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Biomedical subjects

J P Rovers

Publications and source records attributed to J P Rovers.

17 recordsLinked to original sources
PubMed2003

Retained foreign body in a 14-year-old boy.

The authors describe a 14-year-old boy who presented at the emergency department after he deliberately inserted a soda can in his rectum 48 hours before presentation. The authors were able to remove the foreign body in the operating room by squeezing and twisting the upper round of the empty soda can, in this way changing the original cylinder shape into a conus-shape. Retained foreign bodies in the rectum of children are rare. The authors report our case and discuss the relevant literature.

Adolescent↗
PubMed2000

Significantly increased lesion size by using the near-infrared photosensitizer 5,10,15,20-tetrakis (m-hydroxyphenyl)bacteriochlorin in interstitial photodynamic therapy of normal rat liver tissue.

BACKGROUND AND OBJECTIVE: Penetration of tissues by activating light ultimately limits the size of the lesions achievable in interstitial photodynamic therapy. Measurements of the wavelength-dependence of tissue optical properties suggest that substantial improvements may be possible, particularly in pigmented organs such as the liver, by using drugs absorbing at near infrared wavelengths. STUDY DESIGN/MATERIALS AND METHODS: In this study, the extent of light induced necrosis with the photosensitive agents Photofrin (activated at 632 nm), meta-tetra(hydroxyphenyl)chlorin (mTHPC) (activated at 652 nm) and 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) (activated at 740 nm) are compared in normal rat liver. Interstitial irradiation of mTHPBC-sensitized liver tissue resulted in significantly larger necrotic areas than irradiation of Photofrin and mTHPC-sensitised livers. CONCLUSION: The results illustrate the advantage of near-infrared photosensitizer activation and point to a specific role for mTHPBC in the interstitial treatment of liver tumours.

Animals↗
PubMed2000

Biodistribution and bioactivity of tetra-pegylated meta-tetra(hydroxyphenyl)chlorin compared to native meta-tetra(hydroxyphenyl)chlorin in a rat liver tumor model.

It has been proposed that the construction of a photosensitizer-polymer conjugate would lead to an increased selective retention of the drug in tumor tissue resulting in an enhancement of selective tumor destruction by light in photodynamic therapy. In this study the kinetics of a tetra-pegylated derivative of meta-tetra(hydroxyphenyl)chlorin (mTHPC-PEG) were compared with those of native meta-tetra(hydroxyphenyl)chlorin (mTHPC) in a rat liver tumor model. In addition, the time course of bioactivity of both drugs was studied in normal liver tissue. Pegylation of mTHPC resulted in a two-fold increase in the plasma half-life time, a five-fold decrease in liver uptake and an increase in the tumor selectivity at early time intervals after drug administration. However, although mTHPC concentrations in liver decrease rapidly with time, mTHPC-PEG liver concentrations increased as a function of time. This led to a loss of tumor selectivity at all but the earliest time points, whereas with mTHPC tumor selectivity increased with time. For both drugs the time course of bioactivity in the liver parallels drug concentration levels with extensive necrosis after irradiation of mTHPC-PEG-sensitized liver tissue up to drug-light intervals of 120 h. It is concluded that on balance mTHPC-PEG does not appear to show any benefits over native mTHPC for the treatment of liver tumors, as normal liver tissue accumulates the compound. However, pegylation is a potentially promising strategy with an increase in tumor selectivity and reduced liver uptake if accumulation in the liver can be prevented.

Adenocarcinoma↗
PubMed2000

In vivo photodynamic characteristics of the near-infrared photosensitizer 5,10,15,20-tetrakis(M-hydroxyphenyl) bacteriochlorin.

This paper describes the photodynamic characteristics of the new near-infrared photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC or SQN400) in normal rat and mouse tissues. A rat liver model of photodynamic tissue necrosis was used to determine the in vivo action spectrum and the dose-response relationships of tissue destruction with drug and light doses. The effect of varying the light irradiance and the time interval between drug administration and light irradiation on the biological response was also measured in the rat liver model. Photobleaching of mTHPBC was measured and compared with that of its chlorine analog (mTHPC) in normal mouse skin and an implanted mouse colorectal tumor. The optimum wavelength for biological activation of mTHPBC in rat liver was 739 nm. mTHPBC was found to have a marked drug-dose threshold of around 0.6 mg kg-1 when liver tissue was irradiated 48 h after drug administration. Below this administered drug dose, irradiation, even at very high light doses, did not cause liver necrosis. At administered doses above the photodynamic threshold the effect of mTHPBC-PDT was directly proportional to the product of the drug and light doses. No difference in the extent of liver necrosis produced by mTHPBC was found on varying the light irradiance from 10 to 100 mW cm-2. The extent of liver necrosis was greatest when tissue was irradiated shortly after mTHPBC administration and necrosis was absent when irradiation was performed 72 h or later after drug administration, suggesting that the drug was rapidly cleared from the liver. In vivo photobleaching experiments in mice showed that the rate of bleaching of mTHPBC was approximately 20 times greater than that of mTHPC. It is argued that this greater rate of bleaching accounts for the higher photodynamic threshold and this could be exploited to enhance selective destruction of tissues which accumulate the photosensitizer.

Animals↗
PubMed1999

Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model.

The only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for palliation. Photodynamic therapy (PDT) could be a selective, minimally invasive treatment for patients with liver metastases. We studied PDT in an implanted colon carcinoma in the liver of Wag/Rij rats, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). mTHPC tissue kinetics were studied using ex vivo extractions and in vivo fluorescence measurements. Both methods showed that mTHPC kinetics were different for liver and tumour tissue. After initial high levels at 4 h after administration (0.1 and 0.3 mg kg(-1)) mTHPC in liver tissue decreased rapidly in time. In tumour tissue no decrease in photosensitizer levels occurred, with mTHPC remaining high up to 48 h after administration. Both concentration data and fluorescence data showed an increase in tumour to liver ratios of up to 6.3 and 5.0 respectively. Illumination with 652 nm (15 J) resulted in extensive damage to tumour tissue, with necrosis of up to 13 mm in diameter. Damage to normal liver tissue was mild and transient as serum aspartate aminotransferase and alanine aminotransferase levels normalized within a week after PDT treatment. Long-term effects of mTHPC-PDT were studied on day 28 after treatment. Regardless of drug dose and drug-light interval, PDT with mTHPC resulted in complete tumour remission in 27 out of 31 treated animals (87%), with only four animals in which tumour regrowth was observed. Non-responding tumours proved to be significantly larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an intrahepatic tumour and that mTHPC-PDT is capable of inducing complete tumour remission of liver tumours.

Animals↗
PubMed1998

Interstitial photodynamic therapy with the second-generation photosensitizer bacteriochlorin a in a rat model for liver metastases.

Bacteriochlorin a (BCA) is a second-generation photosensitizer that is effective in tumour destruction upon illumination with light of a wavelength of 760 nm. Tissue penetration by light at this wavelength is greater compared with wavelengths at which commonly used photosensitizers are illuminated, making it possible to treat larger tumours. In a model of experimental liver metastases in rats, we measured lesion sizes after interstitial illumination of tumours at different times after intravenous administration of BCA (10 mg kg(-1) bodyweight), as well as BCA concentrations in liver and tumour tissue. In both, BCA concentrations showed a rapid decline within the first 4 h, followed by a slow decrease over the next 20 h, suggesting biphasic pharmacokinetics. No selective uptake in tumour tissue was observed. A near-linear relationship was found between lesion sizes and liver and tumour BCA concentrations, suggesting that optimal results with photodynamic therapy (PDT) could be obtained by illumination within a short time interval after administration, when tissue concentrations are highest. No severe liver toxicity was observed as indicated by serum ALAT levels. However, in all tumours evaluated, islands of vital-looking cells were present leading to tumour regrowth within 35 days. In view of the obtained lesion diameters of approximately 13 mm after BCA-PDT and the rapid clearance rate of BCA, the concept of a near-infrared absorbing photosensitizer for PDT of liver tumours is a potential interesting strategy.

Adenocarcinoma↗
PubMed1997

Algorithms used in adverse drug event reports: a comparative study.

OBJECTIVE: To determine if and how the Kramer and Karch algorithms differ in assigning a probability that a published case was actually an adverse drug event (ADE), and to determine if these algorithms could be used to assess published ADEs. DESIGN: Open, single-rater comparison of Karch and Kramer algorithms in 200 published ADE reports. MAIN RESULTS: The algorithms were not significantly different regarding the proportion of cases deemed definite (p = 0.5204) or probable (p = 0.2972) ADEs. The Kramer instrument was more likely to assign a possible risk of ADE (p = 0.0001), while the Karch instrument was more likely to assign a risk of unlikely (p = 0.0001). The algorithms agreed in 41% of the cases and could be used to assess published ADEs. CONCLUSIONS: The Karch and Kramer algorithms may disagree in how they assign a probability of risk to a potential ADE. This may be due to how algorithms are applied, as well as to structural differences.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Meta-analysis of parenteral clindamycin dosing regimens.

OBJECTIVE: We used meta-analysis to compare clinical cure and success rates for parenteral clindamycin 600 mg q8h or 900 mg q8h therapy to treat adult intraabdominal or female pelvic infections. DATA SOURCES: We located English-language articles describing clindamycin use in humans using MEDLINE, International Pharmaceutical Abstracts, and Embase and from personal and drug information center files, plus all article references. STUDY SELECTION: Eligible studies used parenteral clindamycin 600 mg q8h or 900 mg q8h to treat intraabdominal or pelvic infection in at least 1 arm of a study and provided a definition of clinical outcome. Accepted were comparative trials in adults who were not critically ill or expected to die. DATA SYNTHESIS: The DerSimonian and Laird method was used to calculate weighted overall success rates for cure and success (cure plus improved) rates along with 95% confidence intervals for each dosage in intraabdominal and pelvic infections. Regimens were compared with respect to both cure and success rates using the Mann-Whitney U test. MAIN RESULTS: Twenty-three articles were eligible for inclusion. Abdominal cure rates were 75.6% and 90.5% for clindamycin 600 mg q8h and 900 mg q8h, respectively (p = 0.03): success rates were 89.8% and 92.5%, respectively (p = 0.29). Pelvic cure rates were 82.8% and 89.4%, respectively (p = 0.51): success rates were 87.2% and 89.9%, respectively (p = 0.51). CONCLUSIONS: In pelvic infections, a dosage of clindamycin 600 mg q8h appears to be clinically acceptable for all patients. Although clinical outcomes for intraabdominal infections are generally similar for both regimens, the significantly higher cure rate with a dosage of clindamycin 900 mg q8h suggests that dosage recommendations should be patient specific.

Abdomen↗
PubMed1994

Assessment of methods and outcomes: using modified inpatient ciprofloxacin criteria in community-based drug use evaluation.

OBJECTIVE: To determine if published drug use evaluation (DUE) criteria for inpatients could be modified to describe and evaluate drug therapy in outpatients. DESIGN: Retrospective review of drug profiles and diagnostic codes in outpatients included in the Iowa Medicaid Management Information System database. METHODS: Criteria specifying clinical indication, process indicators, complications, and outcomes were modified from existing inpatient DUE criteria for ciprofloxacin. The Iowa Medicaid database provided demographics, drug profiles, and diagnostic codes for outpatients prescribed ciprofloxacin between March 1 and March 15, 1993. RESULTS: 539 patients were evaluated. Mean (+/- SD) age was 62.1 +/- 23.8 years; 70.9 percent were women, 44.9 percent were nursing home patients who received lower doses (p = 0.04). Of 146 patients (27.1 percent) with infection-related International Classification of Diseases-Clinical Modification, 9th Revision (ICD-9CM) codes, 43.8 percent did not meet indication for use criteria, 15.8 percent met criteria, and 40.4 percent were equivocal/other. Process indicators in 539 patients revealed that 2.4 percent were < 18 years old and potential interactions existed for theophylline (9.3 percent), iron (9.7 percent), warfarin (4.8 percent), sucralfate (2.2 percent). Two patients (0.4 percent) received prenatal vitamins. Dosage and duration of therapy could not be linked to disease severity. Complications of therapy were not evaluable. Outcomes were assessed indirectly by using concurrent antibiotic histories. These histories showed that patients received a mean 2.7 +/- 2.4 (median 2, range 1-16) ciprofloxacin prescriptions during the study period. There was frequent concurrent use of antibiotics, and 29 percent of prescriptions were preceded or followed by additional quinolone therapy within 30 days. CONCLUSIONS: Evaluating appropriateness of therapy with this methodology is feasible if validated ICD-9CM codes are reported consistently in sufficient numbers of patients. Low levels of reporting of relevant disease codes require that large numbers of patients be screened to use this method effectively. Descriptive use data are readily obtained. Data obtained by this method indicated several apparent deficiencies in ciprofloxacin therapy.

Adolescent↗
PubMed1993

Crossover comparison of drug information online database vendors: Dialog and MEDLARS.

OBJECTIVE: To compare Dialog EMBASE with the National Library of Medicine's (NLM's) MEDLARS MEDLINE, TOXLINE, and TOXLIT to evaluate differences among the databases and vendors in a method consistent with routine drug information practice. DESIGN: Crossover comparison. METHODS: NLM MEDLARS databases MEDLINE, TOXLINE, and TOXLIT were searched directly. EMBASE was searched via Dialog Information Services. MEDLINE was searched back to 1980; TOXLINE and TOXLIT were searched back to 1981, reflecting the different database structures. EMBASE was searched back to 1980. To control bias, searches were randomized; identical strategies were used during the same session and were performed by the same trained searcher. RESULTS: Twenty-six drug information requests were compared. The MEDLARS and Dialog databases were generally similar, with no significant differences in the number of potentially relevant references, English references, clinically relevant references, available abstracts, unique citations, time online, and number of questions answered. EMBASE searches were more costly (p = 0.0005). TOXLIT was costlier than TOXLINE and MEDLINE (p = 0.0018). CONCLUSIONS: NLM MEDLARS databases were comparable to Dialog EMBASE. Although MEDLARS provided more total and English-language citations, the differences were small and did not influence the proportion of questions answered. The greatest difference between the vendors was the significantly lower cost of searching on MEDLARS. Although this difference may be partially offset by the significantly shorter search times on EMBASE, the mean 1.9 minutes saved would not recoup the mean $7.89 difference in cost. MEDLARS databases are less expensive for routine drug information requests.

Costs and Cost Analysis↗
PubMed1991

A pilot study of process and outcome assessment in antibiotic therapy.

A quality assurance survey of cefazolin therapy was conducted by pharmacists using process-related and outcome-related assessments. The purpose of this survey was to study the possibility of having pharmacists review and categorize the appropriateness and success of antibiotic therapy. During a three week period, 168 orders for cefazolin were identified and 67 prophylactic and medical therapies were selected and submitted for possible pharmacist review. Thirty-seven therapies were reviewed by staff pharmacists who scored each therapy for the acceptability of risk of adverse drug effect, the cost-effectiveness, and the overall appropriateness. An evaluation form was used, but explicit utilization criteria were not provided. The average scores (+/- SD) on a 10 centimeter visual analog scale were 9.1 (+/- 0.71), 8.7 (+/- 1.21), and 8.8. +/- 0.79) respectively. Twenty-six (70%) of these therapies were monitored to resolution, and 24 (65%) were successful in achieving the therapeutic goal. No adverse effects were noted. The average estimated times to complete the initial review and follow-up review were 10.1 (+/- 5.60) and 3.5 (+/- 2.29) minutes respectively, less than the 19.5 minutes estimated using the Canadian Hospital Pharmacy Workload Measurement System. This survey demonstrated that pharmacists can provide both process-related and outcome-related QA data.

Anti-Bacterial Agents↗
PubMed1989

A critical review of continuous infusion H2 receptor therapy.

Recent studies suggest that continuous infusions of H2-receptor antagonists may be more effective than intermittent iv therapy to control gastric pH for the prevention of stress ulcers. Infusions of cimetidine, ranitidine, and famotidine have been shown either to have a beneficial clinical effect, to control gastric acid secretion, to maintain gastric pH greater than 4, or to have pharmacokinetic properties similar to intermittent doses. In addition, some evidence suggests that continuous infusions may permit the use of lower doses, leading to cost savings. However, as yet there have been no trials that directly compare continuous and intermittent regimens and show improved outcomes with a continuous regimen. Since candidates for parenteral administration of H2-receptor antagonists are most common in the ICU, several practical issues must be addressed. Patients who receive total parenteral nutrition (TPN) may be suitable candidates for continuous infusions of H2-blockers since these agents can be given in the same container as TPN solutions. These patients also usually have a parenteral access site and infusion pump dedicated to TPN administration. In other patients, drug incompatibilities, limited iv access lines, or a lack of infusion pumps may require frequent interruptions of the infusion in order to administer additional medications, which may lead to a loss of gastric pH control. In most patients, administration of an H2-blocker regimen which maintains consistent pH control after intermittent administration may be the most practical method by which to administer these agents.

Cimetidine↗
PubMed1987

The ethics of biomedical research in humans.

Biomedical research is an area fraught with contentious issues. This article will attempt to explore some of those issues. Society's needs and wants for research as well as the responsibilities of the investigator will be discussed. In addition, the various controls which the lessons of history have imposed on human research will be examined. Finally, a brief discussion with examples of unethical research will be presented.

Conflict, Psychological↗
PubMedDate not supplied

Role of the pharmacist in childhood immunizations.

OBJECTIVE: Fewer than half of the 2-year-old children in the United States are fully immunized. This article reviews the literature on barriers to immunization in children and examines how pharmacists can promote childhood immunizations by acting as an educational resource and providing increased access to vaccines. DATA SOURCES: Published data were collected from the literature. Anecdotal data were collected from unstructured interviews with parents and health care professionals at two childhood immunization clinics in Des Moines, Iowa. DATA SYNTHESIS: Data from the literature were compared with data informally collected in the clinics. Both the literature and interviews indicated a variety of structural and personal barriers that may prevent parents from having children vaccinated. CONCLUSION: By collecting and documenting adequate vaccination histories, pharmacists can be a resource for parents and health care professionals who are unsure of a child's immunization status. Pharmacists may wish to establish immunization clinics in their pharmacies as a method to increase access to vaccines.

Adolescent↗
PubMedDate not supplied

Pharmacoepidemiology of urinary tract infections in Iowa Medicaid patients in urban long-term-care facilities.

OBJECTIVE: To describe the therapeutic management of Medicaid patients with urinary tract infections (UTIs) in urban long-term-care facilities (LTCFs) and to link individual therapies to patient outcomes. DESIGN: Retrospective review of medical records in LTCFs of patients who had documented UTIs. METHODS: Patient data were collected from 17 LTCFs in the Des Moines, IA, metropolitan area during a 1-year period starting January 1, 1995. Patients with UTIs were selected from the LTCF infection control logs. Data collected on patients included demographics, concomitant diseases, type of UTI (i.e., symptomatic, asymptomatic, catheter-related), process measures for management, UTI treatment, patient outcomes, and follow-up. Patient outcome data were defined as either cure or no cure. A UTI cure was defined as a negative urine culture while taking antibiotic therapy and/or complete resolution of signs and symptoms, as well as no further treatment given within 2 weeks after the end of treatment. RESULTS: Data were collected on 310 patients who had at least one UTI over the 1-year study period. Patients were primarily elderly (mean age 82.2 +/- 12.3 y), white (95.1%), and female (83.9%). Concomitant diseases were common and about one-fourth (23.0%) of the patients were catheterized. There were 536 UTI events (the unit of analysis) documented over the 1-year period, with about one-half (45.9%) being UTIs with symptoms consistent with uncomplicated lower UTI. Nearly two-thirds (62.3%) of the patients were cured, based on the study definition; there was no association between cure and type of antimicrobial therapy (p = 0.99). Over one-third (35.2%) of the UTIs were treated with a quinolone antibiotic. Others were treated with trimethoprim/sulfamethoxazole (24.4%), nitrofurantoin (13.9%), cephalosporin (10.4%), or ampicillin/amoxicillin (9.8%). Sixty-day follow-up showed no association between type of therapy and hospital readmission, physician follow-up visits, or subsequent UTIs. CONCLUSIONS: There were no differences in cure rates when comparing LTCF UTI patients receiving various regimens. With outcomes being the same, the clinician should closely consider costs of drug therapy in selecting a treatment preference.

Aged↗
PubMedDate not supplied

Cost control and the clinician.

As the cost of health care continues to rise significantly, health care providers, who previously had little interest in the mechanics of health care costing, have had to develop a working knowledge in this area in an attempt to help reduce costs. This article discusses some of the difficulties providers are having in familiarizing themselves with the process of cost control.

Cost Control↗