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Biomedical subjects

Michael D Green

Publications and source records attributed to Michael D Green.

At least 19 recordsLinked to original sources
PubMed2006

Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality.

The proliferation of counterfeit and poor-quality drugs is a major public health problem; especially in developing countries lacking adequate resources to effectively monitor their prevalence. Simple and affordable field methods provide a practical means of rapidly monitoring drug quality in circumstances where more advanced techniques are not available. Therefore, we have evaluated refractometry, colorimetry and a technique combining both processes as simple and accurate field assays to rapidly test the quality of the commonly available antimalarial drugs; artesunate, chloroquine, quinine, and sulfadoxine. Method bias, sensitivity, specificity and accuracy relative to high-performance liquid chromatographic (HPLC) analysis of drugs collected in the Lao PDR were assessed for each technique. The HPLC method for each drug was evaluated in terms of assay variability and accuracy. The accuracy of the combined method ranged from 0.96 to 1.00 for artesunate tablets, chloroquine injectables, quinine capsules, and sulfadoxine tablets while the accuracy was 0.78 for enterically coated chloroquine tablets. These techniques provide a generally accurate, yet simple and affordable means to assess drug quality in resource-poor settings.

Antimalarials↗
PubMed2006

A new tool for assessing standard of care in medical malpractice cases.

BACKGROUND: Physician experts hired and prepared by litigants provide most of the information on standard of care for medical malpractice cases. Since this information may not be objective or accurate, the authors examined the feasibility and potential value of surveying peer physicians to assess standard of care. METHODS: The survey method for assessing standard of care was evaluated for a medical malpractice case involving an abdominoplasty that had a poor cosmetic result. An abstract of the case that included the patient's characteristics and physician's decisions that were most likely to influence patient outcome was created from the transcribed testimony of the plaintiff's expert witness. This abstract and a survey that included questions about four decisions made by the defendant were sent to 28 plastic surgeons in the Midwest who were identified by searches of public documents. RESULTS: Eleven plastic surgeons experienced in abdominoplasty completed the survey. Their responses in all four areas contrasted sharply with those of the highly credentialed medical expert for the plaintiff. CONCLUSIONS: These results suggest that physician surveys are feasible and may provide very different results than those from expert witnesses about standard of care in medical malpractice cases.

Abdomen↗
PubMed2006

Multicentre surveillance of the prevalence and molecular epidemiology of macrolide resistance among pharyngeal isolates of group A streptococci in the USA.

OBJECTIVES: Rates of macrolide resistance in group A streptococci (GAS) were reported to be low in the US in the 1990s. However, we documented an unexpectedly high rate of macrolide resistance among GAS in Pittsburgh, PA, in 2001 and 2002. In an effort to define the current prevalence of macrolide-resistant GAS in the US, a multicentre surveillance project was initiated. METHODS: Between October 2002 and May 2003, 50 pharyngeal GAS isolates per month were requested from each of the nine participating sites representing a wide geographical distribution. Standard susceptibility testing was performed and the macrolide resistance phenotype was assessed using double-disc diffusion testing. Monthly and annual rates of macrolide resistance were calculated for each site. An adjusted overall rate of macrolide resistance was determined to account for differences in the numbers of GAS isolates sent from each centre. RESULTS: Overall, 171 of the 2797 collected isolates of GAS (6.1%) were resistant to erythromycin. The adjusted overall resistance rate was 5.2%. Rates of macrolide resistance varied by site (range 3.0-8.7%) and also by month (<2% to >10%). The M phenotype of macrolide resistance accounted for >60% of all macrolide-resistant isolates recovered in this study. CONCLUSIONS: These data suggest an increasing prevalence and broad geographical distribution of macrolide-resistant GAS in the US, indicating the need for ongoing local and national longitudinal surveillance to define the extent of this problem.

Anti-Bacterial Agents↗
PubMed2006

Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95.

PURPOSE: To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor-negative or stage III tumor with five or more positive axillary nodes. PATIENTS AND METHODS: Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2 plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). RESULTS: After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor-positive tumors benefited significantly from DI-EC. CONCLUSION: There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.

Adult↗
PubMed2006

Counterfeit anti-infective drugs.

The production of counterfeit or substandard anti-infective drugs is a widespread and under-recognised problem that contributes to morbidity, mortality, and drug resistance, and leads to spurious reporting of resistance and toxicity and loss of confidence in health-care systems. Counterfeit drugs particularly affect the most disadvantaged people in poor countries. Although advances in forensic chemical analysis and simple field tests will enhance drug quality monitoring, improved access to inexpensive genuine medicines, support of drug regulatory authorities, more open reporting, vigorous law enforcement, and more international cooperation with determined political leadership will be essential to counter this threat.

Anti-Infective Agents↗
PubMed2006

Anticancer agents and cardiotoxicity.

Although rare, cardiotoxicity is a significant complication of cancer treatment. The incidence and severity of cardiotoxicity are dependent on the type of drugs used, dose and schedule employed, and age of patients, as well as the presence of coexisting cardiac diseases and previous mediastinal irradiation. Anthracyclines are among one of the most active agents in oncology, but their use is often hampered by their cumulative dose-limiting cardiotoxicity. Combination therapy with new drugs in the last decade, such as taxanes and trastuzumab, in the treatment of metastatic breast cancer has yielded impressive results but also unexpected cardiotoxicity. Existing methods of minimizing cardiotoxicity include the use of protective agents such as dexrazoxane, different preparations of anthracyclines such as liposomal formulations, and alternative scheduling techniques. Assessment of left ventricular ejection fraction (LVEF) with two-dimensional (2D)-echocardiography or radionuclide ventriculography (RNVG) remains the most pragmatic means of monitoring for cardiotoxicity. The increasing number of long-term survivors of pediatric cancers, as well as the use of trastuzumab, taxanes, and anthracyclines in adjuvant treatment of breast cancer, means that more than ever, cardiotoxicity will remain an important issue for clinicians.

Adult↗
PubMed2006

Streptococcus pyogenes isolates with high-level macrolide resistance and reduced susceptibility to telithromycin associated with 23S rRNA mutations.

Seven high-level macrolide-resistant Streptococcus pyogenes isolates had reduced activity to telithromycin but were negative for methylation and efflux genes. All were of the constitutive phenotype, were clonally related (emm type 12 and MLST type 36), and had identical dual mutations (A2058G and U2166C) in domain V of 23S rRNA.

Anti-Bacterial Agents↗
PubMed2006

Characterization of counterfeit artesunate antimalarial tablets from southeast Asia.

In southeast Asia, the widespread high prevalence of counterfeits tablets of the vital antimalarial artesunate is of great public health concern. To assess the seriousness of this problem, we quantified the amount of active ingredient present in artesunate tablets by liquid chromatography coupled to mass spectrometry. This method, in conjunction with analysis of the packaging, classified tablets as genuine, substandard, or fake and validated results of the colorimetric Fast Red TR test. Eight (35%) of 23 fake artesunate samples contained the wrong active ingredients, which were identified as different erythromycins and paracetamol. Raman spectroscopy identified calcium carbonate as an excipient in 9 (39%) of 23 fake samples. Multivariate unsupervised pattern recognition results indicated two major clusters of artesunate counterfeits, those with counterfeit foil stickers and containing calcium carbonate, erythromycin, and paracetamol, and those with counterfeit holograms and containing starch but without evidence of erythromycin or paracetamol.

Antimalarials↗
PubMed2005

Pegfilgrastim: evidence in support of its use with cytotoxic chemotherapy.

The advent of granulocyte colony-stimulating factor, in particular filgrastim, in clinical use more than 10 years ago made a significant impact on the management of neutropenia and its complications. More recently, the application of pegylation technology has created a second-generation molecule, pegfilgrastim, with significantly altered pharmacokinetic properties. This has allowed for a once per chemotherapy cycle dosing in contrast to the requirement of daily subcutaneous administration for filgrastim. Several randomized trials in nonmyeloid malignancies have proven that a fixed dose of pegfilgrastim 6 mg is at least equivalent to daily filgrastim therapy. Emerging evidence also suggests that pegfilgrastim may be equally employed in the setting of chemotherapy for acute myeloid leukemia, dose-dense chemotherapy and peripheral stem cell mobilization. If confirmed in subsequent Phase III trials, it is likely that pegfilgrastim will eventually succeed filgrastim as the colony-stimulating factor of choice in clinical practice.

Acute Disease↗
PubMed2005

Undertreatment of elderly patients with non-small-cell lung cancer.

The absolute number of patients with lung cancer is rising as a result of our aging population. Until recently, clinicians have been reluctant to aggressively treat elderly patients with non-small-cell lung cancer (NSCLC) because of a lack of supportive data and concern for potential toxicity. Recently, evidence has emerged that suggests that, similar to younger patients, healthy elderly patients can benefit from therapy in all stages of NSCLC. This review will discuss the findings that indicate that chronologic age alone should not be a barrier to appropriate treatment for NSCLC, but consideration should be given to more important prognostic factors such as comorbidities and performance status.

Age Factors↗
PubMed2004

Chloroquine enhances survival in Bacillus anthracis intoxication.

The intentional release of anthrax in the United States in 2001 resulted in 11 cases of inhalational disease, with an attendant mortality rate of 45%. Current therapeutic options for anthrax are limited; antimicrobials target only replicating organisms, thus allowing bacterial toxins to cause unchecked, devastating physiological derangements in the host. Novel approaches that target the cytotoxic effects of anthrax exotoxins are needed. Chloroquine (CQ), a commonly used antimalarial agent, endows anthrax-intoxicated murine peritoneal macrophages with a 50% and 35% marginal survival advantage at 2 and 4 h, respectively, over that of untreated control cells. The cell rescue is dose dependent and, at lower concentrations, results in delayed cell death. We subsequently studied the effect of CQ in BALB/c mice challenged with anthrax lethal toxin. CQ-treated mice demonstrated reduced tissue injury, as assessed by histopathological examination of the spleen and by peripheral blood differential cell count ratios. CQ significantly enhanced survival and may augment current treatment and prophylaxis options for this otherwise lethal infection.

Animals↗
PubMed2003

Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults.

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) has been increasingly recognized as an important cause of renal transplant dysfunction. We report the role of quantitative viral load monitoring in the management of BKVAN. METHODS: We developed a real-time quantitative polymerase chain reaction (PCR) assay for BKV detection in urine and plasma. Four renal allograft recipients, including two children, with BKVAN were treated with low-dose cidofovir and followed prospectively. RESULTS: The PCR assay showed a detection limit of 10 viral copies with an intra-assay coefficient of variation of 19%. All four patients with BKVAN demonstrated intranuclear inclusions on allograft biopsy and a progressive rise in serum creatinine; three patients underwent multiple biopsies before the diagnosis of BKVAN was made. Three of the patients experienced a "viral syndrome" before the onset of renal dysfunction. One child also demonstrated an echogenic renal mass. All of the patients demonstrated strongly positive urinary PCR values (>100,000 copies/microL). BKV DNA was also detected in the plasma of three patients. All the patients were treated with intravenous low-dose cidofovir (0.25-1 mg/kg per dose, every 2-3 weeks, without probenecid). BK viruria resolved within 4 to 12 weeks (after 1-4 doses) of the cidofovir therapy, and all patients remain with stable renal function 6 to 26 months posttherapy. CONCLUSIONS: Quantitative PCR for BKV is a sensitive and reliable method for following the course of the infection in renal transplant patients. In addition, cidofovir therapy may be useful in the treatment of some of these patients, and its role needs to be investigated further.

Adult↗
PubMed2003

Filgrastim-mediated neutrophil recovery in patients with breast cancer treated with docetaxel and doxorubicin.

STUDY OBJECTIVES: To study the impact of filgrastim 5 microg/kg given once/day through absolute neutrophil count (ANC) recovery on the duration of grade 4 neutropenia (ANC < 0.5 x 10(3)/mm3) and time to ANC recovery. Additional objectives were to study the average number of filgrastim injections/cycle required to achieve ANC recovery and differences in outcome by cycle. DESIGN: Combined analysis of two double-blind, randomized, multicenter trials. PATIENTS: Two hundred twenty-two patients treated for breast cancer. MEASUREMENTS AND MAIN RESULTS: All patients but one were evaluable for efficacy end points. Mean +/- SD duration of grade 4 neutropenia was 1.7 +/- 1.3 days in cycle 1; the duration decreased in cycles 2-4 to between 1.0 and 1.2 days. Fifty percent of patients had ANC recovery to 10 x 10(3)/mm3 or greater by day 11 of the cycle, and 90% by day 13, corresponding to 10 and 12 days of filgrastim administration, respectively. Across all cycles, the mean +/- SD number of filgrastim injections/cycle was 10.51 +/- 1.70, with little variation among cycles. CONCLUSION: When filgrastim is administered as recommended, starting 24 hours after chemotherapy and continuing through an ANC of 10 x 10(3)/mm3 or greater, neutrophil recovery is rapid and predictable. Because the first cycle of chemotherapy has the highest rates of neutropenia and febrile neutropenia, it seems prudent to administer growth factor support preemptively.

Adult↗
PubMed2003

Bone pain associated with once-per-cycle pegfilgrastim is similar to daily filgrastim in patients with breast cancer.

Bone pain is a common side effect of treatment with filgrastim. Pegfilgrastim is a pegylated long-acting analogue of filgrastim that is administered once per chemotherapy cycle. The profile of prospectively defined, patient-reported bone pain judged by the investigators as related to study drug was analyzed retrospectively for each drug using data from two comparable phase III trials. These multicenter, randomized, double-blind, noninferiority trials compared once-per-cycle pegfilgrastim (6 mg, study 1 or 100 microg/kg, study 2) to daily filgrastim 5 microg/kg in patients with stage II-IV breast cancer undergoing multiple cycles of myelosuppressive chemotherapy (doxorubicin/docetaxel). Subcutaneous once-per-cycle pegfilgrastim 6-mg and 100-microg/kg doses were administered to 76 and 150 patients, respectively; subcutaneous daily filgrastim 5 microg/kg was administered to a total of 227 patients. Because bone pain in study 1 was higher (P = 0.044) in every cycle compared with study 2, all analyses were performed separately for each study. No statistically significant differences in incidence, severity, or duration were observed between patients receiving either once-per-cycle pegfilgrastim or daily filgrastim in either study. Bone pain incidence and severity were significantly greater (P < 0.001) in cycle 1 of both studies compared with later cycles. Among patients with bone pain, a trend towards earlier onset with pegfilgrastim was observed but was not associated with increased bone pain severity or duration. In patients who received a fixed 6-mg dose of pegfilgrastim, the overall bone pain incidence was similar when analyzed by body weight (< 60 kg, 60-100 kg, > 100 kg). No patients were withdrawn from either study for bone pain.

Adult↗