Vitamin K: an old vitamin in a new perspective.

The topic of "Vitamin K" is currently booming on the health products market. Vitamin K is known to be important for blood coagulation. Current research increasingly indicates that the antihaemorrhagic vitamin has a considerable benefit in the prevention and treatment of bone and vascular disease. Vitamin K1 (phylloquinone) is more abundant in foods but less bioactive than the vitamin K2 menaquinones (especially MK-7, menaquinone-7). Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically reduced. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, inhibit vessel wall calcification, support endothelial integrity, facilitate bone mineralization, are involved in tissue renewal and cell growth control, and have numerous other effects. The following review describes the history of vitamin K, the physiological significance of the K vitamers, updates skeletal and cardiovascular benefits and important interactions with drugs.

[Magnesium deficiency and therapy in cardiac arrhythmias: recommendations of the German Society for Magnesium Research]. / Magnesiummangel und Magnesiumtherapie bei Herzrhythmusstörungen. Empfehlungen der Gesellschaft für Magnesium-Forschung e. V.

Aim of the recommendations of the German Society for Magnesium Research: Recognition and compensation of magnesium deficiency in patients with risk factors for cardiac arrhythmias or manifest rhythm disturbances. Prevention of arrhythmias by administration of magnesium. Therapeutic administration of magnesium in patients with arrhythmias with and without magnesium deficiency. The current state of knowledge claims for considering the status of magnesium and the possibility of a therapeutic intervention with magnesium within the concept of the treatment of cardiovascular diseases. The use of magnesium as single agent or as an adjunct to other therapeutic actions in the prevention and therapy of cardiac arrhythmias can be effective and, in case of oral administration, very safe. In case of parenteral administration, it is important to use adequate doses, monitor cardiovascular and neuromuscular parameters and to consider contraindications.

[Tubulointerstitial nephritis with uveitis (TINU) syndrome. A relatively rare rheumatological differential diagnosis with unexplained uveitis]. / Tubulointerstitielle-Nephritis-mit-Uveitis (TINU)-Syndrom. Eine eher seltene rheumatologische Differenzialdiagnose bei unklarer Uveitis.

The tubulo-interstitial nephritis and uveitis (TINU) syndrome, first described in 1975, is a rare disease most probably of autoimmune origin that is characterized by unilateral or bilateral uveitis and tubulointerstitial nephritis. Most patients are adolescents and it is sometimes associated with other autoimmune diseases, such as spondyloarthritis, rheumatoid arthritis and hyperthyroidosis. This article reports the case of a 43-year-old female patient who presented with refractory recurrent bilateral uveitis despite therapy with high doses of corticosteroids in combination with cyclosporin. When the patient was referred to this hospital for rheumatological examination after almost 1 year of therapy, mild renal insufficiency and proteinuria were found. The kidney biopsy revealed interstitial nephritis, partly crescent-shaped and partly chronic. A diagnosis of TINU syndrome was made and treatment with adalimumab in combination with methotrexate was started. The favorable clinical outcome indicated that tumor necrosis factor (TNF) alpha may play an important role in the pathogenesis of TINU syndrome.

[Arthritis of the atlanto-axial joint with inflammatory neck pain as a primary manifestation of seronegative rheumatoid arthritis]. / Atlantoaxiale Arthritis mit entzündlichem Nackenschmerz als Erstmanifestation einer seronegativen rheumatoiden Arthritis.

HISTORY AND ADMISSION FINDINGS: A 68-year-old woman with known degenerative joint disease suffered from increasing neck pain. Physical examination revealed painfully restricted movement of the cervical spine. INVESTIGATIONS: Erythrocyte sedimentation rate and C-reactive protein were increased. Tests for rheumatoid factors, antinuclear, anti-citrullinated protein and anti-neutrophil cytoplasmic antibody were negative. Cervical spine x-ray showed osteochondrosis with partially bridging spondylosis at C5/C6, but there was no atlanto-axial dislocation. Magnetic resonance imaging (MRI) revealed bone marrow edema and hyperintensity of the odontoid process, but there were no indications of fissures or fracture lines. TREATMENT AND COURSE: These findings indicated seronegative rheumatoid arthritis, with predominantly active atlanto-axial arthritis. After methotrexate and prednisolone had been administered the symptoms improved rapidly and inflammatory parameters returned to normal. Three months later no atlanto-axial arthritis was seen at MRI. CONCLUSION: Rheumatoid arthritis involving the atlanto-axial region should be considered in patients with persisting neck pain and signs of inflammation.

Limited effects of selenium substitution in the prevention of radiation-associated toxicities. results of a randomized study in head and neck cancer patients.

OBJECTIVE: The substitution of selenium activates the selenium-dependent enzyme glutathione peroxidase, which is important for scavenging free radicals. To date, only limited data are available about the clinical impact of selenium regarding the toxicities due to free radical producing therapies, e.g. irradiation or chemotherapy, and therefore the objective of this study was to investigate the clinical impact of selenium in such therapies. PATIENTS AND METHODS: 39 patients (8 female, 31 male) with advanced head and neck cancer were included in a randomised phase II study. The mean age was 63.52+/-9.31 years. Tumour localizations: oral cavity 15 patients, oropharynx 19 patients, hypopharynx 5 patients, carcinoma of unknown primary 1 patient. Group A (n=22) received 500 microg sodium selenite on the days of radiotherapy and 300 microg sodium selenite on days without radiotherapy. Group B (17) was irradiated without any selenium substitution. Both groups were well balanced according to age, gender, localization and stage of the tumour. The RTOG grade of radiation-associated toxicities was evaluated once per week. RESULTS: The following serious toxicities were observed (group A vs. group B): dysphagia 22.7% vs. 35.3%, loss of taste 22.7% vs. 47.1%, dry mouth 22.7% vs. 23.5%, and stomatitis 36.4% vs. 23.5%. A statistical trend (Fisher's exact test) was only seen for the loss of taste (p=0.172). The weekly patient analysis (Student's t-test) showed a significant reduction of dysphagia in the selenium group (Group 1) at the last week of irradiation. CONCLUSION: This small randomised trial showed limited effects of selenium in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy of head and neck cancer.

Complementary and alternative medicine in lung cancer patients: a neglected phenomenon?

Study on the use of complementary and alternative medicine (CAM) in lung cancer patients has been widely neglected. Therefore, we initiated a study on the use of CAM in lung cancer patients in addition to radiation treatment. Overall, 120 patients from 3 institutions were interviewed by a standardized questionnaire. Besides the tumor parameters and the use of CAM, the reason for the use, patient information of the medication, the information sources and the subjective condition of the patient. Altogether, 54% of the patients reported using CAM (66% of female patients, 52% of male patients). The most frequently used CAM measures were vitamin combinations (17%), mistletoe (15%), and selenium (12%). A total of 52% reported the wish to support the tumor treatment as a reason for using CAM and 27% had a 'better feeling' using CAM. 50% of CAM was bought by the patients themselves and 50% were prescribed by their family physicians. The use of CAM is frequent in lung cancer patients. Our results suggest that it is very important to obtain information on the CAM use of patients and, particularly in controlled clinical trials, to prospectively document it.

Early onset of a decreased intracellular magnesium and phosphate concentration in smooth muscle cell of SHR.

A decrease in total magnesium content is not a direct proof of a decreased magnesium ion concentration. It could reflect a phosphate alteration or an ATP metabolism disorder. Plasma phosphate levels are lower in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto rats (WKYs), and defects in membrane regulation or mitochondrial ATP synthase occur. Only sparse data exist concerning cellular magnesium and phosphate concentrations in hypertensive cells. In aortic smooth muscle cells from 10 SHRs of the Münster strain and 10 age-matched normotensive WKY rats, the intracellular phosphate and magnesium content was measured by electron probe X-ray microanalysis (Camscan CS 24 apparatus, Cambridge, U.K.). The Mg++ content was 0.09 +/- 0.15 g/kg dry weight in SHRs versus 1.15 +/- 0.10 g/kg dry weight in WKY rats (p < 0.01). Vascular smooth muscle phosphate content was 23.6 +/- 0.79 g/kg dry weight in WKY rats versus 15.81 +/- 1.22 g/kg dry weight in SHRs (p < 0.01). In aortic smooth muscle cells of one month old SHRs intracellular magnesium was measured as 1.05 +/- 0.08 versus 1.09 +/- 0.09 g/kg dry weight in WKYs. Intracellular phosphate concentration in one month old SHRs was 18.71 +/- 2.41 versus 21.36 +/- 1.25 g/kg dry weight in WKYs (eight animals in each group). Aortic smooth muscle cells of SHRs are caracterized by markedly lowered intracellular phosphate and magnesium concentrations, resulting in an altered ATP-metabolism, as described earlier. Possibly a membrane defect or a magnesium deficiency or disturbed magnesium channels are responsible for the early onset in the pathogenesis of primary hypertension.

Selenium in the treatment of head and neck lymphedema.

OBJECTIVE: To investigate the impact of selenium in the treatment of lymphedema of the head and neck region after radiotherapy alone or in combination with surgery. SUBJECTS AND MATERIALS: Between June 1996 and June 2001 a total of 36 cancer patients (29 male, 7 female; median age 61 years) were treated with selenium for persistent, extensive or progressive lymphedema of the head and neck region. Twenty had interstitial endolaryngeal edema associated with stridor and dyspnea. All patients received 350 microg/m(2) body surface sodium selenite medication p.o. daily (total dose 50 microg per day) for a period of 4-6 weeks after radiotherapy. The optimal effect of the selenium treatment was assessed after 4 weeks of therapy using the Miller score system. A visual analogue scale on a scale of 0-10 was used to assess the patient's quality of life prior to and after selenium. RESULTS: 75% of the patients had an improvement of the Miller score of one stage or more. The self-assessment of quality of life using the visual analogue scale improved significantly after selenium treatment with a reduction of 4.4 points (p < 0.05). Of the 20 patients with endolaryngeal edema tracheostomy was not necessary in 13 patients (65%), but 5 and 2 received a temporary or permanent tracheostomy, respectively. No episode of erysipelas was observed in all study patients. CONCLUSION: Our results suggest a short positive effect of sodium selenite on secondary head and neck lymphedema caused by radiotherapy alone or in combination with surgery.

Early-onset increased calcium and decreased magnesium concentrations and an increased calcium/magnesium ratio in SHR versus WKY.

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives, our group showed increased calcium and decreased magnesium and an increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4+/-9.8 mmHg) and 13 normotensive rats (NT, systolic blood pressure 118.5+/-7.2 mmHg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron-probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick. The calcium content was 124.7+/-4.5* mmol/kg dry weight in SHR versus 110.3+/-4.1 mmol/kg dry weight in NT (Means+/-SD, p < 0.01), the magnesium content was 35.5+/-3.9* in SHR versus 50.1+/-4.9 mmol/kg dry weight in NT /p < 0.01). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56+/-0.39* versus 2.23+/-0.27, p < 0.01). In hypertensive one month old animals the increase in the calcium/magnesium ratio was not as pronounced as in 9 month old animals. The calcium/magnesium ratio was measured 3.3+/-0.42 in SHR (n = 8) as compared to 2.51+/-0.39 in normotensive animals (n = 8, p < 0.01). Aortic smooth muscle cells from SHR are characterized by markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. The increased calcium/magnesium ratio in hypertensive cells may be a pathogenetic factor for the development of arteriosclerosis and hypertension.

[Use of complementary/alternative therapy methods by patients with breast cancer]. / Anwendung komplementärer/alternativer Therapiemassnahmen bei Patientinnen mit Brustkrebs.

BACKGROUND: Complementary/alternative medicine (CAM) is gaining increasing importance especially in the treatment of patients with breast carcinoma. The purpose of this analysis was to investigate the prevalence of CAM in patients with breast carcinoma, to statistically describe the preparations and therapies used, and to determine the reasons for their use, the source of information and the individual perception. PATIENTS AND METHODS: The statements of 203 patients with breast carcinoma who underwent radiotherapy were analyzed. The median age was 54 years (range 38-77 years). All patients underwent surgery as first therapy. 36 patients received a second-line radiotherapy because of metastases (27 patients) or local recurrence (9 patients). RESULTS: 159 patients (78%) stated to carry out an additional treatment. 31 out of the 36 patients with metastases or local recurrence used CAM. Vitamin preparations (67%), mistletoe therapy (59%), and mineral preparations (33%) were used most frequently. 70% of the patients used a combination of two or more preparations/therapies. The most cited reason for using CAM was the aim of increasing quality of life (28%) and improving the immune system (27%). 72% stated an improvement of their individual perception. The main source of information was the general practitioner or the gynecologist. CONCLUSION: The radiotherapist has to take these complementary/alternative therapies into consideration; their importance should be evaluated in further studies.

Changes in calcaneal trabecular bone structure assessed with high-resolution MR imaging in patients with kidney transplantation.

The purpose of this study was to use high-resolution magnetic resonance (HR-MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after renal transplantation and to compare this technique with bone mineral density (BMD) in predicting therapy-induced bone loss and osteoporotic fracture status. HR-MR imaging (voxel size: 0.195 x 0.195 x 1 mm) was performed at 1.5 T with an axial and sagittal orientation in 48 patients after transplantation, 12 patients before renal transplantation and 20 healthy controls. Structure measures analogous to standard histomorphometry and fractal dimension were determined in these images. BMD measurements of the lumbar spine and the proximal femur were obtained in the healthy female controls and the patients. Vertebral and peripheral fracture status were determined in all patients. The structural measures app.BV/TV, Tb.Sp, Tb.Th and Tb.N showed significant differences between controls and patients (p<0.05) while fractal dimension showed no significant differences. Neither the structural measures nor BMD showed significant differences between patients before and after transplantation. Correlations between time after transplantation versus structural measures and BMD were not significant. Differences between fracture and nonfracture patients were significant for the structural measures app.BV/TV, Tb.Sp and Tb.N (axial images) as well as for app.Tb.Th (sagittal images) and spine BMD (p<0.05) but not for hip BMD. Using odds ratios the strongest discriminators between patients with and without fractures were app. BV/TV, app.Tb.Sp (axial images) and app.Tb.Th (sagittal images), even after adjustment for age and BMD. Using receiver operating characteristic analysis the highest diagnostic performance was found for a combination of BMD and structural measures. In conclusion, our results indicate that structural measures obtained from HR-MR images may be used to characterize fracture incidence in kidney transplant patients; the best results, however, are obtained using a combination of BMD and structural measures.