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Biomedical subjects

H Stracke

Publications and source records attributed to H Stracke.

At least 19 recordsLinked to original sources

Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis.

Recent studies have shown that systemic lupus erythematosus (SLE) is associated with a loss of trabecular bone. However, these changes have not been not described in patients with SLE at the time of diagnosis. To investigate the markers of bone metabolism 20 female patients with a recently manifested clinical picture of SLE were selected. All patients included in this study met the ARA criteria (for classification) of SLE. For comparison, 35 female patients with SLE, which had previously manifested itself and which had been treated with glucocorticoids, were included in a second group. A control group (III) consisting of 20 healthy individuals of the same age was formed to compare the results obtained. Test parameters comprised both serum levels of osteocalcin (OC) as the marker for bone formation and crosslinks excretion (CE) in urine as a specific marker for bone resorption. The bone density (BMD) was examined by dual energy X-ray absorption (DEXA) of the vertebral column (L2-L4), femoral neck, Ward's triangle and trochanter. The patients under study received either no medication or nonsteroidal antirheumatic drugs. The BMD of the vertebral column was significantly lower than expected in SLE-afflicted subjects of group II when compared with the age-matched normal female controls. The reduction of BMD in female patients with SLE was related to the significantly increased excretion of urinary pyridinoline, to hypoparathyroidism, and to the decrease in serum OC. Bone loss in women with fresh manifestation of SLE (I) increases to a degree similar to that of patients in group II. Lowered BMD predicts an increased risk for bone fractures. Therefore, female premenopausal SLE patients should be monitored for osteoporosis.

Absorptiometry, Photon

Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by HMG-CoA reductase inhibition in healthy subjects and a patient with coronary artery disease.

HMG-CoA reductase inhibitors, such as pravastatin, are widely used as lipid lowering drugs in hypercholesterolemia. Pravastatin does not only reduce the atherogenic low density lipoprotein (LDL)-cholesterol, but is also increasing high density lipoprotein (HDL)-cholesterol. However, the mechanism leading to an increase of HDL are unclear. Therefore, the effects of pravastatin on the in vivo kinetics of apolipoprotein (apo) A-I were studied in six normolipidemic subjects and in a patient with coronary artery disease (CAD) utilizing stable isotope tracer techniques. Two turnover studies were performed. The first turnover study was carried out before any drug treatment, the second study after 6 weeks of 40 mg pravastatin/day. Three times deuterium labeled L-leucine (3D-leucine) was given as a primed bolus constant infusion (bolus: 1340 microg/kg; infusion: 22 microg/kg per h), and tracer uptake into HDL apoA-I was determined by gas chromatography (GC)-mass-spectrometry (MS). In the healthy subjects HDL-cholesterol increased by 13% and apoA-I increased by 12% under pravastatin treatment. The HDL in the CAD patient decreased by 3% and apoA-I increased by 2%. Prior to drug treatment the mean apoA-I fractional synthetic rate (FSR) was 0.194 per day (S.D. +/- 0.02) and apoA-I production rate (PR) was 10.8 mg/kg per day (S.D. +/- 2.1). The CAD patient had a FSR of 0.219 per day and a PR of 10.6 mg/kg per day. After treatment with pravastatin the mean apoA-I FSR was 0.204 per day (S.D. +/- 0.02) and apoA-I PR was 12.5 mg/kg per day (S.D. +/- 1.5) in the healthy subjects. Despite only minor changes of HDL and apoA-I in the CAD patient, there were significant changes of FSR (0.267 per day) and PR (13.1 mg/kg per day) with pravastatin treatment. The in vivo kinetic data demonstrate an increased FSR of apoA-I. The increase in apoA-I is due to an increased PR of apoA-I. This study demonstrates increased production of HDL apoA-I as the metabolic cause of the increase in HDL and apoA-I levels under inhibition of HMG-CoA reductase in man.

Adult

Evaluation of serum and urinary estrogen levels in male patients with HIV-infection.

Several endocrine functions are described which are altered in patients with human immunodeficiency virus infection. However, there is limited information available on estrogens and their function in these patients. The aim of this study was to relate the stage of the disease with urinary and serum estrogens and the influence of heroin consumption on gonadal steroids. Forty human immunodeficiency virus infected outpatients without AIDS or the clinical picture of AIDS were involved in this cross-sectional study. The subjects were divided in two groups: heroin addicts and non heroin addicts. Blood samples were taken and 24 h urines collected. Serum follicle stimulating hormone, luteinizing hormone, prolactin, estrone, estradiol, testosterone and urinary total estrogens were measured by commercially available radioimmunoassays. Prolactin levels were not affected in the patients. However, compared with controls, follicle stimulating hormone and luteinizing hormone were significantly higher for both groups tested. In contrast, the elevated serum estrone levels were significantly lower expressed in the patients with heroin abuse compared to those of the other group. Urinary estrogens in human immunodeficiency virus infected patients of both groups were found to be higher than those compared to healthy controls. Since these drugs are known to enhance estrogen levels, we conclude that other factors are modulating estrogen formation and degradation in these patients.

Adult

Elderly onset rheumatoid arthritis and polymyalgia rheumatica: ultrasonographic study of the glenohumeral joints.

The glenohumeral joints of 32 patients (aged 60 or above) were examined using ultrasonography. Thirteen patients were suffering from characteristic polymyalgia rheumatica (PMR) symptoms. In contrast 19 other patients initially had similar complaints, but were diagnosed as having elderly onset rheumatoid arthritis (EORA) upon development of typical symptoms. Ultrasound examination revealed glenohumeral joint inflammation in 61% (8 out of 13) of the patients with PMR and 63.2% (12 out of 19) of the patients with EORA. These findings suggest that a subgroup of patients with PMR and EORA suffers from shoulder joint inflammation and this synovitis/bursitis/intraarticular effusion might play an important role in the understanding of their symptoms. We conclude that overlapping forms of PMR and a predominate rheumatoid factor negative subgroup of EORA might exist and should be further characterized.

Aged

Elevated serum-calcium and parathormone-levels in HIV afflicted female heroin addicts.

Alterations of calcium and bone metabolisms have been observed in numerous studies of small groups of male HIV-infected patients. However, our knowledge regarding the manifestation of AIDS-associated hypoparathyroidism in female subjects is limited. In order to investigate the influence of heroin on the calciotropic hormones we performed a cross-sectional study on 45 female patients with proven HIV infection. The following criteria were used for exclusion from the study: age less than 20/ more than 50 years; confinement to bed; wasting symptoms; treatment with agents containing ketoconazole, renal or hepatic insufficiency; clinical or echographic signs of liver cirrhosis; endocrine diseases, or treatment with drugs known to influence calcium metabolism. A reduced parathormone (PTH) level was found among the female HIV-infected patients. Additional long-term use of heroin resulted in a significant increase of PTH compared to sex- and age matched controls and a second group of non-HIV-afflicted heroin dependent females. Significantly lowered serum magnesium concentrations were found in all three groups. Both serum calcium and urinary excretion of calcium were elevated in the group of HIV-infected heroin addicts and were independent from low vitamin D3 levels (1,25-dihydroxycholecalciferol) and alterations of protein metabolism. Therefore, it is concluded that the changes of PTH secretion are mainly due to mechanisms both of the impaired immune defense of HIV-infected females and the additional effect of opiates.

Adult

Rapid spinal trabecular bone loss in female patients with ileitis terminalis Crohn and additional sacroiliac joint inflammation.

Patients with Crohn's disease are well known to have local and generalized osteopenia of varying degrees. The aim of this study was to investigate whether the additional involvement of the sacroiliac joint as an extraintestinal manifestation has an influence on bone turnover in female patients with Crohn's disease. Osteocalcin and other parameters of bone metabolism were measured in 79 female patients with Crohn's disease. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DEXA). Z scores were obtained by comparison with age- and sex-matched normal values. As regards the sacroiliac involvement (n = 26; group 1), we found a significantly lower BMD in the lumbar spine (L4) and in Ward's triangle of the femoral neck compared to controls (P < 0.05) and those patients (n = 53; group 2) with pure ileitis terminalis Crohn. Furthermore, the duration of the disease process in patients with Crohn's disease and extraintestinal involvement was markedly shorter than that of patients in group 2 (P < 0.05). In conclusion, osteoporosis in female patients with sacroiliac involvement manifested itself in a more severe way.

Adult

A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy.

In a double-blind, randomized, controlled study, the effectiveness of treatment with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy. The results showed a significant improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold. Long-term observation of 9 patients with verum over a period of 9 months support the results. Therapy-specific adverse effects were not seen. The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.

Administration, Oral

Evidence of impaired cartilage/bone turnover in patients with active ankylosing spondylitis.

OBJECTIVES: To compare serum markers of bone formation with the urinary excretion of pyridinium crosslinks (PYR) as a possible measure of bone and cartilage degradation which would detect changes in bone metabolism in patients with ankylosing spondylitis (AS) and to relate them to influences of inflammatory disease activity, and to treatment. METHODS: In 62 patients with AS, serum osteocalcin, alkaline phosphatase (ALP), and skeletal ALP isoenzyme levels were evaluated concurrently in comparison with urinary excretion of pyridinium cross links and were compared with values in 50 healthy controls. RESULTS: Osteocalcin concentrations in AS patients were in the middle normal range (3.5 (SD 1.2) ng/ml) and did not differ significantly from those in control subjects (4.2 (1.3) ng/ml); the same was true for ALP and skeletal ALP isoenzyme fraction (AS: ALP 149 (50.3) U/l, skeletal ALP 12.8 (4.1) micrograms/l; controls: ALP 133 (25.2) U/l, skeletal ALP 11.9 (4.3) micrograms/l). The urinary levels of PYR in AS (51.2 (25.2) nmol PYR/mmol creatinine) were significantly increased compared with controls (33.9 (12.4) nmol PYR/mmol creatinine (p < 0.001)). In the AS group there was a positive correlation between urinary excretion of PYR and inflammatory disease activity (erythrocyte sedimentation rate (ESR)) (r = 0.6, p < 0.0001) and C reactive protein (CRP) (r = 0.3, p = 0.02), but no significant correlation was found with ESR, CRP, and markers of bone formation. CONCLUSIONS: Bone metabolism in patients with AS is characterised by normal bone formation and enhanced cartilage/bone degradation, suggesting that impaired bone turnover is pronounced in active disease. The results clearly indicate that this comparison can be used to demonstrate impairment of cartilage/bone metabolism which correlates with disease activity. The data obtained further emphasise the importance of measuring both serum variables and urinary excretion of PYR crosslinks to obtain adequate evaluation of cartilage/bone metabolism in patients with AS.

Adult

[Mexiletine in treatment of painful diabetic neuropathy].

The objective of this double-blind placebo controlled multicenter study was to prove the efficacy of mexiletine in painful diabetic neuropathy. Treatment was provided for in three dosages. For pain measurements a visual analogue scale (VAS) and McGill's verbal rating scale were chosen. 95 patients were included. A global assessment of the VAS showed no differences in treatment. The total evaluation (PRIT = Pain Rating Index Total) of the McGill scale just failed the level of significance. More specific exploratory evaluation of subclasses of the McGill scale, representing different qualities of pain, gave remarkable differences between mexiletine and placebo. According to types of complaints an evaluation showed substantial advantages of the mexiletine treatment with both the VAS and the McGill scale. There is strong evidence that particularly patients with stabbing or burning pain, heat sensations or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg per day seems to be appropriate in this indication. With an increase in dosage the efficacy does not rise proportionally. Mexiletine proved a very safe therapy with negligible side effects at the medium dose range, even less than placebo. There were no cardiovascular side effects. Further investigations should pay more attention to the variety of the complaints and include the quality of life.

Adult

Function tests on the neuroendocrine hypothalamo-pituitary system following acute midbrain syndrome, with special reference to computertomographical and magnetic resonance imaging results.

Seventeen patients underwent a neuroendocrinological function test at a mean 6.3 years following a severe craniocerebral trauma (CCT) accompanied by midbrain syndrome. An insulin hypoglycaemia test (IHT) and the combined pituitary anterior lobe test (CPALT) were applied. Whereas the IHT as maximum stimulator of the hypothalamo-pituitary system (HPS) showed an adequate reserve capacity, the CPALT yielded a partial limitation of the secretion dynamic in the somatotropic, adrenocorticotropic axis as well as a dysfunction in the FSH secretion. Neuroradiological tests could not establish substantial injury in the regio hypothalamica in any patient.

Adolescent

BGP serum levels in patients with thyroid carcinoma before and 4-14 weeks after radioiodine therapy.

In the present short paper we compared the BGP and AP levels of 26 patients with thyroid carcinoma during radio-iodine therapy. BGP values reflect the bone turnover before and after radio-iodine therapy. There were no significant AP changes during this period. These results suggest that thyroid hormone has a direct effect on osteoblast function and that this effect can be best monitored by determination of BGP levels.

Adolescent

Osteoporosis and bone metabolic parameters in dependence upon calcium intake through milk and milk products.

The bone mineral content of young adults as well as of osteoporotic patients and age-matched controls without bone disease was measured by single-photon absorptiometry. A retrospective nutrition survey was additionally made to study the relationship between bone mineral content and calcium intake in different periods of life. The bone mineral content and bone mineral density of young adults is directly related to the calcium intake through milk and dairy products. The osteoporotics had a significantly lower bone mineral content than the controls. Calcium intake through milk and milk products in childhood and adolescence had been significantly lower in the patients than in the controls, whereas in the later periods of life (20-30 years prior to the study and at the time of the study) there were no significant differences between the calcium intakes of the two groups. It was also found that an adequate intake of calcium protected against increased bone resorption, as evidenced in particular by the reduced levels of serum osteocalcin, a parameter of bone turnover. In conclusion it can be stated that the data support the hypothesis that adequate calcium intake through milk and milk products in childhood and adolescence is a decisive marker for obtaining a maximum bone mass (peak adult bone mass) and for the prevention of osteoporosis. Furthermore, it can be stated that increased calcium intake in the later years may not reduce the accelerated risk of osteoporosis resulting from inadequate calcium intake during childhood and adolescence.

Absorptiometry, Photon

[Diagnosis and therapy of diabetic polyneuropathy].

Distinction is made between peripheral and autonomic neuropathy. The former is usually painful, while the latter is especially associated with cardiovascular, gastrointestinal and urogenital disturbances. In the diagnosis of peripheral neuropathy, a basic neurological examination (reflex status, vibratory sense) takes precedence over measuring the velocity of nerve conduction and determining the temperature and pain thresholds. The diagnostic approach to the autonomic disturbances is organ-specific (testing of cardiovascular reflexes, sonographic and scintigraphic determination of gastric emptying, infusion urography and uroflowmetry). Early diagnosis and optimal diabetes control are the therapeutic consequences. Symptomatic treatment includes the administration of analgesics, antidepressants and carbamazepine. A newer drug being currently tried is mexiletine. High doses of alpha-liponic acid as well as the fat-soluble B vitamins are used for causal therapy. Clinical trials with aldose reductase inhibitors and gamma-linolenic acid are under way.

Autonomic Nervous System

Disappearance of a pituitary tumor after 15 months of treatment with CV 205-502, a new dopamine agonist.

We report the case of a 27-year-old woman with a prolactin-secreting macroadenoma of the pituitary gland who was under treatment with a new dopamine agonist, Sandoz CV 205-502. Immediately after diagnosis of a 12 x 10 mm intrasellar prolactinoma, treatment with CV 205-502 was begun at a daily dose of 0.075 mg. Under this low dose, prolactin in the serum normalized after 4 weeks, the initial hormone value being 189.9 ng/ml. After 6 months of therapy there was still a 6 x 6 mm tumor, and after 15 months of treatment the pathological process could no longer be observed with magnetic resonance imaging. In the 20th month of therapy the patient became pregnant. An ovulatory menstrual cycle had been present for a few months.

Adult

Results of continuous long-term intravenous application of octreotide via an implantable pump system in acromegaly resistant to operative and X-ray therapy.

Long term results after surgery for growth hormone (GH)-secreting adenomas indicate only a limited cure rate, particularly in patients with tumours invading the dural boundaries of the sella with suprasellar extension. Since octreotide had become a treatment option, it was used i.v. via an implantable pump system in five patients (age range 24-46 yr) showing symptoms of uncontrolled acromegaly, in spite of previous surgery and X-ray therapy. The octreotide doses used permanently for a cumulative treatment period of 8.8 yr ranged between 300 and 1000 micrograms/24 h. Serial evaluations of clinical findings, 24-h GH and insulin profiles, insulin growth factor-1 (IGF-1), oral glucose tolerance test and pituitary function revealed sustained GH suppression, without interim escape, below 2 ng/ml in two and below 5 ng/ml in three patients, IGF-1 decrease in all with normalization in two patients and no clinically relevant disturbances of carbohydrate tolerance or thyroid-stimulating hormone secretion. In one case of previous unresponsiveness to dopamine agonists i.v. octreotide application for 29 months facilitated later disease control by bromocriptine only. In two patients octreotide was terminated after 15 and 30 months of i.v. administration, respectively, because the effects of irradiation had occurred. For a subgroup of patients with resistant acromegaly continuous i.v. octreotide can be considered as a safe and effective alternative, which increases patients' independency from the inconvenience of daily repeated s.c. injections.

Acromegaly

Mexiletine in the treatment of diabetic neuropathy.

OBJECTIVE: To prove the efficacy of mexiletine in painful diabetic neuropathy. RESEARCH DESIGN AND METHODS: Treatment was provided in three dosages. For pain measurements, a VAS and McGill's verbal rating scale were chosen. Ninety-five patients were included in the study. RESULTS: A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo. The total evaluation (PRIT) of the McGill scale fell just below the level of significance. More specific exploratory evaluations of subclasses of the McGill scale, representing different degrees of pain, gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items. In special subgroups, which were formed according to types and courses of complaints compiled at the beginning of this evaluation, the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale. CONCLUSIONS: Evidence strongly indicates that, in particular, those patients with stabbing or burning pain, heat sensations, or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg/day seems to be appropriate. With an increase in the antiarryhthmic dosage level, the efficacy does not rise proportionally. Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range, even less than placebo; and remarkably, no cardiovascular side effects were noted. Further studies should avoid global assessments and pay more attention to the variety of complaints and quality of life.

Adult

Surgery, dopamine agonist therapy of combined treatment--results in prolactinoma patients after a 12 month follow-up.

In a non-randomized retrospective study n = 36 prolactinoma patients (n = 7 micro- and n = 29 macroadenomas) were evaluated before (E0), 4 (E1) and 52 weeks (E2) after applying 3 different treatment modalities: A dopamine agonist (DA) therapy (n = 14), B surgery as initial procedure (n = 12) and oral DA therapy, C DA preinjection, subsequent surgery (n = 10) and oral DA medication. T0 outline the effect of the 3 regimens upon serum prolactin (PRL) and tumour size reduction, clinical signs and symptoms, anterior/posterior pituitary lobe function and MRI/CT findings were evaluated in each patient at E0, E1 and E2. In group A, PRL normalization was achieved in n = 10 patients (71%), although the frequency of an empty sella was only one out of 12 macroprolactinoma patients (less than 10%). Patients of group C showed the lowest PRLE2 levels (32 +/- 11 ng/ml, normalization rate 60%), although not statistically significant when compared with the other groups (A: 41 +/- 28 ng/ml, B: 114 +/- 33 ng/ml, normalization rate 31%). According to MRI studies in groups B and C total removal was achieved in 33% and 50% of macroprolactinomas, respectively. The most favourable ratio of the leading pre/posttreatment signs and symptoms was observed in patients of group C. It was concluded that no superiority of either treatment regimen exists for prolactinoma patients. Each mode of therapy has its own benefits which may be applied to the different biological behaviour of a prolactinoma in the respective patient.

Adolescent

Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation.

After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45-65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF-transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time.

Animals