Glitazones and the management of insulin resistance: what they do and how might they be used.

Thiazolidinediones (glitazones) are the only compounds currently available that specifically target tissue insulin resistance. The two currently available drugs in this class, pioglitazone and rosiglitazone,are approved by the Food and Drug Administration for the treatment of type 2 diabetes mellitus only. The therapeutic potential of the glitazones for other consequences of insulin resistance has stirred considerable interest, especially with regard to their potential beneficial impact on atherosclerotic cardiovascular disease and diabetes prevention. They also have been considered in the management of polycystic ovarian syndrome, nonalcoholic fatty liver disease, and other consequences of insulin resistance. The nonglycemic potential of glitazones is a clinical area in rapid evolution, wherein most data are on the impact of the glitazones onsurrogate markers that are associated with diseases, not on disease outcomes. This article provides insight and guidance to clinicians on the diverse nonglycemic potential of glitazones until conclusive outcome data become available.     

Surgical treatment of Pancoast tumours.

Due to its localisation in the apex of the lung with invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, a superior sulcus tumour causes characteristic symptoms, like arm or shoulder pain or Horner's syndrome. If rib invasion is the only feature, lysis of the rib must be evident on the chest radiograph; otherwise the tumour cannot be defined as a Pancoast tumour. It is important to adequately stage the tumour, because staging significantly influences survival. Survival is better for T3 than T4 tumours and mediastinal lymph node involvement has been found to be a negative prognostic factor. Also Horner's syndrome and incompleteness of resection worsen survival. The management of superior sulcus tumours has evolved over the past 50 years. Before 1950 it was considered to be inoperable and uniformly fatal. Shaw and Paulson introduced combined modality treatment and for many years, this combination of radiotherapy and surgery was the treatment of choice with a mean 5-year survival of approximately 30%. Postoperative radiotherapy or brachytherapy does not improve survival in patients with complete or incomplete resection. The tumour can be resected through the classic posterior Shaw-Paulson approach or the newer anterior transcervical approach, introduced by Dartevelle. This method facilitates better exposure of the extreme apex of the lung, brachial plexus and subclavian vessels. Regarding the extent of pulmonary resection, en bloc resection of the involved ribs with a lobectomy is recommended. Recent multimodality studies, involving chemoradiotherapy and surgical resection, show promising results regarding completeness of resection, local recurrence and survival, provided that appropriate staging has been carried out. However, careful patient selection and adequate perioperative management with protection of the bronchial stump or anastomosis are important to achieve reasonable rates of morbidity and mortality. As brain metastases remain one of the most common forms of relapse, further studies are needed to examine the role of prophylactic cranial irradiation in patients with complete resection. Also the addition of other chemotherapy agents or biologic agents such as angiogenesis inhibitors or tyrosine kinase inhibitors gives a new perspective in the treatment of Pancoast tumours.     

Comparison of the effects of fluticasone propionate aqueous nasal spray and loratadine on daytime alertness and performance in children with seasonal allergic rhinitis.

BACKGROUND: Concern has been directed at the relative sedating properties of lipophilic and lipophobic antihistamines, but few studies have sought to determine the comparative benefit of seasonal allergic rhinitis (SAR) treatments in controlling symptoms and consequently improving alertness. OBJECTIVE: To compare the relative contributions of fluticasone propionate aqueous nasal spray and loratadine in enhancing daytime performance in 8- to 17-year-old children. METHODS: All participants had a documented history of SAR, positive response to a skin prick (wheal 3-mm greater than negative control or equal to the positive control) for seasonal aeroallergens, and clinically identifiable symptoms at the time of randomization. Following confirmation during baseline of current SAR symptoms, participants were randomized to 1 of the 2 treatments and returned 2 weeks later for evaluation of symptom control, quality of life, attention, reaction time, and memory. RESULTS: Children in the fluticasone propionate aqueous nasal spray group but not the loratadine group demonstrated improvement in nasal symptoms, nasal quality of life score, and composite verbal memory. No differences were identified on any scores from the Conners Continuous Performance Test. CONCLUSIONS: Treatments that most effectively control SAR symptoms are also likely to provide the greatest benefit to children whose daytime functioning, including their capacity to learn at school, is compromised by their illness.     

The rise of body temperature induced by the stimulation of dopamine D1 receptors is increased in acutely reserpinized mice

In naive mice, the selective D1 agonist, SK&F 38393 (7.5-30 mg/kg s.c.), induced a significant rise of body temperature (0.5-1 degree C) which was antagonized by SCH 23390 (100 micrograms/kg s.c.) and by flupenthixol (0.4 mg/kg i.p.). In mice treated with reserpine (5 mg/kg s.c.) 18 h before testing, which on its own caused intense hypothermia (10-12 degrees C), SK&F 38393 (1.87-30 mg/kg s.c.) induced a dose-dependent and more marked rise of body temperature (5-7 degrees C). Similarly, SK&F 38393 (30 mg/kg s.c.) partially prevented reserpine-induced hypothermia. The central origin of the SK&F 38393 effects in reserpine-treated mice is indicated by the rise of body temperature induced by the i.c.v. administration of the drug (12.5-50 micrograms per mice). The SK&F 38393-induced rise of body temperature in acutely reserpinized mice was antagonized by SCH 23390 (50-200 micrograms/kg s.c.), clozapine (1.87-30 mg/kg i.p.) or chlorpromazine (2-32 mg/kg i.p.) but not by metoclopramide (25 or 100 mg/kg i.p.) or amisulpride (12.5 or 50 mg/kg). In naive mice, apomorphine (1 mg/kg s.c.) or LY 171555 (0.4 mg/kg s.c.) induced hypothermia which was antagonized by amisulpride (12.5 mg/kg i.p.); a transiently increased body temperature was even measured 30 min after apomorphine injection in amisulpride-treated mice. Apomorphine (1 mg/kg s.c.) induced a rise of body temperature in acutely reserpinized mice which was significantly reduced by SCH 23390 (50 and 200 micrograms/kg s.c.) and significantly increased by amisulpride (12.5 and 50 mg/kg i.p.). These data suggest that pharmacologically different dopamine receptor subtypes mediate different effects on body temperature in mice: D1 dopamine receptors mediate a rise of body temperature which is increased in hypothermic reserpinized animals and dopamine receptors of the D4 subtype mediate the decrease of body temperature in naive mice.     

The effect of pre-vertebroplasty tumor ablation using laser-induced thermotherapy on biomechanical stability and cement fill in the metastatic spine

A biomechanical study comparing simulated lytic vertebral metastases treated with laser-induced thermotherapy (LITT) and vertebroplasty versus vertebroplasty alone. To investigate the effect of tumor ablation using LITT prior to vertebroplasty on biomechanical stability and cement fill patterns in a standardized model of spinal metastatic disease. Vertebroplasty in the metastatic spine is aimed at reducing pain, but is associated with risk of cement extravasation in up to 10%. Six pairs of fresh-frozen cadaveric thoracolumbar spinal motion segments were tested in axial compression intact, with simulated metastases and following percutaneous vertebroplasty with or without LITT. Canal narrowing under load, pattern of cement fill, load to failure, and LITT temperature and pressure generation were collected. In all LITT specimens, cement filled the defect without extravasation. The canal extravasation rate was 33% in specimens treated without LITT. LITT and vertebroplasty yielded a trend toward improved posterior wall stability (P = 0.095) as compared to vertebroplasty alone. Moderate rises in temperature and minimal pressure generation was seen during LITT. In this model, elimination of tumor by LITT, facilitates cement fill, enhances biomechanical stability and reduces the risk of cement extravasation.     

Genicular corticoperiosteal flap salvage of resistant atrophic non-union of the distal radius metaphysis

Non-union at the metaphyseal level is rare following a fracture of the distal radius. When a non-union does occur, it is usually easily treated with cancellous bone graft from the iliac crest. Resistant and multiply operated atrophic non-unions more frequently occur at the diaphyseal level of long bones. A corticoperiosteal free flap based on the articular branch of the descending genicular artery has previously been described to treat such difficult non-union cases in various sites, but not at the distal radius. At the distal radius metaphysis, the close relationship with the extensor tendons raises concern regarding the ability to fit this free flap to the non-union site without significant interference with tendon function. By careful technique of crumbling the cortex of the flap without tearing the periosteal continuity, the flap can be contoured and snugly fit to this particular site while preserving tendon function. A unique case is presented of a multiply operated resistant atrophic non-union of the distal radius metaphysis in a heavy smoker that was rapidly healed using the genicular corticoperiosteal free flap.     

Significance of diffuse cardiac activity on In-111 labeled leucocyte scans

To assess the significance of diffuse cardiac activity (DCA) seen on In-111 labeled leukocyte scans, we reviewed 87 studies performed over the last 4 years. Inflammatory cardiac conditions were seen as frequently in patients with DCA (15%) as those without (7%, P=0.3). There was a higher ratio of RBC:WBC in the final WBC preparation in the false-positive DCA group than the true positive DCA and no DCA groups. False-positive studies showing DCA are most likely due to residual blood pool activity.Presented in part, 70th annual meeting, Radiological Society of North America, Washington D.C., 25 November 1984