Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

Costs of neonatal care for low-birthweight babies in English hospitals

Aim:  To estimate mean costs of neonatal care for babies with birthweights ≤1800 g in a regional Level 3 unit and three Level 2 units providing short-term intensive care.
Method:  Babies ≤1800 g admitted to units in four hospitals in England over 15 months in 2001–2002 were audited until discharge. Unit costs (2005–2006 prices) were attributed to their resource items, including neonatal cot occupancy, pharmaceuticals, blood products and ambulance transfers. Bootstrapped mean costs were derived for the Level 3 unit and the Level 2 units combined.
Results:  The mean gestation period for 199 Level 3 babies was 29.5 weeks compared with 30.4 weeks for 192 Level 2 babies (p = 0.003). Mean costs excluding ambulance journeys were £17  861 per Level 3 baby and £12  344 per Level 2 baby. Level 3 babies <1000 g averaged £26  815, whereas Level 2 babies <1000 g were generally less costly than babies 1000–1499 g. Ambulances transported 76 Level 3 babies and 62 Level 2 babies; their adjusted mean costs were £18  495 and £12  881, respectively.
Conclusion:  By comprehensively costing resource components, the magnitude of total costs for low-birthweight babies has been revealed, thus demonstrating the importance of budgets for neonatal units being realistically determined by commissioners of neonatal services.     

Vitamin K status in cystic fibrosis

Appearance of PIVKA-II (protein induced by vitamin K absence-II) in serum is a biochemical sign of insufficient vitamin K-dependent carboxylation of prothrombin. Plasma concentrations of PIVKA-II and vitamin K1 were determined in 24 children with cystic fibrosis. Eight were supplemented with vitamin K1. The purpose of the study was to determine the occurrence of vitamin K deficiency in cystic fibrosis and to evaluate the effect of vitamin K supplementation. PIVKA-II was detectable in only one unsupplemented child. In this patient, the concentration of vitamin K1 was below the limit of detection of 60 ng/l. Vitamin K1 levels in the other unsupplemented children were normal (mean 476 ng/l = 1 mmol/l). The supplemented patients showed extremely high levels of vitamin K1 (mean 22445 ng/l = 50 nmol/l). In conclusion, vitamin K deficiency occurs infrequently in cystic fibrosis. Checking the coagulation system is advised, but routine vitamin K supplementation is not recommended. If additional vitamin K is needed, the starting dose should not exceed 1 mg daily.     

Radiological imaging of a massive dermoid in the male pelvis

A dermold cyst, arising from the posterior aspects of the prostate and seminal vesicles, and extending into the pelvis to masquerade as a full bladder, must be exceedingly rare. Ultrasound, computed tomography and especially magnetic resonance imaging (MRI) proved to be invaluable in making the diagnosis, and MRI in particular was very useful in providing an anatomical road map for surgery.     

Respiratory and hemodynamic effects of thoracic or lumbar epidural alfentanyl after thoracic surgery

OBJECTIVES: The aim of this study was to evaluate the effects on pulmonary function and hemodynamics of three different types of analgesia after thoracotomy. MATERIAL AND METHODS: Forty-five ASA II-IV patients undergoing thoracotomy (for lobectomy or pneumonectomy) were randomized to three groups (n = 15 each) for double-blind study. After a test dose into the epidural space at T5-7 (groups T-A and T-AL) or L2-3 (group L-A) interspace, 10 micrograms/Kg of alfentanil was administered in all groups, followed by epidural infusion of 400 micrograms/h of alfentanil (group T-A and L-A) or 400 micrograms/h of alfentanil with 50 mg/h of lidocaine (group T-AL) during surgery and 24 hours postoperatively. The patients also used a patient-controlled analgesia device to administer intravenous morphine postoperatively. During the study period the following variables were recorded: hemodynamic parameters, lung function, quality of analgesia and respiratory complications. ANOVA was performed and Scheffé and Chi-square tests were applied with 0.05 as the level of statistical significance. RESULTS: No differences were found between groups with respect to patient characteristics or type of surgery. Rescue analgesia requirements were higher in group L-A than in the other groups. PaO2 (6 and 18 hours) and spirometric parameters (12 and 18 hours) were significantly higher in group T-AL than in the other groups (p < or = 0.05). No other statistically significant differences were found. CONCLUSIONS: Respiratory parameters were better after thoracic epidural analgesia with alfentanil and lidocaine than after the other analgesic techniques studied. Group L-A patients had greater need for rescue analgesia than did patients in the other groups.     

Fastrach laryngeal mask, sevoflurane and remifentanil: an anesthetic alternative for the myasthenic patient

A 46-year-old myasthenic man diagnosed two months earlier and experiencing nocturnal dyspnea was scheduled for transsternal thymectomy. The patient was premedicated with midazolam in the operating room. Anesthetic induction and maintenance were with inhaled sevoflurane and an intravenous infusion of remifentanil, with no need for neuromuscular relaxants. Airway management was achieved by inserting a Fastrach laryngeal mask (LM-Fastrach), through which an endotracheal tube could be inserted easily. The tube was withdrawn through the mask at the end of surgery and the mask was removed in the operating room 6 minutes later. Anesthesia in patients with myasthenia gravis is one of the greatest challenges in clinical anesthesiology. The interest of this case lies mainly in that the anesthetic technique chosen allows neuromuscular relaxants to be avoided. Moreover, airway access through the Fastrach laryngeal mask is highly useful for transsternal thymectomy of the patient with myasthenia gravis, providing immobility and adequate hemodynamic stability during sternotomy as well as facilitating safe and rapid postanesthetic recovery.     

Sexual precocity: sex incidence and aetiology

The aetiology of 197 girls and 16 boys presenting with sexual precocity was reviewed. Ninety one girls and four boys had central precocious puberty (M:F 23:1); a cause was identified in all the boys but in only six girls. All boys with precocious puberty need detailed investigation; in girls investigation should be based on clinical findings, particularly the consonance of puberty.     

Thymic cysts in mediastinal Hodgkin disease

Three cases of proved thymic cysts associated with mediastinal Hodgkin disease are presented. Two illustrate regression of lymphoma with chemotherapy but persistence of thymic cysts. The third case demonstrates a thymic cyst in untreated Hodgkin disease. These cases suggest that such cysts are probably neither coincidental with nor a consequence of therapy but are probably related to initial thymic involvement by Hodgkin disease.