Use of participatory training techniques in a right-to-know train-the-trainer course for New Jersey public employees.

The New Jersey Department of Health, in conjunction with the Department of Personnel's Human Resources Development Institute, has developed a Right-to-Know Train-the-Trainer course. In this course, various participatory activities have been utilized since the course's inception in December 1989 to train future trainers who train public employees about recognizing, evaluating, and controlling hazardous substances in their facilities. These participatory training techniques have offered a means by which the trainers can encourage workers to become proactive in making their working conditions safer. With the use of various methods of evaluation, course participants learn the content and develop their skills in the use of participatory training techniques. Though evaluations indicate that participants have a favorable impression of the course, the extent to which these participants take the information back to their worksites has not been formally evaluated.


Implementing right-to-know legislation for health care workers in Manitoba: a bipartite sectoral train-the-trainer approach.

In October 1988, right-to-know legislation was introduced in Canada. This presented a technical and administrative challenge to the health care sector. With over 170 health care facilities in Manitoba to be brought into compliance, some large, some small, some rural, some urban, a cooperative approach was needed. A labor-management steering committee with representatives from a cross-section of facilities as well as the various health care unions was formed to design and implement a train-the-trainer program. A small-group, highly participatory modular program was developed with input from all parties, and delivered across the province by trainers selected jointly by labor and management. The program achieved its goal of assisting member facilities to implement the legislation. Follow-up surveys and discussions with health care workers showed improved understanding of labelling requirements, material safety data sheet interpretation, and requirements for hazard control. This first bipartite program empowered the health care workforce to use its newly acquired right-to-know, and has provided the incentive to implement other cooperative safety and health programs.


Evaluating a training-for-action job health and safety program.

This paper describes an action research evaluation method developed to assess a worker training program which encourages trainees to use knowledge acquired to correct health and safety problems in their workplaces. The project teaches trainees from the same workplace to identify problem areas collectively using a tool called a Risk Chart and then to prioritize problems to work on with the aid of an Action Plan. Follow-up trainee interviews are conducted to determine what impact the training has on trainees. The methodology is presented and preliminary results are discussed, with particular emphasis on the advantages and limitations of this method.


Health and safety education for workers with low-literacy or limited-English skills.

Low literacy and limited English proficiency have become a growing concern for health and safety educators. With one-fifth of the workforce reading below an eighth-grade level and possibly another tenth having limited English skills, health and safety educators and unions have increasingly become aware that current training programs often surpass the language and literacy abilities of workers being trained. This article describes the dilemmas facing health and safety professionals in incorporating knowledge about language and literacy skill levels. It documents creative strategies and new programs, largely based on participatory and popular education approaches, to provide training that simultaneously matches worker needs and leads to worker empowerment.


Waking up the audience: the use of trigger videos in labor education.

Use of trigger videos can enhance union education programs by encouraging an active learning process, in which class members can identify with the problems posed in the video, and are motivated to seek a collective action-oriented solution to those situations which exist in their own workplaces. Such an approach empowers workers to develop their own answers in a supportive and mutually reinforcing context.


Three participatory exercises on empowerment used in health and safety training of trainers course in Connecticut.

In a training-of-trainers course on health and safety sponsored by the Connecticut Council on Occupational Safety and Health and the Division of Worker Education, Workers' Compensation Commission, various participatory exercises have been utilized to train workers who are then expected to train their co-workers. Three of the exercises, including hazard recognition, tackling apathy, and strategies for change are described.


Some lessons learned from using participatory methods in asbestos worker training.

A nonprofit worker training center changed its teaching methods in response to teacher feelings of burnout, student expressions of boredom, and the requests of new staff members. The paper presents one problem-solving case study that was developed. The author discusses some obstacles to using the case study, and her experiences in overcoming those obstacles.


The future of health care.

Future changes in patient care to curb costs and refocus on health versus medical care are discussed, and efforts at the New England Medical Center (NEMC) to measure patient outcomes and reorganize the delivery of care are described. Medical care is not the only determinant of an individual's health; lifestyle choices and the community also play important roles. The rate of increase in the cost of medical care must be contained. The future of health-care reform will be predicated on packages for the administration of care; for any given condition, all of the elements of medical care would be combined so that clinical and functional outcomes are achieved at a given price (episode-of-illness pricing). The success of medical care should be determined on the basis of the patient's ability to function, not on clinical indicators alone. Also, the prices for new generations of drugs should be determined on whether the new drugs improve patients' quality of life. Health-care professionals in hospitals should not be divided according to their specialties; instead, they should compose multidisciplinary teams that can care for patients over time. NEMC is developing a process and structure in which various health-care professionals work together to design health-care plans that cover a full episode of illness. The future of health care will also be influenced by global trends, including international medical-care inflation, standardization of process and outcome measurements, and a shift in emphasis from medicine to health. The health-care industry is in transition as this country searches for the best way to improve the health and functioning of each citizen.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacy practice in 2040.

Pharmacy practice 50 years in the future is discussed. The practice of pharmacy in 2040 will be influenced by many trends and issues, such as increasing cultural diversity, the aging population, evolving drug and information technology, rising drug costs, and increasing third-party coverage. Pharmacy may take one of two paths. In the first scenario, institutional and community practice would drift further apart, with community pharmacy becoming more involved with retailing than with health care. In the second scenario, all pharmacists would become a vital component of an integrated, patient-centered system of health care; pharmacists, like physicians, would be salaried professionals, paid for by health-care programs financed through health insurance. The difference between the two scenarios is the degree to which pharmacists actively participate in their creation: The first will happen if pharmacists do not take action; the second will require a considerable amount of work. If pharmacists wish to see an active system of patient-centered pharmaceutical care in 2040, they must begin to create it now, regardless of their practice setting. Pharmacists must work to create a future in which they are an integral part of the health-care system.


Antibiotic-impregnated cement use in U.S. hospitals.

The results of a survey of the use of antibiotic-impregnated bone cement and cement beads in U.S. hospitals are reported. A random sample of hospitals was selected from all hospitals registered with the American Hospital Association. A questionnaire designed to characterize the extent of use of the products and the degree of pharmacy involvement was mailed to the pharmacy directors at 547 hospitals nationwide. The response rate was 61.7% (336 evaluable returns). Ninety hospitals (26.9%) reported using antibiotic-impregnated bone cement or cement beads. Product use was significantly greater in urban hospitals, hospitals larger than 200 beds, teaching hospitals, and hospitals with pharmaceutical services in the operating rooms. Most facilities using the products were community hospitals. Total hip arthroplasty, total knee arthroplasty, and chronic osteomyelitis were the most common indications for use. Systemic antibiotics were also administered in the great majority of hospitals reporting use of the products. The products were generally used in fewer than one procedure per month. Aminoglycosides and various cephalosporins were the antibiotics most commonly used; most have not been adequately studied for this use. Although nearly all the hospital pharmacies purchased antibiotics for these products, none mixed cement and only two premanufactured antibiotic beads. About one fourth of the hospitals surveyed reported using antibiotic-impregnated bone cement and cement beads, although the total number of patients being treated was small.


Pharmaceutical services to evacuated U.S. military dependents.

Pharmacy operations on Guam during Operation Fiery Vigil are recounted. In June 1991 Mount Pinatubo, a volcano near Clark Air Base in the Philippines, erupted and forced the evacuation of the base's population. Some 20,000 military dependents were transported to Guam. Those evacuees who needed medical attention--some 2500 of them--were escorted to a temporary medical unit located in and around Andersen Air Force Base and consisting of Army, Navy, and Air Force elements. Full-service health care, including 24-hour pharmaceutical services, was available. A central pharmacy and four satellite pharmacies were established. The four-man pharmacy staff went on 12-hour shifts and made frequent trips to all the medical sites. The pharmacy established and maintained drug stocks and supplies and provided drug information, particularly information on therapeutic equivalents. Constant readiness for emergency drug requests was maintained, and the pharmacy was responsible for transporting drugs. The pharmacy also supported the Army Veterinary Service in processing, quarantining, and caring for 1300 pets. Cold, motion sickness, and sunburn preparations and analgesics accounted for more than half the prescriptions filled. Problems included the sheer number of evacuees, language barriers, the difference in formularies used by the pharmacies in the Philippines and Guam, and the physical and psychological stress to which the evacuees were subjected. Teamwork and coordination among the three U.S. military branches made it possible to satisfy the enormous medical and pharmaceutical needs of dependents evacuated from the Philippines after Mount Pinatubo erupted.


How to write and publish scientific papers: scribing information for pharmacists.

The principles of writing and publishing scientific papers are outlined. Scientific writing can be both professionally and financially rewarding, but many pharmacists hesitate to write for publication. A primary obstacle is not knowing how to begin. Thoughtful planning is the first and most important step. Before writing a word, the writer should identify the main message, audience, target journal, resource materials, type of manuscript, and authorship. The sections of a paper reporting original research include the title, abstract, introduction, methods, results, discussion, conclusion, references, and tables and figures. Some of these elements also appear in review papers and columns. In general, information given in one section should not duplicate information in another. The writer typically drafts the methods section first, followed by the results, the discussion, and the introduction. Along with intellectual responsibility for the paper, an author must assume various ethical responsibilities, such as ensuring that it contains no plagiarism, that all sources of funding have been acknowledged, and that the paper has not been simultaneously submitted to other journals. To enhance the likelihood of publication, the writer should edit the manuscript carefully and follow the target journal's instructions to contributors. Once the writer has submitted a paper, it must pass the muster of editors and, for peer-reviewed journals, outside experts. Several revisions may be requested before final acceptance. Pharmacists who adhere to the established pattern for writing and submitting scientific papers have the best chance of seeing their work in print.


Harvey A. K. Whitney Lecture. Of perceived value.

Current issues in pharmacy are discussed and recommendations are made to help pharmacy demonstrate its value in health care. There is a need for pharmacy to actively demonstrate and communicate its value in health care. Educational requirements should reflect the values of the profession. In the debate over the entry-level Pharm.D. degree, the profession must not lose sight of the principal goal of elevating the basic competencies of all pharmacists. Graduate-level education will continue to be valuable, but the degrees and programs should be modified to meet current and future needs. Residency training will become increasingly essential. A well-defined corps of pharmacy technicians is needed. The profession should strive to meet the needs of society rather than confining itself to traditional practice definitions. This will involve increased interaction with patients. Also, pharmacy directors must become more creative in allocating existing resources and building arguments for expansion. When patients recognize the value of pharmacy services, they will seek out and demand those services. Pharmacists must get involved in deliberations regarding health-care reform. They have a responsibility to promote preventive medicine and healthy life-styles. They should actively promote the rational use of all medications. Although tremendous progress has been made in advancing the concept of pharmaceutical care, the profession still has work to do in communicating its value to the public.


Mirror to ASHP: 1942-1992.

Highlights from the history of ASHP are presented on the occasion of the Society's 50th anniversary. Efforts to organize a formal group representing hospital pharmacists, begun in the 1920s, resulted in the formation of a subsection on hospital pharmacy of the American Pharmaceutical Association in 1936. In 1942, ASHP became a distinct organization affiliated with APhA. The body's goals were to establish minimum standards for pharmaceutical services, ensure a supply of well-qualified hospital pharmacists by providing hospital internships, facilitate information exchange, and foster cost-effective use of medicines. The development of practice standards and periodic surveys of hospital pharmaceutical services, educational efforts and accreditation programs, publications, and ASHP's role in the development of principles for hospital formulary systems are described. ASHP's endorsement of unit dose drug distribution and systems for preparation of intravenous admixtures is discussed. The evolution of pharmacists' clinical roles, their increased involvement in drug therapy decisions and the provision of drug information to patients, and the expanded responsibility implicit in the pharmaceutical care concept are traced. Today's ASHP members can build on the work of yesterday's members to provide better pharmaceutical care.


Pharmacokinetic consultation program in a pediatric asthma clinic.

The effect of a clinical pharmacokinetic consultation program for theophylline on the outcomes of pediatric patients with asthma was studied. The program was established in 1989 at a pediatric asthma clinic. For each patient visit, a clinical pharmacist recorded demographic, clinical, and medication-related information and counseled the parents. When an adjustment in the theophylline dosage was indicated, the pharmacist calculated the appropriate dosage using population pharmacokinetic values. If the pediatrician requested a measurement of the serum theophylline concentration, the time when the blood sample was drawn relative to the last dose was recorded, an average serum theophylline concentration at steady state and individualized pharmacokinetic values were calculated, and the dosage was adjusted accordingly. Patient data were compared among three stages: (1) the month before and the month of entry into the program, (2) months 5 and 6 after entry, and (3) months 11 and 12 after entry. A total of 44 patients were studied during each of stages 1 and 2, and 29 patients were reviewed during stage 3. There was a significant improvement in wheezing from stage 1 to stage 2 and in exercise tolerance and nocturnal coughing from stage 1 to stage 2 and stage 1 to stage 3. Forced expiratory volume in one second improved significantly from stage 1 to stage 2, and there was a significant reduction in the necessity for hospital visits for the treatment of exacerbations of asthma between stages 1 and 2. The daily weight-adjusted dose of theophylline increased significantly after the program began. Asthmatic children taking theophylline had improvements in outcome variables after pharmacokinetic consultation and medication counseling were initiated.


Factors affecting pharmacists' selection of rural or urban practice sites in Nebraska.

A questionnaire was used to determine why pharmacists in Nebraska chose urban or rural practice sites and to help the University of Nebraska College of Pharmacy encourage students to consider rural practice. Questionnaires were mailed to 1427 Nebraska pharmacists to gather data about their practice, job satisfaction, location of rearing, location of spouse's rearing, and prepharmacy and clerkship training. Usable responses were sorted into those from urban pharmacists (residing in Omaha and Lincoln and their suburban areas) and those from rural pharmacists (all others). Of the 689 usable responses, 315 (45.7%) were from urban pharmacists and 374 (54.3%) were from rural pharmacists. Of the rural pharmacists, 93% [corrected] grew up in communities of fewer than 100,000 people and 60% grew up in communities of fewer than 5,000 people. Respondents cited income potential, desirability of practice site, influence of spouse and family, and quality of children's schools as factors that most influenced their choice of practice site. Based on the survey results, the University of Nebraska College of Pharmacy took actions to recruit students from rural communities and increase students' exposure to rural practice settings. Pharmacists who were reared or trained in rural areas were more likely to practice in rural Nebraska than pharmacists who had only urban experience.


Therapeutic interchange of cefazolin with metronidazole for cefoxitin.

The effects on patient outcome and drug therapy costs of a therapeutic interchange program using a cefazolin and metronidazole combination in place of cefoxitin were studied. A therapeutic interchange program was initiated in which the pharmacy department automatically replaced orders for cefoxitin with orders for a cefazolin and metronidazole combination. Data were compared for 100 consecutive patients who received cefoxitin before initiation of the program and the first 100 patients who received cefazolin and metronidazole as part of the program. The impact of the program on therapeutic efficacy, adverse effects associated with therapy, and drug therapy costs was assessed. The two patient groups were similar in age, gender, and white blood cell count. The failure rates for treatment or prophylaxis of infection did not significantly differ between the groups. Duration of therapy and incidence of adverse effects did not significantly differ between the groups. The average cost saving was +72 per patient for treatment with cefazolin and metronidazole instead of cefoxitin. A program for therapeutic interchange of cefazolin and metronidazole in place of cefoxitin demonstrated equivalent efficacy and adverse effects, as well as considerable cost savings.


Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.

To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost-effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients.


Cardiac involvement in patients with myeloproliferative disorders.

To evaluate cardiac involvement in myeloproliferative disorders (MPD), two-dimensional and Doppler echocardiographic studies were performed in 30 patients with MPD. There were 18 women and 12 men, with an age range from 35 to 76 years. Eighteen patients had polycythemia vera (PV), 8 had essential thrombocythemia (ET), and 4 had agnogenic myeloid metaplasia (AMM). Echocardiography revealed valvular lesions in 19 of 30 patients (63%) compared with only 1 of 22 patients (4.5%) in a control group of patients referred for echocardiography to exclude a cardiac source for idiopathic systemic thromboembolism (chi 2 = 13.39, p < 0.001, by chi 2 test with Yates' correction). Valvular lesions were found in 77% of patients with PV, 50% with ET, and 25% with AMM (p = NS). The aortic and mitral valves were the most commonly involved valves, and the most common echocardiographic lesion was leaflet thickening, which was found in 12 patients (40%), followed by vegetations, which were observed in 5 patients (16%). In their past history, 14 of 30 (47%) MPD patients had arterial or venous thrombosis or embolism. Twelve of 19 (63%) patients with valvular lesions had thromboembolism compared with only 2 of 11 (18%) patients without evidence of valvular lesions (chi 2 = 3.99, p < 0.05, by chi 2 test with Yates' correction). Pulmonary hypertension, unrelated to the severity of valvular disease and probably resulting from pulmonary venous occlusion, was found in four patients (13%). We conclude that the heart is frequently involved in patients with MPD, particularly when their past history is complicated by a thromboembolic event. Some patients have clinically significant valvular disease. Pulmonary hypertension is another relatively common finding in MPD patients. Echocardiography provides information of clinical significance in MPD patients. A larger number of patients is needed to determine whether the presence of valvular lesions is of prognostic significance and may herald future thromboembolic events.


Ascending aorta distensibility abnormalities in hypertensive patients and response to nifedipine administration.

The purpose of the present investigation was to study the distensibility of the ascending aorta in patients with arterial hypertension and normal subjects before and after administration of a calcium antagonist, nifedipine. The distensibility of the ascending aorta was measured before and after nifedipine administration in 22 male hypertensive patients and 12 age-matched male normotensive subjects. Aortic distensibility was calculated as a function of changes in aortic diameter and pulse pressure, using the formula: 2 x (pulsatile change in aortic diameter)/[(diastolic aortic diameter) x (aortic pulse pressure)]. Aortic diameters were measured by echocardiography and aortic pressures were obtained by catheterization of the ascending aorta. In the basal state, the distensibility of the ascending aorta and aortic strain were lower in hypertensive patients than in normotensive subjects (p < 0.001); the lower aortic distensibility, however, was associated with a greater distending pressure. A good inverse correlation (r = -0.81) was found between mean aortic pressure and aortic distensibility. The aortic distensibility was increased after nifedipine administration in both groups; this increase in aortic distensibility, however, was lower in the patients with hypertension compared with normotensive subjects (p < 0.001). Aortic distensibility is decreased in patients with arterial hypertension. Nifedipine administration increased the distensibility of the ascending aorta both in patients with arterial hypertension and in normotensive subjects. The increase of aortic distensibility after nifedipine administration was lower in hypertensive patients.


Risk factors for coronary artery disease in patients with systemic lupus erythematosus.

To estimate the frequency of and examine risk factors for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE) in a prospective longitudinal study. Patients were SLE are enrolled in The Johns Hopkins Lupus Cohort, a prospective study of outcomes in 229 subjects with SLE. CAD was defined as angina, myocardial infarction, or sudden death. Data on CAD risk factors were obtained prospectively every 3 months and were analyzed using univariate and multiple logistic regression. CAD occurred in 19 (8.3%) of 229 patients with SLE and accounted for 3 (30%) of 10 deaths as of December 31, 1990. Compared to subjects without CAD, those with CAD were more likely to have been older at both diagnosis of SLE (37.1 years versus 28.9 years, p = 0.004) and at entry into the cohort (47.1 years versus 34.7 years, p < 0.0001), to have a longer mean duration of SLE (12.3 years versus 8.1 years, p = 0.013) and a longer mean duration of prednisone use (14.3 years versus 7.2 years, p < 0.0001), to have a higher mean serum cholesterol (271.2 mg/dL versus 214.9 mg/dL, p < 0.0001) or a cholesterol level greater than 200 mg/dL (odds ratio [OR] 14.5, 95% confidence intervals [CI] 1.9, 112.1), and to have both a history of hypertension (OR 3.5, 95% CI 1.3, 9.6) and a history of use of antihypertensive medications (OR 5.5, 95% CI 1.8, 17.2). There were no significant associations with other known CAD risk factors such as smoking, diabetes, family history of CAD, race, or sex, or variables related to steroid therapy including the presence of cushingoid features or ever use of corticosteroids. The best multiple logistic regression model for CAD included age at diagnosis, duration of prednisone use, requirement for antihypertensive treatment, maximum cholesterol level, and obesity (using NHANES-II [National Health and Nutrition Examination Survey] definitions). Primary and secondary prevention strategies directed at hypertension, hypercholesterolemia, and obesity, as well as other known CAD risk factors, should be routinely employed in the management of patients with SLE.


Tuberculous meningitis in patients with and without human immunodeficiency virus infection.

To characterize the symptoms, signs, laboratory findings, and outcome of culture-proven meningitis due to Mycobacterium tuberculosis in patients with and without human immunodeficiency virus (HIV) infection. Retrospective chart review. Urban public general hospital in the United States. Fifteen patients with and 16 without HIV infection. Demographics, symptoms, physical exam findings, serum sodium, complete blood cell count, CD4+ cell count, cerebrospinal fluid findings, imaging data, and in-hospital mortality. Symptoms, signs, chest radiograph appearance, cerebrospinal fluid cell counts and chemistries, and mortality were similar in both groups (p = NS). Median CD4+ cell counts were lower in HIV-infected patients (median 99/mm3, range 7 to 251, versus 384/mm3, range 171 to 724 in those without HIV infection, p = 0.007). Intracerebral mass lesions were more common in the HIV-infected group (60% versus 14% in the uninfected group, p = 0.01), although the presence of a mass did not correlate with focal neurologic deficits, altered level of consciousness, or mortality. With the exception of an increased incidence of intracerebral mass lesions in HIV-infected individuals, HIV infection appears to have little impact on the findings and in-hospital mortality of tuberculous meningitis.


Microalbuminuria in patients with essential hypertension: effects of several antihypertensive drugs.

Microalbuminuria can be present in 10% to 40% of patients with essential hypertension and is associated with an increased incidence of cardiovascular events. The effect of commonly used antihypertensive agents on urinary albumin excretion (UAE) has not been well established. The aim of this study was to evaluate the effects of a converting enzyme inhibitor, a calcium channel blocker, a beta blocker, and a diuretic on UAE and on creatinine clearance in patients with mild to moderate hypertension. We prospectively measured UAE prior to and 4 and 8 weeks after treatment with enalapril, nitrendipine, atenolol, or a diuretic in 48 patients with essential hypertension and microalbuminuria. All these agents were equally effective in reducing arterial pressure. However, enalapril but not the other agents significantly decreased UAE. Eight weeks of therapy with enalapril may reduce UAE in patients with mild to moderate essential hypertension, whereas other agents, such as nitrendipine, atenolol, or diuretics, had no measurable effect on UAE. The clinical and prognostic significance of these observations remains to be established.


Imaging of thoracic Wegener's granulomatosis: the computed tomographic appearance.

Computed tomography (CT) can play a major role in the examination of patients with diffuse infiltrative disorders of the lung. CT patterns of thoracic Wegener's granulomatosis were retrospectively evaluated in this study. The CT appearance was compared with imaging obtained by conventional plain roentgenograms. Fourteen patients with Wegener's granulomatosis seen during the last 5 years are described. Conventional chest roentgenograms and CT scans from these patients are reviewed. The most frequent manifestation found in the lungs of patients with Wegener's granulomatosis was that of rounded opacities with or without cavitation. This was observed in 7 of 14 patients. Relatively unexpected was the frequent occurrence of bronchovascular bundle cuffing with a quite constant and characteristic bronchocentric distribution. This finding was observed in 5 of 14 patients. Vasculitis sign was demonstrated in 2 of 14 patients. Widespread acinar infiltrates, usually confluent, were common and were seen in 5 of 14 of our patients; in 2 of the patients, these infiltrates were due to diffuse pulmonary hemorrhage. Tracheal stenosis was the cause of sudden acute respiratory failure that was observed in one patient. Pleural disease was present in 3 of 14 patients. Hilar and mediastinal lymphadenopathy was observed in one patient. An interstitial pattern was observed in 3 of 14 patients. We conclude that an extremely wide spectrum of radiologic findings may be observed in this disease. In 14 patients we found 11 different roentgenographic manifestations; moreover, in 8 patients it was possible to describe more than 1 radiologic manifestation at the same time or during the course of the disease. This observation is not surprising, if we consider the wide variability and broad spectrum of pathologic features in pulmonary Wegener's granulomatosis. Because conventional roentgenograms failed in a great number of cases to visualize the exact pattern and the extent of thoracic involvement, we believe that CT is particularly helpful for the assessment of pulmonary involvement in Wegener's granulomatosis.


Physician demographics and the risk of medical malpractice.

This study was undertaken to clarify which, if any, physician demographic characteristics are associated with an increased rate of medical malpractice claims. We analyzed the malpractice experience of 9,250 physicians insured for at least 2 years from 1977 to 1987 in the state of New Jersey. After adjusting for years at risk, physician claims per year was categorized into low, medium, and high. Male physicians were three times as likely to be in the high-claims group as female physicians, even after adjusting for other demographic variables (relative risk, 3.1; 99% confidence interval, 2.2 to 4.4). Specialty was strongly associated with claims rate, with neurosurgery, orthopedics, and obstetrics/gynecology having 7 to 12 times the number of claims per year as psychiatry, the specialty with the fewest claims. The rate of claims varied with age (p < 0.001) and peaked at approximately age 40. No association was evident between claims rate and a physician's site of training or type of degree. Male physicians are three times as likely to be in a high-claims category as female physicians. We suspect that the most likely explanation for this finding is that women interact more effectively with patients. Understanding the reasons for the variation in claim rates between physicians may lead to the development of methods to reduce the overall rate of malpractice claims.


Treatment of supraventricular tachycardias with transcatheter delivery of radiofrequency current.

Medical therapy for the treatment of supraventricular tachycardias is frequently ineffective and associated with significant side effects, whereas curative surgical approaches have generally been limited by their considerable morbidity and cost. Greater understanding of the mechanisms underlying supraventricular tachycardias has improved our ability to precisely map endocardial areas critical to arrhythmogenesis. Advances in catheter ablation techniques and particularly the use of radiofrequency current to generate thermal energy for ablation have resulted in dramatic success rates for curative catheter ablation. This review examines the physics of radiofrequency current ablation and its application to the treatment of atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia, and arrhythmias associated with the Wolff-Parkinson-White syndrome. The limitations, risks, and cost-effectiveness of this technique relative to medical and surgical approaches are also evaluated.


Admission screening by thyroid function tests in an acute general care teaching hospital.

To determine the incidence of unrecognized thyroid disease among admissions to a large acute care university teaching hospital, 364 samples taken on consecutive admissions were assayed for thyroid-stimulating hormone (TSH) and free thyroxine index (FTI). Patients with abnormal test results were further evaluated by determination of antimicrosomal and antithyroglobulin antibodies, and charts were reviewed for evidence of prior diagnosis of thyroid disease, especially severe illness, drug treatment that might affect thyroid function tests, and prior diagnosis of thyroid disease. Results of subsequent thyroid function tests performed during the patient's hospitalization were correlated with the admission serum assays, and data on subsequent testing during the following 6 months were also obtained. A total of 3.9% of patients had significantly depressed TSH, and 11.1% of values were significantly elevated. A total of 11.3% of patients had significantly low FTI values, and 1% had significantly elevated values. A total of 7.4% appeared to have the euthyroid sick syndrome, 5.8% appeared to have unrecognized or undertreated primary thyroid failure, 6% had apparent subclinical hypothyroidism, 2% were thyrotoxic, and 2.8% (all women) had suppressed TSH levels for inapparent reasons. Limiting testing to patients over 49 years of age, or to women, would have missed many individuals with abnormal test results. Considering widespread availability of tests, relative costs, and value of the information obtained, it is suggested that the FTI determination would provide an appropriate screening test for patients in a population such as this entering a large, acute care general hospital.


Concomitant oculoglandular and ulceroglandular fever due to herpes simplex virus type I.

Herpes simplex virus is a commonly encountered infectious agent in clinical practice. The syndromes with which it is usually associated are well described and generally easily recognized. This report documents that two uncommon clinical syndromes, ulceroglandular fever and oculoglandular fever, may be caused by this virus. Our patient's case was even more unusual in that both conditions occurred simultaneously.


Case report: acromegaly and Cushing's disease in a patient with synchronous pituitary adenomas.

A 40-year-old white woman presented with hirsutism, amenorrhea, generalized fatigue, diffuse weight gain, acral changes, and coarsened facial features. Physical examination revealed mild diastolic hypertension, acromegalic features, hirsutism, and seborrhea. The growth hormone concentration was elevated and did not suppress after glucose administration. Urinary free cortisol excretion was increased and was not suppressed during a 2 mg low-dose dexamethasone suppression test. Magnetic resonance imaging of the sella demonstrated a 1.3 x 1.2 x 0.8 cm pituitary adenoma. Trans-sphenoidal resection was performed, and portions of the resected tumor were analyzed by routine pathologic methods. Histopathologic and immunohistochemical findings indicated discrete growth hormone- and adrenocorticotropic hormone-producing pituitary adenomas. Coexisting acromegaly and Cushing's syndrome due to pituitary neoplasia was previously reported in two patients. However, to the authors' knowledge, this represents the first description of a patient with acromegaly and Cushing's disease resulting from discrete synchronous adenomas of the pituitary gland as defined by modern histopathologic techniques.


Case report: factitious hypoglycemia in diabetic patients.

Factitious hypoglycemia (FH) in a diabetic patient represents a difficult diagnostic and costly management problem. An adolescent diabetic with FH is reported. A literature search revealed 10 adolescent and 45 adult diabetic patients with FH. Tests currently available for diagnosis are evaluated. The role of psychiatric therapy in relation to overall management and prognosis is stressed.


Case report: acute focal bacterial pyelonephritis (lobar nephronia)--presentation as a palpable abdominal mass.

Acute lobar nephronia, or focal pyelonephritis, is an uncommon form of renal infection with a distinct computerized tomographic appearance. A patient is presented with lobar nephronia characterized by fever, flank pain, urosepsis, and painful abdominal mass. Differentiating this condition from abscess or other renal mass is important, because the treatment of lobar nephronia is nonsurgical. The infection responds to antibiotic therapy.


Hypertension in blacks: socioeconomic stress and sympathetic nervous system activity.

Primary hypertension is almost twice as prevalent among American blacks as among whites. Causes of this increased prevalence of hypertension remain elusive. Elevation of sympathetic nervous system activity, in part secondary to increased levels of socioeconomic stress, is hypothesized as playing a role. Increased sympathetic nervous system activity may increase peripheral vascular resistance directly or through increased vascular reactivity. Microneurography allows direct measurement of peripheral sympathetic nervous system activity. Application of this technique will allow comparison of sympathetic nervous system activity in black and white subjects and provide additional insight into the role of the sympathetic nervous system in the development of hypertension in blacks.


Diuretics in the therapy of hypertension: current status.

Diuretics were the first effective oral agents for treating hypertension. They have proven to be safe and effective. Recently, they have been scrutinized as possibly being responsible for certain side effects that may increase risk for cardiovascular morbidity and mortality. A careful review of the literature suggests this class of agents warrants continued use as first-line therapy of hypertension, especially in certain demographic groups. However, monitoring of potential baleful effects and a general reduction in dosage are appropriate. Furthermore, selection of other (alternative) agents for monotherapy is advised in certain clinical circumstances.


A new twist in the brain-gut axis.

Gastrointestinal functions are precisely regulated by hormonal and neural negative feedback loops. In addition to the classic hormonal and vago-vagal reflex mechanisms, these studies indicate that there are direct actions of gut hormones on the dorsal vagal complex. The current data demonstrate that pancreatic polypeptide is released into the circulation by vagal-cholinergic dependent mechanisms. It travels to the brainstem in the circulation, transverses the blood-brain barrier through "leaky" regions of this barrier in the area postrema and nucleus of the tractus solitarius and binds to specific receptors in the dorsal vagal complex. By binding to these sites, pancreatic polypeptide can directly inhibit vagal input to the pancreas and other gastrointestinal organs. These observations provide an anatomic basis to explain why pancreatic polypeptide is a more potent inhibitor of the action of central stimulants of pancreatic secretion than it is of the response to peripheral secretagogues. They also establish a novel mechanism by which gut peptides can influence brain function directly.


Commingling and complex segregation analysis of fasting plasma glucose in the Lipid Research Clinics family study.

Commingling and segregation patterns of fasting plasma glucose (GL) were examined in family data from 5 clinics (Cincinnati, Stanford, Iowa, Minnesota, and Oklahoma) of the Lipid Research Clinics (LRC) family study. In addition to the primary question of whether there was a major gene for GL, a secondary purpose was to investigate the possibility of genetic heterogeneity among the 5 clinics. No statistical support was found for heterogeneity among clinics, either in the commingling of distributions or in the segregation patterns. For the combined clinics sample, both a major effect and a multifactorial component were significant. However, the major effect (accounting for 73% of the variance) was not found to be consistent with a major gene, as the hypothesis of Mendelian transmission was rejected. The most parsimonious model involved equal transmission probabilities, which suggests that the major effect is not transmitted from parents to offspring. Possible sources of this major non-Mendelian effect were explored. The multifactorial component accounted for 10% of the variance in GL levels, and no generational differences were noted. Although our study was unable to provide evidence in favor of a major gene effect, it should be noted that a major gene cannot be firmly refuted. For example, a variety of interactions, such as genotype-dependent age effects, could have masked the transmission probabilities.


Study of the etiology of deafness in an institutionalized population in Colombia.

To identify causative factors we screened 1,715 deaf individuals from 16 schools for the deaf in Colombia. We found evidence of environmental causation in 579 (33.8%) cases, genetic in 608 (35.4%), and in 528 (30.8%) we were unable to identify the etiology. The degree of hearing loss was severe to profound in 1,238 (72.2%), although in 987 (57.5%) of the deaf population studied the hearing impairment was not noticed until 2 to 5 years of age. The frequent association of deafness with other anomalies underscores the importance of a careful clinical and ophthalmologic evaluation in individuals with hearing loss. Our observations also emphasize the need for programs directed towards the prevention of hearing loss, including primary prevention as well as early diagnosis, investigation of possible genetic causes, and rehabilitation of deaf individuals.


Utilization and evaluation of living-related donors for patients with adult polycystic kidney disease.

Adult onset polycystic kidney disease (ADPKD) causes 10% of all end-stage renal disease in the United States. Use of living-related donors for renal transplants provides significant advantages over cadaver donors. Presymptomatic testing to determine ADPKD status of potential donors by DNA linkage analysis is potentially more accurate than renal ultrasonography for related donors < 30 years old. To determine the utilization of living donor transplants and linkage studies, a survey was mailed to 202 transplant centers in the United Network of Organ Sharing. The 111 respondents reported 5,026 renal transplants done in 1988 of which 390 (7.8%) involved an ADPKD recipient. Only 7% of these 390 transplants utilized a living-related donor compared to the 20% rate reported for all renal transplants. DNA linkage studies were not used by any of the centers performing related donor transplants in 1988 and only 29% reported provision of risk counseling. We conclude that living-related transplants are underutilized for ADPKD recipients due to conservative transplant policies, concern about the inaccuracy of presymptomatic diagnosis, or decreased availability of asymptomatic donors in these families. DNA linkage analysis is also underutilized due to lack of knowledge of its availability and accuracy, concerns about its cost and misconceptions about the accuracy of ultrasonography.(ABSTRACT TRUNCATED AT 250 WORDS)


Patterns of acrorenal malformation associations.

Limb and urinary tract defects have frequently been reported to occur together as components of a single acrorenal field defect or in many multiple malformation syndromes. However, the concordance of such anomalies has rarely been studied on a population basis or the relationships between specific limb and renal defects defined. This paper documents the patterns of acrorenal associations seen in over 1,500,000 infants born in Hungary in 1975-1984. In all, 1 in 1,800 infants had a limb deficiency and 9% of these (75 cases) had a urinary tract anomaly. Urinary tract anomalies were most commonly seen with radial ray defects, micromelia and amelia. The commonest recognized patterns were VACTERL association and the cloacal exstrophy and caudal regression sequences. Chromosomal and single gene defects also occurred. Numerical taxonomic techniques delineated six main clusters of patients. Important groupings included micromelia with renal agenesis, split hand/foot with hydronephrosis, and radial ray anomalies with VACTERL defects. The radial ray groups differed in the nature of the VACTERL anomalies seen and with respect to laterality, symmetry, and non-VACTERL anomalies. There was a strong association of bilateral limb defects with bilateral renal anomalies and unilateral with unilateral. Ipsilateral defects tended to occur in typical VACTERL cases, while contralateral defects tended to occur with additional non VACTERL midline anomalies. Although renal and limb anomalies are associated, in almost all cases malformations in other systems are also present. The precise nature of the malformation patterns seen appear to reflect differences in the nature and magnitude of the underlying dysmorphogenetic processes as well as the timing of their effects.


Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia.

Patients with pseudoachondroplasia have a skeletal dysplasia with marked short stature. The most common cause of this condition is an autosomal dominant mutation, although autosomal recessive inheritance has been reported. Linkage to 2 cartilage-specific candidate genes, type II collagen (COL2A1) and proteoglycan link protein genes (CRTL1), was tested in 9 autosomal dominant families with pseudoachondroplasia. Tight linkage to these candidate genes was excluded with LOD scores for COL2A1 of -2.45 at theta = 0.05 and for CRTL1 of -7.28 at theta = 0.001. Discordant inheritance of the disease phenotype with each of these genes was also observed. Thus, these 2 candidate genes can be excluded as the cause of disease in these families.


Cardiovascular abnormalities in the oculo-auriculo-vertebral spectrum (Goldenhar syndrome).

We describe the phenotypic characteristics of 25 individuals with oculo-auriculo-vertebral spectrum (OAVS) and its variants, seen in Northern Ireland between 1969-1989, with special reference to cardiovascular defects. We report the type and prevalence of cardiovascular findings and also estimate the minimum prevalence rate of OAVS to be 1 in 45,000.


Neonatal hemochromatosis: genetic counseling based on retrospective pathologic diagnosis.

We report a case of neonatal hemochromatosis in which the genetic counseling was initiated by, and based on, retrospective pathologic diagnosis. Perinatal or neonatal hemochromatosis is beginning to be recognized as a distinct clinical entity and one of the most common causes of perinatal cirrhosis. The exact mechanism of liver damage and the relationship to adult type hemochromatosis have not been fully clarified. The pattern of fibrosis in the liver plus the abundant iron deposition in the liver and other organs separate this entity pathologically from other causes of neonatal liver failure. We report on a case of neonatal hemochromatosis that was diagnosed on retrospective autopsy review of an infant with supposed hereditary tyrosinemia, when the family presented for genetic counseling. This case emphasizes to the genetic counselor and pathologist the need to consider the diagnosis prenatally, after birth, or at death, as failure to do so would result in the inability to identify families at genetic risk for neonatal hemochromatosis or in mislabeling a family with another inborn error.


Boy with a chromosome del (3)(q12q23) and blepharophimosis syndrome.

We report on a 6-year-old boy with de novo 46,XY,del(3)(q12q23) and bilateral blepharophimosis, ptosis, epicanthus inversus, in addition to multiple other anomalies. Since 4 previously reported cases of interstitial deletion of 3q involving 3q23 band are clinically similar, we propose this blepharophimosis sequence due to 3q23 deletion as a further "contiguous gene syndrome."


Trisomy 22 with congenital diaphragmatic hernia and absence of corpus callosum in a liveborn premature infant.

We report on a liveborn premature male with trisomy 22 who had multiple congenital anomalies, including congenital diaphragmatic hernia and absence of corpus callosum. He died of pulmonary hypoplasia associated with diaphragmatic hernia within 12 hours of age. Chromosome analysis by multiple banding techniques based on lymphocyte culture confirmed that he had trisomy 22. This may be the first report of congenital diaphragmatic hernia and isolated absence of corpus callosum associated with trisomy 22.


Comparison of phenylketonuric and nonphenylketonuric sibs from untreated pregnancies in a mother with phenylketonuria.

Two children, one with phenylketonuria (PKU) and the other nonphenylketonuric, from untreated pregnancies in a mother with PKU provided the opportunity to compare the degree of damage from maternal PKU between these genotypically different fetuses. Both the phenylketonuric offspring and her nonphenylketonuric sib were microcephalic at birth and had congenital anomalies, esophageal atresia in the former and congenital dislocation of the hip in the latter. However, the phenylketonuric child also had intrauterine growth retardation while the nonphenylketonuric sib had normal weight and length at birth. Both children are mentally retarded with an IQ below 50 in the phenylketonuric child despite early dietary treatment for PKU and an IQ of 54 in the nonphenylketonuric sib. Both children also have hypoplasia of the corpus callosum and enlarged cerebral ventricles. This experience and review of the literature indicates that the residual liver phenylalanine hydroxylase activity of a nonphenylketonuric fetus offers little or no protection from damage in untreated maternal PKU. Consequently, the outcome in maternal PKU is likely to depend on control of the maternal biochemical abnormalities in the mother regardless of whether the fetus has or does not have PKU.


Golgi-Kopsch silver study of the brain of a patient with untreated phenylketonuria, seizures, and cortical blindness.

This report describes the morphological changes observed in the brain of an untreated 27-year-old man with phenylketonuria, cortical blindness, and seizures. Golgi-Kopsch silver, cresyl violet, and hematoxylin and eosin stains were used to study cell structure and organization of the cerebellum, the lateral geniculate nuclei, the visual cortex, frontal cortex, and hippocampus. Extensive neuronal losses occurred in the right lateral geniculate nucleus (LGN), the visual cortex, and hippocampus. The left LGN, cerebellum, and frontal cortex retained neuronal components; there was a reduction in the number of dendritic processes on the Purkinje cells of the PKU subject. The loss of neurons in the LGN and occipital cortex is related to the blindness and the neuronal loss in the hippocampus is related to seizure activity.


Molecular detection of a 4p deletion using PCR-based polymorphisms: a technique for the rapid detection of the Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) results from a deletion of part of chromosome 4p. The region of 4p consistently deleted in WHS is near the tip of 4p. Two loci in this region D4S95 and D4S125 are associated with highly informative VNTR polymorphisms and were recently converted to allow PCR-based screening. PCR analysis was used successfully to identify a small de novo deletion of 4p in a patient suspected of having WHS. This procedure allows a rapid and accurate confirmation of 4p deletions in cases where cytogenetics alone cannot provide a clear answer.


Charcot-Marie-Tooth neuropathy type 1A mutation: apparent crossovers with D17S122 are due to a duplication.

A locus for the slow conducting form of Charcot-Marie-Tooth neuropathy (CMT1A) was localised to the proximal short arm of chromosome 17, in band p11.2, distal to D17S58. Linkage studies of CMT1A in 3 large Australian families with the marker loci D17S58, D17S71, and D17S57 suggested the order, pter-CMT1A-D17S71-D17S58-centromere-D17S57. However, the estimate of the recombination fraction between CMT1A and D17S122, also assigned to p11.2, was incompatible with known map distances. The impasse was resolved when the D17S122 genotypes were revised to take into account a dosage effect due to a duplication. After correction of the genotypes, the maximum lod score between CMT1A and D17S122 increased from 0.53 at a recombination fraction of 0.3 to 34.28 at zero recombination. This result emphasizes that genotypes for markers in the p12-p11.2 region should be examined very carefully as ignoring the duplication changes the linkage results dramatically. The fact that no crossovers were found between CMT1A and D17S122 suggests that the duplication may cause the disease phenotype.


New syndrome involving the visual, auditory, respiratory, gastrointestinal, and renal systems.

A previously undescribed fatal multisystem syndrome involving the eyes, ears, lungs, intestines, and kidneys occurred in sibs. They both presented during early childhood with cataracts, otitis media, intestinal malabsorption, chronic respiratory infection, and failure to thrive. Later, they developed recurrent pneumonia (one was shown to have immotile bronchial cilia) and progressive azotemia leading to end-stage renal disease (ESRD) by late childhood. Both died of overwhelming infection (sepsis, meningitis). An autosomal recessive mode of inheritance is proposed since the normal parents were distant cousins, and 4 other sibs were normal.


Biochemical characterization of a pedigree with mitochondrially inherited deafness.

A large kindred with a predicted 2-locus inheritance of sensorineural deafness, caused by the combination of a mitochondrial and an autosomal recessive mutation, was examined at the biochemical level. Because of the mitochondrial inheritance of this disease, we looked for defects in the oxidative phosphorylation Complexes I, III, IV, and V, the 4 enzymes that include all of the 13 mitochondrially encoded polypeptides. Biosynthetic labelling of lymphoblastoid cells from deaf patients, unaffected siblings, and an unrelated control showed no difference in size, abundance, rate of synthesis, or chloramphenicol-sensitivity of the mitochondrially encoded subunits. Since overall mitochondrial protein synthesis appears normal, these results suggest that the mitochondrial mutation is unlikely to be in a tRNA or rRNA gene. No change in enzymatic levels was seen in lymphoblastoid mitochondria of the deaf patients, compared to unaffected sibs and controls, for Complexes I and IV. Both affected and unaffected family members showed an increase in Complex III activity compared to controls, which may reflect the mitochondrial DNA shared by maternal relatives, or be due to other genetic differences. Complex V activity was increased in deaf individuals compared to their unaffected sibs. Since the family members share the presumptive mitochondrial mutation, differences between deaf and unaffected individuals likely reflect the nuclear background and suggest that the autosomal recessive mutation may be related to the increase in Complex V activity. These biochemical studies provide a guide for sequence analysis of the patients' mitochondrial DNA and for linkage studies in this kindred.


Usefulness of a CACA repeat polymorphism in genotype assignments in Duchenne/Becker muscular dystrophy.

RFLP analysis in Duchenne/Becker muscular dystrophy (D/BMD) has been limited by the lack of informative marker loci at the 3' end of the dystrophin gene. Recently a CACA repeat polymorphism was described in the 3' untranslated end of the dystrophin gene which we have found helpful in genotype assignments of D/BMD families when an RFLP approach is required. The CACA repeat marker has 2 common alleles (1 and 2) that are easily visualized by a nonradioactive PCR method followed by polyacrylamide gel electrophoresis. We present 2 families which demonstrate the use of this polymorphism. Since 35-50% of females are heterozygous, this locus is a useful marker in RFLP analysis of D/BMD families.


Confirmation of a cryptic unbalanced translocation using whole chromosome fluorescence in situ hybridization.

We report on a 7-year-old boy with minor anomalies, growth retardation, and developmental delay with an initial 46,XY,der(18)t(18;?)(q23;?) chromosome constitution. To determine the origin of the additional chromosome segment, several candidate regions were identified including 4q and 18q. Clinical comparison showed more similarities to individuals with partial dup(4q) than to those with a dup(18q). Whole chromosome fluorescence in situ hybridization (FISH) was used to demonstrate the correct origin of the translocated region, clarifying the karyotype as 46,XY,der(18)t(4;18)(q28.2;q22.2), thus generating information of clinical importance. This illustrates the use of whole chromosome FISH to identify chromosome regions that cannot be determined conclusively using standard cytogenetic banding techniques.


Update on a family with hand-foot-genital syndrome: hypospadias and urinary tract abnormalities in two boys from the fourth generation.

We describe a fourth generation of involvement with hand-foot-genital syndrome. The first 3 generations of this family, which included 5 affected females and no affected males, were reported previously by Verp et al. [1983]. In the fourth generation, 2 affected males are identified. To our knowledge, the findings of bilateral vesicoureteral reflux in one boy and bilateral ureteropelvic junction obstruction in his cousin represent the first reports of urinary tract abnormalities in males with this syndrome.


Familial syndrome of endocrine and neuroectodermal abnormalities.

We report on a previously undescribed combination of endocrine and neuroectodermal abnormalities in four sibs from Burma. These abnormalities include low growth hormone levels in response to provocative stimuli, delayed puberty associated with prepubertal levels of gonadotropins in the males and pubertal levels of gonadotropins in the females, type II diabetes mellitus with elevated insulin levels, mild mental retardation, sensori-neural deafness, and alopecia without pili torti. They also had a characteristic facial appearance and fleshy hands and feet. This family appears to have a previously undescribed combination of endocrine and neuroectodermal abnormalities.


Hepatoerythropoietic porphyria in a woman with short stature and deformed hands.

A 23-year-old woman from Honduras was diagnosed to have hepatoerythropoietic porphyria. She had photosensitive skin of early onset, hypertrichosis, and severe scleroderma-like lesions of the hands. Erythrocyte uroporphyrinogen decarboxylase activity was reduced to about 10% of the normal activity.


Smallest terminal deletion of the long arm of chromosome 2 in a mildly affected boy.

We describe a male twin with the smallest terminal deletion of chromosome 2q [46,XY,del(2)(q37.2)] reported to date. His deletion was confirmed by a fluorescence in situ hybridization study using a probe from the deleted region. Only 3 other cases with larger deletions including 2q37.2-->qter have been reported. Clinical manifestations our patient has in common with them include frontal bossing, long eyelashes, micrognathia, infantile hypotonia and developmental delay. His twin brother is physically and developmentally normal and chromosomes of the parents were normal. The mildness of the phenotype in this patient supports less stringent criteria for cytogenetic study of developmentally impaired individuals.


Clinico-pathological conference: a preterm infant with multiple congenital anomalies.

A preterm female infant (28 weeks; 880 g) presented with bilateral ectrodactyly of the feet, small cleft palate, esophageal atresia and T-E fistula, multivalvular dysplasia and VSD, thrombocytopenia, and other minor anomalies. Cytogenetic analysis showed trisomy 18.


Parental sex effect in spina bifida: a role for genomic imprinting?

Fifty families (491 individuals in 137 sibships) with more than one living case of isolated, nonsyndromic spina bifida (SB) were analyzed genetically. There were twice as many gene-carrier females (56) as gene-carrier males (28) (P < 0.005). This was not an artifact of ascertainment bias because the sex ratio of gene-carriers was the same whether the pedigree was obtained through the proband's father or mother. Also, this effect was not observed in other disorders analyzed by the same method. Neither was the effect due to differential fertility because the number and sex of affected and unaffected children per gene-carrier parent were not different for male or female gene-carrier parents. There was no evidence that the missing male gene-carriers were lost by selective spontaneous abortion. There was no deficit of male-to-male or male-to-female transmission, excluding simple X-linked or simple mitochondrial inheritance. If genomic imprinting plays a role in the unequal female and male carrier frequencies in SB, penetrance should differ with parental sex. Penetrance was higher for offspring of female parents than of male parents, but the difference was not statistically significant. In addition, both male and female gene-carriers were frequently found in the same pedigree. Thus, the present data suggest a possible role for imprinting in SB.


Phenotypic evidence for a common pathogenesis in X-linked deafness pedigrees and in Xq13-q21 deletion related deafness.

A structural cochlear abnormality has been observed by high resolution CT scanning in some families where X-linked deafness is segregating. We now present evidence that the same abnormality is present in a deaf patient who has a deletion within Xq21. This observation provides phenotypic evidence that the genotypic basis of deafness is the same in both patient groups. It is also likely that the perilymphatic fluid "gusher" abnormality may be common to both.


Craniofacial dysostosis, hypertrichosis, genital hypoplasia, ocular, dental, and digital defects: confirmation of the Gorlin-Chaudhry-Moss syndrome.

We report clinical, orofacial and radiological manifestations in a 4-year-old girl and a 33-year-old female with the Gorlin-Chaudhry-Moss (GCM) syndrome. Typical findings in the GCM syndrome are short stature, stocky body build, midface hypoplasia, small eyes, downslanting palpebral fissures, conductive hearing loss, highly arched and narrow palate, malocclusion, abnormally shaped teeth, oligodontia, microdontia, low scalp hairline, hypertrichosis of scalp, face, trunk and limbs and genital hypoplasia. Radiological features include premature synostosis of the coronal suture, brachycephaly, and maxillary under-development. Hypoplasia of the distal phalanges of fingers and toes (also present in the 2 original cases) represents a further manifestation of the GCM syndrome.


Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells.

Five young patients with Niemann-Pick disease type B were treated with repeated implantations of amniotic epithelial cells, as a source of exogenous sphingomyelinase. This treatment abolished the recurrent infections, mainly of the respiratory tract, and led to other improvements of the general conditions of the patients. In particular, we noticed a disappearance of vomiting, a recovery from muscular hypotrophy, and significantly reduced pulmonary distress. In four subjects, who were in a prepuberal state, there was a puberal spurt with a concomitant burst of growth. In two cases, characterized by a greater than normal content of sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Finally, sphingomyelinase activity of peripheral leukocytes, when assayed 0.5 to 4 months after some of the implantations, showed a rise to heterozygous values in 30-40% of the assays.


Prader-Willi syndrome in a brother and sister without cytogenetic or detectable molecular genetic abnormality at chromosome 15q11q13.

We report on a 12-year-old boy and his 7-year-old sister with the Prader-Willi syndrome. They both had severe initial hypotonia with feeding problems and later developed an increasing appetite. Both sibs have almond-shaped eyes, triangular mouth, hypogonadism, retarded growth, and mental retardation. An older brother suffered from severe hypotonia and died at 7 days of age. The children have normal chromosomes by high-resolution technique and have inherited the same chromosomes 15 short arm polymorphisms from their parents. The family was informative for one of four DNA markers specific for the 15q11q13 region. No deletion was found using this marker. The parents were healthy and unrelated. Autosomal recessive inheritance or a paternally inherited submicroscopic deletion are possible explanations for the sib occurrence in this family.


Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis.

This study was designed to assess the incidence of amenorrhea with continuous combined therapy by using two different progestogens and to determine whether early bleeding predicts subsequent bleeding and endometrial response. Seventy-nine postmenopausal women on sequential estrogen-progestogen treatment were switched to continuous combined estrogen-progestogen therapy comprising conjugated equine estrogens 0.625 mg daily with either norethindrone acetate 0.35 mg twice daily or medroxyprogesterone acetate 2.5 mg twice daily added continuously for 78 weeks. All bleeding was recorded, and endometrial biopsies were performed at 26 and 78 weeks. Only one third of the women who starting the study had amenorrhea by week 78, but 46 (62%) of these women had withdrawn, mainly because of chronic irregular bleeding. Endometrial atrophy was observed in the majority of biopsy specimens. The two progestogens had similar effects. Bleeding patterns were useful predictors of subsequent bleeding, but not of endometrial response. Persistent irregular bleeding is common with continuous combined estrogen-progestogen therapy. Women with persistent early bleeding should probably revert to sequential treatment. Regular endometrial sampling is advised.


Presacral neurectomy for the treatment of pelvic pain associated with endometriosis: a controlled study.

Our objective was to evaluate the efficacy of presacral neurectomy combined with conservative surgery for the treatment of pelvic pain associated with endometriosis. In a randomized, controlled study performed in a tertiary institution 71 patients with moderate or severe endometriosis and midline dysmenorrhea were randomly assigned to conservative surgery alone (n = 36) or conservative surgery and presacral neurectomy (n = 35). Main outcome measures were relief of dysmenorrhea, pelvic pain, and deep dyspareunia after surgery according to a multidimensional and an analog pain scale. Presacral neurectomy markedly reduced the midline component of menstrual pain, but no statistically significant differences were observed between the two groups in the frequency and severity of dysmenorrhea, pelvic pain, and dyspareunia in the long-term follow-up. After presacral neurectomy, constipation developed or worsened in 13 patients and urinary urgency occurred in three and a painless first stage of labor in two. Presacral neurectomy should be combined with conservative surgery for endometriosis only in selected cases.


The clinical diagnosis of asphyxia responsible for brain damage in the human fetus.

Our objective was to review the clinical findings in infants who died in the perinatal period with brain damage attributable to asphyxia. The neuropathologic findings in 208 perinatal deaths have been reviewed. Thirty cases (22 fetal, eight newborn) had evidence of white matter or neuronal necrosis due to asphyxia. The clinical course of the pregnancy in 22 cases with brain damage attributable to fetal asphyxia were examined. The diagnosis of asphyxia was confounded by several factors: (1) asphyxia may occur at any time in the last half of pregnancy, (2) 50% of the antepartum asphyxia occurred when the pregnancy had no risk factors, (3) periodic fetal assessment in the complicated preterm pregnancies failed to identify the asphyxial episodes in the remaining cases of antepartum asphyxia, and (4) indicators of fetal asphyxia in the cases of intrapartum fetal asphyxia were obtained after the central nervous system injury had occurred. These findings highlight the difficulty in the diagnosis of fetal asphyxia at a stage that could permit intervention to prevent brain damage.


Cold therapy in the management of postoperative cesarean section pain.

Sixty-two patients were randomized to receive either localized cold therapy to the cesarean section incision or routine postoperative care. Evaluation of the amount of analgesia requested, infection rate, and length of hospital stay did not show a significant difference between the two groups. There is no objective evidence to show that the use of cold therapy in postoperative cesarean section pain relief is beneficial.


Perihepatic adhesions: not necessarily pathognomonic of pelvic infection.

Perihepatic adhesions are often considered to be associated with pelvic inflammatory disease and subsequent infertility. Seventeen patients out of 100 undergoing elective laparoscopic sterilization had evidence of perihepatic adhesions. Four of the 17 showed evidence of old pelvic inflammatory disease, but only two gave a history of sexually transmitted disease. All patients had a negative gonorrhea culture and 50 also had a negative chlamydia culture before the procedure. These data suggest that perihepatic adhesions may be observed in otherwise normal fertile women, and its presence does not necessarily imply pelvic inflammatory disease or poor fertility.


Prophylactic amnioinfusion improves outcome of pregnancy complicated by thick meconium and oligohydramnios.

The null hypothesis is that the use of intrapartum amnioinfusion in labors complicated by the presence of thick meconium and oligohydramnios will not decrease the incidence of fetal distress, cesarean delivery, meconium aspiration, or meconium aspiration syndrome. One hundred seventy term and postterm patients with thick meconium and oligohydramnios were randomly chosen to receive amnioinfusion or standard obstetric care without amnioinfusion. The frequency of fetal distress, cesarean section, meconium aspiration, and meconium aspiration syndrome were subject to chi 2 analysis, Student's t test, or Fisher's exact test. The rate of fetal distress was significantly reduced in the amnioinfusion group compared with controls (three of 85 vs 19 of 85, relative risk 0.15, 95% confidence interval 0.06 to 0.42). The rate of cesarean section for fetal distress was significantly reduced in the amnioinfusion group (two of 85 vs 17 of 85, relative risk 0.118, confidence interval 0.03 to 0.49). The rates of meconium aspiration (four of 85 vs 33 of 85, relative risk 0.12, confidence interval 0.0449 to 0.327) and meconium aspiration syndrome (0 of 85 vs five of 85, relative risk 0.09, confidence interval 0.009 to 0.872) were significantly reduced by amnioinfusion. Amnioinfusion improves the outcome in pregnancies complicated by thick meconium and oligohydramnios.


Spontaneous ovarian hyperstimulation syndrome concomitant with spontaneous pregnancy in a woman with polycystic ovary disease.

Ovarian hyperstimulation syndrome has been described after treatment with exogenous gonadotropins, clomiphene citrate, and gonadotropin-releasing hormone. Spontaneous ovarian hyperstimulation syndrome has not been described before, except in association with hypothyroidism. We report on a case associated with spontaneous pregnancy, occurring in a woman with polycystic ovary disease.


Screening for Down syndrome with the femur length/biparietal diameter ratio: a new twist of the data.

The purpose of this study was to determine the value of discordant morphometric measurements as identifiers of Down syndrome by evaluating the relationship of biparietal diameter, femur length, biparietal diameter/femur length ratio, and cephalic index between a group of fetuses with trisomy 21 and a control population. Biometric measurements from 48 fetuses with trisomy were reviewed and compared with 107 normal fetuses of similar gestational age. Data were analyzed in 2-week gestational age intervals to determine the effect of gestational age on ultrasonographic detection of Down syndrome. Outcome measures were subject to least-squares linear regression and the t test for analysis. A positive relationship between abnormal morphometric measurements and fetuses with Down syndrome was detected but only during specific weeks of pregnancy. Although it appears that biometric measurements may be useful for Down syndrome, further study is needed before its widespread introduction into clinical practice.


Rupture of uterine scar with extensive maternal bladder laceration after cocaine abuse.

A relationship between cocaine use and extensive rupture of a uterine scar has not been reported. We report such a case with extensive laceration of the maternal urinary bladder occurring after ingestion of cocaine.


Comparison of the efficacy of different local anesthetics and techniques of local anesthesia in therapeutic abortions.

The objectives of this study were to determine whether carbonated or plain lidocaine provides better pain control during abortions and to determine whether deep injections of lidocaine provide better pain control than regular injections of lidocaine. Phase 1 was a prospective, randomized, double-blind trial comparing 10 cm3 of 2% carbonated lidocaine with plain lidocaine. In phase 2 the plain lidocaine group in phase 1 was compared prospectively with the next group of patients, in whom a new technique of deep injection was used. A pain scale was administered by the counselor after dilatation and at the end of the procedure. The improvement in pain scores with carbonated lidocaine was 8%. The improvement with the deep injection technique was 25%. The improvement in pain scores with deep injection was clinically significant and is recommended.


Simultaneous ovarian and intrauterine pregnancy: case report.

The simultaneous presence of an ovarian and a normal intrauterine pregnancy is a very rare condition. We report such a case seen as an ovarian cyst during gestation. It was immediately and successfully treated, thus allowing for the normal physiologic continuation of the gestation.


Antibodies to Chlamydia trachomatis in sera of women with recurrent spontaneous abortions.

The relationship between high-titer immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortions was evaluated. Sera from the female partners of 258 couples with unexplained infertility, no history of chlamydial infection, and negative cervical cultures were diluted 1:128 and tested for immunoglobulin G antibodies to Chlamydia trachomatis. A subset of patients was also tested for antibodies to cytomegalovirus, cardiolipin, nuclear antigens, lactoferrin, and spermatozoa. Seven (41%) of 17 women with three abortions and 6 (60%) of 10 women with four abortions had chlamydial antibodies as opposed to 20 (13.5%) of 148 with no abortions, 6 (12.8%) of 47 with one abortion, and 4 (12.1%) of 33 with two abortions (p < 0.01). The incidence of > or = 3 spontaneous abortions was 31.8% among women with high-titer chlamydial antibodies and 7.5% among women who had seronegative results (p < 0.001). There was no relation between any of the other antibodies and > or = 3 abortions or antibodies to Chlamydia trachomatis. High-titer immunoglobulin G antibody to Chlamydia trachomatis was associated with recurrent spontaneous abortions. The mechanism may involve reactivation of a latent chlamydial infection, endometrial damage from a past chlamydial infection, or an immune response to an epitope shared by a chlamydial and a fetal antigen.


Randomized, double-blind study of cefotetan and cefoxitin in post-cesarean section endometritis.

The hypothesis of the study is that cefotetan and cefoxitin will be equally efficacious and safe in the treatment of post-cesarean section endometritis. In a double-blind, randomized manner 140 patients with post-cesarean section endometritis were treated with cefotetan, 2 gm intravenously every 12 hours, or cefoxitin, 2 gm intravenously every 6 hours. They were followed prospectively for clinical response and side effects. Cure rates between the two groups were compared with the chi 2 test. The cure rates were 83% for cefotetan and 79% for cefoxitin (p = 0.56). No patient required a change in therapy due to adverse effects, and no abnormal bleeding occurred. In this study cefotetan and cefoxitin appeared equally effective in treating endometritis with no difference in side effects or complications.


Interactions between intrauterine contraceptive device use and breast-feeding status at time of intrauterine contraceptive device insertion: analysis of TCu-380A acceptors in developing countries.

This paper is a reassessment of earlier findings from a preliminary analysis of data from a multicenter international trial regimen on breast-feeding and non-breast-feeding women in which events related to insertion, expulsion, and removal of the TCu-380A intrauterine contraceptive device (ParaGard 380) were investigated. Performance of the TCu-380A through 12 months after insertion was compared with life-table rate analysis, chi 2, Fisher exact test, or Student's t test. Variables were events reported during intrauterine contraceptive device insertion and events throughout the 12 months of study participation by breast-feeding status. Breast-feeding among intrauterine contraceptive device users was associated with fewer insertion-related complaints and lower removal rates for bleeding and pain. No uterine perforations were reported throughout the study. Differences in the performance of the TCu-380A intrauterine contraceptive device suggest physiologic effects associated with lactational amenorrhea. The TCu-380A intrauterine contraceptive device is a viable option for women breast-feeding at the time of intrauterine contraceptive device insertion.


Enhanced follicle regulatory protein levels accompany reinitiation of ovulatory function after parturition.

We examined the changes in follicle regulatory protein, estrone-3-glucuronide, pregnanediol-3-glucuronide, and luteinizing hormone levels in first-morning urine samples from postpartum, fully breast-feeding women to characterize the reemergence of these urinary hormones after pregnancy ovarian quiescence and early postpartum period and to determine whether follicle regulatory protein could be used prospectively to predict the return of fertility. Twenty-five hundred urine samples collected from six postpartum women were evaluated. Daily urine samples collected from normally cycling women were used to establish normal urinary hormone and hormone metabolite cyclicity. Luteinizing hormone, estrone-3-glucuronide, and pregnanediol-3-glucuronide levels were measured by radioimmunoassay. Follicle regulatory protein level was assayed with a double-antibody enzyme-linked immunosorbent assay. Although follicle regulatory protein levels were found to be very low or undetectable in early postpartum urine, they began to rise with episodes of estrone-3-glucuronide and pregnanediol-3-glucuronide secretion. A chi 2 analysis suggests that increasing urinary follicle regulatory protein levels are most closely associated with the luteal phase of the first menstrual cycles in postpartum women. These results suggest that follicle regulatory protein is of little value in predicting either the onset of renewed ovarian activity or the fertile period.


Immunolocalization of the vasoconstrictor endothelin in human endometrium during the menstrual cycle and in umbilical cord at birth.

Our objective was to determine the localization of immunoreactive endothelin in human cyclic endometrium and in umbilical cord during normal delivery and after cesarean section. Fixed dated endometrial tissue (n = 41) and umbilical cord (n = 6) were subjected to immunohistochemistry with an antiserum cross reacting with endothelin-1, -2 and -3. Low levels of stromal endometrial staining were seen throughout the cycle. The strongest staining was in luminal epithelium throughout the secretory phase and in glandular epithelium in the late-secretory phase. In umbilical cord the most intense immunoreactivity was present on the amnion cells on the outer cord, with some staining in intermittent cells in the Wharton's jelly and in umbilical vein cells. No differences were detected between cord from normal delivery or cesarean section. A paracrine role is suggested for endothelin in regulation of endometrial function and a role in vasoconstriction in the umbilical cord at birth.


Reduced platelet tritium-labeled imipramine binding sites in women with premenstrual syndrome.

We studied the possible role of serotonergic systems in the cause of premenstrual affective symptoms. The binding of tritium-labeled imipramine to platelets is thought to parallel central nervous system binding and to indicate serotonergic activity. We measured platelet tritium-labeled imipramine binding sites in the follicular and luteal phases in 12 controls and in 9 women with well-documented late luteal phase dysphoric disorder. In statistical analyses we used repeated measures analysis of variance, with Student-Newman-Keuls and Duncan's one-tailed t tests, and Pearson's r. The values of subjects with late luteal phase dysphoric disorder were lower than those of controls (F [1,39] = 5.13, p = 0.03). Both follicular and luteal phase level were lower in subjects with late luteal phase dysphoric disorder but reached statistical significance only in the follicular phase. Lower platelet tritium-labeled imipramine binding in women with late luteal phase dysphoric disorder supports the hypothesis that alteration of central serotonergic systems may contribute to premenstrual dysphoric symptoms.


The development of ultradian rhythms in the human fetus.

Our objective was to determine the normal sequence of neurobehavioral development in the human fetus between 14 weeks' gestation and delivery. The study was performed by longitudinal ultrasonographic observation of 45 low-risk singleton fetuses. During the first half of the midtrimester there was a high rate of spontaneous movement that appeared randomly distributed. By the end of that trimester an increase in the duration of intervals of quiescence resulted in activity appearing cyclically distributed, with the duration of quiet cycles progressively increasing to term. Fetal mouthing and breathing were linked with cyclic behavior from the time of their emergence. Fetal heart rate pattern A could be recognized from around 32 weeks, due to a reduction in baseline variability in quiet cycles after 30 weeks, whereas pattern B could be recognized several weeks earlier. From the time cyclic behavior and heart rate patterns could be recognized, intervals of coincidence of the fetal behavioral state variables increased progressively with advancing gestation.


Effect of calcitonin gene-related peptide on the uterine vasculature of the nonpregnant ewe.

The current study was designed to evaluate the uterine vascular effects of calcitonin gene-related peptide on the uterine vasculature of nonpregnant sheep and compare them with the effects of prostacyclin. Five nonpregnant oophorectomized ewes were instrumented with uterine and pulmonary artery flow probes and catheters. Dose-response curves were constructed according to increasing doses of calcitonin gene-related peptide (0.01, 0.03, 0.1, 0.3, 1, and 3, micrograms/min) and prostacyclin (0.03, 0.1, 0.3, 1, 3, and 10 micrograms/min) via 10-minute uterine artery infusions. Both calcitonin gene-related peptide and prostacyclin produced a significant increase in uterine blood flow and a decrease in uterine vascular resistance. Calcitonin gene-related peptide was found to be approximately 17 times more potent than prostacyclin as a vasodilator. Local uterine artery infusions of calcitonin gene-related peptide led to significant increases in heart rate but did not alter blood pressure, cardiac output, or total peripheral resistance at the doses tested. In contrast, at doses of prostacyclin that produced similar uterine vasodilatation, prostacyclin led to significant decreases in systemic arterial blood pressure and total peripheral resistance and increases in heart rate and cardiac output. These data strongly suggest that calcitonin gene-related peptide, an endogenously occurring vasoactive peptide, could play an important role in regulating uterine and systemic hemodynamics.


An ultrastructural study of the developing urogenital tract in early human fetuses.

This study examines the gonoducts during the ambisexual stage of human fetal development to define their ultrastructural characteristics, including the origin and antomic relationship of the mesonephric and paramesonephric ducts during gonoductal development. The reproductive tracts from five fetuses ranging in gestational age from 35 to 45 days were processed for ultrastructural examination. The developing mesonephric ducts, paramesonephric ducts, and their surrounding mesenchyme were studied with a Phillips 300 transmission electron microscope. The mesonephric ducts and paramesonephric ducts have distinctive cytoplasmic and cell surface ultrastructural characteristics, as well as different morphologic patterns of epithelial-mesenchymal interaction. Cephalad portions of mesonephric ducts and paramesonephric ducts are separated by mesenchyme, but more caudal aspects move progressively closer until they are juxtaposed but separate. Early mesonephric ducts and paramesonephric ducts may be distinguished because of their distinctive ultrastructural features; epithelial-mesenchymal interaction may be important in their differentiation and maintenance; both gonoducts retain their morphologic identity throughout, supporting their separate origins.


Ethically justified guidelines for family planning interventions to prevent pregnancy in female patients with chronic mental illness.

This article proposes ethically justified clinical guidelines for family planning interventions to prevent pregnancy in female patients. We reviewed literature on family planning and consequences of pregnancy in patients with chronic mental illness and related that literature to ethical principles. Patients with chronic mental illness are ethically unique because they have chronically and variably impaired autonomy. Existing guidelines and proposals for family planning interventions for mentally retarded patients are shown not to apply to such patients. Three sets of guidelines for three groups of patients, representing the continuum of chronically and variably impaired autonomy, are proposed: (1) a set of guidelines for patients who can achieve thresholds of autonomy, (2) a set of guidelines for patients irreversibly near thresholds of autonomy, and (3) a set of guidelines for patients irreversibly below thresholds of autonomy. These guidelines should contribute significantly to the quality of obstetric and gynecologic care for female patients with chronic mental illness.


Activation of protein kinase C stimulates collagenase production by cultured cells of the cervix of the pregnant guinea pig.

Dilatation of the uterine cervix at parturition is achieved by an estrogen-induced, collagenase-mediated degradation of type I collagen in the cervix. The objective was to test the hypothesis that collagenase production in the cervix of pregnant guinea pig in culture is mediated by activation of protein kinase C. The effects of 17 beta-estradiol, prostaglandin F2 alpha, or activation of protein kinase C by phorbol-12-myristate-13-acetate, 1-stearoyl-2-arachidonyl-sn-glycerol and phospholipase C on collagenase production was studied with primary monolayer cultures of cervical cells from Hartley guinea pigs at 50 days' gestation. Results are analyzed for statistical significance with analysis of variance. Collagenase production is increased twofold to threefold by 17 beta-estradiol, prostaglandin F2 alpha, or activation of protein kinase C. The observed stimulation of collagenase production by 17 beta-estradiol and prostaglandin F2 alpha was blocked by the protein kinase C inhibitor 1-(5-isoquinoline sulfonyl) 2-methylpiperazine dihydrochloride. Collagenase production in cultured cervical cells of pregnant guinea pig is stimulated by activation of protein kinase C.


Hydrogen peroxide and reoxygenation cause prostaglandin-mediated contraction of human placental arteries and veins.

Because our previous studies in several vascular preparations suggest that posthypoxic reoxygenation elicits tone responses by generation of hydrogen peroxide we compared the actions of reoxygenation and hydrogen peroxide on isolated human placental arteries and veins. Endothelium-intact and denuded arteries and veins (1 to 2 mm diameter, from normal term deliveries), incubated under 95% oxygen/5% carbon dioxide or 5% oxygen/5% carbon dioxide (balance nitrogen) and precontracted with 1 to 10 nmol/L U46619, were exposed to hypoxia (95% nitrogen/5% carbon dioxide, PO2 8 to 10 torr) followed by reoxygenation and to 1 to 100 mumol/L hydrogen peroxide in the presence and absence of the inhibitor of prostaglandin biosynthesis, 10 mumol/L indomethacin. In both arteries and veins posthypoxic reoxygenation or exposure to hydrogen peroxide produced vascular contraction that was eliminated or reversed to a modest relaxation by indomethacin, consistent with mediation by prostaglandins. Hypoxia after incubation with 5% oxygen, but not 95% oxygen, caused a modest prostaglandin-independent relaxation. Removal of the endothelium did not alter any of these responses. Placental arteries and veins show a similar prostaglandin-mediated contraction to hydrogen peroxide and posthypoxic reoxygenation, consistent with a possible involvement of hydrogen peroxide in the response to reoxygenation.


Changes in expression of the cyclooxygenase gene in human fetal membranes and placenta with labor.

Our objective was to examine the expression of the gene coding for cyclooxygenase, the central enzyme in prostaglandin synthesis, in human placenta and fetal membranes during pregnancy and before and after labor at term. Expression of the gene for cyclooxygenase was examined with Northern hybridization to ribonucleic acid from human placenta throughout pregnancy and human amnion and chorion decidua in the late third trimester. Expression was undetectable in trophoblast during the first and second trimesters. Expression in amnion and trophoblast increased 3.5- and 2.5-fold, respectively, in association with labor. Our results suggest that the increase in prostaglandin synthesis within the uterus that is seen with the onset of labor is associated with an increase in the expression of the gene cyclooxygenase.


A novel change in cytologic localization of human chorionic gonadotropin and human placental lactogen in first-trimester placenta in the course of gestation.

Cytologic localization of human chorionic gonadotropin and human placental lactogen in developing human early placenta was analyzed by avidin-biotin immunoperoxidase techniques with an affinity-purified polyclonal antibody to beta-human chorionic gonadotropin carboxyl terminal peptide and a polyclonal antibody to human placental lactogen. In 4- to 5-week placentas human chorionic gonadotropin and human placental lactogen were found to be primarily localized to cytotrophoblasts, whereas in 6- to 12-week placentas these substances were exclusively localized to syncytiotrophoblast. We previously reported that a similar change in cytologic localization of epidermal growth factor and its receptor from cytotrophoblasts to syncytiotrophoblast in first-trimester placenta appeared between 5 and 6 weeks of gestation. Because epidermal growth factor was demonstrated to stimulate human chorionic gonadotropin and human placental lactogen production by early placental tissues, their simultaneous expression, as well as epidermal growth factor and its receptor in the cytotrophoblast of 4- to 5-week placenta and in the syncytiotrophoblast of 6- to 12-week placenta, implies that human chorionic gonadotropin and human placental lactogen production by first-trimester placenta may be regulated in an autocrine manner, wherein epidermal growth factor may serve as the signal. These findings suggest that in very early placenta, before 6 weeks of gestation, no sequential expression of human chorionic gonadotropin and human placental lactogen closely linked to syncytia formation may exist and that both can be expressed in the cytotrophoblast or undifferentiated stem cell of villous trophoblast in very early placenta.