Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis.

OBJECTIVE: To contrast the effect of the burden of vasculitis activity with the burden of adverse events on 1-year mortality of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study assessed the outcome and adverse events in patients prospectively recruited to four European AAV clinical trials. Data on 524 patients with newly diagnosed AAV were included. The burden of adverse events was quantified using a severity score for leucopenia, infection and other adverse events, with an additional weighting for follow-up duration. A 'combined burden of events' (CBOE) score was generated for each patient by summing the individual scores. Vasculitis severity was quantified using the Birmingham vasculitis activity score and glomerular filtration rate (GFR). RESULTS: 1-year mortality probability was 11.1%; 59% and 14% of deaths were caused by therapy-associated adverse events and active vasculitis, respectively. Using Cox regression analysis, infection score (p<0.001), adverse event score (p<0.001), leucopenia score (p<0.001) and GFR (p=0.002) were independently associated with mortality. The risk of 1-year mortality remained low (5%) with CBOE scores less than 7, but increased dramatically with scores above this. Hazard ratio for death with a CBOE greater than 7 was 14.4 (95% CI 8.4 to 24.8). Age and GFR were independent predictors of CBOE score. CONCLUSIONS: The greatest threat to patients with AAV in the first year of therapy is from adverse events rather than active vasculitis. The accumulation of adverse events, monitored using this scoring method, should prompt increased awareness that the patient is at high risk of death.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Sequential development of anti-GBM nephritis and ANCA-associated Pauci-immune glomerulonephritis.

The medical history is presented of a 23-year-old man experiencing three episodes of pulmonary-renal syndrome. On the first occasion, a diagnosis of anti-glomerular basement membrane (GBM) disease (with linear deposition of immunoglobulin G [IgG] along the GBM) was made, whereas anti-neutrophil cytoplasmic autoantibodies were also present in serum. On the third occasion, 5 years later, p-ANCA-associated vasculitis (with pauci-immune crescentic glomerulonephritis) was diagnosed, whereas anti-GBM antibodies were absent. The current literature on ANCA-positive anti-GBM disease is briefly reviewed. A substantial proportion (20% to 30%) of patients with histologically and serologically proven anti-GBM nephritis display the presence of ANCA as well. In this group of patients with dual antibodies, clinical and histological findings suggest that ANCA are not merely epiphenomena, but are of pathogenetic importance and might be responsible for an initial vasculitic insult to the kidney with resultant secondary anti-GBM nephritis. The clinical course in our patient lends further support to this concept. Histological demonstration of anti-GBM nephritis followed by ANCA-associated pauci-immune glomerulonephritis in a single patient has not been reported before.

Quantitative differences in collateralization of the descending spinal pathways from red nucleus and other brain stem cell groups in rat as demonstrated with the multiple fluorescent retrograde tracer technique.

In 8 rats 'True Blue' was injected into dorsal half of C5-C8 spinal grey, 5 days later 'Nuclear Yellow' was injected in midthoracic, upper lumbar, lumbosacral and sacral cord respectively. The animals were sacrificed about 43 hours after NY injections. The distribution of retrogradely labeled neurons was studied in Red Nucleus, in Ventrolateral Pontine Tegmentum and in Nucleus Raphe Magnus, all of which project to spinal dorsal grey. In Red Nucleus large populations of single TB-labeled neurons and single NY-labeled ones occurred in the dorsomedial and ventrolateral part, respectively. In addition, about 8% of the neurons labeled with TB from C5-C8 were double labeled with NY from L5-S1, and 35% from T7-8, which percentages resemble those of electrophysiological studies. However, in ipsilateral Nucleus Raphe Magnus about 40% of the TB-labeled neurons were double labeled from L5-S1. This percentage resembles the 66% obtained in electrophysiological studies of reticulospinal collaterals. These findings in rat support electrophysiological findings in cat and show, that rubrospinal neurons distribute their fibers primarily to the grey matter of specific groups of spinal segments, while many of the raphe spinal neurons distribute fibers throughout the spinal cord.

Morbidity and mortality during renal replacement therapy: dialysis versus transplantation.

AIM: Many patients with end-stage renal disease are eligible for renal transplantation. To enable a patient to choose between transplantation or to remain on dialysis comparable data on morbidity and mortality should be available. METHODS: Data were collected retrospectively from the medical records of all patients on the waiting list for renal transplantation and of transplanted patients during the period January 1, 1990, to January 1, 1997. All patients were dialyzed in the Kennemer Gasthuis and renal transplantation was performed in the Leiden University Medical Center (LUMC). Morbidity and mortality in both groups were compared. Morbidity was assessed by studying number, length and cause of hospital admissions. RESULTS: During the study period 102 patients had been on the waiting list and 54 patients had been transplanted in the LUMC. Mean length of stay on the waiting list before transplantation was 37 months. During the follow-up period 11 patients (10.8%) died on the waiting list and 6 patients (11.1%) died after renal transplantation. The mean length of stay on the waiting list of these two groups was much longer, being 55 months and 62 months, respectively. Length of hospitalization was significantly different between both patient groups during the first 6 months of treatment (13.24 days for those on the waiting list versus 40.75 days transplanted patients) and after 6 months (32.4 days for those on the waiting list versus 13.1 days transplanted patients). The number of hospital admissions did not differ significantly. Dialysis-related admissions constituted 47% of the total of admissions in the waiting list group and transplantation-related admissions were 43% in the transplanted group. CONCLUSION: In the present study we revealed no difference in overall mortality. However, mortality was influenced by length of stay on the waiting list. Morbidity was increased during the first 6 months after transplantation. Therapy modality greatly influenced the specific cause of morbidity.

Interleukin-8 (IL-8) in synovial fluid of rheumatoid and nonrheumatoid joint effusions.

IL-8 was measured in knee joint synovial fluid of 60 patients with rheumatoid arthritis, 8 with gout, 6 with osteoarthritis and 4 with meniscus lesions. IL-8 could be demonstrated in most SF samples. The highest levels were observed in rheumatoid joint effusions, yet mean levels were not significantly different between the different subgroups (mean +/- SE; RA 1537 +/- 3049 pg/ml, gout 570 +/- 952 pg/ml, OA/ML 178 +/- 188 pg/ml). In RA patients, IL-8 levels could not be related to various serological, clinical or radiological parameters. However, a correlation was observed between SF levels of IL-8 with those of lactate, LDH, beta 2-microglobulin and glucose. These observations suggest that next to the laboratory parameters IL-8 will be a parameter of the activity of the local inflammatory process. The results also demonstrate that IL-8 is not a disease-specific marker of joint inflammation.

[Necrotizing fasciitis caused by Group A beta-hemolytic streptococci]. / Necrotiserende fasciitis door beta-hemolytische streptokokken uit groep A.

A case is presented of a 35-year-old man with necrotizing fasciitis caused by group A beta-haemolytic Streptococci, accompanied by severe systemic toxicity, and necessitating amputation of the leg. After prolonged intensive care treatment the patient recovered.

Listeria peritonitis in patients on peritoneal dialysis: two cases and a review of the literature.

Two cases are reported of patients on continuous ambulatory peritoneal dialysis who presented with peritonitis caused by Listeria monocytogenes. They were successfully treated with intraperitoneal and intravenous administration of amoxicillin. In patients on peritoneal dialysis, Listeria monocytogenes is a very rare cause of peritonitis, with only 11 cases reported to date, and mainly occurring in immunocompromised patients. In contrast to the majority of the reported cases, neither of our patients had received immunosuppressive drugs. To our knowledge, these are the first two cases of Listeria peritonitis reported in the Netherlands.

Branching neurons in the cervical spinal cord: a retrograde fluorescent double-labeling study in the rat.

Branching neurons giving rise to ascending and descending collaterals were studied in the cervical spinal cord of the rat. After unilateral injection of two retrograde fluorescent tracers, i.e. DY.2HCl at T2 or more caudal levels and TB at C1 or more rostral levels, many DY-TB double-labeled neurons were found in C3 to C8. These neurons were located bilaterally throughout the spinal grey matter, as well as in the lateral spinal nucleus (LSN). However, no double-labeled neurons could be detected in the laminae I and II on either side. The double-labeled neurons must represent branching neurons giving rise to a collateral ascending to the rostral injection-site or above, and another collateral descending to the caudal injection-site or below. The descending collaterals were found to extend to various spinal levels, including the lumbosacral cord. However, most of them terminated at shorter distances from their parent cell bodies; thus 20% of the C3-C8 neurons projecting to C1 or above had a descending collateral reaching T2, 8% had a collateral reaching T9, and 3% a collateral reaching L2/L3. The ascending collaterals of the majority of the branching neurons passed into the most caudal part of the medulla oblongata, and about half of these collaterals reached the level of the rostral part of the inferior olive. In regard to the neurons located in the segments C5-C8, about 13% of those projecting to T2 or below distribute an ascending collateral restricted to C2-C4, while 29% of those had an ascending collateral to C1 or above.

Propriospinal neurons with ascending collaterals to the dorsal medulla, the thalamus and the tectum: a retrograde fluorescent double-labeling study of the cervical cord of the rat.

Branching neurons with descending propriospinal collaterals and ascending collaterals to the dorsal medulla, the thalamus and the tectum were studied in the rat's cervical spinal cord (C1-C8), using the retrograde fluorescent double-labeling technique: Diamidino Yellow Dihydrochloride (DY) was injected in the cord at T2, True Blue (TB) was injected in the brain stem. DY-labeled descending propriospinal neurons were present in all laminae, except lamina IX. They were concentrated in lamina I, laminae IV to VIII, and in the lateral spinal nucleus, LSN. TB-labeled neurons projecting to the dorsal medulla were concentrated in lamina IV and the medial parts of laminae V and VI (probably representing postsynaptic dorsal column--PSDC--neurons), but were also present in lamina I, the LSN, the lateral dorsal horn, and in laminae VII and VIII. DY-TB double-labeled neurons giving rise to both a descending propriospinal collateral and an ascending collateral to the dorsal medulla were intermingled with the TB single-labeled neurons. About 4% of the descending propriospinal neurons gave rise to an ascending collateral to the dorsal column nuclei; these double-labeled cells constitute a sizable fraction (10%) of the PSDC neurons. TB-labeled spinothalamic and spinotectal neurons were located in lamina I, the lateral cervical nucleus (LCN), and LSN, the lateral lamina V, lamina VII and VIII, lamina X and in the spinal extensions of the dorsal column nuclei, predominantly contralateral to the TB injections. DY-TB double-labeled neurons were present throughout C1-C8 in the LSN, lateral lamina V, lamina VIII, ventromedial lamina VII, and lamina X. Only very few were observed in lamina I and the LCN, and none in the spinal extensions of the dorsal column nuclei. The double-labeled neurons constituted only a minor fraction of all labeled neurons; 3-5% of the spinothalamic neurons and about 1-7% of the spinotectal neurons were double-labeled. Conversely, only about 1% of the labeled descending propriospinal neurons gave rise to an ascending spinothalamic collateral, and even fewer (0.1 to 0.6%) to a collateral to the dorsal midbrain. The LSN displayed the highest relative content of branching neurons. Up to 20% of its ascending spinothalamic and spinotectal neurons and up to 8% of its descending propriospinal neurons were found to be branching neurons, indicating that the LSN constitutes an unique cell-group in the rat spinal cord.

Spinocerebellar neurons and propriospinal neurons in the cervical spinal cord: a fluorescent double-labeling study in the rat and the cat.

In the cervical spinal cord of the rat and the cat, the distributions of spinocerebellar and of descending propriospinal neurons were investigated using the retrograde fluorescent double-labeling technique. Moreover, a search was made for the presence of neurons with both ascending spinocerebellar and descending propriospinal axoncollaterals. Diamidino Yellow Dihydrochloride (DY) was injected at T2, while True Blue (TB) (in rats) or Fast Blue (FB) (in cats) was injected in the cerebellum. The distributions of labeled neurons were very similar in the rat and the cat. DY-labeled propriospinal neurons, projecting to T2 or below, were most numerous in lamina I and laminae IV to VIII. In the rat, such neurons were also present in the lateral spinal nucleus (LSN). TB- or FB-labeled spinocerebellar neurons were concentrated in the central cervical nucleus (CCN) at C1-C4, in the central part of lamina VII at C5-T1, in the medial part of lamina VI and the adjoining dorsomedial part of lamina VII at C2/C3-T1, and in Clarke's column. They were also found in lamina V at C1 and C7-T1, and in lamina VIII at all levels. In both species only very few DY-TB/FB double-labeled neurons, representing neurons with branching axons, were observed; in C1-T1, only about 0.5% of all TB/FB-labeled spinocerebellar neurons and about 0.05% of all DY-labeled descending propriospinal neurons were double-labeled. The double-labeled neurons were all located centrally in lamina VII at C5-T1, but even in that area they constituted not more than 1.5% (rat) and 4% (cat) of the labeled spinocerebellar neurons. These findings indicate that, in the cervical cord of the rat and the cat, descending propriospinal neurons and spinocerebellar neurons are to a large extent separate populations.

Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by several immunological abnormalities. The pathogenic importance of T cells in this disease is well established. Interleukin-16 (IL-16) is a cytokine which is mainly produced by CD8+ T cells and induces chemotaxis of CD4+ T cells and monocytes. IL-16 levels have been shown to be elevated in SLE patients in a cross-sectional study, but the mechanism is unknown. To explore whether the increased IL-16 levels are associated with genetic background or the disease itself, we investigated the IL-16 level in healthy first-degree family members of SLE patients and SLE patients who were followed over time with regard to disease activity. We observed high IL-16 levels in SLE patients with severe disease compared to SLE patients with non-severe disease and healthy controls. Furthermore, IL-16 levels in first-degree relatives were not different from those in healthy controls. These results suggest that high IL-16 levels are associated with severity of SLE, but not with genetic susceptibility to SLE. Finally, we followed the disease activity of SLE patients over time, which showed significant correlation between the SLE disease activity index and IL-16, ESR and the complement components C3, C4 and CH50. In conclusion, these results implicate an association of IL-16 with SLE.

Topically applied low-dose calcitriol has no calciotropic effect in patients with stable plaque psoriasis.

BACKGROUND: Topical calcitriol, a potent inhibitor of cell proliferation and inducer of terminal cell differentiation, can clear psoriasis. However, possible side effects on calcium and bone metabolism from transdermal absorption have not been evaluated. OBJECTIVE: The calciotropic effects of low-dose calcitriol (3 micrograms/gm) ointment, applied twice daily for 6 weeks, were investigated. METHODS: A double-blind study was carried out in 18 patients with chronic stable plaque-type psoriasis, of whom nine were treated with calcitriol (3 micrograms/gm) and nine with betamethasone dipropionate (500 micrograms/gm). The main end points were calcitriol plasma concentrations, intestinal calcium absorption, and bone turnover. RESULTS: Serum alkaline phosphatase concentrations increased slightly (p < 0.02) and intestinal calcium absorption decreased slightly (p < 0.01) in the calcitriol-treated group. However, the alterations were too small to have any clinical relevance. CONCLUSION: Low-dose calcitriol, topically applied for 6 weeks on a maximal body surface area of 30%, can be considered as safe regarding calcium and bone metabolism.

Revascularization of occluded haemodialysis fistulae with the Hydrolyser thrombectomy catheter: description of the technique and report of six cases.

Our purpose was to describe initial experience with a new mechanical thrombectomy catheter for treating haemodialysis fistulae. The Hydrolyser thrombectomy catheter combines thrombus fragmentation by a saline jet with simultaneous low-pressure aspiration. This catheter was used in six cases of dialysis-fistula occlusion. In four instances this was a polytetrafluoroethylene loop, in two cases a Brescia-Cimino fistula. In all cases rapid revascularization was obtained without complications. Reocclusion occurred in one patient, immediate reintervention being successful. Our initial results suggest that the Hydrolyser is a quick, minimally invasive, and useful alternative to the presently accepted methods of revascularizing occluded haemodialysis fistulae.

Aspergillus peritonitis in peritoneal dialysis: case report and a review of the literature.

Aspergillus peritonitis is a rare complication of continuous ambulatory peritoneal dialysis. The case is described of a 68-year-old man in whom Aspergillus fumigatus was isolated from the peritoneal dialysate after recurrent peritonitis with Gram-negative rods in association with diverticulosis. Treatment consisting of removal of the catheter and intravenous administration of amphotericin B followed by oral itraconazole was successful. A review of the sparse literature (12 cases) displays uncertainties regarding diagnostic awareness, culture diagnosis, and therapeutic management. Next to institution of appropriate antifungal therapy, early removal of the peritoneal dialysis catheter is recommended, as delayed removal of the catheter appears to be associated with increased mortality and morbidity.

Haemolytic uraemic syndrome following bone marrow transplantation. Case report and review of the literature.

Thrombotic microangiopathy (TMA) can be a late complication of bone marrow transplantation (BMT). A patient is described in whom the haemolytic uraemic syndrome developed 10 months after BMT and who died of E. coli sepsis while on maintenance haemodialysis. The literature is reviewed, regarding clinical presentation, incidence, pathogenesis and therapy. TMA can be observed, after an interval of 3-12 months, in about 6-26% of patients following BMT. Reported cases vary considerably in clinical severity, from mild presentations to severe TMA with high mortality rates despite intensive therapy. Important pathogenetic roles are ascribed to the conditioning total body irradiation and the use of cyclosporin A, but other factors may be involved as well. Next to supportive therapy, plasma exchange and the use of ACE inhibitors may be of value in treating BMT-associated TMA.

Reversibility of myocardial dyskinaesia due to severe hypertension.

Two cases of acute left ventricular failure associated with severe essential hypertension are presented. On admission echocardiography indicated severe dyskinaesia of all wall segments of the heart. Anti-hypertensive treatment resulted in significant improvement in clinical and echocardiographic findings.

Absence of callosal collaterals derived from rat corticospinal neurons. A study using fluorescent retrograde tracing and electrophysiological techniques.

In rat the presence of axon collaterals from corticospinal neurons to the contralateral hemisphere has been investigated by means of anatomical and electrophysiological techniques. Anatomical Experiments. Several combinations of fluorescent retrograde tracers were used. In eight rats injections of Evans Blue, "True Blue", "Fast Blue" or DAPI-Primuline were made in areas 10, 6, and 4 and in the most medial part of the S1 granular cortex of one hemisphere, 1.5 mm below cortical surface. These injections were combined with injections of "Fast Blue", DAPI-Primuline, "Granular Blue", "Nuclear Yellow", or Bisbenzimide in the ipsilateral corticospinal tract in the C2 segment. Survival times of the animals varied according to the tracers used. In the non-injected hemisphere the retrogradely labeled corticospinal neurons were present in layer V of especially areas 10, 6, 4 and the medial portion of the S1 granular cortex. However, the retrogradely labeled callosal neurons in these areas were present in all layers except layer I. The labeled callosal and corticospinal neurons in layer V were intermingled and frequently situated very close to one another. However, with none of the tracer combinations were double labeled neurons observed. Electrophysioloogical Experiments. In six rats, layer V neurons of hindlimb-sensorimotor cortex were tested for antidromic responses to stimulation of contralateral corticospinal tract (CST) and corpus callosum (CC). Eighty-five CST neurons were identified, none of which responded antidromically to CC shocks. Eighty-two layer V neurons were identified which responded antidromically to CC shocks, but none of them responded antidromically to CST shocks. CC shocks elicited strong synaptic responses in CST neurons and vice versa. Depth measures indicated extensive intermingling of CST and CC neurons. From both sets of findings it was concluded that, in rat, CST neurons do not give rise to callosal collaterals.