Diminished prolactin response to thyrotropin and insulin in anorexia nervosa.

Although patients with anorexia nervosa (AN) have a variety of endocrine disturbances, it generally is believed that the PRL response to stimulation is not altered in this disorder. We measured basal serum PRL values and serum PRL values after stimulation either with TRH (200 micrograms/m2) or with insulin (4 IU/m2) in 27 women with AN and 9 normal women. Basal values in anorexic women and normal women did not differ significantly, whereas all stimulation variables (mean PRL stimulation values, maximum PRL values, sum of increments, and area under the stimulation curve) were significantly lower in AN patients than in normal women. Furthermore, after TRH stimulation most of these variables correlated positively with the percentage of ideal body wt of the patients, indicating that the diminished PRL response was wt dependent. This diminished PRL response in the patients may accompany starvation and low estradiol values. Both conditions per se are known for their association with diminished PRL responses. Hence, no hypothesis which posits hypothalamic dopamine excess as the basic disturbance in AN seems justified. Moreover, diminished PRL responses in AN are not consistent with an assumption of hypothalamic dopamine depletion in this disorder.

Inspiratory muscle training in patients with Duchenne muscular dystrophy.

PURPOSE: The aim of this study was to assess the usefulness of a specific inspiratory muscle training in Duchenne muscular dystrophy (DMD). PATIENTS AND METHODS: Fifteen patients with DMD started 6 months of training the inspiratory muscles and 15 patients served as a control group. Pulmonary and inspiratory muscle function parameters were assessed 3 months before and at the beginning of training, in the first and third month of training, at the end, and 6 months after its cessation. Maximal sniff assessed esophageal and transdiaphragmatic pressure values served as indices for global inspiratory muscle strength and diaphragmatic strength, respectively. Inspiratory muscle endurance was assessed by the length of time a certain inspiratory task could be maintained. RESULTS: In 10 of the 15 patients, respiratory muscle function parameters improved significantly after 1 month of training. Further improvements were to be seen after 3 and after 6 months. Even 6 months after the end of training, those effects remained to a large extent. In the other five patients, there was no such improvement after 1 month of training, which was therefore discontinued. All these five patients had vital capacity values of less than 25 percent predicted and/or PaCO2 values of more than 45 mm Hg. The 15 control patients had no significant change in their respiratory muscle function parameters. CONCLUSION: We conclude that a specific inspiratory muscle training is useful in the early stage of DMD.

2 Years' experience with inspiratory muscle training in patients with neuromuscular disorders.

PURPOSE: The aim of our study was to assess the long-term effects of specific inspiratory muscle training (IMT) in patients with neuromuscular disorders (NMDs) who have various degrees of respiratory impairment. PATIENTS AND METHODS: Twenty-seven patients with NMDs (Duchenne's muscular dystrophy, 18 patients; spinal muscular atrophy, 9 patients) underwent 24 months of IMT. Patients were divided into three groups according to their vital capacity (VC) values. VC was measured as the parameter for the respiratory system involvement of the disease. Maximal inspiratory pressure (PImax) was assessed as the parameter for respiratory muscle strength, and the results of the 12-s maximum voluntary ventilation test (12sMVV) were assessed as the parameter for respiratory muscle endurance. Pulmonary and inspiratory muscle function parameters were assessed 6 months before training, at the beginning of training, and then every 3 months. RESULTS: The PImax values improved in group A (VC, 27 to 50% predicted) from 51.45 to 87.00 cm H(2)O, in group B (VC, 51 to 70% predicted) from 59.38 to 94.4 cm H(2)O, and in group C (VC, 71 to 96% predicted) from 71.25 to 99.00 cm H(2)O. The 12sMVV values improved in group A from 52.69 to 69.50 L/min, in group B from 53.18 to 62.40 L/min, and in group C from 59.48 to 70.5 L/min. For all three groups, there was a significant improvement of PImax (p < 0.007) and 12sMVV (p < 0.015) until the 10th month when a plateau phase was reached with no decline in the following month until the end of training. CONCLUSION: With IMT, respiratory muscle function can be improved in the long term of up to 2 years.

A combination of spastic paraparesis, polyneuropathy and adrenocortical insufficiency-a childhood form of adrenomyeloneuropathy.

This report describes a combination of spastic paraparesis and symmetrical sensory motor polyneuropathy with a pathological response to the ACTH test in the case of a 16 year-old boy and a borderline response to the ACTH test in the case of his 8-year-old sister. Another sister, aged 14, showed only a pathological response to ACTH testing, the neurological status being unremarkable. The EEG was normal in all three children examined. Visually evoked potentials were borderline in the case of the boy and normal in the case of the clinically involved sister. Although on examination by light microscopy the sural nerve proved to be normal, the clinical diagnosis of adrenomyeloneuropathy (AMN) in its juvenile form may be assumed, in view of the clinical symptoms and the evidence of adrenocortical insufficiency revealed by the ACTH test.

Accumulation of very long chain fatty acids is common to 3 variants of adrenoleukodystrophy (ALD). "Classical" ALD, atypical ALD (female patient) and adrenomyeloneuropathy.

Fatty acids of cholesterol esters were analyzed by gas chromatography in affected CNS white matter of 3 variants of ALD ("classical" ALD, atypical ALD (adult female) and AMN) and of 10 controls with myelin breakdown of an etiology other than ALD. In all 3 ALD variants a marked accumulation of very long chain fatty acids (VLFA) as compared to control material was observed. This was due to the accumulation mainly of saturated C24-C32 fatty acids, particularly of C26:0, C25:0 and, to a lesser extent, C24:0 and C27:0 fatty acids. Our results demonstrate for the first time an accumulation of VLFA in an adult female patient (atypical ALD), who probably is an ALD heterozygote rather than a variant of AMN, and confirm and extend earlier findings in classical ALD and AMN, respectively. It appears that ALD may be a single nosological entity with clinically and morphologically different variants sharing specific ultrastructural (accumulation of paired leaflets) and neuro-biochemical (accumulation of VLFA) diagnostic markers.

Excretion of biogenic amine metabolites in anorexia nervosa.

Urinary metabolites of catecholamines and indoleamines have been investigated in 16 patients with anorexia nervosa (AN) and 13 controls using a HPLC-method. Vanillic mandelic acid, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, 3,4-dihydroxyphenylacetic acid, 5-hydroxyindole acetic acid and indoleacetic acid were significantly decreased in the pre-treatment phase. In four patients long-term treatment including parenteral and enteral nutrition together with psychological methods resulted in an increase in the levels of these substances and this correlated with increased weight gain and urinary creatinine. It is concluded that both central and peripheral disturbances are involved in AN, particularly with regard to biogenic amine metabolism.

Detection of adrenoleukodystrophy by increased C26:0 fatty acid levels in leukocytes.

Very long chain fatty acids of peripheral blood leukocytes were analyzed by gas chromatography in nine members of a family including two hemizygotes and one obligate heterozygote for adrenoleukodystrophy (ALD), as well as in twelve controls. Comparative investigations were done in cultured fibroblasts. Elevated C26:0 levels were observed in leukocytes and fibroblasts of ALD hemizygotes. The obligate heterozygote displayed a clear-cut increase of C26:0 concentration in leukocytes but not in fibroblasts. Determination of C26:0 in leukocytes may serve as diagnostic tool in the detection of ALD gene carriers.

[Ineffectiveness of diltiazem in Duchenne muscular dystrophy: a placebo-controlled double-blind study]. / Fehlende Wirksamkeit von Diltiazem bei Duchenne-Muskeldystrophie: eine placebo-kontrollierte Doppelblindstudie.

In a randomized double-blind study the clinical efficacy of the calcium channel blocker, diltiazem was compared to that of a placebo on the clinical course of Duchenne's dystrophy (DMD) over a 12-month period. Altogether 30 patients, mostly in an advanced state of the disease, were evaluated. The 17 patients in the diltiazem group received 90-360 mg diltiazem per day according to their body weight; the 13 patients of the placebo group received the equivalent amount of a placebo. No significant difference was detected between the two groups regarding muscular power, muscle state, muscular functional ability (Vignos), serum myoglobin and serum creative phosphokinase.

[Basal gonadotropin level and gonadotropin response to stimulation in patients with anorexia nervosa]. / Basale Gonadotropinspiegel und Gonadotropinstimulierbarkeit bei Patientinnen mit Anorexia nervosa.

Serum gonadotropin (GN) levels were examined before and after stimulation with luteinizing-hormone-releasing-hormone (LHRH) (100 micrograms/m2 body surface) in 25 female patients with anorexia nervosa (AN) and in 19 healthy young women. 12 patients were reexamined after clinical improvement. Basal GN levels and the luteinizing hormone (LH) response to stimulation were significantly lower in patients than in controls, whereas the response of follicle-stimulating hormone (FSH) to LHRH was normal. The GN response in patients was weight dependent, displaying an inverse correlation to the weight loss. After clinical improvement the GN response was significantly higher than in the acute stage of the disease. The data demonstrate that the activity of the hypothalamic-hypophyseal-gonadal (H-H-G) axis, evaluated on the basis of the GN response to LHRH, depends on the body weight of the patient. Hence, the alteration in activity of the H-H-G axis seems to be a consequence, and not the cause of AN.

The incidence of Duchenne muscular dystrophy in eastern Austria. The controversy regarding CK screening.

The incidence of Duchenne muscular dystrophy (DMD) in Eastern Austria was investigated. From 1968-1983 302,643 boys were born, 68 of whom were subsequently identified as having Duchenne muscular dystrophy. The overall incidence with respect to live male births is 1:4451 (22.5 x 10(-5)). The mean age of the children at the occurrence of the first symptoms was 3.1 (SD 1.1), at first presentation to a physician 4.8 (SD 2.0), and at diagnosis 5.5 (SD 1.7) years. DMD occurred in 56 families. These families had 73 boys with DMD, 5 of whom were born before or after the observation period. Thirteen families had two affected boys and two families even had three. In 4 families a second boy suffering from DMD was born although the diagnosis of DMD had already been established in another close male relative. If a newborn male screening system had been in function, 13 cases could possibly have been avoided. However, since in 3 cases the affected siblings were not both born within the observation period, they were excluded, leaving 10 cases. Hence, a prevention rate of 14.7% might have been achieved through creatine kinase (CK) screening and genetic counselling.

[Molecular biology in diagnosis and detection of deletion in Duchenne muscular dystrophy]. / Molekularbiologische Diagnostik und Deletionsnachweis bei Duchennescher Muskeldystrophie.

For the purpose of carrier identification and genetic counselling we investigated deletions of the Duchenne muscular dystrophy (DMD) gene in three families of patients with Duchenne muscular dystrophy. Using a limited number of probes of the DMD cDNA in Southern blots, we detected a deletion in only one patient. Additional methodology is necessary to warrant reliable identification of carriers and exact prenatal diagnosis.

[The prognosis of juvenile myasthenia gravis]. / Prognose der juvenilen Myasthenia gravis.

In 18 patients with juvenile myasthenia gravis (MG) the mean age of disease-onset was 12.1 years. The mean observation time was 6.8 years. After classification with regard to the clinical severity of the disease (Ossermann, 1958) 4 patients (22%) could be assigned to type I, 10 patients (56%) to type II A, 2 patients (11%) to type II B, and 2 patients (11%) to type III. 14 patients (77%) could be assigned to type I and type II A, both of them rather benign types. All 4 male patients belonged to this group. The tensilon test, investigated in 15 patients, showed a positive result in 13 cases (87%). The repetitive stimulation was done in 13 patients and was positive only in 6 cases (46%). Investigations in MG-patients without limitation of age showed positive results in about 70%. Increased levels of acetylcholin-receptor-antibody were found in 10 of 11 patients (91%). In 8 patients with the diagnosis MG, type II A and III, a thymectomy was done, 16 patients received cholinesterase-blockers, 1 patient with type II A, and both patients in group III received additionally azathioprin. In 1 patient with type III plasmapheresis was done. 75% of all thymectic patients showed a remission or improvement. Related to all 18 patients we found in 16 cases (89%) a remission or correction of the symptoms. In summary the prognosis in the group of our patients with juvenile myasthenia gravis was good.

[Anorexia nervosa in male adolescents. I: Clinical findings]. / Anorexia nervosa bei männlichen Jugendlichen. Teil I: Klinische Befunde.

In six male patients with anorexia nervosa (a.n.) we describe the anamnestic data, the course of disease and progress in therapy. We also present the results of psychological testing and organic investigations. The mean weight loss at the time of first investigation at the clinic was 70% of ideal body weight. The mean time between first symptoms of a.n. and the first admission at the clinic was 19 months. The psychopathological status showed in all six patients symptoms of obsessive, in two patients additional of depressive behavior. This finding is in contradiction to the result in 61 female patients with a.n., where hysteriformic and depressive symptoms predominated (36). The follow up time reached from 18 to 84 months (mean 49 months). At the time of last control-investigation we found only one patient restored to health, two patients showed a positive progression. In two patient the psychiatric situation was nearly unchanged, one patient committed suicide. The three patients without positive therapeutic effect were three times respectively six times at the inpatient department and discontinued two times or also three times the psychotherapy. In our experience the course of disease in male patients with a.n. seems to be more serious and more resistant to therapy than in female patients.

Adenine metabolism in erythrocytes of patients with Duchenne muscular dystrophy.

The primarily metabolic defect in Duchenne muscular dystrophy (DMD) is still unknown. In addition to the disturbance of muscle cell and erythrocyte membranes of patients with DMD an impairment of purine metabolism has been suggested on the basis of the decreased ATP content of the muscle fibers. To avoid the leakage of adenine nucleotides from cells, allopurinol has been administered to DMD patients to increase the formation of adenine nucleotides via the salvage pathway. The purpose of this study was to investigate this hypothesis of an effect of allopurinol on the formation of adenine nucleotides. Furthermore, the clinical status of allopurinol-treated DMD patients was examined. Biochemical studies were performed on erythrocytes of 19 patients with DMD, and adenine nucleotide concentrations and the incorporation of 14C-adenine into purine nucleotides were assessed before and after 6 months of allopurinol therapy. No improvement of the clinical status could be observed, although a slight increase in ATP formation was seen.

Fatty acid patterns in brain, fibroblast, leukocyte and body fluid lipids in adrenoleukodystrophy.

Fatty acid patterns of certain tissue and body fluid lipids of ALD and control cases were investigated by thin layer and gas chromatography. A high percentage (55.2%) of VLFA was found in the ALD brain white matter cholesterol esters; this was mainly due to increased proportions of 26:0, 25:0, 26:1 and greater than 26 C fatty acids. The percentage of VLFA in the white matter cholesterol esters of pathological controls with myelin breakdown of different etiology was low (0.4-7.1%). In the fibroblast total lipids of an ALD patient an increase of 26:0 and 25:0 fatty acids was found. Moderately increased proportions of hexacosanoic acid were observed in the leukocyte total lipids of 2 severely affected ALD patients, but not in a slightly as well as in a possible affected case. No accumulation of VLFA was detected in cholesterol ester, triglyceride and free fatty acid fractions in the CSF of an ALD patient and in ALD serum sphingomyelin. Our results substantiate the specificity of VLFA accumulation in the white matter cholesterol esters of ALD brain and lend some further evidence to the view that a generalized impairment of VLFA metabolism seems to be present in this disease.

EEG, pattern-evoked potentials and nerve conduction velocity in a family with adrenoleucodystrophy.

In a family with 8 children one case of adrenoleucodystrophy (ALD), verified by autopsy, 2 cases with clinical signs of ALD and four other clinically healthy subjects with pathological ACTH tests were found. As an initial sign in the EEG, temporo-occipital slowing occurred. Further EEG studies showed spread of the primary local abnormalities, indicating diffuse brain dysfunction during progression of the disease. Terminal EEG flattening may be characteristic for late stages of the disease. No correlation could be established between lateralization, paroxysms and actual stage of the disease. Abnormal EEGs occurred not only in clinically and subclinically affected male patients, but also in a girl, who might be a carrier of ALD. Visual evoked potentials showed an increased latency of the P2 wave in the clinically, and in one subclinically, affected subjects. Motor nerve conduction velocity was reduced in only 2 patients. Antidromic sensory nerve conduction velocity of the median nerve was normal in all patients.

Transient bilateral internuclear ophthalmoplegia after minor head-trauma.

Following minor occipital head-trauma, a six-year-old boy developed bilateral internuclear ophthalmoplegia (INO) as the only neurological sign. After having excluded all other possible aetiological causes by careful examination, including magnetic resonance imaging, the symptoms eventually were attributed to the trauma. The course of the INO was documented by electro-oculography. A saccades-training programme specially adapted to the boy's age was performed, and complete remission of the oculomotor symptoms occurred after one year.

[Anorexia nervosa in male adolescents. II. Psychoneuroendocrinologic findings]. / Anorexia nervosa bei männlichen Jugendlichen. Teil II: Psychoneuroendokrinologische Befunde.

Female patients with anorexia nervosa (a.n.) are characterized by distinct endocrine features probably due to hypothalamic pituitary dysfunctions. There is only a limited number of case reports available on patients with a.n.; mostly with few data on hormones. In six male patients with a.n. we examined basal and stimulation values of several hormones performing three pituitary function tests. Basal and stimulated values of luteinizing hormone (LH) and of follicle stimulating hormone (FSH) after LHRH were low comparable to results in prepuberal boys. Similarly, testosterone levels in serum were also markedly reduced. By exploring the pituitary-thyroidal axis total T4 was diminished in one patient and at the lower limit in two patients; concentration of free T4 was in the normal range, while five of six subjects had reduced total T3 concentration and two of six patients showed increased reversed T3 levels; TBG concentration was always in the normal range. Basal TSH was normal, while in two patients the TSH stimulation levels after TRH were diminished; in all patients the TSH stimulation levels were found to be delayed. The basal levels of growth hormone were normal, but the growth hormone response after insulin was diminished in four patients. In all six patients basal prolactin (PRL) and PRL concentration after TRH stimulation was in the normal range. The neuroendocrine results in the six patients with a.n. confirm in males a similar hypothalamic-pituitary dysfunction as it is already known for female patients.

[Hormonal findings in children with central manifestations of Recklinghausen's neurofibromatosis]. / Hormonelle Befunde bei Kindern mit zentraler Manifestation einer Neurofibromatose Recklinghausen.

Hormone parameters were evaluated in 14 children with cerebral manifestation of N.R. to find a possible involvement of the hypothalamo-pituitary axis. In addition to growth hormone and prolactin stimulation, tests of gonadotropic, thyreotropic and adrenocorticotropic function were performed. 6 patients had insufficient growth hormone secretory capacity, and 6 times an increased prolactin-stimulation was found; in one patient ACTH-reserve was diminished. A brain tumour was found in 5 of these 8 patients with impaired hormone results; however, in 3 cases pathologic results were found only after operation.

[Innovative respiratory muscle training for patients with Duchenne muscular dystrophy--a psychological evaluation]. / Innovatives Atemmuskeltraining für Patienten mit Duchenne-Muskeldystrophie-Eine psychische Bewertung.

For neuromuscular patients with progressive respiratory muscle weakness a new training apparatus was developed, which allows a home training of strength as well as endurance of the inspiratory muscles, especially the diaphragma. A significant positive training result could be proved in a comparative study between 2 groups of 15 Duchenne muscular dystrophy (DMD) patients each (8). By the end of the training the satisfaction of patients with the new training equipment was evaluated by means of a questionnaire. The degree of satisfaction was determined at a 10-point scale. Critical ideas were used for improvement of the newly developed training apparatus.