[Disseminated complex vascular malformations]. Diffuse complex vascular malformations are sporadic or hereditary. They usually concern one type of vessel: capillary, venous or arterial (with AV fistula). They involve skin, mucosal membranes and internal organs. They lead to a rich and heterogeneous symptomatology, depending on the lesional localizations. Five out of them are described: cutis marmorata, Rendu Osler disease, Bean syndrome, Maffucci syndrome, and Proteus syndrome.


[Systematized complex vascular malformations]. Various types of systematized vascular syndromes are described, either in the head or in the limbs. The Sturge-Weber syndrome includes a facial portwine stain, ocular anomalies, and a pial vascular malformation. Complex combined vascular malformations with limb overgrowth need careful investigations to clearly define the vascular component and the management.


[Reconstruction of the external ear].

[Reconstruction of the external ear]. The authors after a short morphological description of the microtia, expose the surgical evolution which had led to the actual auricular reconstruction technique, using a costal cartilage framework. This technique requiring several steps is exposed in the typical case of microtia. It is the preferential method. The difficult reconstructions due to the poor quality of the skin are exposed by degree of complexity: in these cases, tissue expansion, fascia temporalis superficialis can be useful and finally auricular prostheses, attached to bone-integrated implants, can be recommended. The functional surgery of the middle ear is also replaced in the context of the auricular reconstruction which is done around 8 years old.


[Bone demineralization and cytokines].

[Bone demineralization and cytokines]. Cytokines are secreted by several cell types in the bone microenvironment. These peptides act on bone cells by a paracrine or autocrine mechanism and play an important role, although not completely clarified, in the regulation of bone remodeling. Postmenopausal osteoporosis could be due to a local overproduction of some osteoclast-stimulating cytokines in response to estrogen deficiency. During chronic inflammatory joint diseases, such as rheumatoid arthritis, synovial cells produce large amounts of cytokines leading to increased local bone resorption and juxta-articular bone destructions. The local action of cytokines is also involved for interactions between tumoral cells and bone cells. These are secreted by the tumoral (metastatic or hemopoietic) cells, bone marrow cells, bone cells, or even could be released from the bone matrix during bone resorption. Recent progress in our knowledge in the field of cytokines have improved the understanding of the pathogenesis of these diseases and let hope future promising developments for more specific treatments.


[Current aspects of inflammatory rheumatic diseases in elderly patients]. Rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) are the most common rheumatologic diseases encountered in older patients. However, other disorders including spondylarthropathy and a variety of connective tissue diseases also occur in the elderly. PMR and the RS3PE syndrome seem to occur only in the elderly, although their symptoms may be difficult to differentiate from those of other conditions. Late-onset RA and, above all, late-onset spondylarthritis may have unusual presentations responsible for diagnostic mistakes. Pitting edema is typical of RS3PE syndrome but may also occur in other rheumatic diseases. This symptom seems to be associated with advanced age rather than with a specific cause. Because of these many unusual features, rheumatologic diseases in the elderly are often difficult to diagnose and to differentiate from a variety of other rheumatologic or nonrheumatologic conditions.


[Antiperinuclear antibodies and corrisponding antigens]. Antiperinuclear factors (APF) are directed to epithelial cell "kerato-hyaline granules". Standardization of the APF test has been achieved, but the way to express the results is still debatable. APF were found to be present in 76% of rheumatoid arthritis (RA) patients: thus the sensitivity and the specificity for RA were 76 and 97%, respectively. No clinical or serological associations were substantiated in RA. The antigens targetted by these auto-antibodies are extremely variable from one to another donor.


[Specific rheumatologic disorders in musicians]. The author reviews the locomotor problems observed in performing musicians. The overall frequency of these problems is high. Three presentations exist: overuse, entrapment and dystonic syndromes. Treatment of these problems implies not only a technical approach, but also consideration of life experience and individual personality.


[Surgery of scoliosis. Decision aid by three-dimensional imaging (3D)]. Scoliosis is a spatial deformations of the spine not reducible to a plan. Usually perception of this phenomena is made from frontal and lateral radiographies and needs a mental process to construct a 3D form. The proposed aid-system consists, firstly, to construct a 3D model from digitalised characteristic points on radiographies, and to visualize this model from any point of view, even the above view. Secondly, corrective bending posture radiographies are used to estimate kinematic spine variables and then to simulate optimal orthopedic correction. Methods and materials are adaptable for other osteo-articular systems.


[Post-traumatic psoriatic rheumatism. Clinical and medico-legal aspects]. The possibility that injury may play a role in the development of some forms of chronic inflammatory rheumatic disease has been a subject of debate for many years. Such a role is accepted for some cases of rheumatoid arthritis, remains controversial for spondylarthropathies, and is poorly understood in psoriatic arthritis. Three cases of post-traumatic psoriatic arthritis are reported herein. The difficulty of establishing the causative role of the injury (despite precise criteria) is underlined, the pathophysiologic mechanism is discussed (deep Koebner phenomenon?), and possible legal consequences are reviewed.


[Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo]. One hundred twenty patients with osteoarthritis of the knees and hips were entered into a randomized, placebo-controlled, double-blind trial designed to evaluate the effectiveness of chondroitin sulfate (Structum). The three-month treatment phase was followed by a two-month treatment-free phase to allow evaluation of carry-over effects. The main endpoint was use of nonsteroidal antiinflammatory drugs (expressed as mg of diclofenac equivalent). At completion of the three-month treatment phase, patients taking chondroitin sulfate (4 capsules/day) were using significantly less NSAIDs; this decrease persisted throughout the two-month treatment-free follow-up phase. The other parameters studied including visual analog scale assessment of pain, the Lequesne pain-function index, and overall patient and physician assessments, all showed a similar significant tendency. Tolerance was outstanding and no patients required premature withdrawal. These findings indicate that chondroitin sulfate is useful for the treatment of osteoarthritis, both as an agent slowly effective against symptoms and to reduce the need for NSAIDs. The carry-over effect of the drug suggests that intermittent administration may be appropriate.


Coverage by four information services of the core journals of rehabilitation and related topics. In this study, three serials databases were used to identify core journals in rehabilitation and related areas. Simple strategies were used to search SERLINE (Serials Online, National Library of Medicine), Ulrich's International Periodicals Directory and SACHET (British Library serials database). Coverage of the journals identified by four secondary information services was then studied. These were Medline, Excerpta Medica, CINAHL (Cumulative Index to Nursing and Allied Health) and CATS (Current Awareness Topics Services, British Library). The results confirmed and extended the findings of earlier work: the number of core journals in rehabilitation is very large and their coverage by information services is very selective. Of the services studied here, CATS seemed to be most comprehensive for the journals identified.


[Gout in Togolese patients].

[Gout in Togolese patients]. A study was carried out to determine the frequency and semiological characteristics of gout in patients attending a hospital clinic in Lomé, Togo. Gout was diagnosed in 71 of the 1,821 patients seen from october 1989 through october 1991. Clinical findings and increased serum uric acid levels were the basis for the diagnosis of gout in 63 patients; in addition, in the eight other patients monosodium urate crystals were demonstrated in joint fluid. All gout patients were male and mean age at onset was 45 years. Mean duration of the disease was 8.5 years, Forty-seven patients had normal hemoglobin, whereas a hemoglobinopathy was present in the 24 other subjects (hemoglobin AS: 15 cases; hemoglobin AC: 7 cases; hemoglobin CC: 2 cases). Twenty-seven patients (38%) were obese and 24 (34%) had hypertension. Forty-six patients (65%) were habitual drinkers. Twenty patients (28%) had tophi. None of the patients had a history of renal colic. The other clinical features of the disease were similar to those seen in Western countries. Results of this study are in striking contradiction with the common belief that gout is exceedingly rare in black Africa.


Measurement of torque of trunk flexors at different velocities. The purpose of this study was to determine the test-retest reliability of recording isometric and isokinetic torque of the trunk flexors and to examine the effect of velocity on the torque curves. Thirty healthy subjects were tested on two occasions for isometric torque of trunk flexion at four angles and eccentric and concentric torque at three velocities. Two subjects repeated these tests in the passive mode to determine the torque produced by the trunk when there was no active flexion effort. Intraclass correlation coefficients were above 0.85 for all isometric and isokinetic measures. Standard errors of measurement ranged from 6.9 to 19.5 Nm. Student t-tests indicated no significant differences between occasions for all outcome measures. Examination of passive and active torque curves indicated that the torque produced by the mass of the trunk increased with increasing velocity. It is concluded that both isometric and isokinetic testing of the trunk flexors are reliable, but that testing at higher velocities may not provide a valid measure of muscle performance.


[Diagnosis of extruded herniated disks]. In a patient with disk herniation it is often difficult to establish that the disk is free in the spinal canal. A retrospective medical record study comparing 65 cases of free herniated disk (FHD) confirmed upon surgery and 65 cases of disk protrusion (DP) demonstrated that FHD was more common in young male blue collar workers, especially those who worked in the sitting position. No clinical findings were diagnostic of FHD although the straight-leg raising test was positive at smaller angles than in disk protrusion. In this study, sensitivity and specificity of CT scan for the diagnosis of FHD were 75% and 80%, respectively. CT scan findings suggestive of FHD included a free disk fragment, found in 22.5% of cases, and an acute connecting angle. Saccoradiculography was more sensitive but less specific than CT scan in this study. In FDH, migration was common and ragged hernia contours were seen on the saccoradiculography images.


Gait in relation to ageing and idiopathic parkinsonism. Distance/time measures of gait in 105 sufferers from idiopathic Parkinsonism, who were able to walk unaided, and 144 healthy controls were examined systematically. Those sufferers with overt fluctuations in control were assessed during their "therapeutic window". Free walking speed was lower for a given cadence in the sufferers, but reached a plateau whilst cadence could still be increased. Age, cognitive function and the range of passive hip flexion were important determinants of gait in them. Even minor degrees of cognitive impairment were associated with reduced free walking speed in sufferers: it appears unwise that they were prescribed more sedatives than the controls. The potential benefit of physiotherapy in maintaining joint flexibility was noted. The deficits in speed of individual sufferers, and hence the estimated potential for prophylaxis and treatment, were unrelated to age at presentation. There was no evidence for a limited period of responsiveness to levodopa therapy in this cross-sectional study.


Blood pressure response to detrusor pressure elevation in patients with a reflex urinary bladder after a cervical or high thoracic spinal cord injury. In 12 patients with a reflex urinary bladder after a cervical or high thoracic spinal cord injury, blood pressure was measured every 30 s during cystometry. Four consecutive cystometries were performed by means of suprapubical catheters and 50 ml/min filling rate. The aim was to improve the methodological basis for cystometrical studies of paroxysmal hypertension and its treatment. In each cystometry there was an elevation of the systolic (20-60 mmHg) and the diastolic (15-55 mmHg) blood pressure. The maximum blood pressure always occurred during the emptying phase and always in close relation to the peak of the detrusor pressure. The amplitude of the blood pressure response varied intraindividually, but did not change in any particular direction during the series of cystometries. Thus, a cystometrical method which stimulates the detrusor in a physiological way is sufficient to give the typical uninhibited blood pressure reaction in most patients with a reflex bladder and a spinal reflex vasomotor function after a high level spinal cord injury. The blood pressure reaction obtained with this method is probably representative for the daily reaction during physiological reflex emptying of the bladder. To describe the maximum blood pressure reaction, it has to be measured during a well defined emptying phase and close to the occurrence of the maximum detrusor pressure. Since repetition of cystometry did not change the blood pressure response, this cystometrical method is useful for evaluation of pharmacological intervention.


[Evaluation of the effectiveness of serotonin (fluoxetine hydrochloride) treatment. Open study in fibromyalgia]. Primary fibromyalgia may involve an anomaly in the metabolism of serotonin responsible for the sleep disorders and diffuse pain. Effectiveness of an agent with pure serotonin-agonist properties (fluoxetin hydrochloride) was evaluated in 23 patients during a three-month open study. Treatment had no effect on pain severity, number of tender sites, or pain score. Sleep disorders improved and 57% of patients believed the treatment was effective. Adverse events were recorded in 43.4% of patients, with the most common being nausea (21.7%). Effectiveness and tolerance of fluoxetin hydrochloride in fibromyalgia are mediocre. A double-blind placebo-controlled trail versus a placebo is needed to clarify these preliminary findings.


[Spontaneous fracture of the femoral neck in hip algodystrophy in pregnancy. Apropos of a case and review of the literature]. A case of reflex sympathetic dystrophy involving the hip with a pathologic fracture of the femoral neck in a pregnant patient is reported. The low incidence of this condition is underlined and its characteristics are reviewed. The role of increased fragility related to pregnancy is discussed.


A comparison of different psychosocial questionnaires in patients with myocardial infarction. In a consecutive study of 140 patients investigated one month after myocardial infarction (MI), a battery of American and English questionnaires was used to measure depression, anxiety, sleep problems, health locus of control and perceived health. These measures were compared with a well-documented generic questionnaire, the Nottingham Health Profile (NHP), and a similarly well-documented mood scale, the Mood Adjective Check List (MACL). There was close agreement among all measures depicting anxiety and tension. The concordance between the measures of anxiety states and depression was lower. Depression and sleep problems seem to constitute separate concepts, since they are not as highly related to the other measures of anxiety. Because psychosocial factors are important measures for the outcome after an infarction, accurate assessments of these variables are required. Further research is clearly warranted to clarify the complicated interaction between psychosocial constructs and to improve the methods used for their evaluation.


Epidemiological research needs access to data. Data protection laws and their implementation have led to serious restrictions on access to personal data for research purposes. This seriously affects the development of social medicine and public health by making effective prevention of illness, and rational planning of health services, and their evaluation impossible in many instances. The conflict between people's need for knowledge about prevention and cure of illness and the control over personal data must be solved. Therefore, it is necessary to change the laws and ensure access to data for research use in accordance with the guidelines laid down by the European Science Foundation.


Assessment of handicap in chronic dialysis diabetic patients (Uremidiab section study). As part of a large epidemiological study concerning 494 diabetic patients undergoing dialysis throughout France--the so-called Uremidiab section study--we collected data with the aim of describing objective as well as subjective aspects of quality of survival. Questionnaires were completed from medical records and from direct interviews by trained collectors. The data included: (a) medical status and impairments; (b) functional status with the Barthel index for basic activities of daily living; (c) subjective aspects through self-estimation of fatigue, pain, care burden, quality of life and working capacity. Only 21% of the patients had type 1 diabetes and more than 71% were currently insulin-treated. Among the various long-term complications registered, visual impairment was a prominent feature: 25% of the patients were blind and the best eye vision scored 0.8 or more for only 20%. The differences found between the two types of diabetes are discussed. As a result of these impairments, functional status was poor even when considering basic activities, with a mean Barthel index (BI) of 80 +/- 19. Type 2 patients and those patients undergoing continuous ambulatory peritoneal dialysis had significantly lower BI. The results are discussed in the light of the literature. Compared with a group of 121 non-dialyzed diabetics, patients scored higher for fatigue and pain, but not for care burden and quality of life.


Mortality in alcohol-related diseases in Sweden during 1971-80 in relation to occupation, marital status and citizenship in 1970. A new Swedish population register, created by linking Census data to the Cause of Death Registry and covering over 99% of the population, has been used to study the relationship between occupational category, marital status and citizenship in 1970 and mortality in closely alcohol-related diseases during 1971-1980 for the ages 25-64 years. Age-standardized rate ratios (SRR) have been computed for mortality in alcoholism, alcohol intoxication and alcohol psychosis ("AAA") and in liver cirrhosis. SRR-values for both diagnose categories and both sexes were higher than average among not gainfully employed (SRR = 3.71 among males and SRR = 1.96 among females in 1976-80 for "AAA"), among employees in the service sector, engine-drivers and unskilled workers and increased in liver cirrhosis among artists and authors. Among females there were smaller variations in mortality for occupational groups than among males. The SRR-values showed a tendency to be higher in 1976-80 than in 1971-75, probably due to health-related selection to some extent. The alcohol-related mortality was also increased among divorced, widows (SRR = 1.37 for "AAA" and 2.81 for liver cirrhosis in 1976-80) and widowers and among never married males. SRR was much higher among Finnish citizens in Sweden (SRR for "AAA" = 3.85 among males and 2.35 among females in 1976-80) than among males and females living in Finland (SRR for "AAA" = 1.13 among males and 0.36 among females) and also higher than among immigrants from other countries, summed (SRR for "AAA" = 0.62 among males and 0.64 among females).(ABSTRACT TRUNCATED AT 250 WORDS)


Further course of mental health and use of alcohol and tranquilizers after cessation or persistence of cannabis use in young adulthood: a longitudinal study. The main question addressed in this study is how cessation or persistence of cannabis use is related to use of legal drugs and mental health problems. In a longitudinal study a representative sample of young people in Norway, age 17-20 years (n = 1997), participated in a postal survey in 1985 and was followed up again in 1987 and 1989. The results showed a decrease in alcohol consumption among men both among those who ceased to use cannabis and those who continued their use, whereas among women who continued cannabis use the alcohol consumption increased. The use of tranquilizers was significantly reduced among those who ceased to use cannabis compared with those who continued cannabis use, while mental health problems were unchanged. The results indicate that use of tranquilizers for self medication is mainly related to a polydrug use in the cannabis using culture.


Knowledge, attitudes and cardiovascular risk factors in Danish adults. A community cardiovascular disease (CVD) prevention programme was undertaken in 1989 in a Danish County (Vejle). A random sample of 5192 adults were asked to complete a mailed questionnaire on knowledge, attitudes, and behaviour in relation to CVD risk factors. The response rate was 56%. The questionnaire produced baseline data for programme planning and measuring the success of on-going interventions. Smoking, overweight, and unhealthy food habits were the most prevalent CVD risk factors. A CVD risk score was calculated from the data on smoking, food habits, exercise, stress, overweight, self-reported presence of hypertension, diabetes, and gender. A high score was commoner in men, in the least educated, in groups who judged their own risk as high, and in groups with negative health beliefs. The level of knowledge about CVD risk factors was high in general. Low knowledge was commonest in the youngest age group, in the least educated, in unskilled workers, and in groups with negative health beliefs. As social position and personality factors seem to play an important role in actions people may take in prevention of CVD, they should be considered in the planning of the health promotion activities in Vejle.


An update on knowledge and sexual behaviour among students in Greenland. Monitoring of the stop-AIDS campaign. Greenland is a considered high risk area for a self-sustained heterosexual HIV-epidemic due to rather relaxed sexual norms in larger segments of the population and a high incidence of sexual transmitted diseases. However, the prevalence of HIV-positives is still low. As part of a monitoring programme longitudinal studies of young peoples' knowledge and sexual behaviour has been established. This paper presents results from the second survey among all students in vocational training and all 10th grade students in the public schools. Previous studies were performed in 1988 and 1989. The present study which took place in April 1991 involved a total of 1201 students, or about 85% of all students in the target groups (95% among students present on the day of surveying). Data collection was based upon standardized self-administered questionnaires. The study showed better knowledge than previously but no marked change in sexual habits. The age of sexual début even appeared to be decreasing. More than half reported a sexual début before the age of 15. More than 20% reported 10 sexual partners or more within the last year. HIV has still not reached the young population in Greenland but when it happens the present sexual behaviour carries a high risk of a self-sustained epidemic.


Health behaviour of fathers of young families expecting their first baby. Health behaviour in fathers of young families expecting their first baby was studied using randomized cluster sampling and confidential questionnaires given to 1414 fathers, of whom 1,279 responded to the questionnaire. The drop-out rate was 9.5%. Participants and drop-outs had matching occupations. Basic educational level, age, occupation and location of home were used as background variables. Health behaviour was studied by means of many questions on habits associated with health, such as alcohol consumption, smoking, physical exercise, dietary habits, and social relations and use of cultural services connected with health. The results showed that the health behaviour of the fathers was related to their childhood family background, level of education and occupation. Health education literature and counselling best reached fathers with a high level of education and those with professional occupations. The most negative health behaviour patterns were seen in fathers working in manufacturing industry or primary production and in the youngest fathers. Maternity health care clinics and Well-baby clinics establish a longstanding relation with young families, and health care staffs have a good opportunity to support the future fathers' health behaviour in a positive direction.


War-wounded refugees. Quality of life after 2-3 years in Sweden. The Medical Center for Refugees in Linköping, Sweden, includes a medical ward for refugees and asylum applicants. It was started in January, 1986 and is financed by the Swedish Immigration Board. Sixty percent of the patients are war-wounded and 40% have diagnoses non-related to war. This article describes a group of 19 refugees who were the war-wounded patients at this ward in June, 1986. In most of them the main medical impairment was amputation. They were followed up in 1988 by interview and self-ratings. The aim was to illuminate their quality of life after 2-3 years in Sweden. Most of them were satisfied with their external living conditions. Their psychological well-being, however, was not so good and they were very occupied by thoughts of their native countries. Their physical handicaps seemed to be of secondary importance.


Do not forget the battered male! A comparative study of family and non-family violence victims. This study is based on interviews with and psychiatric ratings of female family violence victims and male non-family violence victims. Despite differences in the type of violence and the relation to the assailant, the psychological consequences of the battering were very much the same in the two groups. The background and present social situation of the victims were very similar. The conclusion drawn with regard to the medical services, is that both groups of victims need the same attention and treatment when attending the emergency department. Apart from routine medical care, they might need treatment for alcohol problems, depression or other psychiatric conditions frequently occurring in victims of violence.


The Nordland Health Study. Design of the study, description of the population, attendance and questionnaire response. In 1988/89, 10,497 men and women aged 40-42 were invited to a health screening in the County of Nordland in northern Norway. The screening procedure comprised completion of a questionnaire, measurement of blood pressure, weight, height and collection of a non-fasting blood sample. Eighty-two percent of the invited population attended the screening. They were given another questionnaire which covered a broad spectrum of relevant topics. Eighty-seven percent of the attenders returned this questionnaire by mail. Non-attenders to the screening tended to be single. Non-responders to the second questionnaire did not differ much from responders, the most consistent finding was a slightly higher heart rate in non-responders. Non-responding men had somewhat higher serum total cholesterol and tended to be smokers.


Impact of occupations and job tasks on the prevalence of carpal tunnel syndrome. In this investigation reported epidemiologic studies on carpal tunnel syndrome (CTS) (15 cross-sectional studies involving 32 occupational or exposure groups and six case-referent studies) were reviewed. The prevalence of CTS in the different occupational groups varied between 0.6 and 61%. The highest prevalence was noted for grinders, butchers, grocery store workers, frozen food factory workers, platers, and workers with high-force, high-repetitive manual movements. Odds ratios greater than 10 were reported for exposed groups in three studies. On the basis of epidemiologic and other evidence, it was concluded that exposure to physical work load factors, such as repetitive and forceful gripping, is probably a major risk factor for CTS in several types of worker populations. At least 50%, and as much as 90%, of all of the CTS cases in these exposed populations appeared to be attributable to physical work load.


Fetal growth, preterm birth and infant mortality in relation to work with video display terminals during pregnancy. Through register linkage between a trade union file and public health registers 24,352 pregnancy outcomes were selected from a source population of 214,108 commercial and clerical employees. In a case-base study including all recorded cases and a randomly selected base sample, the potential effect of video display terminal (VDT) use in pregnancy on the risk of low birthweight, preterm birth, light weight for delivery date, stillborn, perinatal death, and infant death was investigated. Data on VDT use and potential confounders were collected from postal questionnaires sent to 6312 women and 426 employers. The rate ratio for women exposed to any degree of use was 0.88 for low birthweight [95% confidence interval (95% CI) 0.67-1.16], 1.11 for preterm birth (95% CI 0.87-1.47), 0.99 for light weight for delivery date (95% CI 0.80-1.21), 0.73 for stillborn (95% CI 0.36-1.48), 1.10 for perinatal death (95% CI 0.62-1.94), and 0.20 for infant death (95% CI 0.04-1.03). In conclusion, this investigation did not show an increased risk of the studied adverse pregnancy outcomes among women with VDT use.


Mortality studies of machining-fluid exposure in the automobile industry. II. Risks associated with specific fluid types. Excesses of digestive and respiratory cancers have been reported previously in association with exposure to machining fluids, agents in widespread use as coolants and lubricants in machining operations. Previous studies have had limited power to distinguish the effects of the different types of machining fluids in use. In a cohort of over 30,000 workers employed at two automotive plants in Michigan, mortality patterns were studied in relation to exposure to each of the three major fluid types--straight oils, soluble oils, and synthetic fluids. Standardized mortality ratios were estimated for subgroups of the cohort ever exposed to each of the three fluid types, and Poisson regression analyses were used to assess trends in risk with duration of exposure. The data suggest modest positive associations between exposure to straight oils and rectal, laryngeal, and prostatic cancer and a negative association between soluble and synthetic fluid exposure and lung cancer.


Sources of variance in exposure to postural load on the back in occupational groups. The variability of exposure to postural load on the back was studied in five occupational groups. A random sample of workers in each group was observed for two periods of 30 min during a shift, their posture being classified every 20 s. The estimated percentage of time spent in trunk flexion and rotation formed the principal measures of exposure. The partitioning of the total variability of exposure showed that occupational group status was the principal source of variance. The between-group variance accounted for 47 and 72% of the total variability of exposure to trunk flexion and rotation, respectively. The corresponding percentages were 29 and 16% for the within-worker variance of trunk flexion and rotation and 24 and 12% for the between-worker variance. This type of analysis of the sources of exposure variability may help to establish appropriate measurement strategies for exposure to postural load on the back in epidemiologic studies on low-back pain.


Role of psychosocial risk factors in work-related low-back pain. The experience of low-back pain and its psychosocial associates were directly compared among sufferers drawn from three populations, a blue-collar working group, a white-collar working group, and a patient group. Sufferers drawn from the patient population revealed the expected psychological disturbance. There was no evidence of such involvement for sufferers still at work. Disability resulting from low-back pain was positively linearly related to severity of pain for sufferers drawn from working groups, irrespective of psychological disturbance. For patients, on the other hand, the presence of psychological disturbance modified the relationship between severity and disability such that no simple linear relationship existed between the two variables. Work dissatisfaction was not found to be related to the presence of, and did not account for disability resulting from, low-back pain in working subjects.


Temporary health effects from exposure to water-borne paints. Temporary health effects of exposure to experimental paints were studied. Ten painters feeling nuisance from water-borne paints and eight painters not feeling such nuisance applied eight experimental water-borne paints according to normal work routines. The effects were a decrease in forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow, an increase in urine excretion, and a decrease in urine density. A small, but statistically highly significant, increase in the mean volume of erythrocytes was observed. The effects were similar in the two groups, but the "nuisance group" reacted with a larger urine excretion and a larger increase in the mean volume of erythrocytes. The effects did not influence physical work capacity. The effects on the lungs and urinary excretion were probably not associated with the organic solvents or ammonia in the paints. Instead, they were probably due to derivatives of isothiazolinone. This assumption needs verification.


Work-related behavioral and dental risk factors among confectionery workers. The dietary habits and dental health behavior of 294 employees in a Finnish confectionery company were studied to determine the reasons for their dental caries experience and their caries-promoting salivary microbiological findings. A diary and a questionnaire were used. A caries risk index was constructed for salivary microbiological findings. Daily dietary acidogenic exposures were calculated, and differences between low and high caries-risk groups were analyzed. Statistically significant differences in dietary habits between the low- and high-risk groups were found for the entire study population and for the men, the cookie markers, and the sweets makers. A significant positive correlation was found between untreated caries and the number of sugary meals. No differences were found in dental health behavior or dental knowledge between the study groups. The results show that the nature of between-meal snacks and confectionery workers' freedom to consume their products constitutes a potential hazard to dental health.


Occupationally related ultrasonic findings in carpet and floor layers' knees. Soft-tissue changes in the anterior aspect of the knees were evaluated with ultrasonography among 96 randomly selected carpet and floor layers and 72 painters. The ultrasonography showed thickening of the prepatellar or superficial infrapatellar bursa in 49% of the carpet and floor layers and 7% of the house painters. Fluid collection in the prepatellar or superficial infrapatellar bursa was noted for 10 carpet and floor layers, and this ultrasonographic finding was associated with knee pain in kneeling postures.


Possible mechanisms of formaldehyde-induced discomfort in the upper airways. Occupational exposure to formaldehyde often causes nasal discomfort. The objective of this study was to determine whether chronic exposure to formaldehyde causes annoying symptoms by direct irritation and whether it affects all exposed people (through hyperreactivity in atopic persons, through formaldehyde-induced hyperreactivity also in nonatopic persons, or through an immunologically mediated, immediate type 1 reaction to formaldehyde itself). It was found that about 50% of the studied population of 66 workers occupationally exposed to formaldehyde during formaldehyde production experienced nasal discomfort through hyperreactivity. Atopics were not significantly overrepresented among the persons with occupational nasal symptoms. Two workers with isolated occupational nasal discomfort, and sensitized by long-term inhalation, had a positive radioallergosorbent test for formaldehyde. The conclusion was reached that exposure to formaldehyde should be minimized as much as possible for all people, not only for atopic persons.


Chemotherapy of advanced sarcomas of bone and soft tissue. The chemotherapeutic approach to advanced sarcomas of bone and soft tissue is reviewed. The most active single agents against osteosarcoma are doxorubicin (overall response rate, 21%), methotrexate (30% to 40%), cisplatin (25%), and ifosfamide (28%). Current multimodality treatment for Ewing's sarcoma consists of combination chemotherapy with doxorubicin, vincristine, and cyclophosphamide (or ifosfamide in current trials) prior to and concurrent with radiation therapy for the involved bone. In soft tissue sarcomas, doxorubicin is the most active single agent, with overall response rates ranging from 15% to 35%. Dacarbazine has a single-agent response rate of 16%. Ifosfamide has documented activity in sarcoma patients who have failed treatment with doxorubicin-containing regimens. The combination regimen currently producing the highest response rates in soft-tissue sarcomas is doxorubicin/dacarbazine/ifosfamide. Doxorubicin and dacarbazine should be administered by continuous infusion to reduce the severity of nausea and vomiting and the risk of cardiotoxicity. Ifosfamide can be given by continuous infusion or in divided doses with mesna to mitigate urothelial toxicity.


The history of ifosfamide.

The history of ifosfamide. Ifosfamide was developed by investigators at Asta-Werke in Germany. Its chemical structure differs from that of cyclophosphamide by the transposition of one of the side chain chloroethyl groups to the ring nitrogen. In several preclinical models, ifosfamide had greater activity than cyclophosphamide. It produced less myelosuppression, but more commonly produced hemorrhagic cystitis as its dose-limiting toxicity. This toxicity has been minimized with the urothelial protective agents mesna and N-acetylcysteine. Thus, increasing doses have been administered and a new spectrum of toxicities observed, including neurotoxicity, hematologic toxicity, nephrotoxicity, and acidosis. Ifosfamide has been shown to have a broad spectrum of clinical activity in various cancers. Questions remain as to the optimal doses and schedules.


New perspectives in the treatment of non-Hodgkin's lymphoma. Curability of patients with advanced intermediate- or high-grade non-Hodgkin's lymphoma using front-line anthracycline-containing chemotherapy remains disappointingly low. Novel regimens used as salvage therapy for these patients continue to be explored. Ifosfamide has been shown to have significant single-agent activity against non-Hodgkin's lymphoma and its use in various combinations produces response rates of 20% to 83% in patients with refractory or relapsing disease. In our study of 32 evaluable patients using dexamethasone/ifosfamide/cisplatin/etoposide as salvage treatment, seven patients (22%) achieved a complete response and 15 (47%) had a partial response, for an overall response rate of 69%. Median duration of response is substantial for patients who achieve a complete response (18+ months), and dexamethasone/ifosfamide/cisplatin/etoposide produces useful palliation in some patients who attain a partial response (16+ months). Gastrointestinal side effects are minimal, with myelosuppression being the dose-limiting toxicity. Ifosfamide-containing regimens have now been incorporated either as response-adapted consolidation to front-line therapy or integrated with standard front-line treatment. We have divided our patient population by age and are investigating prednisone/etoposide/mitoxantrone as front-line therapy for patients older than 65 years. Patients younger than 65 are now being entered into a front-line, response-adapted, ifosfamide-containing chemotherapy regimen with a view to enhancing their curability.


Gynecologic Oncology Group studies with ifosfamide. The Gynecologic Oncology Group has conducted a series of phase II studies with ifosfamide and mesna since 1985. Previously untreated patients received ifosfamide 1.5 g/m2 intravenously daily for 5 days. Mesna was given intravenously every 4 hours three times daily at 20% of the daily ifosfamide dose. Because of the toxic effects observed in previously treated patients with ovarian cancer, the ifosfamide dose was reduced to 1.2 g/m2/d in patients with prior chemotherapy or radiotherapy. In epithelial ovarian cancer, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses. In patients with squamous carcinoma of the cervix, an 11.1% response rate (three of 27 patients) was observed in those who had received prior platinum therapy. In 51 previously untreated patients, the response rate was 15.7%. In nonsquamous cervical carcinomas, there were three partial responses among 25 patients (12%). An 8.6% response rate was observed among 23 patients with previously treated endometrial adenocarcinomas. In uterine sarcomas, response rates were 30.7% in mixed müllerian tumors, 17.2% in leiomyosarcomas, and 27.3% in endometrial stromal sarcomas. Patients with ovarian sarcomas responded in 27.8% of cases. Studies with ifosfamide combinations are currently under way by the Gynecologic Oncology Group.


Activity of ifosfamide in breast cancer. Ifosfamide is an alkylating agent that has clearly demonstrated efficacy against advanced breast cancer. In broad phase II trials, ifosfamide produced response rates of approximately 15% to 20%, and up to 30% in patients without exposure to previous chemotherapy. In subsequent studies, in which ifosfamide was evaluated in higher doses with mesna uroprotection in advanced breast cancer patients with or without prior chemotherapy, the combined complete and partial response rate was 28%. Ifosfamide has also been used in combination regimens. The ifosfamide/methotrexate/5-fluorouracil (IMF) combination has produced efficacy similar to that of the cyclophosphamide/methotrexate/5-fluorouracil (CMF) combination in both previously treated and untreated metastatic breast cancer. Combinations of ifosfamide/epirubicin, ifosfamide/mitoxantrone, and ifosfamide/etoposide have shown encouraging results. Response rates of approximately 70% have been obtained with regimens that include ifosfamide/doxorubicin or ifosfamide/epirubicin. The dose-limiting toxic reactions of ifosfamide, with administration of mesna uroprotection, are myelosuppression, renal tubular acidosis, and renal insufficiency. Additional studies are needed to determine the role of ifosfamide in well-defined patient subsets, to assess its cross-resistance with other alkylating agents, and to determine the slope of the dose-response curve in patients with breast cancer. Further, the role of ifosfamide in front-line combinations needs to be defined.


Current studies of ifosfamide for pediatric solid tumors and leukemia in the United States. This paper reviews current approaches to the use of ifosfamide/mesna alone or in combination with other agents or modalities in the treatment of pediatric malignancies. Included are data from current or recently completed studies conducted by major pediatric oncology cooperative groups and large individual oncology centers for patients with newly diagnosed or recurrent tumors. Sarcomas, neuroblastoma, lymphomas, recurrent solid tumors, brain tumors, and acute lymphoblastic leukemia are discussed. Randomized trials to determine the relative efficacy of ifosfamide and cyclophosphamide in various childhood malignancies are under way. The long-term consequences of ifosfamide in survivors of childhood cancer, in terms of development of bladder cancer or other malignancies thought to be associated with alkylating agents, are not known, and will only be determined through follow-up studies of adult survivors. Ifosfamide's future role in pediatric oncology will depend on evaluation of its therapeutic benefits against long-term toxicity.


Oral mesna: a review.

Oral mesna: a review. Oral administration of mesna can facilitate outpatient ifosfamide therapy. Blood and urinary mesna concentrations are more steady and prolonged after oral delivery compared with after intravenous delivery. The incidence of hematuria observed during partial oral mesna therapy is no greater than that during intravenous mesna therapy. The pharmacology, pharmacokinetics, efficacy, safety, and reported schedules of administration are reviewed.


Single-dose ondansetron for the prevention of cisplatin-induced emesis: efficacy results. Ondansetron 0.15 mg/kg, given intravenously (IV) every 4 hours for three doses, has replaced metoclopramide as standard antiemetic therapy for patients receiving cisplatin-based chemotherapy. Several clinical observations suggested that ondansetron may be effective when given in a single dose: (1) demonstration of efficacy over a wide dose range, (2) similar efficacy with dosing intervals of 2, 4, 6, and 8 hours, and (3) efficacy of single-dose regimens with high-dose metoclopramide and other 5-hydroxytryptamine3 antagonists. In this study, patients receiving cisplatin-based chemotherapy were randomized to receive one of three ondansetron dosing regimens: ondansetron 0.15 mg/kg IV every 4 hours x 3 (standard schedule), ondansetron 32 mg IV x 1, or ondansetron 8 mg IV x 1. All patients were chemotherapy naive, at least 18 years of age, Karnofsky performance status > or = 60%, and inpatients. The number of emetic episodes, nausea, and food intake were measured during the 24 hours following cisplatin administration. Six hundred eighteen evaluable patients were randomized to the three ondansetron treatment groups; 301 received moderate-dose cisplatin (50 to 70 mg/m2) and 317 received high-dose cisplatin (> or = 100 mg/m2). Patients in both cisplatin groups receiving ondansetron 32 mg had a higher complete response rate, lower failure rate, fewer total emetic episodes, less nausea, and more food intake than did patients receiving ondansetron 8 mg. In addition, the 32-mg schedule was superior to the standard three-dose schedule in that it had a lower failure rate and higher food intake and was equivalent to the standard regimen in all other comparisons. All three schedules were well tolerated. Ondansetron 32 mg given prior to cisplatin is superior to a single 8-mg dose and is at least as effective, if not superior to, the standard three-dose schedule (0.15 mg/kg every 4 hours). On the basis of these data, ondansetron 32 mg should be considered standard therapy in patients receiving cisplatin-based chemotherapy and should be the schedule with which new antiemetics and alternate dosing schedules are compared.


Mechanisms by which cancer chemotherapeutic drugs induce emesis. Because the area postrema seems essential for chemotherapy-induced vomiting, both circulating and/or neurally mediated stimuli in this area could trigger the emetic response. In our laboratories results of cross-circulation and direct intracerebroventricular infusion experiments in dogs do not support a role for circulating substances. The large increases in serum vasopressin induced by cisplatin were not blocked by inhibitors of the angiotensin-converting enzyme. In the ferret inhibition of serotonin synthesis with p-chloro-phenylalanine, administration of selective antagonists of 5-hydroxy-tryptamine3 (5-HT3) receptors, or visceral deafferentation inhibited the emetic response evoked by cisplatin or high-dose cyclophosphamide. The results suggest that serotonin plays an important role and that peripheral neural mechanisms are involved in the emetic response. The strong antiemetic efficacy of selective 5-HT3 antagonists also has been confirmed in humans. In cancer patients high-dose cisplatin increased the plasma and urinary levels of 5-hydroxy-indoleacetic acid (5-HIAA), but did not affect platelet and free plasma serotonin. The changes in 5-HIAA levels paralleled the onset and development of vomiting. No evidence of serotonin depletion has been obtained after high-dose cisplatin. Dacarbazine, another strongly emetogenic agent, increased urinary 5-HIAA; however, only small increases in 5-HIAA were produced with low-dose cisplatin or cyclophosphamide-containing regimens. Thus, emetogenicity appears to be directly related to the ability of the cytotoxic agent to release serotonin. In humans, antiemetics such as ondansetron, metoclopramide, and dexamethasone did not effect high-dose cisplatin-induced increases in serotonin metabolism. Therefore, these antiemetics seem not to affect the amount of serotonin released. The mechanism by which chemotherapeutic drugs induce serotonin release is unknown; however, release may occur by direct cytotoxicity on the gastrointestinal mucosa, including the enterochromaffin cells. Delayed emesis appears to be mediated by 5-HT3-independent mechanisms. It is proposed that emesis that develops despite high-dose ondansetron (residual emesis) should be considered delayed emesis. Residual and delayed episodes of emesis have similar time courses, are characterized by very mild emetic episodes and poor response to 5-HT3 antagonists, and are not associated with increases in serotonin metabolism.


Efficacy of ondansetron tablets in the management of chemotherapy-induced emesis: review of clinical trials. The selective 5-hydroxytryptamine3 antagonist ondansetron has been shown to be effective in preventing nausea and vomiting associated with highly emetogenic cisplatin chemotherapy. Two multicenter, placebo-controlled, dose-comparison studies (S3A-361 and S3A-362) were undertaken to investigate the efficacy and safety of oral ondansetron in patients receiving non-cisplatin, cyclophosphamide-based regimens in the outpatient setting. Chemotherapy-naive patients undergoing their first cycle of cyclophosphamide-based (> or = 500 mg/m2) chemotherapy were randomized to receive placebo or ondansetron, 1, 4, or 8 mg, three times per day for 3 days. In addition to cyclophosphamide, all patients received doxorubicin, methotrexate, or another low-to-moderately emetogenic agent. In study S3A-361, 318 of 349 patients were evaluable for efficacy; 297 of 324 patients in study S3A-362 were evaluable for efficacy. All patients in both studies were evaluable for safety. All ondansetron groups were superior to placebo groups in both studies for all measured efficacy parameters. In the two studies combined, 14%, 47%, 65%, and 66% of patients in the placebo, 1-, 4-, and 8-mg ondansetron groups, respectively, experienced no emetic episodes. The rate of therapeutic failure was statistically lower in the ondansetron groups in both studies compared with the placebo groups. In addition, therapeutic failure decreased in a dose-dependent manner. Severity of nausea, food intake, time to first emetic episode, and need for rescue antiemetics were also improved for the ondansetron groups. When the patients were stratified for doxorubicin-containing regimens, those patients receiving doxorubicin had a lower response rate with placebo and ondansetron than those on non-doxorubicin regimens. However, a dose-related improvement in efficacy was still observed with ondansetron in this subset of patients. In patients receiving the more emetogenic high-dose cyclophosphamide (> or = 600 mg/m2) regimens, a dose-related improvement in efficacy also was observed. In conclusion, oral ondansetron was found to be an effective and safe antiemetic for patients receiving cyclophosphamide-based chemotherapy in the outpatient setting. The 8-mg dose was optimal, particularly in patients receiving doxorubicin-containing or high-dose cyclophosphamide regimens.


Clinical safety of ondansetron.

Clinical safety of ondansetron. The safety of intravenous (IV) and oral ondansetron has been evaluated in over 7,000 cancer patients in world-wide clinical trials. In adult patients receiving single-day chemotherapy, the incidence of adverse events was 45% with IV ondansetron (n = 317) and 59% with metoclopramide (n = 279). Headache occurred in 17% of ondansetron patients and 10% of metoclopramide patients, whereas diarrhea symptoms were reported in 15% of the former and 29% of the latter. The incidence and types of adverse events were similar following three 0.15 mg/kg IV ondansetron doses and 8- or 32-mg single IV doses. There was a slight increase in the incidence of headache following a single 32-mg dose (25%) compared with a single 8-mg dose (18%) or three 0.15 mg/kg doses (18%). The safety profile of oral ondansetron was similar to that of the IV formulation. Following an 8-mg oral dose administered three times a day for 3 days, the most frequently reported adverse events were headache (21%), constipation (7%), and abdominal pain (5%). In a group of 209 pediatric patients receiving chemotherapy, the incidence of adverse events following IV and oral ondansetron was 19%. The most commonly reported adverse event was headache (4%). In comparative clinical trials, extrapyramidal symptoms were reported in 5% of the metoclopramide patients but none of the ondansetron patients. In open-label trials, two patients who received ondansetron reported symptoms consistent with, but not diagnostic of, extrapyramidal reactions. The incidence of vascular occlusive events and seizure disorders was identical for ondansetron and comparative agents. Serum transaminase values increased significantly in 6% to 8% of ondansetron patients and 2% of metoclopramide patients who received cisplatin. There was no apparent relationship between the dose of ondansetron administered and the incidence of increased transaminase abnormalities. However, there was an apparent relationship between the dose of cisplatin administered and the incidence of transaminase abnormalities. In patients who received non-cisplatin chemotherapy, there was no difference in serum transaminase values between oral ondansetron and placebo. These data demonstrate that ondansetron is better tolerated than metoclopramide and is safe for IV and oral administration to patients receiving chemotherapy. In addition, ondansetron is well tolerated when administered as a single 32-mg infusion over 15 minutes.


Results of a compassionate-use program using intravenous ondansetron to prevent nausea and vomiting in patients receiving emetogenic cancer chemotherapy. This study reports the effectiveness and side effects of intravenous ondansetron as a single-agent antiemetic therapy for patients receiving emetogenic cancer chemotherapy under a compassionate-use program for patients not enrolled in controlled clinical trials. Patients were > or = 7 years old and had uncontrolled nausea and vomiting or intolerable side effects with standard antiemetics administered with previous cancer chemotherapy. All patients received ondansetron 0.15 mg/kg every 4 hours x 3 daily doses beginning 30 minutes prior to emetogenic chemotherapy. Patients could receive ondansetron for up to 5 consecutive days of chemotherapy. One hundred ninety patients received ondansetron during chemotherapy treatments that were similar to previous cycles of chemotherapy during which the patients had received standard antiemetics (identical chemotherapy or differing only by addition/deletion of chemotherapy agents of low emetogenicity). Chemotherapy regimens included cisplatin (n = 99; 52%), doxorubicin (without cisplatin, n = 52; 27%), and other drugs (n = 39; 21%). Patient experiences with nausea and vomiting and side effects with ondansetron and with previous standard antiemetics were rated on a scale of 1 to 10 (1, did not experience; 10, as bad as could be). On the nausea and vomiting scale, 74% of patients improved on ondansetron relative to standard antiemetics. Mean nausea and vomiting scales were 3.9 for ondansetron and 7.7 for standard antiemetics (P < .001). On the side effects scale, 62% of patients improved with ondansetron. Mean side effect scores were 1.8 for ondansetron and 4.5 for standard antiemetics (P < .001). One hundred nine patients assessed the effect of nausea and vomiting on their quality of life by means of the Functional Living Index-Emesis. On a 100-point scale (100=best quality of life), quality of life scores were 65.5 for ondansetron and 39.5 for standard antiemetics (P < .01). Functional Living Index-Emesis scores were higher for 76% of patients during ondansetron treatment as compared with previous chemotherapy with standard antiemetic regimens. Twenty-eight patients (15%) were withdrawn from the study because of nausea and vomiting. Forty-four patients (23%) experienced other adverse effects (headache, 17 patients; diarrhea, eight patients; all other events occurred in two or fewer patients). Only six patients were withdrawn due to adverse effects. In conclusion, ondansetron therapy resulted in significantly improved control of nausea and vomiting, fewer side effects, and better quality of life than standard antiemetic therapy in the same patients receiving similar chemotherapy regimens.


Radiation-induced emesis: effects of ondansetron. The incidence, severity, and onset of radiation-induced emesis (RIE) are related to field size, site, and dose per fraction. Radiation-induced emesis can occur (1) within 2 to 3 weeks in approximately 50% of patients after conventional fractionated radiotherapy (200 cGy/fraction) to the upper abdomen, (2) acutely in more than 90% of patients receiving fractionated total body irradiation (TBI) for bone marrow transplantation, and (3) within 30 to 60 minutes in more than 80% of patients following single high-dose (> 500 cGy)/large field hemibody irradiation (HBI). The increased frequency of emesis associated with TBI and HBI has renewed the interest in the mechanism and treatment of RIE. A number of studies have reported a significant difference in the incidence of emesis following doses of > or = 500 cGy to the upper-mid (> 80%) and lower (20% to 40%) hemibody. The data suggested that the organ responsible for emetic response was in the upper abdomen. However, the mechanism of RIE is not well understood, although degradation products from normal tissues and tumor have been suggested. The introduction and effectiveness of the 5-hydroxytryptamine3 receptor antagonists in chemotherapy-induced emesis and the location of these receptors in the upper abdomen (possible site of the radiation-associated emetic response) suggested that this group of compounds may have a role in RIE. Lucraft and Palmer (Clin Radiol 33:621-622, 1982) reported no differences between levonantradol and chlorpromazine in preventing RIE in patients treated with single doses of more than 10 Gy to a small upper abdominal field. Priestman (Eur J Cancer Clin Oncol 25:529-533, 1989 [Suppl]) reported on a pilot and randomized study with ondansetron after single doses of 8 to 10 Gy to the upper abdomen. In the pilot study, ondansetron achieved major or complete control of vomiting in 77% to 90% of patients; subsequently, he reported a significant difference between ondansetron (97%) and metoclopramide (45%) in controlling RIE on the day of radiotherapy. Hewitt et al (Bone Marrow Transpl 7:431-433, 1991) reported a complete or major response on 93% of the days of ondansetron therapy during pretreatment therapy with cyclophosphamide and TBI for bone marrow transplantation. A preliminary analysis of 41 patients treated with HBI at the Rex Cancer Center confirms the role of ondansetron in RIE. Twenty-eight patients (upper-mid 16 patients/lower HBI 12 patients) did not receive pretreatment antiemetics (group A); seven received non-ondansetron pre-HBI (group B); and six received ondansetron (group C).(ABSTRACT TRUNCATED AT 400 WORDS)


Diagnosis and management of patients with ambiguous genitalia. Ambiguous genitalia in the newborn is an emergency requiring a multidisciplinary approach to diagnosis and management. The differential diagnosis includes gonadal differentiation disorders, female pseudohermaphroditism, and male pseudohermaphroditism. The initial evaluation includes a history, physical examination, radiologic studies, and a karyotype, with subsequent specifically directed laboratory tests. Gender assignment involves consideration of future sexual functioning, fertility, and physical appearance. The information required to assign sex of rearing is usually available within 48 to 72 hours of birth. Management involves ongoing medical follow-up, timely surgical repair, and psychological counselling as needed. Parents require education with respect to sex differentiation and the specific disorder of their child. Normal psychosocial development is dependent on parents' confidence in their ability to raise their child according to the assigned sex.


Can ethnography save the life of medical ethics? Since its inception contemporary medical ethics has been regarded by many of its practitioners as 'applied ethics', that is, the application of philosophical theories to the moral problems that arise in health care. This 'applied ethics' model of medical ethics is, however, beset with internal and external difficulties. The internal difficulties point out that the model is intrinsically flawed. The external difficulties arise because the model does not fit work in the field. Indeed, the strengths of that work are its highly nuanced, particularized analyses of cases and issues and its appreciation of the circumstances and contexts that generate and structure these cases and issues. A shift away from a theory-driven 'applied ethics' to a more situational, contextual approach to medical ethics opens the way for ethnographic studies of moral problems in health care as well as a conception of moral theory that is more responsive to the empirical dimensions of those problems.


Innovation in primary care: community health services in Mexico and the United States. Providing adequate health care to a nation's citizens is a challenge in every country. Despite large differences in wealth, health care organization, and health politics, both Mexico and the United States undertook similar efforts to expand primary care to previously underserved populations during the past 30 years. This study analyzes common antecedents, contexts of change, elements of the innovations, problems with entrenched interests, and resources that have allowed both programs to survive in difficult environments. We show that new forms of primary health care can face similar problems and prospects in very different countries because of similar political, bureaucratic, and economic limitations.


Workable competition in health care: prospects for the Dutch design. Since 1989 a gradual restructuring of the Dutch health care system is taking place to realize a multiple choice social health insurance system with workable competition among insurers and among health care providers. This paper investigates whether the structural change will induce the intended competition. An examination of the characteristics of the market for health insurance, physician services and hospital services in the Netherlands points out that the scope for competition is limited. If competition is to work, rather extensive government regulation to monitor the conduct of both providers and insurers is needed. Without an effective antitrust policy a high degree of concentration and collusion is likely.


The anthropology of sexually transmitted disease in Liberia. In sub-Saharan African countries where AIDS is established, HIV transmission is primarily by means of heterosexual intercourse. A major co-factor in such transmission is the presence of other, sexually transmitted diseases (STDs). Efforts to limit the heterosexual transmission of HIV in Africa must therefore address the high prevalence of other, standard STDs. The present study attempts to establish a preliminary information base for interventions to prevent the spread of HIV in Liberia where there is relatively high incidence of standard STDs but low incidence of HIV seropositivity. Employing in-depth, key-informant interviews with traditional healers, prostitutes and others, as well as focus group discussions with groups selected on the basis of several criteria, knowledge, beliefs, attitudes and behavior related to AIDS and STDs were elicited. Although evidence of exposure to scientific concepts was found, traditional, ethnomedical views predominated. Notions of sorcery, taboo violation and contamination were often expressed when describing the etiologies of locally-recognized sexually transmitted diseases. More 'naturalistic' explanations were often based on simplified notions of human anatomy and biochemistry. Three basic messages about AIDS that were broadcast in a recent radio campaign were retained, namely 'AIDS kills;' 'there is no cure for it;' and 'it is transmitted through sex.' There was also evidence of Liberians beginning to view AIDS in frameworks of interpretation compatible with traditional ethnomedical beliefs, such as sorcery. Most traditional healers reported they knew little or nothing about AIDS, including those who had a lot to say about other STDs that are well-established in Liberia. Many cases of STDs seem to be handled by traditional healers. Treatment typically consists of decoctions from the leaves and roots of various medicinal plants, administered as teas--less often as enemas or vaginal implants--to be taken over a 2-4 day period. It is recommended that efforts to lower incidence of standard STDs be given priority comparable to promotion of condom use and 'safer sex' in efforts to slow the transmission of HIV in Liberia. Strategies for combating STDs will have to take into account popular beliefs and attitudes regarding STDs as well as the role and influence of traditional healers. Strategies of this sort are recommended.


Led (astray) by genetic maps: the cartography of the human genome and health care. Advocates of projects to map the human genome claim that the information produced will illuminate the causes of human disease, improve treatment and, in general, increase our health and well-being. While concerns about the costs of mapping and the possible discriminatory and eugenic applications of the information it will provide have received some attention, assumptions implicit in the biomedical discourse in which its 'benefits' are proposed and which are shaping definitions of illness and health, normality and abnormality, have not yet been adequately analyzed. This paper examines how the genetic stories about mapping and its potential products being told in the biomedical (and popular) literature continue a tradition of reductionism and determinism. This new 'cartography', by adopting the blueprint as a metaphor for genes, leads to restricted conceptions of health and illness, reinforces inequities in the distribution of health and, by privatizing and individualizing responsibility for health, creates and legitimizes a new arena for social control.


Primary care training for patent medicine vendors in rural Nigeria. The provision of essential drugs and the involvement of various potential and existing health care providers (e.g. teachers and traditional healers) are two important primary health care strategies. One local group that is already actively supplying the medication needs of the community is the patent medicine vendors (PMVs), but the formal health establishment often views their activities with alarm. One way to improve the quality of the PMVs' contribution to primary care is through training, since no formal course is required of them before they are issued a license by government. Primary care training was offered to the 49 members of the Patent Medicine Sellers Association of Igbo-Ora, a small town in western Nigeria. Baseline information was gathered through interview, observation and pre-test. A training committee of Association members helped prioritize training needs and manage training logistics. Thirty-seven members and their apprentices underwent the 8 weekly 2-hr sessions on recognition and treatment (including non-drug therapies) for malaria, diarrhoea, guinea worm, sexually transmitted diseases, respiratory infections, and malnutrition, plus sessions on reading doctor's prescriptions and medication counseling. The group scored significantly higher at post-test and also showed significant gains over a control group of PMVs from another town in the district. The Igbo-Ora experience shows that PMVs can improve their health care knowledge and thus increase their potential value as primary health care team members.


Fair law, unfair practices? Benefiting from protective legislation for pregnant workers in Italy and France. Protective Maternity Legislation (PML) for pregnant workers is well established in Italy and France, but little is known about the way it fulfils some of its aims, such as the protection of mothers' and babies' health and of the rights of women workers. In this paper, we present the results of two surveys, one carried out in Italy and the other in France, concerned with the implementation of these regulations. Results show that women who were regularly employed generally could benefit from PML, while non-eligible workers, most of them holding manual jobs, were not protected at all. Among eligible workers, inequalities existed: women with less qualified jobs and those employed in the private sector were less likely to benefit from the protective measures considered. A number of specific measures, such as the possibility of taking an early maternity leave for work reasons and of being moved to another job within the same firm were underused in both countries. Some limitations of PML are discussed, namely the fact it covers some but not all pregnant workers, that it ignores domestic work and the tendency to remove the pregnant worker rather than to modify her working conditions.


The gap between legal rules and practice in advertising non-registered pharmaceutical products. A new method of analysis. The market of non-registered pharmaceutical products is growing fast in number and overall costs, not only in the Netherlands, but also in other European countries. These products often give the impression that the consumer may expect 'an effect as from a drug'. Legally, there is a clear distinction between 'drugs' and 'commodities' in the Netherlands; the question is whether legislation and practice concur. In an investigation we analysed texts of advertisements for non-registered pharmaceutical products published in a popular magazine. A method was developed, based on the legal definition of a drug and jurisprudence, to determine in a qualitative and quantitative way the application of medicinal claims. It transpired that in 65% of the analysed advertisements explicit or implicit claims were made. These products should therefore be subject to drugs legislation. Thus, in the Netherlands there is a gap between legislation and practice in advertising non-registered pharmaceutical products.


The relationship between work stress and oral health status. This study investigated whether oral health status is associated with work stress. 164 male workers aged from 35 to 44 years, equally distributed over four socio-economic groups took part in the study. Three work characteristics related to stress were studied: mental demand, control and variety. Age, socio-economic status, sugar consumption, frequency of dental attendance, toothbrushing frequency, type of toothpaste used, years of residence in Belo Horizonte and marital quality were considered in the data analysis. The results of simple regression analysis (dental caries data) and simple logistic regression analysis (periodontal data) showed a significant relationship between periodontal health status and work-related mental demand (P < 0.001), marital quality (P < 0.01) and socio-economic status (P < 0.05). Dental caries status was significantly associated with age (P < 0.001), socio-economic status (P < 0.05), sugar consumption (P < 0.01) and marital quality (P < 0.0001). Socio-economic status did not remain significantly associated with dental caries after adjusting for all the variables studied.


Optimizing bereavement outcome: reading the road ahead. After a death has occurred, those most affected are left to make sense of the illness and the awesome event that has taken place. When the death is caused by cancer, many skills may have been employed to ensure that the palliative care was of a high enough standard. Yet still many mourners reflect with sadness and bitterness about the experience that was unique to them. In the process of evaluating a volunteer bereavement support programme, the key carers were asked to reflect upon their experience before, during and after the death. If we listen to them, we can learn the ways in which our skills can enable the death to be an enriching experience and not one which interferes with mourning.


Disease concordances amongst marital partners: not 'way of life' or mortality data artifact. Mortality statistics for Great Britain (1979-80, 1982-3) for more than 500 occupations and 20 different causes of death were examined. The paper demonstrates that there is clear concordance of cause of death between men and married women which can be linked to the occupation of the male. Various possible explanations are considered including shared social class and way of life and the suggestion that the associations reported are the result of various forms of statistical bias inherent in Standardized Mortality Ratio statistics. It is proposed that this is consistent with a psychosocial hypothesis, although longitudinal empirical research would be required to establish this.


[Peroperative endoscopic papillosphincterotomy]. The authors describe their experience with combinations of endoscopic and surgical procedures when dealing with stenoses of the papilla Vateri. They give a detailed account of the endoscopic phase of surgical intervention. In their opinion the most important thing is exclusion of duodenotomy which should reduce the risk of a duodenal fistula. Another important advantage is more rapid convalescence and a shorter hospitalization period as well as a shorter time required for the intervention. Next the authors discuss possible complications described in the literature and their relationship to endoscopic papillotomy. The authors evaluate contemporary possibilities of endoscopic treatment and emphasize the necessity to extend the use of endoscopic methods in everyday surgical practice.


[Intensive care in patients with intra-abdominal septic complications]. The authors investigated diagnostic and therapeutic possibilities of intensive care units when treating septic conditions in intraabdominal surgery. The authors emphasize the comprehensive and systematic character of the follow up of patients who are threatened by sepsis. Care involves in particular aimed antimicrobial therapy, immunotherapy, normalization of haemodynamics and the acid-base balance and rational parenteral nutrition. Only a thus conceived therapeutic regime makes it possible to control such serious conditions as sepsis.


[Initial experience with use of fibrin glue in the treatment of acute gastroduodenal hemorrhage]. A new therapeutic method of acute haemorrhage into the upper gastrointestinal tract is the application of fibrin sealants to the bleeding site. The authors present their own experience with the method of endoscopic haemostasis of haemorrhage into the upper gastrointestinal tract in a total of 56 patients with haemorrhage into the gastrointestinal tract. Five patients with oesophageal varices were treated by the injection technique--Polidocanol was used for sclerotization. In 35 patients with haemorrhage Forrest I haemostasis was ensured by use of a fibrin sealant. In 28 patients this was preceded by electrocoagulation or thermocoagulation. In these 35 patients fibrin sealing had to be repeated in three patients and only one of the patients was operated. Another patient was operated on account of a relapse of haemorrhage without repeated endoscopic intervention. From the total number of 35 patients only four were operated--two patients because of local permanent haemostasis after endoscopic treatment, two patients on account of relapse of haemorrhage. Both died during the postoperative period. One man committed suicide--complete haemostasis after endoscopic treatment was confirmed on autopsy. In a total of 35 patients in 33 permanent haemostasis was achieved incl. 30 were the lesion healed completely.


[The modern approach to dressing wounds]. The author evaluates from the pathophysiological aspect the impact of various dressings applied to wounds with regard to the permeability of secretions, gases, maintenance of a stable temperature and preservation of an optimum pH as well as with regard to preventing penetration of toxic substances, bacteria and foreign bodies. The author also pays attention to the important condition of non-adhesiveness of the dressing to the surface of the healing wound. From this aspect he evaluates cotton, paraffin, hydrocolloid, porous and silicon dressings. Based on the study of extensive literature and his own experiments, the author reaches the conclusion that it is essential to provide optimal mechanical and thermal protection of the wound and that for every type and stage of wound healing an appropriate dressing must be selected.


[A vesico-sigmoid fistula in a 15-year-old girl]. The authors diagnosed in a fifteen-year-old girl. other wise healthy, a double vesicosigmoidal fistula. It developed probably at the age of two after an acute abdominal attack of inflammatory character which was treated conservatively. The fistulae caused repeated inflammations of the urinary pathways. In the late diagnosis participated among others evaluation of miction cystography which was imperfect from the technical aspect. When repeated, this examination contributed to the diagnosis. After surgery the girl recovered.


Alterations in cerebral vessels in experimental animals and their possible relationship to the development of aneurysms. Aneurysmal changes were studied by light and electron microscopes in experimental monkeys to elucidate their pathogenesis. Early changes were found not at the medial defect but in one branch near the apex. Degeneration of the elastic lamina was always more than that of the media throughout the process of aneurysm formation. Endothelial injury was present even at the bifurcation without a bulge. The present study suggests that aneurysmal changes are initiated by degenerative changes in the endothelium, which are followed by alterations in the underlying elastic lamina and, in turn, in the medial layer.


Compression of thoracic nerve root by a facet joint synovial cyst: case report. Synovial cysts are not an uncommon feature in the mobile spinal segments. The lack of reports at the thoracic level has stimulated us to present this patient with compression of the 10th dorsal root.


Ruptured suprasellar dermoid associated with middle cerebral artery aneurysm: case report. Dermoid tumor associated with cerebral aneurysm is extremely rare. We report here a case of ruptured suprasellar dermoid cyst associated with middle cerebral artery (M1) aneurysm and stenosis of adjacent arterial trunks. The characteristic feature of this association is the tight adhesion of the vascular lesion to the tumor capsule.


Giant aneurysm of the distal anterior cerebral artery: associated with an anterior communicating artery aneurysm and a dural arteriovenous fistula. We describe an unusual case of a giant pericallosal artery aneurysm, producing psychomotor depression from mass effect, associated with a smaller aneurysm of the anterior communicating artery, a dural arteriovenous fistula, and a meningioma. Magnetic resonance imaging (MRI) and cerebral angiography demonstrated the giant aneurysm and the meningioma. Cerebral angiography provided a detailed appreciation of the cerebral circulation, including both aneurysms, the dural arteriovenous fistula, and the potential collateral supply to the involved anterior cerebral distribution. The anterior communicating artery aneurysm was successfully clipped as was the distal anterior cerebral branch supplying the giant aneurysm before its resection. The patient made a full recovery but with persisting, slight dysphasia. We conclude that computed tomography, cerebral angiography, and MRI are of specific value in the assessment of giant aneurysms, but only angiography can provide detailed characterization of the aneurysm and demonstrate other possible cerebrovascular pathology such as multiple aneurysms and arteriovenous fistulas.


Selective and superselective infusion of urokinase for embolic stroke. Intraarterial administration of urokinase using Tracker microcatheter was performed in 11 patients with acute cerebral infarction caused by embolic occlusion of the internal carotid or the middle cerebral artery. Recanalization was observed in seven cases (64%) following the fibrinolytic therapy, and the time until recanalization from the start of the treatment was on the average 2.8 hours. Recanalization was seen in five out of six cases that received superselective infusion of urokinase, while it was seen in two out of five cases that received selective infusion. This study suggests that superselective infusion of urokinase is an excellent therapeutic method for embolic occlusion of the cerebral artery.


Unruptured intracranial aneurysms in elderly patients. A total of 556 patients with 769 intracranial aneurysms, of which 256 were unruptured and 513 were ruptured, were included in the present study. The patients were divided into three age groups: those aged 59 years or younger, those aged 60 to 69 years, and those aged 70 years or older. Small aneurysms of 4 mm or less in diameter were more common in the series of unruptured aneurysms than in the ruptured aneurysms. The rupture rate in anterior communicating artery aneurysms was the highest, and it increased with age. A follow-up study was performed on 47 patients with 55 unruptured aneurysms, and only one giant basilar artery aneurysm ruptured during the average follow-up period of 5.2 years. Direct operation was performed on 52 patients with unruptured aneurysms. While the surgical mortality rate was 0%, the morbidity rate was 6% (three of 52 cases), which was not directly related to the patients' age. When considering surgery for unruptured aneurysms, rupture rate of aneurysms at each site is one of the most important factors, especially in elderly patients.


Detection and management of gangliogliomas in children. Forty-two children treated for gangliogliomas were reviewed to identify the best methods of detection and management. Thirty-two of the tumors were supratentorial, four infratentorial, and six were in the spinal cord. Twenty-five patients presented with seizures; the mean duration of symptoms was 5 years in contrast to 1 year in non-seizure patients. Of 31 children studied by computed tomography (CT), calcification in the tumor lesion was found in 19. Magnetic resonance imaging (MRI) showed abnormal high-signal intensity on T2 imaging in six of eight patients. All patients underwent surgical resection and were diagnosed pathologically. Twenty-four patients had total resection, and 14 underwent temporal lobectomies including hippocampectomy. The management of this tumor remains surgical resection without the need for any adjuvant therapy.


Transoral-transclival clipping of a giant lower basilar artery aneurysm. The authors discuss the choice of the transoral-transclival approach for the repair of a lower basilar artery aneurysm in a 32-year-old sickle-cell patient. Efficiency of approach and minimization of damage to vital structures support the use of this technique. The risks of cerebrospinal fluid fistula and meningitis are considered. One year after operation, the patient is neurologically intact.


Skull base reconstruction in cases of intracranial teratoma extending into the extracranial structures. Recently experienced were two cases of postnatally diagnosed intracranial teratoma, one a mature teratoma and the other an immature teratoma, both extending into the extracranial structures. In each case, tumor resection was performed in which a barrier was created between the intracranial and extracranial spaces with a temporalis muscle flap. The technical aspect of skull base reconstruction is described, and previously reported cases of intracranial teratoma involving the skull base are reviewed.


Use of tissue adhesive to secure spinal epidural stimulating electrodes: technical note. Securing spinal cord stimulating electrodes (SCS) within the epidural space is often a challenging task. Complications of the technique include development of cerebrospinal fluid leaks and electrode migration. We report four patients who underwent a limited laminectomy for placement of epidural spinal cord stimulating electrodes to relieve pain and/or spasticity. Suturing electrodes to the dura was not possible, and a tissue adhesive was used. Two-year follow-up shows no migration of the electrodes. Tissue adhesive of "fibrin glue" is a viable alternative for securing epidural SCS electrodes.


Quantitative variability and multilocus polymorphism under epistatic selection. We study multilocus polymorphism under selection, using a class of fitness functions that account for additive, dominant, and pairwise additive-by-additive epistatic interactions. The dynamic equations are derived in terms of allele frequencies and disequilibria, using the notions of marginal systems and marginal fitnesses, without any approximations. Stationary values of allele frequencies and pairwise disequilibria under weak selection are calculated by regular perturbation techniques. We derive conditions for existence and stability of the multilocus polymorphic states. Using these results, we then analyze a number of models describing stabilizing selection on additive characters, with some other factors, and determine the conditions under which genetic quantitative variability is maintained.


Relatedness and inclusive fitness with inbreeding. Relatedness arising in kin selection theory is measured by a variable taking as values two pedigree indices in populations with inbreeding when selection is weak. This variable reduces to a single pedigree index when inbreeding is caused by partial selfing or partial sib-mating. General inclusive fitness formulations of kin selection models based on such a variable of relatedness are proposed.


An optimizing principle of natural selection in evolutionary population genetics. This paper brings together two themes in evolutionary population genetics theory. The first concerns Fisher's Fundamental Theorem of Natural Selection: a recent interpretation of this theorem claims that it is an exact result, relating to the so-called "partial" increase in mean fitness. The second theme concerns the desire to find an optimality principle in genetic evolution. Such a principle is found here: of all gene frequency changes which lead to the same partial increase in mean fitness as the natural selection gene frequency changes, the natural selection values minimize a generalized distance measure between parent and daughter generation gene frequency values.


[Epidemiology and risk factors of venous thromboembolism]. Venous thromboembolism (deep venous thrombosis (DVT) and pulmonary embolism (PE)) is a serious and quite frequent disease. In this review, we summarize the present state of knowledge regarding clinical epidemiology and risk factors. These features should allow the general practitioner to assign each individual patient to a particular risk group and to order an personalized prophylaxis.


[Diagnosis of deep venous thrombosis].

[Diagnosis of deep venous thrombosis]. The clinical diagnosis of deep venous thrombosis (DVT) is unreliable. Phlebography, an invasive method, has gained wide diffusion and is considered as gold standard, but it has several draw-backs such as elevated costs and x-ray exposure. For these reasons, other, non-invasive techniques for diagnosing DVT have been looked for. Among them, CW-Doppler, occlusion plethysmography and, more recently, colour-Duplex-sonography have gained most acceptance. While the first two methods are able to diagnose with sufficient sensitivity and specificity proximal DVT, they are unreliable for isolated calf vein thrombosis. The colour-Duplex-sonography, on the other hand, produces results similar to phlebography for proximal thrombosis and succeeds in detecting isolated calf vein thrombosis with sufficient accuracy. We propose therefore the following non-invasive proceeding when confronted with the question of DVT: The first investigation to be done is a (colour)-Duplex examination. If one lacks such an infrastructure, an investigation with CW-Doppler or occlusion plethysmography has to be performed. If the results are positive, the patient will be treated. Otherwise, the exam will be repeated after five to seven days for CW-Doppler and plethysmography. If now the result is positive, the patient will be treated, otherwise, as with a negative Duplex study, the suspicion of DVT will be dismissed.


[Radiologic and nuclear medicine diagnosis of lung embolism]. The imaging methods used in diagnosing pulmonary embolism and their appropriate indication in individual situations are discussed. Chest radiography is needed to exclude other diseases, whereas nuclear ventilation and perfusion scans are the main screening method and have not been replaced by intravenous digital subtraction angiography up to now. As long as these non-invasive methods are clearly negative or positive, no other method is needed. With questionable findings (intermediate scan probability), pulmonary angiography is needed, above all when there is a contraindication to anticoagulation.


[Prevention of venous thromboembolism in surgery]. Incidence of postoperative deep venous thrombosis extends from 7% (transurethral prostatectomy) to more than 50% (hip surgery) depending on the magnitude of trauma and due to the corresponding surgical procedure. Although more common with higher age, younger patients suffer from postoperative thromboembolic complications as well. This insight leads to the conclusion that all immobilized adult patients or those needing an operation are to receive thromboembolic prophylaxis should there be no contraindication. As 50% of all postoperative thromboses develop sometime during the operative procedure, thromboembolic prophylaxis has to be effective intraoperatively as well. The first dose must therefore be preoperative. Duration of prophylaxis depends on the ambulation of the individual patient and should be maintained for at least seven days. Physiotherapeutic measures and drug therapy should complement each other. Low molecular heparins have been very successful lately. Their effect on thrombosis in visceral surgery has been equal when compared with unfractioned heparin whereas the effect in hip surgery compared to unfractioned heparin has been even more promising. Due to the longer half-life of low molecular heparin when compared with unfractioned heparin and its better bioavailability, one dose of low molecular heparin a day is sufficient. This is certainly a benefit for the patient and the nursing staff. To our current knowledge the tendency toward bleeding does not differ basically if low molecular heparins or standard heparin is being used. In patients with spinal anaesthesia, as with low molecular heparins, the first dose has to be administered preoperatively. Different ways of application are possible.


[Prevention of venous thromboembolism in internal medicine patients]. In the entirety of medical patients, mechanical prophylactic measures and subcutaneous application of heparin have a documented efficiency and few side effects. With them the hospital mortality can be lowered by about 30%. When analysing the risks for patients of internal medicine, immobilisation respectively absence of the muscle pump play a central role in the list of risk factors. Possibilities for improving prophylaxis comprise an individual adjustment of heparin dosing (the improved efficiency in comparison with fixed dosing is not yet proven, but probable on the basis of experience made with surgical patients), the combination with mechanical/physical measures and the more consistent realisation in patients at risk. For achieving this the dosing only once per day with low molecular heparin is favourable, the latter being at least equally efficient.


[Internal medicine therapy of venous thromboembolism]. Treatment of venous thromboembolism aims at the reduction of mortality of massive pulmonary embolism, the arrest of further thrombotic processes and at avoiding late post-thrombotic sequelae. Anticoagulation with heparin and oral anticoagulants remains the treatment of choice. Heparin is administered intravenously or subcutaneously for four to five days. Oral anticoagulation follows thereafter for three to six months or even life-long. Low molecular weight heparin will probably be able to substitute for the unfractionated heparin in the initial treatment phase. Therapeutic fibrinolysis or surgical treatment are considered as alternative treatment modalities. Furthermore, new potent thrombin or platelet inhibitors appear as promising future antithrombotics.


[Prevention of venous thromboembolism with heparin in risk patients during pregnancy: monitoring by measuring thrombin-antithrombin III complex]. Women at high risk for thromboembolism deserve prophylactic treatment with heparin in the course of pregnancy. Since activation of the coagulation system is associated with an increase of TAT complexes which may well precede the clinical thrombosis, this parameter was used to determine start as well as dosage of the heparin prophylaxis. Thereby, the increase of TAT complexes during a normal pregnancy without thrombolic events had to be taken in account. 43 pregnancies of 40 patients who had already suffered from thrombotic events before pregnancy or had a positive family history were monitored by this method; in none of them any thromboembolic complication occurred. Duration of treatment and maximal amount of heparin showed wide individual variations and could not be predicted by clinical criteria. However, the total dose of heparin necessary was in many patients far below of what is usually administered, thus reducing the risk of heparin-induced osteoporosis and of local allergic reactions.


[Evaluating the origin of thrombophilia: indications and implementation]. The overall incidence per year of deep vein thrombosis is about one per thousand, but may be much higher in the presence of certain clinical risk factors such as advanced age, immobilization, surgical procedures, pregnancy, puerperium, use of oral contraceptive agents and malignancy. Moreover, homocystinuria, nephrotic syndrome, systemic lupus erythematosus and hematological disorders such as paroxysmal nocturnal hemoglobinuria or myeloproliferative syndromes predispose to thrombotic disease. Evaluation of the patient with thromboembolism should include detailed history, clinical examination and laboratory investigation to exclude these secondary thrombophilic states. Primary or hereditary thrombophilia is suspected mainly in patients suffering from (venous) thromboembolism at an early age (< 45 years), especially if recurrent and/or familial thrombosis is present. Hereditary thrombophilia may be due to deficiency of antithrombin III, protein C, protein S or plasminogen, some other defects being less well-established prethrombotic risk factors. These currently recognized primary prethrombotic molecular defects are found in 10 to 30% of patients with idiopathic thromboembolism. In the majority of cases the cause of thrombosis remains unknown.


[Thromboembolic diseases from the hematologic viewpoint: 13 case examples]. Numerous patients with a thromboembolic history are referred to our Central Haematology Laboratory for a complete investigation of thrombophilia. Among them, patients with idiopathic thromboembolism represent the largest group. In collaboration with the obstetrician we control pregnant women at increased risk for thromboembolic complications. Individuals with myeloproliferative disorders often suffer from thromboembolism and are investigated at our Laboratory as well. Thirteen illustrative cases are presented, which are of diagnostic and/or therapeutic interest for the practitioner.


[Injuries following a hurricane in Nordmøre]. In this article we describe the efforts of local authorities to detect and treat casualties caused by a hurricane that struck the west coast of Norway January 1st, 1992 and prevent further injuries. Wind velocity exceeded 100 knots (117 mph), the strongest ever recorded in Norway. The damage to buildings, trees and power lines was so devastating that the Nordmøre area, with approximately 50,000 inhabitants, was left without electricity for five days. Altogether 56 casualties were reported by physicians and the local hospital (one death, caused by hypothermia and exhaustion, and six admissions to hospital) in the period 1-5 January. Nine old people suffered injuries by falling in the dark in their houses, and ten men were injured during repair work.