Zinc as a non-hormonal contraceptive: an alternative to the copper intrauterine device (IUD).

In brief: The many side effects of current contraceptives leave a large proportion of women without adequate protection. This study shows that zinc, a highly physiologically compatible metal, provides effective long-acting reversible contraception in rats, without requiring the use of hormones. Abstract: Long-acting and reversible contraceptives (LARC) are the most widely used form of female contraception worldwide; however, they have significant side effects that often result in early removal. Most LARCs are hormonal, but the use of exogenous hormones is not suitable for all women and causes side effects in many others. The copper IUD (CuIUD) is the only non-hormonal LARC, but a large proportion of users suffer severe side effects. This study proposes the use of zinc as a suitable alternative to the CuIUD. A rat intrauterine device (IUD) model was established to test the efficacy of a zinc IUD (ZnIUD) against a CuIUD. The IUD was surgically implanted into one uterine horn while the other remained untreated. Both the ZnIUD and CuIUD resulted in zero implantation sites which were significantly fewer compared to non-treated horns. Histological assessment revealed damage and inflammation in the endometrium of CuIUD-treated horns but only minor epithelial changes in ZnIUD-treated horns. This suggests ZnIUDs may not share the side effect profile of the CuIUD. To test the long-term efficacy of the ZnIUD, rats had a ZnIUD surgically implanted into both horns and cohoused with males for 3 months. These rats mated regularly but did not get pregnant, confirming long-term effectiveness. Reversibility of the ZnIUD was also established, as removal of the ZnIUD after 3 months resulted in no significant difference in the number of implantation sites between treated and untreated horns. This study demonstrated the contraceptive efficacy of zinc and its potential as a LARC.

Integrating behavioral assessment in instructional design for competency-based medical education.

As institutions continuously strive to align with the standards set forth within competency-based medical education, there is an increased need to produce evidence of learner achievement in the form of observable behaviors. However, the complexity of healthcare education and clinical environments make it challenging to generate valid and reliable behavioral assessments. In this article, we utilize our interdisciplinary knowledge from the perspectives of experts in medical education, assessment, and academic administration to provide tips to successfully incorporate behavioral assessments into instructional designs. These include tips for identifying the best assessment methods fit for purpose, guiding instructors in establishing boundaries of assessment, managing instructors, selecting raters, generating behavioral assessment guides, training raters, ensuring logistics support assessment strategies, and fostering capacity for iteration. These can be used by institutions to improve planning and implementation for longitudinal behavioral assessments.

Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model.

Oxazolidinone antibiotics have activity against Mycobacterium tuberculosis. Linezolid, the only marketed oxazolidinone, has been used off-label in combination regimens to treat multidrug-resistant tuberculosis, but its precise contribution to the efficacy of such combinations is unclear. Another oxazolidinone, PNU-100480, has been demonstrated to have more potent activity in vitro and in a murine model of tuberculosis. In this study, we compared the pharmacokinetics and the antituberculosis activities of these two oxazolidinones over a range of doses and found that linezolid has limited activity at clinically relevant doses in the murine model compared to that of PNU-100480, which has potent bactericidal activity, even at lower drug exposures. These findings were unexpected, given the similar in vitro activities of PNU-100480, its major metabolites, and linezolid. Moreover, the incorporation of PNU-100480 dramatically improved the bactericidal activities of regimens containing current first-line antituberculosis drugs and moxifloxacin. For example, the addition of PNU-100480 (100 mg/kg of body weight/day) to the standard daily regimen of rifampin (rifampicin), isoniazid, and pyrazinamide resulted in an additional 2.0-log(10)-unit reduction in lung CFU counts during the first 2 months of treatment. The combination of PNU-100480, moxifloxacin, and pyrazinamide, which does not contain either rifampin or isoniazid, was also more active than rifampin, isoniazid, and pyrazinamide. These results suggest that PNU-100480 may have the potential to significantly shorten the duration of therapy for drug-susceptible as well as multidrug-resistant tuberculosis.

Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid injections for chronic pain.

We report a case of epidural haematoma following a steroid injection into the cervical epidural space. The complication occurred on the seventh such injection over a 2 year period for chronic spinal pain. Surgical decompression over the seventh cervical and the upper 3 thoracic vertebrae was required to alleviate the symptoms of paralysis and anaesthesia. The patient subsequently required skin grafting to the surgical site and two trans-urethral resections of the prostate gland during his 6 week hospital admission. He made a full recovery.

A computer system for clinical microbiology.

The Department of Clinical Microbiology at St Thomas' Hospital has been producing bacteriological reports on a computer for more than three years and is now producing some 2300 reports per week. The system is operated entirely by laboratory staff without special training, and involves the use of optical mark reader (OMR) forms as worksheets, automatic validation and release of most reports, the use of local terminals, and scrutiny of reports by pathologists using a visual display unit. The OMR worksheet records not only the final result but also most of the tests and observations made on the samples; it is the only working document used by technicians. One specialist clinic submits its laboratory requests on an OMR form, which is subsequently used to record the results. The reports are printed and also filed in the computer to produce analyses for hospital, laboratory, and clinical management.

Self-administration of D-Ala2-Met-enkephalinamide at hypothalamic self-stimulation sites.

The relationship between the action of enkephalin and the reinforcing action of electrical stimulation in the posterior lateral hypothalamus of the rat was studied with the self-administration approach. Adult male albino rats implanted with a combination cannula and stimulation electrode in hypothalamus were pretested for the reinforcing effects of electrical stimulation. Only subjects that self-stimulated at moderate to high rates were given self-administration tests. The chamber for the self-administration tests was fitted with one lever at each end of a rectangular plexiglass box. In a session, one lever was 'active', the other not. The active lever, if depressed, yielded 20 nl of CSF (artificial cerebrospinal fluid), or CSF in which one of the test substances was dissolved. Each subject was tested repeatedly for the reinforcing effects first of a control solution (CSF), then of D-Ala2-Met-enkephalin (DALA), a long-acting synthetic analogue of enkephalin, then of morphine, and then of opioids mixed with naltrexone or naloxone. Following these tests, the subjects were once again given self-stimulation tests to ascertain the functional integrity of the 'reward' system after the repeated self-administration tests. The results demonstrate that when the test solution was DALA instead of CSF the subjects pressed the active lever at a higher rate than for CSF, and they exhausted the supply more rapidly than for CSF. The rate on the active lever was also significantly higher than on the inactive lever. DALA at 1 and 5 microgram/microliter concentrations proved more reinforcing than at 0.1 microgram/microliter. Naltrexone did not block the reinforcing effect of DALA, whereas naloxone blocked DALA-induced reinforcement. These data extend the report of ventricular methionine-enkephalin positive reinforcement to DALA injected directly into the lateral hypothalamus.

Signal onset and task variables in auditory evoked potentials.

Two auditory evoked potential studies were run to determine the effects of stimulus rise times on amplitude of N1-P2 onset and offset potentials. Onset potentials were reduced with increased onset durations. No consistent relationship was found in N1-P2 offset potentials as a function of stimulus rise time. The effects of listening tasks and stimulus duration were also examined.

Crafting effective tobacco counteradvertisements: lessons from a failed campaign directed at teenagers.

Focus group research conducted by the Centers for Disease Control and Prevention's Office on Smoking and Health suggested that the desire of teenagers to gain control over their lives would make them responsive to a counteradvertising strategy aimed at exposing the predatory marketing techniques of the tobacco industry. On the basis of this strategy, the office developed draft print advertisements and a rough TV commercial featuring such theme lines as "You get an image. They get an addict." In those ads, "they" referred to cigarette companies. Subsequent testing of the campaign materials, however, indicated that the subtle, sophisticated execution of this concept of manipulation by the industry did not communicate clearly and effectively to an audience of young teens. In fact, 38 percent of those who viewed the rough TV spot believed that the main message promoted smoking. These negative test findings underscore the critical need for ongoing audience research throughout the creative process to ensure that campaign planners stay "in tune" with their consumers.

The influence of gender on incidence and outcome of patients with bladder cancer in Harlem.

Although African Americans have a lower incidence of bladder cancer, overall survival is worse compared with American whites. This phenomenon has been attributed to the higher incidence of advanced disease at diagnosis and poor follow-up. Fifty-nine cases of bladder cancer were identified through the Tumor Registry at Harlem Hospital and reviewed retrospectively. Complete data were obtained for 42 patients. The primary independent variables of interest were primary care utilization, comorbid conditions, social variables, and gender. The outcome variables of interest were stage of disease at presentation and death. The median age at diagnosis in this group was 73 years compared with 68 for bladder cancer patients in the United States. There was no statistically significant correlation between primary care utilization or severity of comorbidities, and clinical stage at presentation. Similarly, these variables did not influence the occurrence of death as an outcome. For women, the mean age at diagnosis was 74.2 years compared with 67.3 in men (P = .112). The ratio of male-to-female cases in this group was 1.3 to 1 compared with 2.7 to 1 for the general US population. Women had lower odds of being diagnosed with superficial disease (OR = 0.24, 95% CI, 0.06-0.94) and a higher incidence of a cancer-specific death (OR = 2.7, 95% CI). The poor outcome and high incidence of bladder cancer cases among women in Harlem is intriguing. Overall, primary care utilization, comorbidities, and other social factors did not seem to influence stage or death as an outcome. The significantly elevated prevalence of smoking among women in this community, increased age at diagnosis, and possible environmental influences may play a role.

Screening for postpartum depression. An antepartum questionnaire.

OBJECTIVE: To develop and evaluate a questionnaire used antepartum to screen for postpartum depression. STUDY DESIGN: Demographic and clinical data, based on previously identified variables, were obtained from 106 second-trimester gravidas (sample I) by interview, self-administered questionnaire and medical record review. The Beck Depression Inventory (BDI) was administered at 1, 6 and 12 weeks postpartum (PP). Statistical analysis, including stepwise linear regression with maximum r-squared improvement, identified a subset of the 24 most predictive variables. This antepartum questionnaire (APQ) was validated retrospectively in the original sample and prospectively in a second group of 99 women (sample II). RESULTS: In both sample populations the APQ had acceptable sensitivity (80-82%) and specificity (78-82%). The incidence of postpartum depressive symptoms (PPDS) rose from 10% to 17% by six weeks without an appreciable decline at 12 weeks (15%). The percentage of women showing more than mild depressive symptoms increased with PP time from 30% at 1 week to 47% at 12. CONCLUSION: The APQ is now available for screening and evaluating early therapeutic intervention in PPDS.

Peripheral blood mononuclear cell-derived erythroid progenitors and erythroblasts are decreased in burn patients.

Patients with large burns suffer from anemia of critical illness. Administration of exogenous erythropoietin is ineffective, and transfusion remains the only effective treatment. We have previously shown that erythroid precursors are decreased 1 week after burn in an animal model. Therefore, we have used a two-phase liquid culture system to quantify peripheral blood mononuclear cell (PBMC) compartment-derived erythroid progenitors (EPs) in burn patients. Institutional review board approval and informed consent were obtained. Blood samples were collected at 1 to 30 days after burn, with a mean TBSA of 37.7 ± 15.8% (n = 10; 90% men; age, 46.0 ± 18 years). Four healthy volunteers served as controls. PBMCs were isolated by Ficoll-Hypaque density-gradient centrifugation and were placed in serum-free expansion medium containing cyclosporine A (1 ng/ml), granulocyte macrophage colony-stimulating factor (20 ng/ml), stem cell factor (30 ng/ml), and interleukin-3 (5 ng/ml; phase I). On day 7, cells were reseeded in serum-free expansion medium containing erythropoietin (1 U/ml), holotransferrin (0.3 mg/ml), and stem cell factor (10 ng/ml; phase II). Aliquots from the phase II culture system on day 6 were incubated with anti-CD71, CD235a, and CD36. EPs (CD71 CD36) and erythroblast subpopulations (colony-forming unit erythroids, Proerythroblasts, and intermediate erythroblasts) were identified based on the expressions of CD71 and CD235a by flow cytometry, calculated per million expanded cells, and expressed as a percentage of controls. Total EPs were significantly decreased by days 28 to 31 after the burn (19%; P < .05). Among the erythroblast subpopulations, colony-forming unit erythroids (11%; P < .004) and proerythroblasts (24%; P < .05), were decreased significantly by days 28 to 31 after the burn. PBMCs of burn patients can be used to study impaired erythropoiesis and anemia of critical illness.

Foreign medical graduates and their impact on the quality of medical care in the United States.

The literature on the level of quality of care delivered by foreign medical graduates (FMGs) has been reviewed in order to derive policy recommendations concerning their use in the United States. This review revealed a paucity in information on direct measures of the level of quality of care provided by FMGs. Differences between U.S. medical graduates (USMGs) and FMGs, especially with regard to the less than fully licensed FMGs and those FMGs at the start of graduate training, were found on examining proxy measures of quality, such as achievement of standard professional credentials or the quality of clinical training. Given this lack of evidence as to differences in performance between FMGs and USMGs, it is difficult to formulate recommendations, but four are advanced. These include (1) acknowledgment of the crucial significance of their heterogeneity, especially in regard to the quality of care provided, (2) assurance of the principle that peer-review activities are administered even-handedly to FMGs and USMGs alike, (3) improvement of the medical care capabilities of the less able provider, and (4) performance of quality of care studies, in both hospital and office practice settings, which compare FMGs with USMGs, not to ideal standards.

Implications of differential impacts of care-giving for future research on Alzheimer care.

As the primary caregivers for the millions afflicted with Alzheimer's disease, family members have been the focus of research for the past two decades. Differences in care patterns and deleterious effects of care provision have been clearly established. However, similar demands and hardships associated with care-giving result in different consequences for different families. A greater understanding of the care-giving context and its determinants will enhance knowledge of the differential impacts of care-giving. The most critical determinant of care-giving context is the role relationship between the caregiver and the care recipient. Future research must address role relationship as the primary determinant of what care is provided by whom, and in what manner. This will enhance the understanding of specific caregiver outcomes and lead to optimal targeting of interventions. Future research must also focus on the interface between the family and other social institutions. Evidence calls into question the equity, quality, and capacity of the current system of care, which assumes that family care is best. It will be important for future studies to explore alternate options for long-term care policy. Families and patients will also benefit from studies that assess strategies to ensure an adequate labor pool of qualified formal caregivers.

Quality of health care for the disadvantaged.

Literature review points out that: (a) differentials in health status between the disadvantaged and the nondisadvantaged persist, often to a large degree; (b) differentials in the overall amount of care received are less striking now than heretofore, but standardization by level of need demonstrates measurable discrepancies in health services provided to the disadvantaged compared with the nondisadvantaged; (c) the quality of health care for the disadvantaged is not strikingly poorer than care for the nondisadvantaged, but, in view of demonstrable shortcomings in the quality of health care in general, this is not viewed as a positive statement; and (d) attempts to improve quality of care for the disadvantaged have not had the hoped-for impact. Four new avenues are suggested for possible further research; increased patient responsibility, increased consumer knowledge, financial accountability, and quality assurance activities. Because of the likelihood of only marginal changes in health status, rigorous evaluation of any experimental program is emphasized. During the last decade, many attempts have been made by private and governmental bodies to improve the health of the American people. In general, these efforts have focused on improving the health of members of disadvantaged groups and have included such diverse activities as building OEO health centers, developing maternal and infant care programs, and financing care for the elderly. During the last few years, a different movement, concerned with assuring high quality care for all people, has produced efforts such as quality assurance activities in health maintenance organizations, the Professional Standards Review Organization program, and the medical care evaluation program of the Joint Commission on the Accreditation of Hospitals. Consideration of these two issues, i.e., improving the health of disadvantaged groups and improving the quality of care for all people, has led to two policy-relevant questions: "Can the health of disadvantaged groups be substantially improved by assuring that a high level quality of care is delivered to them?" and "Can the quality of care delivered to disadvantaged groups be improved?" The purpose of this paper is to review some available data pertinent to both these issues and to suggest some ideas for future research.

Effect of medical care review on the use of injections: a study of the New Mexico Experimental Medical Care Review Organization.

Evaluation of peer review activities in the New Mexico Medicaid program (1971 to 1973) showed that it can affect aspects of quality, that is, the appropriateness of the use of injections as judged by medical criteria. Use of injections, nearly 50% of which were antibiotics, declined by more than 60%, from 41 to 16 per 100 ambulatory visits. Still, at the end of the study, 40% of the injections given were considered medically unnecessary. Analyses showed that [1] groups used injections more appropriately; [2] for solo physicians, being board-certified, being a doctor of medicine, and being a pediatrician were all associated with more proper use of injections; [3] 6% of the physicians gave 40% of the medically unnecessary injections, but even their behavior changed dramatically for the better as a result of the peer review system.

The oesophageal detector device. A prospective trial on 100 patients.

Misplacement of a tracheal tube in the oesophagus remains a significant cause of mortality and morbidity in anaesthesia, despite decades of effort aimed at prevention, or perhaps more importantly, detection, of such an event. We have evaluated a cheap, simple and quick device which relies mainly on the reflation or otherwise of an Ellick's evacuator applied to the supposed 'tracheal' tube. Identical tracheal tubes were passed into the trachea and oesophagus of 100 patients; the left and right position in the mouth was chosen at random. The test was conducted by a second anaesthetist, not present at intubation, and unaware of which tube was in the trachea. There were no false positive results and the correct deduction of which was the tracheal tube was reached in 100 tests using this device. Its use is recommended for widespread evaluation as a valuable adjunct to existing methods of detecting misplacement.

Unexpected, difficult laryngoscopy: a prospective survey in routine general surgery.

A prospective study of unexpected, difficult laryngoscopy was carried out. During a 7-month period, all general surgery patients in whom the trachea was intubated were assessed; only those with obvious neck pathology were excluded. Ease or difficulty of laryngoscopy was graded by a standard method. There were no grade 4 cases and no failed intubations in a total of 1387 cases. There were significant differences in the results recorded by different individuals; this did not correlate with seniority or with the type of surgery. Four factors have been identified which help to explain these discrepancies. These findings are analysed in relation to the training of junior staff, with particular reference to obstetric anaesthesia.