Fabry disease in patients with hypertrophic cardiomyopathy (HCM).

Fabry disease is an X-linked recessive lysosomal storage disorder with variable phenotype characterized by the accumulation of glycosphingolipid in various tissues. Unlike patients with the classical systemic Fabry disease entity, who present with multiple organ involvement, patients with a cardiac variant of Fabry disease are characterized mainly by myocardial hypertrophy. Therefore, the cardiac variant of Fabry disease may be defined as a cardiomyocytic storage disorder, thus, mimicking the clinical features of hypertrophic obstructive and especially non-obstructive cardiomyopathy. In patients with unexplained left ventricular hypertrophy the diagnosis of a cardiac variant of Fabry disease is performed by light- and electron microscopic evaluation of endomyocardial catheter biopsy specimens and/or serologic investigations (decreased activity of alpha-galactosidase A in plasma or leucocytes). Several studies show that between 4% and 8% of unselected patients with the clinical features of hypertrophic non-obstructive cardiomyopathy have a cardiac variant of Fabry disease. In each patient with unexplained myocardial hypertrophy concealed myocardial storage disease, especially cardiac Fabry disease has to be considered and should be ruled out or confirmed by endomyocardial catheter biopsy. This is important because of the recently reported alpha-galactosidase A enzyme replacement therapy in Fabry disease. Randomized, multicenter studies are mandatory to test the hypothesis that enzyme replacement therapy leads to a beneficial clinical effect in the cardiac variant form of Fabry disease and may prevent the progression of the disease in asymptomatic patients.

Gene expression profiles in the acutely dissected human aorta.

OBJECTIVES: heritable connective tissue abnormalities and arterial hypertension may predispose to aortic dissection. This study evaluates gene expression profiles in the acutely dissected human aorta. DESIGN, MATERIALS AND METHODS: Atlas Human Broad Arrays I, II, and III (Clontech) were used to compare gene expression in acutely dissected (6 patients) and normal ascending aortas (6 multiorgan donors). The tissues were also compared macroscopically. RESULTS: of 3537 genes analysed, 1250 (35%) were expressed in aortic tissue. For statistical analysis we focused on 627 genes, which had an intensity>0.95 of the mean patients or controls. Dissected and adjacent macroscopically intact aorta displayed similar gene expression patterns. On the contrary, 66 genes were expressed significantly different in dissected aorta, compared with undiseased control aorta of multiorgan donors. Genes, predominantly upregulated in dissection, are involved in inflammation, in extracellular matrix proteolysis, in proliferation, translation and transcription. Predominantly downregulated genes code for extracellular matrix proteins, adhesion proteins and cytoskeleton proteins. CONCLUSION: our results demonstrate for the first time the complexity of the dissecting process on a molecular level. The ultimate dissection seems to be the dramatic endpoint of a long-lasting process of degradation and insufficient remodelling of the aortic wall. Altered patterns of gene expression suggest a pre-existing structural failure of the aortic wall, resulting in dissection.

[The site and extent of arteriosclerosis. Comparative planimetric studies of the left descending coronary artery, internal carotid artery, superficial femoral artery and abdominal aorta in 104 cadavers]. / Lokalisation und Ausdehnung der Arteriosklerose. Vergleichende planimetrische Untersuchungen an der linken absteigenden Kranzarterie, den Aa. carotides internae, den Aa. femorales superficiales und der Bauchaorta von 102 Verstorbenen.

BACKGROUND: Arteriosclerosis is generally considered to be a generalized disease, involving different vascular regions to approximately the same extent. PATIENTS AND METHODS: In order to assess the extent of ateriosclerosis quantitatively, all arteriosclerotic lesions and additionally the complicated (calcified, ulcerated, thrombosed) arteriosclerotic lesions of the abdominal aorta, the superficial femoral arteries, the left descending coronary artery and the internal carotid arteries were measured by planimetry in 102 autopsies (64 male, 38 female; mean age: 62 +/- 16 years). RESULTS: Arteriosclerosis increased with age. The overall extent of arteriosclerotic lesions of each artery was classified to one of the following 4 degrees of intimal involvement (0-25, 26-50, 51-75%, 76-100%). When comparing the 4 different vascular regions of each patient we found maximal deviations by 1 degree in 34%, by 2 degrees in 41% and by 3 degrees in 20%. In only 5% of the patients studied were all arteriosclerotic lesions of the same degree. In order to analyze the complicated plaques 7 degrees were used (intimal involvement: 0, 1-10, 11-20, 21-30, 31-40, 41-50% and > 50%). In 14 patients we found no complicated plaques. The remaining 88 showed complicated lesions in at least 1 vascular region. Deviations by 1 degree were found in 22%, by 2 degrees in 32%, and by 3 or more degrees in 46%. In the paired arteries (carotid, femoral) there were no significant differences comparing the mean values of the extent of arteriosclerotic lesions on the right and left side. In many cases, however, remarkable intraindividual differences occurred. Patients with main risk factors usually had more pronounced arteriosclerotic lesions than those without. In patients who died from coronary artery disease the extent of arteriosclerotic lesions was also usually larger in the other vascular regions as compared to those patients who died from other reasons. Comparing postmortem and intravital extent of arteriosclerotic lesions some peculiarities of postmortem specimens should be considered. CONCLUSIONS: A uniform involvement of all vascular regions by arteriosclerosis occurs only rarely. Considerable intraindividual differences are the rule and a severe, generalized uniform affection is an exception. This, however, does not exclude in patients with severe arteriosclerosis of one region that a larger involvement of other vascular regions may also occur, as this was found for patients with severe arteriosclerosis in coronary arteries. Regarding the extent of arteriosclerosis there are artery- and additional localization-specific features.

Surgical treatment of 50 carotid dissections: indications and results.

PURPOSE: This article analyzes the course of 48 patients with 49 chronic carotid dissections (who were treated surgically at our institution after a median anticoagulation period of 9 months because of a persistent high-grade stenosis or an aneurysm) and the course of one additional patient with acute carotid dissection (who underwent early operative reconstruction 12 hours after onset because of fluctuating neurologic symptoms). METHODS: All medical and surgical records and imaging studies were reviewed retrospectively. All histologic specimens were reevaluated by a single pathologist to assess the cause of dissection. Follow-up of 41 patients (85%) after 70 months (range, 1-190 months) consisted of an examination of the extracranial vessels in the neck by Doppler ultrasound scanning and a questionnaire about the patients' medical history and their personal appraisals of cranial nerve function. RESULTS: Seventy percent of the dissections had developed spontaneously; 18% were caused by trauma; 12% of all patients (22% of the women) had a fibromuscular dysplasia. Indication for surgery was a high-grade persisting stenosis and a persisting or newly developed aneurysm. Flow restoration was achieved by resection and vein graft replacement in 40 cases (80%) and thromboendarterectomy and patch angioplasty in three cases (6%). Gradual dilatation was performed and effective in two cases (4%). Five internal carotid arteries (10%) had to be clipped because dissection extended into the skull base. One patient died of intracranial bleeding. Five patients (10%) experienced the development of a recurrent minor stroke (ipsilateral, 4 patients; contralateral, 1 patient). Cranial nerve damage could not be avoided in 29 cases (58%) but were transient in most of the cases. During follow-up, one patient died of unrelated reasons, and only one patient had experienced the development of a neurologic event of unknown cause. CONCLUSION: Chronic carotid dissection can be effectively treated by surgical reconstruction to prevent further ischemic or thromboembolic complications, if medical treatment for 6 months with anticoagulation failed or if carotid aneurysms and/or high-grade carotid stenosis persisted or have newly developed.

Impact of school and vocational education on smoking behaviour: results from a large-scale study on adolescents and young adults in Germany.

While level of school education has been related to prevalence of cigarette smoking in a number of studies, less information is available on the role of vocational education and related occupational contexts. This study analyses the relative contribution of different types of educational experience to explaining prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees in Germany. A standardized questionnaire on smoking behaviour and educational performance was applied in 27 educational centers across the country, covering a total of 20,527 respondents (77.3% of the original sample; women: 59.5%, men: 40.5%). Bivariate analysis revealed a high prevalence of current smokers among vocational trainees, both men (51.2%) and women (49.4%). Men were more likely to be heavy smokers, especially with increasing age. In both sexes, prevalence of smoking was particularly high in the following occupational groups: hairdressers, butchers, painters, service personnel (hotels, restaurants), shop assistants/sellers and cooks. Multivariate analysis taking educational level, type of vocational training (occupation), age, sex and urban-rural background into account revealed the highest prevalence odds ratios (POR) of smoking in subjects with the lowest educational level (POR = 5.19 for men and 4.56 for women). Even stronger effects were observed with smoking intensity (> or = 20 cigarettes/day): in men with the lowest educational level the risk of being a heavy smoker was 8.92, and in women 13.54 compared to subjects with a high-school leaving qualification. Poor school education must be considered the relatively strongest predictor of prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees. Preventive efforts should be directed at specific target groups such as those identified by this study.

[Transmyocardial laser revascularization--morphologic, pathophysiologic and historical principles of indirect revascularization of the heart muscle]. / Transmyokardiale Laserrevaskularisation--morphologische, pathophysiologische und historische Grundlagen der indirekten Revaskularisation des Herzmuskels.

Under normal conditions the coronary system of the human heart is not hermetically isolated from the surrounding structures nor the ventricles, but is in various ways connected to the adjacent arteries and the cardiac chambers. These natural connections have been models for most surgical efforts to revascularize the myocardium. Numerous anastomoses between the aorta and the coronary branches functionally resemble aorto-coronary bypass grafts. Coronaro-ventricular anastomoses do also exist in the myocardium and therefore transmyocardial laser revascularization should allow blood to penetrate from the ventricle into the myocardium. This process should not be called "reptilization" of the human heart, as in large reptilian hearts the nutrition of an extensive amount of myocardium only by diffusion is highly unlikely. Transmyocardial laser revascularization results in a relevant reduction of clinical symptoms and an increase of exercise capacity in approximately two thirds of the patients treated. Objective data of enhanced myocardial perfusion as assessed by positron emission tomography and stress echocardiography has up to now only been presented by smaller studies. Open laser channels are rarely visualized by conventional ventriculography for the limited resolution of the technique. Possibly contrast-echocardiography may offer a more appropriate option to proof the systolic filling of the laser channels, as recently reported in patients. This would allow a correlation between clinically successful revascularization and functioning channels in contrast to an early or late failure due to the closure of the channels. As to the current opinion, transmyocardial laser revascularization is no alternative to established medical, interventional or surgical therapies but may in conjunction with bypass surgery or as a sole procedure offer a new option for those patients, who were recently considered to be refractory to conventional treatment. Experimental studies in particular should contribute to the understanding of therapeutic mechanisms and lead to standardized indications in the surgical treatment of end-stage coronary heart disease. Even though in transmyocardial laser revascularization the perioperative risk depends mainly on the degree of cardiac disease and the overall state of the patient, and impaired left ventricular function is per se no exclusion criterium, if viable myocardium is detectable. Many questions concerning indications, long-term prognosis and pathophysiological mechanisms are still open to discussion and have to be answered in order to find standardized applications for treatment of end-stage coronary artery disease.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): response to methotrexate and mercaptopurine.

We report a 3-year-old girl presenting with bilateral cervical lymph node enlargement persisting for > 3 months. Leukocytosis, elevated erythrocyte sedimentation rate, a marked hypergammaglobulinemia, and a moderate hepatosplenomegaly were also found. The diagnosis of sinushistiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, was established histologically by the demonstration of characteristic sinushistiocytosis with lymphocytophagocytosis. Treatment was started with high dose steroids, and a decline of lymph node size and a normalization of laboratory parameters occurred. However, when steroids were tapered, lymph node size rapidly reincreased. Chemotherapeutic treatment was started using etoposide, which was completely ineffective. Therefore, treatment was changed to a combinatory low dose methotrexate therapy and 6-mercaptopurine for 4 months. Whereas a prompt and complete remission was reached, single 6-mercaptopurine therapy was maintained and treatment has been discontinued after a total of 2 years. The child has remained healthy for 7 years. This case would recommend the use of methotrexate and 6-mercaptopurine for treatment of complicated SHML.

Spatial heterogeneity of blood flow in the dog heart. I. Glucose uptake, free adenosine and oxidative/glycolytic enzyme activity.

The spatial heterogeneity of myocardial perfusion and metabolism was studied in 11 anaesthetized dogs under resting conditions. In each heart local myocardial blood flow was assessed using the tracer microsphere technique in 256 samples (mean mass: 83.1 mg) taken from the left anterior ventricular wall. In the same samples, the following biochemical parameters were determined: accumulation of [3H]-deoxyglucose (a measure of glucose uptake), free cytosolic adenosine (S-adenosylhomocysteine accumulation technique, a measure of tissue oxygenation and a possible mediator of blood flow regulation), and the specific activities of oxidative (citrate synthase, cytochrome-c-oxidase) and glycolytic (hexokinase, phosphoglycerate kinase) enzymes. Capillary density and mitochondrial and myofibril volume densities were determined by morphometry. Myocardial perfusion in each sample (average 0.77 ml min-1 g-1) varied between 0.1 and 2.5 times the mean (coefficient of variation 0.30+/-0.02). [3H]-deoxyglucose was deposited locally in proportion to perfusion. Samples showing low flow (<0.2 ml min-1 g-1) did not exhibit increased levels of cytosolic adenosine. The specific activities of the oxidative and glycolytic enzymes, however, were uniformly distributed between low and high flow areas. Furthermore, capillary density and mitochondrial and myofibril densities were similar in high and low flow regions. The results show firstly that local glucose metabolism in the heart occurs in proportion to local blood flow, suggesting that high flow regions have a higher than average metabolic rate. Secondly, regions of low flow are not compromized by critical oxygenation and most likely have a lower than average oxygen demand and finally, the homogeneous distribution of oxidative and glycolytic enzymes, as well as the homogeneous myocardial ultrastructure, suggest that areas with high and low blood flow under resting conditions may increase their metabolic rate to similar levels when required.

Color-flow Doppler-assisted duplex imaging fails to detect ulceration in high-grade internal carotid artery stenosis.

PURPOSE: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, plays a key role in the destabilization of internal carotid artery stenosis. Until now, the validity of color-flow Doppler-assisted duplex imaging in detecting such pathoanatomically defined plaque surface abnormalities is unclear. METHODS: We prospectively determined the interobserver reliability and validity of detecting plaque ulceration by means of preoperative color-flow Doppler-assisted duplex imaging in 43 consecutive patients with high-grade (> or = 70%) internal carotid artery stenosis, comparing these ultrasonographic findings with pathoanatomic evaluations of the corresponding endarterectomy specimens. RESULTS: Interobserver reliabilities for detecting carotid plaque ulceration were kappa= 0.57 for ultrasonography and kappa = 0.82 for the pathologic reference method. Color-flow Doppler-assisted duplex imaging (observer consensus) failed to detect pathoanatomically defined ulceration (chi square = 0.43; p = 0.51). Likewise, sensitivity, specificity, overall accuracy, and positive predictive value were poor (33%, 67%, 56%, and 46%, respectively). CONCLUSIONS: We conclude from our data that color-flow Doppler-assisted duplex imaging is not a reliable or valid means to identify plaque ulceration in high-grade carotid artery lesions.

[An interventional study against cigarette smoking among Dusseldorf high school students 1992-94]. / Interventionsstudie gegen das Zigarettenrauchen von Düsseldorfer Hauptschülern 1992-94.

Between 1992 and 1994, an interventional program was held in the secondary schools ("Hauptschulen") in Düsseldorf contra cigarette smoking. The program was conducted in the following way. Half of the schools (intervention schools) were involved in this program which consisted of 15 sessions. The other schools served as control groups. During the first year of this program school-teachers and a physician taught students about the function and the abilities of the healthy heart and lung. The students developed adversions to smoking. In addition, the students learned by role-plays how to say no to a cigarette without embarrassment. These role-plays were videotaped. During the second year of this program the role-plays were repeated and teaching about the heart and the lungs was augmented. Also, every student got the opportunity to meet and talk with a famous athlete. Furthermore, smoking-cessation programs were hold in four intervention schools. The program started in the sixth grade with a questionnaire administered to 878 schoolchildren. During this time the average age of the children was 13 years. Because of a large fluctuation, the questioning could be repeated with only 630 of these children (71.8%) after 2 years. At the end of the study the number of smokers had increased two times greater in the control schools than in the intervention schools (boys: 20.5% points vs 9.4% points; girls: 44.3% points vs 21.0% points). Obviously, the continuation of the program during the second year was important in making the program successful. Among the participants of the intervention program there was a trend to stop smoking. But the program was not able to prevent non-smokers from starting the habit. On the other hand, of the children who started smoking during the program, more girls in the intervention schools quit smoking than in the control schools. At the end of the program more girls than boys (mean age 15 years) smoked. Almost one-fourth of the boys, and from the control schools one-third of the girls were already daily smokers. The smokers obtained cigarettes from kiosks, from friends, vending machines, vendors or shops, but seldom from their homes.

[Repeated ingestion with suicidal intent of potentially lethal amounts of thallium]. / Wiederholte Ingestion potentiell letaler Thalliummengen in suizidaler Absicht.

30 minutes after drinking half a cup of rat poison a 16-year-old girl was admitted to hospital. In addition to various enteric detoxification measures forced dialysis was instituted and, after the urinary thallium level had become known (9 mg/l), haemodialysis was begun and ferric ferrocyanide (Prussian blue) administered (0.5 mg daily for six days). She had no symptoms at any time. After 10 days she was discharged. Five days after discharge she was again admitted, with colic-like abdominal pain, vomiting, paraesthesias of the hands and feet, and in a state of agitation. She had once again ingested rat poison, about one cup. Physical examination revealed little of consequence, except diffuse alopecia. Urinary thallium concentration was 37 mg/l. In the electrocardiogram the P-R interval was shortened to 0.11 s and T waves inverted in leads III and V1. Electronmicroscopy of cardiac and skeletal biopsies revealed lipid droplets, increased sarcoplasm and widening of some of the tubules. Treatment consisted of haemodialysis, forced diuresis (1 l urine/h), administration of ferric ferrocyanide, orthograde intestinal infusions and potassium substitution (serum level: 5 mmol/l). After 28 days the patient was discharged into psychiatric care.

Malignant fibrous histiocytoma of the heart--case report of a rare left-atrial tumor.

The present report describes the case of a 57-year-old patient with malignant fibrous histiocytoma of the left atrium operated on for a suspected atrial myxoma. Surgery was performed as radically as possible and included resection of the atrial wall. Clinical investigation and echocardiography performed 29 months after surgery revealed no signs of tumor recurrence. Diagnostic procedures, topography, pathohistology as well as options for therapy are discussed with regard to the latest literature. A radical surgical approach represents the only effective therapeutic measure. Owing to a lack of sufficient experience, there is no additional therapeutic recommendation on hand. Neither radiation nor chemotherapeutic treatment concepts have proved efficient. Echocardiography represents the best examination procedure for both diagnosis and follow-up in patients with cardiac tumor.

[Dysplastic intramyocardial arteries with subaortic septum in patients with hypertrophic obstructive cardiomyopathy]. / Dysplastische intramyokardiale Arterien im subaortalen Septum von Patienten mit hypertroph-obstruktiver Kardiomyopathie.

Abnormal, dysplastic intramyocardial arteries were reported in autopsied hearts of hypertrophic cardiomyopathy. To elucidate their significance, the operatively-excised myectomy specimens of 24 patients with hypertrophic-obstructive cardiomyopathy (HOCM), of 18 patients with valvular aortic stenosis and of 10 postmortem normal hearts were investigated. Eight patients with HOCM had dysplastic intramyocardial arteries (greater than 100 microns external diameter) as well as dysplastic arterioles (less than 100 microns external diameter). The value of the scores for the thickness and fibroelastosis of the media was nearly doubled, the tunica intima was frequently thickened, and the lumen was relatively reduced in dysplastic vessels. Neither in controls nor in aortic stenosis dysplastic arteries were found. Volume density of patchy fibrosis (scars) was increased in patients with dysplastic arterial vessels (HOCM II) (7.2 +/- 4.4 Vv%) (p less than or equal to 0.05) as compared with HOCM without dysplastic vessels (HOCM I) (0.8 +/- 2.3 Vv%), with aortic stenosis (0.9 +/- 1.6 Vv%) or with controls (0 Vv%), Patients with HOCM II were significantly (p less than or equal to 0.05) younger (30 +/- 13 years) than those with HOCM I (53 +/- 12 years), aortic stenosis (56 +/- 12 years), or controls (63 +/- 21 years). The anterior septum was significantly thicker in HOCM II (29 +/- 7 mm) than in HOCM I (22 +/- 4 mm), in aortic stenosis (19 +/- 3 mm), or in controls (12 +/- 2 mm). Syncopes were complained by about 75% (6/8) of patients in HOCM II, by 54% (9/16) in HOCM I, and by 44% (8/18) in aortic stenosis (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Endomyocardial biopsy in infants and children: experience in 60 patients.

In 60 children, aged between 1 month and 22 years (median 3.54 years) and with a body weight of 3-67 kg (median 12.6 kg), transvascular endomyocardial biopsy (EMB) was performed from the right (35 children) or left ventricle (30 children). The specimens were investigated by light and electron microscopy. There were three indications for biopsy: (1) poorly functioning, dilated left ventricle (seven patients with endocardial fibroelastosis, 16 with dilated cardiomyopathy, six from healing/healed or chronic myocarditis); (2) unexplained left ventricular hypertrophy (10 with hypertrophic cardiomyopathy, four with secondary hypertrophy, three with storage diseases); (3) to answer certain questions in eight children (four with hypoxic and two with cytoxic myocardial damage). Retrospectively, there were five nonindicated biopsies. There were no serious complications. Biopsies were diagnostic in 11.7% of cases, helpful in 71.7%, and of no help in 16.6%. Thus even in childhood endomyocardial biopsy is a diagnostic tool which can add useful information on the etiology or pathogenesis of an underlying myocardial disease.

Well-differentiated papillary mesothelioma of the peritoneum: a borderline mesothelioma. Report of two cases and review of literature.

Well-differentiated papillary mesothelioma (WDPM) is considered to be a distinct subtype of peritoneal mesothelioma. Although the WDPM is usually qualified as benign, the natural history of this lesion has not been clearly established. This report relates to two WDPMs which were found incidentally. In a 51-year-old man the WDPM developed over a period of 5 years into a typically malignant diffuse mesothelioma. Thus, although the WDPM morphologically lacks signs of malignancy, it should be regarded as a borderline mesothelioma.

[Pathologic anatomy of congenital heart defects]. / Pathologische Anatomie angeborener Herzfehler.

The heart of neonates and infants with marked hypoplastic left- or right-heart-syndrome contains--despite the very low weight in the hypoplastic parts--myocytes of approximately the same size as in the non-hypoplastic ventricular wall. This means that the number of cells is not constant, because in contrast to the regularly developed right and left ventricular walls, the total number of myocytes in the hypoplastic parts is significantly lower. Hypertrophy of the myocardium in congenital heart disease shows histological and ultrastructural findings that are similar to those found in other forms of myocardial hypertrophy. Hypertrophy is reversible after successful surgical correction. However, regression is often incomplete, especially if surgery is delayed until adolescent or adult life. During this time scar formation in the hypertrophic ventricular wall may develop. In addition to these scars, also postoperative scar formation may contribute to the origin of arrhythmias. In hearts with cyanotic and non-cyanotic vitia distances between capillaries and capillary lengths are approximately the same as in normal hearts. Obviously, these parameters are genetically determined.

[Secondary diseases of the heart muscle and their differential diagnosis in childhood]. / Sekundäre Herzmuskelerkrankungen und ihre Differentialdiagnose im Kindesalter.

Possible causes of specific cardiac muscle disease, diagnosis, follow-up and the therapeutic management are discussed on the basis of a series of cases. 8 out of 30 patients who showed the clinical picture of dilative cardiomyopathy (DCM) were found to have a specific cardiac muscle disease. 4 patients had DCM following adriamycin therapy. Fibromuscular dysplasia with renal hypertension, thalassaemia major with secondary haemosiderosis, long-overlooked and untreated athyroidism each caused one case of dilative specific cardiac muscle disease. Once DCM was preceded by the Kawasaki syndrome for over 2 years. Amongst 47 patients with hypertrophic cardiomyopathy there were two children who had undergone ACTH treatment, 6 children born of diabetic mothers, 4 cases of Pompe's disease, and one patient with hypothyroidism resulting in reversible hypertrophy of the cardiac muscle. Different neurodegenerative diseases were associated with cardiac muscle disease in 4 cases, partly dictating the clinical course. Extremely rare was the development over 6 years of cardiac hypertrophy following a burns injury.

Ultrastructural findings in endomyocardial biopsy of patients with Kearns-Sayre syndrome.

Kearns-Sayre syndrome is clinically defined by progressive external ophthalmoplegia, atypical retinitis pigmentosa and the potential occurrence of complete atrioventricular (AV) block. Right septal endomyocardial biopsy specimens from nine patients (four men and five women with a mean [+/- SD] [corrected] age of 36.3 +/- 14.4 years) with chronic progressive external ophthalmoplegia and mitochondrial skeletal myopathy were studied. Three patients had atypical retinal pigmentation. An atrioventricular or intraventricular conduction defect was observed in five patients. A pacemaker was prophylactically implanted in one patient because of abnormal conduction distal to the His bundle. Ultrastructural investigations revealed mitochondriosis in many heart muscle cells and an increased variability of mitochondrial form and size in all patients. In seven patients, 0.4 to 2.1% of all examined myocytes contained exclusively abnormal mitochondria. Three main types were observed: huge, mainly round mitochondria with concentric cristae; large, round or oval mitochondria with transverse or curved cristae; and small, vacuolated mitochondria. The volume density of myofibrils was reduced (41.9 +/- 11.1 compared with the normal value of 56.5 +/- 2.5 volume density [in percent], p less than 0.01) in these myocytes. Increasing numbers of vacuolated mitochondria correlated significantly with a reduction of myofibrils (r = -0.64, p less than 0.01). The data suggest that the ventricular myocardium of most patients with complete and even incomplete Kearns-Sayre syndrome is affected by disseminated mitochondrial cytopathy.

[The combination of atrial myxoma and multiple skin myxomas: a characteristic symptom complex?]. / Kombination von Vorhofmyxom und multiplen Hautmyxomen: ein eigener Symptomenkomplex?

In 1980, a then 7-year-old boy from Yugoslavia had an atrial myxoma removed. Since then there have been no abnormal cardiac signs or symptoms. Between 1982 and 1986 five cutaneous myxomas in the trunk region were removed. None of the tumours had histological signs of malignancy. These observations can be fitted into the symptom complex (described in 1985 by Carney et al.) of cardiac myxoma, cutaneous myxoma, changes in skin pigmentation, and abnormal endocrine functions--although not all signs need be present together. A disposition towards the development of myxomatous tumours is to be assumed in these patients. One should, therefore, always suspect an occult cardiac myxoma in the presence of multiple cutaneous myxomas. Appropriate diagnostic measures need to be taken before the typical and sometimes lethal consequences of a cardiac myxoma have occurred.