Inhaled nitric oxide during emergency neonatal transportation

ABSTRACT Inhaled nitric oxide is currently being investigated as a selective pulmonary vasodilator for neonates with persistent pulmonary hypertension. The use of continuous inhaled nitric oxide during emergency transportation of three critically ill neonates with meconium aspiration and pulmonary hypertension is described. The successful application of this technique may allow safer transportation of neonates who require high level intensive care including ongoing nitric oxide, high frequency ventilation and/or extracorporeal life support. Regionally based nitric oxide-equipped retrieval teams may relieve the pressure on smaller neonatal intensive care units to provide inhaled nitric oxide therapy and allow centralization of nitric oxide resources, thus facilitating development of expertise and the completion of meaningful research programs with substantial recruitment.     

Health care and its costs for children with perinatally acquired HIV infection

Objective : To describe survival patterns, use of health services and related costs for Australian children with perinatally acquired human immunodeficiency virus (HIV) infection.
Methodology : A retrospective cross-sectional survey was made of 20 children with HIV infection (91% of those diagnosed) and 13 children with maternal antibodies who subsequently seroreverted, treated at 10 medical centres. Details of disease progression and use of health services were obtained from hospital medical records. Monthly costs for three phases of infection were estimated by linking service usage rates with estimates of the unit cost of each service. The average lifetime cost was estimated by combining monthly costs and phase duration estimates from the literature.
Results : Patterns of disease progression were similar to those reported internationally, with a median survival of 8 years. Use, of health services increased with severity of illness. Mean monthly costs were $120 per month (1992 Australian dollars) for children with maternal antibodies who subsequently seroreverted, $320 per month for children with HIV infection but no acquired immunodeficiency syndrome (AIDS)-defining illness, and $1830 per month for children with AIDS. The present value of total lifetime cost for a child with HIV infection was $48174,46% of which was for treatment of AIDS.
Discussion : The mean lifetime cost for a perinatally infected child was just over half that for a man with HIV in Australia. Health service usage and costs were lower for Australian than American children with HIV.     

Molecular analysis of PKU in Ireland

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromsome background in the Irish/Celtic population.     

Moyamoya syndrome with intraventricular hemorrhage in an adult with factor V Leiden mutation

OBJECTIVE: To report a case of proximal occlusion of 2 major cerebral vessels associated with moyamoya network circulation that manifested by spontaneous intraventricular hemorrhage. DESIGN: Case report. PATIENT AND RESULTS: A 36-year-old Syrian man presented with symptoms of sudden-onset headache, neck stiffness, and confusion. The computed tomography scan of his brain showed intraventricular bleeding, and the subsequent 4 vessel angiographies revealed occlusion of the left middle and anterior cerebral arteries with moyamoya appearance in the terminal branches. The coagulation profile showed the presence of heterozygous factor V Leiden mutation. The patient was treated conservatively until resolution of his blood clot, and later he was started on oral anticoagulation. CONCLUSION: Factor V Leiden mutation may cause large cerebral vessel occlusion with moyamoya syndrome in adults.     

Continuous perfusion with morphine of the orbitofrontal cortex reduces allodynia and hyperalgesia in a rat model for mononeuropathy

Recent imaging reports demonstrate the activation of the orbitofrontal cortical (OFC) area during acute and chronic pain. The aim of this study was to compare the effects of chronic perfusion of this area with morphine on nociception in control rats and in rats subjected to mononeuropathy. Chronic perfusion of morphine, using miniosmotic pumps, produced significant and naloxone-reversible depression of tactile and cold allodynias and thermal hyperalgesia, observed in neuropathic rats, while it produced significant elevation and naloxone insensitive increase of acute nociceptive thresholds in control rats. The observed results support the idea that this area is a component of a flexible cerebral network involved in pain processing and perception.     

Chronic thalamotomy increases pain-related behavior in rats

The thalamus has been traditionally considered as the 'chief organ' by which pain is perceived (Head H, Holmes G. Sensory disturbances from cerebral lesions. Brain 1911;34:102-254). However, several clinical and experimental observations led to a challenge of this traditional view. In this report, we demonstrate that chronic thalamic lesions, instead of producing hypoalgesia, increased pain reactivity in rats. Different groups of rats were subjected to either subtotal, lateral or medial thalamic lesions. Their reactions to nociceptive stimuli were then assessed for a period of 1-2 months. Rats in the different groups showed an increased reactivity to acute mechanical and thermal nociceptive stimuli and an increase in the pain scores of the formalin test. These results suggest an important role of the thalamus in pain modulation in addition to that of nociceptive transmission.     

Percutaneous drainage access: a simplified coaxial technique

We describe an access technique that we have used in 150 nephrostomy and biliary drainage procedures and for access to some abscesses and viscera. The system provides safe coaxial access with a 22-gauge removable hub needle, which then acts as a guide wire and is replaced by an 18-gauge cannula. A major advantage is that only one guide wire is used (0.038-inch) for the entire drainage procedure. No significant complications have occurred to date with this method.     

Production of genetically stable high-titer retroviral vectors that carry a human gamma-globin gene under the control of the alpha-globin locus control region

The ability to generate stable high-titer vectors that give rise to high levels of expression of transduced globin genes in erythroid cells is a prerequisite for effective retroviral-mediated globin gene therapy. The human beta-globin gene with its immediate flanking sequences does not contain all the regulatory elements necessary for regulated high-level and position-independent expression in erythroid cells. The regulatory element known as the beta-globin locus control region (BetaLCR) can provide a linked Beta-globin gene with these properties. However, addition of BetaLCR sequences to a retrovirus carrying a beta-globin gene increases its genetic instability. We have developed a new generation of retroviral vectors in which a human gamma- globin gene is placed under the control of the alphaLCR, the major regulatory element of the alpha-globin gene cluster. We demonstrate that these retroviruses are genetically stable in producer cell lines and can be produced at high titers that exceed 5 x 10(6) colony-forming units (CFU)/mL. In addition, we show that the transduced gamma-globin gene can be expressed in the adult erythroid environment of mouse erythroleukemia (MEL) cells at a level comparable to that of a single endogenous Betamaj-globin gene. These retroviruses can also transduce primary murine bone marrow progenitor cells as efficiently as retroviruses that carry the neomycin resistance (neor) gene. This new generation of globin retroviral vectors may prove useful for gene therapy of human beta-globin gene disorders such as sickle cell disease and beta-thalassemia.