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H Bailey

Publications and source records attributed to H Bailey.

At least 19 recordsLinked to original sources
PubMed2003

A Systemic Hyperthermia Oncologic Working Group trial. Ifosfamide, carboplatin, and etoposide combined with 41.8 degrees C whole-body hyperthermia for metastatic soft tissue sarcoma.

BACKGROUND: Based on earlier clinical and preclinical studies, we conducted a phase II trial in metastatic sarcoma patients of the combination of 41.8 degrees C (x60 min) radiant heat (Aquatherm) whole-body hyperthermia (WBH) with 'ICE' chemotherapy. The ICE regimen consists of ifosfamide (5 g/m(2)), carboplatin (300 mg/m(2)) and etoposide (100 mg/m(2)), concurrent with WBH, with etoposide also on days 2 and 3 post-WBH. METHODS: Therapy was delivered every 4 weeks for a maximum of 4 cycles. All patients received filgrastim or lenograstim. RESULTS: Of 108 patients enrolled as of September 2001, 95 are evaluable for response. Of the evaluable patients (mean ECOG performance status approximately 1; mean age 42.3; 58% male) 33 had no prior therapy for metastatic disease, and 62 were pretreated (mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For no prior therapy, the response rate was 36%; in pretreated patients it was 24%. The median overall survival by Kaplan-Meier estimates was 393 days (95% CI 327, 496); the median time to treatment failure was 123 days (95% CI 77, 164). The major toxicity (287 cycles) was grade 3 or 4 neutropenia and thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7 episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving disease progression and ureteral obstruction. CONCLUSION: These results are consistent with continued clinical investigation of this combined modality approach.

Adolescent↗
PubMed2001

Does vocational training encourage continuing professional development?

The aim of this study was to compare the continuing professional development of young dentists who had participated in a vocational training scheme with that of young dentists who had not. It was encouraging to find both groups were actively involved in a broad range of continuing educational activities.

Education, Dental, Continuing↗
PubMed2001

Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome.

BACKGROUND: The purpose of the present study is to determine whether airway pressure release ventilation (APRV) can safely enhance hemodynamics in patients with acute lung injury (ALI) and/or adult respiratory distress syndrome (ARDS), relative to pressure control ventilation (PCV). METHODS: Patients with severe acute lung injury or ARDS who were managed with inverse-ratio pressure control ventilation, neuromuscular blockade and a pulmonary artery catheter were switched to APRV. Hemodynamic performance, as well as pressor and sedative needs, was assessed after discontinuing neuromuscular blockade RESULTS: Mean age was 58 +/- 9 years (n = 12) and mean Lung Injury Score was 7.6 +/- 2.1. Temperature and arterial oxygen tension/fractional inspired oxygen (FiO2) were similar among the patients. Peak airway pressures fell from 38 +/- 3 for PCV to 25 +/- 3 cmH2O for APRV, and mean pressures fell from 18 +/- 3 for PCV to 12 +/- 2 cmH2O for APRV. Paralytic use and sedative use were significantly lower with APRV than with PCV. Pressor use decreased substantially with ARPV. Lactate levels remained normal, but decreased on APRV. Cardiac index rose from 3.2 +/- 0.4 for PCV to 4.6 +/- 0.3 l/min per m2 body surface area (BSA) for APRV, whereas oxygen delivery increased from 997 +/- 108 for PCV to 1409 +/- 146 ml/min for APRV, and central venous pressure declined from 18 +/- 4 for PCV to 12 +/- 4 cmH2O for APRV. Urine output increased from 0.83 +/- 0.1 for PCV to 0.96 +/- 0.12 ml/kg per hour for APRV. CONCLUSION: APRV may be used safely in patients with ALI/ARDS, and decreases the need for paralysis and sedation as compared with PCV-inverse ratio ventilation (IRV). APRV increases cardiac performance, with decreased pressor use and decreased airway pressure, in patients with ALI/ARDS.

Adult↗
PubMed2001

Phase I clinical and pharmacokinetic trial of irofulven.

PURPOSE: To evaluate the clinical tolerability of a new schedule of 6-hydroxymethylacylfulvene (irofulven, MGI 114, HMAF, NSC 683863), a semisynthetic sesquiterpene derived from the cytotoxic mushroom metabolite illudin S. Irofulven has been shown to induce DNA damage and apoptosis in vitro and has shown activity in a number of human tumor xenograft models. A number of drug-resistant cell lines including those that express the mdr phenotype, retain sensitivity to irofulven. METHODS: We conducted a phase I trial of irofulven given as an intravenous infusion (30 min) on a daily x5 schedule every 28 days. A total of ten patients were enrolled and treated at three dose levels, 6, 8, and 11 mg/m2 per day. RESULTS: Irofulven reached steady-state concentrations during the 30-min infusions with biexponential kinetics. Irofulven disappeared rapidly from plasma and was detectable for only 15-30 min after the end of the infusion. The mean half-life was 4.91 min and the mean clearance was 4.57 l/mm per m2. Peak plasma concentrations of irofulven of approximately 300 ng/ml were achieved. Pharmacokinetic parameters did not differ significantly from day 1 to day 5. Irofulven was highly emetogenic. Other prominent toxicities included anorexia and fatigue. One case of delayed-onset metabolic acidosis possibly secondary to irofulven was observed. No other renal or metabolic toxicity was encountered. One patient experienced a late-onset grade 3 extravasation skin injury thought to be secondary to extravasation of irofulven. Minimal marrow suppression was observed. No objective tumor responses were observed. CONCLUSIONS: The recommended phase II dose on this schedule is 6 mg/m2.

Acidosis↗
PubMed2000

Can preclinical medical students be integrated into the continuing medical education process by instructing prehospital care providers?

OBJECTIVE: To develop a model introducing medical students (MS) to the continuing medical education (CME) process while simultaneously developing a curriculum to enhance the relevant surgical anatomy knowledge base of the advanced prehospital care provider. METHODS: A CME curriculum for teaching human anatomy was developed and approved by the governing state agencies for prehospital education. The curriculum focused on structures relevant to the prehospital care of the trauma patient in a case based format using common scenarios presented by surgery and emergency medicine faculty. Five year-one medical students who completed gross anatomy served as teaching staff and were given a structures list one week prior to the CME course. Human cadavers were prosected by the medical students prior to the CME program under the guidance of the surgical faculty. Course attendees and medical student staff were anonymously surveyed at the end of the program (rating scale 1 = low to 5 = high). Prehospital providers were given a multiple-choice posttest and surveyed at 3 months after the course with regard to applicability to their current practice. Data are means +/- SD. RESULTS: Nineteen licensed practicing paramedics attended the course. All of the paramedics scored above the 85% passing cutoff on the posttest (95. 6% +/- 6.2%). Instructor qualities were rated highly (4.62 +/- 0.49) with no instructor rating less than a 3. MS believed themselves well prepared to teach (5 +/- 0), and spent 2 +/- 0.81 hours in preparation. They were only infrequently faced with questions they were not well prepared to answer (1.25 +/- 0.5) and would uniformly participate in CME offerings in the future (5 +/- 0). The CME program improved the MS view of CME (3 +/- 0), prehospital education (3 +/- 1.4), and the surgeon as educator (3.25 +/- 1.5). At 3 months, the paramedics felt that the CME program significantly impacted the care they rendered (4.37 +/- 0.76), and improved their understanding of injury complexes (4.53 +/- 0.61), and resuscitation (4.26 +/- 0. 73). The cadaver course was uniformly recommended to coworkers (5 +/- 0). CONCLUSIONS: This model provided prehospital care providers direct contact with clinically relevant human anatomy, enhanced their understanding of pertinent anatomy, and positively impacted their patient care. MS were introduced to the CME process and found it to be one with which they would become reinvolved. Furthermore, the MS felt prepared to present human anatomy, met the expectations of the course attendees, improved their understanding of prehospital education, and positively altered their perception of the surgeon as an educator. This process holds promise as both a model for prehospital education and as a tool for integrating MS into the role of allied health educator early in their career.

Anatomy↗
PubMed2000

Atlanto-occipital dislocation: an unusual lethal airbag injury.

Airbag-induced injury fatality is increasing in frequency. We present the case of a 6-year-old passenger who sustained a fatal atlanto-occipital dislocation associated with airbag deployment in a low-speed motor vehicle crash. The current literature regarding airbag fatalities and methods to ameliorate airbag-induced injury are reviewed.

Accidents, Traffic↗
PubMed1998

Audit activity and uptake of postgraduate dental education among general dental practitioners in Yorkshire.

The aim of this study was to assess the involvement of general dental practitioners in Yorkshire in clinical audit activity and in postgraduate dental education and to compare the results with those of a previous survey undertaken in 1989. There is a need to find ways of encouraging all general dental practitioners to become actively involved in continuing professional development and in improving the quality of general dental practice through the use of clinical audit.

Adult↗
PubMed1998

A phase II study of irinotecan (CPT-11) in patients with advanced squamous cell carcinoma of the cervix.

BACKGROUND: This study was conducted to determine the efficacy and safety of irinotecan (CPT-11) as second-line therapy in patients with advanced cervical carcinoma. METHODS: Sixteen patients with platinum-resistant squamous cell carcinoma were treated with CPT-11 as second-line therapy. CPT-11 was administered in repeated 6-week cycles comprised of the administration of CPT-11 once weekly for 4 weeks, followed by a 2-week rest. The starting dose of CPT-11 was 125 mg/M2 given intravenously over 90 minutes; subsequent doses were adjusted based on individual patient tolerance. RESULTS: The median age of the patients was 43 years (range, 27-69 years). Three patients had a baseline Eastern Cooperative Oncology Group performance score (PS) of 0, 8 had a PS of 1, and 5 had a PS of 2. All patients had received cisplatin-based chemotherapy and 13 of 16 patients (81.3%) had been treated with prior pelvic/abdominal radiation therapy. Fourteen patients were evaluable for response. There were no objective responses although subjective decreases in symptoms were observed in some patients. Grade 3 to 4 toxicities included diarrhea in three patients, nausea and emesis in one patient, leukopenia in six patients, and neutropenia in five patients. Eighteen of 25 cycles required dose reductions leading to a median dose intensity of only 59.4 mg/M2/week, which was 71% of the planned dose of 83.3 mg/M2/week. CONCLUSIONS: The amount of CPT-11 actually delivered to the patients under the conditions of this pilot study failed to result in an antitumor response. However, the marked subjective improvement of symptoms observed in this study and the significant activity reported by other investigators justify future studies of CPT-11 in patients with cervical carcinoma.

Adult↗
PubMed1994

The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin-associated repetitive element: implications for a role of chromatin structure in the pathogenesis of the disease.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant form of muscular dystrophy. The FSHD locus has been linked to the most distal genetic markers on the long arm of chromosome 4. Recently, a probe was identified that detects an EcoRI fragment length polymorphism which segregates with the disease in most FSHD families. Within the EcoRI fragment lies a tandem array of 3.2 kb repeats. In several familial cases and four independent sporadic FSHD mutations, the variation in size of the EcoRI fragment was due to a decrease in copy number of the 3.2 kb repeats. To gain further insight into the relationship between the tandem array and FSHD, a single 3.2 kb repeat unit was characterized. Fluorescence in situ hybridization (FISH) demonstrates that the 3.2 kb repeat cross-hybridizes to several regions of heterochromatin in the human genome. In addition, DNA sequence analysis of the repeat reveals a region which is highly homologous to a previously identified family of heterochromatic repeats, LSau. FISH on interphase chromosomes demonstrates that the tandem array of 3.2 kb repeats lies within 215 kb of the 4q telomere. Together, these results suggest that the tandem array of 3.2 kb repeats, tightly linked to the FSHD locus, is contained in heterochromatin adjacent to the telomere. In addition, they are consistent with the hypothesis that the gene responsible for FSHD may be subjected to position effect variegation because of its proximity to telomeric heterochromatin.

Base Sequence↗
PubMed1992

A phase I trial of 5-fluorouracil, leucovorin, and dipyridamole given by concurrent 120-h continuous infusions.

A phase I trial of 5-fluorouracil (FUra) and leucovorin (LV) given with and without dipyridamole (DP) by concurrent 120-h continuous infusion was performed in 27 patients with advanced solid malignancies, 8 of whom had previously received FUra. The LV and DP doses were fixed at 500 mg/m2 daily and 7.7 mg/kg daily, respectively, whereas the FUra dose was escalated. Level 3 (450 mg/m2 FUra daily) represented the maximum tolerated dose for both FUra/LV+DP and FUra/LV. Dose-limiting stomatitis (greater than or equal to grade 3 or grade 2 occurring during the infusion) was encountered in 75% of the first courses given at level 4 (600 mg/m2 daily). Stomatitis was observed in 44/78 (56%) courses. Diarrhea was infrequent and mild. DP infusions were complicated by mild to moderate headache, which was controlled with narcotic analgesics, and mild to moderate nausea/vomiting. FUra-related toxicity was not enhanced by DP administration. Limited pharmacokinetic sampling at levels 3 and 4 revealed mean steady-state FUra concentrations of around 1.0 microM with infusions of FUra/LV+DP. Among three paired courses given with and without DP, no statistically significant difference was found in the total body clearance of FUra (P = 0.44). One partial response was seen in a patient with metastatic gastric carcinoma. For phase II trials, we recommend that concurrent 120-h continuous infusions of FUra (450 mg/m2 daily) and LV (500 mg/m2 daily) be given with and without DP (7.7 mg/kg daily) every 21 days.

Adult↗
PubMed1992

Phase I evaluation of 773U82-HCl in a two-hour infusion repeated daily for three days.

One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity in in vitro and in in vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series (crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m2/d x 3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing < or = 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m2/d x 3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2 beta averaged 6 hours and the total body clearance was 75.9 L/hr/m2. The volume of distribution (Vdss) was large, averaging 470 L/m2.

Adult↗
PubMed1991

Phase I clinical trial of fazarabine as a twenty-four-hour continuous infusion.

A phase I trial of fazarabine (ara-AC, 1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 24 adults with solid tumor malignancies. The majority of patients had received prior marrow-suppressive therapy. Level 7 (54.5 mg/m2/h for 24 h) was the maximum tolerated dose since during 6 evaluable first courses, 2 episodes of grade 4 granulocytopenia and 3 episodes of grade 3 occurred. Moderate thrombocytopenia also occurred at level 7 with 3 episodes of grade 1 and 1 episode of grade 4 thrombocytopenia during 6 first course treatments. Minimal myelosuppression, principally leukopenia, was seen prior to level 7. The nadir WBC through 47 courses had a linear relationship with plasma steady-state concentrations of ara-AC. The only other toxicity noted was moderate nausea/vomiting, which did not appear to be dose related. Plasma steady-state concentrations of ara-AC were reached in all patients within 4-6 h and ranged from 1.1 microM (11 mg/m2/h for 24 h) to 7.5 microM (54.5 mg/m2/h for 24 h). The mean total body clearance of ara-AC for 47 courses, levels 1-7, was 592 +/- 147 (SD) ml/min/m2 which is similar to prior pharmacokinetic data from the 24-h and 72-h infusion trials of the Pediatric and Medicine Branches, respectively. There were no objective disease responses during the trial. The recommended adult phase II dose for a 24-h infusion of ara-AC is 45-50 mg/m2/h.

Adult↗
PubMed1991

A phase I study of SR-2508 and cyclophosphamide administered by intravenous injection.

SR-2508, a less lipophilic ane neurotoxic analogue of the nitroimidazole, misonidazole, has exhibited significant chemosensitization properties in preclinical studies with alkylating agents. A phase I trial was carried out to assess toxicity and possible pharmacological interactions of the combination of short infusions of SR-2508 and cyclophosphamide (CP). Patients were randomly assigned to receive either CP alone followed in 3 wk by CP + SR-2508, or CP + SR-2508 followed by CP alone. All additional courses were CP + SR-2508. The maximum tolerated dose of the combination was determined by dose escalation of SR-2508 while the dose of CP remained fixed, initially 1.0 g/m2, and then a second maximum tolerated dose was determined with CP at 1.6 g/m2. One hundred seventeen evaluated courses were administered to 39 patients, the majority of whom had received prior treatment. Somewhat unexpectedly, reversible grade 4 granulocytopenia was the dose-limiting toxicity occurring in four of five evaluable first combination courses at level 6 (SR-2508, 11.3 g/m2; CP, 1.0 g/m2), the initial maximum tolerated dose. SR-2508 enhanced CP-induced myelosuppression as exhibited by the significant difference (p less than 0.001) between the 27 paired courses (CP versus CP + SR-2508) for WBC nadirs over levels 1 to 6. The neurotoxicity encountered was similar to that seen in past clinical trials, being reversible, mild, and usually peripheral in nature. There was one treatment-related death (neutropenic sepsis) on study. No other significant toxicity was seen. SR-2508 exhibited linear pharmacokinetics over the dose range studied. The SR-2508 area under the concentration-time curve increased linearly with dose (r = 0.858; p less than 0.001). No other parameters were dose related. Neither drug appeared to affect the pharmacokinetics of the other, and CP pharmacokinetic values were consistent with those from prior studies. Due to the interaction noted between the two agents and the preclinical data suggesting preferential enhancement of antitumor efficacy under this combination, phase II study appears warranted.

Adult↗
PubMed1991

Intrathoracic osteosarcoma diagnosed by CT scan and pleural biopsy.

Osteosarcoma rarely presents as a primary lesion in the chest, whereas pulmonary metastases are common. The diagnosis of primary intrathoracic osteosarcoma has invariably been by thoracotomy or autopsy. We present a case of a densely calcified, primary intrathoracic osteosarcoma where diagnosis was made antemortem by pleural biopsies and computed tomography scan.

Aged↗
PubMed1990

Prevention of central nervous system toxicity of the antitumor antibiotic acivicin by concomitant infusion of an amino acid mixture.

Acivicin is an investigational amino acid antitumor antibiotic currently being evaluated in Phase II clinical trials. In humans acivicin causes reversible, dose-limiting central nervous system (CNS) effects including somnolence, ataxia, personality changes, and hallucinations. We have observed and reported previously that acivicin-treated cats exhibit symptoms (ataxia, sedation, somnolence) resembling CNS toxicity reported in humans. We hypothesized that if acivicin uptake into brain were mediated by a saturable transport system common to endogenous amino acids, drug uptake and CNS toxicity might be blocked by elevation of normal amino acid concentrations in circulating plasma. To test this hypothesis, cats received constant-rate i.v. infusions of either saline or Aminosyn, 10% (a commercially available mixture of 16 amino acids not containing glutamine, glutamate, aspartate, or cysteine) for 4 h prior to and 18 h subsequent to administration of acivicin at a dose producing marked behavioral changes in control cats. Presence or absence of ataxia and sedation were noted at intervals after acivicin treatment. Results showed that Aminosyn infusion prevented CNS symptoms in six of eight cats. Subsequent experiments showed that acivicin levels in brain tissue of Aminosyn-treated cats were 13% of the drug levels in saline-infused cats. Acivicin levels in most peripheral tissues were also decreased significantly by Aminosyn infusion but not to the extent observed in brain. Decreased brain uptake was shown to be due to a combination of amino acid blockade of drug transport into that organ and of increased total body clearance of drug. Concomitant Aminosyn treatment did not alter the efficacy of acivicin in mice bearing L1210 leukemia or MX-1 human mammary carcinoma. Further studies demonstrated that a solution containing only four large neutral amino acids (leucine, isoleucine, phenylalanine, and valine) could also protect cats from acivicin-induced CNS toxicity, apparently without increasing acivicin total body clearance. However, a mixture of several other amino acids contained in Aminosyn (alanine, arginine, tyrosine, histidine, proline, serine, and glycine) failed to prevent CNS toxicity. We conclude that cotreatment with Aminosyn or a mixture of large neutral amino acids could protect cancer patients from acivicin-induced CNS toxicity without ablating antitumor efficacy.

Amino Acids↗