Tryptase, a neutral protease of human mast cells, is a potentially important indicator of mast cell involvement in various clinical conditions. The current study examined the time course of appearance and disappearance of tryptase in the circulation after an anaphylactic event and the stability of both endogenous and exogenous tryptase in terms of freeze-thawing and temperature. The peak level of tryptase after an experimentally induced systemic anaphylactic reaction occurred 1-2 h after the initiating bee sting in each of three subjects, in contrast to histamine levels which peaked at 5-10 min. In some cases elevated levels of tryptase may not be detected during the initial 15-30 min. Tryptase levels then declined under apparent first order kinetics with a t/2 of -2 h. Similar disappearance kinetics were observed for two subjects presenting in the emergency room with immediate type reactions, one with severe asthma after indomethacin ingestion, the other with systemic anaphylaxis after a bee sting. Histamine levels declined rapidly and were back to baseline by 15-60 min. Measured levels of tryptase in serum or plasma were not diminished by up to four freeze-thaw cycles. Incubation of serum samples taken from subjects with elevated levels of tryptase at 22 and 370C indicated that > 50% of endogenous tryptase was still detected after 4 d. Purified tryptase added to serum or plasma and incubated as above was less stable: -50% of exogenous tryptase in serum and -15% in plasma was detected after 2 d of incubation. Therefore, optimally samples should be stored frozen, but even those stored at room temperature for up to 4 d should be satisfactory. The best time to obtain samples for tryptase determinations is 1-2 h after the precipitating event, but depending on the magnitude of the initial response elevated levels of tryptase may be present in the circulation for several hours.

The cartilaginous endplates (CEPs) are thin layers of hyaline cartilage found adjacent to intervertebral discs (IVDs). In addition to providing structural support, CEPs regulate nutrient and metabolic exchange in the disc. In IVD pathogenesis, CEP undergoes degeneration and calcification, compromising nutrient availability and disc cell metabolism. The mechanism(s) underlying the biochemical changes of CEP in disc degeneration are currently unknown. Since calcification is often observed in later stages of IVD degeneration, we hypothesised that elevations in free calcium (Ca 2+) impair CEP homeostasis. Indeed, our results demonstrated that the Ca 2+ content was consistently higher in human CEP tissue with grade of disc degeneration. Increasing the levels of Ca 2+ resulted in decreases in the secretion and accumulation of collagens type I, II and proteoglycan in cultured human CEP cells. Ca 2+ exerted its effects on CEP matrix protein synthesis through activation of the extracellular calcium-sensing receptor (CaSR); however, aggrecan content was also affected independent of CaSR activation as increases in Ca 2+ directly enhanced the activity of aggrecanases. Finally, supplementing Ca 2+ in our IVD organ cultures was sufficient to induce degeneration and increase the mineralisation of CEP, and decrease the diffusion of glucose into the disc. Thus, any attempt to induce anabolic repair of the disc without addressing Ca 2+ may be impaired, as the increased metabolic demand of IVD cells would be compromised by decreases in the permeability of the CEP.

Context:Invasive sinonasal aspergillosis is a silently progressive disease that, left untreated, may invade the adjacent intracranial and intra-orbital compartments incurring serious morbidity.Aim:To evaluate our results of a collaborative surgical management plans for patients with invasive sinonasal aspergillosis with orbitocranial extension.Setting and Design:Retrospective study.Materials and Methods:Between the years 2000 and 2012, 12 patients with Aspergillus sinusitis with orbitocranial extension were treated at our institution. Preoperative CT and MRI scans were done in all cases and cerebral angiography in two patients with subarachnoid hemorrhage (SAH). Surgical combined transcranial and endonasal approaches to the skull base were considered in all patients. Adjuvant antifungals were administered postoperatively with regular clinical and radiologic follow up.Results:All cases had a long history of headache and nasal obstruction (n = 12). Five presented with unilateral proptosis, one with meningitis, one with epilepsy, two with SAH, and one patient presented with trigeminal neuralgia. Craniotomy alone was chosen for the patients with isolated sphenoiditis (n = 2) while a combined cranial and endonasal approach was elected for the other patients (n = 10). Adjuvant antifungal therapy was used for 3-12 months. Patients were followed up clinically and radiologically for an average 36-month period (range = 12-50 months) with disease eradication achieved in eight patients (67%). Two died as consequence to SAH. Follow up also showed that three patients (25%) had sinunasal recurrence requiring evacuation through an endonasal approach.Conclusions:Surgical intervention, with adjuvant antifungal therapy, aiming for safe total removal of the fungal burden, whenever feasible, has a major role in the management of invasive sinonasal aspergillosis with orbitocranial extension with minimal morbidity and good outcomes.

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Primary central nervous lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin's lymphoma with a especially poor prognosis. The diagnosis is usually encountered in immunodeficient patients but is also encountered, albeit uncommonly, in the immunocompetent. We present a 50-year-old male who developed signs and symptoms of increased intracranial pressure. Imaging revealed the presence of a fourth ventricle mass with obstructive hydrocephalus. First, the patient underwent emergency endoscopic third ventriculostomy followed, few days later, by complete tumor resection via a posterior fossa craniotomy. Postoperative histopathology revealed the lesion to be a PCNSL. He received adjuvant chemotherapy and radiation and remained with no recurrence on regular imaging studies for 18-month followup. We report herein the fourth case of isolated PCNSL lesion to the fourth ventricle in the literature and provide the rationale for our belief that craniotomy and tumor resection, if feasible, should be the initial line of management in similar cases to relieve hydrocephalus and achieve the diagnosis.