The role of patient education and physician support in self-efficacy for skin self-examination among patients with melanoma.

OBJECTIVE: This project aims to elucidate the relationships between skin self-examination (SSE), perceived physician support of SSE, and self-efficacy for SSE among melanoma patients. METHODS: A longitudinal study of patients diagnosed with melanoma was conducted over the span of 18 months. Participants filled out questionnaires at four assessment points and participated in an SSE education about the early signs of melanoma. RESULTS: Among the 242 patients enrolled, the level of self-efficacy for SSE was 23% higher immediately after the educational intervention (p<.001) and the increase was retained three months (p<.001) and twelve months later (p<.001). Additionally, a one-way repeated measures ANOVA revealed that the perceived physician support of SSE positively corresponded to the level of patient self-efficacy with higher patient-reported physician support being related to higher self-efficacy (p=.001). CONCLUSION: Patient education and perceived physician support of SSE are positively associated with patients' level of self-efficacy. PRACTICE IMPLICATIONS: Physicians caring for melanoma survivors should be aware that, both SSE education and patients' perception of high physician support of SSE may be associated with higher self-efficacy for checking one's own skin for signs of cancer recurrence.

Self-efficacy and comfort with partner-assisted skin examination in patients receiving follow-up care for melanoma.

The objective of this study was to examine the role of interpersonal variables on melanoma survivors' self-efficacy for performing skin self-examinations (SSEs) during melanoma follow-up care. Specifically, the impact of comfort with partner assistance for SSE, SSE support received from one's partner, general partner support, relationship satisfaction, as well as partner attendance at a SSE education session, were examined. One hundred and thirty-seven patients with melanoma between the ages of 18 and 70 years, who also reported being involved in a romantic relationship, received a standardized education on SSE, and completed self-report questionnaires. Results indicate that SSE support and SSE comfort predicted patients' SSE self-efficacy. Partner attendance at the SSE education moderated the relationship between SSE comfort and SSE self-efficacy. In other words, SSE self-efficacy was found to be affected by partner attendance at the SSE education only in cases where the patient reported lower levels of comfort having his or her partner assist with SSE. Results highlight the importance of partner involvement in SSE education, as well as patient comfort with a partner's assistance during skin examinations. Findings inform potential modifications to the follow-up care provided to melanoma survivors by demonstrating the importance of partner involvement in SSE education.

Association of pre-transplantation positron emission tomography/computed tomography and outcome in mantle cell lymphoma.

Positron emission tomography/computed tomography (PET/CT)-positive findings before autologous SCT (auto-SCT) are associated with inferior PFS and OS in patients with relapsed Hodgkin's and diffuse large B-cell lymphoma. We classified pre-transplant PET/CT performed before auto-SCT as positive or negative to evaluate the impact of pre-transplant PET/CT in mantle cell lymphoma (MCL). In 29 patients, 17 were PET/CT(-) and 12 were PET/CT(+). PET/CT(+) patients were younger (P=0.04), had lower MCL International Prognostic Index (MIPI, P=0.04) scores, but increased bulky adenopathy >5 cm (45% vs 13%, P=0.09). With a median follow-up of 27 months (range: 5-55 months), 7 patients relapsed (4 in the PET/CT(-) group and 3 in the PET/CT(+) group) with 2 deaths in the PET/CT(+) group without a documented relapse. The estimated 2-year PFS was 64% (95% confidence interval (CI): 0.30-0.85) vs 87% (95% CI: 0.57-0.97) in PET/CT(+) and PET/CT(-) patients, respectively (P=0.054). OS was significantly decreased in PET/CT(+) patients (P=0.007), with 2-year estimates of 60% (95% CI: 0.23-0.84) vs 100% in PET/CT(-) patients. A positive pre-transplant PET/CT is associated with a poor prognosis in patients with MCL. Additional factors may impact the prognostic value of PET/CT, as several PET/CT(+) patients remain in remission.

Protein oxidation and enzyme susceptibility in white and gray matter with in vitro oxidative stress: relevance to brain injury from intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating stroke sub-type with high mortality and morbidity. ICH frequently occurs in subcortical white matter generating hematomas that contain high heme iron levels. In this study, we examined the consequences of iron-induced oxidation (1-100 microM Fe2+ for 30 min. or 50 microM Fe2+ for 1-120 min.) on the activities of two oxidatively sensitive enzymes, creatine kinase (CK) and glutamine synthetase (GS), and on an oxidative stress marker, protein carbonyl formation, in porcine cerebral cortical white and gray matter. In vitro iron oxidation produced time and concentration dependent decreases in both CK [maximum decreases of 49.3+/-1.2% and 44.3+/-4.1% (average +/- SEM, N=3) for white and gray matter, respectively] and GS activities (maximum decreases of 16.9+/-1.7% and 13.2+/-1.0% for white and gray matter, respectively) and increases in protein carbonyl formation. Interestingly, protein carbonyl concentrations were significantly greater (p<0.05) in white vs. gray matter at 100 microM iron (30 min.) and 50 microM iron (120 min.). Additionally, CK and GS activities were lower for white versus gray matter at several time points and iron concentrations. It is our hypothesis that iron induced oxidative stress contributes to the pathogenesis of perihematomal brain injury following ICH.

Effect of 2-cyclohexene-1-one-induced glutathione diminution on ischemia/reperfusion-induced alterations in the physical state of brain synaptosomal membrane proteins and lipids.

Glutathione is able to protect membrane proteins from oxidative stress. In ischemia/reperfusion injury, free radicals cause synaptosomal membrane protein and lipid oxidation that is prevented by the free radical scavenger N-tert-butyl-alpha-phenylnitrone (Hall N. C. et al. (1995) Neuroscience 64, 81-89; 69, 591-600). We wondered if diminution of glutathione would lead to further membrane alterations. Accordingly, the effects of glutathione depletion, by intraperitoneal administration of 2-cyclohexene-1-one, on the physical state of cortical synaptosomal membrane proteins and lipids, with and without global ischemia/reperfusion, were studied in vivo and in vitro in adult and aged gerbils utilizing electron paramagnetic resonance spectrometry. 2-Cyclohexene-1-one (100 mg/kg, i.p.) was administered 30 min prior to 10-min ischemia followed by 1 or 14 h reperfusion. This glutathione reduction agent was also administered to gerbils under the same temporal schedule in the absence of ischemia and compared to untreated controls. Synaptosomal membranes were labeled with a protein-specific spin label, 2,2,6,6-tetramethyl-4-maleimidopiperidine-1-oxyl, or a lipid-specific spin probe, 5-doxylstearic acid. There were no significant changes in the physical state of the lipid portion of synaptosomal membranes when comparing ischemia reperfusion and 2-cyclohexene-1-one-treated ischemia reperfusion in either the adult or aged gerbils. However, glutathione depletion without ischemia/reperfusion caused significant changes in the physical state of the protein portion of cortical synaptosomal membranes in both the adult and aged models. Glutathione depletion, without ischemia/reperfusion, in the adult model showed a maximum change at 3 h that returned to control values by 14 h. In contrast, the aged model showed significant changes at 1 h reperfusion, which did not return to control values by 14 h reperfusion. Glutathione depletion combined with ischemia/reperfusion caused initial protein change in both adult and aged models at 1 h reperfusion, which did not return toward control values by 14 h reperfusion. The results of this study suggest that glutathione depletion increases the severity of membrane protein damage associated with ischemia/reperfusion injury.

Prevention of ischemia/reperfusion-induced alterations in synaptosomal membrane-associated proteins and lipids by N-tert-butyl-alpha-phenylnitrone and difluoromethylornithine.

Previous studies in our laboratory demonstrated the alteration in the physical state of synaptosomal membrane lipids and proteins in ischemia/reperfusion injury using selective spin labels and electron paramagnetic resonance spectroscopy [Hall et al. (1995) Neuroscience 61, 84-89]. Since many investigations have provided evidence for free radical generation during ischemia/reperfusion injury, we investigated whether a free radical scavenger would prevent the membrane damage, in gerbils. Further, experiments to determine if a secondary effect of polyamine generation at 14 h reperfusion could be blocked by this free radical scavenger or by an inhibitor of ornithine decarboxylase were also carried out. The alterations in synaptosomal membrane integrity observed during ischemia/reperfusion injury were selectively neutralized by treatment with the free radical spin trap N-tert-butyl-alpha-phenylnitrone or an inhibitor of ornithine decarboxylase, difluoromethylornithine. Administration of N-tert-butyl-alpha-phenylnitrone prior to ischemia totally abrogated both lipid and protein alterations observed at 1 and 14 h reperfusion. Pretreatment with difluoromethylornithine neutralized only the 14 h change in lipid label motion. Treatment with N-tert-butyl-alpha-phenylnitrone at 6 h post ischemia showed only a slight attenuation of the 14 h lipid effect and no change in the protein effect. Difluoromethylornithine treatment at 6 h post ischemia negated the 14 h ischemia/reperfusion injury-induced lipid effect and had no effect on the protein change. These data support previous suggestions that free radicals and polyamines play a critical role in neuronal damage and cell loss following ischemia/reperfusion injury and that the polyamine effect is dependent upon free radical generation during ischemia/reperfusion injury.

Structural alterations in synaptosomal membrane-associated proteins and lipids by transient middle cerebral artery occlusion in the cat.

We have previously reported that ischemia reperfusion injury results from free radical generation following transient global ischemia, and that this radical induced damage is evident in the synaptosomal membrane of the gerbil. [Hall et al, (1995) Neuroscience 64: 81-89]. In the present study we have extended these observations to transient focal ischemia in the cat. We prepared synaptosomal membranes from frontal, parietal-temporal, and occipital regions of the cat cerebral cortex with reperfusion times of 1 and 3 hours following 1 hour right middle cerebral artery occlusion. The membranes were selectively labeled with protein and lipid specific paramagnetic spin labels and analyzed using electron paramagnetic resonance spectrometry. There were significant motional changes of both the protein and lipid specific spin labels in the parietal-temporal and occipital regions with 1 hour reperfusion; but, both parameters returned to control values by 3 hours reperfusion. No significant changes were observed in the normally perfused frontal pole at either reperfusion time. These results support the argument that free radicals play a critical role in cell damage at early reperfusion times following ischemia.

Ischemia/reperfusion-induced changes in membrane proteins and lipids of gerbil cortical synaptosomes.

The effects of transient bilateral carotid occlusion on the physical state of synaptosomal membrane proteins and lipids were studied in adult and aged gerbils employing electron paramagnetic resonance. Transient ischemia was produced in adult and aged gerbils by bilateral occlusion of the common carotid arteries with reperfusion times ranging from 0 to 24 h. Synaptosomes of the cerebral cortices were isolated and labeled with a protein-specific spin probe (2,2,6,6-tetramethyl-4-maleimido-piperidine-1-oxyl) and a lipid-specific spin probe (5-doxylstearic acid). Changes in the physical state of the protein peaked at 60 min reperfusion for both adult and aged gerbil models, with a more intense change in aged, but did not return to control values by 24 h. A biphasic change occurred with the lipid-specific label in both the aged and adult models. The onset of the first phase of change occurred at an earlier time (30 min reperfusion) for aged gerbil tissue than for adult tissue (between 3 and 6 h reperfusion), while the second phase of change occurred at 12 h reperfusion for both adult and aged. These results are consistent with the hypothesis that protein oxidation and lipid peroxidation are direct results of free radicals produced during the reperfusion following ischemia and that protein oxidation may be intensified by peroxidation of the surrounding lipids. Phospholipase A2 activation is implicated to cause changes in membrane phospholipid organization as seen in these studies.

Effects of dehydroabietic acid on the physical state of cytoskeletal proteins and the lipid bilayer of erythrocyte membranes.

Dehydroabietic acid (DHAA) is a major aquatic toxic resin acid usually found in unbleached pulp mill effluents. This compound has been reported to accumulate in the red cells of rainbow trout and to cause hemolysis. To elucidate further understanding to the mechanism of action of this resin, the interaction of DHAA with human erythrocyte membranes has been monitored by electron paramagnetic resonance techniques of spin labeling. Results presented in this paper indicate that DHAA, in a concentration-dependent manner, significantly altered both the motion and order of the lipid bilayer and the physical state of cytoskeletal proteins, while DHAA had no effect on isolated lipids. It is proposed that the increase in the 'fluidity' of the lipid bilayer induced by DHAA is a secondary effect of primary changes in the physical state of the cytoskeletal proteins of the membrane, and that the latter effect is critically associated with the toxicity of DHAA.

Effects of beta-(N-methylamino)-L-alanine on cytoskeletal proteins of erythrocyte membranes.

The interaction of the amino acid beta-(N-methylamino)-L-alanine, a neurotoxin found in the seed of the false sago palm, with erythrocyte membranes has been monitored by electron paramagnetic resonance techniques of spin labeling. This neurotoxin did not alter the motion or order of bilayer lipids, but a highly-significant and dose-dependent alteration in the physical state of cytoskeletal proteins was observed. These results are discussed in reference to potential mechanisms involved in the neurotoxicity produced by beta-(N-methylamino)-L-alanine and in reference to the unusual neurological disorders among the Chamorro population of Guam and other Marianas Islands.

New obstacles in the path of marketing new medical devices.

Approval of a new medical device's safety and effectiveness by the Food and Drug Administration (FDA) is only one step in the typical device's passage into the marketplace. A review of 10 new Class II and III devices found an average of 62 months elapsing between the beginning of FDA-approved clinical trials and the device's final approval for general marketing. However, FDA marketing approval does not mean a new device can be sold because, for many new devices, the Health Care Financing Administration (HCFA) requests a technology assessment from the Office of Health Technology Assessment (OHTA) in order to determine whether the device's use is "reasonable and necessary" and thus appropriate for Medicare payment. The Medicare decision often guides other third parties. OHTA assessments of 93 devices and procedures required an average of 26 months to complete; of 16 FDA-approved Class III devices, OHTA reported to HCFA that insufficient data existed to recommend coverage for 12 (75 percent). Under the Medicare prospective payment system (PPS) for hospital care, a third step has been added to the process, consideration by the Prospective Payment Assessment Commission (ProPAC) and HCFA of the new device's impact on PPS payment rates. Further, under recent legislation, OHTA is mandated also to consider a device's cost effectiveness. Duplicative reviews of new devices should be eliminated, and until they are, medical equipment developers must recognize that delays and conflicting payment rulings may have serious impacts on the ability to market a new device.