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Biomedical subjects

K Mann

Publications and source records attributed to K Mann.

At least 73 records · Page 4Linked to original sources

[Rhabdomyolysis, hyponatremia and fever in a patient with Schmidt's syndrome].

HISTORY: A 38-year-old man had fever (40 degrees C) and a swollen right leg. Two weeks before admission he had received non-steroid anti-inflammatory drugs (paracetamol and ibuprofen) after a tooth extraction. Some weeks before he had noticed a rough voice and a dry skin. INVESTIGATIONS: The patient had a sinus tachycardia of 145/min (blood pressure of 130/80 mm Hg). Laboratory data revealed a CK of 16,650 U/l (< 80 U/l), myoglobin of 2420 U/l (< 90 microg/l) and LDH of 1250 U/l (<240 U/l), leukocyte count of 12,000 / microl and C-reactive protein of 3.0 mg/dl (<0.5 mg/dl). Sodium was markedly decreased (110 mmol/l (135 - 145 mmol/l)). Determination of thyroid hormone showed primary hypothyroidism with an elevated TSH of 62.6 mU/l (0.3 - 4.0 mU/l); T4 of 38 nmol/l (58 - 154 nmol/l), T3 1.17 of nmol/l (1.23 - 3.08 nmol/l) and fT4 of 6 pmol/l (10 - 25 pmol/l). The thyroid autoantibodies were increased (thyroxine peroxidase antibodies of 684 U/l (<35 U/l) and thyroglobulin antibodies of 173 U/l (<40 U/l)). Ultrasound of the thyroid revealed an nonhomogeneous structure. Cortisol at 8.00 a. m. was reduced by 63 mmol/l (180 - 640 mmol/l) and did not increase after administration of ACTH (60 min. cortisol at 90 mmol/l (>550 mmol/l)). ACTH was increased (141 pg/ml; normal range 17 - 52 pg/ml). TREATMENT AND COURSE: The initial therapy consisted of hydrocortisone (100 mg i.v as bolus and 100 mg during the next 24 hours) and levothyroxine replacement (200 micro g) was initiated. During the following 8 days clinical symptoms regressed. Values of sodium, myoglobin and LDH decreased. After therapy with cephalosporin (Ceftriaxon) and penicillin (Flucloxacillin) fever and inflammation parameters decreased. CONCLUSION: This is a rare case of a rhabdomyolysis and hyponatriaemia due to hypothyroidism and Addison's disease (Schmidt's syndrome).

Addison Disease↗

Glucose and lipid metabolism in young lean normotensive males with the G protein beta3 825T-allele.

The 825T-allele of the C825T polymorphism in GNB3, the gene for the G protein beta3 subunit, has been reported to be associated with essential hypertension and obesity. Expression of Gbeta3s, the gene product of GNB3 associated with the GNB3 825T-allele, causes increased signal transduction which may contribute to pathogenetic mechanisms ultimately resulting in hypertension and obesity. Given the known involvement of heterotrimeric G proteins in insulin secretion and insulin action on the cellular level, we analysed insulin sensitivity in each 15 young lean normotensive males with TC- and CC-genotypes, respectively. Blood glucose and serum insulin samples were taken during a standard oral glucose tolerance test. Insulin-stimulated glucose disposal was analysed by euglycemic-hyperinsulinemic clamp. Both groups did not differ with regard to the time-courses for glucose or insulin concentrations in the oral glucose tolerance test. Furthermore, insulin-stimulated glucose disposal was virtually independent of genotype. The TC-genotype is not associated with a primary defect in insulin secretion or sensitivity suggesting that obesity and hypertension in carriers of 825T do not likely result from primary alterations in glucose and insulin homeostasis. However, GNB3 825T-associated obesity may predispose to insulin resistance, an issue which remains to be investigated. Furthermore, fasting cholesterol was significantly higher in TC compared to CC genotype (4.71 versus 3.96 mmol/l; p = 0.007) suggesting that enhanced G protein signalling might be associated with alterations of cholesterol metabolism.

Adult↗

[Drug treatment of immune hyperthyroidism (Basedow disease). Patient selection, long-term follow-up and prevention of recurrence].

Since theraphy of Graves' disease is not directed towards the cause of the disease, medical theraphy is still the first choice and symptomatically effective in treating hyperthyroidism. Antithyroid drugs are effective in restoring euthyroidism in >90% of the patients durning 4-6 weeks, but 30-50% of the patients experience relapse after withdrawal. Previous prospective randomized studies evaluated prognostic parameters and the use of levothyroxine for prevention of relapse of hyperthyroidism. Recent studies have addressed the period after withdrawal amd focused on the natural course of disease. The results of a recent prospective randomized and controlled multicenter study were as follows: supplementation of levothroxine does not prevent relapse of hyperthyroidism. Basal TSH (4 weeks after withdrawal of antithyroid drugs) is the best prognostic marker. Smoking and positive TSH-receptor-antibodies at the end of antithyroid theraphy are other risk factors.

Antithyroid Agents↗

[Hypophyseal coma].

Pituitary coma is a rare case of emergency and primarily due to ACTH and TSH deficiency. Pituitary coma occurs more often in patients with well-known pituitary deficiency than in patients with intrasellar tumor. Clinical manifestations are hypotonia, bradycardia, decreased skin and nipple pigmentation, muscle weakness, vomitus, nausea, obstipation, hypothermia, and hypoventilation. A postpartal agalactia is often the first sign of Sheehan's syndrome. Unlike primary adrenal insufficiency (Addison's disease) ACTH deficiency does not cause hyperpigmentation, hyperkalemia, or salt loss. The suspicion of pituitary coma requires replacement with 100 mg hydrocortisone iv, 200 mg hydrocortisone iv/24 h, 500 micro g levothyroxine iv and fluid substitution. Since thyroxine accelerates the degradation of cortisol and can precipitate adrenal crisis in patients with limited pituitary reserve, hydrocortisone replacement should always precede levothyroxine therapy. ACTH stimulation test, CRH stimulation test and insulin tolerance test (optional) should be performed after therapeutic compensation to determine pituitary function.

Adrenal Insufficiency↗

[Outpatient alcohol detoxification].

Increasing significance is being attributed to outpatient detoxification treatment of alcohol-dependent patients. Many patients want to undergo outpatient detoxification or even carry it out without professional supervision. In some Scandinavian countries and in the USA, outpatient detoxification under medical supervision has increased substantially. In these countries,numerous studies describe outpatient alcohol detoxification as a safe and cost-reducing method. These studies vary in many aspects, especially regarding the nature and dose of the withdrawal medication, but also concerning the inclusion criteria of patients. Medications to treat or prevent alcohol withdrawal symptoms are rather heterogeneous. Besides well-known standard medication established in inpatient treatment (e.g.,benzodiazepines and carbamazepine), interesting studies report the application of rather uncommon substances such as physostigmine and psychotropic analgesic nitrous oxide (PAN) for alcohol detoxification. This article provides an overview on outpatient alcohol detoxification and discusses its transfer to practical application.

Alcohol Deterrents↗

[Standardized documentation procedure as a basis for improvement of process quality of treatment in psychiatric hospitals].

A standardized documentation system is presented for detailed description and analysis of treatment procedure for psychiatric inpatients. In the first step of a pilot study limited to patients with depressive syndromes at the Department of Psychiatry, University of Mainz, for each subject the clinical status was assessed weekly using psychopathological ratings and depicted in its temporal course along with therapeutic activities. Visualization of the treatment process turned out to be useful for everyday work by supporting the application of practice guidelines for clinical decisions. Beyond optimization of the individual treatment process, aggregation of the data also allows global assessment of treatment processes in the clinic. Thus, in addition to established basic documentation, the presented documentation procedure allows the development of a powerful quality management system in psychiatric clinics, due to its process orientation. Moreover, in psychiatric care research, it is an adequate basis for evaluating the effectiveness and efficiency of treatment procedures.

Adult↗

Myocardial perfusion abnormalities in patients with active acromegaly.

Cardiomyopathy is often seen in patients with a long history of acromegaly. In order to screen for perfusion abnormalities, patients with active acromegaly without evidence for coronary heart disease were examined by single photon emission computed tomography (SPECT). The study included a group of 11 strictly selected patients with active acromegaly (7 males and 4 females; age 51 +/- 12 y [mean +/- S.D.]) with elevated age-adjusted IGF-I levels (IGF-I 569 +/- 193 micro g/l; GH 31.2 +/- 56.3 micro g/l) compared to an age- and sex-matched non-acromegalic control group with comparable muscle mass index of the left ventricle (126 +/- 41 active vs. 122 +/- 33 g/m 2 control group) and body mass index (26.6 +/- 2.7 vs. 27.0 +/- 5.0 kg/m 2). To address this issue, myocardial perfusion was investigated by single photon emission computed tomography (SPECT) using a triple head gamma-camera. 70 MBq 201TlCl was injected, and post-stress (from bicycle ergometer) images were obtained. Images were interpreted quantitatively by bull's eye polary map (16 regions of the left ventricle) and were compared to the control group. In the patients with active acromegaly, the mean nuclide uptake of the 16 regions of the left ventricle after bicycle stress examination was lower than in the control group (82.99 +/- 2.85 active vs 85.48 +/- 1.29 control group, p < 0.01). Non-homogeneity of nuclide uptake was defined as the standard deviations of the 16 regions and was higher in patients with active acromegaly (11.11 +/- 2.35 active vs. 8.77 +/- 1.39 control group, p < 0.01). In conclusion, myocardial perfusion is impaired in patients with active acromegaly, thus representing an early stage of cardiac involvement in acromegaly that may be directly mediated by growth hormone excess.

Acromegaly↗

The influence of gender and emotional valence of visual cues on FMRI activation in humans.

Emotional neuroscience maps neurocircuits associated with the processing of affective stimuli. To assess gender differences in brain activation elicited by affective stimuli, we used pictures from the International Affective Picture System in a functional magnetic resonance imaging (fMRI) study. Ten male and ten female age-matched healthy volunteers were included and viewed affectively negative versus positive pictures, which were presented in an event related design. There was a significant interaction between valence of emotional stimuli and gender in the sublenticular extended amygdala (SLEA) and the rostral anterior cingulate. fMRI activation in these regions was stronger for negative compared to positive cues in women. In men fMRI activation was independent of stimulus valence. These results suggest to take gender differences into account when emotional paradigms are tested in functional brain imaging.

Adult↗

The nacre protein perlucin nucleates growth of calcium carbonate crystals.

Atomic force microscopy (AFM) in aqueous solution was used to investigate native nacre of the marine snail Haliotis laevigata on the microscopic scale and the interaction of purified nacre proteins with calcium carbonate crystals on the nanoscopic scale. These investigations were controlled by scanning electron microscopy (SEM), light microscopy (LM) and biochemical methods. For investigations with AFM and SEM, nacre was cleaved parallel to the aragonite tablets in this biogenic polymer/mineral composite. Multilamellar organic sheets consisting of a core of chitin with layers of proteins attached on both sides lay between the aragonite layers consisting of confluent aragonite tablets. Cleavage appeared to occur between the aragonite tablet layer and the protein layer. AFM images revealed a honeycomb-like structure to the organic material with a diameter of the 'honeycombs' equalling that of the aragonite tablets. The walls of the structures consisted of filaments, which were suggested to be collagen. The flat regions of the honeycomb-like structures exhibited a hole with a diameter of more than 100 nm. When incubated in saturated calcium carbonate solution, aragonite needles with perfect vertical orientation grew on the proteinacous surface. After treatment with proteinase K, no growth of orientated aragonite needles was detected. Direct AFM measurements on dissolving and growing calcite crystals revealed a surface structure with straight steps the number of which decreased with crystal growth. When the purified nacre protein perlucin was added to the growth solution (a super-saturated calcium carbonate solution) new layers were nucleated and the number of steps increased. Anion exchange chromatography of the water-soluble proteins revealed a mixture of about 10 different proteins. When this mixture was dialysed against saturated calcium carbonate solution and sodium chloride, calcium carbonate crystals precipitated together with perlucin leaving the other proteins in the supernatant. Thus perlucin was shown to be a protein able to nucleate calcium carbonate layers on calcite surfaces, and in the presence of sodium chloride, is incorporated as an intracrystalline protein into calcium carbonate crystals.

Calcium Carbonate↗

Impact of smoking on the response to treatment of thyroid associated ophthalmopathy.

BACKGROUND: In patients with Graves' disease, smoking considerably increases the incidence and severity of thyroid associated ophthalmopathy (TAO). The authors sought to determine if smoking also influences the course of TAO during treatment, and the efficacy of therapy. METHODS: 41 smokers and 19 non-smokers with moderate untreated TAO were included in this prospective study. All patients were treated with steroids and, 6 weeks after the beginning of drug therapy, with orbital irradiation. Follow up was performed 1.5, 4.5, 7.5, and 12 months after the beginning of the study. Proptosis, clinical activity score (CAS), and motility were evaluated. The extent of smoking was derived from the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV), a parameter of long term smoking. RESULTS: There was no difference in the clinical manifestations of TAO between smokers and non-smokers at the beginning of treatment. However, CAS decreased (p<0.05) and motility improved (p<0.02) significantly faster and to a greater extent in non-smokers than smokers. Inverse correlations between the CAS decrease and the HEV levels observed 4.5 and 7.5 months after the beginning of treatment and between the improvement of motility and the HEV levels after 1.5, 4.5, and 7.5 months indicated a dose dependence. Mean HEV levels did not vary much during the follow up period and were significantly different in smokers (mean 5.4 (SD 2.7) micro g/l) and non-smokers (mean 1.8 (1.3) micro g/l; p<0.01). CONCLUSION: Smoking influences the course of TAO during treatment in a dose dependent manner. The response to treatment is delayed and considerably poorer in smokers.

Adolescent↗

Tumor- and pregnancy-derived isoforms of human chorionic gonadotropin: biological and diagnostic relevance.

OBJECTIVES: Human chorionic gonadotropin (hCG) and hCG variants are of high clinical importance for the diagnosis of pregnancy, monitoring of abnormal and ectopic pregnancies, testing for Down's syndrome or monitoring therapy of hCG-secreting malignancies. In serum and urine, hCG appears in microheterogeneous isoforms with respect to protein backbone structure and the extent of glycosylation. The present study reports on the identification, immunological characterization, biological activity of glycosylation isoforms of pregnancy (preg) and tumor-derived (tu) hCG, and the impact of glycosylation on diagnostic immunoassays. METHODS: Twenty-two urinary preg- and tu-hCG isoforms were separated by preparative isoelectrofocusing (hCG-pI variants) and characterized by Western blot. Number, topography and accessibility pattern of epitopes on their surface was evaluated by two-site radioimmunoassays using 14 different monoclonal antibodies (mabs). Binding of hCG isoforms to four different LH/CG receptors was investigated in radioreceptor assays, and their biological activity determined by measuring cAMP elevation. RESULTS: All 22 hCG glycosylation variants appeared immunologically intact: each isoform, even when highly acidic, expressed all 14 surface epitopes which were arranged in a topographical manner indistinguishable from crude hCG. hCG isoforms were able to bind to four different receptor variants, with slightly varying affinities, but orientations indistinguishable from each other as shown by identical epitope accessibility patterns. Each of the hCG-pI variants was able to activate the LH/CG-Rs, but with varying reactivities. CONCLUSIONS: We conclude that in contrast to deglycosylated hCG, all hCG glycosylation isoforms investigated act as receptor agonists. Moreover, there is no overspecificity of mabs to certain hCG isoforms due to carbohydrate variability that exclude others from diagnostic measurement.

Adult↗

Diagnosis of adrenal insufficiency: Evaluation of the corticotropin-releasing hormone test and Basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease.

The aim of the study was to evaluate the diagnostic value of the human CRH test and the basal morning serum cortisol for the diagnosis of adrenal insufficiency. Putative peak cortisol cut points for the CRH test and basal cortisol cut points were determined by receiver operating characteristic (ROC) analysis with the insulin tolerance test as reference test. Fifty-four patients with suspected hypothalamic-pituitary-adrenal disease were tested. In 20 healthy controls, CRH led to a mean peak cortisol of 594.8 +/- 21.7 nmol/liter. The lower limit of a normal response was calculated as 400 nmol/liter. ROC analysis of peak cortisol levels during CRH testing of patients with suspected hypothalamic-pituitary-adrenal disease suggested an optimal peak cortisol cut point of < or 377 nmol/liter for the diagnosis of adrenal insufficiency and a 96% specificity but poor sensitivity of 76%. The baseline cortisol in the healthy control group showed a mean of 439.3 +/- 24.9 nmol/liter, resulting in a lower limit of 267 nmol/liter. ROC analysis of patients suggested the highest accuracy for basal cortisol levels of 285 nmol/liter or more for the diagnosis of adrenal insufficiency (100% sensitivity and 61% specificity). Within this patient group, a cortisol of more than 98 nmol/liter excluded adrenal insufficiency among those without the disorder, yielding 100% specificity. Using these criteria of upper (285 nmol/liter) and lower (98 nmol/liter) cut-off points with high sensitivity and specificity can reduce the number of individuals who need provocative tests. Basal cortisol is less expensive, and we therefore suggest to use it as a first-line test of adrenal insufficiency. Because of the low sensitivity of the human CRH test, we do not recommend it as a second test.

Adrenal Gland Diseases↗

Purification of ovocalyxin-32, a novel chicken eggshell matrix protein.

The eggshell is a highly ordered structure resulting from the deposition of calcium carbonate and an organic matrix from the acellular uterine fluid. Characterization of the individual matrix components is necessary to determine their influence upon calcite crystal shape, size, and orientation during eggshell calcification. We have purified and sequenced a novel 32-kDa protein, ovocalyxin-32 (OCX-32), which is present at high levels in the uterine fluid during the terminal phase of eggshell formation, and is localized predominantly in the outer eggshell. Database searches identified expressed sequence tags (ESTs) whose alignment yielded the complete cDNA. OCX-32 protein possesses limited identity (32%) to two unrelated proteins: latexin, a carboxypeptidase inhibitor expressed in rat cerebral cortex and mast cells, and to a skin protein that is encoded by a retinoic acid receptor-responsive gene, TIG1. The timing of OCX-32 secretion into the uterine fluid suggests that it may play a role in the termination of mineral deposition.

Animals↗

Development of alcohol-associated cues and cue-induced brain activation in alcoholics.

The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.

Adult↗

Acromegaly: evidence for a direct relation between disease activity and cardiac dysfunction in patients without ventricular hypertrophy.

BACKGROUND AND AIMS: Cardiac abnormalities, such as cardiomegaly and congestive heart failure, occur frequently in advanced acromegaly. Abnormalities of systolic and diastolic function, mostly associated with left ventricular (LV) hypertrophy, have been reported. The impact of disease activity on LV performance in patients with normal or slightly elevated LV muscle mass has not been demonstrated. PATIENTS AND METHODS: Conventional two-dimensional/Doppler echocardiography and tissue Doppler imaging (TDI) of the mitral annulus were performed in 13 patients with active acromegaly (AA) and normal or slightly elevated LV muscle mass (< 140 g/m2) and in 19 cured/well-controlled patients (CA). A group of 21 volunteers without symptoms or signs of cardiac disease served as controls (CON). The combined myocardial performance index (Tei-Index) was determined in all patients and controls. RESULTS: Muscle mass index of the left ventricle, ejection fraction, fractional shorting, E/ET-ratio, systolic (ST) and late diastolic (AT) annular velocities did not differ significantly between the three groups. In the AA group, the early diastolic annular velocity ET[7.13 +/- 2.11 (AA); 9.83 +/- 3.29 (CA); 10.10 +/- 1.70 m/s (CON); P < 0.05 AA vs. CA, P < 0.005 AA vs. CON] and the ET/AT-ratio [0.71 +/- 0.26 (AA); 0.95 +/- 0.33 (CA); 1.00 +/- 0.15 m/s (CON); P < 0.05 AA vs. CA, P < 0.005 AA vs. CON] were significantly reduced. Patients with AA had a longer deceleration time [209 +/- 19 (AA); 179 +/- 22 (CA); 185 +/- 26 ms (CON); P < 0.05]. The Tei-Index was significantly higher in AA in comparison with CON [0.50 +/- 0.15 (AA); 0.48 +/- 0.12 (CA); 0.41 +/- 0.10 (CON); P < 0.05 AA vs. CON]. Subjects with CA did not differ significantly from controls with respect to 2-D/Doppler echo- and TDI-derived parameters. CONCLUSION: The data demonstrate that diastolic dysfunction can be verified by tissue Doppler imaging in patients with active acromegaly with normal or slightly elevated muscle mass of the left ventricle and seems to be related to disease activity. The Tei-Index as a sensitive combined myocardial performance index can be used to complete the assessment of systolic and diastolic LV performance in acromegalic patients.

Acromegaly↗

Maturation of thyroidal dendritic cells in Graves' disease.

Because thyroidal dendritic cells (t-DC) may be implicated in the pathogenesis of Graves' disease (GD), we compared t-DC in thyroid sections of patients with GD (n = 15) and control patients with toxic (TG; n = 12) or non-toxic goitre (NG; n = 12). Goitres in GD, but not TG or NG, were populated with three discernible t-DC phenotypes. (i) Immature t-DC (major histocompatibility complex (MHC) II+/CD40-/CD80-) were located perifollicularly (95% of the patients with GD, but only 55% of TG and 51% of NG patients); numbers of such t-DC were significantly elevated in GD (P < 0.001). (ii) Partially matured CD80+ t-DC were present in connective tissue (73% of the patients) and focal interstitial clusters (40% of the patients). In 53% of the patients with GD, single as well as clustered interstitial t-DC expressed CD40. (iii) However, phenotypically mature t-DC (MHC II+/CD40+/CD80+/RFD1+) were only present in clusters and colocalized with activated CD4+/MHC class II+ T-helper (Th) cells. Expression of CD54 and CD83 did not significantly differ among the groups. The phenotype of intrathyroidal DC in GD thus supports their role as potential (co)stimulators of thyroid autoimmunity.

Adult↗