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We have cloned the zebrafish homolog of the receptor tyrosine kinase flk-1 to provide us with a tool to study normal vascular pattern formation in the developing zebrafish embryo and to compare it to mutants in which vascular pattern is perturbed. We find that during normal development the first angioblasts arise laterally in the mesoderm and then migrate medially to form the primordia of the large axial vessels, the dorsal aorta (axial artery) and the axial vein. Lumen formation occurs shortly before onset of circulation at 24 hr postfertilization. We examined the specification of vascular progenitors in the mutant cloche, which fails to form both vessels and blood. cloche lacks all flk-expressing cells and therefore appears to lack angioblasts. The axial vessels of the trunk form in close proximity to notochord and endoderm, which may provide cues for their formation. The dorsal aorta is normally just ventral to the notochord; the axial vein is just below the dorsal aorta and above the endoderm. floating head (flh) and no tail (ntl) mutants both have defects in the formation of notochord. Both are cell-autonomous lesions, flh abolishing notochord and ntl preventing its differentiation. In both mutants the dorsal aorta fails to form, while formation of the axial vein is less affected. Mosaic analysis of mutant embryos shows that transplanted wild-type cells can become notochord in mutant flh embryos. In these mosaic embryos flh cells expressing flk assemble at the midline, beneath the wild-type notochord, and form an aortic primordium. This suggests that signals from the notochord may guide angioblasts in the fashioning of the dorsal aorta. The notochord seems to be less important for the formation of the vein.

To gain a better understanding of the effects on medical schools of ongoing transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) formed the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. Six working groups were appointed to address different issues of importance. This article is a report of the findings and recommendations of the Working Group on Adapting to Resource Constraints. That group was charged to consider how leaders in academic medicine can respond to the challenges of external forces and the anticipated diminishing of resources, and to focus on medical schools and how they can maintain quality while reengineering to effect needed changes. The group members developed their thinking within four categories: size of the academic enterprise; organizational models and their relationships to the clinical enterprise; faculty tenure and compensation; and partnerships with capital-intensive entities. Three recommendations for action, to which the APMOMS unanimously agreed, were made to the AAMC, which has already acted upon them in ways described in the article. The group also developed a series of "ideas for consideration," which represent a range of the members' perspectives. The working group did not seek (and probably could not have obtained) unanimous agreement on many of the issues that these ideas focus upon. The ideas are presented as a series of resolutions designed to stimulate discussion and foster better-informed planning.

A point mutation in PKCalpha was originally discovered in a subpopulation of human pituitary tumors characterized by their invasive phenotype, and the same mutation was also seen in some thyroid neoplasms. To investigate the role of this mutation in tumorigenesis, normal and mutant human PKCalpha cDNAs were overexpressed in Rat6 embryo fibroblasts (R6). When extracts of R6 cells that expressed either the normal or mutant PKCalpha were assayed in the presence of calcium, phosphatidylserine and the phorbol ester TPA, for phosphorylation of either histone IIIS or the EGF-receptor peptide, both extracts gave similar results. However, the subcellular localization of the two proteins differed. Immunohistochemistry studies indicated that after treatment with TPA normal PKCalpha mainly translocated to the plasma membrane, but mutant PKCalpha translocated mainly to the perinuclear region and slightly to the nucleus. Furthermore, the cells that expressed the mutant PKCalpha displayed a decreased requirement for serum when compared to the cells expressing the normal human PKCalpha, and they formed small colonies in soft agar. By contrast, the cells expressing the normal human PKCalpha failed to form colonies in soft-agar. Thus, ectopic expression in rat fibroblasts of this mutant human PKCalpha sequence alters the growth properties of these cells and, when activated, the mutant PKCalpha displays aberrant intracellular translocation. Therefore, this mutation in PKCalpha could contribute to the process of tumor progression in certain human tumors.

Objectives: To determine whether changes in injecting drug use and sexual behavior over a 12-month follow-up are associated with HIV counseling and testing (C and T) of injecting drug users in methadone maintenance treatment programs (MMTP) in Massachusetts and Connecticut., Methods: Clients were invited to participate in a longitudinal study involving five interviews. Data were also obtained by ethnographers and from clinical records. Behavioral outcomes of interest were number of drug injections, sharing of unclean 'works' (injecting equipment), number of unprotected sex partners, and number of unprotected sexual episodes. Data analyses included multiple regression, odds ratios, and quantitative analysis of text-based data., Results: Subjects reported reductions in both injecting drug use and sexual behavior Primary associations with reduced injecting drug use were remaining in the MMTP and attending HIV-positive support groups. A reduction in high-risk sexual behavior was associated with an HIV-positive test result and duration of HIV counseling in the MMTP. Increase in drug injecting use was associated with an HIV-positive test result. Inconsistent condom use was associated with enrollment in the MMTP where condoms were available only upon request and abstinence and monogamy between uninfected partners were promoted., Conclusions: Injecting drug users who self-select to participate in MMTP and HIV C and T, two public health HIV-prevention interventions, reduce their HIV-risk behaviors. Clients should be encouraged to remain in MMTP and HIV-infected clients should attend support groups for HIV-positive persons. MMTP staff should promote a variety of safer sex behaviors and provide condoms without request.

As part of a large-scale mutagenesis screen of the zebrafish genome, we have identified 58 mutations that affect the formation and function of the cardiovascular system. The cardiovascular system is particularly amenable for screening in the transparent zebrafish embryo because the heart and blood vessels are prominent and their function easily examined. We have classified the mutations affecting the heart into those that affect primarily either morphogenesis or function. Nine mutations clearly disrupt the formation of the heart. cloche deletes the endocardium. In cloche mutants, the myocardial layer forms in the absence of the endocardium but is dysmorphic and exhibits a weak contractility. Two loci, miles apart and bonnie and clyde, play a critical role in the fusion of the bilateral tubular primordia. Three mutations lead to an abnormally large heart and one to the formation of a diminutive, dysmorphic heart. We have found no mutation that deletes the myocardial cells altogether, but one, pandora, appears to eliminate the ventricle selectively. Seven mutations interfere with vascular integrity, as indicated by hemorrhage at particular sites. In terms of cardiac function, one large group exhibits a weak beat. In this group, five loci affect both chambers and seven a specific chamber (the atrium or ventricle). For example, the weak atrium mutation exhibits an atrium that becomes silent but has a normally beating ventricle. Seven mutations affect the rhythm of the heart causing, for example, a slow rate, a fibrillating pattern or an apparent block to conduction. In several other mutants, regurgitation of blood flow from ventricle to atrium is the most prominent abnormality, due either to the absence of valves or to poor coordination between the chambers with regard to the timing of contraction. The mutations identified in this screen point to discrete and critical steps in the formation and function of the heart and vasculature.

We have identified mutations that perturb the formation or differentiation of the first embryonic blood cells in the zebrafish embryo. These 'primitive' red blood cells originate in the intermediate cell mass of the trunk, a derivative of the dorsal lateral plate mesoderm. By transfusion of blood between embryos we demonstrate that this cohort of cells provides the embryo with all, or nearly all, of its blood cells until at least day 5 postfertilization. Larval lethal mutations generated by ENU mutagenesis affect different steps in the development of these cells. Some cause defects in precursor generation, others defects in differentiation, and others an increase in cellular photosensitivity.

Hearing impairment in adults is a prevalent chronic condition, associated with psychosocial and quality-of-life handicaps. Recent investigations have demonstrated that individuals with handicapping hearing impairments do indeed benefit from the rehabilitative services offered by audiologists, with the primary intervention being hearing aid provision. My objective here is to review the experimental research, program evaluation data, and case studies documenting the efficacy of hearing aids, with an emphasis on the functional and communicative benefits accruing from hearing aid use. It is hoped that the information contained herein will provide clinicians with outcome data to share with the hearing impaired, toward the goal of encouraging such individuals to take advantage, at least for a trial period, of one of the many technologies available to assist them to function better in their daily lives.

The purpose of the present study was to determine whether peripheral blood lymphocytes (PBL) from primary open angle glaucoma (POAG) patients have reduced 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity as was previously found in POAG-derived cultured trabecular meshwork cells. The availability of PBL from both POAG and control patients makes this a useful system for studying the association of decreased 3 alpha-HSD activity with POAG. PBL were isolated from the venous blood of 17 POAG patients and 22 non-glaucoma controls and assayed for 3 alpha-HSD activity with tritiated 5 beta-dihydrocortisol as a substrate. The mean 3 alpha-HSD activity +/- S.E.M., expressed in comparable units of specific activity, of the POAG derived PBL was 13.8 +/- 1.3 U as compared to 32.8 +/- 2.0 U for control cells. This reduction (> 50%) was statistically significant (P < 0.001). Quantitative immunoblot analysis of PBL indicated that the POAG and control cells, despite their difference in 3 alpha-HSD activity, had nearly identical amounts of 3 alpha-HSD protein. The molecular weight of PBL 3 alpha-HSD from both groups of patients was 38,000, the same as previously reported for human liver. The results of this study show an association of decreased PBL 3 alpha-HSD activity and POAG which was not related to antiglaucoma therapy. The reduced levels of 3 alpha-HSD activity in the readily obtainable PBL may serve as a marker for POAG or those at risk for developing the disease.

Purpose: Because standard methods to determine intraocular lens power are not adequate in eyes that have had radial keratotomy, we undertook this study to evaluate the corneal power derived from computerized videokeratography for use in intraocular lens power calculations., Methods: We examined four eyes of three patients who had radial keratotomy and who underwent phacoemulsification cataract surgery with implantation of a posterior chamber intraocular lens. We used a computerized videokeratography-derived corneal curvature value in the Holladay formula for intraocular lens calculations. We determined the ideal intraocular lens power and the keratometric value that would have led to the ideal intraocular lens power from the postoperative refraction at 6.1 +/- 1.1 months after cataract extraction. The ideal keratometric value was compared with the keratometric values derived from computerized videokeratography, standard keratometry, contact lens overrefraction, and refractions before and after radial keratotomy., Results: The postoperative refraction at approximately six months averaged -0.32 +/- 0.63 diopter (range, -0.88 to +0.75 diopter) different than the aim. The mean power in ring 3, which was the closest keratometric value to the ideal, disclosed only 0.09 +/- 0.73 diopter and -0.10 +/- 0.72 diopter of deviation from the ideal keratometric and intraocular lens powers, respectively. One to two weeks after phacoemulsification cataract surgery with implantation of a posterior chamber intraocular lens, the videokeratographic differential map disclosed steepening at the wound site with variable regression by six months in all patients., Conclusion: Results suggest that, after radial keratotomy, using the keratometric value derived from computerized videokeratography in intraocular lens calculations is more accurate than using keratometric values measured by routine methods.

We are using the zebrafish, Danio rerio, to identify genes that generate and pattern the vertebrate vasculature. We have isolated a recessive mutation, gridlockm145 (grlm145) in which blood flow to the tail is impeded by a localized vascular defect. Using a novel microangiographic method, we show that the blockade is in the anterior trunk, where the paired lateral dorsal aortae normally merge to form the single midline aorta. Arterial-venous shunts and collateral vessels develop in most mutant embryos, bypassing the lesion and reconstituting caudal blood flow. The grl defect resembles coarctation of the aorta, a human congenital cardiovascular malformation of unknown aetiology, in the location of the lesion and its consequences and in the mutants' dependence on collateral vessels for survival.

Endothelial and hematopoietic cells appear synchronously on the extra-embryonic membranes of amniotes in structures known as blood islands. This observation has led to the suggestion that these two ventral lineages share a common progenitor. Recently, we have shown in the zebrafish, Danio rerio, that a single cell in the ventral marginal zone of the early blastula can give rise to both endothelial and blood cells as well as to other mesodermal cells (Stainier, D. Y. R., Lee, R. K. and Fishman, M. C. (1993). Development 119, 31-40; Lee, R. K. K., Stainier, D. Y. R., Weinstein, B. M. and Fishman, M. C. (1994). Development 120, 3361-3366). Here we describe a zebrafish mutation, cloche, that affects both the endothelial and hematopoietic lineages at a very early stage. The endocardium, the endothelial lining of the heart, is missing in mutant embryos. This deletion is selective as evidenced by the presence of other endothelial cells, for example those lining the main vessels of the trunk. Early cardiac morphogenesis proceeds normally even in the absence of the endocardium. The myocardial cells form a tube that is demarcated into chambers, beats rhythmically, but exhibits a reduced contractility. This functional deficit is likely due to the absence of the endocardial cells, although it may be a direct effect of the mutation on the myocardial cells. Cell transplantation studies reveal that the endothelial defect, i.e. the endocardial deletion, is a cell-autonomous lesion, consistent with the possibility that cloche is part of a signal transduction pathway. In addition, the number of blood cells is greatly reduced in cloche mutants and the hematopoietic tissues show no expression of GATA-1 or GATA-2, two key hematopoietic transcription factors that are first expressed during early embryogenesis. These results show that cloche is involved in the genesis and early diversification of the endothelial and blood lineages, possibly by affecting a common progenitor cell population.

To determine whether the simultaneous, partial repeal of needle prescription and drug paraphernalia laws in Connecticut affected purchasing and usage of needles and syringes (syringes) by injecting-drug users (IDUs) and risk of needlestick injuries to police officers, we conducted two serial cross-sectional surveys with IDUs recruited in drug treatment centers, correctional facilities, and health department settings. Reports of needlestick injuries among Hartford police officers were reviewed before and after the new laws. Among IDUs who reported ever sharing a syringe, syringe-sharing decreased after the new laws (52% before vs. 31% after; p = 0.02). Fewer IDUs reported purchasing syringes on the street after the new laws (74% before vs. 28% after; p < 0.0001). More IDUs reported purchasing syringes from a pharmacy after the new laws (19% before vs. 78% after; p < 0.0001). Eight to eleven months after the new laws were enacted, over two thirds (91 of 134) of active IDUs interviewed were aware of both new laws. Needlestick injury rates among Hartford police officers were lower after the new laws (six injuries in 1,007 drug-related arrests for 6-month period before new laws vs. two in 1,032 arrests for 6-month period after new laws). The changes in Connecticut laws were associated with decreases in self-reported syringe-sharing and increases in purchasing by IDUs of sterile syringes from reliable sources, suggesting that the simultaneous repeal of both prescription and paraphernalia laws is an important HIV prevention strategy.

In May 1992, the Connecticut legislature passed new laws aimed at increasing injecting drug users' (IDUs) access to sterile needles and syringes (syringes); as of July 1992, pharmacists were permitted to sell and individuals were permitted to possess up to 10 syringes without medical prescriptions (nonprescription syringes). We evaluated the impact of the new laws by conducting (1) prospective surveillance of syringe sales and policies at selected community pharmacies (pharmacies) and (2) a telephone survey of pharmacy managers' reports of syringe sales and policies at a statewide stratified random sample of pharmacies. Our data provide direct evidence that most, but not all, Connecticut pharmacies sold nonprescription syringes when permitted to do so by the new laws. For example, using the telephone survey data, we estimate that during November, 1993, 83% [95% CI: 77-89%] of all Connecticut pharmacies sold nonprescription syringes and 56,000 [95% CI: 44,000-68,000] nonprescription syringes were sold, during November 1993. Our data provide indirect evidence that IDUs were purchasing nonprescription syringes at pharmacies. For example, in five Hartford pharmacies located in neighborhoods where injection drug use was prevalent, the total number of nonprescription syringes sold per month increased significantly from 460 in July 1992 to 2,482 in June 1993 (p = 0.0001). The data suggest that the new laws increased IDUs' access to sterile syringes in Connecticut.

Dizziness is a common and potentially disabling complaint among older patients. A major consequence of dizziness is falls, which can lead to death or significant functional disability. Dizziness can be separated into four broad categories: vertigo, disequilibrium, near-syncope, and nonspecific. Given its multitude of possible etiologies, dizziness often poses a diagnostic dilemma for the physician. Symptoms can result from a disturbance in any number of balance control systems, including the visual pathways, vestibular apparatus, cardiovascular system, and CNS. In evaluating dizziness, the physician should first obtain a careful medical history and perform a targeted physical examination. Depending upon the organ system involved, an audiologist, otolaryngologist, neurologist, cardiologist, and/or psychiatrist should then be consulted for further assessment and management.

In this era of spiraling health care costs, audiologists are being held accountable for the rehabilitative interventions that they are uniquely qualified to deliver. Accountability data in the rehabilitative arena should address the efficacy of short- and long-term treatment. If a treatment such as a hearing aid is dispensed for the purpose of reducing the communicative and psychosocial handicap associated with hearing loss, efficacy data should demonstrate whether such a goal has been attained. Increased attention has been focused on the value of self-assessment questionnaires as instruments that are predictive of candidacy for hearing aids, intent to purchase hearing aids, and outcomes with a given hearing aid treatment. Case studies demonstrate the advantage of engaging the client in the rehabilitative process through the use of responses to self-assessment questionnaires. It is evident that the client's appraisal of the handicapping effect of a given impairment is associated with treatment efficacy.

Medical student organizations--including the American Medical Student Association (AMSA), the Association of American Medical Colleges's Organization of Student Representatives (AAMC-OSR), and the American Academy of Family Physicians' National Congress of Student Members (AAFP-NCSM)--are responding to the increased need for generalist physicians. Through a variety of initiatives drawing on each organization's unique strengths and capabilities, students are developing curricular and extracurricular initiatives to increase trainees' exposure to and knowledge about generalist medicine. These projects indicate that future physicians are interested in learning about generalist careers and in working with generalist mentors early in their medical training. Students are addressing these needs through community-based experiences, student interest groups, legislative activity, curricular reform, and research in generalist medicine.

We have examined the zebrafish embryo to ascertain the location of endocardial and myocardial progenitors prior to gastrulation, in an attempt to define the earliest stages of cardiac patterning. Currently there is uncertainty as to the spatial and lineage relationship of the progenitors for these two phenotypically distinct cell types that form the two concentric layers of the primitive heart tube. By single-cell injection and tracking, we distinguish a region in the early and midblastula which has the properties of a heart field, in that it defines a zone of cardiac progenitors within which there is a spatial gradient of propensity to generate heart cells, and which regulates, in the sense of adapting to the transplantation of pluripotential cells. This zone extends from the future ventral axis dorsally along the margin, with cardiogenic propensity tapering off laterally and dorsally. Myocardial progenitors are spread throughout this region, but endocardial precursors are restricted to the ventral marginal region. The cardiovascular progeny of the ventral cells include, in addition to endocardium and myocardium, cells in the endothelium and blood.

Hearing loss is prevalent among older adults and is associated with depression, cognitive decline, reduction in functional status, and emotional and social handicaps. Screening by physicians is important, because older adults tend to underestimate the degree of their hearing impairment. The most important predictor of hearing aid candidacy is not the severity of hearing loss but rather the patient's motivation and perception of the handicapping effects of his/her hearing impairment. A variety of hearing aid styles is available. In-the-ear units and in-the-canal hearing aids are the most popular. New digitally programmable aids are often acoustically superior, but they cost more and require considerable training. Assistive listening devices may be used with or without a hearing aid to amplify sound, television, or telephone conversations.

Sexual harassment can be a difficult problem to identify in the workplace. Scenarios are used to help define and identify harassment. Discussion also includes explanations of why sexual harassment is unethical and illegal.

Can we legitimately speak of ethics experts? Recent literature in philosophy and medical ethics addresses this important question but does not offer a satisfactory answer. Part of the problem is the absence of an examination of what it means to be an 'expert' in general. I therefore begin by reviewing my analysis of expertise which appeared earlier in this journal. We speak of two kinds of experts: persons whose expertise is in virtue of what they know ('epistemic' expertise), or what they do ('performative' expertise). Applying this analysis to the domain of ethics, I argue that we may speak of ethical expertise in three epistemic senses: a) expertise in descriptive ethics, b) expertise in metaethics, c) expertise in normative ethics, and in a performative sense: d) expertise in living a good life. I conclude with a brief description of some social roles of ethics experts.

The effectiveness of 3 alpha, 5 beta-tetrahydrocortisol (3 alpha, 5 beta-THF), a metabolite of cortisol, in lowering intraocular pressure (IOP) in rabbits made ocular hypertensive with glucocorticoids suggested its use in patients with Primary Open Angle Glaucoma (POAG). Patients with well-documented POAG were treated with a 1% suspension of 3 alpha, 5 beta-THF administered to one eye four times daily for up to six weeks. Eight out of nine patients experienced an appreciable decrease in IOP in the treated eye (average decrease 4.9 mm Hg). There was no conjunctival irritation, corneal pathology, visual field changes, alteration in liver or renal function tests or blood count during the treatment period. The present study demonstrates that 3 alpha, 5 beta-THF, a naturally occurring steroid metabolite, is effective in lowering IOP in patients with POAG. Antiglucocorticoids may represent a new therapeutic modality for the management of POAG.

A recent survey found that many residents lack adequate audiological services despite a high prevalence of hearing loss. Upgrading hearing health services is one way to dramatically improve quality of life.

Experts play an important role in society, but there has been little investigation about the nature of expertise. I argue that there are two kinds of experts: those whose expertise is a function of what they know (epistemic expertise), or what they do (performative expertise). Epistemic expertise is the capacity to provide strong justifications for a range of propositions in a domain, while performative expertise is the capacity to perform a skill well according to the rules and virtues of a practice. Both epistemic and performative experts may legitimately disagree with one another, and the two senses are conceptually and logically distinct.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) was purified greater than 500-fold from human liver cytosol. The purification was monitored using 5 beta-[3H]dihydrocortisol (5 beta-DHF) as substrate. Electrophoretically homogeneous enzyme was obtained using a procedure that involved ammonium sulfate precipitation and three successive column chromatography steps: DEAE-cellulose, hydroxylapatite and Blue-Sepharose. The enzyme is a monomer since the native molecular weight was found to be 37,000, using a calibrated Sephadex G-75 column, and the denatured subunit molecular weight was determined to be 38,500, by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The enzyme had a pI of 5.6-5.9. The 3-ketosteroids: cortisol, testosterone, progesterone and androstenedione, were not substrates for 3 alpha-HSD indicating that a saturated 4,5 double bond was required for substrate activity. The conformation at the 5 position, however, did not influence substrate activity since 5 alpha- and 5 beta-DHF and 5 alpha-dihydrotestosterone were all reduced at similar rates. The purified enzyme preferred NADPH to NADH as a cofactor and showed a broad peak of activity in the pH range of 6.8-7.4. The apparent Km for 5 beta-DHF was 18 microM. The enzyme was markedly stabilized by 50 mM phosphate buffer containing 10 to 20% glycerol at 4 degrees C. Freezing and thawing of the enzyme resulted in a large loss of activity during early stages of the purification. This is the first report of the purification to homogeneity of 3 alpha-HSD from human tissue.

3 alpha-Hydroxysteroid dehydrogenase is a cytosolic, monomeric, NADPH-dependent oxidoreductase which reduces 3-keto-5-dihydrosteroids to their tetrahydro products. We present here the first partial amino acid sequence data for the human liver enzyme and show these sequences to be identical to the deduced amino acid sequence for human hepatic chlordecone reductase. In addition, these two enzymes exhibit similar substrate and cofactor specificities and immunological reactivity. The results suggest that the natural substrates for chlordecone reductase are 3-keto-5-dihydrosteroids and that these two proteins may be identical.

A new magnetic material with appreciable optical transmission in the visible region at room temperature has been isolated as a gamma-Fe(2)O(3)/polymer nanocomposite. The synthesis is carried out in an ion-exchange resin at 60 degrees C. Magnetization and susceptibility data demonstrate loading-dependent saturation moments as high as 46 electromagnetic units per gram and superparamagnetism for lower loadings where particle sizes are less than 100 angstroms. Optical absorption studies show that the small-particle form of gamma-Fe(2)O(3) is considerably more transparent to visible light than the single-crystal form. The difference in absorption ranges from nearly an order of magnitude in the "red" spectral region to a factor of 3 at 5400 angstroms. The magnetization of the nanocomposite is greater by more than an order of magnitude than those of the strongest room-temperature transparent magnets, FeBO(3) and FeF(3).

The classical analyses of phage morphogenesis provide experimental paradigms for dissecting other assembly pathways. A new set of results, derived from examination of the quantitative controls of tubulin levels and microtubule assembly in Saccharomyces cerevisiae, evokes the 'balance of components' hypothesis. These results show that balanced levels of the tubulin proteins are crucial for microtubule assembly. Imbalances leading to excess beta tubulin have far more deleterious consequences than those leading to excess alpha tubulin, including dramatic cellular toxicity, quantitative depolymerization of cellular microtubules, and self-aggregation of the excess beta tubulin. These and other results suggest that beta tubulin may possess a unique ability to interact with a component of microtubule nucleating sites, and provide a rationale for the universal polarity of nucleated microtubules.

The test-retest reliability of the Hearing Handicap Inventory for Adults (HHIA) was assessed on a sample of 28 hearing-impaired adults. Reliability estimates were obtained to set the stage for using the HHIA as an outcome measure in aural rehabilitation. The test-retest reliability was quite high (r = 0.97) and the standard error of measurement was low for the HHIA and its screening version (HHIA-S). In light of the psychometric adequacy, the HHIA and HHIA-S have potential as indices of hearing aid benefit in hearing-impaired adults.

Glucocorticoids have long been implicated in the etiology of primary open-angle glaucoma (POAG) and cataract. Cortisol metabolites have biologic activity and may affect aqueous humor dynamics. This study was done to determine whether these metabolites are found in human aqueous humor and can be produced by ocular tissues. Radioimmunoassays (RIA) were developed for 5 alpha-dihydrocortisol (5 alpha-DHF) and 5 beta-dihydrocortisol (5 beta-DHF). These assays, as well as a cortisol RIA, were used to quantify these three steroids in 20 surgically derived aqueous humor specimens from patients with and without POAG. The mean concentrations of cortisol and 5 alpha-DHF were 2.5 and 1.3 ng/ml, respectively. In the small group studied, there was no statistically significant difference between the aqueous humor steroid levels in patients with and without POAG. The amount of 5 beta-DHF was at the lower limits of detection of the assay system and could not be uniquivocally shown. Human lenses metabolized cortisol in vitro to 5 alpha-DHF and 3 alpha,5 alpha-tetrahydrocortisol (3 alpha,5 alpha-THF). There was no 5 beta-DHF or cortisone formed. The 5 alpha-DHF and 3 alpha,5 alpha-THF were identified by their positions on thin-layer chromatography, their retention times on high-performance liquid chromatography, and recrystallization with authentic standards to constant specific activity. The data suggest that the lens is the source of 5 alpha-DHF in aqueous humor.

This article provides an ethical and legal analysis of a previously reported case involving an HIV-positive dental student at the Medical College of Georgia. We conclude that the college acted appropriately from an ethical point of view and probably exceeded its legal obligations to accommodate the student.

Self-assessment handicap scales are gaining recognition as objective measures of audiologic intervention, including benefit derived from hearing aid use. A short form of the Hearing Handicap Inventory for the Elderly (HHIE-S) comprised of 10 items (5 emotional and 5 social/situational) was administered to 91 new hearing aid users prior to and 3 weeks following hearing aid provision. A significant reduction in perceived emotional and social/situational effects of hearing impairment was observed following this brief interval of hearing aid use. The magnitude of hearing aid benefit was not affected by pure-tone sensitivity or word recognition ability. Further, a 95 percent confidence interval was established for the HHIE-S (9.3 points) in order to determine a true change in self-perceived handicap and pre- and post-hearing aid fitting for a given subject. Our findings support the use of the HHIE-S as an expedient approach for quantifying hearing aid benefit in a busy clinical practice.

Moral problems in dentistry have both a technical and an evaluative component, but expertise in clinical dentistry does not confer expertise in clarifying evaluative issues. Ethical expertise consists of the capacity either to provide strong justifications for a range of ethical propositions or to perform a skill well according to the moral rules and virtues of a practice. I consider four areas of ethical expertise, the contributions that ethics experts might make to the practice of dentistry, and who the likely candidates to be ethics experts are.

The Hearing Handicap Inventory for the Elderly (HHIE) was modified for use with younger hearing-impaired adults (less than 65 years of age). Similar to the HHIE, the Hearing Handicap Inventory for Adults (HHIA), is a 25-item self-assessment scale composed of two subscales (emotional and social/situational). Replacement questions from the HHIE which form the HHIA focus on the occupational effects of hearing loss. For 67 hearing-impaired adults, the HHIA demonstrated high internal consistency reliability and a low standard error of measurement. Audiometric correlates of the HHIA revealed weak, yet statistically significant relationships with pure-tone sensitivity and supra-threshold word recognition ability. These findings support the use of self-report handicap measures with adults in that audiometric measures alone are insufficient in describing a patient's reaction to their hearing loss.

The metabolism of cortisol by human liver homogenates has been studied. Cortisol delta 4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5 beta-dihydrocortisol were reduced to 3 alpha,5 beta-tetrahydrocortisol, and 5 alpha-dihydrocortisol was reduced to 3 alpha,5 alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase for their substrates (cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol) all ranged from 18 to 27 microM. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol with a Ki ranging from 11 to 32 microM. NADPH was the preferred cofactor for the cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase. No end product inhibition was observed.