Plateletpheresis in the management of thrombocytosis

Acute thrombotic and hemorrhagic manifestations of thrombocytosis associated with myeloproliferative disorders may be life threatening. Conventional therapy with radioisotopes and/or cytotoxic drugs may require weeks for effective control of platelet counts. In five patients, plateletpheresis by discontinuous-flow (Haemonetics) or continuous-flow (Aminco Celltrifuge) centrifugation was used as a means of reducing platelet counts acutely. With each procedure, approximately 2-9 X 10(12) platelets were removed, resulting in decrements in platelet counts and relief of symptoms. Plateletpheresis is a useful and safe acute means of controlling platelet counts in myeloproliferative disorders.     

Acute small bowel obstruction secondary to intestinal endometriosis,an elusive condition: a case report

Background  

Endometriosis is a benign condition affecting females of reproductive age. Although intestinal endometriosis is common it is rare for the condition to manifest as an acute bowel obstruction secondary to ileocaecal and appendicular endometriosis. This case is important to report as it highlights the diagnostic difficulty this particular condition presents to an emergency surgeon.     

Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats

OBJECTIVE: A reduction of the Ca(2+)-independent transient outward potassium current (I(to)) in epicardial but not in endocardial myocytes of the left ventricle has been observed in cardiac hypertrophy and is thought to contribute to the electrical vulnerability associated with this pathology. METHODS: In the present study we investigated the molecular mechanisms underlying regional alterations in I(to) in hypertrophied hearts of spontaneously hypertensive rats (SHR) using the whole-cell patch-clamp technique, quantitative RT-PCR and heterologous expression of underlying ion channel subunits. RESULTS: I(to) was significantly smaller in epicardial myocytes of SHR than in Wistar-Kyoto (WKY) controls (11.1+/-0.9 pA/pF, n=20 vs. 16.8+/-1.7 pA/pF, n=20, p<0.01), but not different in endocardial myocytes from both groups. Quantitative RT-PCR analysis of the genes encoding I(to) revealed significantly lower levels of Kv4.2 and Kv4.3 mRNA in the epicardial region of SHR rats compared to WKY rats. In contrast, mRNA expression levels of all three splice variants of the beta-subunit KChIP2 were significantly higher in both endo- and epicardial myocytes from SHR than from WKY rats. In parallel, inactivation of I(to), which is negatively modulated by KChIP2, was slowed down in SHR while recovery from inactivation remained unchanged. Heterologous co-expression of increasing amounts of KChIP2b together with a fixed amount of Kv4.2 in Xenopus laevis oocytes revealed a hyperbolic relation of recovery from inactivation and inactivation time constant, demonstrating that KChIP2 preferentially affects inactivation, if its expression level is high. CONCLUSION: These results suggest that downregulation of I(to) in the left ventricle of SHR is mediated by a reduced expression of Kv4.2 and Kv4.3 (but not of KChIP2), whereas the slower inactivation of I(to) can be explained by increased expression levels of KChIP2 in SHR.     

Activation of iGluR5 kainate receptors inhibits neurogenic dural vasodilatation in an animal model of trigeminovascular activation

Background and purpose:

Migraine is a disabling neurological disorder involving activation, or the perception of activation, of trigeminovascular afferents containing calcitonin gene-related peptide (CGRP). Released CGRP from peripheral trigeminal afferents causes dilatation of dural blood vessel, and this is used to measure trigeminal nerve activation. Kainate receptors with the GluR5 subunit (iGluR5, ionotropic glutamate receptor) are present in the trigeminal ganglion and may be involved in nociception. We investigated the possible involvement of prejunctional iGluR5 kainate receptors on CGRP release from trigeminal afferents.

Experimental approach:

We used neurogenic dural vasodilatation, which involves reproducible vasodilatation in response to CGRP release after electrical stimulation of the dura mater surrounding the middle meningeal artery. The effects of the specific iGluR5 receptor antagonist UBP 302 and agonist (S)-(-)-5-iodowillardiine were investigated on neurogenic and CGRP-induced dural vasodilatation in rats, by using intravital microscopy.

Key results:

Administration of 10 and 20 mg·kg⁻¹ of iodowillardiine inhibited electrically induced dural vessel dilatation, an effect blocked by pretreatment with 50 mg·kg⁻¹ UBP 302. Administration of the iGluR5 receptor antagonist UBP 302 alone had no significant effect. CGRP (1 mg·kg⁻¹)-induced dural vasodilatation was not inhibited by the iGluR5 receptor agonist iodowillardiine.

Conclusions and implications:

This study demonstrates that activation of the iGluR5 kainate receptors with the selective agonist iodowillardiine is able to inhibit neurogenic dural vasodilatation probably by inhibition of prejunctional release of CGRP from trigeminal afferents. Taken together with recent clinical studies the data reinforce CGRP mechanisms in primary headaches and demonstrate a novel role for kainate receptor modulation of trigeminovascular activation.     

Anti-nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors

Background and purpose

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase, used primarily in the treatment of hyperuricemia and gout. It is well known that purines exert multiple effects on pain transmission. We hypothesized that the inhibition of xanthine oxidase by allopurinol, thereby reducing purine degradation, could be a valid strategy to enhance purinergic activity. The aim of this study was to investigate the anti-nociceptive profile of allopurinol on chemical and thermal pain models in mice.

Experimental approach

Mice received an intraperitoneal (i.p.) injection of vehicle (Tween 10%) or allopurinol (10–400 mg kg⁻¹). Anti-nociceptive effects were measured with intraplantar capsaicin, intraplantar glutamate, tail-flick or hot-plate tests.

Key results

Allopurinol presented dose-dependent anti-nociceptive effects in all models. The opioid antagonist naloxone did not affect these anti-nociceptive effects. The non-selective adenosine-receptor antagonist caffeine and the selective A₁ adenosine-receptor antagonist, DPCPX, but not the selective A_2A adenosine-receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261, completely prevented allopurinol-induced anti-nociception. No obvious motor deficits were produced by allopurinol, at doses up to 200 mg kg⁻¹. Allopurinol also caused an increase in cerebrospinal fluid levels of purines, including the nucleosides adenosine and guanosine, and decreased cerebrospinal fluid concentration of uric acid.

Conclusions and implications

Allopurinol-induced anti-nociception may be related to adenosine accumulation. Allopurinol is an old and extensively used compound and seems to be well tolerated with no obvious central nervous system toxic effects at high doses. This drug may be useful to treat pain syndromes in humans.     

Paroxysmal disorders in infancy and their risk factors in a population‐based cohort: the Generation R Study

Aim To examine the incidence of paroxysmal epileptic and non‐epileptic disorders and the associated prenatal and perinatal factors that might predict them in the first year of life in a population‐based cohort. Method This study was embedded in the Generation R Study, a population‐based prospective cohort study from early fetal life onwards. Information about the occurrence of paroxysmal events, defined as suddenly occurring episodes with an altered consciousness, altered behaviour, involuntary movements, altered muscle tone, and/or a changed breathing pattern, was collected by questionnaires at the ages of 2, 6, and 12 months. Information on possible prenatal and perinatal determinants was obtained by measurements and questionnaires during pregnancy and after birth. Results Information about paroxysmal events in the first year of life was available in 2860 participants (1410 males, 1450 females). We found an incidence of paroxysmal disorders of 8.9% (n=255) in the first year of life. Of these participants, 17 were diagnosed with febrile seizures and two with epilepsy. Non‐epileptic events included physiological events, apnoeic spells, loss of consciousness by causes other than epileptic seizures or apnoeic spells, parasomnias, and other events. Preterm birth (p<0.001) and low Apgar score at 1 minute (p<0.05) were significantly associated with paroxysmal disorders in the first year of life. Continued maternal smoking during pregnancy and preterm birth were significantly associated with febrile seizures in the first year of life (p<0.05). Interpretation Paroxysmal disorders are frequent in infancy. They are associated with preterm birth and a low Apgar score. Epileptic seizures only form a minority of the paroxysmal events in infancy. In this study, children whose mothers continued smoking during pregnancy had a higher reported incidence of febrile seizures in the first year of life. These findings may generate various hypotheses for further investigations.     

Improved hospital-level risk adjustment for surveillance of healthcare-associated bloodstream infections: a retrospective cohort study

Background  

To allow direct comparison of bloodstream infection (BSI) rates between hospitals for performance measurement, observed rates need to be risk adjusted according to the types of patients cared for by the hospital. However, attribute data on all individual patients are often unavailable and hospital-level risk adjustment needs to be done using indirect indicator variables of patient case mix, such as hospital level. We aimed to identify medical services associated with high or low BSI rates, and to evaluate the services provided by the hospital as indicators that can be used for more objective hospital-level risk adjustment.     

Difficulties in diagnosing intrinsic spinal cord tumours

Thirteen children with intrinsic spinal cord tumours were seen between 1984 and 1995. In only one was this the presumptive diagnosis at referral, despite a high incidence of characteristic features. Eight had presented to their local paediatrician, four to local orthopaedic teams, and one to a general surgeon. Eleven had back pain. Eleven had either spinal curvature or change in gait. The interval between onset of symptoms and diagnosis ranged from one week to six years, with a mean of 17.5 months. In nine children symptoms had been present for four or more months. In nine, unrewarding investigations had been carried out. This paper highlights typical presenting features of these tumours and how earlier diagnosis can be achieved.     

Hepatic portoenterostomy for biliary atresia. A comparative study of histology and prognosis after surgery

Specimens of excised tissue from the porta hepatis in 26 infants with extrahepatic biliary atresia undergoing hepatic portoenterostomy were analysed histologically for the presence and size of biliary ductules. No correlation could be found between the establishment of effective biliary drainage and the number or size of biliary ductules. it is suggested that prognosis after surgery may be related to the intrahepatic lesion and age of the child at operation rather than to the histology of the extrahepatic bile duct remnants.