Perceptions of the ethical acceptability of using medical examiner autopsies for research and education: a survey of forensic pathologists.

BACKGROUND: Forensic pathologists face difficult moral questions in their practices each day. Consistent ethical and legal guidelines for autopsy tissue use extending beyond usual clinical and legal imperatives have not been developed in this country. OBJECTIVE: To obtain the perceptions of medical examiners regarding the ethical acceptability of autopsy tissue use for research and education. METHOD: A written, self-report questionnaire was developed and piloted by a multidisciplinary team at the University of New Mexico, Albuquerque. All individuals who attended a platform presentation at the National Association of Medical Examiners Annual Meeting in September 1997 were invited to participate. RESULTS: Ninety-one individuals completed the survey (40% of all conference registrants and approximately 75% of presentation attendees). Sixty-three percent of respondents had encountered an ethical dilemma surrounding autopsy tissue use, and one third reported some professional ethics experience. Perspectives varied greatly concerning the ethical acceptability of using autopsy tissues to demonstrate or practice techniques (eg, intubation, brachial plexus dissection) and of fulfilling requests to supply varying kinds and quantities of tissues for research and education. Most respondents indicated that consent by family members was important in tissue use decisions. Respondents agreed on the importance of basic values in education and research, such as integrity, scientific or educational merit, and formal institutional approval of a project. Characteristics of the decedent did not influence decisions to release tissues, except when the individual had died from a mysterious or very rare illness. Attributes of medical examiners, with the exception of sex, also did not consistently predict responses. CONCLUSION: Significant diversity exists in beliefs among medical examiners regarding perceptions of the appropriate use of autopsy tissues for education and research. There is need for further inquiry and dialogue so that enduring policy solutions regarding human tissue use for education and research may be developed.

Effects of energy-matched pulsed and continuous ultrasound on tumor growth in mice.

BACKGROUND AND PURPOSE: A diagnosis of cancer is a contraindication for the use of therapeutic ultrasound (US). Continuous US applied to murine tumors has resulted in larger and heavier tumors compared with controls. We compared tumor growth using low-power continuous US and energy-matched pulsed US. SUBJECTS: Female C57BL/6 mice (N = 174) were used. METHODS: Animals received subcutaneous injections of methylcholanthrene tumor cells. The mice were randomly divided into three groups: 60 mice that received low-power continuous US for 5 minutes at 0.75 W/cm2 (LC US group), 63 mice that received pulsed US for 12.5 minutes at 1.5 W/cm2 (pulsed US group), and 51 mice that served as a control group. The LC and pulsed US groups received equal US energy. Both experimental groups received 10 treatments of 3-MHz US, which was applied directly over the tumor. The control group received identical handling but no US. After treatment, the tumors were excised, weighed, and measured. A one-way analysis of variance, followed by Newman-Keuls post hoc testing, was used to analyze the data. RESULTS: Mean tumor weights (in grams) and volumes (in cubic millimeters) were 0.563 g and 564 mm3 for the LC US group, 0.560 g and 525 mm3 for the pulsed US group, and 0.516 g and 406 mm3 for the control group. CONCLUSION AND DISCUSSION: Reducing total US energy will result in less growth of murine tumors. When infusing equal energy, continuous and pulsed US will produce similar effects on tumor growth.

The visual function of professional baseball players.

PURPOSE: To measure the visual acuity, stereoacuity, and contrast sensitivity of professional baseball players. METHODS: Three hundred eighty-seven professional baseball players underwent several tests of visual function including distance visual acuity. Stereoacuity was evaluated at near by the Randot test and at distance by both contour and random dot targets. Distance stereoacuity was also tested under timed and untimed conditions. Contrast sensitivity was evaluated by the Vision Contrast Test System, Contrast Sensitivity Viewer, and Binocular Visual Acuity Tester. RESULTS: Visual acuity (measured with players' regular distance correction) in 774 eyes ranged from 20/8.89 to 20/100. Near stereoacuity ranged from 23 to 37 seconds of arc, mean untimed distance contour stereoacuity from 55 to 35 seconds of arc, and mean untimed distance random dot stereoacuity from 98 to 76 seconds of arc. The results under timed conditions were 86 to 65 seconds of arc (timed distance contour stereoacuity) and 104 to 83 seconds of arc (timed distance random dot stereoacuity). Statistically significant differences were found between major and minor league players on tests of untimed distance contour and random dot stereopsis, and on contrast sensitivity testing with the 3.0- and 6.0-cpd gratings using the Contrast Sensitivity Viewer. CONCLUSIONS: Professional baseball players have excellent visual skills. Mean visual acuity, distance stereoacuity, and contrast sensitivity are significantly better than those of the general population.

Experimental reduction of eggshell conductance during incubation. I. effect on the susceptibility to ascites syndrome.

Two hundred-four fertile broiler chicken eggs were obtained from a commercial source and divided into three equal groups. On day 1 of incubation, 68 eggs were selected randomly and four strips of vinyl tape were applied to the shell below the air cell (tape-day 1) to reduce eggshell conductance. This procedure was repeated with an additional group of 68 eggs on day 14 (tape-day 14). Sixty-eight eggs were incubated without treatment, as controls. One week after hatch, 20 chickens from each treatment group and control group were placed into a hypobaric chamber (simulated altitude of 2500 m) for 5 weeks. The remaining chickens in each group were maintained under normobaric conditions. The hematocrit and the mean frontal resultant electrical vector (MRV) of the heart were measured following 1 week, 3 weeks, and 5 weeks of hypobaric or normobaric exposure. Surviving chickens were euthanized at the end of 5 weeks. The weight ratio of right ventricle to left ventricle plus septum (the hypertrophy index [HI]) and the cardiac index, the HI divided by body weight, were determined. All mortality during the study was subjectively scored for the presence of ascites syndrome lesions. The percentage of chickens dying during, or exhibiting ascites syndrome at the completion of, the 5-week hypobaric exposure was 16.7%, 66.7%, and 58% for control, tape-day 1, and tape-day 14 treatments, respectively. MRV values of birds following hypobaric exposure were significantly different between treatment and control groups of the hypobaric exposure and between the two tape treatments. These results suggest that reducing conductance of the eggshell during incubation significantly potentiates the development of ascites syndrome in the broiler chicken.

Biochemical quantification of triamcinolone in subconjunctival depots.

OBJECTIVE: To biochemically quantify the amount of active triamcinolone acetonide remaining after subconjunctival administration and to assess the effectiveness of surgical management for glaucoma induced by triamcinolone. DESIGN: Case series. PARTICIPANTS: Seven eyes of seven patients whose ages ranged from 47 to 84 years underwent excision of depot triamcinolone. Six of seven eyes required surgical intervention for medically unresponsive intraocular pressure (IOP) elevation. RESULTS: Pharmacologically active triamcinolone was identified up to 13 months following injection (range, 3 to 13 months). The mean amount in the excised sample was 5.4 mg (range, 2.0 to 8.8 mg), and the mean percentage of the original sample remaining was 20% (range, 4.2% to 44%). Glaucoma was diagnosed a mean of 3 months after injection (range, 1 to 6 months). Mean IOP was 37 mm Hg before excision and 16 mm Hg after removal. Surgical excision of visible triamcinolone normalized IOP in six of seven patients without need for glaucoma medications. CONCLUSIONS: Periocular injection of triamcinolone necessitates careful monitoring of IOP. Medically unresponsive IOP elevation may occur as late as 6 months following periocular triamcinolone injection. Surgical excision of remaining triamcinolone depot is an effective therapy for IOP elevation. Guidelines for safely using triamcinolone are discussed.

Effects of continuous therapeutic ultrasound on growth and metastasis of subcutaneous murine tumors.

BACKGROUND AND PURPOSE: The use of therapeutic ultrasound (US) in the presence of malignant neoplasms has been contraindicated in physical therapy practice despite a lack of convincing scientific evidence. Some studies have shown that high levels of US, which increase tissue temperatures greater than 42 degrees C, can kill tumors. We sought to determine whether the application of continuous therapeutic US would alter the growth or metastasis of methylcholanthrene-induced solid tumors in mice. SUBJECTS: Seventy-one female C57BL/6 mice, age 6 to 8 weeks, received subcutaneous injections of 5 x 10(5) tumor cells. METHODS: When tumors grew to 0.5 cm in diameter, the mice were randomly assigned to either a control group (n = 34) or an experimental group (n = 37). The experimental group received 10 treatments over a 2-week period of 3-MHz continuous US at 1.0 W/cm2 for 5 minutes, using a 0.5-cm2 sound head directly over the tumor. The control group received the same handling except for the US treatment. Tumor dimensions were measured on days 1 (baseline), 7 (midtreatment), and 14 (preexcision and postexcision). Tumors were weighed after excision, and the mice were evaluated by necropsy and histopathology of regional lymph nodes. RESULTS: All tumors grew larger over time, but final tumor volume and weight were larger in the experimental group (789 mm3 and 0.932 g) than in the control group (395 mm3 and 0.506 g). No significant difference existed in the number of metastatic lymph nodes between groups. CONCLUSION AND DISCUSSION: Continuous therapeutic US increased the volume and weight of subcutaneous murine tumors in mice. We urge caution in the use of continuous therapeutic US in the areas of tumors or suspected tumors.

A victimization assessment tool: instrument development and clinical implications.

Although most health care providers now recognize the importance of crisis intervention, support, and/or treatment for survivors of violence and abuse, such care is compromised unless early detection becomes a routine part of intake and assessment protocols in nursing and other facets of health care. This paper describes the development of a tool to assist nurses and other primary care providers with routine assessment for victimization in diverse health and mental health settings. It includes outcomes of preliminary validity and reliability studies, and concludes with suggestions for use in clinical work with victims/survivors of abuse in an era of increasing international concern regarding the health implications of violence.

Treatment of large subchondral tumors of the knee with cryosurgery and composite reconstruction.

The radiographic and clinical outcomes of 9 patients with large benign aggressive or low-grade malignant periarticular tumors of the knee who were treated with cryosurgery and composite reconstruction (cementation, bone graft, and internal fixation) in lieu of primary resection were analyzed. The minimum followup was 2 years (range, 24-103 months). There were 6 giant cell tumors and a single case each of chondroblastoma, chondrosarcoma, and fibrosarcoma in the study group. Six lesions involved the distal femur and 3 the proximal tibia. Functional outcomes were graded according to the Enneking Modified System for the Functional Evaluation of Tumor and The Knee Rating Scale of The Hospital for Special Surgery. All lesions extended to within 2 mm of the articular surface. Local tumor control was achieved in 8 patients (89%). The single local recurrence was successfully managed with repeat curettage, cryosurgery, cementation, and internal fixation. All 9 patients had excellent functional outcomes according to both evaluation scales.

Evaluation of iontophoretically applied dexamethasone for painful pathologic temporomandibular joints.

The effects of iontophoretically applied dexamethasone in a lidocaine vehicle were compared with those of saline placebo in 53 patients with one of three diagnoses of painful temporomandibular joint pathologic conditions: disk displacement with reduction, disk displacement without reduction, and osteoarthritis. Both dexamethasone and the saline placebo produced a significant reduction in pain scores from baseline levels after the first two of three treatments. There were no observed differences, however, in pain report or mandibular range of motion between the dexamethasone and placebo groups. A trend for pain relief was noted in the subgroup that received dexamethasone with a diagnosis of osteoarthritis. Results may reflect varying degrees of inflammation or central nervous system hyperexcitability, or both, in this heterogeneous study sample. Potential confounding variables were lack of knowledge of actual drug penetration, the effects of electric current transmitted by the iontophoresor, and pain reduction caused by cyclic fluctuations in symptoms. These data suggest that iontophoretically applied dexamethasone is no more effective than saline placebo in providing pain relief in patients with temporomandibular joint pain.

Intravascular immunoglobulin crystalloids in monoclonal cryoglubulinemia-associated dermatitis: ultrastructural findings.

A 46-year-old woman developed polyarthritis, purpuric skin rashes, nasal septal perforation and marginal furrowing of corneas in 1980. Monoclonal IgG, kappa cryoglobulinemia was found in the patient's serum. No underlying lymphoproliferative disorder has been found in ten years since her original diagnosis. In 1991, she developed palpable purpura on both lower extremities with subsequent necrosis and ulceration. A skin biopsy revealed fibrin thrombi within capillaries in the papillary dermis, and immunofluorescence studies showed IgG and light chain kappa within the fibrin thrombi. An electron microscopy study showed intravascular immunoglobulin crystalloid structures with a mean diameter of 80.3A degrees (8.03 nm), mixed with fibrin and red blood cells. The exclusive vascular location of these crystalloids may have implication in the pathogenesis of skin lesions.

The large non-collagenous domain (NC-1) of type VII collagen is amino-terminal and chimeric. Homology to cartilage matrix protein, the type III domains of fibronectin and the A domains of von Willebrand factor.

Type VII collagen, the major component of anchoring fibrils, consists of a central collagenous triple-helical segment flanked by non-collagenous domains, NC-1 and NC-2. In this study, we examined the domain organization of human type VII collagen through analysis of deduced amino acid sequences derived from cloned complementary and genomic DNAs, as compared to peptide segments derived from amniotic membrane type VII collagen. The results revealed that the peptide segments derived from the NC-1 domain of type VII collagen could be assigned to the 5' portion of the composite cDNA, indicating that NC-1 resides at the amino terminal end of the molecule. Several sub-domains with homology to adhesive molecules were also identified within NC-1. These protein domains may confer adhesive properties to NC-1, thereby facilitating the binding of type VII collagen to the lamina densa in the cutaneous basement membrane and the anchoring plaques within the dermis.

Syndrome of inappropriate secretion of antidiuretic hormone in a patient with carcinoma of the nasopharynx.

A patient with a primary undifferentiated carcinoma of the nasopharynx manifested the clinical syndrome of inappropriate antidiuretic hormone secretion (SIADH). Immunohistochemical techniques demonstrated the presence of vasopressin, neurophysin, and their precursor (propressophysin) in the cancer cells. In situ hybridization additionally confirmed the expression of propressophysin messenger RNA in these cells. To the knowledge of the authors, this represents not only the first case of SIADH caused by carcinoma of the nasopharynx, but also the first report of pathologic confirmation of the syndrome with the use of both molecular and immunologic probes.

Evaluation of vectorelectrocardiographic analysis of young broiler chickens as a predictive index for susceptibility to ascites syndrome.

Vectorelectrocardiographic (VCG) analysis was performed on 50 male broiler chicks (1 week of age) before placement in a hypobaric chamber. During 5 weeks of exposure to hypobaric hypoxia (simulated altitude of 2900 m), all recorded mortality (38%) was due to the development of ascites syndrome. There was a positive correlation (r = 0.74, P less than 0.01) between the increment in the frontal plane mean resultant vector magnitude divided by body weight (designated as the cardiac index [CI]), with the severity of right ventricular enlargement. Chicks developing ascites syndrome had a greater CI (P less than 0.05) at 1 week of age when compared with chicks that did not develop the syndrome. Therefore, the CI calculated by VCG analysis recognizes right ventricular enlargement, suggesting that a pre-hatch or early post-hatch functional cardiac stress has occurred, predisposing the 1-week-old broiler chick to ascites syndrome. Application of the CI has a physiological index may prove useful in future studies targeted for selection of ascites syndrome resistance in broiler chickens.

Effects of an intervention program for pregnant adolescents: educational outcomes at two years postpartum.

Examined postpartum effects of a school-based intervention program for pregnant adolescents. Interviews were conducted with 102 innercity black, low-income, school-aged mothers who had attended the program, and their academic and medical records were reviewed. For teenagers who had been poor students prior to becoming pregnant, a strong linear effect was found for duration of program attendance: with sufficient time in the program, poorer students became indistinguishable from better students in educational success. Most of the better students were educationally successful at 2 years postpartum, independent of their length of time in the program. For all students, longer durations of postnatal intervention were predictive of lower likelihood of subsequent childbearing. Numerous academic, medical, social, and demographic variables were ruled out as possible confounding factors that might have produced the positive educational outcomes for poorer students. The results suggest that adolescents who appear to have minimal academic promise prior to their pregnancy are nevertheless very responsive to school-based intervention.

Generation and characterization of an antiserum directed against neurohypophyseal prohormones.

Abstract An antiserum to neurohypophyseal prohormones was generated by immunization of rabbits with a synthetic peptide fragment bridging the prohormone cleavage site between the vasopressin (AVP) and human AVP-neurophysin sequences of pro-pressophysin. Polyclonal antibodies directed against this peptide cross-reacted with intact human pro-pressophysin (ED(50) of 260fmol), but not with either of the final products of enzymatic processing, AVP and human AVP-neurophysin. Gel electrophoresis and Western immunoblotting of pituitary or hypothalamic extracts from multiple species including mouse, cow and man identified a protein band of molecular weight consistent with intact pro-pressophysin; in hypothalamic extracts from normally-hydrated rats no protein bands were stained, but in extracts from Brattleboro rats a faint band in the area of pro-oxyphysin was identified. Immunohistochemical studies using the antiserum demonstrated the presence of only very small amounts of immunoreactive prohormone in a few widely scattered cells in the hypothalami of normally-hydrated rats. However, after 5 days of solute loading with 2% NaCl as drinking solution, staining for intact prohormone was prominent in the supraoptic and paraventricular nuclei of the hypothalamus. Combined immunoperoxidase-immunofluorescence labeling for prohormone and either AVP-neurophysin or oxytocin-neurophysin revealed prohormone staining in both types of magnocellular neurons in rat hypothalami. These studies suggest that during states of accelerated synthesis and secretion of neurohypophyseal hormones some accumulation of intact prohormone occurs in both AVP and oxytocin magnocellular neurons.

Expression of neurophysin-related precursor in cell membranes of a small-cell lung carcinoma.

A monoclonal antibody (mAb L6) to a small-cell lung carcinoma surface antigen recognizes a common epitope of vasopressin-neurophysin and oxytocin-neurophysin in hypothalamic nuclei. We now report on the identification of a neurophysin-like precursor in human lung carcinoma (LX-1) cell membrane. mAb L6 immunoaffinity chromatography of solubilized membranes resulted in a single band of approximately 45 kDa. Western blot analysis demonstrated immunoreactivity of this band with mAb L6, anti-vasopressin, and an antibody to the vasopressin precursor, pro-pressophysin. N-terminal sequencing of this band demonstrated a 21-amino acid homology with the N terminus of human pro-pressophysin, and substitution of a Cys33 residue in the tumor antigen with Arg33. Absence of immunoreactivity with the antibodies described above in cytosolic extracts and culture medium suggests nonsecretion of processed or intact pro-pressophysin-like peptide. Northern analysis of LX-1 mRNA with a 30-mer to the C terminus of rat pro-pressophysin resulted in a band of approximately 1000 base pairs, 250 base pairs larger than hypothalamic message. In situ hybridization of LX-1 tumor-bearing nude rat brain with the same probe demonstrated specific hybridization in rat hypothalamus and xenografted tumor. These findings suggest expression of a pro-pressophysin-like protein in this tumor cell line that is preferentially targeted to the cell membrane.