in their intensive care and who had lower APACHE II scores. While with some antibiotics the elevated V would imply difficulty in achieving therapeutic drug levels, 99 (89%) of the 111 concentrations were at or above the in vitro susceptibility breakpoint of 8 micrograms/mL. Despite observations of markedly increased and highly variable V in critically ill surgical patients, a standard dosage of aztreonam was usually sufficient to maintain adequate serum drug levels.

Adolescent↗
PubMed1997

Pharmacokinetics of meropenem in animals, healthy volunteers, and patients.

Meropenem is a carbapenem antibiotic that appears to be widely distributed in tissues and is eliminated by both excretion and metabolism. Approximately 70% of meropenem is excreted via the kidneys, thus dosage adjustments are required for patients with renal impairment. The pharmacokinetic parameters for meropenem are similar to those for imipenem/cilastatin, with the exception of meropenem's smaller volume of distribution. The urinary recovery of meropenem is as high as that of imipenem in combination with cilastatin, an inhibitor of renal dehydropeptidase. Therefore, unlike imipenem, meropenem can be used without dehydropeptidase inhibitors to obtain a consistently high concentration in the urine without nephrotoxic effects.

Adult↗
PubMed1997

Factors associated with antihypertensive prescribing.

OBJECTIVE: To investigate factors associated with treatment approaches to hypertension, a major risk factor for coronary heart and cerebrovascular disease and significant healthcare problem in the US. The study reports on three cross-sectional national surveys of patient-physician encounters. POPULATION: Visits were selected for adults with hypertension diagnoses from the National Ambulatory Medical Care Surveys, which represent office encounters during a given year. Years of observation included 1989, 1990, and 1991. METHODS: Multiple variable logistic regression was used to identify predisposing need, enabling, and health utilization characteristics associated with whether the visit resulted in a prescription of an antihypertensive. Additionally, the association of these visits with combination therapy is determined. RESULTS: For each of the 3 years, 69-75% of the encounters were associated with a prescription for drugs to treat hypertension. Prescribing is consistent with current literature demonstrating decreasing reliance on diuretics and beta-blockers, and increasing reliance on calcium antagonists. Combination therapy decreased as a percentage of prescriptions in 1990 and 1991. Variables associated with receiving an antihypertensive prescription included predisposing characteristics (patient age > 65 y), need characteristics (diagnosis of congestive hear failure [CHF]), and health utilization characteristics (physician specialty, previous diagnosis of hypertension). The most significant variables associated with combination therapy were predisposing characteristics (patient age > 65 y), need (CHF diagnosis, diagnosis of hypertension with end organ involvement), and health utilization characteristics (physician specialty). CONCLUSIONS: These national estimates reinforce previous regional data regarding the categories of hypertension medications used. Patient visits involving multiple diagnoses, cardiologists, or patients older than 65 years, are more likely to generate prescriptions for combination antihypertensive therapy.

Adult↗
PubMed1996

Meropenem versus tobramycin with clindamycin in the antibiotic management of patients with advanced appendicitis.

BACKGROUND: Meropenem (MP), a new carbapenem antibiotic, has excellent antimicrobial activity against the enteric flora commonly encountered in acute appendicitis. Although similar to imipenem, it may have clinical advantages. STUDY DESIGN: We compared patients with advanced appendicitis (gangrenous or perforated) treated with 1,000 mg MP every eight hours with those given the combination of tobramycin 5 mg/kg/day at eight hour intervals and clindamycin 900 mg every eight hours. Both treatments were given intravenously. Patients were randomized to either group of the double-blind study. RESULTS: Of 129 evaluable cases, 63 received MP and 66 received both tobramycin and clindamycin (T/C). The two groups were similar in age, sex, and severity of disease. The mean number of days of postoperative fever (MP = 3.1 +/- 1.7 SD compared to T/C = 4.4 +/- 2.2 SD, p < or = 0.01), days of antibiotic therapy (MP = 6.1 +/- 1.6 SD compared to T/C = 7.3 +/- 2.2 SD, p = 0.01), and therefore hospital stay (MP = 8.0 +/- 3.5 SD compared to T/C = 9.4 +/- 2.6 SD, p < 0.01) were significantly better for patients treated with MP. No difference was found between the numbers of failures in each group (MP = 5 compared to T/C = 6). CONCLUSIONS: This study demonstrates a small but significant reduction (approximately one day) in post-operative fever, duration of antibiotic treatment, and hospital stay for patients treated with MP compared to those treated with T/C.

Adult↗
PubMed1995

Stability of granisetron hydrochloride in a disposable elastomeric infusion device.

The stability and sterility of granisetron hydrochloride in 5% dextrose injection or 0.9% sodium chloride injection when stored in a disposable elastomeric infusion device were studied. Granisetron was diluted to 0.02 mg/mL (as the hydrochloride salt) in 5% dextrose chloride injection. The solution was placed in the drug reservoir of a disposable elastomeric infusion device and refrigerated at 4 degrees C for 14 days. A total of eight pumps were prepared, four containing granisetron 0.02 mg/mL in 5% dextrose injection and four containing granisetron 0.02 mg/mL in 0.9% sodium chloride injection. The solutions were assayed for granisetron concentration by stability-indicating high-performance liquid chromatography at 0 hours, 24 hours, 48 hours, 7 days, and 14 days. Each solution was inspected for clarity, color, and precipitation, and sterility testing was performed. Throughout the study, the mean concentration of granisetron remaining was more than 92% of the initial concentration both in 5% dextrose injection and in 0.9% sodium chloride injection. Individual solutions in 0.9% sodium chloride injection consistently maintained more than 90% of the initial drug concentration for only seven days. No microbial growth was detected. No precipitation, color change, or haziness was seen. Granisetron 0.02 mg/mL (as the hydrochloride salt) was stable and free of microbial growth in 0.9% sodium chloride injection for up to 7 days and stable and free of microbial growth in 5% dextrose injection for up to 14 days when stored at 4 degrees C in a disposable elastomeric infusion device.

Antiemetics↗