Sustaining diabetes prevention and care interventions: A multiple case study of translational research projects.

BACKGROUND: This study identifies the barriers and enablers for sustainability of interventions in primary and secondary prevention of diabetes. In the context of translational research, sustainability is defined as the continued use of program components and activities for the continued achievement of desirable program and population outcomes. METHODS: In this study, eleven translational research projects, supported by the BRIDGES program of the International Diabetes Federation, were investigated. By theoretically-informed semi-structured interviews and analyses of project reports, qualitative data was collected on the sustainability outcomes and the barriers and enablers. RESULTS: The sustainability outcomes can be grouped in three main areas: (1) sustainability at the intervention site(s); (2) diffusion to the wider community; and (3) replication of the intervention at other site(s). Each of the outcomes has their own set of enablers and barriers, and thus requires consideration for a different sustainability strategy. CONCLUSIONS: This study is the first international study that relates the sustainability outcomes of translational research project to specific barriers and enablers, and develops an evidence-based framework which provides practical advice on how to ensure the sustainability of health interventions.

Fatty acid esters of monochloropropanediol (MCPD) and glycidol in refined edible oils.

Recently, fatty acid esters of monochloropropanediol (MCPD) and that of glycidol have been reported in refined edible oils. Since then a wealth of research has been published on the factors influencing the formation of these contaminants in foods. It can be noted that the predominant precursors in a given matrix will not necessarily be the same as in other matrices. Further, proven relationships in the past between precursors responsible for free MCPD or free glycidol formation will not necessarily be valid for their fatty acid-esterified counterparts. This review attempts to summarise the current status of the literature as it pertains to the reasons surrounding the manifestation of MCPD esters and glycidyl esters in oils and fats. Recent efforts to mitigate the levels of these contaminants were highlighted and put into the context of their respective reaction matrices. As more accurate occurrence data for MCPD esters and glycidyl esters in other foods are collected, more targeted mitigation experiments can be formulated with respect to the reaction matrices under investigation.

Combination of flavor enhancement and chemosensory education improves nutritional status in older cancer patients.

BACKGROUND: Abnormalities in taste and smell functioning occur with elevated frequency in both older adults and patients with cancer. With the predicted increase in both of these populations in the coming decades, it is imperative to evaluate potential interventions that are designed to help older cancer patients compensate for the additive burden of this disease and its treatment on age-related taste and smell losses. OBJECTIVE: The purpose of the current study was to determine if providing instruction and products for flavor enhancement of foods to elderly cancer patients in addition to nutritional information would improve their nutritional status, and, by extension, functional and immune status as well as quality of life. DESIGN: One hundred and seven subjects enrolled in the study. Fifty-four subjects were in the experimental group that received flavor enhancement plus nutritional information; fifty-three control subjects received only nutritional information. Subjects were evaluated 1 month, 3 months, and 8 months after beginning chemotherapy. At every session, subjects completed taste and smell assessments as well as questionnaires related to nutritional status, activities of daily living, and quality of life. Blood samples were also obtained to determine immune parameters. RESULTS: At the eight-month time point, experimental subjects had better scores on the mini nutritional assessment (MNA) and the physical function assessment of the quality of life questionnaire. Also at eight months, self-reported taste and smell perception for experimental subjects was better than that of controls as well as better than at earlier time points. Tests that assessed quantity and quality of food intake, as well as a number of immune parameters declined over time and did not differ significantly between groups. CONCLUSION: The combination of flavor enhancement, chemosensory education, and nutritional information for elderly cancer patients improved their nutritional assessment on the MNA and physical function over time. On the whole, experimental subjects perceived themselves to be better functioning at eight months than did their control counterparts.

Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.

PURPOSE: The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGFbeta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. PATIENT AND METHODS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which < or = one grade 4 (life-threatening) late toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities occurred. RESULTS: Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities. CONCLUSION: It is feasible to use plasma TGFbeta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy.

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

The maximum tolerated dose of conformal radiation therapy delivered at 1.6 Gy bid is being assessed in patients with unresectable stage IIB-IIIB non-small cell lung cancer who have been treated with induction regimens consisting of carboplatin plus paclitaxel or carboplatin plus vinorelbine. Data from the early stages of this parallel phase I study show that the two induction regimens are similar in toxicity and that both induce partial responses in 45% of patients. Both regimens can be followed by conformal radiotherapy using an accelerated hyperfractionated schedule to a dose of at least 80 Gy without experiencing unacceptable toxicity. Key morbidity observed thus far has involved the esophagus. Further cohorts of patients will receive higher doses of conformal radiotherapy (in 6.4 Gy increments) until the maximum tolerated dose is reached.

In Grignard reagent formation from cyclopropyl bromide in diethyl ether, trapping by DCPH is consistent with diffusing cyclopropyl radical intermediates.

[reaction: see text] For reactions of magnesium with cyclopropyl bromide in diethyl ether, added DCPH decreases the yield of cyclopropylmagnesium bromide by as much as 75%, while solvent-derived products disappear and cyclopropylcyclohexylphosphine and tetracyclohexyldiphosphine appear. These changes reflect trapping of diffusing intermediate cyclopropyl radicals.

Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy.

PURPOSE: To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with non-small-cell lung cancer were randomized to receive daily filgrastim (5 microg/kg/d) or a single injection of SD/01 (30, 100, or 300 microg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts. CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.

Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m(2)) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m(2)) after CPT-11 administration on day 1. RESULTS: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1-year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32. 7% ) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to < or = 40 mg/m(2) in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. CONCLUSION: CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.

Diagnosis of posttransplant granulocytic sarcoma by fine-needle aspiration cytology and flow cytometry.

We describe a patient who developed granulocytic sarcomas of the mesentery and breast approximately 4 yrs following an allogenic bone marrow transplantation for acute myeloblastic leukemia. The diagnosis was made by a combination of fine-needle aspiration cytology and flow cytometry. The differential diagnoses of localized masses in posttransplant patients and how the combination of fine-needle aspiration cytology and flow cytometry may be used are discussed.

Tumor lysis syndrome and acute renal failure after treatment of non-small-cell lung carcinoma with combination irinotecan and cisplatin.

Tumor lysis syndrome, characterized by multiple metabolic abnormalities resulting from abrupt tumor cell death and release of intracellular constituents and metabolites, is most commonly associated with the treatment of highly chemotherapy-sensitive lymphoid and leukemic neoplasms. The authors report a case of tumor lysis syndrome accompanied by acute renal failure that occurred in a patient with stage IV non-small-cell lung cancer who was treated with topoisomerase I inhibitor, irinotecan, and cisplatin. Consistent with the rapid tumor lysis, an objective, marked, early clinical response was observed. Attention to adequate hydration, electrolytes, and renal function should be given to outpatients with non-small-cell lung cancer who receive newer chemotherapeutic agents that have greater efficacy toward this group of tumors.

Growth inhibition of a human lung adenocarcinoma cell line by genetic complementation with chromosome 11.

Two regions on chromosome segment 11p15.5 have frequent allele loss in lung cancer. LOH11A is centromeric between loci D11S1758 and D11S12, and LOH11B is telomeric between HRAS and D11S1363. We studied the biological significance of this allele loss using microcell-mediated transfer of human chromosomes 11, 11p, and two radiation-reduced fragments of 11p into human lung adenocarcinoma cell lines. Chromosome 12, which has not been implicated in lung carcinogenesis, was used as a control. All four chromosome 11-containing hybrid clones showed significantly reduced tumorigenicity in nude mice and growth in liquid culture. These findings support the notion of a tumor suppressor gene located in the LOH11A region on chromosome segment 11p15.5.

Wrist arthrodesis. Technique and functional evaluation.

Wrist arthrodesis is a reliable procedure that, although it sacrifices motion for stability, provides the patient with relief from pain. This review of 26 wrist arthrodeses performed in 24 patients using the AO technique, with plate and screw fixation and iliac crest bone graft, shows a 100% union rate and high patient satisfaction. Using a questionnaire, the patients revealed that they adapted to their fused wrists but still had difficulty with some activities, such as getting the hand into tight places, heavy lifting, and positioning the hand for some specific activities. The most common complication was fracture at the ends of the plate. Removal of the plate after solid healing of the fusion is recommended strongly.

Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer.

BACKGROUND: Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF, also known as PEG-rHuMGDF), a recombinant molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and platelet production and reduces the severity of thrombocytopenia in animals receiving myelosuppressive chemotherapy. METHODS: We conducted a randomized, double-blind, placebo-controlled dose-escalation study of MGDF in 53 patients with lung cancer who were treated with carboplatin and paclitaxel. The patients were randomly assigned in blocks of 4 in a 1:3 ratio to receive either placebo or MGDF (0.03, 0.1, 0.3, 1.0, 3.0, or 5.0 microg per kilogram of body weight per day), injected subcutaneously. No other marrow-active cytokines were given. RESULTS: In the 38 patients who received MGDF after chemotherapy, the median nadir platelet count was 188,000 per cubic millimeter (range, 68,000 to 373,000), as compared with 111,000 per cubic millimeter (range, 21,000 to 307,000) in 12 patients receiving placebo (P = 0.013). The platelet count recovered to base-line levels in 14 days in the treated patients as compared with more than 21 days in those receiving placebo (P<0.001). Among all 40 patients treated with MGDF, 1 had deep venous thrombosis and pulmonary embolism, and another had superficial thrombophlebitis. CONCLUSIONS: MGDF has potent stimulatory effects on platelet production in patients with chemotherapy-induced thrombocytopenia.

Proprioception after arthroplasty: role of the posterior cruciate ligament.

To test the hypothesis that retaining the posterior cruciate ligament during total knee arthroplasty helps preserve the threshold of proprioceptive sensation, a machine was designed that permitted direct measurement of passive angular deflection from a resting point to the threshold of patient perception. Sixty patients with unilateral primary total knee arthroplasties were evaluated; 30 with posterior cruciate ligament retaining prostheses and 30 with posterior cruciate ligament substituting prostheses. All patients had a minimum postoperative followup of 1 year, a good or excellent result as defined by the Hospital for Special Surgery Knee Score, and no evidence of peripheral neuropathy. The gender and age distributions were equivalent between groups. The average threshold of perception for the posterior cruciate ligament retention group was 2.4 degrees. The average threshold of perception for the posterior cruciate ligament substitution group was also 2.4 degrees. Substitution or retention of the posterior cruciate ligament makes no clinical difference in proprioception as measured by threshold testing. This study provides new information for surgeons performing total knee arthroplasty to aid in the decision to retain or substitute the posterior cruciate ligament. Previous proprioception evaluation in patients with posterior cruciate ligament retaining versus posterior cruciate ligament substituting arthroplasties, using different testing methods, has revealed different results.

Vascular injuries associated with elbow fractures and dislocations.

The association between elbow fractures and dislocations and vascular injury was reviewed at our institution over a ten year period from 1983 to 1993. A total of fifty-six cases of acute elbow fracture or dislocation which required operative treatment were reviewed and of these two had a concomitant vascular injury. In both these cases diagnostic imaging studies confirmed the clinical diagnosis and arterial reconstruction was done. These cases are reviewed along with the arterial anatomy about the elbow which allows for significant collateral circulation. The general principles of fracture or dislocation reduction followed by vascular reassessment and arterial reconstruction if needed are reviewed.

Abscesses of the upper extremity from drug abuse by injection.

A 4-year retrospective review of 59 consecutive upper extremity abscesses associated with drug abuse by injection is reported. There were 57 patients, with the most common location being the forearm. All abscesses were treated with incision, drainage, and intravenous antibiotics. Seventeen patients required more than one debridement; nine were complicated by fasciitis, osteomyelitis, septic arthritis, or septic tenosynovitis. Thirty-one patients had human immunodeficiency virus testing, and nine results were positive. Bacteriology showed the most common organisms to be streptococcus, Staphylococcus aureus, and Eikenella corrodens. Nineteen percent of the abscesses had anaerobes cultured. Most of the organisms cultured were common oral or skin flora.

Treatment of moderate to severe slipped capital femoral epiphysis with extracapsular base-of-neck osteotomy.

Extracapsular base of femoral neck osteotomy was performed in 36 hips with moderate to severe slipped capital femoral epiphysis (SCFE). Follow-up ranged from 2 to 24 years (average 9 years). According to modified Southwick's criteria, 90% of the hips had excellent or good result. There were no cases of avascular necrosis (AVN). Prevention of permanent limb-length discrepancy > 15 mm, as occurs in unilateral cases, warrants close follow-up and contralateral epiphysiodesis when necessary. We highly recommend this osteotomy as a safe and effective way to prevent further slippage and improve hip range of motion (ROM) in severe chronic slips.

Compartment syndrome of the thigh with osteogenesis imperfecta. A case report.

Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively.

The effects of selected bulky substituents on the pulmonary toxicity of 3-furyl ketones in mice.

Preliminary studies examined the toxicity of a series of simple alkyl 3-furyl ketone congeners of perilla ketone, 1-(3-furyl)-4-methylpentan-1-one (1), in mice, but little was known about how aromatic or bulky side chains might affect toxicity. Therefore, 3-furylphenyl ketone (2) 3-furylphenethyl ketone (3) and 1-3-furyl-4, 4-dimethylpentan-1-one (4) were synthesized to examine this problem. The 48-h LD50 (i.p.) in Notre Dame Swiss mice for each analog was greater than that of the parent toxicant, perilla ketone (1, 30 +/- 5; 2, 173 +/- 4; 3, 150 +/- 11; 4, 79 +/- 5 mumol/kg). Absorption and distribution of these compounds should be similar based on their lipophilicities. Preliminary evidence suggested that the reduced toxicities of 2, 3 and 4 compared with 1 cannot be explained on the basis of 13C-NMR (electron density) characteristics. Instead, the reduced potency likely is the result of steric hindrance of bioactivation by the bulky side chain substituents and(or) alternative metabolism on the phenyl ring rather than the furan ring of 2 and 3.