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A coronary arteriographic investigation has been made of 492 patients, most of whom had different cardiac diseases. Eighty patients died during an observation period from 1 1/2 up to about 7 years. In 45 patients a postmortem investigation was made. Comparison between arteriographic and post mortem findings in the arteries and the myocardium, as well as the study of other clinical facts at or before the time of investigation, led to the following conclusions. 1 A coronary arteriogram of good quality gives a reliable picture of the intraluminal condition in the big predominantly epicardial coronary arteries. 2 An occlusion or critical obstruction of the coronary arterial stems are in the majority of hearts combined with myocardial disease in the form of old infarction scar or local, patchy fibrosis. 3 Coronary arteriography is of good help to demarcate a group of patients with diffuse non-atherosclerotic, myocardial disease. 4 Early changes of atherosclerotic coronary artery disease seem to be rather evenly distributed among the big coronary arteries. In the living patients the majority of severe obstructions are present in the right and the left descending artery. This distribution is probably due at least partly to the selection of patients in the study. 5 Roughly half of all myocardial infarctions can be clinically traced. 6 The results emphasize that angina pectoris, clinical picture of myocardial infarction and abnormal Q waves in the ECG are not synonymous with coronary heart disease. This may be particularly true in hospitalized patients, who may overrepresent non-atherosclerotic heart diseases, leading to symptoms and signs shared by the atherosclerotic, coronary heart disease.

Ten boys 9-12 years of age with severe perennial asthma participated in a physical exercise programme lasting 8 months. Pulmonary function and psychological tests were performed before training, immediately after, and one year after the end of the exercise programme. Static lung volumes, flow-volume variables and histamine tolerance were used as indicators of pulmonary function. Ego structure, body image, social development and concentration capacity were used as indicators of personality development. Before the study, the group had high FRC (p less than 0.05) and RV (p less than 0.001), low FEV1, MEF50 and MEF25 (all p less than 0.001) and low histamine tolerance. They showed marked disturbances in their personality development with low scores in psychological variables. During the training period, MEF50 and MEF25 increased slightly (p less than 0.01). Marked improvement was observed in all psychological variables (p less than 0.001). The positive effects remained during the following year. The marked and lasting improvement in personality development was regarded as an essential factor behind the more modest positive clinical and pulmonary function changes. The results emphasize the importance of including exercise programmes in the treatment of children with asthma.

The clinical value in neuropediatrics of [99mTc]HM-PAO brain single photon emission computed tomography was preliminary evaluated by the consecutive investigation of 79 children. Planned epilepsy surgery was the most common indication for the investigation. In 56 children investigated because of epilepsy, SPECT yielded relevant information in 79% of cases examined. The corresponding figures for magnetic resonance imaging and CT were 49% of 35 and 36% of 56 cases, respectively. All 22 children with an epileptic focus, ascertained by freedom from seizures after removal of the area or by consistent neurophysiological and neuroradiological findings, also had abnormal perfusion in the relevant area. Twenty-three children were examined because of neurological signs and symptoms other than epilepsy. SPECT findings were useful for elucidating neonatal brain impairments. Hypoperfused areas in the brain of asphyxiated infants and in posthemorrhagic hydrocephalus corresponded to neuroradiological and autopsy findings. SPECT was found to be an excellent tool when analysing cerebrovascular accidents. In cases with signs and symptoms of a diffuse severe encephalopathy, SPECT did not clarify the etiology but provided information on the distribution of the lesions and probable underlying pathophysiological mechanisms.

Sixteen Rett syndrome (RS) girls and 1 24 year old RS woman were compared with 16 neurologically healthy children as to the regional cerebral blood flow (rCBF). Hypoperfusion of the frontal lobes and parts of the midbrain was found in RS, with significant differences to controls at latest by the age of three to four years. The findings were in accordance with previous reports of morphological, neuroradiological and functional abnormalities in these areas, compatible with a statement that structures in the midbrain and in the frontal lobes may have particular pathophysiological relevance in RS.

Four methods of calculating the activity of 99Tcm-hexamethylpropyleneamine oxime to be administered in cerebral blood flow investigations of children were evaluated in patient studies. Three of the methods were based on the size of the child. We also constructed a theoretical dosage model based on physiological data and attenuation effects. The aim of the study was to find a dosage calculation method that gave the same image quality for children of all ages as well as for adults. The results showed that the dosage method based on body weight is the only one of the four methods that does not exhibit an age-dependent variation in image quality and therefore this method is recommended.

The influence of the breathing pattern on transcutaneous blood gases was evaluated in 18 boys and 8 girls 7-18 years of age, with bronchial asthma, during bronchial provocation with histamine-HCl. Transcutaneous oxygen tension (tcPO2), carbon dioxide tension (tcPCO2) and the breathing pattern assessed by the transthoracic impedance technique were continuously monitored during the provocation. At reaction, when the fall in the forced expiratory volume in 1 s (FEV1) was 20% or more, the tcPO2 fell by 15% or more below the baseline in 22/26 and by 20% or more in 14/26 children. In some children, a marked fall in the tcPO2 was already noted after the saline inhalation and the first histamine dose steps without simultaneous changes in the FEV1. This early fall in the tcPO2 correlated to changes in the breathing pattern and was interpreted as a sign of compensatory hypoventilation secondary to the hyperventilation observed during the inhalations. We conclude that transcutaneous oxygen tension can be used as an indicator of a bronchial reaction during bronchial provocation tests in children only if one takes account of the fact that the breathing pattern during the inhalation of the challenge compound per se has an effect on the oxygen tension.

Bronchial reactivity was assessed in 66 children with bronchial asthma (aged 8–15 years) by provocation with histamine-HCl during a symptom-free period. A significant bronchial reaction to histamine was defined as a 50% increase in the resistance of the respiratory system (Rrs) determined by the forced oscillation technique. The provocative dose causing a 50% increase in the Rrs (PD50Rrs) was interpolated from the log dose-response curve. The mean PD50Rrs was significantly lower in children with asthma (0.22 mg/mL) compared with a group of healthy children in the same age range (1.55 mg/mL) (P < 0.001). In children with clinically severe asthma, the mean PD50Rrs was lower (0.13 mg/ml) than in children with mild asthma (0.34 mg/mL) (P < 0.001). Transcutaneous Po2 (Ptco2) was monitored in 25 of the children with asthma. In this group the proportion of mild and severe asthma, the baseline lung function variables, and the PD50Rrs were not significantly different from those of the whole group of children. During the reaction, the Ptco2 fell on average by 29% of the baseline value (P < 0.001); in 88% of the children, the fall in Ptco2 was 20% or more of the baseline value. We conclude that histamine provocation tests using the forced oscillation technique and transcutaneous Po2 to assess a bronchial reaction have a good discriminatory capacity for different degrees of clinical severity of asthma in children. © 1993 Wiley-Liss, Inc.

The effect of salbutamol inhalations on transcutaneous blood gases was investigated in 23 children (aged 11 months-2.5 years) with asthmatic symptoms. After one salbutamol inhalation there was a mean increase in transcutaneous PO2 (tcPO2) of 0.5 kPa (P less than 0.01); after a second dose given 30 minutes later, the mean increase was 1.2 kPa (P less than 0.001). The increase in tcPO2 after only one dose of salbutamol was significantly correlated to age (P less than 0.01). No such correlation was observed after a second dose. The overall increase in tcPO2 after two salbutamol inhalations showed a negative correlation to the duration of the current symptomatic period (P less than 0.05). We conclude that salbutamol inhalations have beneficial effects in young children with acute asthmatic symptoms, even below the age of 18 months, provided that an adequate dose reaches the lung and preferably at an early stage of obstruction.

In this study the prevalence of bladder dysfunction in 18 children with gross bilateral reflux was investigated via cystometric recordings. In all except 1 infant maximal voiding detrusor pressure was 100cm. or greater water (range 86 to 244). Pronounced instability during filling (overt instability) with pressure waves above baseline (mean 65cm. water, range 42 to 194) was found in 9 infants. Another 5 children had evidence to suggest an uninhibited bladder, not manifested as unstable contractions during filling but as covert instability, meaning that the first unstable contraction was transformed into a premature and forceful voiding contraction. The high detrusor pressures found in 18 children with gross bilateral reflux during the voiding phase but also during the filling phase in half of the children suggest that a hypercontractile detrusor may be a contributory factor for the development of reflux even in this age group.

The increasing numbers and survival of children with shunt-treated hydrocephalus make it mandatory to refine the methods for cerebrospinal fluid (CSF) shunt function evaluation. Radionuclide shuntography with 99mTc-DTPA, which has proved to be a safe and effective method, was performed in eight children with suspected CSF-shunt dysfunction. Characteristic shuntography patterns were found for proximal and distal CSF-shunt catheter obstruction as well as for overdrainage and normal CSF-shunt function. Shuntography contributed to the explanation of suspected CSF-shunt dysfunction in all children investigated.

The lung function of 31 children, aged 6-13 years, who had whooping cough as infants and 32 control children matched for age, sex, and residence area were compared in a community based cohort study. Family history of obstructive airway disease, smoking habits in the family, atopy, and other background factors examined were similar in the two groups. The ratios of recalled repeated acute respiratory infections did not differ among the groups. Children in the control group were slightly more involved in physical activities. History of obstructive airway disease, findings on chest radiography, and distribution of immunoglobulin concentrations, including IgE, did not differ significantly. Lung function before and after exercise and after inhalation of salbutamol were not different. No impairment of small airways was detected. Our data do not support the hypothesis that whooping cough in itself is a causal factor for later obstructive respiratory disease.

The laryngeal chemoreflex involves bradycardia, apnea, swallowing and peripheral vasoconstriction. This reflex was studied in twelve infants, aged 5 days-28 weeks, who had sustained an apparent life-threatening event or were siblings of infants who had died of the sudden infant death syndrome. The bradycardic and apneic components of the reflex were found to be significantly, and sometimes powerfully, reinforced when elicited by pharyngeal water instillation during acute, mild hypoxia (transcutaneous PO2 4.6-8.3 kPa). Apnea duration during normoxia was 0.7-15 sec, and during hypoxia 2-30 sec. Heart rate change ranged from +26% to -21% during normoxia, as compared with -4% to -63% during hypoxia. The percentage change in heart rate was found to inversely correlate with the transcutaneous PO2-level prevailing when the reflex was elicited. The conclusion is that there is a significant reinforcement of the cardiorespiratory adjustments when the laryngeal reflex is activated during simultaneous excitation of the peripheral arterial chemoreceptors. One infant, showing a particularly strong increase of the cardiorespiratory response to laryngeal receptor stimulation during hypoxia, later died of sudden infant death syndrome.

Recurrences of bacteriuria after treatment occur in 50% to 80% of asymptomatic patients. Previous experience with short-term treatment as well as longterm prophylaxis has been disappointing, with a significant risk of infections, ie, development of symptoms after treatment. Results with nontreatment are described in this report with reference to clinical course, renal growth, and glomerular filtration rate in 26 asymptomatic girls with established renal scarring and bacteriuria. Acute pyelonephritis was not seen in those with continuing bacteriuria or spontaneous clearance. Neither in scarred nor in unscarred kidneys did the duration of bacteriuria influence renal growth or glomerular filtration rate. Asymptomatic patients with bacteriuria may gain from nontreatment and may have a reduced risk of pyelonephritic attacks.

Summary The carboxyhaemoglobin (COHb) concentration in blood, which is assumed to reflect the degree of haemoglobin catabolism, was determined in 62 newborn infants selected because of significant jaundice associated with ABO incompatibility, and in 46 infants with ABO incompatibility, selected without regard to the degree of bilirubinaemia. Furthermore, the COHb level was determined in 46 icteric infants without haemolytic disease, and in 61 infants of ABO homospecific pregnancies, selected without regard to their bilirubin level. In infants with ABO incompatibility increased COHb concentrations were found not only in infants with unequivocal signs of haemolytic disease but also in infants with a clinical picture indistinguishable from physiological jaundice. During the first days the relation between COHb and bilirubin in infants with ABO incompatibility was the same, whether the infants were selected because of significant jaundice or irrespective of the degree of bilirubinaemia. This indicates a common pathogenesis of the bilirubinaemia in the two groups. The COHb and bilirubin levels in infants of ABO heterospecific pregnancies and in infants of ABO homospecific pregnancies, selected without regard to the degree of bilirubinaemia, were compared. It is concluded that the COHb level probably is a more sensitive indicator of haemolysis than the bilirubin concentration. Increased COHb concentrations were also found in icteric infants without blood group incompatibility, but the relation between COHb and bilirubin indicates that in ABO incompatibility increased haemolysis is of greater importance in the pathogenesis of the jaundice.

Haematocrit, plasma volume and viscosity were not notably different at rest in fifteen diabetics from those in ten controls. After moderate exercise, plasma volume was reduced and haematocrit was increased significantly more than those in controls. In the diabetic subgroups based on varying degrees of dermal angiopathy, no significant differences were demonstrated. In circulatory steady state during exercise the diabetics responded with a marked increase of systolic blood pressure. The amount of filtrate from the vascular bed to the interstitial tissues was not correlated to increasing systolic pressure. The difference in work intensity between the groups is not of such an order that it can be assumed to influence haematocrit or plasma volume. These findings may indicate increasing permeability of the capillary walls because of changes characteristic of diabetic microangiopathy.

In a group of 68 middle-aged sedentary men participating for 2 months in hard physical training, 5 were initially advised against participation for medical reasons; 54 subjects completed the training program. The frequency of orthopaedic complications was high. A slight decrease of the number of abnormal ECG findings at rest and at work (premature beats and ST-changes) was found after training. The blood pressure reaction during work in relation to the heart rate response was not changed. A significant reduction of the iron and cholesterol levels in the serum occurred.

Fifteen previously sedentary men (38–55 years old) participated in an endurance training program which consisted of running for 2–3 half-hours a week for 8–10 weeks. Maximal oxygen uptake increased in all subjects, mean increase from 2.68 to 3.06 l/min, i.e. 14 per cent. This increase was brought about by a 13 per cent increase in maximal cardiac output, from 18.7 to 21.1 l/min. Heart rate was 8–17 beats/min lower during submaximal exercise. The maximal heart rate decreased by 6 (from 182 to 176) beats/min. Thus stroke volume was increased 7–17 ml at submaximal and 17 ml (16 per cent) at maximal exercise. Heart volume determined from X-rays did not change. After the training, mean arterial blood pressure was on the average 5 mm Hg lower at a given submaximal oxygen uptake; no change was observed at maximal exercise.

The effect of graded hypoxia on the distribution of pulmonary blood flow was studied in 10 sitting healthy subjects using the Xe133 technique. The distribution of lung perfusion became more

Summary One hundred and thirteen full-term infants with bilirubin values of 18 mg% or more during the neonatal period, have been followed-up at the age of 2–3 years, and compared with 51 full-term, non-icteric infants, born during the same period. Exchange transfusion was carried out in 30 of the children with jaundice. No cases of kernicterus could be demonstrated. Play audiometry was carried out in 125 children (86 with jaundice, 39 controls). No deafness of central type was revealed. At the paediatric follow-up examination no relevant abnormalities were found. Merrill-Palmer testing produced evidence of a similar I.Q. distribution among the icteric as among the non-icteric children. A cerebral lesion was diagnosed in 3 cases, but in all these another aetiology (disturbance at the time of birth) occurred in addition to hyper-bilirubinaemia. Hyperbilirubinaemia alone did not give rise to any cerebral lesion.

SUMMARY The COHb concentration has been determined in 35 normal non-icteric newborn infants and in 29 infants with icterus of unknown origin. It is stated that the COHb concentration in blood well reflects the degree of red cell destruction. The results indicate that there is an increased haemoglobin catabolism during the newborn period and that increased degradation of haemoglobin contributes to the neonatal hyperbilirubinaemia in cases without known haemolytic disease.

Fifty patients aged 11 to 78 years with untreated idiopathic scoliosis were studied. An increased frequency of respiratory impairment was found, especially in patients with a severe degree of scoliosis. Seven patients under 60 years were unable to work and all had thoracic curves exceeding 100°. None of the patients between 20 and 65 years of age was engaged in hard work and 22% had a disability pension, all because of respiratory impairment. A tendency to increased shortness of breath was noted with increasing curves as well as age. Dynamic and static spirometry was performed and airway closure was studied with the xenon-133 bolus technique. With increasing degrees of scoliosis there was a reduction in all lung volumes. Seventeen of 40 patients showed evidence of airway closure at lung volumes greater than functional residual capacity; 6 of these patients were under 40 years of age, and all had thoracic scoliosis exceeding 90°.

Summary One hundred and thirteen full-term infants with bilirubin values of 18 mg% or more during the neonatal period, have been followed-up at the age of 2–3 years, and compared with 51 full-term, non-icteric infants, born during the same period. Exchange transfusion was carried out in 30 of the children with jaundice. No cases of kernicterus could be demonstrated. Play audiometry was carried out in 125 children (86 with jaundice, 39 controls). No deafness of central type was revealed. At the paediatric follow-up examination no relevant abnormalities were found. Merrill-Palmer testing produced evidence of a similar I.Q. distribution among the icteric as among the non-icteric children. A cerebral lesion was diagnosed in 3 cases, but in all these another aetiology (disturbance at the time of birth) occurred in addition to hyper-bilirubinaemia. Hyperbilirubinaemia alone did not give rise to any cerebral lesion.

The diminished standing height in scoliotic patients is mainly due to an increase in the lateral curvatures of the spine. A method is described by which this reduction in trunk height can be measured. A formula for the calculation of the height loss due to the scoliosis in relation to the angulation of the primary curve is given.

Twenty-seven infants who survived intensive care during early infancy in the pioneering period of neonatal intensive care (1956-1965) were investigated after 8-17 years. The selection criterion was maintenance of a tracheotomy for more than 15 days during the first 12 months of life. A variety of clinical, physiological, radiological and psychiatric sequelae was found. Respiratory symptoms were the dominating problem during the post-tracheotomy period. The long-term follow-up revealed that these symptoms had a strong tendency to subside. At the time of the follow-up, as many as 20 children (74%) did not experience any functional impairment.

One hundred and forty school children, 75 boys and 65 girls, aged 7-18 years, underwent the following lung function tests: closing volume, slope of the alveolar plateau, maximal expiratory and inspiratory flows at 75, 50 and 25% of vital capacity, static and dynamic lung volumes. Lung volumes and maximal flows increase with height in an exponential way, the exponents varying between 2.6 and 3.1, while closing volume in per cent of vital capacity and the slope of the alveolar plateau decrease linearily with increasing height. Regression equations are given for each sex with height as determinant.

Infants who died showing the syndrome of sudden infant death (SIDS) and infants who survived attacks of lifelessness (AL) were examined in a prospective epidemiological multicentre study over 24 months covering close to 40% of all births in Sweden. Seventy SIDS cases and 34 cases of AL were observed, giving an incidence for SIDS of 0.94/1000 and for AL of 0.46/1000. This SIDS incidence is higher than that observed during the seventies. The boy/girl ratio was 1.4:1 for SIDS and 1.6:1 for AL. The age distribution for AL resembled that for SIDS. Similarities were also seen with regard to place of occurrence. Sixty per cent of the SIDS cases occurred during the daytime/evening. Twenty-nine per cent of the infants with AL had more than one apneic spell during the three-day-period around the attack, indicating a period of respiratory instability, but only 12% had such spells later on. None of the infants who had had AL died from SIDS. The possible relationship between AL and SIDS is discussed.

During the years 1965--1974, 125 cases of posterolateral diaphragmatic hernia have been operated at five departments of pediatric surgery in Sweden. The overall operative mortality was 50%. A follow-up investigation included 19 cases, where in 12 cases spirometry and in 11 cases studies of the mobility of the diaphragm were included. Physical examination revealed excellent results in most cases. Lung function studies, however, show a moderate (20--30%) reduction, which is not surprising with regard to lung hypoplasia and impaired movement of the diaphragm on the operated side. In adolescence and younger age, these patients are mostly in excellent condition; but later, when lung function is also reduced by the age factor, their neonatal condition may be of importance.

A SIDS sibling is described who showed a normal respiratory regulation at 1.5 months but who was equipped with an apnea monitor at home on psychological indications. At 3 months he had a near-miss SIDS episode. He was then found to have developed a reaction to hypoxia with appearance of periodic breathing. With theophylline this response pattern was normalized but despite theophylline medication episodes of prolonged apnea occurred.

Autoantibodies to the Tamm-Horsfall (TH) protein were analyzed in sera from 116 patients with pyelonephritis. The increases in antibody levels were limited in 23 patients with radiological detected renal damage during 31 attacks of acute pyelonephritis. 8 children with abnormally low total and/or unilateral 51Cr EDTA clearance had significantly lower IgG antibody levels to TH protein, than 14 children with normal clearance rate. All 61 children with renal damage had significantly low IgG, IgA and IgM antibody levels to TH protein 6 months after last infection as compared to the reference group. For IgG antibodies, the mean was well below -2 S.D. 12 children with increased serum creatinine had significantly lower IgG antibody levels than those with

A stepwise bicycle exercise test up to maximum was performed in a random population sample of 793 Swedish men, all aged 54 years. High respiratory rate during exercise characterized those who later suffered myocardial infarction (MI) or sudden coronary death (SD). In addition to high cholesterol, high blood pressure (BP), and smoking, low maximal performance, but not ST changes during exercise, increased the risk of MI + SD also in multivariate analysis. Pulse rate, systolic BP at both submaximal and maximal work load were positively correlated with the initial blood pressure level. BP at these work loads was also positively correlated with subsequent BP increase.

Lindberg, U., Hanson, L. a., Jodal, U., Lidin-Janson, G., Lincoln, K. and Oiling, S. (Department of Paediatrics and Departments of Immunology and Clinical Bacteriology, Institute of Medical Microbiology, University of Goteborg, Goteborg, Sweden). Asymptomatic bacteriuria in schoolgirls. II. Differences in Escherichia coli causing asymptomatic and symptomatic bacteriuria. Acta Paediatr Scand, 64:432, 1975.–Three hundred and forty-three E. coli strains isolated from the urine of patients with asymptomatic bacteriuria (ABU), symptomatic cystitis, or pyelonephritis were analysed with regard to O group distribution and sensitivity to the bactericidal effect of normal serum. Strains of O groups 1, 2, 4, 6, 7, 16, 18 and 75 were found in 31·3% in ABU, in 58.7% in cystitis and in 79·8% in pyelonephritis. Spontaneous agglutination was noted in 45.2% of ABU, 6·5% of cystitis and 1·7% of pyelonephritis strains. The strains from patients with ABU were significantly more sensitive to the bactericidal effect of normal serum than were those from patients with symptomatic urinary tract infection. In some patients with untreated ABU, changes in the characteristics of the urinary strains isolated were noted. The strains tended to become spontaneously agglutinating as well as more sensitive to the bactericidal activity of normal serum. The strains found in patients with ABU probably had an altered cell wall compared with those found in patients with symptomatic infections such that they produce fewer symptoms and possibly be less virulent.

A follow-up study, including clinical examination, X-ray and function tests, of 27 children with acute epiglottitis treated with tracheotomy at the ENT-Department, Molndal Hospital during 1971–1975 has been performed. The function tests were an important part of the investigation and included measurement with the He-dilution technique, flow—volume curves and the forced oscillation technique. No child had any detectable tracheal stenosis or any other serious per- or postoperative complication. The only complication at all was one ugly scar on the neck. The tracheotomized patient needs very little sedation and the time spent at the intensive care unit can be shorter than for those patients treated with nasotracheal intubation.

Variables obtained with the forced oscillation technique (total respiratory resistance and impedance at 2, 4 and 12 Hz) and with the forced vital capacity manoeuvre (FVC, FEV1, MMEF, MEF75, MEF50, MEF25) were used in the evaluation of the bronchial allergen challenge test in 2 groups of asthmatic children. Each method was applied in 15 provocation tests and the changes of the different variables, allowing for their respective variations, were compared with the clinical assessment. Agreement with the clinical evaluation was found in 15 of 15 occasions with the forced oscillation technique and in 12 of 15 occasions with the forced vital capacity manoeuvre. With the forced oscillation technique a bronchial reaction was detected in 6 of 10 patients at 1/10 of the allergen concentration that gave positive clinical signs and the single most sensitive variable was resistance determination at 4 Hz, with significant change in 5 of 10 cases. The forced vital capacity manoeuvre allowed detection of a bronchial reaction preceding clinical signs at a tenfold lower allergen concentration in 2 of 9 cases and the most sensitive variables were FEV1 and MEF25.

Von den Patienten mit der Sammeldiagnose Harnwegsinfektion (HWI) entwickeln nur wenige progrediente Nierenparenchymschaden. Bisher haben wir keine einfache und sichere Moglichkeit, diese Risikopatienten fruh ausfindig zu machen, um bei ihnen eine Nierenschadigung zu verhuten. Trotz zahlreicher Studien uber die HWI ist das gesicherte Wissen uber den Krankheitsablauf ungenugend und die Bedeutung von Unterschieden im klinischen Bild nur unzureichend geklart.