Considerations for physicians caring for older adults with periodontal disease.

Periodontal disease is a generic term encompassing a variety of inflammatory conditions affecting the supporting tissues of the teeth. Periodontitis is inflammation associated with net resorption of supporting alveolar bone and periodontal ligament. Gingivitis is inflammation limited to the covering gingival tissues and does not directly lead to tooth mobility or loss. Periodontal diseases are very prevalent. Because the bone and ligament resorption are essentially irreversible, accumulated tissue damage of periodontitis is reflected in a prevalence and severity that increase with age. Periodontitis is not caused by aging per se but by a complex host-parasite relationship in which specific pathogens among the subgingival microbiota not only injure tissues directly but stimulate a cascade of inflammatory mediators to damage host tissues. Analytic epidemiology has identified several risk indicators for advanced periodontitis in older adults. These are microbiologic (prevalence of certain anaerobes in the microbiota), behavioral (tobacco smoking and infrequent professional dental care), medical (older age, preexisting and generalized periodontitis, gingival bleeding), and social (financial worries). Periodontitis in older adults is treated by reducing the impact of these risk indicators. The infections are controlled by combinations of debridement, antimicrobial agents, and surgical procedures as indicated. Medically well older adults can be treated similarly to younger adults. Management of periodontal conditions can be complicated for patients who are medically compromised. Communication between physicians and dental personnel is often required to ascertain the medical history and list of medications taken by older patients. Many of the medications prescribed for medical problems associated with aging impact on treatment choices for managing periodontitis. Moreover, periodontists frequently prescribe analgesics, antibiotics, and anti-inflammatory agents that might interact with others among the numerous drugs taken by older patients. Older adults with cognitive or physical disabilities have special needs for individualized hygiene instruction and implements. Periodontal health promotion and improving access to periodontal care for the elderly are challenges, because dental services are most often in the private sector and dental insurance does not often apply after retirement. Because they grew up in an era in which tooth loss due to "gum" diseases was considered inevitable, their current motivation toward regular preventive care must be improved by removing barriers and impediments to care. In addition to life-threatening medical conditions, frail individuals institutionalized in collective living centers face compounded problems concerning the provision of adequate, not even optimal, dental care. Their periodontal health often deteriorates rapidly after institutionalization, and in some instances it can possibly predispose to aspiration pneumonia or other disseminated infections.(ABSTRACT TRUNCATED AT 400 WORDS)


Oral and maxillofacial surgical therapy for the older adult.

Older adults can present with a wide range of oral and maxillofacial diseases and conditions, and many of these are best treated surgically. One of the distinguishing features of geriatric surgery is the large percentage of older adults who have medical conditions that must be planned for perioperatively. Good communication between the surgeon and the primary care physician is important for this perioperative management. Orofacial infections, the most common of which are odontogenic in origin, require some form of surgical treatment and may or may not require treatment with antibiotics. Preprosthetic and reconstructive surgery may be necessary to treat the sequelae of oral and maxillofacial fractures, the sequelae of tooth loss, or surgical defects incurred during the treatment of cancer, osteomyelitis, osteoradionecrosis, or disorders of the TMJ.


Conventional and implant oral prostheses.

Despite advances in preventive dentistry, many elderly persons present with several missing teeth replaced by oral prostheses of various kinds. An increasing number of prostheses are retained and supported by oral implants. Maintaining a complete dentition with fixed, removable, or implant-retained prostheses improves function and patient self-esteem. Irrespective of the prosthesis type, periodic functional and health reassessments are necessary. Strict oral hygiene protocols must be reinforced continually and appropriate modifications (relines) and repairs should be performed to prevent possible degeneration of supporting structures. Although implants promise enhanced function and greater patient satisfaction, they too require careful maintenance. Thus, all oral prostheses require close monitoring and maintenance care. A physician can make an important contribution to a patient's health and quality of life by ensuring that he or she receives routine oral health care.


Oral health and the quality of life.

The study of the impact of oral diseases and conditions on individuals and societies has been slow to develop but has made major progress during the 1980s. Not only did improvements in understanding oral quality of life require developing and using more social and behavioral outcome measures, it required reassessing clinical indices. Reports on oral quality of life to date are often based on investigations that originally had other purposes; consequently there is inconsistent evidence about the associations among oral health, general health, and quality of life. In fact, in much of the cited literature the evidence is equivocal. Yet, in more recent research designed specifically to investigate quality of life (Meei-Shia Chen, PhD, personal communication, 1991), it is evident that orofacial conditions, diseases, and pain can be disruptive and can have considerable impacts at both the individual and societal levels in terms of reduction in normal activities; conversely, medical and social conditions can affect oral health. It is notable that across studies there is an incongruence between health care professional and patient assessments of quality of life--they view the issues differently. Although oral diseases are very prevalent, the early symptoms are often not severe, leading many individuals to disregard them, or if acknowledged, to define them as normal or unimportant. This may reflect a form of fatalism, i.e., their oral health is as good as could be expected. It is necessary to assess oral health and quality of life over time. Individuals indicating satisfaction or dissatisfaction with appearance, function, and self-esteem at one point in time are doing so against a framework of immediate or long-term expectations. In regard to specific procedures, such as surgery or dentures, it is necessary to know what the individual expects if the health care professional is to provide improvements in perceived and actual quality of life. Similarly, it is difficult to provide meaningful interpretation of self-assessed physical and social functioning and appearance against clinical measures, if the level of earlier dysfunction is not known. For example, in the case of full denture wearers, the evidence might be interpreted to suggest that these individuals have excellent oral quality of life. Without taking into account the extent of physical and social dysfunction and poor appearance prior to the dentures, and the consequent improvement against this base, it is impossible to evaluate and consequently improve quality of life. Understanding this process requires longitudinal studies.(ABSTRACT TRUNCATED AT 400 WORDS)


Problems in oral health care financing for the elderly.

The oral health of America's aged has improved dramatically. As the number of elderly swell, their collective need and demand for comprehensive dental services will increase significantly. Payment for those services will pose problems for many, because few options exist for financing dental care among the elderly. Currently most charges are covered by individuals out-of-pocket. Although more older people than ever before have sufficient funds to include dental visits in their health services use, a large proportion of the elderly lack the personal resources necessary to have their numerous dental conditions treated. Innovation is critical. Greater public and private sector support for accessible and affordable dental services must be offered in the future to ensure that the oral health gains of the past decades are not lost because of a lack of financial mechanisms for supporting an adequate level of care.


The meaning of quality of life for bone marrow transplant survivors. Part 2. Improving quality of life for bone marrow transplant survivors.

Surviving bone marrow transplant (BMT) represents a major victory against malignant disease but also creates challenges of survivorship for patients and the professionals who care for them. Part 2 of this report presents the findings of a qualitative study (N = 119) related to improving quality of life (QOL) for BMT survivors. Results are shared based on BMT survivors' perceptions of (a) what makes QOL better, (b) what makes QOL worse, and (c) what doctors or nurses could do to enhance QOL. The findings of the study have been useful in constructing a quantitative instrument to measure QOL in BMT and in understanding the conceptual basis of QOL for the BMT population. Nursing interventions can improve the QOL for the BMT patient across all phases of the transplant process and long-term issues related to survival.


The optimal functioning plan. A key element in cancer rehabilitation.

Individuals with cancer should be assisted to achieve optimal levels of functioning before, during, and after cancer treatment. However, to reach optimal functioning a well-defined plan of action is required. This article presents an Optimal Functioning Plan (OFP) aimed at attaining the best possible outcomes for all individuals treated for cancer. The OFP centers on physical functioning, nutritional adequacy, a practical level of independence in activities of daily living, self-care competence, a realistic optimistic outlook, and effective management of side effects. The OFP is a key element of cancer rehabilitation. It represents a way of packaging cancer care in a health-oriented framework.


Nursing diagnoses in an oncology population.

The purposes of this study are to identify the nursing diagnoses occurring in an oncology population, to validate these using the clinical validation model, and to determine whether clusters of defining characteristics and etiologies occurred among the diagnoses identified. Secondary analysis was conducted using the patient care records of 48 oncology patients. Twenty-five nursing diagnoses were identified. The most common diagnoses were alteration in comfort (pain) and alteration in nutrition (less than body requirements). The etiologies of stress, pain, life changes, disease, and treatment occurred in some combination in 14 diagnoses. The defining characteristics of pain and fatigue/weakness occurred in over six diagnoses. Clusters of defining characteristics occurred with eight diagnoses. Clusters of etiologies occurred with the diagnosis of sleep/rest disturbance. Validation of defining characteristics and etiologies indicated variation from those proposed by the North American Nursing Diagnosis Association. One overriding variation was in the degree of specificity of defining characteristics used in clinical practice. The findings of this study support the need for continued validation of nursing diagnoses and continued education of nurses in the use of nursing diagnoses. The findings also contribute to the body of knowledge in nursing diagnoses in oncology patients, and contribute to the work beginning to be done in the field of nursing diagnosis with research into the existence of clusters of defining characteristics, etiologies, and/or nursing diagnoses.


The effects of treatment for cancer on male fertility and sexuality.

The sequelae of some treatments for cancer, by virtue of their systemic action, adversely affect three aspects of male sexuality: desire, physical function, and cytokinetic gonadal processes. Other more localized therapies, such as surgery and radiation therapy, may affect only one aspect. Frequently, the effects of cancer therapy are interrelated, thus making it difficult to identify any single problem. This article discusses the impact of medical therapy, including chemotherapy, surgery, radiation therapy, and hormonal manipulation, as they relate to male sexuality. Interventions to promote sexual rehabilitation, either by intensive therapy or nursing actions, are discussed.


Comparison of two breast self-examination palpation techniques.

In this randomized clinical trial, we compared the vertical strip (VS) and the concentric circle (CC) patterns of breast palpation in order to determine which pattern provided the most thorough self-examination and the best lump detection in breast models. The sample consisted of 34 adult women from a Veterans Outpatient Clinic in the Northwest who were assigned according to breast size (large or small) to one of two groups. Subjects were pretested and randomly taught one method of palpation. Proficiency in the palpation technique, area covered, and number of lumps detected were evaluated. Interrater reliability for proficiency evaluation was 86%. During breast self-examination, the VS group covered significantly more area than the CC group (t = 2.72, p = 0.01). Breast size did not affect breast area covered. Lump detection using breast models did not differ between the two groups. Though this study did not support the conclusion that increased thoroughness leads to increased lump detection, there is support in the literature. Lack of difference in lump detection in this study may have been due to the constraints of the breast models used. However, further research is needed.


Distress in cancer patients and primary nurses' empathy skills.

This descriptive, correlational study was designed to explore the relationship between the empathy skills of primary nurses and the distress level of their primary patients. Data on empathy skills were generated from the La Monica Empathy Profile. Data on patient distress were generated from the Profile of Mood State Inventory and a Visual Analogue Scale. A nonprobability convenience sample of 65 primary nurses employed on surgical primary nursing care units of a large teaching hospital participated in the study. Sixty-five cancer patients assigned to the participating primary nurses also took part in the study. Descriptive statistics of each variable were examined. Pearson product-moment correlations were used to examine the hypothesis and the demographic variables for nurses and patients. Analysis of variance was used to assess relationships among many of the demographic variables. A significant correlation (but not in the expected direction) was found between the perceiving/feeling/listening empathy skill and patient distress. Nurses' age, years of experience, and education were significantly correlated with some empathy skills. Distress levels of female patients were higher than those of male patients. In general, nurses scored low in the use of empathy skills, and patients scored low in distress. The complex nature of defining and measuring communication skills and relating these skills to outcomes in patient care, such as distress, requires more study. Research questions exploring how and why nurses' interpersonal skills make a difference to patients and their health care outcomes must be generated by nurse administrators, nurse educators, nurse researchers, and practicing nurses.


Using diversional activity to enhance coping.

Diversional activity deficit, a nursing diagnosis that occurs with prolonged hospital treatment, requires creative and practical ways for nurses to support patients. A tool designed to assess diversional needs is described. Benefits include improved relationships and enhanced patient coping with a minimum of cost and inconvenience.


Exploration of home care resources for rural families with cancer.

The purpose of this qualitative study was to explore the availability and perceived adequacy of formal resources to assist family caregivers of rural persons with cancer. Ten participants who had provided home care for a family member with cancer throughout their illness and death were interviewed in two focus groups. An important finding was that the more rural the family, the more limited and inadequate the formal resources available to assist the family. A second major finding was that the longer the dying trajectory and the greater the deterioration of the person with cancer, the more resources became inadequate and the greater the caregiver burden.


[Silent ischemic cardiopathy: a study with dynamic electrocardiogram and ergometric test].

Ninety-two patients with effort angina were retrospectively studied to define the prevalence, the daily distribution and the prognostic value of silent ischemic attacks. All patients had positive Holter monitoring and exercise test; coronary angiography, performed in 75/92 patients, showed 1, 2 or 3-vessels disease. Six hundred ninety-three ischemic episodes, 481 (69.5%) silent and 212 (30.5%) symptomatic, were recorded by Holter monitoring, with the highest incidence in the morning; 74/92 patients (80%) showed silent ischemic attacks. Mean duration of the symptomatic and silent ischemic attacks was respectively 9.8 +/- 5.2 and 6.4 +/- 4.2 min (p less than 0.0001); mean ST-segment depression was respectively 2.8 +/- 1.2 and 2.3 +/- 0.8 mm (p less than 0.0001). During exercise testing 86 patients (93%) had both chest pain and ST-segment changes, 2 patients (2%) only angina and 4 patients (5%) only ST-segment depression. Mean heart rate at onset of ischemia was higher during exercise testing compared with Holter monitoring (119 +/- 20 vs 95 +/- 22 b/min; p less than 0.0001). No significant difference was shown between patients with and without silent ischemia about the prevalence of 1, 2 and 3-vessels disease; 1-year cardiovascular mortality in the 2 groups of patients was respectively 6.8% and 5.5% (p:NS). In patients with effort angina, silent ischemia has not a poor prognostic value; Holter monitoring is very useful to the correct assessment of these patients.


[Intraoperative evaluation of tricuspid valve annuloplasty with transesophageal echocardiography].

The present study shows a new application of transesophageal echocardiography (TEE) to optimize tricuspid valve annuloplasty. Eighteen patients with tricuspid regurgitation (TR) underwent De Vega tricuspid annuloplasty. After cardiopulmonary bypass the tension on the suture was adjusted until the surgeon could not feel any regurgitant jet by intraatrial palpation; subsequently, the tension was further adjusted on the basis of TEE. The post-pump residual tricuspid regurgitation was assessed by semiquantitative grading of tricuspid regurgitation (0 to 4+), area of regurgitant jet and percentage of right atrial area subtended by jet area. The data obtained by intraatrial palpation were compared with the data obtained by TEE. A significant reduction of residual tricuspid regurgitation was shown by TEE when compared to intraatrial palpation. After a follow-up period of 2 weeks, no significant changes in the grade of TR were observed. The results showed that the use of TEE was able to optimize the De Vega's tricuspid annuloplasty.


[Ambulatory coronary arteriography with 5 French catheters: experience with 604 procedures].

Ambulatory coronary arteriography was carried out in 604 patients, 143 women and 461 men, mean age 53 +/- 14 years. An absolutely stable clinical condition was the main criterion of selection for this investigation and the protocol consisted in day-hospital admission, absence of routine anticoagulation, small calibre (5 French = 1.7 mm diameter) catheters, mobilization 4 hours and discharge 6 hours after the end of the procedure. The percutaneous femoral approach was used in 95% of cases; 56% of patients presented significant single-or multi-vessel coronary artery disease: there were 7 cases of left main coronary artery narrowing; 31 patients required full hospital admission, mainly because of the severity of coronary lesions. Minor complications occurred in 2% of cases.


[Color-Doppler echocardiography in electromechanical dissociation. Study of 2 cases].

Electromechanical dissociation (EMD) is a condition of cardiac arrest occurring despite the persistence of apparently effective cardiac electric activity. Secondary EMDs are consequence of catastrophic circulatory failure (i.e. great vessel rupture, massive pulmonary embolism, cardiac tamponade), resulting in sudden and critical changes in hemodynamic load. Primary EMDs, on the other hand, occur in presence of intact circulatory system; they are known to be associated with global cardiac ischemia and contraction failure; however, the exact pathophysiologic change, triggering the onset of primary EMD, is still unknown. The current hypothesis of electromechanical uncoupling (a supposed derangement of excitation and contraction linking) has not been demonstrated. On the contrary, in a previous series of 22 2D-echocardiographic evaluations of patients with EMD, wall and valvular motion was visible in the majority of cases. In our Coronary Care Unit we had the opportunity to perform 2D and color-Doppler echocardiogram in 2 patients, developing primary EMD just while the examination was in course; we subsequently completed the examinations in the short pauses of cardio pulmonary resuscitation. Both patients died and necropsy showed in both cases recent large myocardial infarction, without hemopericardium. The analysis of the echocardiograms emphasized the presence of a residual cardiac mechanical activity: minimal segmental wall motion of left ventricle (LV); residual mitral valve motion, but no visible closure; diastolic low-velocity orthograde transmitralic flow; systolic regurgitant flow from LV to left atrium. On the other hand, we didn't observe any systolic flow directed to the LV outflow tract and to the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)


[Anomalous insertion of the mitral valve. A rare form of subaortic obstruction in children].

Among different anatomical causes of subaortic obstruction, anomalous attachment of the mitral valve on ventricular septum is one of the rarest. We report our experience with 4 such cases of subaortic obstruction. Their age at first observation ranged between 1 and 6 months. All patients had viscero-atrial situs solitus, levocardia and normal atrio-ventricular and ventriculo-arterial connections. None had associated cardiac septal defects. Cases with atrio-ventricular canal were excluded. All patients showed a systolic ejection murmur and electrocardiographic features of left ventricular hypertrophy; 3 presented congestive heart failure in the first 3 months of life. Diagnosis was made by 2D-echocardiography and cardiac catheterization in 3 patients and intraoperatively in 1. Only in the last 2 patients, correct diagnosis was made at the initial 2D-echocardiographic examination. Due to left ventricular hypertrophy, in the first 2 patients hypertrophic obstructive cardiomyopathy was originally suspected. One patient died intraoperatively during attempted transaortic resection of subaortic obstruction. Other 2 patients underwent left ventricle-aortic conduit implantation. Of these 2 patients, 1 died 3 months later for sepsis and the other was reoperated upon 3 years later for mitral valve replacement and conduit take-down, with good clinical result. The fourth patient is waiting for surgical intervention. Subaortic obstruction due to anomalous attachment of the mitral valve on ventricular septum may present with early congestive heart failure; the best diagnostic tool is 2D-echocardiography. Left ventricle-aortic conduit may represent a surgical alternative to transaortic resection.


Ambulatory (Holter) electrocardiography technology.

Ambulatory ECG is an evolutionary cardiovascular discipline with regard to both its clinical applications and technology. With the technologic advances of the past decade, powerful personal computers have expanded the traditional clinical role of ambulatory ECG examination for cardiac arrhythmias to detection of ST-segment changes, heart-rate variability, QT interval measurement, and the signal-averaged ECG. These expanded clinical applications increase the practicality of a 24-hour ambulatory ECG on an individual cardiac disease patient and make the 24-hour ambulatory ECG one of the most cost-effective cardiovascular diagnostic tests when used properly. The current clinical developments make valid ST-segment detection and quantitation readily available and heart-rate variability an easily applied investigative tool to a wide spectrum of diseases. Automatic QT interval measurements and signal averaging of ambulatory ECG are just technologically emerging and can be expected to develop more in the near future.


Ambulatory electrocardiography evaluation of supraventricular tachyarrhythmias and bradyarrhythmias.

Long-term ECG recordings are of great value in the diagnosis and management of patients with cardiac arrhythmias. Information from programmed stimulation studies and intracardiac recordings has markedly improved the diagnostic abilities of the person examining the long-term ECG recording. This article discusses how knowledge from intracardiac electrophysiologic studies has resulted in much better recognition of the type and mechanisms of a supraventricular arrhythmia on the Holter record.


Evaluating patients with ventricular arrhythmia. Role of the signal-averaged electrocardiogram, exercise test, ambulatory electrocardiogram, and electrophysiologic studies.

There are several methods available for the evaluation of patients with ventricular arrhythmia. The most effective approaches, however, involve the use of techniques that provide objective data. These include ambulatory monitoring and exercise testing (a noninvasive approach), and electrophysiologic testing (invasive). The information derived from these two approaches is complementary, and both are important for patient evaluation and management. These methods are useful for establishing the risk of arrhythmia occurrence in certain patient groups and for establishing the effect of antiarrhythmic agents. The signal-averaged ECG is of help in establishing risk in some patient groups, but it has no role for evaluating drug therapy.


Drug-induced early and late proarrhythmia.

Proarrhythmia is the provocation of a new arrhythmia or the exacerbation of a spontaneously occurring arrhythmia due to drug therapy. A drug's toxic effect may occur early after its initiation, and specific definitions have been offered to detect its presence. Primary and secondary forms of proarrhythmia as well as the type of early proarrhythmic events (fatal, serious, and nonserious) have been recognized. More recently, the concept of a late proarrhythmic event (enhanced arrhythmic death) has been defined using placebo-controlled trials. This late proarrhythmic response is extremely important in defining the benefit versus risk ratio that is the key to proper use of drug therapy.


Current concepts of pathophysiology, circadian patterns, and vasoreactive factors associated with myocardial ischemia detected by ambulatory electrocardiography.

Transient ST-segment changes during continuous ECG monitoring occur not only in many clinical ischemic syndromes, but also in a proportion of the normal population. The pathophysiology of episodes of ST-segment change that represent transient periods of myocardial ischemia varies according to the underlying disease process, which may include stable coronary artery disease, unstable angina, variant angina, and syndrome X. Patients with stable coronary artery disease have episodes of ischemia as a result of an imbalance between increases in myocardial oxygen demands and changes in coronary blood flow due to physiologic changes in coronary vasomotor tone. Both these factors are subject to a circadian rhythm that results in a preponderance of ischemia in the morning hours. Vasospasm, often beyond the physiologic range, in localized segments of epicardial coronary arteries causes ischemia and ST-segment changes in variant angina, whereas luminal thrombosis with superimposed vasoconstriction is an important cause of continued ischemia in unstable angina.


Ambulatory electrocardiography evaluation of asymptomatic, unstable, and stable coronary artery disease patients for myocardial ischemia.

Transient episodes of myocardial ischemia can be reliably detected by AEM in patients with known CAD. AEM appears to be particularly useful for patients in whom symptom control has been achieved with conventional antianginal drugs because many of these patients (up to 50%) continue to have residual silent ischemia that would otherwise remain undetected. Despite the lack of symptoms, numerous studies in patients with stable and unstable coronary syndromes have shown that the presence of silent ischemia during AEM is associated with an increased risk of subsequent coronary events and cardiac death. Although Holter monitoring is a practical and reliable tool for prolonged evaluation of myocardial ischemia, its routine use can not be advocated until its clinical role has been clearly defined in the ongoing large prospective studies.


Ambulatory electrocardiography evaluation of the post-coronary artery bypass graft and post-percutaneous transluminal coronary angioplasty patient. Diagnostic and prognostic value.

Investigations carried out in recent years have shown that patients with coronary heart disease display partial to considerable extent transient ST-segment changes that can be determined with ambulatory ECG. An interesting question is how often transient ST-segment changes are present in patients in whom the indication for an aortocoronary bypass operation or percutaneous transluminal coronary angioplasty (PTCA) has already been determined. In the patients who are waiting for a bypass operation or PTCA, the proof of myocardial ischemia has been determined, and which subgroups of patients display ST changes in the ambulatory ECG must be tested. It is interesting to ask what happens to such transient ischemic episodes as a result of surgical or catheter intervention, how often such episodes are present even after these interventions, and whether the latter has a clinical significance in view of the success of the intervention (graft patency in coronary artery bypass graft patients or reocclusion in PTCA patients). Furthermore, it is to be tested whether transient ST-segment changes take on a prognostic significance in the long-term follow-up after bypass operation or PTCA.


Do silent myocardial ischemia and ventricular arrhythmias interact to result in sudden death?

The relationship between silent myocardial ischemia and sudden death depends on the severity and duration of the ischemia. Severe, transmural and persistent ischemia, as occurs in myocardial infarction, can trigger sudden death. When the ischemia is severe and transmural but not long-standing (e.g., Prinzmetal angina), ventricular arrhythmias appear frequently, but they are rarely malignant. In cases of subendocardial ischemia, there is no definitive proof of this relationship.


Complementary role of ambulatory electrocardiographic monitoring and exercise testing in evaluation of myocardial ischemia.

For detection of myocardial ischemia, exercise testing is a better tool than AEM and therefore should be preferred procedure for this purpose. In patients who exhibit ischemic changes on exercise testing, the presence of ischemic changes on AEM carries significant prognostic information beyond the results of exercise testing; therefore, it is recommended that this test be performed in those who have ischemic changes on exercise at a moderate or low workload. AEM together with exercise testing can be used to assess efficacy of anti-ischemic drugs, can help to define the underlying mechanism of ischemia during daily life, and in certain groups of patients, like those with unstable angina, peripheral vascular disease, or after cerebrovascular events, it can replace exercise testing as a method for detecting ischemic changes.


The role of ambulatory monitoring in assessing cardiac risk in peripheral vascular surgery.

Patients undergoing vascular surgery have a uniformly higher risk for postoperative cardiac events, and this risk has traditionally been difficult to quantify. Research has focused on the addition of noninvasive testing to the preoperative assessment of patients at moderate risk by clinical criteria. Current data suggest that preoperative ambulatory monitoring successfully identifies risk for cardiac events in patients undergoing vascular surgery and represents a practical alternative, particularly when patients cannot exercise. Postoperative monitoring appears to be particularly useful in heralding cardiac events in high-risk patients with enough lead time to make prophylactic and preemptive intervention feasible.


Myocardial dysfunction in silent myocardial ischemia as demonstrated by ambulatory radionuclide left ventricular function studies.

Until recently, it has not been possible to combine both ambulatory electrocardiographic monitoring, monitoring and ambulatory left ventricular function monitoring, but new developments have helped solve this problem. A technique based on the nuclear probe was introduced in the early 1980s to allow continuous recording of left ventricular volumes and ejection fraction over a 4 to 6 hour period during ambulatory activities following a single injection of radioisotope; the device was termed the VEST. In addition to validation studies, left ventricular function during ambulatory activities of various types has been measured with the VEST, and there are now several reports that document reduction in left ventricular ejection fraction in patients with coronary artery disease. These episodes meet the criteria for silent ischemia: objective evidence of myocardial ischemia in the absence of angina or anginal equivalents. Thus, patients with coronary artery disease can be followed for hemodynamic evidence of myocardial ischemia (even when they are not aware of the episodes) and results of therapy better monitored than by the ambulatory ECG alone.


Efficacy of therapeutic interventions for silent myocardial ischemia and clinical trial benefit.

This article reviews the efficacy of medical and revascularization therapeutic interventions directed at the reduction or elimination of silent myocardial The review focuses on the use of standard anti-ischemic medications, including nitrates, calcium antagonists, and beta-blockers. In addition, data suggesting therapeutic benefit of antiplatelet agents are discussed. Finally, the results of studies evaluating the efficacy of revascularization with PTCA and coronary artery bypass graft surgery are reviewed.


Time domain measurements of heart rate variability.

Assessment of HRV through time domain variables is a simple and practical method of assessing autonomic function. In this capacity its utility has been demonstrated in normal subjects and in diverse cardiac and noncardiac pathologic states. It can be used to assess the effects of drugs and other interventions, including exercise and psychological and physical stress on cardiac autonomic tone. Importantly, decreased HRV is almost uniformly associated with adverse outcome. The prognostic information appears to incorporate both alterations in autonomic tone and longer term components and is best assessed using ambulatory ECG recordings. Defining the clinical applicability and physiologic mechanisms of changes in HRV remain active areas of research.


Heart rate variability. Frequency domain analysis.

Experience with frequency domain analysis over the past two decades strongly suggests that it represents a unique, noninvasive tool for achieving a more precise assessment of autonomic function in both the experimental and clinical settings. Available studies indicate that the significance of the HF component is far better understood than that of the lower frequency components. In general, it is considered to reflect vagal activity, and because it is readily manipulated pharmacologically, is used as a an index of that activity. However, some caution is required because this parameter also is strongly influenced by the degree of coupling between respiration and heart rate, which, in turn, reflects the intensity of the respiratory effort as well as of parasympathetic activity. Respiratory pattern also can significantly influence HF power. The use of controlled breathing minimizes these problems, improves reproducibility of test findings, and also facilitates quantitative comparisons. The situation with respect to LF power is more complicated because it is modulated by both sympathetic and parasympathetic outflows (see previous discussion) as well as by other factors, including baroreceptor activity. Therefore, LF analysis per se cannot afford a precise delineation of the state of sympathetic activation. Determinations of the LF/HF ratio, an index of sympathovagal balance both under control conditions and in conjunction with interventions that maximize sympathetic and parasympathetic activity, provide additional insights, as do correlations between spectral activity and direct nerve recordings, plasma norepinephrine concentrations, and radionuclide imaging of adrenergic nerves. Renewed interest has recently been evinced in frequencies lower than 0.04 Hz in view of reports that the VLF portion of the spectrum (0.01-0.04 Hz) reflects a purer form of sympathetic activity than does the LF band. Despite the potential applicability to clinical problems, only very little is known about the physiologic basis of the VLF and ULF bands. Further study is required. However, it is important to note that meaningful determinations of VLF and ULF power may be difficult because decreases in frequency to such low levels are associated with an increasing propensity to violate the rules governing power spectral determinations (see previous discussion and appendix), violations that diminish reliability despite the most sophisticated preprocessing. It is also noteworthy that the reliability of spectral power determinations diminishes with decreases in the power of the signal and of the signal-to-noise ratio.(ABSTRACT TRUNCATED AT 400 WORDS)


Ambulatory electrocardiography signal averaging. Practicalities, clinical value, and potential applications.

Ability to perform high-resolution ECG from Holter tapes would significantly increase the utility of ambulatory monitoring as a screening tool for detecting the risk of serious ventricular arrhythmias without the cost and inconvenience of making a separate real-time recording. Despite some theoretical objections focusing on the relatively poor high-frequency response of Holter systems, it has nevertheless been shown to be both reasonable and practical to use them for late potential analysis. Technical issues, history, clinical results, and bibliography are presented in reviewing the current status of this emergent technique that shows promise for combining two techniques already shown to have independent diagnostic and prognostic value.


Appropriate indications for ambulatory electrocardiographic monitoring. A clinical perspective.

This article summarizes the clinical indications for ambulatory monitoring using current information from the Cardiac Arrhythmia Suppression Trial and utility of the procedure to detect both drug efficacy and proarrhythmia. It also discusses silent ischemia detection and heart rate variability as an indicator of autonomic tone.


[Medical ethics--an independent medical specialty].

Medical ethics as a discipline was not taught systematically since 1952. Some ethical problems were, however, solved; the author presents therefore the history of medical ethics and reasons for and circumstances under which the Institute of Medical Ethics was created at the Third Medical Faculty in Prague. Workers of the mentioned department (H. Haskovcová, V. Spalek, J. Simek) after presentation of an exposé became the initiators of the new independent discipline. The text of the exposé is submitted in extenso. Since 1991 medical ethics are an independent medical discipline in the Czech Republic and lectures on the subject are part of the curriculum of medical students.


[Use of flow cytometry in the diagnosis of acute leukemias in childhood].

The authors examined, using the method of flow cytometry, 56 children with acute lymphoblastic leukaemia. Leukaemic cells of the bone marrow aspirate and peripheral blood were examined on a FACS 440 apparatus for establishment of the diagnosis before treatment was initiated. Individual immunological subtypes were differentiated by means of a panel of monoclonal antibodies. 80.5% of acute lymphoblastic leukaemias originated from different developmental stages of B cells, 12.5% were formed by leukaemias from T cells and 7% were non-differentiated leukaemias. The mean follow-up period in the group was 33 months. According to the therapeutic results children with leukaemia ensuing from precursors of B cells had a more favourable prognosis than children with T leukaemia and children with non-differentiated leukaemia. Quantitative examination of nuclear DNA of leukaemic cells revealed in 55% of the patients of the group aneuploidy with clear predominance of hyperdiploidy, 45% of the patients suffered from diploidy. The least number of relapses was recorded in the investigation period in children with hyperploid acute lymphoblastic leukaemia. The proliferating activity of leukaemic blasts was expressed by the number of cells in the S + G2M stage of the cellular cycle and was higher in the bone marrow than in peripheral blood but did not differ in individual immunological subtypes or in diploid leukaemias. The authors were not able to prove its prognostic importance. Flow cytometry is a rapid and sensitive diagnostic method which makes it possible to characterize more satisfactorily the heterogeneous group of acute lymphoblastic leukaemias.


[Personal experience with detection of antibodies against neutrophil cytoplasm].

Detection of antibodies against components of neutrophil cytoplasm (ANCA) is of diagnostic value in Wegener's granulomatosis and in some other types of vasculitis. In the submitted paper the authors discuss methodical aspects of ANCA detection. The most frequently used method for assessment of ANCA is indirect immunofluorescence, at present it is possible to use also the ELISA method. Based on their own group of patients the authors discuss the association of ANCA with various types of diseases and the importance of assessing ANCA during monitoring of immunosuppressive treatment.


[Antibodies against neutrophil cytoplasm. A new group of autoantibodies].

Antibodies against cytoplasmic antigens of neutrophils are a recently described group of autoantibodies associated with some types of primary systemic vasculitis and necrotizing glomerulonephritis. In clinical practice they are a useful laboratory examination which helps with the diagnosis of this group of diseases and to follow up their activity and response to treatment. The existence of ANCA implies also a new aspect of classification of vasculitis. The autoimmune reaction of ANCA with lysosomal enzymes is also another possible mechanism of development of tissue damage. The submitted paper is a review of literature on the importance of ANCA from the practical as well as theoretical aspect.


[Patients' rights in the Czech Republic].

The ethical code, the so-called Patients' rights, was published on February 25, 1992 and applies in Bohemia and Moravia. The initiative in this matter was taken by the Central ethical commission of the Ministry of Health of the Czech Republic. The latter commission prepared a draft of the Czech version and after comments supplemented the text approved and proclaimed it. In the submitted paper the text of the document is presented in extenso and the author explains the history of patients' rights in Europe.


[EDRF-NO. The endothelium-derived relaxing factor is nitric oxide].

The author reviews findings assembled during the last 20 years on the endothelium-derived relaxing factor (EDRF), and in particular findings assembled the last five years which revealed that EDRF is identical with nitric oxide, NO. The enzyme NO synthetase produces NO from l-arginine with the concurrent formation of citrulline and is present not only in the endothelium of the vascular wall but also in cerebral neurons and other tissues. NO is probably also the effective factor of the vasodilatating action of organic nitrates (nitroglycerol, amyl nitrite, sodium nitroprusside). In recent years these findings are applied also in clinical work. In atherosclerosis of the coronary vessels NO formation is obviously reduced and l-arginine infusion may improve the coronary blood supply in patients with hypercholesterolaemia. Inhalation of NO has been tried in pulmonary hypertension. Antidotes of NO (methylene blue) conversely may prevent hypotension in hepatic failure. Infusion of an antidote of l arginine prevents hypotension in septic shock. This is due to the fact that an excess of NO is formed from macrophages during infections. NO is, however, also mutagenic and there are reports on its participation in the genesis of genetic and neoplastic diseases.


[Sonographic findings in Crohn's disease].

In 59 subjects (25 men and 34 women) with confirmed Crohn's disease 91 sonographic examinations were made, using dynamic records by means of a sector probe with a frequency of 3.5 and 5 MHz. The disease had persisted on average for 7.1 years. A positive sonographic finding was recorded in 68% of the examined subjects, incl. 42% where the finding on palpation of the abdominal cavity was negative. During examination the following typical findings were recorded: the symptom of a tubular structure with a thickened intestinal wall (frequency 77.5%), cockade symptom (65%), convolution of the loops (62.5%), congestion in the intestinal loops (10%) and abscess in the abdominal cavity (7.5%). Ultrasonography is a significant diagnostic method which can help in the differential diagnosis of resistance on palpation and in the follow up of the disease and the effect of therapy in patients with Crohn's disease.


[Long-term home parenteral nutrition using a totally implanted cannulation system].

A 29-year-old patient suffering from stenosis of the rectum and a periproctal fistula due to a severe form of Crohn's disease was completely fed by the parenteral route for 15 months, incl. 13 months at home, via a totally implanted cannula system Implantofix, Braun Co.. The patient felt throughout the period of parenteral nutrition very well, he worked and the secretion from the fistula stopped after four weeks. After 15 months of complete parenteral nutrition and elimination of oral food intake a marked improvement of the local finding in the rectum was observed. All laboratory findings (haemogram, liver tests, urea, creatinine, transferrin, albumin, cholinesterase and pre-albumin, serum levels of sodium, potassium, chlorides, calcium and phosphates) were throughout the observation period within a normal range. The body weight of the patient increased during the 15 months by 1 kg. The described case is the first one where domiciliary parenteral nutrition was used in Czechoslovakia under ambulatory conditions.


[Favorable effect of methylprednisolone pulse therapy in dysphagia and primary idiopathic polymyositis/dermatomyositis].

In five previously not treated patients with active primary idiopathic polymyositis/dermatomyositis and severe dysphagia persisting for 3-8 weeks treatment with a series of 4-5 intravenous pulses a 1 g methylprednisolone was provided. In four patients dysphagia disappeared within 2-14 days, in one patient within 30 days marked improvement was recorded. During the 12-64-month follow up period in none of the patients relapse or deterioration of dysphagia was observed. One female patient died 12 months after establishment of the diagnosis during reactivation of the basic disease with marked fibrosis of the pulmonary interstitium, the remaining patients are in permanent remission.


[Actinomycosis of the ovary as a cause of cachexia in a young patient].

The authors describe the case of a 40-year-old female patient treated for prolonged periods unsuccessfully with several antibiotics on account of a febrile condition of obscure aetiology and subsequently repeatedly subjected to laparotomy on account of intra-abdominal abscesses. The cause of the fever, abdominal pain and gradual cachectization was an abdominal form of actinomycosis. After establishment of the diagnosis the patient was successfully treated by long-term penicillin administration and recovered completely. The authors discuss experience reported in the literature and therapeutic possibilities in actinomycosis.


Calcium and calmodulin.

A description of the value of calcium and calmodulin is given in terms of their dynamics and structures. It is insisted that a full appreciation of their value demands recognition of the time domain, motion, in evolution in concert with structure. Only in this way can homeostasis of resting states as well as triggering, assisted by calcium/calmodulin, be described. The best analogy is with a regulatory electrical control such as household central heating system where calcium carries the current and calmodulin triggers the heating (cellular work) and the pumps (cellular pumps). There is full feed-back control.


The linker of calmodulin--to helix or not to helix.

The linker regions of the central helices of calmodulin and of troponin C are observed to be alpha-helices in crystal and in solution. However, these linkers are predicted to be non-helical by standard algorithms. Further, there is strong evidence that when calmodulin interacts with some of its targets this linker helix bends. The linker appears to be delicately balanced between helical and non-helical conformations. A review of this subject suggests that one can anticipate more unpredicted conformations for the central helices of the score of other proteins that have four EF-hand domains.


Male fertility regulation: a study on acceptance among men in Zimbabwe.

Both traditional and modern methods of family planning widely practised currently in most countries, especially in sub-Saharan Africa, focus solely on the woman. There is hardly data on male directed methods of fertility regulation, or indeed whether, or not, such contraceptive options are acceptable. Contraception, whether for spacing, avoiding unintended pregnancy or limiting family size, is almost always a female prerogative. This, in certain circumstances, is despite the available female method being contraindicated. Acceptance of male sterilisation (vasectomy), condom use and male contraceptive pill were investigated in a representative sample of 711 Zimbabwean men. Only 14 pc of men considered vasectomy an acceptable method of contraception and none of the men had current or previous use of this method. Seventeen percent of the men had prompted knowledge of this method, compared to 53 pc who had prompted knowledge of female sterilisation. Only six percent of respondents reported current use of condoms and amongst condom non-users, 58.9 pc would not use the method if asked by a wife or partner. Surprisingly, 31.7 pc of the male respondents reported that they would consider a male contraceptive pill or injection if available. Should husband want no more children, 42.2 pc of men said they would agree to wife sterilisation and 19.5 pc could consider vasectomy. Previous use of condoms was reported by 33.8 pc of the men. Eighty eight (88 pc) percent of respondents had some formal education, although acceptance rates decreased with less education and older ages. Circumstances during which a male method could be considered, reasons and socio-economic determinants for acceptance of male fertility regulatory methods are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)


Solution structure of calmodulin and its complex with a myosin light chain kinase fragment.

The solution structure of Ca2+ ligated calmodulin and of its complex with a 26-residue peptide fragment of skeletal muscle myosin light chain kinase (skMLCK) have been investigated by multi-dimensional NMR. In the absence of peptide, the two globular domains of calmodulin adopt the same structure as observed in the crystalline form. The so-called 'central helix' which is observed in the crystalline state is disrupted in solution. 15N relaxation studies show that residues Asp78 through Ser81, located near the middle of this 'central helix', form a very flexible link between the two globular domains. In the presence of skMLCK target peptide, the peptide-protein complex adopts a globular ellipsoidal shape. The helical peptide is located in a hydrophobic channel that goes through the center of the complex and makes an angle of approximately 45 degrees with the long axis of the ellipsoid.


The solution structures of calmodulin and its complexes with synthetic peptides based on target enzyme binding domains.

Small-angle X-ray and neutron scattering experiments have given important information on the solution structures of calmodulin and its complexes with synthetic peptides used to model target enzyme interactions. In combination with crystallographic data, site directed mutagenesis and various spectroscopic studies, these experiments have contributed to our understanding of the solution structure of calmodulin in different functional states. We have gained important insights into the conformational flexibility in calmodulin that appears to be crucial to its regulatory functions. Specifically, flexibility in the interconnecting helix region of calmodulin has been shown to play a critical role in facilitating calmodulin's binding to a wide variety of target enzymes whose activities are thus regulated. This review will focus mainly on the contributions small-angle scattering has made to our understanding of the solution structure of calmodulin in the context of other studies, with particular regard to circular dichroism and Fourier transform infrared studies that complement the small-angle scattering data.


Mutational analysis of calmodulin in Saccharomyces cerevisiae.

Calmodulin is well characterized as an intracellular Ca2+ receptor in nonproliferating tissues such as muscle and brain. Several observations indicate that calmodulin is also required for cellular growth and division. Deletion of the calmodulin gene is a lethal mutation in Saccharomyces cerevisiae, Schizosaccharomyces pombe and Aspergillus nidulans. Expression of calmodulin antisense RNA in mouse C127 cells causes a transient arrest at G1 and metaphase. Although these results indicate calmodulin plays a critical function during proliferation, they do not reveal the function. S. cerevisiae offers an excellent system for identifying calmodulin functions. Because calmodulin mutants can be readily constructed by gene replacement the consequences of mutations in calmodulin can be directly examined in vivo without interference from wild-type calmodulin. The available wealth of information concerning all aspects of the yeast life cycle provides a large framework for interpretation of new results. The recent dissection of cell cycle regulation is just the latest example of the important insights provided by analyzing basic cellular processes in yeast. Whether studies of calmodulin in yeast will reveal a universal function is unknown. One encouraging result is that yeast cells relying on vertebrate calmodulin as their only source of calmodulin survive and grow well, even if the amount of vertebrate calmodulin is equivalent to the normal steady state levels of yeast calmodulin. This review discusses the varied techniques we are using to identify the functions of calmodulin in yeast. As part of the analysis, we are defining the essential elements of calmodulin structure.


Drug prescribing in paediatric in-patients at Harare and Parirenyatwa Central Hospitals.

Two-hundred-and-fifty records were examined at Harare and 250 at Parirenyatwa Central Hospitals over a six-month period to investigate drug prescribing patterns for paediatric in-patients. The majority of the patients were between one to three years and weight 6 to 7.9 kg. A total of 1,725 prescriptions were received by these patients with an average of 3.45 (range = 0-18 drugs) per patient. The most frequently used pharmacological groups at both hospitals were anti-infectives (51 pc), intravenous fluids and supplements (22 pc) and analgesics (10.6 pc). Benzylpenicillin accounted for 14.6 pc at Harare and 12.9 pc at Parirenyatwa hospital of the anti-infectives respectively. Infections (49 pc) and gastro-enteritis (11.5 pc) were the main diagnoses in all age groups at both hospitals. Respiratory tract infections accounted for 13.5 pc at Harare and 15.2 pc at Parirenyatwa hospital respectively. There was a rational correlation between prevalent diagnosis and drugs used.


Yeast calmodulin: structural and functional elements essential for the cell cycle.

The budding yeast Saccharomyces cerevisiae is a suitable organism for studying calmodulin function in cell proliferation. Genetic studies in yeast demonstrate that vertebrate calmodulin can functionally replace yeast calmodulin. In addition, expression of half of the yeast calmodulin molecule is found to be sufficient for cell growth. Characterization of conditional-lethal mutants of yeast calmodulin as well as the intracellular distribution of calmodulin have suggested that at least two cell cycle steps require calmodulin function. One is nuclear division and the other is the maintenance of cell polarity. A current focus is to understand which kinds of target proteins are involved in mediating the essential functions of yeast calmodulin in these processes. Thus far, three yeast enzymes whose activity is regulated by calmodulin have been identified.


Regulation of expression of calmodulin and calmodulin-related genes by environmental stimuli in plants.

Plants are very sensitive to environmental stimuli and have evolved the ability to adapt to many environmental stresses by altering development. In particular, mechanical stimuli such as touch or wind, result in growth changes that result in plants with greater resistance to such mechanical stimuli. We have initiated a molecular dissection of the pathways that enable perception of and responses to these environmental stimuli in plants. We have discovered five genes--termed the TCH genes--whose expression levels are strongly and rapidly increased in response to stimuli such as touch, wind, rain, wounding and darkness. Three of the TCH genes encode proteins related to calmodulin thereby implicating roles for calcium ions and calmodulin in the transduction of signals from the environment.


Current prevalence and some clinical associations of childhood anaemia in urban and rural communities of central Nigeria.

The current prevalence of anaemia was determined among children in the age group half to fourteen years in one urban and two rural communities in the middle belt region of Nigeria. A total of 1,775 apparently healthy and 660 sick children were investigated using capillary packed cell volume, PCV, as the diagnostic index. Packed cell volume of healthy children was found to vary between 23 pc and 48 pc. The mean PCV for the whole group was 35.90 pc but the relatively better economic and educational status of urban elite children was reflected in the higher PCV levels. Using the WHO recommended cut-off values for anaemia in children, prevalence of anaemia in the healthy children study was found to be 35.8 pc. When compared with figures recorded in Nigerian children in earlier studies, this finding represents a deterioration and occurs at a time of declining national economy. There were significant differences between groups when classified by age and socio-economic status, with the highest prevalence of 55 pc being found in the rural school-age group and the lowest of 20 pc in the economically better-off urban pre-school children. The overall prevalence of anaemia among sick children was 55 pc with the school age group having the worst value of 70 pc. In most cases, the anaemia was associated with nutritional and infectious conditions.


Hysterectomy in the rural tropics.

A retrospective study of hysterectomy at a rural hospital in Ghana revealed a high incidence of emergency cases. Uterine fibroids were the commonest indication for elective hysterectomy, followed by surgery for suspected cervical carcinoma. Most emergency hysterectomies were performed because of uterine rupture. The difficulties of managing these problems against the background of the diagnostic and therapeutic facilities available are discussed.


Flexor tendon injuries: the result of primary management: a retrospective review of 50 cases treated at Whiston Hospital, England.

A retrospective review of 50 cases treated over a 12-month period with 95 tendon injuries was carried out. Post-operative management utilising a modified Kleinert method was used for cases over eight years of age, while those under eight were immobilised in plaster cast. Our results after a mean follow up period of 14 weeks compared well with other series using the Kleinert method. Zone II injuries gave an unexpected better results than those in other zones.


Molecular pharmacology of calmodulin pathways in the cell functions.

In this paper we summarize much of the pharmacological evidence that has led to our current understanding of calmodulin-regulated cell function, with emphasis on aspects that may be relevant to drug design. These newly developed compounds are one of the most powerful tools as molecular probes for pharmacological approach, and will shed light on the physiological significance and molecular mechanisms of calmodulin-dependent pathways in various cell functions.


Biosocial factors affecting menarche in a mixed Nigerian population.

A prospective study of school girls in a mixed Nigerian population revealed that the mean menarcheal age was 13.98 +/- 1.30 years. The mean menarcheal age was influenced by the social class of the parents, being higher in the lower social class, there were considerable variations in the biologic measurements (height, weight and body mass index) among girls who attained menarche.


Anatomical sex conversion in a 21-year-old--case report and review of literature.

A case of anatomical sex conversion in a 21-year-old genotypic male Nigerian with ambiguous genitalia but who was reared as a girl is presented. The clinical features observed in this particular case and the result obtained after surgery, adjuvant hormone therapy and supportive psychotherapy are discussed. The relevant literature pertaining to the clinical entity is reviewed.


Human immunodeficiency virus and Guillain 'Barre' syndrome in intensive care unit patients.

Among 155 medical admissions to the intensive care unit during the period 1989 to 1990, 16 patients had Guillain-'Barre' Syndrome (GBS), five of whom were HIV positive. Out of the five cases, three had manifested herpes zoster and one had TB. The impact of HIV infection o GBS is discussed.


A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter.

Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine that produces a model of Parkinson's disease. Taking advantage of selection in MPP+, we have used gene transfer followed by plasmid rescue to identify a cDNA clone that encodes a vesicular amine transporter. The sequence predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. We have detected messenger RNA transcripts for this transporter only in the adrenal gland. Monoamine cell populations in the brain stem express a distinct but highly related protein.


Connectin: a homophilic cell adhesion molecule expressed on a subset of muscles and the motoneurons that innervate them in Drosophila.

Each abdominal hemisegment in the Drosophila embryo contains a stereotyped array of 30 muscles, each specifically innervated by one or a few motoneurons. We screened 11,000 enhancer trap lines, isolated several expressing beta-galactosidase in small subsets of muscle fibers prior to innervation, and identified two of these as inserts in connectin and Toll, members of the leucine-rich repeat gene family. Connectin contains a signal sequence, ten leucine-rich repeats, and a putative phosphatidylinositol membrane linkage; in S2 cells, connectin can mediate homophilic cell adhesion. Connectin is expressed on the surface of eight muscles, the motoneurons that innervate them, and several glial cells along the pathways leading to them. During synapse formation, the protein localizes to synaptic sites; afterward, it largely disappears. Thus, connectin is a novel cell adhesion molecule whose expression suggests a role in target recognition.


Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor.

Signaling through the T cell antigen receptor (TCR) results both in rapid increases in tyrosine phosphorylation on a number of proteins and in the activation of the phosphatidylinositol pathway. It is not clear how stimulation of the TCR leads to these signaling events. Mutants of the Jurkat T cell line have been previously isolated that fail to show increases in calcium following receptor stimulation. Analysis of one of these mutants, JCaM1, which is defective in the induction of tyrosine phosphorylation, revealed a defect in the expression of functional lck tyrosine kinase. The lack of lck activity was caused in part by a splicing defect. Expression of the lck cDNA in JCaM1 restores the ability of the cell to respond to TCR stimulation. These results indicate that lck is required for normal signal transduction through the TCR.


The growth arrest-specific gene, gas1, is involved in growth suppression.

This report describes the structure of the mRNA, the protein product, and the growth-regulating activity of one of the growth arrest-specific genes, gas1. From the predicted amino acid sequence, in vitro translation of gas1 mRNA, and immunofluorescence of cells in culture, it appears that the gas1 protein is an integral plasma membrane protein whose expression is linked to growth arrest. When gas1 is overexpressed from a constitutive promoter in quiescent cells, the serum-induced transition from the G0 to the S phase of the cell cycle is inhibited without affecting the normal early serum response. Ectopic expression of the gas1 gene by microinjection in normal and transformed NIH 3T3 cell lines with the notable exception of SV40-transformed 3T3 cells leads to inhibition of DNA synthesis. Thus, gas1 appears to be one component of a negative circuit that governs growth suppression. Its effect is, however, abolished in SV40-transformed cells.


Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein.

Loss-of-function mutations in the yan gene result in the differentiation of supernumerary photoreceptors in the Drosophila eye. The yan gene encodes a protein with an ETS DNA-binding domain that accumulates in the nuclei of undifferentiated cells during the early stages of eye development. Our data suggest that yan functions as a cell-autonomous negative regulator of photoreceptor development; in the presumptive R7 and cone cells, yan appears to act antagonistically to the proneural signal mediated by sevenless and Ras1.


A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition.

A human cDNA was cloned that encodes a DNA-binding protein (SATB1) that is expressed predominantly in thymus and binds selectively to the nuclear matrix/scaffold-associating DNAs (MARs/SARs). Missing nucleoside experiments showed that SATB1 selectively binds in a special AT-rich sequence context where one strand consists of mixed A's, T's, and C's, excluding G's (ATC sequences). When this feature is destroyed by mutation, SATB1 binding is greatly reduced even if the direct contact sequence remains intact. Conjunctional SATB1-binding sequences become stably unpaired in supercoiled DNA. Specific mutations that diminish the unwinding potential greatly reduce SATB1 binding. However, SATB1 does not bind single-stranded DNA. Chemical interference assays show that SATB1 binds along the minor groove with very little contact with the bases. This suggests that SATB1 recognizes the ATC sequence indirectly through the altered sugar-phosphate backbone structure present in the double-stranded DNA.


Autoregulation of the yeast lysyl-tRNA synthetase gene GCD5/KRS1 by translational and transcriptional control mechanisms.

We cloned the GCD5 gene of S. cerevisiae and found it to be identical to KRS1, which encodes lysyl-tRNA synthetase (LysRS). The mutation gcd5-1 changes a conserved residue in the putative lysine-binding domain of LysRS. This leads to a defect in lysine binding and, consequently, to reduced charging of tRNA(Lys). Mutant gcd5-1 cells compensate for the defect in LysRS by increasing GCN4 expression at the translational level. GCN4 protein in turn stimulates transcription of GCD5, leading to increased LysRS activity. We propose an autoregulatory model in which uncharged tRNA(Lys) stimulates the protein kinase GCN2, a translational activator of GCN4, and thereby increases transcription of GCD5 and other genes regulated by GCN4.


Recombination between similar but not identical DNA sequences during yeast transformation occurs within short stretches of identity.

Interactions between similar but not identical (homeologous) DNA sequences play an important biological role in the evolution of genes and genomes. To gain insight into the underlying molecular mechanism(s) of genetic recombination, we have studied inter- and intramolecular homeologous recombination in S. cerevisiae during transformation. We found that homeologous DNAs recombine efficiently. Hybrid sequences were obtained between two mammalian cytochrome P450 cDNAs, sharing 73% identity, and between the yeast ARG4 gene and its human homeologous cDNA, sharing 52% identity. Sequencing data showed that the preferred recombination events are those corresponding to the overall alignment of the DNA sequences and that the junctions are within stretches of identity of variable length (2-21 nt). We suggest that these events occur by a conventional homologous recombination mechanism.


A new mechanism of transcriptional regulation: release of an activator triggered by small molecule binding.

The FadR protein of E. coli activates transcription of the fabA gene, a key enzyme of fatty acid synthesis. We report that FadR binds to a DNA sequence positioned at -40 relative to the start site of the FadR-regulated fabA transcript (the location favored by positive activators). This binding was found to be specifically antagonized by long chain acyl-CoAs. The chain length specificity of the disassociation of the FadR-DNA complex by acyl-CoAs observed in vitro reflects that seen in the repression of fabA transcription observed upon addition of fatty acids to bacterial cultures. Acyl-CoA antagonism of FadR-DNA interactions is readily reversible. These data indicate that repression of fabA transcription by fatty acids is the first reported example of a repression system mediated by positive control.


Integration of human alpha-satellite DNA into simian chromosomes: centromere protein binding and disruption of normal chromosome segregation.

Centromeres of mammalian and other complex eukaryotic chromosomes are dominated by one or more classes of satellite DNA. To test the hypothesis that alpha-satellite DNA, the major centromeric satellite of primate chromosomes, is involved in centromere structure and/or function, human alpha-satellite DNA was introduced into African green monkey (AGM) cells. Centromere protein binding was apparent at the sites of integrated human alpha-satellite DNA. In the presence of an AGM centromere on the same chromosome, human alpha-satellite was associated with bridges between the separating sets of chromatids at anaphase and an increased number of lagging chromosomes at metaphase, both features consistent with the integrated alpha-satellite disrupting normal chromosome segregation. These experiments suggest that alpha-satellite DNA provides the primary sequence information for centromere protein binding and for at least some functional aspect(s) of a mammalian centromere, playing a role either in kinetochore formation or in sister chromatid apposition.


Three-dimensional solution structure of the src homology 2 domain of c-abl.

SH2 regions are protein motifs capable of binding target protein sequences that contain a phosphotyrosine. The solution structure of the abl SH2 product, a protein of 109 residues and 12.1 kd, has been determined by multidimensional nuclear magnetic resonance spectroscopy. It is a compact spherical domain with a pair of three-stranded antiparallel beta sheets and a C-terminal alpha helix enclosing the hydrophobic core. Three arginines project from a short N-terminal alpha helix and one beta sheet into the putative phosphotyrosine-binding site, which lies on a face distal from the termini. Comparison with other SH2 sequences supports a common global fold and mode of phosphotyrosine binding for this family.


[Multiple pregnancies in the IVF and ET programs at the Institute for Maternal and Child Care].

Of the 71 clinical pregnancies achieved in the IVF and ET programme at the Institute for the Care of Mother and Child between January 1989 and June 1991 22 were multiple (30.9%). In seven cases (31.3%) spontaneous reduction occurred. A total of six patients underwent a multifoetal pregnancy reduction.


[Results of transvaginal ultrasound screening for endometrial carcinoma in women at risk after menopause].

Vaginal sonography was used as a prebioptic examination for screening of endometrial carcinoma in postmenopausal women in a risk group (diabetes, hypertension, obesity) without a history of haemorrhage. The examination was made in 104 women. In 23 patients the ultrasonic finding was suspect and subsequent abrasion revealed in three instances carcinoma of the endometrium (2.88%). The authors consider vaginal sonography as important prebioptic method of endometrial cancer in the risk group of women after the menopause.


[Ca 125 during normal and pathologic pregnancy].

In 44 women in the first trimester of pregnancy a single examination of the Ca 125 serum level was made. In 10 women of the control group after mini-interruptions of pregnancy almost in all instances serum concentrations within the normal range were recorded. In 23 women with the diagnosis of spontaneous abortion in the first trimester a mean concentration of 58 U/ml of this protein was found. In a group of 11 women with the diagnosis of imminent abortion with a favourable prognosis, on the other hand, the mean serum concentration was only 42 U/ml, which is close to the mean concentration recorded in the control group of healthy pregnant women (46 U/ml). The difference between the two groups of pathological pregnancies is, however, not statistically significant.


[Side effects of amitriptyline in relation to its plasma levels].

In a 21-day investigation in 15 patients with depression the authors investigated the incidence of undesirable side-effects in relation to plasma amitriptyline levels. The authors found the upper range of plasma concentrations when the patient's risk is minimal as regards serious undesirable complications. This upper limit is 350 micrograms/l; as compared with previous work, they consider amitriptyline levels from 150 to 350 350 micrograms/l safe and therapeutically effective. The authors consider investigation of plasma levels indicated in risk patients and in patients with an inadequate response to treatment.


[Prevention of suicidal activity in patients with affective disorders by treatment with lithium].

The authors expressed in 1984 the assumption that lithium is the drug of the phenomenon of suicidal action in affective disorders. In the present paper the authors describe in a group of 56 patients with affective disorders in the course of lithioprophylaxis a marked decline of the suicide rate at the 4% level of significance. Therefore the authors are still in favour of the view that lithium is the drug in suicidal behaviour in affective disorders. This mechanism can be explained by the antiaggressive as well as prophylactic action of lithium. In the authors' opinion it is possible that the mechanism of this action may be conditioned by the interference of lithium with the dysfunction of the central serotonergic system.


[Development of diagnostic classification systems in psychiatry].

The author presents a historical account of classifications of mental disorders. He follows the development from simple classifications at the onset of the 19th century via Morel's, Kraepelin's, Kuffner's and Bleuler's classification to the new diagnostic classification of North American psychiatrists (DSM-III), International classification of diseases (ICD 10) to the contemporary multiaxial classification of mental disorders.


[Terminology problems in schizophrenia].

The author submits a new classification of schizophrenias, schizotype, hallucinatory and other disorders as found in the 10th revision of the International Classification of Diseases (ICD 10) in the chapter bearing the code F20-F29. Some new units will be found (post-schizophrenic depressions, schizotype disorders); paraphrenia and paranoia are no longer separate units. The new revision will be valid from Jan. 1, 1993; by a five-digit classification it will make as regards symptoms and course of mental disorders a more accurate diagnosis possible.


[Results, problems and perspectives of modern classification systems in psychiatry].

The new international classification of mental disorders (ICD 10) changes to a considerable extent the logical pattern, terminology and nomenclature of mental diseases. The prerequisite for its understanding is knowledge of general principles of medical classification and knowledge of basic theoretical problems associated with the classification of mental disorders. The paper summarizes these areas.


[Use of automated quantitative analysis of electroencephalograms in the diagnosis of dementia].

The submitted paper demonstrates the differential diagnostic value of automatic quantitative analysis of electroencephalograms in the diagnosis of dementia and functional mental disorders in old age. By quantitative autoregression analysis of electric activity of the brain in a group of 53 hospitalized patients (incl. 33 cases of dementia) the conclusions of visual analysis were confirmed as well as the comparability of results obtained by other methods of automatic analysis. Signs characterizing the electroencephalogram in dementia (reduced ratio of alpha activity and increase of slow activity, low value of A/T index, shift of the peak frequency towards slow activity) make differential diagnosis of dementia in organic diseases from pseudodementia possible. Analysis of the results indicates that automatic analysis can be very successful in the detection of Alzheimer's disease.


[Intensive psychiatric care of patients with psychogenic eating disorders].

The authors summarize their therapeutic results in anorexia nervosa achieved at the unit of specialized care for eating disorders at the Psychiatric Clinic of the First Medical Faculty, Charles University, Prague. They find that applications for hospitalization of these patients have a rising trend and that in recent years in the unit mainly patients with severe forms of these diseases are admitted. During the past 7 years in the unit a total of 147 patients were hospitalized. By comprehensive regime treatment 84% of the patients with bulimia nervosa. As to basic symptoms, in bulimia nervosa the results were achieved in vomiting and bulimic attacks and in anorexia nervosa as regards appetite, hunger and general attitude to food. Finally the authors summarize the advantages of the unit specialized care for psychogenic eating disorders.


[Results of a clinical trial of levoprotiline].

The authors submit results of a double blind clinical trial of levoprotiline controlled by maprotiline. In the multicentre study (which is processed and interpreted in stages) participated after written informed consent 58 patients with the diagnosis of a major depressive disorder. During the first three weeks the results of levoprotiline and maprotiline (from 26 patients each) were processed. The trial lasted 42 days. The psychopathology of the patients was evaluated by independent blind raters by means of Montgomery and Asberg's scale (MADRS), Hamilton's scale for depression (HRDS) and general clinical impression (CGI). In all patients also the pharmacological and EEG response was assessed. In comparison to maprotiline, levoprotiline was clinically ineffective. Its plasma levels (40 ng/ml) were one third to one half of the values obtained with maprotiline in the same daily dosage (150 mg). Although levoprotiline has an EEG profile typical for classical thymoleptics, its clinical antidepressive action is negligible.


Induction of class 3 aldehyde dehydrogenase in the mouse hepatoma cell line Hepa-1 by various chemicals.

The mouse hepatoma cell line Hepa-1 was shown to express an aldehyde dehydrogenase (ALDH) isozyme which was inducible by TCDD and carcinogenic polycyclic aromatic hydrocarbons. The induced activity could be detected with benzaldehyde as substrate and NADP as cofactor (B/NADP ALDH). As compared with rat liver and hepatoma cell lines, the response was moderate (maximally 5-fold). There was an apparent correlation between this specific form of ALDH and aryl hydrocarbon hydroxylase (AHH) in the Hepa-1 wild-type cell line--in terms of inducibility by several chemicals. However, the magnitude of the response was clearly smaller for ALDH than for AHH. Southern blot analysis showed that a homologous gene (class 3 ALDH) was present in the rat and mouse genome. The gene was also expressed in Hepa-1 and there was a good correlation between the increase of class 3 ALDH-specific mRNA and B/NADP ALDH enzyme activity after exposure of the Hepa-1 cells to TCDD. It is concluded that class 3 ALDH is inducible by certain chemicals in the mouse hepatoma cell line, although the respective enzyme is not inducible in mouse liver in vivo.


32P-postlabelling analysis of DNA adducts from Fischer-344 rats administered 2,4-diaminotoluene.

Using 32P-postlabelling and thin layer chromatography, DNA adduct formation by the potent animal carcinogen 2,4-diaminotoluene in Fischer-344 rats was investigated. DNA from four different organs, liver, mammary gland, kidney and lung, were examined for adducts following single administration of this compound. DNA binding was detected in all four organs, with each producing one major and two minor adduct spots on autoradiograms. The adducts induced were qualitatively identical among the different organs, but quantitative differences were observed. The two target organs of 2,4-diaminotoluene induced carcinogenesis, the liver and mammary gland produced higher adduct yields, with levels up to 30-times higher than those for the two non-target organs. Since the liver is the principal target for 2,4-diaminotoluene induced carcinogenesis, we further examined DNA adducts from this site for the effects of different doses and time points. DNA binding in liver was detected following doses as low as 4.1 mumol/kg. At the highest concentration examined (2046 mumol/kg), the level of the major adduct was 29.2 adducted nucleotides per 10(7) total nucleotides. The yields for the two minor adducts were approximately one-tenth that for the major adduct. Following a 410 mumol/kg dose, DNA adduct removal over time was examined. DNA adduct removal exhibited biphasic kinetics, with a rapid initial phase followed by a slower rate of elimination. Up to 60% of maximum adduct levels persisted after 2 weeks. DNA binding by 2,4-diaminotoluene was also compared to that by its weakly carcinogenic analog, 2,4-dinitrotoluene. The two compounds produced identical adduct patterns, suggesting that they share common metabolites and adducts. Adduct yields from 2,4-dinitrotoluene, however, were lower. The results of our studies suggest that the differences in carcinogenic potency between 2,4-diaminotoluene and 2,4-dinitrotoluene, as well as the organotropic effects of 2,4-diaminotoluene may be explained, in part, by quantitative differences in the extent of DNA adduct formation.


A mechanism for the development of Clara cell lesions in the mouse lung after exposure to trichloroethylene.

Female CD-1 mice exposed to trichloroethylene (6 h/day) at concentrations from 20-2000 ppm developed a highly specific lung lesion after a single exposure, characterised by vacuolation of the Clara cells, the number of cells affected increasing with increasing dose level. At the highest dose levels pyknosis of the Clara cells was apparent. After 5 days of repeated exposures the lesion had resolved but exposure of mice following a 2-day break resulted in recurrence of the lesion. The changes in mouse lung Clara cells were accompanied by a marked loss of cytochrome P-450 activities. No morphological changes were seen in the lungs of rats exposed to either 500 or 1000 ppm trichloroethylene. Isolated mouse lung Clara cells were shown to metabolize trichloroethylene to chloral, trichloroethanol and trichloroacetic acid. Chloral was the major metabolite. Trichloroethanol glucuronide was not detected. In comparative experiments using mouse hepatocytes the major metabolites were trichloroethanol and its glucuronide conjugate. The activity of UDP-glucuronosyltransferase was compared in mouse lung Clara cells and hepatocytes using two phenolic substrates and trichloroethanol. Hepatocytes readily formed glucuronides from all three substrates whereas Clara cells were only active with the two phenolic substrates. The three major metabolites of trichloroethylene, chloral, trichloroethanol and trichloroacetic acid were each dosed to mice and of these metabolites, only chloral had an effect on mouse lung causing a lesion (Clara cell) identical to that seen with trichloroethylene. It is proposed that the failure of Clara cells to conjugate trichloroethanol leads to an accumulation of chloral which results in cytotoxicity. The known genotoxicity of chloral suggests that this lesion may be related to the development of lung tumours in mice exposed to trichloroethylene by inhalation.


The anti-carcinogenic plant compound indole-3-carbinol differentially modulates P450-mediated steroid hydroxylase activities in mice.

Indole-3-carbinol (I3C), a component of cruciferous vegetables, exhibits anti-carcinogenic activity in a variety of model systems. This activity has been attributed in part to the induction of cytochrome P450 CYP1A subfamily members and the resulting increased metabolic inactivation of chemical carcinogens. The present study was undertaken to assess the effects of I3C on several constitutive P450 activities that contribute to both carcinogen and steroid hormone metabolism. Mice were administered I3C in their diet at estimated daily doses of 250, 500 and 750 mg/kg for 1 week. Liver microsomes from treated and untreated mice were subsequently assayed for CYP1A-mediated ethoxy-resorufin O-deethylase (EROD) activity, estradiol 2-hydroxylase activity and seven different testosterone hydroxylase activities. I3C elevated EROD, estradiol 2-hydroxylase and testosterone 6 alpha-hydroxylase activities in a dose-dependent manner. The other six testosterone hydroxylase activities were not significantly affected by in vivo treatment with I3C. In addition to its effects on steroid hydroxylase activities, I3C also elevated NADPH-cytochrome P450 reductase activity, a necessary component to the P450 monooxygenase system. We next examined the direct in vitro effects of I3C and its acid condensation products, as are generated in the stomach following ingestion, on the P450 catalytic activities. Testosterone 6 beta-hydroxylase, the major testosterone hydroxylase activity in untreated mice, was significantly inhibited (IC50 approximately 12 micrograms/ml) by the acid condensation products of I3C. In contrast, all other P450 activities were not appreciably affected by I3C or its acid condensation products. These results indicate that I3C can elicit both inductive and suppressive effects on the constitutive P450s that participate in carcinogen and steroid hormone metabolism. This pleiotropic effect on hepatic catalytic enzymes may contribute to the anti-carcinogenic properties of this compound.


Activity of the human metallothionein promoter (hMT-IIA) in cell populations isolated from varying depths in multicell spheroids following exposure to cadmium.

In order to evaluate whether tumor microenvironment might influence the response of the metallothionein promoter to heavy-metal exposure, we transfected HT-29 colon carcinoma cells with the vector phMTIIA-CAT-neo, containing a fusion gene consisting of 426 bp of the human metallothionein-IIa (hMT-IIA) promoter immediately upstream of the bacterial chloramphenicol acetyl transferase (CAT) gene. We grew one of the stable transfectants (clone 20) as three-dimensional multicell tumor spheroids, exposed them to CdCl2 and measured CAT expression in cells isolated from various depths into the spheroids. Cellular populations were isolated by flow cytometry on the basis of Hoescht 33342 fluorescence intensity, taking advantage of the dye's diffusion gradient to isolate cells from inner (dim) and outer (bright) regions of stained spheroids. When intact spheroids were incubated for 18 h in the presence of 5 microM CdCl2, CAT activity was induced in all cell fractions isolated from the spheroids, but induction was 10-fold greater in cells in the outermost fraction (fraction 10) than inner fraction (fraction 2). When spheroids were dissociated, sorted into individual fractions and then incubated with cadmium, CAT expression was maximized in all fractions. Exposure of intact spheroids to 30 microM CdCl2 resulted in increased CAT induction in cells isolated from the internal fractions of the spheroids. The data suggest that limited diffusion of cadmium through cells organized in a tissue-like arrangement may account for the lower levels of hMT-IIA promoter activity observed in cells collected from increasing depths into the spheroids.


Glutathione depletion, lipid peroxidation, DNA double-strand breaks and the cytotoxicity of 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone in rat renal cortical cells.

The mechanisms involved in the cytotoxicity of 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone, a model compound for hydroquinone derived mercapturic acids, were investigated in rat renal proximal tubule cells. 2-Bromo-3-(N-acetylcystein-S-yl)hydroquinone induced a time- and concentration-dependent decrease in cell viability and in the levels of cellular glutathione. Antioxidants such as N,N'-diphenyl-p-phenylene diamine and ascorbic acid and the iron chelator desferrioxamine very efficiently protected the cells from 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone without influencing glutathione depletion. The acetoxymethyl ester of the Ca2+ chelator Quin-2, the inhibitor of the Ca(2+)- and Mg(2+)-dependent endonucleases, aurintricarboxylic acid and the poly(ADP-ribose)-polymerase inhibitor 3-aminobenzamide also ameliorated 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone cytotoxicity. Moreover, 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone depleted Ca2+ from isolated kidney mitochondria, increased the amount of malondialdehyde in rat kidney cells and induced DNA double-strand breaks in renal cells in culture. These results suggest that renal cells oxidize 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone to the corresponding quinone; this soft electrophile reacts rapidly with glutathione, thus depleting cellular glutathione concentrations as indicated by the tentative identification of a 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone thioether in the incubation medium of renal cells treated with the mercapturate. As a result of the massive glutathione depletion, peroxidative mechanisms then cause an elevation of the cytosolic concentrations of ionized calcium; impairment of the ability of the mitochondria to sequester Ca2+ plays an important role in the elevation of the Ca2+ concentration. Finally, activation of Ca(2+)- and Mg(2+)-dependent endonucleases results in DNA damage and cell death.


Monolayer characteristics and thermal behaviour of phosphatidic acids.

The monolayer and thermal behaviour of different phosphatidic acids are presented. At neutral pH and 22 degrees C dilauroylphosphatidic acid and unsaturated phosphatidic acids form liquid-expanded monolayers, while dipalmitoyl- and distearoylphosphatidic acid form condensed monolayers. Dimyristoylphosphatidic acid undergoes a transition from the liquid-expanded to the condensed state. With long-chain saturated and unsaturated phosphatidic acids little change in molecular area is observed between pH 2 and 7. In contrast, the short chain saturated phosphatidic acids, dilauroyl- and dimyristoylphosphatidic acids, undergo a condensation in the pH range 2 to 7. This is so in spite of the fact that the phosphoric acid group dissociates and the phosphatidic acid molecule attains one negative charge over this pH range. This finding is interpreted to indicate that the electrostatic repulsion between negatively charged phosphatidic acid molecules is compensated for or even outweighed by other intermolecular forces. Hydrogen bonding at the lipid/water interface is supposed to play a major role. All phosphatidates studied exhibit a significant expansion in the pH range 7 to 12. The second apparent pK of the primary phosphate group of phosphatidic acids is 8.6 and the expansion observed in this pH range is therefore due to electrostatic repulsion. At neutral pH the ether analogues of saturated phosphatidic acids have monolayer properties similar to those of the ester compounds. Considering the total pH range of 2 to 12 studied the force-area curves of the ether analogues are more condensed compared to the ester compounds. Synthetic phosphatidates and their ether analogues give reversible sharp crystal(gel)-to-liquid crystal transitions while the naturally occurring egg phosphatidate gives a broad, asymmetric one. The transition temperature Tm of saturated phosphatidates increases with increasing hydrocarbon chain length and at a given chain length Tm decreases markedly with unsaturation. The Tm values of the ether analogues are about 10 degrees C higher and the delta H values are 10-15% lower than those of the corresponding esters.


Enterocolitis due to methicillin-resistant Staphylococcus aureus--report of two cases.

Two cases of postoperative enterocolitis due to methicillin-resistant Staphylococcus aureus (MRSA) after gastrectomy were experienced. Case 1: A 59-year-old male underwent subtotal gastrectomy for advanced gastric cancer. Diffuse peritonitis progressed after the first operation, so reoperation for drainage was required. Two days after the second operation, a profuse watery diarrhea developed. Case 2: A 46-year-old male underwent total gastrectomy for early gastric cancer. On the fourth postoperative day, frequent vomiting and cholera-like diarrhea started, followed by profound shock several hours later. Both cases were treated successfully by the administration of vancomycin. Stool cultures of both cases revealed MRSA and it had the same minimal inhibitory concentration, coagulase type and enterotoxin type, so that nosocomial infection was indicated.


Clinical assessment of the knowledge base of an expert system for data analysis in laboratory medicine.

Despite the apparent demand for a consultation system, only a few expert systems have been developed for laboratory medicine. Some studies on the diagnostic precision of such systems have been reported, but the efficiency of their knowledge bases has not yet been investigated. An expert system, named BLOOD, for data analysis in a hematology laboratory, which is written in C-Prolog and runs on VAX-station, has already been reported to have excellent diagnostic reliability and ability to cope with the fuzziness involved in clinical diagnostic procedures. A quantitative examination of the knowledge base of BLOOD using real laboratory data from 58 patients diagnosed as having iron deficiency anemia clearly revealed the verbosity of the knowledge base, and proved that it was effective for obtaining a group of essential diagnostic rules.


Rat cerebellar granule cells in culture associate and metabolize differently exogenous GM1 ganglioside molecular species containing a C18 or C20 long chain base.

A study has been made of the association properties of the two GM1 ganglioside molecular species GM1-C18 and GM1-C20 (containing C18 and C20 long chain bases, respectively) to rat cerebellar granule cells in culture. Both gangliosides recognized, to the same extent, and associated with them to give a form of association, the trypsin-labile form. This form was removed by treatment with trypsin enzyme. Both gangliosides associated stably with the cells to become components of the cell membranes. Although similar amounts of the two gangliosides entered the cells, being then metabolized, the time course of the association was different for the two gangliosides: after 15 h of ganglioside-cell incubation the amount of GM1-C18 inserted into the cell membrane was 2.43 times higher than that of GM1-C20.