Biomedical subjects
Publications and source records attributed to H J Anders.
The elevated cardiovascular mortality seen in patients with renal insufficiency makes it imperative that this condition be detected and treated in good time. The results of recent studies have led to fundamental changes in the therapeutic approach to the patient with kidney disease. A range of new medications is now available for the treatment of complications of renal failure.
Toll-like receptor (TLR)-9 recognizes CpG motifs in microbial DNA. TLR9 signalling stimulates innate antimicrobial immunity and modulates adaptive immune responses including autoimmunity against chromatin, e.g., in systemic lupus erythematosus (SLE). This review summarizes the available data for a role of TLR9 signalling in lupus and discusses the following questions that arise from these observations: 1) Is CpG-DNA/TLR9 interaction involved in infection-induced disease activity of lupus? 2) What are the risks of CpG motifs in vaccine adjuvants for lupus patients? 3) Is TLR9 signalling involved in the pathogenesis of lupus by recognizing self DNA?
BACKGROUND: Psoriatic onycho-pachydermo-periostitis is a rare manifestation of psoriatic arthritis. It is characterized by the trias of psoriatic onychosis, tender soft tissue thickening, and osteoperiostitis of the distal phalanges in the absence of distal interphalangeal arthritis. Recommendations for the treatment of symptomatic POPP are not available. AIM OF THE STUDY: Treatment of a symptomatic 49-year old male. METHODS: Sulfasalazine 1000mg b.i.d., p.o. for 8 months followed by radiotherapy of both hands with 6x0.5 Gy. RESULTS: No clinical response was observed with either of the two treatments. CONCLUSIONS: The course of this single case does not support sulfasalazine treatment or radiotherapy in psoriatic onycho-pachydermo-periostitis.
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Pentalogy of Fallot is a rare cyanotic congenital heart disease characterized by biventricular origin of the aorta above a large ventricular septal defect, obstruction of the pulmonary outflow, right ventricular hypertrophy (tetralogy of Fallot), and an atrial septal defect. Mortality due to syncope, arrhythmia or congestive heart failure is about 75% by the age of 10 years and 97% by the age of 40. We report a 69-year old female with uncorrected pentalogy of Fallot who suffered from recurrent syncope during classic cyanotic spells. Treatment with bisoprolol is recommended in symptomatic children and also improved symptoms in our patient. We conclude that single patients with pentalogy of Fallot reach the seventh decade and that cyanotic congenital heart disease is a rare cause of syncope in the elderly.
The chemokine receptors CCR2 and CCR5 play important roles in the recruitment of monocytes/macrophages and T cells. To better understand the role of both receptors in murine models of inflammatory diseases and to recognize potential problems when correlating these data to humans, we have generated mAbs against murine CCR2 and CCR5. In mice CCR2 is homogeneously expressed on monocytes and on 2--15% of T cells, closely resembling the expression pattern in humans. In contrast to humans, murine NK cells are highly CCR5 positive. In addition, CCR5 is expressed on 3--10% of CD4 and 10--40% of CD8-positive T cells and is weakly detectable on monocytes. Using a model of immune complex nephritis, we examined the effects of inflammation on chemokine receptor expression and found a 10-fold enrichment of CCR5(+) and CCR2(+) T cells in the inflamed kidneys. The activity of various chemokines and the antagonistic properties of the mAbs were measured by ligand-induced internalization of CCR2 and CCR5 on primary leukocytes. The Ab MC-21 (anti-CCR2) reduced the activity of murine monocyte chemotactic protein 1 by 95%, whereas the Ab MC-68 (anti-CCR5) blocked over 99% of the macrophage-inflammatory protein 1alpha and RANTES activity. MC-21 and MC-68 efficiently blocked the ligand binding to CCR2 and CCR5 with an IC(50) of 0.09 and 0.6--1.0 microg/ml, respectively. In good correlation to these in vitro data, MC-21 almost completely prevented the influx of monocytes in thioglycollate-induced peritonitis. Therefore, both Abs appear as useful reagents to further study the role of CCR2 and CCR5 in murine disease models.
BACKGROUND: Nailfold capillary microscopy is a routine procedure in the investigation of patients with Raynaud's phenomenon (RP). As a standard method, nailfold capillary morphology is inspected with a stereomicroscope to look for capillary abnormalities such as giant loops, avascular areas, and bushy capillaries, which have all been found to be associated with certain connective tissue diseases. AIM: To investigate prospectively whether nailfold capillary inspection using an ophthalmoscope is of equivalent diagnostic value to standard nailfold capillary microscopy. METHOD: All the fingers of 26 patients with RP were examined in a blinded fashion and compared with the final diagnosis one month later. RESULTS: All giant loops, large avascular areas, and bushy capillaries were identified by both methods. The correlation for moderate avascular areas and crossed capillaries was 0.93 and 0.955 respectively. The correlation for minor abnormalities that do not contribute to the differentiation between primary and secondary RP was 0.837 and 0.861 respectively. All patients were classified identically by the two methods. CONCLUSION: For the evaluation of patients with RP, nailfold capillary morphology can reliably be assessed with an ophthalmoscope.
The estimation of glomerular filtration rate is important for the medical treatment of patients with rheumatoid arthritis (RA). However, the determination of endogenous creatinine clearance (Clcr) from a 24-h urine collection is an unreliable and time-consuming procedure. We therefore tested the accuracy of six equations and one nomogram for the prediction of Clcr from serum creatinine (Scr) in 38 patients with RA and 20 controls. A positive correlation was found for all methods in the controls (r = 0.83-0.94) and RA patients (r = 0.51-0.69). The methods did not overestimate Clcr in RA. In the RA group the simple formula published by Cockcroft [Clcr = ((140 - age) x body weight)/(72 x Scr), x 0.85 for females] showed the best correlation with the measured Clcr. In RA the Cockroft formula can reliably be used to predict Clcr from Scr.
Over the past 25 years, nailfold capillary microscopy (NCM) has gained diagnostic value in the field of rheumatology based on descriptive data from patients with distinct connective tissue diseases (CTD). We prospectively analysed NCM findings from 116 patients selected for NCM by one of the following indications: (1) suspected diffuse or limited scleroderma or dermatomyositis, (2) evaluation of Raynaud's phenomenon (RP) or (3) suspected small-vessel vasculitis. Nailfold haemorrhages, and enlarged and tortuous nailfold capillaries ('lupus pattern') were found to comparable degrees in patients with CTD and primary RP. Only giant loops, bushy capillaries and avascular areas indicated CTD; 92% of patients with Wegener's granulomatosis (WG) had avascular areas. From all nailfold capillary abnormalities, only bushy capillaries, giant loops and avascular areas support a suspected CTD. A lupus-like pattern is not diagnostic. Avascular areas are a typical abnormality in patients with WG, for which NCM findings have not been described previously.
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Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.
Scleroderma renal crisis is characterized by intimal thickening of the afferent glomerular arterioles resulting in hypertension and fibrinoid necrosis of the capillary tuff. We report a 67-year-old man with long-standing systemic sclerosis who developed normotensive progressive renal failure, proteinuria, and a nephritic urinary sediment with serum myeloperoxidase-antineutrophil cytoplasmatic antibodies (MPO-ANCA). Renal biopsy showed pauci-immune crescentic glomerulonephritis but none of the typical vascular changes of scleroderma renal crisis. Because comparable cases have recently been reported from Japan, normotensive MPO-ANCA-positive crescentic glomerulonephritis may form an entity of progressive renal failure in scleroderma.
In patients with acquired immune deficiency syndrome (AIDS), hypoosmolality is frequently observed, whereas hypernatremia is distinctly rare. We report two patients with advanced AIDS and cytomegalovirus (CMV) encephalitis, who developed severe hypernatremia without any thirst sensation, that is, adipsic hypernatremia. Both developed severe hypernatremia of up to 164 and 162 mmol/L, with serum osmolalities of 358 and 344 mOsmol/kg while remaining alert and denying thirst. Serum antidiuretic hormone (ADH) levels were 0.9 and 1.5 pg/mL, inappropriately low for the concomitant serum osmolalities. Vital signs were stable. During hypernatremia, urine osmolalities were 327 and 340 mOsmol/kg, and urine Na+ levels were 56 and 119 mmol/L, respectively. Periventricular white matter lesions were seen on cerebral nuclear magnetic resonance imaging (NMRI) in case 1, but the pituitary appeared normal in both cases. Survival after onset of hypernatremia was 6 and 4 weeks, respectively. Autopsy in case 1 showed typical findings of CMV encephalitis but normal pituitary, confirming that infection with HIV or CMV most likely caused the dysfunction of the central osmostat.
OBJECTIVES: To study the prevalence and possible mechanisms of hypocalcaemia in HIV infection and AIDS. SUBJECTS: 828 patients with HIV infection or AIDS and 549 controls. INTERVENTIONS: Measurements of total serum calcium and albumin levels. Parameters of calcium homeostatis were determined in a subgroup of 21 hypocalcaemic AIDS patients. RESULTS: Mean serum calcium was 2.34 +/- 0.13 mmol L-1 in the HIV group vs. 2.46 +/- 0.10 mmol L-1 in controls (P < 0.0001). After adjusting for serum albumin, hypocalcaemia was present in 6.5% of the HIV group vs. 1.1% of controls. Mean serum calcium was declining according to CDC groups, and differed significantly from controls in each group. Regression coefficients of cacium vs. albumin were 0.147 amongst HIV-infected patients and 0.106 for controls. In the subgroup of hypocalcaemic patients with AIDS, 10/21 had vitamin D deficiency, six of these with low ionized calcium levels. Low serum PTH was found in 2/21 patients. Magnesium deficiency in 1/21. Of the remaining eight patients, only one had secondary hyperparathyroidism, while the other seven lacked an adequate PTH response, despite low ionized calcium levels in four subjects. CONCLUSIONS: Mean serum calcium concentrations were lower through all CDC stages, irrespective of albumin, resulting in a higher prevalence of hypocalcaemia in HIV-positive patients compared with controls. In a considerable number, this seems to be caused by vitamin D deficiency and potentially a lack of adequate PTH secretion, but further studies are needed to confirm this.
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Cytomegalovirus (CMV) infection is one of the most important opportunistic infections in AIDS. The most common manifestation of neurological CMV disease in HIV infection is retinitis followed by encephalitis, polyradiculopathy, and multifocal neuropathy. Untreated necrotizing retinitis proceeds to blindness but can readily be diagnosed by ophthalmological examination. CMV polyradiculopathy presents as subacute leg weakness, paraesthesia, and urinary retention. Untreated patients develop ascending paralysis and die within weeks. Multifocal neuropathy commonly affects the radial, ulnar, and peroneal nerves but cranial nerves may also be involved. Confusion, cranial nerve palsies, and hyperreflexia are signs of ventriculoencephalitis, whereas the presentation of diffuse micronodular encephalitis is often asymptomatic. The diagnostic approach relies on the detection of CMV DNA in the cerebrospinal fluid for polyradiculopathy, encephalitis, and neuropathy. Neuroimaging can exclude other causes of encephalitis and polyradiculopathy. Ganciclovir, foscarnet, and cidofovir monotherapy are current medical treatment options. Intraocular administration can be used for refractory retinitis, but additional systemic prophylaxis is required to suppress extraocular disease. Ganciclovir and foscarnet have improved the prognosis of multifocal neuropathy and polyradiculopathy, but response rates for encephalitis are low. However, despite therapy survival of central nervous CMV disease is still limited to months. Recently highly active antiretroviral therapy (HAART) has decreased the overall incidence of CMV disease in AIDS. Furthermore (HAART) has become a mainstay for CMV therapy by improving the patient's immunocompetence against CMV.
Myocardial involvement in polymyositis is commonly suspected in noninvasive studies, but symptomatic cardiac disease is rare. We describe a 27-year-old woman with a 6 year history of severe polymyositis and persistent elevation of creatine phosphokinase-MB isoenzyme who suddenly developed congestive heart failure and bradycardia-tachycardia syndrome. Autopsy revealed severe myocardial fibrosis without inflammatory cell infiltrates concomitant to active polymyositis of the skeletal muscles despite intensive longterm immunosuppressive therapy.