bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical Examination of Dual Individualization Principles (II): The Rate of Bacterial Eradication at the Same Area under the Inhibitory Curve is More Rapid for Ciprofloxacin Than for Cefmenoxime
Authors: Goss Thomas F. , Forrest Alan , Nix David E. , Ballow Charles H. , Birmingham Mary C. , Cumbo Thomas J. , Schentag Jerome J. 
Published: January 2017

OBJECTIVE: To compare two antibiotics at equal ranges of area under the inhibitory curve (AUIC) exposure to determine if the rate of bacterial eradication differed between these antibiotics. DESIGN: Retrospective comparison of two previously collected studies of similar patients with nosocomial pneumonia. SETTING: Hospitalized patients, most intubated in critical care units with nosocomial pneumonia. PARTICIPANTS: Patients treated with either iv ciprofloxacin (n=74) or the iv third-generation cephalosporin cefmenoxime (n=43) were compared for their length of treatment required to eradicate bacterial pathogens from their respective infection sites, using serial cultures from the site of infection. All patients were also assessed for clinical outcomes. Serum samples were obtained to evaluate individual patient antibiotic pharmacokinetics, which were used to model pharmacodynamics of response. The HPLC assay used for each antibiotic had interday coefficients of variation <10 percent. Serum concentration versus time profiles were fit using the computer program ADAPT II to determine pharmacokinetic parameters for each patient. The primary drug exposure measure that related to response was the AUIC, calculated as steady-state AUC0–24/minimum inhibitory concentration. RESULTS: AUIC values in the patients ranged from 6.0 to more than 7000, yet the AUIC value was highly predictive of time to bacterial eradication (p<0.OO 1). Although more than 75 percent of patients eventually achieved eradication of pathogens from tracheal aspirate cultures, ciprofloxacin and cefmenoxime differed significantly in the time required to sterilize these cultures. At appropriate AUIC values (>250) for ciprofloxacin, the median time to eradication was two days, while cefmenoxime (also at AUIC values >250) required six days to achieve the same result. CONCLUSIONS: We conclude that the more rapid in vitro bacterial killing, which is characteristic of ciprofloxacin at optimal AUIC values, can manifest in vivo as more rapid clearance of bacteria from the respiratory tract of patients, even when both agents are controlled for initial antibacterial exposure (i.e., same AUIC).
Concurrent Use of Foscarnet and Ciprofloxacin May Increase the Propensity for Seizures
Authors: Fan-Havard Patty , Sanchorawala Vaishali , Oh Julee , Moser Eileen M. , Smith Stephen P. 
Published: January 2017

OBJECTIVE: To report a possible interaction between foscarnet and ciprofloxacin in two patients with AIDS, cytomegalovirus (CMV) retinitis, and disseminated Mycobacterium avium complex (MAC) infection and to review the available literature related to foscarnet associated seizures. DATA SOURCE: Case report information was obtained from Medical Service Daily Rounds during the patients' hospitalization and from the patients' medical records. Computerized (MEDLINE) and manual ( Index Medicus) search methods were used to obtain English-language literature published between 1980 and 1993. DATA SYNTHESIS: Foscarnet is a synthetic antiviral agent with activity against herpes viruses and HIV. The incidence of seizures with foscarnet infusion is high, ranging from 13 to 15 percent. Predisposing factors such as renal impairment, electrolyte and metabolic abnormalities, and underlying neurologic disorders have been associated with seizures during foscarnet therapy. We describe two patients with AIDS who developed generalized tonic-clonic seizures while receiving foscarnet and ciprofloxacin for the treatment of CMV retinitis and disseminated MAC infection, respectively. Neither of the patients had any of the aforementioned risk factors for foscarnet-associated seizures. CONCLUSIONS: Concurrent administration of ciprofloxacin, a known epileptogenic agent, and foscarnet may predispose patients to the development of seizures.
Indomethacin-Induced Colonic Ulceration and Bleeding
Authors: Oren Ran , Ligumsky Moshe 
Published: January 2017

OBJECTIVE: To report a case of nonsteroidal antiinflammatory drug (NSAID)-induced lower gastrointestinal (GI) bleeding. CASE SUMMARY: A patient in whom short-term ingestion of indomethacin was associated with colonic ulceration and significant gastrointestinal bleeding is described. DISCUSSION: The bleeding ulceration of the ascending colon, associated in our patient with short-term indomethacin intake, confirms previous reports of the drug's deleterious effect on the lower GI tract. The incidence of NSAID injury of the small intestinal colon may be higher than that previously reported. CONCLUSIONS: A prospective study of NSAID users could assess the magnitude of lower GI lesions, concomitant with upper GI evaluation, and help determine limitations in the use of this drug class.
Misadventures with Activated Charcoal and Recommendations for Safe Use
Authors: Mauro Laurie S. , Nawarskas James J. , Mauro Vincent F. 
Published: January 2017

OBJECTIVE: To review published reports of adverse effects associated with single- and multiple-dose activated charcoal therapy, and to formulate recommendations for safe use of activated charcoal therapy. DATA SOURCES: A manual search of Index Medicus from 1970 to December 1993 was conducted for English language articles; bibliographies of the resultant articles were also scanned. STUDY SELECTION: Cases were included if they were described in full detail, resulted in significant morbidity or mortality, and uniquely contributed to the formulation of recommendations for safe use of activated charcoal therapy. DATA SYNTHESIS: The major causes of morbidity and mortality secondary to activated charcoal therapy are aspiration of charcoal, gastrointestinal obstruction, and fluid and electrolyte abnormalities. Aspirations have occurred as a result of a number of circumstances that may be avoided. These include use in patients with unprotected airways, use of excessive charcoal dose, administration of inappropriately diluted charcoal, and administration of charcoal in the field. Gastrointestinal obstruction has occurred when multiple doses of activated charcoal have been administered without a cathartic and in cases in which a cathartic was administered if the patient had impaired peristalsis. Fluid and electrolyte abnormalities have occurred secondary to excessive cathartic administration. CONCLUSIONS: Activated charcoal therapy should be used judiciously so that related morbidity and mortality can be prevented. Adequate consideration for the patient's airway protection capability is necessary. Judicious dosing of charcoal and concomitant cathartic therapy, along with adequate monitoring of fluid and electrolyte status, abdominal physical assessment, and clinical condition are all vital to the safe use of activated charcoal therapy.
Intravitreal Ganciclovir for Cytomegalovirus Retinitis in Patients with AIDS
Authors: Montero Ma Carmen , Pastor Maite , Buenestado Catalina , Lluch Amparo , Atienza Manuela 
Published: January 2017

OBJECTIVE: To assess the evolution of cytomegalovirus (CMV) retinitis and evaluate the possible complications associated with the use of intravitreal injections to treat this disease. DESIGN: A nonrandomized, retrospective study with case series was performed. The study took place over 34 months. SETTING: The study included patients with AIDS who developed CMV retinitis, and who were treated in the hospital, as outpatients, or both. PATIENTS: Twelve patients with AIDS and CMV retinitis diagnosed between June 1990 through April 1993 were included in the study. MAIN PATIENT PARAMETERS AND OUTCOME MEASURES: For each patient, the following data were recorded: age, risk factors, other systemic findings, dates of AIDS and CMV retinitis diagnoses, stage of AIDS, extent of the retinitis, CD4 lymphocyte count at the time of diagnosis of the retinitis, visual acuity, clinical evolution of the ocular infection, therapy, complications caused by the treatment, development of nonocular CMV, and the use of zidovudine or didanosine during the study period. RESULTS: Vision improved or remained stable in nine patients and worsened in three. Two patients developed optic neuritis. The retinitis progressed to the other eye in only one of the eight patients who had unilateral involvement. The rate of relapse with maintenance therapy was 8.3% (n = 1) within the first 8 weeks. Treatment was well tolerated. There was no evidence of toxicity after a total of 226 intravitreal ganciclovir injections. All patients were able to tolerate zidovudine or didanosine concomitantly with intravitreal ganciclovir. CONCLUSIONS: Intravitreal ganciclovir appears to be an effective alternative to systemic ganciclovir in patients with severe neutropenia and in patients who choose to continue receiving systemic zidovudine or didanosine. Early treatment and long-term maintenance therapy is essential for preserving sight.
Pain Assessment of Subcutaneous Injections
Authors: Jørgensen Jan T , Rømsing Janne , Rasmussen Mette , Møller-Sonnergaard Jørn , Vang Lisbeth , Musæus Lise 
Published: January 2017

OBJECTIVE: To compare injection pain after subcutaneous administration of four different solution volumes. DESIGN: Double-blind, randomized, prospective, multiple crossover study. SETTING: Steno Diabetes Centre, Gentofte, Denmark. PARTICIPANTS: Eighteen healthy volunteers, 9 women and 9 men, aged 21-30 years. METHODS: The subjects were injected with four different volumes (0.2, 0.5, 1.0, 1.5 mL) of NaCl 0.9%. The study was performed on 2 days with a 1-week washout period between the study days. On each study day the subjects received four injections in each thigh. To evaluate the validity of our pain assessing model the subjects received eight injections of 0.5 mL on one of the study days. Pain assessment was done immediately after each injection using both a 10-cm visual analog scale (VAS) and a six-item verbal rating scale (VRS). RESULTS: A significant difference in pain score on both the VAS (p < 0.05) and the VRS (p < 0.01) was seen between the four injection volumes. The pain was significantly increased with volumes of 1.0 and 1.5 mL. No significant difference in injection pain could be detected between 0.2 and 0.5 mL and between 1.0 and 1.5 mL. No significant period or carryover effect could be detected in the study. A significant correlation between the pain score on the VAS and the pain score on the VRS was found (r = 0.79, p < 0.0001). CONCLUSIONS: The pain of a subcutaneous injection is related to injection volume in the thigh. The results show that increasing the volume from 0.5 to 1.0 mL increases the pain significantly. The findings from this study should be considered when injection preparations for subcutaneous administration are formulated. The volume should generally be less than 1.0 mL if injected into the thigh.
Use of Salivary Caffeine Tests to Assess the Inducer Effect of a Drug on Hepatic Metabolism
Authors: Soto Javier , Sacristan Jose A , Alsar Maria J 
Published: January 2017

OBJECTIVE: To validate the use of successive salivary caffeine tests in evaluating how long inducer drugs affect hepatic metabolism. The time course of the inducer effect of rifampin found in other studies using different methodologies was chosen as the time course of reference. DESIGN: Open-label, prospective, longitudinal study. SETTING: A university hospital. PARTICIPANTS: Five healthy volunteers. MAIN OUTCOME MEASURES: Rifampin 600 mg/d was administered for 21 days. Anhydrous caffeine 300 mg was concurrently administered on each study day. Salivary caffeine tests were carried out on the following days: predose (baseline), and days 1, 5, 9, 13, and 17. Salivary tests were performed for up to 13 days after the last dose of rifampin (study days 21, 25, 29, and 33). RESULTS: The mean systemic caffeine clearance was increased for up to 17 days after the intake of rifampin, reaching the maximum inducer effect between days 5 and 9, and returning to previous values progressively during several days after rifampin was discontinued. CONCLUSIONS: Our results suggest that successive salivary caffeine measurements could be a safe, reliable, noninvasive, and suitable test for exploring the time course of the inducer effect of drugs on hepatic metabolism activity.
Impact of Pharmacist-Operated General Medicine Chronic Care Refill Clinics on Practitioner Time and Quality of Care
Authors: Cassidy Irving B , Keith Matthew R , Coffey Edward L , Noyes Margaret A 
Published: January 2017

OBJECTIVE: To assess the impact of pharmacist-operated refill clinics on practitioner (physician/physician assistant) time. Secondary objectives included assessment of disease state control, drug acquisition costs, and human resource allocation. DESIGN: The study ran from October 1, 1993 through January 31, 1994. At one clinic the pharmacist performed chart review only and did not see the patient. At the second site the pharmacist also interviewed the patient. The pharmacist used no treatment algorithms. Practitioner and pharmacist time before and after implementation of the refill clinics was measured on 3 consecutive days of normal clinic operation. SETTING: TWO state correctional facilities. PATIENTS: The study population consisted of patients receiving chronic care who were observed during regular clinic hours. MAIN OUTCOME MEASURES: We evaluated pharmacist and practitioner time before and after pharmacist involvement. Hypertension was the only disease state yielding sufficient numbers for statistical analysis. We used a two-tailed paired t-test with the a priori level set at 0.05. We also evaluated the number of patients with disease state control before and after clinic implementation, drug acquisition costs, and human resource allocation. RESULTS: The refill clinic pharmacist reduced practitioner time commitment in both clinics. The greatest impact on practitioner time was found in the interview clinic. Quality of care was maintained equally between the two clinics, with a positive impact on human resource allocation. CONCLUSIONS: In the managed care environment, pharmacist-run refill clinics can decrease practitioner time commitment allowing reallocation of human resources while maintaining current quality of care.
Modified Oral Ondansetron Regimen for Cyclophosphamide-Induced Emesis in Lupus Nephritis
Authors: Yarboro Cheryl H , Wesley Robert , Amantea Michael A , Klippel John H , Pucino Frank 
Published: January 2017

OBJECTIVE: To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. DESIGN: A before-after prospective observational pilot project. SETTING: A federal research hospital. PATIENTS: Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75–1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4–16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. MAIN OUTCOME MEASURES: The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. INTERVENTIONS: To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy. RESULTS: NO emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/ dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/ dexamethasone tablets and oral administration of ondansetron using the intravenous formulation. CONCLUSIONS: This study suggests that a modified oral ondansetron/ dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis.
Stability and Compatibility of Fluorouracil with Morphine Sulfate and Hydromorphone Hydrochloride
Authors: Xu Quanyun A , Trissel Lawrence A , Martinez Juan F 
Published: January 2017

OBJECTIVE: To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with morphine sulfate 1 mg/mL and with hydromorphone hydrochloride 0.5 mg/mL in dextrose 5% injection and in NaCl 0.9% injection. DESIGN: Test solutions of the drugs in dextrose 5% and in NaCl 0.9% were prepared in triplicate and stored at −20, 4, 23, and 32°C. Samples were removed immediately and at various time points over 35 days and stored at −70 °C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. RESULTS: The morphine test solutions all rapidly developed crystalline precipitation when admixed with fluorouracil. Further, substantial loss of morphine content, usually around 60-80%, occurred in all samples within 24 hours at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the fluorouracil with hydromorphone test solutions at any of the time points. Further, there was no loss of fluorouracil over 7 days at 32 °C and 35 days at 23, 4, and −20 °C. Hydromorphone also was stable for 7 days at 32 °C and for 35 days at the other temperatures when combined with fluorouracil 1 mg/mL and at −20 and 4 °C with fluorouracil 16 mg/mL. However, with fluorouracil 16 mg/mL, hydromorphone was stable only for 3 days at 32 °C and for 7 days at 23 °C, exhibiting approximately 10% loss after those times. CONCLUSIONS: When admixed in dextrose 5% injection and NaCl 0.9% injection, fluorouracil 1 and 16 mg/mL and morphine 0.5 mg/mL were immediately physically incompatible in all samples resulting in substantial loss of morphine content as precipitated crystals. Fluorouracil 1 mg/mL plus hydromorphone 0.5 mg/mL were compatible and stable for at least 7 days at 32 °C and for at least 35 days at 23, 4, and −20 °C. Admixed with fluorouracil 16 mg/mL, hydromorphone was stable for 3 days at 32 °C, 7 days at 23 °C, and 35 days at 4 and −20 °C.
Phenytoin in Wound Healing
Authors: Anstead Gregory M , Hart Lisa M , Sunahara Janice Fong , Liter Melvin E 
Published: January 2017

OBJECTIVE: To describe a patient with a massive Grade IV pressure ulcer that responded rapidly to treatment with topical phenytoin and to review the literature supporting the use of this therapy. CASE SUMMARY: A 55-year-old morbidly obese white man (266 kg), with respiratory failure secondary to obesity-hypoventilation syndrome and heart failure, developed pressure ulcers on his lower back and sacrum within the first 2 weeks of hospitalization. Traditional methods of treatment were unsuccessful, and by day 79, the wound involved the entire lumbosacral area and buttocks, and had extensive undermining and sinus tract formation. Within 2 days of applying topical phenytoin, fresh granulation tissue was apparent. After 54 days of treatment, nearly all the sinus tracts were healed. Four months after treatment with topical phenytoin was begun, the sacral wound was nearly healed and the lumbar wound was much reduced in size. It was evident that phenytoin had facilitated the healing of the wounds, even though the patient's multiple underlying medical problems had not resolved. DISCUSSION: Phenytoin has been used in the healing of pressure sores, venous stasis and diabetic ulcers, traumatic wounds, and bums. Many of the existing clinical studies have methodologic flaws, such as inappropriate statistical analysis, inadequate control groups, and the absence of randomization and double-blinding. Nevertheless, all the studies have reported enhancement of wound healing, with insignificant adverse effects. Phenytoin may promote wound healing by a number of mechanisms, including stimulation of fibroblast proliferation, facilitation of collagen deposition, glucocorticoid antagonism, and antibacterial activity. CONCLUSIONS: Phenytoin promoted the healing of a massive, necrotizing soft tissue wound that was unresponsive to conventional treatment. Clinical success in this difficult case and the other reports in the literature suggest that phenytoin is effective in wound healing and deserves further investigation.