Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

Blazar spectral variability as explained by a twisted inhomogeneous jet.

Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement and contraction of the variability timescales, so that most blazars appear as luminous sources characterized by noticeable and fast changes in brightness at all frequencies. The mechanism that produces this unpredictable variability is under debate, but proposed mechanisms include injection, acceleration and cooling of particles, with possible intervention of shock waves or turbulence. Changes in the viewing angle of the observed emitting knots or jet regions have also been suggested as an explanation of flaring events and can also explain specific properties of blazar emission, such as intra-day variability, quasi-periodicity and the delay of radio flux variations relative to optical changes. Such a geometric interpretation, however, is not universally accepted because alternative explanations based on changes in physical conditions-such as the size and speed of the emitting zone, the magnetic field, the number of emitting particles and their energy distribution-can explain snapshots of the spectral behaviour of blazars in many cases. Here we report the results of optical-to-radio-wavelength monitoring of the blazar CTA 102 and show that the observed long-term trends of the flux and spectral variability are best explained by an inhomogeneous, curved jet that undergoes changes in orientation over time. We propose that magnetohydrodynamic instabilities or rotation of the twisted jet cause different jet regions to change their orientation and hence their relative Doppler factors. In particular, the extreme optical outburst of 2016-2017 (brightness increase of six magnitudes) occurred when the corresponding emitting region had a small viewing angle. The agreement between observations and theoretical predictions can be seen as further validation of the relativistic beaming theory.

In vitro experiments demonstrate that monocytes and dendritic cells are rendered apoptotic by extracorporeal photochemotherapy, but exhibit unaffected surviving and maturing capacity after 30 Gy gamma irradiation.

Extracorporeal photochemotherapy (ECP) has been shown to induce apoptosis in lymphocytes. Until recently the prevailing opinion has been that the monocytes were mainly not affected by this treatment. This study has investigated the effect of ECP and gamma irradiation on monocytes and immature dendritic cells (DC) in vitro and followed the ability of the cells to differentiate and survive post treatment. ECP induced apoptosis in lymphocytes, monocytes and immature DC within 72 h following treatment, in contrast to 30 Gy gamma irradiation, which seemed mainly to affect lymphocytes. The minority of the surviving ECP-treated monocytes presented a reduced ability to differentiate into immature DC within this time frame. We also demonstrated that immature DC after ECP-treatment lost their normal ability to mature on stimulation with lipopolysaccharide. As monocytes and immature DC seem to have a reduced ability to differentiate after ECP-treatment, it is suggested that the therapeutic effect of ECP is caused by in vivo effects of reinfused apoptotic cells, rather than by infusion of monocytes induced to differentiate into immature DC.

Renal involvement in primary Sjögren's syndrome.

Renal involvement was evaluated in 62 patients with primary Sjögren's syndrome, classified according to criteria proposed by The European Classification Criteria Group. Urine concentration capacity was tested using intranasal 1-desamino-8-D-arginine-vasopressin. For patients with urine pH>5.5 without metabolic acidosis (n=28), an acidification test with ammonium chloride was performed. Urinary citrate, albumin, NAG, ALP and beta2-microglobulin were measured and creatinine clearance was calculated. Maximum urine concentration capacity and creatinine clearance were reduced in 13 (21%). Albumin excretion was >30 microg/min in only one patient (1.6%). Seven patients (11.3%) had complete or incomplete distal renal tubular acidosis (dRTA), four had reduced creatinine clearance and five had reduced maximum urine concentration capacity. The ratio of citrate/creatinine in spot urine was below the 2.5 percentile in all patients with complete or incomplete dRTA. The prevalence of dRTA was lower than in previous studies. There were also few patients with signs of glomerular disease (1.6%). The use of citrate:creatinine ratio in spot urine can be a helpful method in identifying patients with complete or incomplete dRTA.

Design analyses of a new selective filtration system for removal of uremic toxins.

A new system for removal of uremic toxins is described, The system is based on selective removal of small (urea, creatinine) and large uremic toxins through a multimembrane filter/dialyzer unit. Theoretical calculations show that the system is capable of removing the desired range of molecules from uremic plasma, while retaining a large portion of non-toxic elements in the blood. The SElective DUal Filtration ARtificial Kidney can be optimized and assembled into a single compact unit, which is simple to use and requires minimal monitoring equipment. Preliminary clinical trials indicate that SEDUFARK is a feasible system for treatment of uremic patients.

Removal of uremic toxins and regeneration of hemofiltrate by a selective dual hemofiltration artificial kidney (SEDUFARK) system.

A new system for the treatment of patients with end-stage renal failure has been developed. The SElective DUal Filtration ARtificial Kidney (SEDUFARK) is based on a dual filtration technique combined with low flow dialysis. Primary hemofiltrate containing large molecular weight substances is regenerated through a second filter followed by dialysis before the fluid containing essential substances of low molecular weight is returned to the patient. The ability of SEDUFARK to purify blood from uremic patients has been evaluated using a human macrophage assay system. Uremic plasma post SEDUFARK treatment was significantly less toxic than matched pre treatment plasma and the SEDUFARK regeneration system was found superior to conventional hemofiltration treatment.

Transport of uremic toxins through conventional hemodialysis membranes.

Human mononuclear phagocytes cultured in vitro were tested after preincubation with uremic plasma dialyzed in vitro and the effects of pre and post hemodialysis plasma were compared with the effect of dialyzates equilibrated with uremic plasma in vivo. Factors in uremic blood plasma inhibiting phagocytosis of Candida albicans could not be removed by means of conventional hemodialysis with cuprophan (CPN) or polyacrylonitrile (PAN) membranes. Hemofiltrates of uremic blood plasma produced by PAN membranes caused a significant inhibition of phagocytes in our test system while CPN hemofiltrates did not.

A survey of therapeutic hemapheresis in Norway year 2000.

In a survey of therapeutic hemapheresis in Norway, we sent a questionnaire to all regional and central hospitals, asking about hemapheresis activities, patients, indications, and adverse events. All units responded to the questionnaire: 17 dialysis units, 7 blood units, and 2 specialized units for stem cell apheresis. In total, they performed 2141 procedures that is 5.0 stem cell collections and 42.5 therapeutic apheresis procedures per 100,000 inhabitants. The most frequent indications were Guillain-Barré syndrome, hypercholesterolemia, and myasthenia gravis. Adverse effects were frequent, but mild. Dialysis units performed a majority of the procedures, leading to an extensive use of filtration techniques.

Extracorporeal photochemotherapy in patients with cutaneous T-cell lymphoma: is clinical response predictable?

BACKGROUND: Extracorporeal photochemotherapy (ECP) has been accepted as a standard therapy in cutaneous T-cell lymphomas (CTCL), a category of lymphomas mainly resistant to conventional therapies. Approximately one half of patients demonstrate a reduction in skin affliction by at least 50% within 12 months of therapy and are categorized as responders to ECP. Predictive criteria for selecting patients who will respond to ECP are lacking. Such criteria would however, be of great benefit. OBJECTIVES: This study compared T-cell clonality and serum levels of soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase (LD), neopterin, beta2-microglobulin (beta(2)-M) and granzyme B in CTCL patients in order to evaluate their potential usefulness as predictive markers. PATIENTS/METHODS: Serum and T lymphocytes obtained from 16 patients with CTCL receiving ECP treatment were evaluated in an open retrospective study. RESULTS: We found no evident correlation between detected T-cell clonality and response to ECP. The non-responding group had on average a higher level of serum sIL-2R. This difference was significant after 6 and 12 months of therapy, but not pretreatment. An individual reduction in serum sIL-2R, neopterin and beta(2)-M during a 6-month course of ECP was well correlated to clinical remission. CONCLUSIONS: Seven out of 16 patients were classified as responders. Neither T-cell clonality nor any of the serum markers assessed pretreatment could reliably predict the response to ECP treatment. However, the individual relative changes in sIL-2R, neopterin and beta(2)-M during 6 months of ECP treatment coherently displayed correlation to the clinical response, as assessed after 12 months of ECP treatment.

Biocompatibility of different hemodialysis and plasmapheresis membranes.

The biocompatibility of different membranes was assessed by measuring changes in different white blood cell counts, PGE2 concentrations, thromboplastin activity, production of anaphylatoxins and clinical parameters during treatment. The in vivo recorded complement activation was compared with in vitro experiments. Hemodialysis (HD) treatment was performed with 5 different membranes. Plasmapheresis was run with cellulose diacetate membranes in single (SMF) and double (DMF) membrane filtration and with a new polycarbonate membrane in SMF. The polysulfone membrane was found to be the most, and the cuprophane membrane the least biocompatible membrane in HD. However, large individual differences from one HD patient to the other were found. In contrast to the cellulose diacetate membrane, the polycarbonate membrane apparently activated no complement along the blood-membrane interface during plasmapheresis, but activated large amounts within the membrane matrix. High blood concentrations of C5a were promptly cleared in the body, while high concentrations of C3a seemed to block the removal of this substance from the blood compartment. Even when the patients had high blood concentrations of anaphylatoxins throughout the plasmapheresis treatments using cellulose diacetate membranes and when a significant activation of PGE2 was found in patient plasma, no activation of thromboplastin was recorded on the surface circulating monocytes.

Uraemic toxins of high molecular weight inhibiting human mononuclear phagocytes cultured in vitro.

Uraemic plasma and normal serum were separated into fractions of different molecular sizes by means of molecular filtration through Pellicon filters and liquid chromatography on Sephadex G-15. The amount of substance was considerably higher in uraemic fractions than in comparable normal fractions. When normal human mononuclear phagocytes were cultured in the presence of the uraemic fraction containing the largest molecules, detachment of phagocytes from the glass coverslips was significantly increased. The digestion capacity of the remaining cells was decreased. The results indicate that substances in uraemic plasma responsible for the impaired function of human mononuclear phagocytes cultured in vitro consist of molecules of a molecular weight higher than 10 000.

Systemic cardiovascular response in hemodialysis without and with ultrafiltration with membranes of high and low biocompatibility.

In order to test whether dialyzer membrane biocompatibility influences systemic cardiovascular function, we treated 8 hemodialysis patients (4 men and 4 women, aged 24-73 years) with a low-biocompatible (cuprophane) and a high-biocompatible (polyacrylonitrile) membrane in a randomized double-blind crossover protocol using bicarbonate hemodialysis without ultrafiltration for the first 60 min and with ultrafiltration for the remaining treatment time. Left ventricular function and systemic hemodynamics were assessed noninvasively at baseline and during treatment by Doppler echocardiography combined with external subclavian artery pulse trace calibrated with oscillometrically measured brachial artery blood pressures. There was no significant difference in the cardiovascular response to the 2 membranes, neither during isolated hemodialysis nor when ultrafiltration was added. Mean arterial pressure increased 10% (p < 0.001) during isolated hemodialysis and returned to baseline levels with ultrafiltration. The cardiac index decreased 22% (p < 0.001) during ultrafiltration, due to the greater decrease in left ventricular stroke index (30%, p < 0.001) than increase in heart rate (9%, p < 0.05). Total peripheral resistance increased 10% (p < 0.05) during isolated hemodialysis and a further 19% (p < 0.01) when ultrafiltration was added. Hence, profound cardiovascular alterations were observed during hemodialysis treatment; however, these changes were not related to the biocompatibility of the membranes.

Subdural hematoma presenting as headache in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) affects the nervous system in 75% of cases (1). A female with several neurological manifestations in the case history presented with severe headache, psychiatric disturbances, and increasing paraparesis. She was found to have bilateral subdural hematomas, and after evacuation her neuropsychiatric symptoms, including headache, disappeared. It is speculated that the reported low incidence of subdural hematomas in SLE may be more apparent than real. On the basis of our case, we recommend repeated neuroradiological investigations to uncover this important, treatable and otherwise potentially fatal cause of headache.

Inhibitory effects of plasma from uraemic patients on human mononuclear phagocytes cultured in vitro.

Human mononuclear phagocytes were cultured in plasma from uraemic patients. The presence of uraemic plasma during the engulfment or digestion of 125I-labelled Candida albicans did not inhibit these functions in mononuclear phagocytes cultured for 8 days under normal condition. When normal human macrophages were cultured in the presence of uraemic plasma for 2-4 days, a marked detachment of the cells from the glass coverslips was registered. The phagocytic function of the remaining cells was impaired. Creatinine, urea and methylguanidine in concentrations higher than those usually measured in plasma from uraemic patients did not influence the functional properties of the cells. The inhibitory effect of uraemic plasma on the mononuclear phagocytes is suggested as an explanation for the increased frequency of infections in uraemic patients.

[Pulmonary lymphangioleiomyomatosis]. / Pulmonal lymfangioleiomyomatose.

Pulmonary lymphangioleiomyomatosis is a rare disease with a haphazard proliferation of smooth muscle throughout the lung. Little knowledge about the disease, its clinical presentation and the diagnostic methods used may be a reason for underdiagnosing the disease. In Ostfold county, Norway, with only 250,000 inhabitants, we have seen four patients with this disease in the last few years. The diagnosis was based on histological examination of transbronchial biopsy material in three patients who underwent bronchoscopy the presence of lymphangioleiomyomatosis was not recognized at the initial pathological examination. The disease can be misinterpreted as fibrosis at histological examination. Specific procedures for detecting smooth muscle can be used, eradicating the need for open lung biopsy. Transbronchial biopsy is a valid and useful method for confirming the diagnosis of lymphangioleiomyomatosis. High resolution CT has also shown to be an important diagnostic tool. We emphasize the importance of raising the question of lymphangioleiomyomatosis with the pathologist when this rare, but probably underdiagnosed disease, is suspected by the clinician.

Toxicity of middle molecules: clinical evaluation using a selective filtration artificial kidney.

The effect of four uremic patients, treated 4-6 months with a new artificial kidney system aimed to remove molecules between 10,000-40,000 daltons returning substances with mol wt 200-10,000 back to the patients, was compared with the effect of conventional hemodialysis. The patients treated with this system obtained a more stable hemoglobin concentration without blood transfusions. They got an increased mean nerve conduction velocity and their plasma increased in quality as culture medium on human mononuclear phagocytes grown in vitro.

Acute abdominal pain as presenting symptom in lymphangiomyomatosis. Case report.

A case of lymphangiomyomatosis presenting with acute abdominal pain is described. Laparotomy revealed a multiloculated cystic mass on the posterior abdominal wall with typical histological pattern. In the ensuing 3 years the respiratory manifestations of this rare disorder have slowly progressed. Possible causal factors and management are discussed.