The paternal inheritance of the centrosome, the cell's microtubule-organizing center, in humans, and the implications for infertility.

Successful fertilization in humans, achieved when parental chromosomes intermix at first mitosis, requires centrosome restoration and microtubule-mediated motility. Imaging of inseminated human oocytes reveals that the sperm introduces the centrosome. The centrosome then nucleates the new microtubule assembly to form the sperm aster--a step essential for successful fertilization. Oocytes from some infertile patients failed to complete fertilization because of defects in uniting the sperm and egg nuclei, indicating that failure to properly effect the cytoplasmic motions uniting the nuclei results in human infertility. These discoveries have important implications for infertility diagnosis and managing reproduction.

Bright, coherent, ultrafast soft X-ray harmonics spanning the water window from a tabletop light source.

We demonstrate fully phase-matched high harmonic emission spanning the water window spectral region important for nano- and bioimaging and a breadth of materials and molecular dynamics studies. We also generate the broadest bright coherent bandwidth (≈300 eV) to date from any light source, small or large, that is consistent with a single subfemtosecond burst. The harmonic photon flux at 0.5 keV is 10³ higher than demonstrated previously. This work extends bright, spatially coherent, attosecond pulses into the soft x-ray region for the first time.

Spatially coherent, phase matched, high-order harmonic EUV beams at 50 kHz.

By focusing a high repetition rate (50 kHz), compact, femtosecond laser system with low pulse energy (25 muJ) using a tight-focusing geometry, we demonstrate fully phase matched high-order harmonic generation for the first time at very high repetition rates, resulting in EUV light with full spatial coherence. The result is a practical, single-box, coherent source useful for applications in metrology, ultrafast spectroscopy, imaging and microscopy. The soft x-ray flux can be improved further by increasing the laser pulse energy and/or repetition rate.

Physician intention to recommend complete diagnostic evaluation in colorectal cancer screening.

Primary care physicians (PCPs) often do not recommend complete diagnostic evaluation (CDE; i.e., diagnostic colonoscopy or the combination of flexible sigmoidoscopy and barium enema X-ray procedures) for patients with an abnormal screening fecal occult blood test (FOBT+) result. Information is needed to understand why PCPs do not recommend CDE. In the spring of 1994, a telephone survey was carried out using a random sample of 520 PCPs in Pennsylvania or New Jersey who had patients that were targeted for an FOBT screening program. Survey data were obtained from 363 (70%) PCPs on physician practice characteristics; personal background; perceptions concerning FOBT screening, CDE performance, and patient behavior; social influence related to CDE; and intention to recommend CDE for FOBT+ patients. Physician CDE intention scores were distributed as follows: low (22%), moderate (51%), and high (27%). Multivariate analyses demonstrate that physician board certification status, time in practice, belief in CDE efficacy, and belief that CDE is standard practice were positively associated with CDE intention, whereas concern about CDE-related costs was negatively associated with CDE intention. Among physicians in larger practices, perceived FOBT screening efficacy was negatively associated with CDE intention, and belief in the benefit of CDE was positively associated with outcome. There is substantial variability in CDE intention among PCPs. Physician perceptions about FOBT screening and follow-up are associated with CDE intention, are likely to influence CDE performance, and may be amenable to educational intervention. Additional research is needed to evaluate the impact of educational interventions on CDE intention and performance.

Written case simulations: do they predict physicians' behavior?

Written case simulations are often used to investigate physicians' decision making and clinical competence. Their use rests on the assumption that physicians' responses to written simulations closely agree with their responses to actual clinical encounters, yet this assumption of criterion validity has received little attention. To determine the ability of written case simulations to predict actual clinical behavior, we applied methodologic criteria to published articles that used written simulations. Only 11 (15%) of 74 articles included an assessment of the criterion validity of their written case simulations. Only 2 of those 11 studies were designed and executed in such a way that criterion validity could be fully interpreted. No clear consensus emerged from an examination on the 11 studies on how well responses to written case simulations perform as proxy measures of actual behavior. More work is needed before assuming that written case simulations measure actual behavior.

A specific radioimmunoassay for evaluation of serum antibodies to zona pellucida antigens.

A radioimmunoassay procedure has been developed for detecting antibodies to porcine zonae pellucidae antigens using Staphylococcus aureus Protein A cells (Pansorbin) as the immunoadsorbent. This method offers a rapid and reproducible procedure for detecting specific antibodies to zona antigens. The zona antigens detected by antibodies in this assay were found not to cross-react with antigens in 11 other tissues. Immune serum produced against a variety of other antigens, including protein hormones, steroid hormones, porcine serum and red blood cells, did not bind to any zonae components in this assay. This assay is compared with other methods which have been used to detect antibodies to zona antigens and has been found to be more specific than immunofluorescence methods and more sensitive than either immunofluorescence or immunoelectrophoresis methods.

The use of a mobile laboratory cart in a successful university-based human in vitro fertilization program.

The use of a mobile laboratory unit for a successful university-based IVF program is described. The construction of the cart is described in detail. The laboratory cart can be pushed to any site where ovum aspiration is carried out (either operating theater or ultrasound facilities). Aspirated oocytes can be transferred immediately to culture media and transported back to the gamete handling laboratory for embryo culture. Developing embryos can also be transported to any location in the hospital for transfer. This system is inexpensive and has eliminated the need to duplicate specialized equipment for a gamete handling laboratory adjacent to the operating room. New construction charges have been eliminated; and as new egg retrieval methodologies are developed, the use of the mobile laboratory cart will provide our IVF program with maximum flexibility in changing sites within the hospital. Used in conjunction with an extensive quality control program, this modification has not interfered with oocyte fertilizability or with the overall pregnancy rate in the University of Wisconsin IVF program.

Comparison of the hamster sperm motility assay to the mouse one-cell and two-cell embryo bioassays as quality control tests for in vitro fertilization.

The hamster sperm motility assay, mouse one-cell embryo, and mouse two-cell embryo bioassays were used to test modified Tyrode's solution and modified Ham's F-10 (Gibco, Grand Island, NY) medium prepared in tap water versus ultrapure water. Factors influencing the ability of each assay to discriminate water quality were evaluated to characterize these assays for quality control use in the in vitro fertilization laboratory. The hamster sperm motility assay reproducibly detected differences in treatment without significant interanimal, interanalyst, or interassay variation. Interanalyst and interanimal variation significantly affected the ability to detect treatment differences using the mouse bioassays. Sample sizes needed to predict clinically significant treatment effects were calculated using varying assay conditions. Ham's F-10 medium can be tested with the hamster sperm motility assay.

Evaluating change in medical school curricula: how did we know where we were going?

This chapter compares and contrasts the primary outcomes and methods used to evaluate the curricular changes at the eight schools participating in The Robert Wood Johnson Foundation "Preparing Physicians for the Future: Program in Medical Education." Each school evaluated its own program. The eight evaluators formed an ad hoc group to share information, but the schools did not use a common evaluation system. Although the evaluations were done without common standards, many of the measures were similar. The schools used such quantitative methods as measuring students' performances and their choices of specialties, as well as such qualitative methods as asking students to evaluate their courses and to participate in focus groups. The authors describe the ways in which evaluative data were collected and how evaluation drove curricular change. The authors conclude that program evaluation can sustain schools through the turbulence of curricular change, and that qualitative data and communicating the results of evaluations with faculty and students are essential to successful reform.

Ethanol inhibits the naloxone-induced release of luteinizing hormone-releasing hormone from the hypothalamus of the male rat.

It has been inferred that ethanol suppresses the secretion of luteinizing hormone (LH) in the male by depressing the release of LH-releasing hormone (LH-RH) from the hypothalamus. Direct support for this inference has been difficult to obtain, however, because of significant technical difficulties in measuring LH-RH release under in vivo conditions. To circumvent these problems, we made use of the opiate antagonist naloxone, as a neuroendocrine probe, to elicit the release of LH-RH under in vivo conditions. We found that ethanol was a potent suppressor of the increase in serum LH levels evoked by naloxone at extremely low blood ethanol concentrations ( less than 60 mg/dl). Furthermore, we observed that the antagonism between ethanol and naloxone appeared to be competitive in nature since a fixed dose of ethanol (1 g/kg, blood ethanol concentration 60 mg/dl) shifted the naloxone dose-response curve significantly to the right and high doses of the antagonist overcame ethanol's effects. Finally, we found that the interaction between ethanol and naloxone took place at the level of the hypothalamus. Our results, therefore, seem to provide the first in vivo evidence supporting the widely-held hypothesis that ethanol reduces serum LH levels by depressing the hypothalamically-medicated release of LH-RH. The mechanisms underlying ethanol's depression of naloxone-induced increases in the release of LH-RH are not fully understood at this time, but one prominent possibility is that ethanol enhances the synthesis or release of endogenous opioids which in turn override naloxone's effects.

The MacArthur Foundation Depression Education Program for Primary Care Physicians: background and rationale.

In order to improve the assessment and management of depression in general medical care, the John D. and Catherine T. MacArthur Foundation supported the development, evaluation, and dissemination of an eight-hour depression education program (DEP) for primary care physicians. This publication includes a paper describing the background and educational rationale for the program structure, the complete participant's workbook, and a facilitator's guide for teaching the program. Given in two separate four-hour workshops by a psychiatrist and a primary care physician, DEP is delivered to small groups of learners (about 12) using an interactive adult learning model and multiple teaching techniques including targeted yet flexible objectives, two lectures, videotape demonstration and discussion, role-play exercises, a focused monograph on depression, an interview checklist, structured assessment and outcomes tools, clinical case studies, and audiotape review of actual patient interviews. DEP has been shown in a prospective randomized trial to improve physicians' interview-ing skills as well as simulated-patient satisfaction scores. Over 150 PCPs in four states have taken DEP in more than 30 separate programs given by 24 trained facilitators. Participants, despite a wide diversity of background knowledge and skills, have uniformly reported remarkably positive learner satisfaction with all dimensions of the Program.

Interventions to improve physicians' well-being and patient care: a commentary.

Dr. Firth-Cozens begins her paper by reviewing a broad range of research related to physicians' stress, depression, and alcoholism (Firth-Cozens, 2001, Social Science and Medicine, 52, 215-222). She then argues that these psychological problems have a negative impact on patient care and describes the possible causes of these problems. Finally, she proposes a system of organizational and individual interventions to address these problems. Before accepting her conclusions and proposed system of interventions, an important issue should be considered. Is physicians' well-being an important goal in and of itself, or do we need strong evidence that physician stress, depression, and alcoholism lead to poor patient care and outcomes?

The association of physician attitudes about uncertainty and risk taking with resource use in a Medicare HMO.

PURPOSE: To explore the association between the attitudes of primary care physicians toward uncertainty and risk taking, as measured by a validated survey, with resource use in a Medicare HMO. DESIGN: All primary-care internists (n=20) in a large, multi-specialty clinic were surveyed to measure their attitudes about uncertainty and risk taking using three previously developed scales. Results were linked with administrative data for 792 consecutive patients in a recently created Medicare HMO. The patients' index visits occurred between April 1, 1995, and November 30, 1995. ANALYSIS: Charges stemming from several claim types (primary care and subspecialty physician, laboratory, radiology, and ambulatory procedures) in the 30 days following the index visit were summed. The physician scales were dichotomized at the median to seek unadjusted associations with charges. Generalized estimation equations were used to account for the correlation of charges resulting from patients' being nested within physicians and adjusted for physician characteristics (age, sex, years in practice) and patient characteristics (age, sex, comorbidity). MAIN RESULTS: The physician response rate was 90%. Most physicians (90%) were male. The mean age of the patients was 74 years, and 69% were female. The mean cost (+/-SD) per patient was $621.61+/-1,737.31. From the unadjusted analysis, high "anxiety due to uncertainty" was associated with higher patient charges ($197.85 vs $158.21, p=0.01). From the multivariable analysis, each standard deviation increase in "anxiety due to uncertainty" (3.5 points) corresponded to a 17% increase in mean charges (p < 0.01) and each similar increase in "reluctance to disclose uncertainty to patients" (1.92 points) corresponded to a 12% increase (p=0.03). However, increasing "reluctance to disclose mistakes to physicians" and increasing physician risk-taking propensity were associated with decreased total charges [-10% per standard deviation (1.34 points), p=0.02, and -8% per standard deviation (3.26 points), p=0.02, respectively]. CONCLUSION: Physician attitudes toward uncertainty were significantly associated with patient charges. Further investigation may improve prediction of patient-care charges, offer insight into the medical decision-making process, and perhaps clarify the relationship between cost, uncertainty, and quality of care.

Improving the recognition and management of depression: is there a role for physician education?

BACKGROUND: Many patients who visit primary care physicians suffer from depression, but physicians may miss the diagnosis or undertreat these patients. Improving physicians' communication skills pertaining to diagnosing and managing depression may lead to better outcomes. METHODS: We performed a randomized controlled trial involving 49 primary care physicians to determine the effect of the Depression Education Program on their knowledge of depression and their behavior toward depressed patients. After randomization, physicians in the intervention group completed the Depression Education Program, which consists of 2 4-hour interactive workshops that combine lectures, discussion, audiotape review, and role-playing. Between sessions, physicians audiotaped an interview with one of their patients. Two to 6 weeks following the intervention program, physicians completed a knowledge test and received office visits from 2 unannounced people acting as standardized patients with major depression. These "patients" completed a checklist and scales. Logistic and linear regression were used to control for sex, specialty, and suspicion that the patient was a standardized patient. RESULTS: For both standardized patients, more intervention physicians than control physicians asked about stresses at home, and they also scored higher on the Participatory Decision-Making scale. During the office visits of one of the standardized patients, more intervention physicians asked about at least 5 criteria for major depression (82% and 38%, P = .006), discussed the possibility of depression (96% and 65%, P = .049), scheduled a return visit within 2 weeks (67% and 33%, P = .004), and scored higher than control physicians on the Patient Satisfaction scale (40.3 and 35.5, P = .014). CONCLUSIONS: The Depression Education Program changed physicians' behavior and may be an important component in the efforts to improve the care of depressed patients.

Legislative efforts affecting the reproductive biology laboratory.

Legislative initiatives recently enacted in the USA will affect daily operations in the reproductive biology laboratory. These regulations affect laboratory safety, staffing, quality assurance, and record keeping. They mandate laboratory accreditation including certification, inspection, and proficiency testing. Laboratory standards of practice and costs of operation may be increased with mandatory compliance.

The role of the medical librarian in the use of a MeSH-indexed computerized test question bank.

The University of Missouri-Kansas City School of Medicine utilizes a full-time medical librarian in a non-conventional position as indexer-bibliographer for its computerized Item Library. The responsibilities of the librarian are to edit, index, and reference items for inclusion in the data base; maintain the currency of the Item Library; search the collection; and construct examinations, including a comprehensive quarterly examination, required of all students in this six-year school. Early research in computer-assisted test construction suggested the need for a comprehensive, standard approach to the classification of item content. A professional medical librarian using MeSH descriptors satisfies this need. In existence since 1973, the Item Library is now composed of over 12,000 multiple-choice questions in the basic sciences and clinical medicine. All questions are indexed with up to fifteen MeSH descriptors and referenced to literature sources. The items may be retrieved using any single MeSH term or combination of terms. The collection is available at all times on terminals, and students are encouraged to make use of it for self study. Selected examinations are made available to other institutions by arrangement. Experience has proven both the value of this resource for self study and student evaluation, and the necessity of establishing and continuing the librarian's role.

What do applicants look for when selecting internal medicine residency programs? A comparison of rating scale and open-ended responses.

OBJECTIVE: To develop reliable scale measures of factors most important to applicants when they select internal medicine residencies and to assess their validity by comparing scores from these measures with responses to open-ended questions. DESIGN: All 353 applicants ranked by the University of North Carolina at Chapel Hill (UNC-CH) for the 1988 National Residency Match Program received a questionnaire after submitting their match lists. First, they listed the three most important factors considered in ranking residency programs and starred the single most important factor out of the three. Then, they rated 41 items on a five-point Likert scale ranging from 1 (not important) to 5 (extremely important). SETTING: Categorical internal medicine residency program at an academic medical center. MEASUREMENTS AND MAIN RESULTS: 315 (88%) applicants responded to the survey. Three reliable scales, Interpersonal Issues (7 items, alpha = 0.78), Reputation (5 items, alpha = 0.77), and Work Issues (11 items, alpha = 0.89), were developed using exploratory factor analysis of applicants' responses to the 41 items. Applicants felt interpersonal issues were very important (mean score = 4.2 +/- 0.5), academic reputation was important (3.3 +/- 0.8), and work issues were less important (2.8 +/- 0.7). The differences between these scores were significant (F = 3.76, p < 0.05). The ratings for the top five items not in these scales also indicated that education and location were very important. These results were corroborated by applicants' responses to the open-ended request to list the three most important factors in ranking residencies. CONCLUSION: These findings suggest that work issues are important, but greater emphasis is placed on interpersonal issues, education, location, and a program's reputation when applicants select residency programs. Furthermore, this study provides evidence supporting the reliability and validity of the three scales.

Quality control in the in vitro fertilization laboratory: comparison of bioassay systems for water quality.

Three mouse embryo bioassays [mouse one-cell and two-cell embryos and in vitro fertilization (IVF)] were tested for their ability to discriminate between three sources of water for medium preparation: tap water, high-performance liquid chromatography (HPLC)-grade water, and Milli-Q purified water. No differences could be detected using these assays. The lack of sensitivity of the mouse bioassays could not be attributed to the protein source or medium type. The hamster sperm motility assay (HSMA) permitted quantitative discrimination between water sources (Milli-Q greater than HPLC greater than tap). Media prepared for use in human IVF using water that exceeded minimal HSMA quality standards resulted in pregnancy rates that were greater than those attained with a lot of HPLC water that did not meet these standards. The HSMA can serve as a basis for a quality-control program in the human IVF laboratory.