PREOS NPS (Allelix/Nycomed)

NPS Allelix and Nycomed are developing PREOS, an injectable recombinant human parathyroid hormone, for the potential treatment of osteoporosis. In May 2005, NPS filed a market authorization application for PREOS in the US which was accepted for review in July 2005.     

The effect of cyclosporine on the development and expression of cannabinoid tolerance in mice

Cyclosporine, beside its immunosuppressive action, has several effects on different neuronal functions, such as modulation of neurotransmitter release, the inhibition of nitric oxide synthesis and release, the reduction of cAMP production and inhibition of morphine-induced tolerance. In the present study, the effect of cyclosporine on the expression and development of tolerance to WIN 55,212-2, a cannabinoid receptor agonist, was studied. Intra peritoneal (i.p.) injection of WIN 55,212-2 (2-6 mg/kg) induced time-dependent and dose-dependent analgesia and catalepsy in mice. Administration of cyclosporine (20 mg/kg i.p.), 30 min before WIN 55,212-2 (6 mg/kg i.p.), did not change the analgesic and cataleptic effects of WIN 55,212-2. When WIN 55,212-2 (6 mg/kg i.p.) was injected once a day, animals became completely tolerant to the analgesic and cataleptic effects within five and nine days respectively. Cyclosporine (20 mg/kg i.p.) injected once daily, 30 min before WIN 55,212-2, attenuated the development of tolerance to the analgesic and cataleptic effects of WIN 55,212-2 but did not affect the expression of tolerance. Since cyclosporine given chronically by itself did not alter the analgesia and catalepsy induced by acute administration of WIN 55,212-2, our findings suggest cyclosporine may act with some selectivity on the mechanisms involved in development of cannabinoid tolerance.     

Inhibition of erythrocyte “apoptosis” by catecholamines

Osmotic shock, oxidative stress and Cl⁻ removal activate a non-selective Ca²⁺-permeable cation conductance in human erythrocytes. The entry of Ca²⁺ leads to activation of a scramblase with subsequent exposure of phosphatidylserine at the cell surface. Phosphatidylserine mediates binding to phosphatidylserine receptors on macrophages which engulf and degrade phosphatidylserine exposing cells. Moreover, phosphatidylserine exposure may lead to adherence of erythrocytes to the vascular wall. In the present study, we explored whether activation of the non-selective cation conductance and subsequent phosphatidylserine exposure might be influenced by catecholamines. Phosphatidylserine exposure has been determined by FITC-annexin V binding while cell volume was estimated from forward scatter in FACS analysis. Removal of Cl⁻ enhanced annexin binding and decreased forward scatter, an effect significantly blunted by the β agonist isoproterenol (IC₅₀ approx. 1 μM). Fluo-3 fluorescence measurements revealed an increase of cytosolic Ca²⁺ activity following Cl⁻ removal, an effect again significantly blunted by isoproterenol exposure (10 μM). Whole-cell patch-clamp experiments performed in Cl⁻ free bath solution indeed disclosed a time-dependent inactivation of a non-selective cation conductance following isoproterenol exposure (10 μM). Phenylephrine (IC₅₀<10 μM), dobutamine (IC₅₀ approx. 1 μM) and dopamine (IC₅₀ approx. 3 μM) similarly inhibited the effect of Cl⁻ removal on annexin binding and forward scatter. In conclusion, several catecholamines inhibit the Cl⁻ removal-activated Ca²⁺ entry into erythrocytes, thus preventing increase of cytosolic Ca²⁺ activity, subsequent cell shrinkage and activation of erythrocyte scramblase. The catecholamines thus counteract erythrocyte phosphatidylserine exposure and subsequent clearance of erythrocytes from circulating blood.     

Field evaluation of a recombinant glutathione S-transferase-based pyrethroid quantification assay

A recombinant glutathione S-transferase (GST)-based pyrethroid quantification assay was field-tested in Ifakara, Tanzania. Initial laboratory tests suggested that all reagents used in the assay should be sufficiently stable for field use, provided that domestic refrigeration facilities were available. Insecticide-impregnated bednets were collected from a region where a social marketing programme was in progress. A total of 100 bednets were collected and the assay plus standard HPLC analysis was performed on the residues extracted from four replicate areas of each net. Insecticide residue estimations for assays performed on white and pale green bednet samples were accurate when compared with residue analysis by HPLC. However, for dark green or blue bednets, there was no correlation between the GST-based assay and HPLC pyrethroid quantification results. The assay failure with the dark coloured nets was caused by the extraction of the dyes along with the insecticide, which subsequently interfered with the GST assay. When the same samples were analysed by HPLC, the dyes were separated from the insecticide by reverse phase column chromatography and hence did not affect the results.     

Angiographic embolization of a traumatic pulmonary pseudoaneurysm

We present a case report of a 50-year-old male who sustained a gunshot wound to the right chest. The initial thoracotomy demonstrated a nonbleeding gunshot wound in the middle lobe and was otherwise unremarkable. Later that day, after continued resuscitation, his chest tube output dramatically increased and he was taken back for redo thoracotomy. An injury to the lateral branch of the middle lobe pulmonary artery was encountered and suture ligated. The patient presented several weeks later with hemoptysis. Computed tomography of the chest demonstrated pooling of contrast in the middle lobe. Angiography confirmed the diagnosis of a pulmonary artery pseudoaneurysm and was coil embolized without difficulty. This report represents a case of coil embolization of traumatic pulmonary artery pseudoaneurysm.     

Preventing the withdrawal response associated with rocuronium injection: a comparison of fentanyl with lidocaine

We compared the efficacy of IV fentanyl with IV lidocaine as pretreatment for the prevention of withdrawal response after rocuronium injection. For this prospective, randomized, placebo-controlled, double-blind study we recruited 90 patients aged between 18 and 65 yr, ASA physical status I or II, who had undergone elective surgery requiring general anesthesia and positive pressure ventilation. Patients were randomly allocated to 1 of 3 groups: group F received 2 mL IV fentanyl 50 microg/mL (100 microg), group L received 2 mL of preservative-free lidocaine 2% (40 mg), and group P (placebo) received 2 mL of normal saline. The incidence of withdrawal response after rocuronium was 57%, 30%, and 7% in the placebo, lidocaine, and fentanyl groups, respectively. We found a significant reduction in incidence of withdrawal response in both the fentanyl and lidocaine groups when compared with the placebo group (P < 0.05), with the fentanyl group being most effective (P < 0.05). In conclusion, both fentanyl and lidocaine are effective clinical treatments to alleviate the withdrawal response associated with rocuronium injection, with fentanyl being more effective.     

A 2-year follow-up of orphans' competence, socioemotional problems and post-traumatic stress symptoms in traditional foster care and orphanages in Iraqi Kurdistan

BACKGROUND: This paper aims to compare orphans' development in two different care systems. METHODS: Based on age, sex, psychological trauma scores, competence and psychological problem scores, two comparable samples were found representing orphans in the traditional foster care (n = 94) and the orphanages (n = 48) in a middle-large city in Iraqi Kurdistan. At an index interview, Child Behaviour Checklist (CBCL), Harvard-Uppsala Trauma Questionnaire for Children and Post-traumatic Stress Symptoms for Children (PTSS-C) were administered to the caregivers. After 1 year the CBCL, and after 2 years both the CBCL and the PTSS-C, were-re-administered, consecutively. RESULTS: Although both samples revealed significant decrease in the means of total competence and problem scores over time, the improvement in activity scale, externalizing problem scores and post-traumatic stress disorder-related symptoms proved to be more significant in the foster care than in the orphanages. While the activity scale improved in the foster care, the school competence deteriorated in both samples, particularly among the girls in the orphanages. The improvement of boys' activity scores in the foster care, and deterioration of girls' school competence in the orphanages were the most significant gender differences between samples over time. CONCLUSIONS: Even if the two orphan care systems showed more similarities than differences, the foster care revealed better outcomes over time. The results are discussed in relation to gender, age, socio-economic situation, cultural values and the characteristics of each care system.     

Extra-cranial metastasis of glioblastoma multiforme presenting as acute parotitis

We present an unusual case of extracranial metastasis of glioblastoma multiforme (GBM) to the parotid gland and cervical lymph nodes. The patient had previously undergone two craniotomies to debulk a left frontal GBM, followed by radiotherapy. After the second craniotomy, while waiting for chemotherapy, the patient was re-admitted with a short history of a painful swelling of his left parotid gland. The initial diagnosis was infective parotitis; however, as there was no improvement with broad-spectrum antibiotics, CT was undertaken, which revealed a mass in the parotid gland with a necrotic centre and enlarged cervical lymph nodes. Parotid gland biopsy revealed a parotid GBM metastasis. This case illustrates how GBM behaves in an aggressive manner even outside the CNS. A brief review of the literature and of the theories, which might explain the extra-neural metastasis of this tumour is also presented.     

Insulin, C-peptide, and restenosis after femoral artery balloon angioplasty in type II diabetic and nondiabetic patients

PURPOSE: Endogenous and exogenous insulin is suggested to stimulate hypertrophic wound-healing responses and therefore may promote neointimal hyperplasia and restenosis after balloon angioplasty. The ratio of C-peptide to insulin reflects endogenous insulin secretion. In diabetic patients with insulin substitution, lower ratios display a higher proportion of exogenous insulin. The association and interaction of insulin and C-peptide with restenosis after percutaneous transluminal angioplasty (PTA) was investigated in type II diabetic and nondiabetic patients. MATERIALS AND METHODS: The study group included 76 patients (median age, 68 years; interquartile range [IQR], 58-74 years; 55 men [72%]; 31 patients [41%] with type II diabetes) with intermittent claudication (n = 49; 64%) or critical limb ischemia (n = 27; 36%) who underwent primary successful femoral PTA. C-peptide and insulin levels were measured at baseline, and patients were followed to determine restenosis (> or =50%) at 12 months by color-coded duplex sonography. RESULTS: Restenosis was found in 34 patients (45%) at 12 months. Patients with restenosis had higher insulin levels (median, 21.3 microU/mL IQR, 11.3-35.5 microU/mL) and a lower C-peptide/insulin ratio (median, 16; IQR, 10-21) compared with patients without restenosis (median insulin level, 11.6 microU/mL; IQR, 9.1-22.0 microU/mL [P = .008]; median ratio, 19 [IQR, 17-25], P = .039). In nondiabetic patients, insulin levels were significantly associated with restenosis (P = .046), whereas the ratio of C-peptide to insulin showed no association with restenosis. In patients with type II diabetes (n = 31; 41%), in contrast, the C-peptide/insulin ratio was associated with restenosis (P = .047), whereas insulin levels showed no significant association with restenosis (P = .14). CONCLUSIONS: Insulin levels and the C-peptide/insulin ratio were associated with restenosis after femoral PTA. Exogenous and endogenous insulin may play a role in the pathogenesis of recurrent lumen loss after balloon angioplasty.