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Biomedical subjects

K Helmke

Publications and source records attributed to K Helmke.

At least 37 records · Page 2Linked to original sources

The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica.

OBJECTIVES: To determine the correlation between inflammatory cytokines and adrenal hormones in patients with polymyalgia rheumatica (PMR) and to compare the ratio of serum cortisol and androstenedione (ASD) or dehydroepiandrosterone sulphate (DHEAS) in normal subjects with PMR patients. METHODS: In 102 patients with PMR (32 beginning and 70 chronic disease) and 31 age-matched and sex-matched healthy subjects, ASD, cortisol, DHEAS, interleukin-6 (IL-6), and tumour necrosis factor (TNF) were measured by immunometric assays. RESULTS: Serum levels of IL-6 were elevated in patients with PMR as compared with normal subjects (10.0 +/- 1.6 vs 2.1 +/- 0.1 pg/ml, P = 0.01), which was not found for TNF. In PMR patients, serum levels of IL-6 were positively correlated with serum levels of ASD (P < 0.001), cortisol (P < 0.001), and DHEAS (P = 0. 038) irrespective of corticosteroid treatment. Serum levels of cortisol in relation to IL-6 were significantly lower in patients with chronic disease and long-standing corticosteroid administration as compared with patients with recent onset of the disease and without corticosteroid therapy (P < 0.01). CONCLUSIONS: In PMR, as expected, there was an increase in IL-6 serum levels that was associated with elevated serum levels of ASD, DHEAS, and cortisol which was more marked in patients with recent-onset disease and without corticosteroids. However, serum levels of cortisol in patients with and without corticosteroids were lower than expected by considering the inflammatory status (increased IL-6). This may indicate a change in the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to inflammatory stimuli such as IL-6 during chronic disease. Furthermore, there seems to be a shift of biosynthesis to cortisol in relation to DHEAS or ASD in chronic disease.

Adrenal Glands↗

Favorable role of interleukin 10 in patients with polymyalgia rheumatica.

OBJECTIVE: To determine the relationship between the antiinflammatory molecule interleukin 10 (IL-10) and disease symptoms, IL-1beta, tumor necrosis factor (TNF), and IL-1 receptor antagonist (IL-1ra) in patients with polymyalgia rheumatica (PMR). METHODS: In 102 patients with PMR, we determined the severity of the disease by the presence of typical clinical symptoms (symptom score with a maximum of 10 points). IL-10, IL-1beta, TNF, and IL-1ra were measured in all patients and 31 age matched healthy controls by enzyme immunometric assays. RESULTS: Compared to patients with elevated serum levels, patients with normal serum levels of IL-10 (below the mean + 3 SD of controls, 7.79 pg/ml) more often had adynamia (p = 0.045), bilateral muscular pain in shoulders, upper arms or neck (p = 0.045), bilateral muscular pain in the pelvic girdle (p < 0.001), headache (p = 0.014), morning stiffness (p < 0.001), symptoms of depression (p = 0.013), and initial weight loss (p = 0.011), and had a higher symptom score (5.5+/-0.4 vs 3.7+/-0.3; p < 0.001). The overall symptom score correlated negatively with IL-10 serum levels (Rrank = -0.421, p < 0.001). IL-10 correlated negatively with IL-1beta (p = 0.013) and TNF-alpha (p = 0.039). The association between elevated serum levels of IL-10 and low serum levels of IL-1beta and TNF was observed only in patients with corticosteroid treatment. In these patients, elevated serum levels of IL-10 were positively associated with an increased ratio of IL-1ra to IL-1beta. CONCLUSION: Elevated serum levels of IL-10 were associated with a more mild form of PMR. This study indicates a favorable role of IL-10 in patients with PMR.

Aged↗

Diagnosis of congenital absence of internal carotid artery by power angio sonography.

This case report describes aplasia of the internal carotid artery (ICA) in a preterm infant. The collateral circulation could be mapped with power angio mode (PAM) and was confirmed by conventional angiography. In the literature, there is no case of ICA aplasia diagnosed at this early age. PAM is a method for imaging infantile cerebral vessels as reliably as angiography.

Carotid Artery, Internal↗

Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests.

Raised intracranial pressure leads to increased pressure around the optic nerve (ON), which underlies the formation of papilledema and the enlargement of the dural optic nerve sheath (ONS). In clinical practice, the presence of widened ONSs is demonstrable on neuroimaging, but their relationship to cerebrospinal fluid (CSF) pressure remains unknown. The authors investigated the ONS response to pressure during CSF absorption studies in 12 patients undergoing neurological testing. The ONS diameter was evaluated by serial B-mode ultrasound scans of the anterior ON near its entry into the globe. All patients tested showed ONS diameter changes that exhibited covariance with the alteration of lumbar CSF pressure and were completely reversible during the infusion tests. The maximum difference in ONS diameter between baseline and peak pressure conditions was 1.8 mm on average (range 0.7-3.1 mm), corresponding to an average ONS diameter variation of 45% (range 15-89%). Regression analysis yielded a linear covariance between ONS diameter and CSF pressure with different slopes across subjects (0.019-0.071 mm/mm Hg, mean r = 0.78). However, this linear relationship was only present within a CSF pressure interval. This interval differed between patients: ONS dilation commenced at pressure thresholds between 15 mm Hg and 30 mm Hg and in some patients saturation of the response (constant ONS diameter) occurred between 30 mm Hg and 40 mm Hg. With a single exception, definitely enlarged ONS diameters (> 5 mm) were present when CSF pressure exceeded levels of 30 mm Hg. Retrospectively, discrimination between normal and elevated outflow resistance was possible on the basis of the ONS response to intrathecal infusion alone. It is concluded that the human ONS has sufficient elasticity to allow a detectable dilation in response to intracranial hypertension. Because of a variable pressure-diameter relationship, the subarachnoid pressure cannot be predicted exactly by single scans. Therefore, the clinical relevance of this method relies on the demonstration of pathologically enlarged sheaths or ongoing enlargement on serial ultrasonography studies.

Adult↗

Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension. I. Experimental study.

The optic nerve, ontogenetically part of the central nervous system, is surrounded by subarachnoidal cerebrospinal fluid (CSF) and dura mater. Because of the connection with the intracranial subarachnoidal space, CSF pressure variations influence the optic nerve sheath (ONS) diameter. Histologic studies revealed a segment of the optic nerve in which maximal diameter fluctuations could be expected, namely the bulging dura mater region approximately 3 mm behind the papilla. Twenty preparations of optic nerves obtained post mortem were examined sonographically before and after dilatation of the ONS, by means of measurement from three different projections. After gelatine-induced widening of the subarachnoidal space, the mean diameter increased by 60% at 3 mm behind the optic nerve head, but only by 35% at 10 mm distance. Independent measurements by two examiners correlated highly, which indicates excellent reproducibility of the sonographic measurements. The optimal experimental scanning position was at a right angle to the optic nerve (longitudinal section). Under clinical conditions, however, only axial sections can be obtained using anterior probe positions with transbulbar sound directions. Using such axial projections the 3 mm position proved reliably reproducible. The reduced resolution of the optic nerve itself, allowing it to be distinguished from its surrounding sheath, proved to be somewhat disadvantageous from this projection angle.

Adult↗

Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension II. Patient study.

Up to now, the presence of elevated intracranial pressure (ICP) in acute neurological disorders is suspected by clinical and neuroimaging findings, but its verification depends on invasive techniques. Based on our experimental findings of rapid dilatation of human optic nerve sheaths (ONS), we investigated whether this phenomenon not only happens under chronic, but also under acute conditions of intracranial hypertension. Using optic nerve sonography the ONS was measured at 3 mm behind the papilla in axial transbulbar view. Thirty-nine children admitted to the intensive care unit (ICU) were examined. Of these 24 were being treated for elevated ICP (head trauma, metabolic disorder) and were compared to control patients (outpatients). The ONS diameter (ONSD) found in ICU patients with elevated ICP ranged up to 6.8 mm and was significantly enlarged compared with normal data (Wilcoxon's test, P = 0.007). The ONSD of ICU patients without pressure elevation was in the same range as that of control patients (2.7-4.0 mm). Considering the error of measurement (0.35 mm), the ONSD is regarded as definitely enlarged when 5 mm is exceeded in children above age 4. In younger children, smaller ONSD have to be taken into consideration. We conclude that ultrasound studies of the optic nerve may contribute information about the acutely increased ICP in critically ill patients.

Adolescent↗

The subarachnoid space surrounding the optic nerves. An ultrasound study of the optic nerve sheath.

The presence of enlarged optic nerve sheaths (ONS) suggests that raised intracranial pressure is transmitted to the perineural subarachnoid space (SAS). This phenomenon has gained interest because ultrasound methods are able to quantify the optic nerve sheath diameter (ONSD) in-vivo non-invasively with a resolution below 0.5 mm. In order to study the normal variation and distensibility of the human ONS. Histologic techniques and sonographic measurements were applied to 54 human optic n. specimens before and after exposure to pressure. In untreated postmortem specimens, the largest diameters were found 3 mm behind the globe (baseline range: 2.1 to 4.8 mm). Following volume injection into the orbital perineural SAS, all n. sheaths were enlarged (maximum ONSD 6.5 mm). The sheath expansion affected predominantly its anterior section (mean 1.6 mm, e.g. 50.2%); the posterior regions showed markedly less dilatation (31.6%). No relation was found between the change of ONSD and the baseline diameter. Variance analysis of the sonographic results showed that the observed ONSD change depends on (a) the position of measurement along the nerve, as well as on (b) the origin of the nerve (different/same subject), whereas lateral (left/right) or inter-investigator differences proved negligible. Our results suggest that individual factors determine both baseline sheath diameter and distensibility. The different extent of pressure-induced sheath expansion along the nerve may be partly due to the non-uniform distribution of subarachnoid trabecular fibers between nerve and sheath. In conclusion, measurements of the ONSD for clinical purposes should be targeted to the region immediately behind the globe. Under conditions of raised pressure around the intraorbital optic n., bilateral ONSD measurements should give comparable findings.

Humans↗

Tumor size and prognosis in aggressively treated osteosarcoma.

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.

Adolescent↗

Chronic consumption coagulopathy due to an occult splenic haemangioma: Kasabach-Merritt syndrome.

UNLABELLED: We report an 11-year-old girl with a 2-year history of bruising associated with thrombocytopenia and dysfibrinogenaemia. On admission she presented with a large subcutaneous haematoma and splenomegaly and was severely anaemic. Laboratory investigations revealed signs of consumption coagulopathy. Radiological examination showed splenic, retroperitoneal and intra-ossal haemangiomas. After splenectomy, platelet count and coagulation parameters returned to normal. CONCLUSION: Contrary to widely held views, occult visceral haemangioma can lead to Kasabach-Merritt syndrome beyond infancy and is not necessarily associated with visible cutaneous haemangioma. It should be included in the differential diagnosis of chronic thrombocytopenia at any age. Early determination of fibrinogen degradation product levels is advised in order to detect an underlying chronic consumption coagulopathy prompted by an extensive search for multifocal haemangioma.

Afibrinogenemia↗

Precocious puberty and decreased melatonin secretion due to a hypothalamic hamartoma.

Hypothalamic hamartomata are benign malformations of the brain consisting of heterotopic nervous tissue, and are often associated with precocious puberty and gelastic seizures in early childhood. We report for the first time the melatonin plasma values of a girl with central precocious puberty and gelastic seizures due to a hypothalamic hamartoma. The melatonin plasma levels were low for the chronological age but appropriate for the pubertal status, making a causal relationship between lowered melatonin plasma levels and precocious puberty possible.

Female↗

[Immunologic therapy for glomerulonephritis with combined immunoadsorption and IVIG therapy].

Immunoadsorption is an improvement of extracorporeal therapy which differs from plasmapheresis. After plasma perfusion on a special adsorption filter the patient's plasma is reinfused. Meanwhile more than 270 immunoadsorptions have been performed. 7 patients with SLE and glomerulonephritis as well as 3 patients suffering from Wegener's vasculitis and glomerulonephritis had been treated with combined immunoadsorption and IVIG therapy. After three sessions of immunoadsorption (2-3 1 plasma filtrate) the patients received 10 g 7S-immunoglobulin infusions on three consecutive days. Patients with SLE and end-stage kidney involvement (2 patients) did not show any benefit by the above mentioned treatment regimen. Patients with Wegener's vasculitis and glomerulonephritis showed no significant improvement, except in one of three patients who showed a remarkable decrease in proteinuria. On the other hand, patients with SLE and "moderate" kidney involvement (short course of disease, no fixed structural changes) showed improvement on combined immunoadsorption and IVIG therapy.

Adsorption↗

[Case report: treatment of anti-basement membrane glomerulonephritis with immunoadsorption].

Immunoadsorption (IMAD) is a particle extracorporeal therapy in treatment of various autoimmune diseases which differs from plasmapheresis. In the case presented here IMAD was helpful in the therapy of an acute renal failure due to an antiglomerular basement membrane disease. IMAD resulted in a quick recovery and stabilisation of the renal function. In addition to IMAD, the patient was treated with steroids, an immunosuppressive therapy was started immediately after IMAD. Considering the course of this patient's disease, we are convicted that IMAD was a major factor in the therapeutic success. IMAD was well tolerated by the patient, no side effects were seen.

Acute Disease↗

[Current applications of immunoglobulin therapy].

Treatment with immunoglobulins, initially taking the form of passive immunization and replacement therapy, has been successfully practiced for some time now. In recent years, the possibilities offered by monoclonal antibodies and immunomodulation by immunoglobulins have been added to the therapeutic armamentarium. These forms of therapy have proved successful in particular in the treatment of autoimmune diseases. Their use in the treatment of ITP, the Guillain-Barré syndrome, myasthenia gravis and Kawasaki's disease has, in the meantime, proved successful. Other autoimmune diseases, too, in particular rheumatic diseases, also appear to respond favorable to this form of treatment. These observations, together with the belief that this form of treatment is both reliable and largely free of side effects, has resulted in attempts to use immunoglobulins to treat almost all the so-called autoimmune diseases.

Autoimmune Diseases↗

The direct carotid cavernous fistula: a clinical, pathoanatomical, and physical study.

In order to further elucidate the pathogenesis of the direct carotid cavernous fistulas (dCCF) clinical, patho-anatomical, and physico-mechanical studies were performed. In 27 of 42 patients the dCCF were found to be localized in the segment C4 (according to Teufel, 12), in 13 patients in segment C2 and in only 2 patients in segment C3. The patients with dCCF in segment C4 were significantly younger than those with dCCF in the segments C2 or C3. In none of the patients fractures of the bony walls of the cavernous part of the internal carotid artery (ICA) could be ascertained. On human cadavers it was affirmed that the cavernous branches of the ICA arise nearly exclusively from the top of segment C3 and from the lateral wall of segment C2. The strength of the wall of the cavernous part of the ICA was shown to decline with age as revealed by means of a tensile machine. There were no significant differences between the four segments investigated. As revealed by roentgenograms the distensibility of the ICA within its coverings was shown to be greatest in the segments C2 and C4 and lowest in segment C3. A sudden increase of the intraluminal pressure ruptured the ICA exclusively in the segments C2 and C4. Histological preparations revealed that the trabeculae of the cavernous sinus insert tangentially into the adventitia of the ICA. Taken together these findings strongly support the view that the dCCF are mainly due to a sudden increase of the intraluminal pressure of the ICA.

Adult↗