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Biomedical subjects

L E Shepherd

Publications and source records attributed to L E Shepherd.

16 recordsLinked to original sources
PubMed2006

Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer.

BACKGROUND: Aromatase inhibitors are widely employed in the adjuvant treatment of early stage breast cancer. The impact of aromatase inhibitors has not been established in ethnic minority women. PATIENTS AND METHODS: The purpose of this study was to evaluate the impact of letrozole on minority women in MA.17, a placebo-controlled trial of letrozole following 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Retrospective comparison of disease-free survival (DFS), side effects, and mean changes in quality of life (QOL) scores from baseline between Caucasian and minority women was performed. RESULTS: Minority (n = 352) and Caucasian (n = 4708) women were analyzed. There was no difference between these groups in DFS (91.6% versus 92.4% respectively for 4 year DFS). Letrozole, compared with placebo, significantly improved DFS for Caucasians (HR = 0.55; P < 0.0001) but not for minorities (HR = 1.39; P = 0.53). Among women who received letrozole, minorities had a significantly lower incidence of hot flashes (49% versus 58%; P = 0.02), fatigue (29% versus 39%; P = 0.005), and arthritis (2% versus 7%; P = 0.006) compared with Caucasians. Mean change in QOL scores for minority women who received letrozole demonstrated improved mental health at the 6-month assessment (P = 0.02) and less bodily pain at the 12-month assessment (P = 0.046). CONCLUSION: Letrozole improved DFS in Caucasians but a definite benefit in minority women has not yet been demonstrated. Minority women tolerated letrozole better than Caucasians in terms of toxicity. These results need confirmation in other trials of aromatase inhibitors.

Adult↗
PubMed2001

A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients.

BACKGROUND: Adjuvant chemotherapy is standard treatment for patients with resected colon cancer who are at high risk for recurrence, but the efficacy and toxicity of such treatment in patients more than 70 years of age are controversial. METHODS: We performed a pooled analysis, based on the intention to treat, of individual patient data from seven phase 3 randomized trials (involving 3351 patients) in which the effects of postoperative fluorouracil plus leucovorin (five trials) or fluorouracil plus levamisole (two trials) were compared with the effects of surgery alone in patients with stage II or III colon cancer. The patients were grouped into four age categories of equal size, and analyses were repeated with 10-year age ranges (< or =50, 51 to 60, 61 to 70, and >70 years), with the same conclusions. The toxic effects measured in all trials were nausea or vomiting, diarrhea, stomatitis, and leukopenia. Patients in the fluorouracil-plus-leucovorin and fluorouracil-plus-levamisole groups were combined for the efficacy analysis but kept separate for toxicity analyses. RESULTS: Adjuvant treatment had a significant positive effect on both overall survival and time to tumor recurrence (P<0.001 for each, with hazard ratios of death and recurrence of 0.76 [95 percent confidence interval, 0.68 to 0.85] and 0.68 [95 percent confidence interval, 0.60 to 0.76], respectively). The five-year overall survival was 71 percent for those who received adjuvant therapy, as compared with 64 percent for those untreated. No significant interaction was observed between age and the efficacy of treatment. The incidence of toxic effects was not increased among the elderly (age >70 years), except for leukopenia in one study. CONCLUSIONS: Selected elderly patients with colon cancer can receive the same benefit from fluorouracil-based adjuvant therapy as their younger counterparts, without a significant increase in toxic effects.

Adenocarcinoma↗
PubMed2001

Prospective randomized study of reamed versus unreamed femoral intramedullary nailing: an assessment of procedures.

OBJECTIVE: To determine whether the procedure of unreamed femoral nailing is simpler, faster, and safer than reamed femoral intramedullary nailing. DESIGN: Prospective randomized. SETTING/PARTICIPANTS: One hundred femoral shaft fractures without significant concomitant injuries admitted to an academic Level 1 urban trauma center. INTERVENTION: Stabilization of the femoral shaft fracture using a reamed or unreamed technique. OUTCOME MEASUREMENTS: The surgical time, estimated blood loss, fluoroscopy time, and perioperative complications were prospectively recorded. RESULTS: One hundred patients with 100 femoral shaft fractures were correctly prospectively randomized to the study. Thirty-seven patients received reamed and sixty-three patients received unreamed nails. All nails were interlocked proximally and distally. The average surgical time for the reamed nail group was 138 minutes and for unreamed nail group was 108 minutes (p = 0.012). The estimated blood loss for the reamed nail group was 278 milliliters and for the unreamed nail group 186 milliliters (p = 0.034). Reamed intramedullary nailing required an average of 4.72 minutes, whereas unreamed nailing required 4.29 minutes of fluoroscopy time. Seven perioperative complications occurred in the reamed nail group and eighteen in the unreamed nail group. Two patients in the unreamed group required an early secondary procedure. Iatrogenic comminution of the fracture site occurred during three reamed and six unreamed intramedullary nailings. Reaming of the canal was required before the successful placement of three nails in the unreamed group because of canal/nail diameter mismatch. CONCLUSIONS: Unreamed femoral intramedullary nailing involves fewer steps and is significantly faster with less intraoperative blood loss than reamed intramedullary nailing. The unreamed technique, however, was associated with a higher incidence of perioperative complications, although the difference was not statistically significant (p = 0.5).

Adolescent↗
PubMed2001

The role of ankle arthroscopy on the surgical management of ankle fractures.

Nineteen patients were prospectively randomized for operative treatment of their ankle fracture to be supplemented with or without ankle arthroscopy. All patients had an SER or PER fracture with an intact medial malleolus requiring operative treatment without evidence of intra-articular debris preoperatively. All patients underwent plate fixation of their fibula fracture and had a similar postoperative protocol. Ten patients were randomized to the control group with plate fixation only and nine patients randomized to the plate fixation plus operative arthroscopy. The average follow-up was 21 months. The arthroscopic examination of the study group revealed eight of the nine patients to have articular damage to the dome of the talus. Minimal arthroscopic treatment of these joints was required. All patients healed their fractures. No difference was noted between SF-36 scores or lower extremity scores between the two groups. At short-term follow-up, it does not appear that the arthroscopic procedure will impact upon the patient's eventual outcome in this small group of patients.

Ankle Injuries↗
PubMed2001

Bioabsorbable versus stainless steel screw fixation of the syndesmosis in pronation-lateral rotation ankle fractures: a prospective randomized trial.

Thirty-two patients who had pronation-lateral rotation (PLR) fractures occurring four centimeters or more proximal to the ankle joint or lower if the talus was displaced greater than one centimeter laterally were enrolled in this study. Seventeen patients were randomized to fibular plate fixation with a 4.5 ml polylactic acid (PLA) bioabsorbable syndesmotic screw, and fifteen patients randomized to fibular plate fixation with a 4.5 mm stainless steel syndesmotic screw. All thirty-two patients had uncomplicated healing of their fibular fracture without loss of reduction. There was neither evidence of osteolysis nor sterile effusion in the patients who were treated with the PLA screw. There were no wound complications in either group. No difference in range of motion or subjective complaints was noted in either group. Use of the PLA syndesmotic screw at short-term follow-up was well tolerated and avoided the need for subsequent screw removal.

Absorbable Implants↗
PubMed2000

Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro.

We studied the inhibitory effects of the fluoroquinolones levofloxacin, ciprofloxacin, and trovafloxacin on growth and extracellular matrix mineralization in MC3T3-E1 osteoblast-like cell cultures. Levofloxacin had the least inhibitory effect on cell growth, with a 50% inhibitory concentration of approximately 80 microg/ml at 48 and 72 hours. Ciprofloxacin had an intermediate degree of inhibition, with a 50% inhibitory concentration of 40 microg/ml at 48 and 72 hours. Trovafloxacin exerted a profound inhibitory effect on cell growth, with a 50% inhibitory concentration of 0.5 microg/ml, lower than clinically achievable serum levels. The decreased cell counts with up to 2.5 microg/ml of trovafloxacin and with up to 40 microg/ml of ciprofloxacin were not associated with decreased rates of 5-bromo-2'-deoxyuridine incorporation per cell. Alatrovafloxacin, the L-alanyl-l-alanine prodrug of trovafloxacin, exerted effects on proliferation and 5-bromo-2'-deoxyuridine incorporation similar to those of the parent compound. The quinolones evaluated also inhibited extracellular matrix mineralization by MC3T3-E1 cells. Treatment of confluent cultures with trovafloxacin, ciprofloxacin, or levofloxacin resulted in strong inhibition of calcium deposition, as determined on day 14 by alizarin red staining and biochemical analysis. The effect was apparent with 2.5-5 microg/ml of each of the three antibiotics tested and progressively increased to more than a 90% decline in the calcium/protein ratio with 20-40 microg/ml antibiotic concentration. Further in vivo studies are advocated to evaluate the relevance of the in vitro cytotoxicity reported here to bone healing in orthopaedic patients.

Animals↗
PubMed2000

Mucormycosis of the tibia: a case report and review of the literature.

Mucormycosis is an uncommon but highly aggressive fungal infection most commonly occurring in hosts who are immunologically predisposed to infection. Only seven previously documented cases of tibial osteomyelitis attributable to Mucorales infection exist in the literature. An unusual case is reported of mucormycosis osteomyelitis developing in a patient who was immunocompromised after routine tibial Steinmann pin placement for the application of traction. Surgical debridement and amphotericin B were not sufficient to control the infection, and the patient subsequently underwent above-knee amputation. To the authors' knowledge this is the first description of mucormycosis causing osteomyelitis as a result of Steinmann pin tract infection.

Bone Nails↗
PubMed2000

Sepsis and osteomyelitis about the ankle joint.

Sepsis and osteomyelitis about the ankle joint present a challenging clinical problem. Osteomyelitis usually follows open fracture of the distal tibia, often with a pilon fracture component. This article outlines the prevention of osteomyelitis in these difficult fractures. Treatment of subsequent osteomyelitis and sepsis, including the authors' experiences, is discussed. Septic ankle arthritis can occur hematogenously. In some patients, the optimal treatment for concomitant osteomyelitis and sepsis is a below knee amputation.

Adult↗
PubMed1999

Salvage of tibial pilon fractures using fusion of the ankle with a 90 degrees cannulated blade-plate: a preliminary report.

Six patients with ankle joint destruction and delayed metaphyseal union after tibial plafond fracture were surgically treated with tibiotalar arthrodesis and metaphyseal reconstruction, using a fixed-angle cannulated blade-plate. The procedure was performed through a posterior approach in five cases and a lateral approach in one case. The subtalar joint was preserved in all cases. Metaphyseal union and a stable arthrodesis were obtained in all cases without loss of fixation and with no mechanical failure of the blade-plate. Union was obtained in an average of 26 weeks. No secondary procedures were required to obtain union. All six patients were ambulatory at last follow-up. Stable internal fixation for simultaneous tibiotalar fusion and metaphyseal reconstruction can be achieved with a cannulated blade-plate while preserving the subtalar joint in complex plafond fractures.

Adult↗
PubMed1998

Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the relative efficacy of an intensive cyclophosphamide, epirubicin, and fluorouracil (CEF) adjuvant chemotherapy regimen compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive breast cancer. PATIENTS AND METHODS: Premenopausal women with node-positive breast cancer were randomly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14; methotrexate 40 mg/m2 intravenously (i.v.) days 1 and 8; and fluorouracil 600 mg/m2 i.v. days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14; epirubicin 60 mg/m2 i.v. days 1 and 8; and fluorouracil 500 mg/m2 i.v. days 1 and 8. Each cycle was administered monthly for 6 months. Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy. RESULTS: The median follow-up was 59 months. One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients. The corresponding 5-year relapse-free survival rates were 53% and 63%, respectively (P = .009). One hundred seven CMF patients died compared with 85 CEF patients. The corresponding 5-year actuarial survival rates were 70% and 77%, respectively (P = .03). The rate of hospitalization for febrile neutropenia was 1.1% in the CMF group compared with 8.5% in the CEF group. There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group. Acute leukemia occurred in five patients in the CEF group. CONCLUSION: The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer.

Adult↗
PubMed1998

Local or free muscle flaps and unreamed interlocked nails for open tibial fractures.

The treatment of open tibial fractures associated with severe soft tissue injuries remains a difficult dilemma, even to the experienced fracture surgeon. To ascertain the efficacy of nailing tibial fractures with severe soft tissue injuries, a review of all open tibial fractures treated at the authors' institution was done. Those fractures initially stabilized with nonreamed nails which required muscle flaps for coverage were selected for study. Thirty-three patients (26 men, seven women) were treated with intramedullary nailing and muscle flap coverage for the soft tissue defects. The average length of followup was 12.1 months (range, 7-42 months). The average time to union was 27 weeks (range, 14-45 weeks). There were five (15%) infections: two (6%) superficial wound infections, one (3%) flap infection, and two (6%) cases of osteomyelitis. In no patient did the infection result in limb ablation. Thirteen of 33 (42%) patients required secondary procedures to enhance union. In this study, it was found that although delayed procedures frequently were required to promote fracture union, the time to union, and infection rates were not significantly different from those reported for external fixation of fractures that require local or free muscle transfers.

Adolescent↗
PubMed1997

Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group.

PURPOSE AND METHODS: By the mid 1980s, tamoxifen alone was considered standard adjuvant therapy for postmenopausal women with node-positive, estrogen receptor (ER)- or progesterone receptor (PgR)-positive breast cancer. From 1984 through 1990, 705 eligible postmenopausal women with node-positive, ER- or PgR-positive breast cancer were randomized to a National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study that compared tamoxifen 30 mg by mouth daily for 2 years (TAM) versus TAM plus chemotherapy with all-intravenous cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 given every 21 days for eight cycles (CMF). RESULTS: There were no significant differences in overall survival, recurrence-free survival, locoregional recurrence-free survival, or distant recurrence-free survival between the two treatment arms. However, there was significantly greater severe toxicity, which included leukopenia (P < .0001), nausea and vomiting (P < .0001), and thromboembolic events (P < .0001), as well as significantly more mild or greater toxicity, which included thrombocytopenia (P = .04), anemia (P = .02), infection (P = .0004), mucositis (P = .0001), diarrhea (P = .0001), and neurologic toxicity (P = .006), in women who received TAM plus CMF. CONCLUSION: The addition of CMF to TAM adds no benefit and considerable toxicity in this group of women.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Escalated as compared with standard doses of doxorubicin in BACOP therapy for patients with non-Hodgkin's lymphoma.

BACKGROUND AND METHODS: In 1981 the Clinical Trials Group of the National Cancer Institute of Canada completed a pilot study in patients with advanced-stage non-Hodgkin's lymphoma with aggressive tumor histology. That study demonstrated the potential efficacy of escalating the dose of doxorubicin used in a regimen of bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP). In the present study, we compared standard BACOP (s-BACOP) with BACOP that included escalated doses of doxorubicin (esc-BACOP) in 238 patients 16 to 70 years old with previously untreated, advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma. During the first 28-day cycle all patients received doxorubicin in a dose of 25 mg per square meter of body-surface area on days 1 and 8. Patients randomly assigned to receive s-BACOP subsequently received five identical cycles, whereas those assigned to receive esc-BACOP received 40 mg of doxorubicin per square meter on days 1 and 8 of five subsequent cycles if granulocytopenia (< 1000 cells per cubic millimeter) had not developed during the first cycle. RESULTS: The 119 patients assigned to the esc-BACOP regimen received doxorubicin at a significantly higher mean weekly dose intensity (13.5 vs. 10.4 mg per square meter per week, P < 0.001) and mean total dose (296 vs. 231 mg per square meter, P < 0.001). Because of granulocytopenia during the first cycle of therapy, only 56 of these patients (47 percent) received the escalated doses of doxorubicin. During a median follow-up of 65 months, there were no differences between the s-BACOP and esc-BACOP groups in response rate, overall survival, or survival without disease progression. When the patients who actually received the escalated doses of doxorubicin were compared with the patients in the s-BACOP group in whom neutropenia did not develop during the first treatment cycle, no difference between their outcomes was observed. Toxicity was greater in the esc-BACOP group. CONCLUSIONS: In patients with advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma, escalating the dose of doxorubicin in the BACOP regimen increases toxicity but does not improve the rate of response or survival.

Adolescent↗