Low plasma concentrations of indinavir are related to virological treatment failure in HIV-1-infected patients on indinavir-containing triple therapy

All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (800 mg three times a day) as part of their triple drug regimen were included in a study to determine the importance of low plasma concentrations of indinavir as a cause of virological treatment failure. The indinavir concentration and a number of patient characteristics at baseline were tested as risk factors for virological treatment failure (defined as a viral load above 200 copies/ml after 24 weeks of treatment) in univariate and multivariate analyses; 65 patients were included. Virological treatment failure occurred in 36.9% of the patients. Multivariate analysis showed that a low plasma concentration of indinavir (odds ratio 0.1), a high viral load at baseline (odds ratio 2.6) and pretreatment with another protease inhibitor (odds ratio 10.0) were independent factors related to virological treatment failure. Monitoring of indinavir plasma concentrations may be an important tool for the optimization of triple drug combination therapy.     

Prospective evaluation of ischemia in brachial-basilic and forearm prosthetic arteriovenous fistulas for hemodialysis.

Ischemia is a devastating complication after arteriovenous fistula (AVF) creation. When not timely corrected, it may lead to amputation. Symptomatic ischemia occurs in 3.7-5% of the hemodialysis population. Upper arm AVFs have a higher incidence of ischemia compared to forearm AVFs. As more patients may need upper arm AVFs in the growing and older hemodialysis population, occurrence of symptomatic ischemia may increase. The purpose of this study is to identify predictors for occurrence of ischemia. METHODS: A prospective evaluation of ischemia was performed in patients randomised for either a brachial-basilic (BB-) AVF or a prosthetic forearm loop AVF. Clinical parameters, preoperative vessel diameters, access flows, digital blood pressures, digit-to-brachial indices (DBI) and interventions for ischemia were recorded. RESULTS: Sixty-one patients (BB-AVF 28) were studied. Seventeen patients (BB-AVF 8) developed ischemic symptoms. Six patients (BB-AVF 3) needed interventions for severe symptoms. Age, history of peripheral arterial reconstruction and radial artery volume flow were significant predictors for the occurrence of ischemia. CONCLUSION: Symptomatic ischemia occurred in 28% of patients with brachial-basilic and prosthetic forearm AVFs. Age, history of peripheral arterial reconstruction and radial artery volume flow might be important for prediction of ischemia.     

Differential susceptibility to lethal endotoxaemia in mice deficient in IL-1α, IL-1β or IL-1 receptor type I

Joosten LAB, van de Veerdonk F, Vonk AG, Boerman OC, Keuter M, Fantuzzi G, Verschueren I, van der Poll T, Dinarello CA, Kullberg BJ, Van der Meer JWM, Netea MG. Differential susceptibility to lethal endotoxaemia in mice deficient in IL‐1α, IL‐1β or IL‐1 receptor type I. APMIS 2010; 118: 1000–7. The role of intereukin‐1 (IL‐1) in mortality caused by endotoxaemia remains controversial. While IL‐1 receptor antagonist (IL‐1Ra) protects mice from lethal endotoxaemia, mice deficient in IL‐1β (IL‐1β^{? /?}) display normal susceptibility to lipopolysaccharide (LPS). The aim of this study was to identify the source of these discrepancies. Mice deficient in IL‐1α, IL‐1β or IL‐1R type I were injected intraperitoneally with Escherichia coli or Salmonella typhimurium LPS. Survival of the mice was examined and compared with C57/Bl6 wild‐type mice. In addition, serum cytokine concentrations were determined after LPS challenge and in vitro cytokine production by peritoneal macrophages was analysed. Clearance of radioactive IL‐1α was examined in IL‐1α^?/? and wild‐type mice. IL‐1β^?/? mice were normally susceptible to endotoxaemia and cytokine production did not differ from that in control mice. Surprisingly, LPS mortality in IL‐1α^?/? mice was significantly greater than that in control mice, accompanied by higher interferon‐γ release. These effects were mediated by a distorted homeostasis of IL‐1RI receptors, as shown by a strongly delayed clearance of IL‐1α. In contrast to the IL‐1α^?/? and IL‐1β^?/? mice, IL‐1RI^?/? mice were completely resistant to high doses of LPS. In conclusion, IL‐1RI‐mediated signals are crucial in mediating mortality occurring as a result of lethal endotoxaemia. Investigation of IL‐1‐mediated pathways in IL‐1 knock‐out mice is complicated by a distorted homeostasis of IL‐1Rs.     

Innervated full thickness grafts in distal finger amputations

Innervated full thickness graft will be presented as an option to reconstruct a fingertip defect which might result in better sensibility than standard reconstruction using a full thickness graft without innervation. Also, anastomosing the nerve stumps can decrease the chance of developing neuroma.     

The Dutch multidisciplinary guideline entitled 'Medically unexplained physical symptoms and somatoform disorder'

The Dutch multidisciplinary guideline called 'Medically unexplained physical symptoms (MUPS) and somatoform disorder' presents a disease-management approach based on three pillars: (a) maintaining patient profiles estimating the risk of iatrogenic harm as well as chronicity, (b) stepped-care treatment starting at a level appropriate for the patient's profile, and (c) the introduction of the family physician as case manager (in serious cases: the medical specialist or psychiatrist) whose task is to channel use of the health care system. Patients with a 'minor risk' profile require psycho-education and two-track treatment by the family physician. The 'moderate risk' profile is complicated by co-morbid depression, anxiety disorder or a somatic disorder; the prognosis is favourable when this co-morbidity is treated. The 'serious risk' profile is assigned to patients with long-term somatoform disorders and a history of surgery for MUPS in addition to disturbed patient-doctor relationships. Limiting iatrogenic harm is of highest priority in these patients. Implementation should focus on providing access to care as described in the guideline.     

Struktur der Zellwandpolysaccharide in der Futtereiweiß-Hefe Candida spec. H. I. Struktur des alkalistabilen Mannan-Proteins

The isolated manno-protein contains about 80% mannose and 10% glucose. Methylation analysis established the highly branched nature of this polysaccharide and the presence of 1,2-, 1,3- and 1,6-linkages, as well as the linkages of the branchpoints. The research of the acetolysis fragments revealed that the molecule is composed of mannose and mannooligosaccharides with DP2 to DP12. These oligosaccharides are terminated in the nonreducing end by α(1,2)- and α(1,3)-linked mannose residues. The pentasaccharide is terminated only by an α(1,3)-mannose. Glucose was only found in the monosaccharide fraction corresponding to the nonsubstituted backbone and in the α(1,3)-disaccharide fraction (reducing and nonreducing end) of the acetolysis. A heptasaccharide fraction corresponding to the N-glycosidical linkage region between polysaccharide and protein parts of the glycoprotein had been isolated. ¹H-NMR spectroscopy and chemical characterization made it probable that the unit with the first side chain, mannopentaose, is linked by di-N,N′-acetylchitobiose or by 4-0-β-D-glucosyl-N-acetyl-D-glucosamine to the asparagine residue of the protein.     

Non-traumatic atlanto-axial dislocation associated with nasopharyngeal infections (Grisel's disease)

Zusammenfassung Die Griselsche Krankheit — eine nicht traumatisch verursachte atlanto-axiale Verschiebung im Zusammenhang mit zervikalen entzündlichen Prozessen — kommt bei Kindern häufiger vor als bei Erwachsenen.Die Arbeit beschreibt drei Erwachsene mitGriselscher Erkrankung, bei denen zunächst der Verdacht auf eine Meningitis im Zusammenhang mit einer nasopharyngealen Infektion bestanden hatte. Die klinischen, pathogenetischen, radiologischen und therapeutischen Gesichtspunkte werden dargestellt.

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Dislocación atlanto-axial no traumática asociada a infección nasofaringea (Enfermedad de Grisel)

Resumen La enfermedad deGrisel — dislocación atlanto-axial no traumática asociada a un proceso cervical inflamatorioes más frecuente en niños que en adultos.Este trabajo describe tres casos de adultos con enfermedad deGrisel, en los cuales en un principio se sospechó una meningitis con infección nasofaringeal.Se pasa revista a los aspectos clínicos, patogénicos, radiológicos y terapéuticos.

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Dislocation axo-atloidienne non traumatique associée à des infections nasopharyngiennes (maladie de Grisel)

Résumé La maladie deGrisel est plus fréquente chez les enfants que chez les adultes.Ce travail décrit 3 adultes atteints de maladie deGrisel, prise d'abord pour méningite associée à une infection naso-pharyngée.L'auteur passe en revue les aspects clinique, radiologique, pathogénique et thérapeutique de cette maladie.

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Dislocazione atlanto-assiale non traumatica associata ad infezione nasofaringea (Malattia di Grisel)

Riassunto La malattia diGrisel — dislocazione atlantoassiale non traumatica associata a processi infiammatori cervicali e' piu' comune nei bambini che negli adulti. Vengono descritti tre casi di malattia diGrisel che inizialmente suscitarono il sospetto di meningite associata ad infiammazione nasofaringea.Gli aspetti clinici, patogenetici, radiologici e terapeutici vengono passati in rassegna.