Complementary and alternative medications consumed by patients with head and neck carcinoma: a pilot study in Germany.

Complementary and alternative medicine (CAM) represents a wide range of treatment modalities. CAM products may interact with enzymes, transport proteins, and may therefore influence drug metabolism. The prevalence and patterns of CAM usage among patients with head and neck carcinoma (HNC) are largely unknown. This cross-sectional study was designed to document pattern of CAM consumption in patients with HNC. Statistical differences in a significantly higher prevalence of CAM consumption between tumor patients (n = 107) and the control group (n = 112) could be detected. Concerning the frequency of CAM usage, we could document a significant increased consumption of CAM among tumor patients (42.8% vs. 62.6%) especially for herbal teas (P < 0.05), phytotherapy (P < 0.001), supplement products (P < 0.05), and "other" supplements (P < 0.005) comparing the controls. Furthermore a significant influence of female gender and an increased CAM usage could be illustrated. Concerning the knowledge of potential interactions of CAM consumption, only 6.25% of the controls and 19.6% of tumor patients know about possible side effects but only 1.7% of the controls and 6.5% of the tumor patients informed their physician about the CAM usage. The frequency of CAM in head and neck tumor patients seems to be relevant in the supervision of anticancer therapies.

Herb-drug interactions in nephrology: documented and theoretical.

Renal patients consuming herbal drugs are at risk for herb-drug interactions by various mechanisms. In transplant recipients, toxicity and underdosage of calcineurin inhibitor-based immunosuppression have been linked to phytochemically triggered activity changes of cytochrome P-450 isoenzyme CYP3A4 metabolism and drug transport proteins. This type of interaction might be triggered by many other plant products besides grapefruit juice and St. Johnâs wort, less well-known for this risk. Other potential herb-drug interactions in renal patients, for example with antidiabetics, anticoagulants or antihypertensives are discussed, although they have not yet been reported. Herb-drug interactions might possibly often go unnoticed, because physicians are not informed about herbal drug consumption by their patients. For better future detection and handling of herb-drug interactions, physicians should expand their knowledge about phytochemicals in herbs and foods.

Reduction of soluble complement receptor 2/CD21 in systemic lupus erythomatosus and Sjogren's syndrome but not juvenile arthritis.

A soluble form of the complement receptor CD21 (sCD21) is shed from the lymphocyte surface. The amount of sCD21 in serum may modulate immunity as sCD21 levels are correlated with several clinical conditions. We report here the serum levels of sCD21 in juvenile arthritis (JA), systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). Using enzyme-linked immunosorbent assay, we determined sCD21 levels in SLE, SS and JA patients. Mann-Whitney test for nonparametric two-tail P value was performed to obtain statistical significance. Cytometrical analysis of synovial fluid leucocytes of JA patients was done on a FACSsort. While sCD21 levels in SLE and SS are reduced to levels previously found in rheumatoid arthritis (RA), JA sCD21 levels were normal. sCD21 levels did not correlate with clinical parameters and immunophenotype of synovial cells. CD4 T cells in the synovium were almost all of the CD45RO memory type and 13 of 40 patients displayed synovial expansion of gammadeltaT cells. CD21 shedding in JA differs from RA/SS/SLE. JA sCD21 levels in synovial fluid are always lower compared to blood levels of the same patients. Analysis of JA synovial T cells indicates a T-cell driven response.

Effects of anti-neutrophil cytoplasm autoantibodies on tissue factor activity by HL-60 cells in vitro.

The effects of cytoplasmic anti-neutrophil cytoplasm autoantibodies (C-ANCA) and perinuclear ANCA (P-ANCA) immunoglobulin G (IgG) on tissue factor (TF) activity using HL-60 cells in vitro were compared with those of medium, lipopolysaccharide (LPS) and control IgG. Cells were also incubated with both ANCA IgG and control IgG in the presence of a submaximal concentration of LPS capable of upregulating TF procoagulant activity (TF-PCA) measured in arbitrary units of TF equivalent (AU-TFEq). The purpose was to search for an additive effect between LPS and ANCA IgG. All IgG preparations increased HL-60 cell TF-PCA in comparison with the medium. When cells were incubated with P-ANCA IgG and LPS (1 micro g/ml), a larger increase was seen (151.23 +/- 31.6 SEM (standard error of the mean) AU-TFEq) than when incubated with control IgG plus LPS (91.01 +/- 18.4 SEM AU-TFEq; P < 0.005), P-ANCA IgG alone (73.68 +/- 12.7 SEM AU-TFEq; P < 0.005) or LPS (1 micro g/ml) (58.11 +/- 7.9 SEM AU-TFEq; P < 0.005). There was concordance between PCA and TF total antigen content by enzyme-linked immunosorbent assay (ELISA). The fact that P-ANCA IgGs upregulate the function of TF in HL-60 cells in combination with LPS adds to information regarding the possible role of ANCAs in the enhancement of TF by different cells, although it does not support the fact that ANCAs alone play a role in mononuclear cell TF upregulation. The additive effects of LPS underline the possible role of pro-inflammatory stimuli in the pathogenesis of ANCA-associated diseases.

ANCA titres, even of IgG subclasses, and soluble CD14 fail to predict relapses in patients with ANCA-associated vasculitis.

BACKGROUND: Antineutrophil cytoplasmic autoantibodies (ANCA) are presumed to reflect disease-activity and to be useful for guidance of immunosuppressive therapy of ANCA-associated systemic vasculitis (AASV), but with respect to conventional ANCA assays this is controversial. ANCA titres, measured in the IgG3 subclass and modern capture ELISAs, have been said to be superior predictors of relapses of AASV. METHODS: In this retrospective study serial measurements of ANCA parameters and soluble CD14 (sCD14) were performed in 169 consecutive sera over a median of 21 months in 18 patients with AASV and related to disease activity, assessed by Birmingham Vasculitis Activity Score (BVAS) for new or deteriorated (BVAS1), and for chronic disease activity (BVAS2). Fourteen patients had Wegener's granulomatosis (WG) and were C-ANCA positive with Pr 3-antibodies and four patients had microscopic polyangiitis (MPA) with P-ANCA and MPO-antibodies. In WG patients ANCA by IIF, Pr 3-ELISA for IgG, IgG1, IgG3, IgG4 and sCD14 were measured, as well as capture ELISA for Pr 3, and in MPA patients ANCA by IIF, MPO-ELISA for IgG and IgG1, IgG3, IgG4, and sCD14 respectively. In eight patients, data collection started at diagnosis, in 10 patients at remission. RESULTS: The parameters predicted neither the nine major relapses (increase of immunosuppression necessary), nor the 26 minor relapses (increase of BVAS1>2) with sufficient sensitivity (>80%) or specificity (> 90%90%), and they also failed to predict relapses within the following 2 months. ANCA-IgG3 and capture ELISA for Pr 3 were not advantageous for prediction of relapses (sensitivity 0.45 and 0.19 respectively), and sCD14 remained elevated in all samples irrespective of disease activity. CONCLUSIONS: There is no rationale for serial measurements of ANCA in AASV. For changes of therapy, the ANCA parameters should only be used in conjunction with clinical information.

Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement.

Successful maintenance therapy with mycophenolate mofetil (MMF) 2 g/d and low-dose oral corticosteroids (OCS) over a period of 15 mo was given to patients with Wegener's granulomatosis (WG) (n = 9) and microscopic polyangiitis (MPA) (n = 2). All patients had severe generalized disease with pauci-immune necrotizing glomerulonephritis and received standard induction therapy with oral cyclophosphamide and OCS for a mean of 14 wk until remission was achieved. Of 11 patients, only one WG patient relapsed in the 14th month of maintenance therapy. Maintenance therapy with MMF was able to further reduce grumbling disease activity as measured by the Birmingham vasculitis activity score (BVAS2) and proteinuria that were still present by the end of induction therapy. OCS could be reduced to a median daily dose of 5 mg and discontinued in three patients. Possible drug-related adverse effects were transient and included abdominal pain, respiratory infection, diarrhea, leukopenia, and a cytomegalovirus-colitis in one patient that was successfully treated with ganciclovir. It is concluded that MMF in combination with low-dose OCS is well tolerated and effective for maintenance therapy of WG and MPA. Long-term treatment with MMF in these diseases is attractive because of its low toxicity. MMF will have to be studied further and compared with cyclophosphamide or azathioprine maintenance therapy in randomized trials.

Familial occurrence of systemic vasculitis and rapidly progressive glomerulonephritis.

Two familial clusters of systemic vasculitis are described. In one family, microscopic polyangiitis and rapidly progressive glomerulonephritis occurred in HLA-identical siblings; in the second family, 3 second- and fourth-degree related members were affected by Wegener's granulomatosis. Published clusters of systemic vasculitides and Goodpasture's syndrome are reviewed, and, together with the observed families, the evidence for genetic susceptibility and a causative role of environmental factors for these diseases with special emphasis on the HLA system is discussed.

Treatment of immunoglobulin A nephropathy.

In this review, therapeutic trials for treatment of IgA nephropathy (Berger's disease) are reviewed and discussed. No disease-specific therapy exists. For treatment of hypertensive patients, angiotensin converting enzyme (ACE) inhibitors are preferred. They also decrease proteinuria and probably slow disease progression. However, there are still no controlled data on the effectiveness of ACE-inhibitors in the absence of hypertension or proteinuria. Renewed enthusiasm for treatment with fish oil arose after the publication of a randomized controlled trial in 1994 and long-term follow-up data of the trial cohort in 1998. Corticoid therapy in IgA nephropathy has been advocated for patients with nephrotic syndrome or crescentic disease. A recent non-randomised trial with long-term follow-up suggests that, in the presence of moderate proteinuria, corticosteroids may ameliorate renal function if administered before the creatinine clearance has decreased below 70 ml/min. Preliminary data suggest that mycophenolate mofetil (MMF) may reduce the risk of clinically significant IgA nephropathy recurring in kidney allografts. Many other promising treatment approaches have been tested, but in most instances results are insufficient for unequivocal conclusions. Several randomized controlled clinical trials are currently testing prednisone, fish oil, ACE-inhibitors, cyclophosphamide, MMF and vitamin E. In the absence of a disease-specific treatment, control of hypertension, proteinuria and probably dyslipidemia are pivotal. Chronic or recurrent infection including ton-sillitis should be treated effectively. Control of daily protein intake to 0.7-0.8 g/kg body weight may retard disease progression.

Calcium ketoglutarate versus calcium acetate for treatment of hyperphosphataemia in patients on maintenance haemodialysis: a cross-over study.

Since dietary restrictions and phosphorus removal by haemodialysis (HD) are not sufficient to control serum phosphate (s-phosphate) levels in dialysis patients the use of oral phosphate binders is mandatory. Calcium ketoglutarate (CaKE) is an analogue of glutamic acid exerting phosphate binding properties. Therefore we compared this substance to calcium acetate (CaAC) in a 24-weeks open cross-over trial in 28 maintenance HD patients. Medications and HD prescriptions were kept unchanged during the trial. Following 2 weeks of withdrawal of phosphate binders, patients were randomly assigned to one of the calcium salts for 12 weeks; after a second withdrawal of 2 weeks, all patients were shifted to the other treatment for another 12 weeks. All patients received equimolar doses of CaKE and CaAC with respect to the amount of prescribed elemental calcium. Treatment with CaAC and CaKE significantly reduced s-phosphate levels after 4 weeks (CaAC 1.95+/-0.6 vs. 2.4+/-0.53 mmol/l, P = 0.004; CaKE 1.95+/-0.4 vs. 2.47+/-0.63 mmol/l, P = 0.0001) reaching a virtually stable plateau over the remaining observation time without significant differences between the groups. The incidence of hypercalcaemia defined as a serum calcium level > or =2.8 mmol/l was significantly higher in CaAC than in CaKE treated patients (n = 8 vs. n = 1, P = 0.03). There were no significant differences in serum intact parathyroid hormone (PTH) bicarbonate, albumin or calcitriol levels between the groups after 12 weeks treatment. We conclude that CaKE is as effective as CaAC for treatment of hyperphosphataemia in chronic HD patients and may be particularly helpful in patients who are prone to develop hypercalcaemia.

New developments in pathogenesis of systemic vasculitis.

Aspects of pathogenesis of primary systemic vasculitis are highlighted in this review. The cause of these entities is still obscure, although new information on the possible role of infections has emerged. Success of antimicrobial treatment to ameliorate systemic vasculitis, for which proof was recently provided, adds to the new information. Apart from new data that point to a precipitating role for environmental toxins the background for development of these diseases is most likely genetic predisposition. Reports on hereditary alpha 1-antitrypsin deficiency, the link between systemic vasculitis and human leukocyte antigen molecules, and an animal model of spontaneous granulomatous arteritis in mice with a hereditary deficit in Fas-mediated apoptosis, are some of the new data that strongly favor genetic predisposition. Progress has been made in the process of identification of the agonists and antagonists in the front line of vasculitic inflammation. The interaction of blood cells (e.g., neutrophils and monocytes) with vascular endothelium has become more evident as have the signals for the release of harmful proteolytic enzymes. Antineutrophil cytoplasmic antibodies, which are important markers of disease, may be actively involved in these processes.

Rapidly progressive IgA nephropathy with anti-myeloperoxidase antibodies benefits from immunosuppression.

CLINICAL OBSERVATIONS: Three patients with previous pulmonary infections were recently admitted with rapidly progressive renal failure. Renal biopsy showed crescentic glomerulonephritis with deposits of IgA, C3c and C3d. Serology disclosed P-ANCA with high-titer anti-myeloperoxidase antibodies. Two out of three patients became dialysis dependent despite immunosuppression with methylprednisolone and cyclophosphamide. Renal function improved in both patients after 2 weeks and 9 months, respectively, permitting termination of hemodialysis. All patients benefited from immunosuppressive treatment which is currently still being continued. CONCLUSION: The data suggest that early immunosuppression is beneficial in patients presenting with crescentic rapidly progressive IgA GN and anti-myeloperoxidase antibodies, which may represent a novel subset of crescentic IgA GN associated with high-titer anti-myeloperoxidase antibodies constituting an overlap group between microscopic polyangiitis and IgA GN.

Differential effects of ACE inhibitors and vasodilators on renal function curve in patients with primary hypertension.

OBJECTIVE: In experimental studies differential effects of antihypertensive agents on the renal function curve have been observed: in SHR captopril lowered the slope of the renal function curve, i.e. blood pressure (BP) became salt sensitive, whereas hydralazine shifted the curve without changing its slope. To evaluate whether ACE inhibitors and vasodilators have different effects on salt sensitivity of BP in humans, we compared the effect of the ACE inhibitor cilazapril and the vasodilator dihydralazine on the renal function curve in a randomized prospective single blind cross-over study. DESIGN: Nine patients (1 f, 8 m, mean age 41 +/- 4 y) with mild to moderate primary hypertension were put on low (20 mmol/d) and on high salt diet (200 mmol/d). Drugs were given in random low salt+cilazapril, high salt+cilazapril; low salt+dihydralazine, high salt+dihydralazine; or in reverse order. RESULTS: All antihypertensive interventions lowered BP, but the averaged posttreatment MAP was significantly (p < 0.02) lower with cilazapril on low salt intake (83.6 +/- 2.8 mmHg) than with all of the following: cilazapril on high salt intake (86.4 +/- 2.9 mmHg), dihydralazine on low (91.6 +/- 3.2 mmHg) and high salt (90.1 +/- 3.3 mmHg) intake. Probably as a result of sympathetic activation, average daily heart rate was higher after dihydralazine on low (72.9 +/- 2.9 b/min) and high salt intake (72.4 +/- 2.8 b/min) than after cilazapril on either salt intake (68.7 +/- 3.1 and 62.7 +/- 3.2 b/min). CONCLUSIONS: The results document that BP reduction after acute ACE inhibition is a function of salt intake, i.e. with ACE inhibitor therapy, BP is "salt sensitive". In contrast, vasodilators of the dihydralazine type have similar antihypertensive effects on low and high salt intake. To the extent that the findings of this short-term study can be extrapolated to long-term effects they suggest that intrarenal mechanisms, i.e. resetting of the pressure-natriuresis relationship, are involved in the long-term antihypertensive action of ACE inhibitors.

Effects of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection.

The goal of this study was to quantitate the effect of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection. The study was carried out on low and normal salt intake to assess potential interaction with salt balance. Eighteen healthy normotensive volunteers were examined in a double placebo-controlled parallel group design. Subjects were randomly put on either low-salt (20 mmol/day) or normal-salt (110 mmol/day) diet. In either arm of the diet volunteers were first treated orally with placebo for 1 week and subsequently with 2.5 mg/day of the angiotensin-converting enzyme inhibitor cilazapril for another 1 week. Cumulative 24-h urinary sodium excretion was measured on the 6th day of the respective week after sham injection and on the 7th day after injection of 40 mg furosemide. Compared to pretreatment with placebo, pretreatment with cilazapril resulted in a higher cumulative sodium excretion after furosemide injection (day 7) than after the sham injection (day 6) on both salt intakes. The difference in natriuresis (cilazapril versus placebo) was evident 2 and 3 h after injection of furosemide. Neither the time of onset nor the magnitude of antinatriuresis were affected by cilazapril. Following furosemide angiotensin II increased significantly even after cilazapril pretreatment. Cilazapril tended to reduce urinary furosemide excretion. At any given urinary furosemide concentration, the increment in urinary sodium excretion was significantly greater with cilazapril irrespective of salt intake. The study shows that (a) cilazapril increases furosemide-induced natriuresis irrespective of salt intake, (b) antinatriuresis is not affected by cilazapril, and (c) angiotensin II levels rise after furosemide on cilazapril in therapeutic doses.