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Global introspection is considered an unreliable method for attribution of causality of serious adverse events (SAEs), yet remains widely used for cancer drug clinical trials. Here, we compare structured case abstraction (SCA) to the routine method for detecting, evaluating, and reporting ADEs during cancer drug clinical trials to an Institutional Review Board (IRB). We obtained all SAE reports (2001-2008) received by one IRB for six clinical trials involving bevacizumab or oxaliplatin for treatment of gastrointestinal cancers. We compared the routine IRB SAE method to SCA for adverse event detection and causality attribution. Of 205 adverse events, 182 events (75%) were not reported; of these, 6 (20%) of 30 SAEs requiring an IRB report were unreported. For the 10 item Naranjo score, the amount of information useful for causality attribution was higher with SCA than the routine method (6.0 vs. 2.4 items, P .0001). One-fifth of SAEs requiring an IRB report were unreported to the IRB via the routine method. SCA provided more useful information as to whether an SAE was caused by a cancer drug exposure. Our results suggest that SCA may improve SAE detection and the accuracy of attribution of causality during cancer drug clinical trials.

Amylin is a 37 amino-acid peptide which is secreted from the pancreatic islets of Langerhans. It has major sequence homology with calcitonin gene related peptide. Amylin can precipitate out in these cells to form amyloid. Amylin is secreted by similar stimuli to those that secrete insulin. Amylin has a number of effects that may counteract the effect of secreted insulin, i.e., decreased second phase insulin secretion, increased hepatic glucose output, and inhibition of insulin effects on skeletal muscle. It must, however, be recognized that in many cases the doses necessary to produce these effects appear to be supraphysiological. The putative role of amylin in the hyperglycemia of aging and Type II diabetes mellitus therefore remains controversial. Amylin has a number of other effects including inhibition of osteoclastic activity, vasodilatation, anorectic effects and enhanced memory retention. This review postulates a role for amylin in the pathogenesis of a number of age-related changes.

The objective of this prospective study was to evaluate the frequency of low bone density in elderly males seen in an academic geriatric practice and to evaluate physician awareness of male osteoporosis among academic geriatricians. The participants were elderly community-dwelling ambulatory males aged 65 years and older (n = 35). The mean age was 80.7 +/- 8.2 years, with eight subjects in the 65-74 years range, 16 in the 75-84 years range and 11 over 85 years. Only 5/35 utilized an assistive device for ambulation. Bone mineral density (BMD) was measured using a heel ultrasound (QUS-2 calcaneal ultrasonometer). Clinical risk factors, gait and balance were evaluated (Tinetti scale). Results of BMD were communicated to the attending geriatrician. In all 7/35 participants had a calcaneal T-score ofor = -2.5 indicating osteoporosis, of these 50% were85 years; 7/35 had t score of -1 to -2.5 indicating osteopenia, of these 50% were 75-84 years; and 21/35 had a T-score-1 indicating normal BMD). Overall, 14 of the 35 subjects studied had low bone density. Gait disorders were seen in 18/35 subjects (p0.05), more commonly in the oldest subjects. Risk factors for osteoporosis-related fractures included smoking (n = 22, 63%, p = 0.57), gait abnormalities (n = 18, 51%, p0.05) and alcohol use (n = 13, 37%, p = 0.39). Low bone mass (osteopenia or osteoporosis) was not addressed (by record notations, request for DEXA, laboratory testing or medical treatment) within 6 months by the majority of geriatricians (3/5). This pilot study shows a high frequency of low bone density in elderly males seen in an academic geriatric practice. This frail population presents with significant balance and gait disorders, and the coexistence of these two risk factors predisposes them to the development of hip fracture. This study also underscores the importance of increasing awareness of osteoporosis in males among geriatricians. Limitations to this study are that bone density was measured with the QUS-2 calcaneal ultrasonometer, and that female reference values were utilized. These limitations potentially under-estimate the prevalence of bone loss in males.

Osteoporosis is an important public health problem. Over the next few years the health-care demands of osteoporosis and hip fractures are expected to increase ten-fold. In this article, the pathogenesis and classification of age-related osteoporosis are analyzed. Treatment options are examined and a rational management plan for this entity is discussed.

The transplantation of organs has a historical background that parallels the emergence of general bioethics, rather than the traditional authoritarian paternalism of medical ethics. Some ethical and moral issues brought forth by the transplantation technology are the determination of death, allocation of scarce resources, donor and recipient selection, and research status.

The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The physiologic effects of 12-hour lung preservation were assessed in six mongrel dogs studied for 20 hours after double-lung allograft implantation. Donor animals were pretreated with allopurinol (30 mg/kg) and methylprednisolone (500 mg) intravenously at anesthesia induction. Heart-lung blocks were harvested after cardioplegic arrest, and a simple pulmonary artery flush of 4 degrees C modified Collins' solution was administered at 15 ml/kg/min. The lungs were ventilated with 100% nitrogen during flushing and inflation. Recipient animals received an infusion of deferoxamine (20 mg/kg) during implantation and were pretreated with methylprednisolone (500 mg) intravenously. All six implantations were technically successful. Two animals died of cardiac standstill 12 and 24 hours postoperatively. Gas exchange deteriorated after implantation compared with donor levels but remained in a range compatible with survival, and at 20 hours arterial oxygen tension (FiO2 0.4) was 138 +/- 91 mm Hg. Similar changes were seen in alveolar-arterial oxygen gradients and arterial-alveolar oxygen tension fraction. Elimination of carbon dioxide was satisfactory. Pulmonary venous shunt fraction rose significantly at the end of the study. Hemodynamic changes consisted of a gradual increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated, with a gradual rise in airway resistance and a fall in compliance. The double-lung model allows detailed assessment of the early effects of preservation and may have certain advantages over heart-lung models of preservation. The preservation technique warrants further study.

pp scattering in the 1D2 state is investigated in a multichannel N/D formalism with pp → pp, pp → NΔ, and NΔ → NΔ as the coupled channels. The driving force is calculated in the OPE and OBE approximations. The resulting 1D2 amplitude has the standard resonance-like features but has no complex pole corresponding to a diproton resonance.

An extension of Doi theory for non-homogeneous flows which attempts to account for spatial distorsions in the director field has been recently presented; this theory involving the orientational distribution fonctions equation has not been carried over to the approximate, but much simpler continuum forum of the Doi theory involving the order parameter tensor. The form that these equations should take in order to make this step are presented

Nursing must keep pace with the technological revolution and radical new treatment modalities of patient care, many of which cause ethical dilemmas. To address the unique ethical concerns of staff nurses and managers, the authors discuss the development, implementation, and evaluation of a Nursing Bioethics Committee. The findings of a questionnaire measuring staff nurses' perceptions of the degree of difficulty and frequency of ethical problems in clinical practice are described. The benefits of the committee are presented from the perspective of staff nurses and nurse executives.

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