Uninformed Decisionmaking The Case of Surrogate Research Consent

A New York court recently struck down state Office of Mental Health regulations governing research involving subjects with impaired decisionmaking capacity. The court held that neither incapacitated adults nor minors could participate in any research protocol that contained a nontherapeutic element, irrespective of possible benefits to the subject or the importance of the knowledge to be gained. Although the decision rested on a technical point of law and dealt only with psychiatric research, the court's holding has significantly broader implications.     

The Role of the Clinical Research Coordinator in Multicenter Clinical Trials

The clinical research coordinator plays a crucial role in organizing a site's participation in the expanding arena of multicenter medical and pharmacologic clinical trials. This summary clarifies the role of the clinical research coordinator for inexperienced staff members assuming these responsibilities and outlines planning procedures leading to successful implementation. Emphasis is placed on establishing an interdependent relationship with the principal investigator, careful protocol assessment, team building, and staff feedback. Useful tools such as study manuals and physicians' study orders are described.     

Phase I and pharmacologie study of liposomal daunorubicin (DaunoXome)

Summary We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial doseescalation steps from 10 to 60 mg/m². At 80 mg/m², two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m². Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m² in previously treated and 120 mg/m² of DaunoXome in previously untreated patients with solid tumors.EDW is supported in part by ACS award 92-14-1     

Induction of collagenase synthesis in chondrocytes by a factor synthesized by inflamed synovial tissue

Rabbit inflamed synovial tissue grown in culture synthesizes a factor that induces collagenase synthesis in chondrocytes and in cartilage. Synthesis of this factor by the synovial tissue is inhibited by cycloheximide but not by indomethacin. The factor has an apparent molecular weight of 30,000, is stable to heat and to trypsin treatment but is inactivated by acid. Induction of collagenase synthesis in chondrocytes occurs after a lag period of 6 hours.     

Comparative effects of plateletderived growth factor-BB and insulin-like growth factor-I, individually and in combination, on periodontal regeneration in Macaca fascicularis

Platelet-derived growth factor (PDGF) and insulin-like growth factor I (IGF-I) in combination have previously been shown to enhance periodontal regeneration. The objective of this study was to further characterize the biological effects of this combination of growth factors in non-human primates and compare the effects to those of each growth factor individually. Ligature-induced periodontitis was initiated in 10 cynomolgus monkeys. After periodontal lesions were established, surgery was performed, and either a methylcellulose gel vehicle or vehicle containing 10 μg each of either PDGF-BB, IGF-I or both PDGF-BB and IGF-I was applied to exposed root surfaces. Biopsies were taken 4 and 12 wk after treatment and the extent of periodontal regeneration was assessed by histomorphometry. At both 4 and 12 wk vehicle-treated lesions generally revealed minimal osseous defect fill (ODF) (8.5±2.1% and 14.5±5.7%, respectively) and new attachment (NA) (34.1±5.2% and 26.6±10.5%, respectively). IGF-I treatment did not significantly alter healing compared to vehicle in any parameter at both 4 and 12 wk. PDGFBB-treated sites exhibited significant (p<0.05) regeneration of NA (69.6±12.0%) at 12 wk; trends for PDGF-BB treatment effect were also observed in other parameters at 4 and 12 wk. although these increases were not statistically significant. Treatment with PDGF-BB/IGF-I resulted in 21.6±5.1 % and 42.5±8.3% ODF at 4 and 12 wk, respectively, and 64.1±7.7% and 74.6±7.4% NA at 4 and 12 wk, respectively (all significantly greater than vehicle, p<0.05). The results from this study demonstrated that: 1) IGF-1 alone at the dose tested did not significantly alter periodontal wound healing; 2) PDGF-BB alone significantly stimulated NA, with trends of effect on other parameters; and 3) the PDGF-BB/IGF-I combination resulted in significant increases in NA and ODF above vehicle at both 4 and 12 wk.     

Systematic review of the treatment of cancer-associated anorexia and weight loss.

PURPOSE: We systematically assessed the efficacy and safety of appetite stimulants in the management of cancer-related anorexia. Literature databases were searched for randomized controlled trials of appetite stimulants in the treatment of cancer anorexia. MATERIALS AND METHODS: Studies were graded according to quality. Fifty-five studies met inclusion criteria. RESULTS: Only two drugs have evidence to support their use for anorexia (progestins and corticosteroids). There is strong evidence against the use of hydrazine sulfate. The outcomes of these trials have been mixed and patient population heterogeneous. CONCLUSION: The optimal dose, time to start, and duration of treatment for many appetite stimulants for cancer anorexia is still unknown. A more systematic approach to research methodology with universal outcome measure and prospective randomized studies are need. Combination regimens are needed but this cannot at the present time be supported by the data presented.     

Flow cytometric analysis of testicular tissue: Detection of injury and recovery

Summary DNA flow cytometry was used to examine the effects of five chemotherapeutic agents, vinblastine, cisplatinum, 5-fluorouracil, cyclophosphamide and Adriamycin, on mouse testes. Alterations in the haploid (1C), diploid (2C) and tetraploid (4C) cell compartments were assessed at 11, 29 and 56 days after giving mice a single intraperitoneal injection of each agent. Analysis of the histograms proved to be a rapid and reproducible method of monitoring injury in this animal model. Because this procedure can detect subtle testicular injuries, it is predicted that DNA histograms obtained from fine needle aspirates will gain increasing acceptance in the management of the oligo- and azoospermic patient.