High-altitude training. Aspects of haematological adaptation.

Physical training at high altitude improves performance at high altitude. However, studies assessing performance improvements at sea level after training at higher altitudes have produced ambiguous and inconclusive results. Hypoxia-induced secondary polycythemia is a major contributor to increased work capacity at altitude. The common finding upon exposure to hypoxia is a transient increase in haemoglobin concentration and haematocrit because of a rapid decrease in plasma volume followed by an increase in erythropoiesis per se. Both nonathletes and elite endurance athletes have maximal reticulocytosis after about 8 to 10 days at moderate altitude. Training periods of 3 weeks at moderate altitudes result in individual increase of haemoglobin concentration of about 1 to 4%. A more accentuated increase in haemoglobin can be obtained with longer sojourns at moderate altitude. The normal erythropoietin reaction upon exposure to hypoxia comprises initially increased levels followed by a decrease after about 1 week. Thus, the maintenance of a high erythropoietin concentration is not a prerequisite for a sustained increase in erythrocyte formation at high altitude. The main pharmacological modulator of erythropoietin production seems to be adenosine. But modulators such as growth hormone and catecholamines may also potentiate the effect of hypoxia per se on erythropoietin production. On the other hand, there is a risk that the stress hormones may induce a relative depression of the bone marrow particularly in the early phase of altitude training when the adaptation is minimal and the stress reaction is most accentuated. The most important 'erythropoiesis-specific' nutrition factor is iron availability which can modulate erythropoiesis over a wide range in humans. Adequate iron stores are a necessity for haematological adaptation to hypoxia. However, at moderate altitude, there is a need for rapid mobilisation of iron and even if the stores are normal there is a risk that they cannot be mobilised fast enough for an optimal synthesis of haemoglobin. Data from healthy athletes training at moderate altitudes suggest a true increase in haemoglobin concentration of about 1% per week. Complete haematological adaptation occurred when sea level residents have similar haemoglobin concentrations at moderate altitude compared with residents. The normal difference in haemoglobin concentrations can be estimated to be about 12% between permanent residents at sea level and at 2500m above sea level. This difference indicates a necessary adaptation time of about 12 weeks. If the training period at moderate altitude must be shorter, several sojourns at short intervals are recommended. The important factor in haematological adaptation in athletes at moderate altitude is hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS)


Exercise training for patients with coronary artery disease. Cardiac rehabilitation revisited.

Medically prescribed and supervised physical activity forms the keystone for cardiac rehabilitation. A patient's potential and limitations for successful participation in an active restoration programme are determined by the degree of symptomatic recovery and physiological adaptations to a standardised, multistage exercise test. Confirmation of the effects of physical activity intervention is measured by the performance of the same exercise test under near identical conditions at periodic intervals. The prescribed physical activity regimen is usually performed minimally 3 times per week in sessions which last from 30 to 60 minutes. The object is to utilise from 100 to 200 kcal per exercise session. The demonstrated benefits of regular physical activity include reduction of the systolic blood pressure and heart rate at supine rest and while performing submaximal work, an increased level of physical work capacity, reduction in the myocardial oxygen cost at rest and during performance of submaximal exercise, reduction in percentage body fat with a concomitant increase in muscle mass, and reduction in plasma triglycerides. Regular physical activity, in and of itself, does not effect a reduction in plasma cholesterol or an increase in high density lipoprotein cholesterol, nor does it affect such lifestyle habits as cigarette smoking and alcohol consumption. While contraindications to performing medically prescribed and supervised physical activity are usually restricted to the physically incapacitated patient, failure to achieve an exercise threshold for systolic blood pressure of 140mm Hg or higher is probably a contraindication. This conclusion is based on findings which indicate that treated and control patients with this physiological limitation experience the same mortality rates over 3 years. Regularly performed physical activity by coronary artery diseased patients is associated with reductions in mortality from all cardiovascular causes except sudden death. This intervention does not effect morbidity. Although the scientific evidence warrants the prudent use of physical activity for coronary artery disease patients, the case for its long term benefits remains to be proved.


Running injuries. A review of the epidemiological literature.

Running is one of the most popular leisure sports activities. Next to its beneficial health effects, negative side effects in terms of sports injuries should also be recognised. Given the limitations of the studies it appears that for the average recreational runner, who is steadily training and who participates in a long distance run every now and then, the overall yearly incidence rate for running injuries varies between 37 and 56%. Depending on the specificity of the group of runners concerned (competitive athletes; average recreational joggers; boys and girls) and on different circumstances these rates vary. If incidence is calculated according to exposure of running time the incidence reported in the literature varies from 2.5 to 12.1 injuries per 1000 hours of running. Most running injuries are lower extremity injuries, with a predominance for the knee. About 50 to 75% of all running injuries appear to be overuse injuries due to the constant repetition of the same movement. Recurrence of running injuries is reported in 20 to 70% of the cases. From the epidemiological studies it can be concluded that running injuries lead to a reduction of training or training cessation in about 30 to 90% of all injuries, about 20 to 70% of all injuries lead to medical consultation or medical treatment and 0 to 5% result in absence from work. Aetiological factors associated with running injuries include previous injury, lack of running experience, running to compete and excessive weekly running distance. The association between running injuries and factors such as warm-up and stretching exercises, body height, malalignment, muscular imbalance, restricted range of motion, running frequency, level of performance, stability of running pattern, shoes and inshoe orthoses and running on 1 side of the road remains unclear or is backed by contradicting or scarce research findings. Significantly not associated with running injuries seem age, gender, body mass index, running hills, running on hard surfaces, participation in other sports, time of the year and time of the day. The prevention of sports injuries should focus on changes of behaviour by health education. Health education on running injuries should primarily focus on the importance of complete rehabilitation and the early recognition of symptoms of overuse, and on the provision of training guidelines.


Stress fractures in the athlete. Diagnosis and management.

Stress fractures can be a troublesome injury for the sports medicine clinician. The first description was in military personnel, but recently there is an increasing awareness and diagnosis of stress fractures in the athletic population. Stress fractures have been described in all extremities. Some fractures appear to have a degree of sports specificity. Bone is a dynamic tissue which strengthens and remodels in response to stress. Maladaptation to stress causes osteoclastic activity to supersede osteoblastic activity, thereby allowing weakening of the bone. These areas of weakening may fracture and create prodromal symptoms and clinical findings. Localised pains of insidious onset which are activity related are the hallmarks in the clinical history. The physical examination can exhibit localised tenderness, redness and swelling. Radiographs can be negative for up to 4 months. The gold standard for diagnosis is the triple phase 99mtechnetium bone scan. The treatment of a stress fracture is usually conservative. Very few cases require surgical management. The algorithm of conservative management includes: rest, appropriate education for treatment and preventive care, analgesics, serial radiographs, icing and physical therapy modalities, appropriate exercise to prevent detraining, rehabilitation and a regimented return to participation and competition.


[Endosonography: progress in the diagnosis of endocrine pancreatic tumors].

Diagnostic procedures for secreting endocrine pancreatic tumors comprise biochemical tests, CT scans, conventional abdominal sonography, angiography and occasionally MR imaging and isotope scans. Due to their small size, insulinomas and gastrinomas, the most common of these tumors, elude these diagnostic procedures. Preoperative sonography and CT scans were negative in over 60%, angiograms in 35% of the patients. The example of a patient with insulinoma demonstrates that in the future endosonography will offer itself as an accurate method with little risk.


[The treatment of hemifacial spasm using botulinum toxin].

Hemifacial spasm is a disagreeable disturbance with involuntary unilateral twitching of the facial muscles. Its most common form is supposedly due to an irritation of the facial nerve at its proximal intracranial segment by vascular structures. Various forms of treatment including surgical procedures are employed, very often without satisfactory results but frequently involving the risk for severe complications. For a few years a new method has been using injection of botulinum toxin into the affected muscles, which in the majority of patients relieves the abnormal movements for about half a year; therefore, this very effective and secure procedure is recommended as first-line treatment of hemifacial spasm.


[Adrenal cortex carcinoma: diagnosis, therapy and course in 10 cases].

Data from ten cases with carcinoma of the adrenal cortex, diagnosed between 1981 and 1988, have been extensively reevaluated. Six patients suffered from a hormonally active tumor with proven clinical and laboratory signs of hypercortisolism and/or hyperandrogenism. Female patients dominated the cohort (eight of ten). No preference for particular age (35 to 64, mean 52) or lateralisation of the tumor was recognisable. In all cases signs for endocrinopathy and/or tumor disease lead to investigative intervention. Nonspecific symptoms like pain, reduction of weight and fatigue were registered most frequently. In three patients an abdominal tumor was palpable. Investigation of hormone levels and imaging procedures (sonography and CT scan) assured correct diagnosis in all cases. Since prior to operation metastases have been detected in five cases and in eight cases capsular invasion was proven histologically only, one patient was free of tumor after operation but developed hepatic metastases later on. Altogether nine of ten patients developed metastases later on. Seven of the patients died from the perioperative period up to 8.4 +/- 8.15 months. Mean survival of all patients was 20.5 +/- 24.5 months. Histological grading and assessment of anaplasia did not correlate with either survival or tumor stage. None of the patients presented with tumor stage I according to the TNM system by MacFarlane (55). All four patients with advanced disease in stage IV died within the first year after operation. Eight patients were treated with 1 to 6 g of the adrenolytic o,p'DDD (mitotane, Lysodren). In one of these cases, a sonographically documented remission lasting for over eight years was observed. A second patient with anaplastic carcinoma showed a reduction of the size of pulmonary metastases under continuous therapy with o,p'DDD and a cyclic polychemotherapy. After the latter was discontinued, the course was progressive.


[Priapism: review of current knowledge and presentation of a diagnostic and therapeutic algorithm].

In medicine, priapism is defined as pathological state: a prolonged, generally painful erection not accompanied by sexual desire not ending with an ejaculation. Rare before 1980, priapism became more frequent after introduction of erection-inducing drugs by intracavernosal injections for treatment of impotence. Therefore, the medical practitioner can be faced with this problem, and the authors present with an algorithm the current diagnostic and therapeutic steps based on knowledge of pathology, physiopathology and etiology of this disease.


[Clinical-experimental testing of the effects of a new hypnotic on respiratory function in healthy subjects and in patients with chronic-obstructive syndrome].

In a placebo-controlled double-blinded study with ten healthy volunteers and ten patients with obstructive airway disease, the effect of the test compound on respiratory function was measured. Results show that in healthy persons as well patients with obstructive lung disease of slight to moderate degree respiratory functions were not impaired.


[Medical ethics: innovation due to deficiencies?].

A historical follow-up using three examples--euthanasia, choice of therapy for tuberculosis of bones and articulations and economic management of a medical office reveals that comprehensive timeless medical ethics independent from cultural and social influences ('hippocratic oath') do not exist. There are, however persistent as well as increasingly new fields of conflict in daily practise. The latter are partly related to increased medical efficiency. Deficiencies in explicit ethic reflexions and empiric research for coping with such problems led to interdisciplinary medico-ethical work groups and journals over the last years. In this context traditional subjective ethics of care founded on altruism still remain important: The present essay shows, why the new objective and the older subjective approach to moral dimensions of healing professions are mutually founded on each other and should converge in the course of a decision process.


[Medicine between technique and ethics].

In modern medicine technical and ethical questions develop continuously into a tension-loaded relationship. The actual controversy between technical and ethical imperative concerns primarily the fundamental dichotomy and dialectics of modern medical technology. In a second part the ethical challenge for physicians and nurses operating in our increasingly perfect hospitals is analysed. An outlook for future conditions for more harmony between medical technology and ethics is finally presented. A new medical spirit is needed to animate medical technology and to expand it to real art of healing.


[Ethical problems from the caregivers' viewpoint].

In a first part the different perspective of physician and nurse is outlined. Then the ethical principles of the health professionals are outlined. The variant views--descriptive and normative--are described. In a second part the dilemmas emerging in daily practice of health care workers are demonstrated. Questions regarding the importance of well-being and illness are raised. Does CAN mean also that one SHOULD, i.e. for transplantation of organs? What are the guiding criteria for this advanced medicine. Since ethical decisions always touch at least two human beings they touch us over and over--profoundly.


[Ethical problems in geriatrics from the family physician's viewpoint].

The picture of the 'youthful elderly' will develop further in a positive way because elderly people will not only experience a further increase of their average life-expectancy but also of their physical and psychic health and efficiency. Strict adhesion to calendar data means for the elderly that he is easily excluded from social performance and functionality of life. In order to meet the needs and expectations of the elder generation we need more overlapping linking of the different life periods, i.e. more sensitivity for individual arrangements. Increasing burden on the younger generation by increasing multimorbidity and needs for nursing may evoke responsibility for our patients. Therefore we practitioners should readily fulfill our duty to be in charge for the wellbeing of our aging patients. Social sensitivity for dignity in borderline situations depends on the acceptance of illness and needs for nursing as a natural part of our human existence.


[Ethics in psychiatry].

In psychiatry there are two major problem areas where ethical questions are of greatest importance. On one hand these are problems arising from commitment to an institution, e.g. forced hospitalisation and forced treatment. Swiss civil law requires in articles 397a to f that such patients may appeal to a judicial court. When this court is a commission comprised of an attorney and of psychiatric and psychotherapeutic specialists, it is of greatest importance that the patient himself be heard by the attorney and not just by a member of the commission and that this attorney also takes into account statements of relatives, as an incompetent patient may say things that are inconsistent with actual facts. As existing or planned hospitalization laws apply mainly to acutely ill patients who are dangerous to themselves or to others, the treatment of chronically ill psychiatric patients cannot be guaranteed. Thus conflicts of conscience arise, since physicians are required to provide medical aid; therefore if such aid is not given or if it is refused, a physician can be sued for inflicting heavy injury. Hence there is an urgent need for judicial measures that guarantee also the treatment of the chronically ill who, like all patients, have a right to be treated. A second problem area is represented by the ethical commissions that decide which scientific investigations may be performed on psychiatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Current aspects of analgetics-induced asthma].

Up to 10% of all asthmatics are intolerant to aspirin reacting with bronchospasm after intake of this drug. The triad aspirin-intolerance, glucocorticoid-dependent intrinsic asthma and nasal polyps is common in these patients. The reaction to aspirin is not mediated by IgE. Cross-intolerance is observed with all non-steroidal antiinflammatory drugs inhibiting the enzyme cyclooxygenase. If intolerance to aspirin is suspected such drugs have to be strictly avoided. Paracetamol is the alternative in most instances. Only rarely an adaptive desensitization with acetylsalicylic acid is indicated. This method may help to overcome the intolerance. Non-acetylated salicylates occurring also in some foods, preservatives, and food dyes must not generally be avoided in aspirin-induced asthma.


[Therapeutic aspects in the treatment of juvenile bronchial asthma].

The most important goal of the treatment for bronchial asthma in infants and children is to avoid structural damage to bronchi and lung by the underlying allergic and immunologic inflammatory process. This inflammation is caused by an inherited predisposition to exaggerated mediator-release in the mucosa. Repeated actions of trigger factors maintain this inflammation and provoke exacerbations of asthmatic symptoms. The protective task of the bronchial mucosa can not be fulfilled anymore. General measures of asthma treatment such as prophylaxis against house-dust mite exposure, improved breathing technique and improvement of lung clearance are indispensable measures of an individually adapted, effective symptomatic (bronchodilators) and protective (cromolyn, topical steroids) drug therapy in infants and children with bronchial asthma. A successful therapy should ensure a physiological development of the child.


[Bronchial asthma and sports].

Physical exercise can induce an acute attack in most asthmatics. Exercise-induced asthma (EIA) is therefore a common clinical presentation of bronchial asthma. EIA is likely a consequence of bronchial hyperreactivity whereby alterations in bronchial osmolarity, heat-loss by hyperventilation and physical activity per se are discussed as pathogenic triggers. Clinical presentation, pathogenesis and diagnosis of exercise-induced asthma are summarized. Pharmacologic and non-pharmacologic possibilities are covered in some depth. In this context the value of sports-therapy in treatment of asthma is redefined. The possibilities and limitations for this form of treatment are explained.


[Asthma and ozone].

Ozone and other photochemical oxidants are secondary air pollutants which can damage the respiratory epithelium by their peroxidative properties. As a consequence, inhaled ozone produces diffuse inflammation of the airways, combined with an obstructive ventilatory impairment and long-lasting bronchial hyperresponsiveness. In physiopathological terms, the features observed reflect the characteristics of an asthmatic airway reaction. Thus, ozone seems to be a potential trigger of newly generated asthma in healthy persons and, in addition, may deteriorate the course of the disease in patients with preexisting asthma. The damage induced by ozone depends on the concentration as well as on the amount of inhaled pollutants. According to the duration and the physical activities during ozone-exposure, slight lung function defects have been demonstrated even at concentrations up to 120 micrograms/m3 (60 ppb). Long-term effects of ozone on human health are not yet fully explored; however, the results of a few epidemiological studies give strong evidence of harmful effects by repeated or chronic exposure to photochemical oxidants. So far an increased prevalence of respiratory symptoms and deterioration of lung function could be demonstrated in populations living in areas of high atmospheric pollution.


[Epidemiology of falls and hip fractures].

The risk of falling increases with age and with many of the disorders common in late life. Approximately 35 to 40% of community-dwelling people over the age of 65 and up to 50% of institutionalized elderly fall at least once every year. The incidence is highest in women and the very old. Hip fracture, one of the most serious injuries associated with falls, assumes epidemic proportions in old people. In addition to physical injury, falls can have other serious consequences for the older person. Repeated falls are a common reason for the admission of previously independent elderly persons to long-term care institutions. This article examines why older people fall and what factors place persons at risk for falling. The multiple reasons for an inconsistency of the epidemiological data are discussed.


[Cardiovascular causes of falls].

Falls with transitory loss of consciousness (syncopes) are mainly due to cardiovascular incidents and show a significant higher risk of injuries than falls without loss of consciousness. The frequency of syncope is increasing with advancing age. Syncope represents an important disease with epidemiologic consequences in the older age group. The broad etiologic spectrum of syncope and the significance of diagnostic methods are discussed. Five case reports are added as illustration. Medical history, clinical examination and ecg-recordings are the most important diagnostic tools in the evaluation of syncope. An in depth investigation of patients with syncope reduces the rate of recurrence and risk for injury, it increases the quality of life and results in lower medical costs.


[Epidemiology of osteoporosis].

A representative inquiry (n = 4217) in Zürich revealed that 22% of the female population eats a diet poor in calcium. A connection between calcium-deficient nutrition and other unhealthy lifestyles such as lack of exercise, smoking (> 10 cigarettes/day) and regular alcohol intake (several glasses/day) has been shown by multivariate analysis. Therefore one has to suspect, that every third to fourth woman having several risk factors is at risk at entry in menopause. Primary prevention as a population-oriented strategy is therefore sought by general health-education and prevention of accidents in order to lower risks for fractures. Fractures of the collum femoris alone are on the basis of actual life expectancy in Switzerland responsible for 157,000 hospital days in women and 18,000 in men, corresponding to the annual capacity of an acute-cave hospital with 500 beds. With the aid of a risk-group strategy therefore attempts at secondary prevention are necessary. As a cost-effective screening-test every postmenopausal woman should receive a peripheral quantitative computer-tomography. Women with relatively high bone loss-rates and/or low bone density (insufficient stability) could thus be recognized and offered the benefit of an individualized compliance-promoting protective treatment.


[Prevention of osteoporosis using hormone substitution].

Since osteoporosis in the postmenopause is predominantly due to estrogen deficiency, adequate hormone replacement therapy is of utmost importance. Estrogens are preventing bone loss and decrease the fracture rate by 95%, but they also improve vasomotor symptoms, psychic complaints and urogenital atrophy and lower the cardiovascular risk very significantly. Since results depend on long term compliance; motivation, appropriate dose, application mode and treatment schedule are therefore decisive.


[Rehabilitation following falls of undetermined etiology: results of an intervention study].

In a population of 355 nursing-home patients 35 could be identified with "idiopathic senile gait disturbance" or falls. Out of these, twelve patients were motivated to participate in a trial to improve the gait. Six patients participated in an intensive daily physiotherapy-program for five weeks, six patients served as a control group. Five of the six patients in the intervention group improved the gait to a high degree. The gait analysis documented an abnormal posture due to a long use of walking aids, which was not influenced by the training. The study documents that very old nursing home patients can improve the mobility by intensive gait training if they can be motivated for such therapy.


[25 years of pathology at Neuchâtel].

The article introduces the Neuchâtel Institute of Pathology (INAP) which celebrated its 25th anniversary in 1991. The institute is organised according to the statutes of a private foundation, the State of Neuchâtel covering the excess running costs. The task of INAP is fulfilled by its services of clinical pathology which have evolved differently according to each sector. The autopsies reached their peak in 1979, a progressive decline in number is noted since then. The biopsies have increased regularly, especially since 1985. The service of cytopathology has had an irregular development and is actually in full expansion. The article then shows the solutions that INAP has found in the technical and medical fields. The role of medical informatics, introduced in 1983, is pointed out. In conclusion, we discuss the current and future questions of our discipline and their possible solutions in an institution such as ours.


[Medical informatics as a complementary method in medical education].

The practice of the decision making at the bed side especially highlights the place to be devoted to medical informatics both at the pre- and post-graduate levels. Still in a relatively recent past, say the 50s-60s, most of the medical educational efforts were delivered when watching and then imitating the medical behaviour of an older physician. The medical educators were aware that besides the formal lessons related to selected chapters of medical textbooks, there were an obvious need for better training in the ability to make sound clinical judgements. If this ability has been considered only as an artful and intuitive process neither subjected to theoretical analysis nor to be captured in a formal quantitative model, now things have changed to such an extent that it becomes broadly shared that a science of medical decision making can be reasonably founded and this threefold: 1) Upon a formulated logic, 2) The probability theory, and 3) A value theory. The first gives the hand to artificial intelligence (AI) technics, the third to medical information data bases dealing either with patients (like in hospital information systems) or with literature like MEDLINE or electronic "cookbooks". Basically the probabilistic theory is based here upon a priori probabilities related to patients informations and data and opens the way to bayesian decision making. After this little summary it is stressed that educational informatics in medicine would appear either very central or very marginal, if not optional.


Cutaneous malignant melanoma: epidemiological considerations.

Large geographic and ethnic variations in incidence and mortality rates of cutaneous malignant melanoma (CMM) suggest inverse correlations with the degree of skin pigmentation and latitude. Increases in CMM incidence and mortality rates have occurred in virtually all white populations, more markedly in those that permanently (immigrants) or temporarily (tourists/vacationers) reside in very sunny areas outside their primitive living environment. The interpretation of data from case-control studies is, however, hampered by the difficulties in quantifying retrospectively, but reliably, CMM risk correlates (e.g., host factors, sun exposure, clothing habits, sunburns) in various periods during the life span. There is, thus, a need for large prospective studies on the development of CMM and naevi, ideally in different contexts as concerns host factors, sun exposure, and other life-style habits within and across different populations.


Cellular and molecular biology of melanoma.

Melanoma cells have surface markers that are expressed differently than in normal melanocytes and nevus cells. Monoclonal antibodies may define a phenotypic map of the various melanocytic lesions and can be used in immunohistopathology and immunoscintigraphy. Monoclonal antibodies directed against melanoma-associated glycoproteins and glycolipids are being tested for therapy. Rearrangements or deletions on chromosome 1, 6, and 7 are the most frequently observed cytogenetic abnormalities. Molecular studies have not given a clear picture. A subset of HRAS alleles has been reported to be associated with melanoma. NRAS activation by point mutation has been found in one fourth of the cases. Allele losses at different loci have been reported. Genetic linkage studies have given conflicting results on the presence of a gene for the melanoma-dysplastic nevus syndrome on the short arm of chromosome 1.


Precursor lesions of melanoma: do they exist?

The question of whether definite precursors to melanoma exist is answered in the affirmative. Three cutaneous lesions likely to be such precursors are described and discussed as to their clinical and histologic appearance and incidence. Additionally, a type of conjunctival melanosis that has been associated with malignant melanoma of the conjunctiva is discussed and an attempt is made to define it; a proposed classification of this entity is reviewed. Basic approaches to management and analysis of precursor lesions are elaborated.


Surgical management of primary melanoma.

The outline of the surgical treatment of a primary cutaneous malignant melanoma may be divided into the problems of biopsy, definitive excision and reconstruction of the defect. An excisional, in contrast to an incisional, biopsy provides the full scope of prognostic parameters and should be used whenever possible. General anesthesia is not necessary, and frozen-section examination is inaccurate. An immediate excision biopsy should therefore be performed under local anesthesia as an outpatient procedure. Whenever possible, a margin of 10 mm should be used, as this would mean an adequate and definitive treatment in melanomas up to 1 mm, and possibly 2 mm, in Breslow thickness. In melanomas more than 1-2 mm in thickness a 3-cm free margin instead of a 5-cm free margin is recommended. Many patients, especially those with trunk lesions with a 3-cm free margin may not need a complicated repair, such as a skin graft or a flap. The excision in depth is recommended to be carried perpendicular to the skin and inclusion of underlying fascia is optional, as no study has proved it to be beneficial. The defect after the excision should whenever possible be closed directly. If this is not possible the defect is covered with either a skin graft or a flap and the latter is recommended from both a cosmetic and a functional point of view. If a skin graft has been used, the secondary defect may be reconstructed with a skin expansion technique.


[Epidemiology of cerebrovascular accidents].

Recent studies concerning secular trends in stroke incidence and mortality and identification of independent risk factors for stroke are reviewed. Stroke mortality has declined in many industrialized countries in recent decades. In France, it has been declining by more than 30% between 1968 and 1982 in all age groups and in both sexes except for women under 40 years. The decline in stroke mortality seems to be partly real and partly apparent. In the community-based study of Rochester, Minnesota, stroke incidence decreased by 54% between 1945-49 and 1975-79. Recent data from Rochester, however, suggest that the incidence of stroke may no longer be declining. Survival after stroke has also apparently been improving but several sources of potential bias may also have influenced the decrease in reported survival rates. Hypertension is a major risk factor for stroke. Prolonged differences in "usual" diastolic blood pressure of 5 to 10 mmHg are associated with about 40% difference in stroke incidence. Recent analysis suggests that stroke incidence reduction could arise rapidly after hypertension control and that a lower blood pressure should confer a lower risk of vascular disease, even in individuals conventionally considered as "normotensive". There is evidence that cigarette smoking is an important risk factor for stroke with an overall relative risk of 1.5 and that the risk of stroke declines rapidly after the cessation of smoking. A cardiac condition may be a marker for another risk factor or the primary substrate for cerebral embolism. In patients with atrial fibrillation, the risk of stroke is increased through both of these mechanisms. Diabetes mellitus, chronic alcohol consumption (> 3 drinks/day), and high fibrinogen levels are other independent risk factors for stroke. While high levels of cholesterol may be associated with ischemic stroke, an inverse association of the serum cholesterol with the occurrence of intracerebral hemorrhage in men has been reported. In patients with asymptomatic internal carotid stenosis, higher degrees of stenosis convey a higher risk of stroke. However, far from all these strokes are due to thromboembolism from an atheromatous plaque in the ipsilateral internal carotid artery. The relative risk of stroke during the first 5 years following a transient ischemic attack is 7 times that in persons without transient ischemic attack. More than a third of the subsequent strokes occur in a vascular territory different from that of the incident TIA. While the use of oral contraceptives may increase the relative risk of stroke, postmenopausal estrogen treatment may have a protective effect on the risk of vascular diseases.


Treatment of regional nodes.

The appearance of nodal metastases from cutaneous melanoma represents a poor prognosis. Surgery is the only possible treatment for these patients since chemotherapy or immunotherapy have no confirmed specific efficacy in adjuvant or therapeutic schedules. If, for clinically metastatic regional nodes, there is complete agreement on the opportunity of dissection, in the case of clinically uninvolved nodes some controversy exists. For melanomas of the extremities, two different randomized studies have demonstrated no difference in the long-term outcome of patients with stage I melanoma, whether immediate or delayed node dissection is performed. For axial melanomas, although definitive data are not available, there are preliminary statistical results as well as anatomical and technical reasons, suggesting an identical surgical approach to that performed for primaries of other sites. Therefore, apart from specific cases, there is good evidence that node dissection should be planned only for patients with clinically involved regional nodes.


[Hemorrhage of the brain after therapeutic fibrinolysis. 11 cases].

Ten cases of cerebral hemorrhage and one of intraspinal subdural hematoma after thrombolytic therapy are reported. Six patients were treated with streptokinase, four with rt-PA and one with a combination of both drugs. The incidence was 0.5 to 2% and was higher in case of rt-PA therapy (3.7%). In all cases, CT scan showed primary hemorrhage rather than hemorrhagic infarction. Four patients died of stroke. Among the survivors, residual disability was severe in one and mild in five. Only one patient recovered completely. In patients treated with streptokinase, the hemorrhage was probably due to a more than 80% decrease in plasma fibrinogen. In those receiving rt-PA, either excessive dosage (2 cases in our series) or lysis of cerebral microthrombi are thought to be responsible for the hemorrhagic complications. Treatment consists of infection of aprotinin (an anti-fibrinolytic drug), cryoprecipitates with factors V and VIII and protamine sulfate.


[Obsessive-compulsive behavior (arithmomania). Atrophy of the caudate nuclei].

We report the case of a 56-year-old woman who died after a 2.5 years progressive course of behavioral disorders associating severe obsessive-compulsive counting with disinhibition. Neuropathological examination showed severe gliosis of the caudate nuclei whereas the lentiform nuclei and frontal cortex were not involved. In contrast with previous reports, this case lacked psychic akinesia which is usually combined with obsessive-compulsive behavior. It is a further illustration of how subcortical lesions can produce a frontal like syndrome. It suggests a fundamental role of the caudate nuclei in the control of behavior.


Hyperthermic antiblastic perfusion in the treatment of local recurrence or "in-transit" metastases of limb melanoma.

On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multiparametric analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P < 0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P < 0.08). In turn, the complete response rate was a determinant as far as locoregional control (75.3%; P < 0.0009) and disease-free (51.4%; P < 0.009) and overall survival (63.2%; P < 0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P < 0.0014), sex (P < 0.04), and the number of disease recurrences (P < 0.01) appear to influence overall survival.


[Postural hypotension with myoclonia in multisystemic atrophy].

Each time he stood up a 60-year old man experienced myoclonic jerks, quickly followed by a syncope due to major postural hypotension. Progressive autonomic failure was associated with pyramidal, extrapyramidal and cerebellar features in a pattern characteristic of Shy-Drager disease. Myoclonic jerks suggested seizures, but no electroencephalographic epileptiform activity was found. This case together with data from the literature suggest, that such involuntary movements may result from cerebral anoxia.


[Neurosarcoidosis with meningoencephalitis and tumoral granuloma].

A 24-year old woman had neurosarcoidosis with meningoencephalitis and frontal granuloma. After corticosteroid therapy for two years, CT showed that the granuloma had nearly disappeared and that there was a hydrocephalus.


[Sacral perineural cysts. Contribution of magnetic resonance imaging].

In a 41-year old woman complaining of episodic bilateral sciatic pain, MRI showed large sacral cysts developed in the pelvis. The fact that these cysts communicated with the subarachnoidal spaces was not clearly demonstrated by CT. The mechanism underlying the development of this perineural variety of extradural cysts is discussed.


[Pilot study of Ginkgolide B, a PAF-acether specific inhibitor in the treatment of acute outbreaks of multiple sclerosis].

Ten patients with relapsing-remitting multiple sclerosis in acute relapse were treated with a five-day course of intravenous ginkgolide B, a specific inhibitor of PAF-acether. Eight patients had improvement of their neurological score, beginning 2 to 6 days after the initiation of therapy. This improvement was sustained in 5 patients and only transient in 3. Two out of these 3 patients with secondary failure and the other 2 who did not respond to ginkgolide therapy, received i.v. methylprednisolone. Three patients experienced mild side effects under ginkgolide therapy but none of the patients had any serious adverse effect. A controlled randomized study is underway, in order to confirm these results and test higher dosages and more prolonged administration.


[Epidemiology of micro-organisms responsible for community-acquired pneumonia].

Pneumonias occupy a prominent situation among lower respiratory tract infections where they are remarkable for their potential mortality and for our relative knowledge of the responsible micro-organisms. Analysis and synthesis of each series published must answer several questions, such as: what are the lung diseases considered? which investigations have been performed? which criteria of imputability have been used? in which patients has the study been carried out? in which place, which period and which structure? In spite of methodological lacunae and of the inhomogeneous answers to the questions asked, there is some concordance between the series found in the literature. Thus, more than 90% of community-acquired pneumonias with microbiological identification are caused by Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci (or pneumoniae), or Influenza A virus.


Surgical management of distant melanoma metastases.

Disseminated melanoma remains a tumour that is poorly responsive to chemotherapy and radiotherapy. However, this review demonstrates that surgical removal of visceral metastases such as at the, lung or digestive sites, as well as the brain, yields consistent median survivals, often longer than 12 months, and long-term survivors. Such surgery is followed by little complication cost and low perioperative mortality. Our experience tends to confirm that complete debulking offers longer survivors as compared to partial. Also, one site of metastases, whatever its anatomical location, when operated on, gives a better chance for survival than when there are multiple sites.


Cutaneous melanoma: prognosis and treatment results worldwide.

This first metanalysis of melanoma from treatment centers worldwide consisted of 15,798 patients with localized melanoma (stages I and II) and 2,116 stage II melanoma patients with nodal metastases. Comparisons of dominant prognostic variables showed consistent results from center to center, despite the heterogeneity of the patient population. Six of eight centers that performed a multivariate analysis ranked ulceration among the first three most dominant prognostic factors. Men had a higher proportion of ulcerated lesions than did women. There was a positive correlation between ulceration and thickness. Patients with melanoma of the scalp had a worse prognosis than did those with lesions of the face and neck; those with melanomas on the hands had a significantly worse prognosis than did those with lesions on the arms or legs. In this study, women had a statistically significant survival advantage over men. Their melanomas arose in more favorable sites, were thinner, and less ulcerative and had a lower stage of disease at presentation. Stage III melanomas were more common in males, thicker, and more ulcerated and had a nodular growth pattern. Patients with clinically occult nodal metastases detected by pathological examination and those with a single metastatic node fared the best. Five of six centers identified the number of metastatic nodes to be the most significant prognostic factor. Distant metastases (stage IV were analysed at only two centers, which found that the number and site of metastases appeared to be the dominant prognostic features of stage IV melanoma. When all factors were analyzed in a Cox regression analysis, the dominant factors for stage IV melanoma patients were (1) the number of metastatic sites, and (2) the remission duration. There were no histologic criteria of the primary melanomas that predicted the patient's clinical course once distant metastases had developed.


[Photodynamic therapy of bronchogenic cancer].

Photodynamic therapy (PDT) means the activation by light of an exogenous photosensitizer previously retained by tumors. This therapeutic method is under current investigation for lung cancer. A review of the literature presents the preliminary results bearing upon more than 200 epidermoid bronchus carcinomas. A complete response rate of 75% can be anticipated for early tumors. Several survivals beyond five years, due to PDT alone, have already been reported. Two phase III trials are opened, comparing PDT vs YAG laser for obstructing tumors and PDT+Radiotherapy vs Radiotherapy alone for non-operable small tumors. PDT should be developed in selected indications of lung cancer, because it is an original and interesting therapeutic solution.


[Isolated pulmonary choriocarcinoma].

The author report a case of isolated choriocarcinoma of the lung revealed in a young woman by a tumoral syndrome of the right base with haematoma. The diagnosis of isolated pulmonary choriocarcinoma was based on the lack of previous gynaecological history and tumour, on the singleness of the lung tumour at CT, and on the high initial beta-CGH level (3,300 ng/ml) in the absence of pregnancy. Surgical resection confirmed the diagnosis and lowered the beta-CGH level to 7 ng/ml. The various aetiopathogenic theories put forward and their relations with the prognosis disparity found in the literature are reviewed. The authors compare the prognosis of isolated pulmonary choriocarcinoma in a non-nulliparous woman to that of placental choriocarcinoma.


[Inflammatory polyp: a rare benign endobronchial tumor].

We report a case of inflammatory polyp in a male patient, which was totally obstructing the left main bronchus but could be removed by simple endoscopic traction. The polyp was responsible for an absence of left lung ventilation which in turn produced by reflex an absence of left lung perfusion completely reversible after removal of the polyp. Inflammatory polyp is a rare benign tumour. Its physiopathology is controverted, but it seems to result from local irritation of the bronchial mucosa. Bronchial endoscopy is the essential examination which in most cases make it possible to diagnose and treat the tumour.


[Models of experimental Haemophilus influenzae and Streptococcus pneumoniae pneumonia in mice].

Streptococcus pneumoniae and Haemophilus influenzae are the bacteria most frequently involved in bronchopulmonary and E.N.T. diseases. Experimental models are useful to analyse in vivo the physiopathological interactions between bacteria and lung tissue and to study the activity of various antibiotics in the focus of infection. Models for pneumococci are devised according to the virulence of the strain, the inoculation technique and the type of animal used. When strains of different virulence and hosts of different lineage are combined, several experimental models with different natural histories are obtained. These experimental models make it possible to study therapeutic measures at different stages, comparing the relative activities of fluoroquinolones, ampicillin and macrolides. For fluoroquinolones, no correlation has been found between in vivo and in vitro data in these models, but the effectiveness of new compounds has been studied. As regard Haemophilus influenzae, lung infection models are rare, either because their septicaemic component is too important or because they do not enable this organism to multiply. Moreover, the models obtained do not lend themselves easily to therapeutic trials and favour those antibiotics that have high serum concentrations. Developing a better model would enable us to improve our knowledge of the pathogenicity of this micro-organism.


[Perineal aponeuroses. An anatomical study leading to the concept of perineal pubic-sacral cord].

On the basis of anatomical dissections, the authors offer a description of the perineal thickness (centred on the study of its aponeuroses) which corresponds better with medical imaging (ultrasonography, MRI) findings. Situated between the pelvic floor (deep layer of the deep perineal aponeurosis) and the perineal skin (covering the superficial layer of the superficial perineal aponeurosis), the perineal thickness is organised around an antero-posterior functional entity: the pubic-sacral perineal cord. This is made up, from behind and going forwards, of: the urethro-clitorido-vulval entity, the peri-vulval insertion of the perineal aponeuroses, the tendinous centre of the perineum and the ano-coccygeal raphe. It forms the keystone of the perineal thickness by closing off the floor of the urogenital fossa, the transit point for prolapses. This organisation of the perineal thickness explains how the vulval orifice, with no truly effective specific muscular structure, opposes the forces of abdominal pressure, thus avoiding the development of prolapse under normal circumstances. The ischio-rectal fossa is also studied.


[Uretero-vesical injuries during pelvic surgery in women].

Injuries to the ureter and the bladder are common complications in female pelvic surgery. Unfortunately, they remain often unrecognized per operatively. Intravenous pyelography and renal ultrasonography are very efficient for post operative diagnosis. The indications of nephrectomy have became rare because of the efficacity of the procedures of plastic and reconstructive urological surgery.


[Meta-analysis of management seeking to prevent ovular infection].

The prevention of chorioamnionitis after preterm rupture of membranes is still controversial. This is due to the lack of power of most studies. These seem to show that the outcome is mostly determined by the gestational age at membrane rupture and a trend at lower chorioamnionitis when antibiotics are used.


[Evaluation of the method of delivery in breech presentation].

The authors report a retrospective study based upon 543 breech deliveries at term, collected between 1987 and 1990. The cesarean section rate was 18.4 per cent. It was prophylactic in 56 cases. When the possibility of vaginal delivery was accepted, cesarean section was performed in 9 per cent of cases. Fetal mortality and morbidity were higher with vaginal delivery. However, maternal morbidity was greater in the cesarean section group. Study of the literature shows that the increase in cesarean section rate in recent years is not the only factor responsible for improved fetal prognosis. It is therefore important to restrain this increase and find the optimum percentage rate.


[A comparative study of 2 uterotonic drugs during assisted delivery. Ergometrine versus ergometrine combined with oxytocin].

Ergometrine and ergometrine combined with oxytocin were used during assisted delivery for respectively 65 and 60 labours associated with a risk of hemorrhage. Both these substances have a remarkable hemostatic action, though that of ergometrine combined with oxytocin was found to be superior.


The pathogenetic aspects of spondyloarthropathies from the point of view of HLA-B27.

The association of HLA-B27 and seronegative spondyloarthropathies, especially ankylosing spondylitis has been known for almost two decades. The spontaneous development of spondyloarthropathy like joint disease in HLA-B27 transgenic rats verifies the suspicion that the HLA-B27 antigens are directly responsible for disease development. With the recently revealed crystal structure of HLA-B27 and understanding of the class I molecule in general, a new hypothesis can be formulated based on the assumption that the pathogenesis of these diseases is a subversion of the physiological function.


[Characteristics of pregnancy and delivery in women with heart diseases].

The authors report 78 cases of pregnancy in women with heart disease during a 4 year period (1985-1988). Heart disease involved a rheumatic valve lesion in 90 per cent of cases. Heart disease was properly monitored in these patients (74.5 per cent) but the pregnancy in only 50 per cent of cases. These patients gave birth to 78 newborn infants. Labour was premature in 15.38 per cent of cases. Labour was of short duration: less than 6 hours (73 per cent of cases). There was only delivery by cesarean section. Bleeding at the time of delivery was common (12.4 per cent of cases). There were two maternal deaths during the post-partum period (2.56 per cent). Essential risks to the newborn included low birth weight (17.5 per cent) and prematurity (15.38 per cent). Neonatal mortality was 2.5 per cent.


Damage of cultured chondrocytes by hydrogen peroxide derived from polymorphonuclear leukocytes: a possible mechanism of cartilage degradation.

To study the mechanisms of chondrocyte damage, chondrocyte cytotoxicity as shown by chromium-51 release induced by polymorphonuclear leukocytes (PMNLs) was examined. PMNLs significantly enhanced chondrocyte cytotoxicity in the presence of phorbol dibutyrate. This chondrocyte damage was abolished by the addition of catalase, whereas superoxide dismutase and scavengers of hydroxyl radicals and protease inhibitors failed to reverse it. When cartilage matrix components such as hyaluronic acid and various proteoglycans were added to the PMNL-chondrocyte cultures, these components failed to affect the chromium-51 release. These results suggest that the increase in chondrocyte cytotoxicity is due to hydrogen peroxide generated by the PMNLs, and that cartilage matrix components do not prevent it. Hydrogen peroxide from PMNLs may therefore play an important role in cartilage degradation through direct damage of chondrocytes during inflammatory process.


Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis.

Recent clinical observations support the hypothesis that persistent parvovirus B19 is a triggering factor of rheumatoid arthritis (RA) in certain genetically predisposed individuals. If this hypothesis is correct, a number of RA patients may exhibit parvovirus B19 DNA in their synovial membranes. We tested the synovial tissue and peripheral blood leukocytes of 20 patients with RA, 24 patients with other arthritides or osteoarthritis (non-RA), and 34 healthy blood donors for the presence of parvovirus B19 DNA using specific DNA amplification by polymerase chain reaction (PCR). Using this technique, parvovirus B19 DNA was demonstrated in the synovial biopsies of 75% of patients with RA but in those of only 16.7% of patients with non-RA. In autologous peripheral blood mononuclear cells the percentage of PCR-positive patients was about 15% in both RA and non-RA groups and did not differ from that in healthy controls. When the PCR data were correlated with the presence of anti-parvovirus B19 IgG antibodies in serum and synovia all patients with parvovirus B19 DNA in peripheral blood alone or in both peripheral blood and synovial membrane were seropositive. In contrast, about 40% of patients with parvovirus B19 DNA restricted to the synovial membrane were seronegative. These data indicate a highly disease-related persistence of parvovirus B19 in the rheumatoid synovium.


[Disseminated peritoneal leiomyomatosis. Apropos of a case].

The authors report a case of disseminated peritoneal leiomyomatosis (DPL) occurring in a post-menopausal woman not using hormone replacement therapy. Her past history included a subtotal hysterectomy, with preservation of the adnexae, for metromenorrhagia due to a leiomyomatous uterus. This case confirms data in the literature concerning presentation, symptomatology, macroscopic appearance and histology. No electron microscopy study was undertaken, nor were hormonal receptors evaluated. The originality of this case lies in the onset of DPL in a post-menopausal (with laboratory confirmation) woman with very slow progression over several decades confirming the hormone-dependent nature and the good prognosis of this rare condition.


Phenotypic analysis of functionally associated molecules on peripheral blood and synovial fluid monocytes from arthritis patients.

Surface expression of 16 different membrane molecules was analyzed in peripheral blood and synovial fluid monocytes from patients with rheumatoid arthritis and reactive arthritis compared to controls. The most significant findings were modulated expression of function-associated FcRI, CR1, CR3, MHC class II and activation-associated CD31, M5, and M6 molecules in arthritis patients compared to controls. Of these molecules, only upregulated expression of MHC class II has previously been reported in synovial fluid monocytes of patients with rheumatoid arthritis.


[Vesico-uterine fistulas. Apropos of 2 cases].

Vesico-uterine fistulas (VUF) are an increasingly rare entity (5% of all urogenital fistulas). The authors report two cases of VUF following cesarean section. The literature is reviewed briefly, indicating that Youssef syndrome is the commonest presentation. This lesion is certainly benign but is a source of discomfort for sexually active women. Treatment is above all preventive. It is based per-partum on perfect management of all cases of difficult labour. Peroperatively, the technique used during each cesarean section must be carefully defined and followed. Treatment of a confirmed VUF is essentially surgical.


Interleukin-8 in inflammatory rheumatic diseases: synovial fluid levels, relation to rheumatoid factors, production by mononuclear cells, and effects of gold sodium thiomalate and methotrexate.

The content of interleukin-8 (IL-8) in the synovial fluid and its production by blood and synovial fluid mononuclear cells (PBMC and SFMC) was compared in rheumatoid arthritis (RA) and various other inflammatory rheumatic disorders. The study included 125 patients and 20 healthy individuals. The highest concentrations of IL-8 were found in the synovial fluids and culture supernatants of PBMC and SFMC from patients with seropositive RA. Only PBMC from seropositive patients, and not from other rheumatic diseases, exhibited significant spontaneous release of IL-8 that correlated with serum IgM rheumatoid factor titers. Gold sodium thiomalate (GST) and methotrexate (MTX) inhibited the spontaneous and stimulated IL-8 production by PBMC by 55-86% at 50 and 10 micrograms/ml, respectively. Two main conclusions were drawn: (1) rheumatoid factors appeared to be a major cause of enhanced IL-8 production in seropositive RA, and (2) inhibition of IL-8-mediated neutrophil migration and activation could be part of the mechanism of action of GST and MTX.


Place-specific derived cochlear microphonics from human ears.

The high-pass noise masking technique was used to obtain derived frequency-specific cochlear microphonics (CM) from subtracted waveforms to rarefaction and condensation stimuli recorded with a tympanic membrane electrode. Two characteristics suggest that the response is place-specific CM: the derived response retains the same frequency as the stimulating toneburst and the response follows the stimulus polarity. For click stimulation, derived neural responses make the place-specific CM difficult to observe except in the 2-1 kHz derived band. In contrast, place-specific CM evoked by 0.5 and 1 kHz tonebursts can usually be detected in at least three derived bands. The amplitude of the response is largest in the derived band with center-frequency (CF) just above that of the toneburst. This discovery of a place-specific CM offers the possibility of assessing (outer) hair cell function in the apical part of the human cochlea.


Behaviour of delayed evoked otoacoustic emission under forward masking paradigm.

The behaviour of delayed evoked otoacoustic emission (DEOAE) has been studied in normally hearing adults under a conventional forward-masking paradigm, and subjective measurements were carried out additionally for comparison. The clicks served as signals and the noise bursts were used as masker. In different experimental sets, signal and masker intensity, masker duration, and the interval between masker and maskee were altered. At masker levels corresponding to the subjective post-masking threshold of the clicks, the DEOAE was unaffected, i.e. had no noticeable alteration, compared with click stimulation without masking. Even at higher masker levels the inaudible clicks elicited clearly discernible DEOAEs. The forward-masking detection threshold of DEOAE ('DEOAE post-masking threshold') was reached at masker levels approximately 35 dB above the subjective post-masking threshold. The gap between subjective and DEOAE post-masking threshold vis-à-vis the masker level was also evident at different masker durations and different time intervals between masker and maskee. Central neural and peripheral receptor mechanisms are suggested to be the constituents of the masking phenomenon. The neural mechanism is involved at low masker levels. The receptor mechanism effectively joins the neural one at masker levels exceeding the threshold of psychoacoustic masking. The progressive increase in the number of auditory units from the periphery to the centre in the hearing system, linked with an increase in inhibition, can help to explain these effects.


Effects of adaptation on electrocochleography and auditory brain-stem responses in the elderly.

Changes in the amplitude and latency of the evoked potentials in electrocochleography (ECochG) and auditory brainstem responses (ABR) produced by increased stimulus rates (adaptation) were investigated using an extratympanic ECochG technique with simultaneous recording of the ABR in 12 elderly patients, and compared with those of eight normally hearing young adult subjects. Although the absolute latencies of the action potential (AP) and ABR waves were delayed in the elderly, the shift in latency of these components with increased stimulus rate was similar in both groups of subjects. Amplitudes of the AP and wave III component were reduced with increased stimulus rate to a degree which again was similar in both the elderly and young adults. On this basis we suggest that synaptic connections to nerve fibres from surviving hair cells in the elderly are functioning so that disturbance of this part of the acoustic nerve is not a feature of presbycusis.


The I' potential of the brain-stem auditory-evoked potential.

We have consistently recorded a positive wave which precedes wave I, and is called I', within the human brain-stem auditory-evoked potential. It is postulated that I' represents initial neural activity of the auditory nerve, which presumably has as its origin auditory nerve dendrites. Thus, I' may represent a summed far-field dendritic potential from currents of excitatory postsynaptic potentials. We report latency and amplitude values of I'.


The super-bass bone-anchored hearing aid compared to conventional hearing aids. Audiological results and the patients' opinions.

Twelve patients with severe mixed hearing loss (PTA ranging from 70 to 108 dB HL) were provided with the percutaneous 'super-bass HC 220' bone-anchored hearing aid (BAHA) to replace their former hearing aid. Five had previously worn an air-conduction hearing aid (behind-the-ear type, BTE) which could no longer be used because of recurrent otorrhoea; the others had previously worn a conventional (transcutaneous) bone-conduction hearing aid (CBHA) which had caused serious complaints, such as headaches or skin irritation. Free-field speech audiometry in the subgroup of patients who used to wear a CBHA revealed that the maximum intelligibility score with the BAHA was equal to or better than that obtained with the CBHA (range from 0 to +27%). In three of the five patients who used to wear a BTE, the speech scores were poorer with the BAHA than with the BTE (range from -13 to -40%). For the remaining two patients, the difference in scores was 0 and +10%. In conclusion, speech recognition with the BAHA HC220 in the patients with severe mixed hearing loss was comparable to, or better than, that with a CBHA. Compared to an air-conduction hearing aid, the results may be considerably poorer. The results of the questionnaire were in good agreement with the measurements and support the conclusions.


Cardiovascular adjustments to high- and low-intensity exercise do not regulate temporary threshold shifts.

Sixteen adults cycled for 10 min at low and high intensities--with and without noise. The noise consisted of a 1/3 octave band-filtered noise with a 2,000 Hz center frequency at 104 dB SPL. Regardless of whether or not noise was present, systolic blood pressure increased 14% and 40% above rest during low- and high-intensity exercise, respectively. Heart rate also increased above rest (36% and 90%) during low- and high-intensity exercise, respectively. Temporary threshold shifts (TTS) at 3,000, 4,000 and 6,000 Hz could not be differentiated following low- and high-intensity exercise when noise was not present. We report significant TTS at the three frequencies following 10 min of noise exposure with or without low- or high-intensity exercise. TTS was not influenced by either the 14-40% increase in blood pressure or the 36-90% increase in heart rate induced by exercise. The inability of noise alone to influence either blood pressure or heart rate appears to implicate systems other than the cardiovascular in the regulation of hearing sensitivity.


The feasibility of using oto-acoustic emissions to monitor cochlear function during acoustic neuroma surgery.

The feasibility of using evoked oto-acoustic emission (EOAE) measurement for intra-operative monitoring of cochlear function was assessed during removal of an acoustic neuroma in a 53-year-old woman with normal hearing on the operated side prior to surgery. The high level of noise in the operating theatre was the only material problem encountered and this was not sufficient to prevent recording of identifiable waveforms. During manipulation of the brainstem, damage to the cochlea was indicated by an increase in EOAE latency and its eventual disappearance. A total hearing loss in the operated ear was revealed after surgery. Monitoring cochlear function with EOAEs is probably best considered at present as an adjunct to auditory brainstem response monitoring of the composite cochlea and eighth nerve, thus providing differential information.


Phase coherence of the middle-latency response in the elderly.

We compared phase coherence of the auditory-evoked, middle-latency response (MLR) and the 40-Hz steady-state evoked potential (SSEP) in two groups of elderly listeners, matched for degree of audiometric hearing sensitivity loss. In group A, speech understanding was appropriate to the degree of audiometric sensitivity loss. In group B, speech understanding was disproportionately poor in relation to the degree of loss. In both modes of measurement (MLR and SSEP) phase coherence was significantly poorer in group B than in group A. In the case of MLR, maximum phase coherence was observed at the expected 40 Hz in group A, but at 30 Hz in group B. In the case of SSEP, maximum phase coherence was observed at 40 Hz in both groups but was poorer at almost all Fourier components in group B.


Cochlear and neural dysfunction in acoustic neuroma: can they be separately revealed by auditory brain-stem wave V latency?

Cochlear and retrocochlear lesions may be differentiated by a diagnostic index (D5), which is derived from the patient's auditory brain-stem wave V latency and pure-tone hearing threshold at 2 to 4 kHz. The D5 values obtained from 49 cases of acoustic neuroma (AN) have been shown to share some properties with D5 values of patients with cochlear hearing loss (280 cases), indicating a lesser prolongation of wave V latency in cases with pronounced hearing loss. Assuming this finding is indicative of some degree of cochlear impairment concomitant to the neural dysfunction, AN data were corrected in an attempt to remove the effects of cochlear impairment. The resulting D5 values could reflect the delay in wave V solely due to the neural dysfunction. A significant relationship between these D5 values and tumour size seems to support this hypothesis.


Psychometric evaluation of the hearing measurement scale on patients registered in a Swedish hearing centre.

The hearing measurement scale (HMS), targeting the experience of being hearing impaired, was translated into Swedish and answered by 122 patients with slight to moderate hearing losses. According to the item analysis the test construction of the HMS functions well with a relevant division of the sections. In all sections there were individuals utilizing all response possibilities and the homogeneity (alpha) of the test was high. One exception was section II (hearing non-verbal sounds), which may be due to lack of awareness, indicating that it might not be possible to pursue this dimension by a questionnaire approach. Normative descriptions were given for two age groups: 40 to 60 and 61 to 74 years, including both sexes. The groups had a similar outcome on the HMS, even though the older subjects, on average, had worse hearing problems, measured by pure-tone audiometry. The section covering speech perception had the strongest correlation with hearing loss, while the section covering emotional response entirely lacked such correlations for the younger group.


Indices of hearing in patients with central auditory pathology. II. Choice response time.

The response times of three groups of subjects with pathology of the auditory pathway, localized either to the eighth nerve or to the right or left temporal cortex, were compared on three psychoacoustic tasks. These tasks included detection, frequency discrimination and duration discrimination. Measurements were made at two stimulus frequencies, 500 and 2000 Hz, in combination with two durations, 50 and 300 ms. The results were compared to those obtained for normal hospitalized and non-hospitalized control subjects. All subjects, except those with acoustic neuroma, had age-corrected normal hearing. Statistically significant group differences were apparent in discrimination but not detection, indicating the importance of task demands for response time measures, especially in patients with cortical pathology. The outcomes were not related to neuropsychological measures of speed or accuracy, supporting the conclusion that the time for decision-making rather than motor function had been affected.


Indices of hearing in patients with central auditory pathology. I. Detection and discrimination.

This paper describes the effect of site of lesion on auditory detection, discrimination and speech processing. Three groups of ten patients with confirmed pathology of the eighth nerve and right and left temporal cortex and two normal-hearing control groups, differing with respect to hospitalization, participated. In each of the fifty subjects, measurements were made of detection thresholds, and difference limens for frequency and duration for 50 and 300 ms pure tones of 500 Hz and 2000 Hz. Consonant discrimination was assessed using the Four Alternative Auditory Feature Test (Foster & Haggard, 1979), presented in quiet. Subjects with left temporal pathology had the largest frequency and duration difference limens. Those with either left temporal or eighth nerve pathology had significantly lower speech intelligibility scores that were correlated with the duration difference limen for short stimuli and detection thresholds, respectively. These findings challenge traditional views of cortical processing and highlight differences between peripheral and central mediators of speech processing.


Magnesium deficiency diagnosed by an intravenous loading test.

Magnesium deficiency is common but difficult to diagnose and to assess in clinical practice. The use of a magnesium loading test was therefore evaluated to diagnose magnesium deficiency in 661 hospitalized patients with medical conditions assumed to interfere with magnesium uptake and excretion. Thirty millimoles of magnesium sulphate were administered intravenously during 8 h as a loading test and related to the urinary excretion in the following 24 h. A group of 30 patients without any known predisposition for magnesium deficiency and a group of 27 healthy volunteers served as controls. The mean (with 95% confidence interval) magnesium retention was 4 (-2-10)% in the control group of patients and 3 (-2-8)% in healthy subjects. A significantly higher retention was observed in all the groups of the patients: atrial fibrillation 18 (11-25)%, other arrhythmias 18 (11-24)%, hypertension 27 (20-33)%, coronary artery disease 25 (20-30)%, congestive heart failure 31 (26-37)%, cerebrovascular events 38 (24-51)%, gastrointestinal disorders 22 (14-29)%, diabetes mellitus 16 (9-22)%, and alcoholics 33 (29-36)%. The percentage of patients with a retention greater than mean + 2 SD of the two control groups varied between 22% and 54% among the different patient groups. The mean serum magnesium among the patient groups was similar to the control group of patients, except for the alcoholics, hypertensives and young healthy controls, who had significantly reduced levels. Magnesium retention was significantly correlated to age and renal function, and among the alcoholics negatively correlated to serum magnesium.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum methylmalonic acid before and after oral L-isoleucine loading in cobalamin-deficient patients.

Over a 1 1/2-year period, we measured concentrations of methylmalonic acid in serum before and after a standardized loading with oral L-isoleucine (100 mmol) in 13 patients admitted for evaluation of cobalamin deficiency. All patients had serum cobalamin values below 100 pmol l-1, but only 12 of the 13 patients were clinically confirmed cobalamin deficient. The clinically non-cobalamin-deficient patient had folate deficiency and was excluded. The serum methylmalonic acid concentrations before loading with isoleucine were above the upper reference limit (0.37 mumol l-1) in all the patients and L-isoleucine caused an increase in serum methylmalonic acid of more than 1.00 mumol l-1 in 11 of the 12 deficient patients. In the remaining patient the increase was 0.35 mumol l-1. The results show that a significant increase of an initially elevated serum methylmalonic acid concentration after isoleucine loading is a general finding in tissue cobalamin deficiency which strongly supports the diagnosis.


Clinical evaluation of the Takeda Medical (A & D) TM 2420 ambulatory blood pressure monitor. Practical experience and comparison with direct and indirect measurements.

Takeda Medical (A & D) TM 2420 is an automatic ambulatory blood pressure monitoring system employing the auscultatory technique. The device was used under stable conditions and compared to readings from the Hawksley random-zero sphygmomanometer using a double headset stethoscope and a Y-connection. We tested 85 subjects (aged 13-89 years, systolic blood pressure 85-212 mmHg, diastolic blood pressure 40-116 mmHg) and found a difference amounting to 1.6 +/- 6.7 mmHg (mean +/- SD) for systolic and 2.1 +/- 4.5 mmHg for diastolic readings (Hawksley-TM 2420). In 62 subjects a comparison with simultaneous measurement on the opposite arm with the Hawksley manometer showed similar results. When comparing intra-arterial readings from 10 subjects, a difference (intra-arterial-TM 2420) of -1.9 +/- 12.1 mmHg was found for systolic pressures, while the diastolic difference was -10.7 +/- 8.7 mmHg. Twenty-four hour monitoring was performed on 80 subjects; 70 of these yielded usable tracings. The proportion of successful recordings was acceptable, but the device was not suitable for bicycle stress testing. The quality of the accessories provided with the equipment could be improved, but in spite of this the monitoring system was found to be recommendable for clinical use.


Lipoprotein metabolism following gastroplasty in obese women.

In order to elucidate the long-term alterations in cholesterol transport and esterification as a part of the changes in the carbohydrate and lipoprotein metabolism subsequent to calorific restriction, 15 obese women were investigated before and after treatment with vertical banded gastroplasty. Insulin resistance and production, lipid levels in plasma, lipoproteins and the lecithin: cholesterol acyl transferase (LCAT) rate were assessed. There was a 60% decrease in mean calorific intake six months after surgery. A slight hyperglycaemia was almost normalized concomitant with a reduction of serum insulin and C-peptide after 1 year. The very low density lipoprotein (VLDL) level was unchanged. The high density lipoprotein (HDL) levels tended to rise after 1 year, when there was a significant increase of the HDL-2 subfraction. The lipid levels in the lipoprotein fractions showed a rise in mean HDL-2 cholesterol. Both the molar and fractional rates of LCAT were decreased. These results suggest that long-term calorific restriction reduces insulin resistance and production, and lowers VLDL levels and VLDL and cholesterol synthesis. However, the low density lipoprotein cholesterol levels are unchanged, probably because of a decrease in the previously elevated fractional cholesterol removal.


Evidence of decreased fibrinolytic activity in hypertensive premenopausal women.

In 29 lean, premenopausal, never-treated hypertensive women (142 +/- 2/93 +/- 1 mmHg, mean +/- SEM) plasminogen activator inhibitor (PAI-1) was elevated (11.0 +/- 1.5 U/ml vs 6.3 +/- 1.0 U/ml, p less than 0.05) compared to healthy, normotensive women (113 +/- 2/71 +/- 2 mmHg). Euglobulin clot lysis time tended to be longer in the hypertensive than in the normotensive women (p = 0.06). PAI-1 was positively correlated to triglycerides (r = 0.60, p less than 0.001), haematocrit (r = 0.45, p less than 0.05), insulin (r = 0.38, p less than 0.05) and body mass index (r = 0.38, p less than 0.05), and inversely correlated to HDL cholesterol (r = -0.43, p less than 0.05) in the hypertensive women. Fibrinogen was not significantly different in the hypertensive and normotensive women, while the hypertensive smokers had higher fibrinogen than the hypertensive non-smokers (3.01 +/- 0.17 g/l vs 2.54 +/- 0.10 g/l, p less than 0.05). All participants were investigated in the same phase of the menstrual cycle. Despite that, oestradiol was significantly lower in the hypertensive than in the normotensive women (0.57 +/- 0.06 vs 0.81 +/- 0.09 nmol l-1, p less than 0.05), while progesterone was similar in the two groups. These results suggest that premenopausal, never-treated hypertensive women are characterized by low oestradiol levels as well as decreased fibrinolytic activity. PAI-1 seems to be associated with other risk factors for cardiovascular disease in hypertensive women.


Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma.

The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma.


Reference intervals based on hospitalized 'healthy' patients and medical students in relation to analytical bias for serum potassium.

The reliability of reference intervals for measurements of serum (S)-potassium in Danish hospital laboratories was investigated (i) by estimation of reference interval based on two different, healthy subpopulations and (ii) by comparison of reference intervals for S-potassium with analytical bias in each of 52 Danish laboratories. (i) The reference values from 227 hospitalized 'healthy' patients were obtained during the period 1979 to 1987 from the first-drawn serum specimen from the hospitalized patients, who were later discharged from the hospital without a diagnosis. The estimated 0.95 reference interval was 3.34 to 4.52 mmol l-1. The other reference sample group consisted of 314 medical students from whom blood was collected in the period from 1983 to 1987. Here the estimated reference interval was from 3.44 to 4.53 mmol l-1. The concentration values from both reference sample groups were corrected for analytical bias (+0.05 mmol l-1). (ii) The 52 Danish laboratories revealed a considerable variability in reference intervals which, regarding the lower reference limit, ranged from 3.2 to 3.7 mmol l-1 in strong contrast to the analytical bias (ranging from -0.08 to +0.15 mmol l-1) in 50 laboratories (two outliers). There was no relationship between lower reference limit and analytical bias in the individual laboratories. It is concluded that analytical performance allows for more uniform (even common) reference intervals throughout the Danish and perhaps Nordic hospital laboratories.


Lack of evidence for altered complement and immunoglobulin levels in patients with sickle cell anaemia.

Forty-three patients with homozygous sickle cell disease (haemoglobin SS), 24 heterozygous (AS) subjects and 24 controls (AA) from Sudan were investigated by haemolytic activation for complement function via the classical and the alternative pathways, respectively, and by determination of the plasma levels of C3, C4 and factor B as well as of immunoglobulins IgG, IgA and IgM. The study failed to reveal any direct involvement of the complement system in sickle cell disease and nor was any alteration of the immunoglobulin levels registered as a possible cause of increased susceptibility to infections in patients with homozygous sickle cell anaemia.


Reference intervals for trace elements in blood: significance of risk factors.

A random sample of 100 men and 100 women was examined for whole-blood concentrations of mercury, lead, cadmium and selenium, and the serum concentrations of selenium, nickel, fluoride, aluminium, zinc and copper. Major predictors were sex, hormonal factors (pregnancy, menopause, use of oral contraceptives), age, tobacco smoking and alcohol drinking. Among notable associations, increased blood-mercury was related to the presence of more than four amalgam fillings in the teeth. Blood-mercury correlated with blood-selenium, but a relation to fish intake could only be demonstrated for the former parameter. In women, blood-lead appeared to increase with age, with the highest levels seen after the menopause. Serum-nickel was slightly lower in patients with nickel-related contact eczema. Only the selenium concentrations showed a slight increase in individuals taking mineral supplements. Serum-zinc concentrations decreased considerably during the day. Thus, due to the substantial influence of physiological and environmental factors, individual results must be interpreted in the light of the known predictors for the trace element concentration. However, population-based reference intervals for trace elements in blood are useful to explore geographic and temporal variations.


Primary hyperparathyroidism or hypercalcaemia of malignancy?

The introduction of two-site immunometric assays measuring intact parathyroid hormone (PTH) and radioimmunoassays measuring PTH-related peptide (PTH-RP) have simplified the evaluation of patients with hypercalcaemia. We present a 63-year-old man with recurrent hypercalcaemia after surgical treatment for primary hyperparathyroidism 3 years previously. PTH measured with a mid-region radioimmunoassay gave normal values, at the same level as during his primary hyperparathyroidism. Intact PTH was, however, clearly suppressed, and he had a highly elevated level of PTH-RP. This suggested that he had humoral hypercalcaemia of malignancy. The patient died after 2 months, and at autopsy an adenocarcinoma of the pancreas with no skeletal metastases was found.


Serum methylmalonic acid in uraemia.

During a 3 month period we measured serum methylmalonic acid concentrations monthly in 37 patients, all on chronic haemodialysis because of end-stage kidney disease. Concentrations of methylmalonic acid in serum were above the upper reference limit in 36 of the 37 subjects. All patients were in regular cobalamin therapy, with intramuscular injections every third month, and all had normal to very high values of serum cobalamin. We found no normalization of serum methylmalonic acid during the examination period after cobalamin injections, and we could not demonstrate any relationship between concentrations of methylmalonic acid and creatinine, cobalamin and creatinine or methylmalonic acid and cobalamin in serum of these subjects. We conclude that an elevated serum methylmalonic acid concentration is a general finding in uraemic patients, and so the assay cannot be used to establish the diagnosis of tissue cobalamin deficiency in these patients.


Amount of secondary dentin as an indicator of age.

The amount of secondary dentin in a tooth has been used as one of several parameters in methods for age estimation. Dentin deposition has been measured according to various scoring systems, and the Pearson correlation coefficient with age has been found to be approximately 0.6. In the present study of 1000 teeth, molars excluded, secondary dentin was estimated according to three scoring systems. The teeth were prepared according to the half tooth technique. In addition, the area of the coronal pulp and the widths of the root and pulp chamber were measured in a stereomicroscope at the cemento-enamel junction and at three other defined points along the root. The Pearson correlation coefficient between age and secondary dentin varied in different types of teeth. Of the scoring systems, scores according to Johanson were most strongly correlated with age (r = 0.59 to 0.74). Correlation between age and the coronal pulp area varied from -0.47 to -0.72, and the range between age and ratio between pulp- and tooth width at the cemento-enamel junction was from -0.46 to -0.77. Correlations between age and ratio between sum of pulp widths and the sum of tooth widths for all four such measurements ranged from -0.58 to -0.81. Multiple regression analyses showed that by combining several types of measurements, the correlation with age was increased. A tendency was also observed towards reduced speed of secondary dentin formation in the elderly and in women.


Effect of stannous fluoride and tetracycline on periodontal repair after delayed tooth replantation in dogs.

Previous studies have indicated that inflammatory resorption and ankylosis, which are frequent sequela after delayed tooth replantation, can be greatly reduced by treating the root surface with 1% solutions of stannous fluoride and tetracycline. However, the SnF2 conditioning leaves a long-standing inflammatory reaction in the periodontal ligament. To examine whether a more dilute SnF2 solution would reduce postoperative inflammation without jeopardizing any beneficial effects, anterior teeth in three young adult beagles were extracted and allowed to air-dry for 45 min. They were then immersed in 0.1% SnF2 for 5 min, rinsed in saline, immersed in 1% doxycycline HCl for 5 min, rinsed, and replanted. Control teeth were air-dried and replanted without further treatment. Block biopsies were harvested after 4 wk of healing and processed for histometric analysis. In experimental teeth, 85% of the root surface area showed normal healing, compared to 33% in control teeth. Conversely, resorption and ankylosis were more frequent in controls than in experimental teeth. A persisting inflammatory reaction either adjacent to or at a distance from the root surface was seen in limited areas in both experimental and control teeth. Compared to preceding studies, the findings indicate that reducing the strength of the SnF2 solution from 1% to 0.1% may result in less persistent inflammation, at the cost, however, of less complete prevention of inflammatory resorption and ankylosis.


Evidence for xylitol 5-P production in human dental plaque.

The Turku sugar studies indicated that xylitol may possess a caries-therapeutic effect. More recent data show that xylitol exhibits a bacteriostatic activity on a wide range of bacteria based on uptake and expulsion of xylitol. Intracellular xylitol 5-P appears to be a key substance associated with inhibition of bacterial metabolism by xylitol. This has been shown in studies with pure strains of bacteria, mainly Streptococcus mutans. The aim of the present study was to examine if production of xylitol 5-P occurs in freshly collected dental plaque which is exposed to labeled xylitol. Plaque extracts were analyzed by thin-layer chromatography combined with autoradiography and high performance liquid chromatography. Strong indications were obtained that xylitol 5-P is readily produced by dental plaque. No other significant xylitol metabolites were identified. The bacteriostatic properties of xylitol in plaque are a mechanism which may well account for the caries-therapeutic effect of xylitol.


Evaluation of a photographic method for diagnosis of gingivitis and caries.

The aim of the present study was to determine the value of a photographic method when diagnosing gingivitis and caries. 78 patients participated in the investigation. The validity of the photographic method could not be established, since the reproducibility of the clinical diagnosis was not 100%. Instead, the value of the method was determined by comparing the reproducibility of the clinical and the photographic diagnosis. For gingivitis the intra- and inter-examiner reproducibilities were best for the photographic readings. For caries the reproducibility of the clinical diagnosis was highest. The photographic method was not limited by method variation when diagnosing redness of the gingiva and caries. However, limitations due to variation were present when diagnosing gingival swelling. The paper also describes the bias reducing capacity of the photographic method.


Changes in amount of gingival crevicular fluid after a single episode of periodontal treatment.

A total of 51 periodontal sites from 6 adults with no systemic diseases or medication were selected for the study. All sites showed radiologic bone loss and pockets of 4 mm or more. Crevicular fluid (CF) was collected by inserting filter paper strips into periodontal pockets for 5 s and was measured by Periotron. Samples were collected before and 2, 5, 10, 20, and 40 days after a single episode of periodontal treatment (scaling, root planing and curettage). Plaque Index (P1I), Papilla Bleeding Index (PBI) and pocket depth (PD) were measured before and 40 days after treatment. The amount of bone loss was estimated from orthopantomograms taken immediately before the trial. Two days after treatment an increase in the amount of CF was seen. After this the amount of CF decreased, reaching the pretreatment level on day 5 after treatment and a level clearly below pretreatment level on day 10 after treatment. Forty days after treatment a slight increase in the amount of CF was seen. The difference between pretreatment values and values at days 2, 10, 20, and 40 was highly significant. In pretreatment samples, positive correlations were found between the amount of CF and PD, PBI and bone loss and, in samples collected 40 days after treatment between CF and PD. CF measurements made before treatment were of no value in predicting the changes in clinical parameters after treatment.


Relationship of collagenase and cathepsin G activity in gingival crevicular fluid.

Human neutrophil cathepsin G has been identified as a potent proteolytic activator of latent human neutrophil collagenase in vitro. In order to examine the role of cathepsin G in the activation mechanism of latent human neutrophil collagenase in vivo, gingival crevicular fluid was collected from periodontal pockets of patients with adult periodontitis and the relationship of cathepsin G to the proportion of endogenously active collagenase and total collagenase activity was determined. The changes in these parameters were monitored before and after periodontal therapy and compared to control values obtained for periodontal sites without clinical signs of inflammation or increased pocket depth. A significant decrease in cathepsin G and collagenase activity in gingival crevicular fluid collected from initially deep periodontal pockets was observed in response to scaling and root planing (P less than 0.025, Wilcoxon signed rank test). Also the proportion of endogenously active collagenase decreased (P less than 0.05). There was a significant correlation of cathepsin G and total collagenase activity. However, no correlation of cathepsin G activity and endogenously active collagenase was observed. The results indicate the existence of several distinct activation pathways for latent human neutrophil collagenase in vivo and suggest that, apart from cathepsin G, other proteolytic activation cascades and/or non-proteolytic activation pathways participate in the activation of latent human neutrophil collagenase in vivo.


Immune-activation in recurrent oral ulcers (ROU).

Tissue specimens from eight patients with recurrent oral ulcers (ROU) were analyzed for possible signs of active lymphocyte involvement. A total of 13 specimens were analyzed, eight (8) taken at the ulcer site and five (5) from clinically unaffected mucosa at a site opposite the ulcer. Monoclonal antibodies or heterologous antisera were applied using the avidin-biotin-peroxidase complex (ABC) or peroxidase-antiperoxidase complex (PAP) methods to visualize cell-activation-associated marker proteins. In specimens from the ulcer area, approximately 43 +/- 18% of all inflammatory cells were positive for the MHC locus II coded Ia antigen. Furthermore, markers for cycling cells, interleukin-2 (CD25, 13 +/- 6%) and transferrin (CD71, 23 +/- 14%) receptors, were frequent in the specimens studied. Staining for CD1 (5 +/- 2%) disclosed dendritic intraepithelial cells in diseased and in clinically unaffected mucosa. Mobilization of such cells is suggested by their presence in submucosa in ROU specimens, but not in clinically unaffected mucosa. The presence of CD1 cells, presumably denoting their identity as potent antigen-presenting Lagerhans' cells, and the rich presence of Ia suggest that local conditions are favorable for induction of T-cell-mediated responses. The simultaneous presence in such infiltrates of activation marker positive T-cells suggests activation de facto. This together with the rarity of activated B-cells, i.e. plasmablasts/cells containing cytoplasmic immunoglobulin, suggests active involvement of the local cells of the T-lymphocyte lineage in the pathogenesis of ROU.


Force-distance relation and properties of repelling Sm-Co5 magnets in orthodontic clinical use: an experimental model.

In recent years, magnets and magnetic forces have been suggested as an alternative to traditional orthodontic devices such as elastics, springs and wires. The purpose of this study was to analyze the reliability and the output of forces for prefabricated orthodontic repelling Sm-Co5 magnets and the force conditions for the magnets after 5 months of maximal loading. The test-machine consisted of a jig where the tested pair of repelling magnets was mounted close to the clinical situation. With a cylindrical strain gauge transducer, a micrometer screw, a bridge-amplifier, and a Mingograph jet recorder, force-distance diagrams were constructed. The force-distance diagrams showed that the force-distance curve was hyperbolic and that the mean force when the magnetic pole faces were almost in contact with each other was 214.9 g, SD 13.42 g. The variation of magnetic force between different Sm-Co5 magnets was 6-9%. The difference in force before and after 5 months of maximal loading of the magnets was not significant. The test results indicate that with proper handling of the forces according to the new force diagrams, the system is reliable for orthodontic use.