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.     

Acidosis-induced apoptosis in human and porcine heart

BACKGROUND: Acidosis-mediated injury to cardiac myocytes during surgery may lead to progressive heart failure. The nature of this injury, although not well defined, may be caused by induction of apoptosis in cardiac myocytes. We applied fluorescence imaging and biochemical techniques to assess apoptosis in cardiac myocytes excised from human patients and porcine subjects maintained on cardiopulmonary bypass to demonstrate the relationship between acidosis and apoptosis. METHODS: Multiphoton microscopy was used to image fluorescence signals generated in myocytes deep within atrial and ventricular biopsies for identification of apoptotic changes. The biopsies, obtained during cardiac surgery, were subjected to ex vivo or in vivo acidosis. Proapoptotic markers such as exposure of phosphatidyl serine, cytochrome c, apoptotic protease-activating factor-1, and caspase-3 were identified using fluorescence-based imaging and biochemical assays. RESULTS: Within 30 minutes of storage in low pH (<7) buffers, apoptosis was detected in human atrial samples, the severity of which correlated well with low pH. Apoptosis was also detected in atrial and ventricular biopsy samples obtained from three porcine subjects maintained on cardiopulmonary bypass and undergoing 110 minutes of aortic cross-clamp and 10 minutes of reperfusion, in which the cardiac pH was 6.36, 7.14, and 7.48. The apoptosis level detected in postacidotic reperfused cardiac tissue was pH dependent and approximately threefold greater than the precross-clamp levels. CONCLUSIONS: Using fluorescence multiphoton microscopy and biochemical techniques we have assessed a direct correlation between low pH and induction of apoptosis in cardiac samples obtained both from human patients undergoing cardiac surgery and porcine subjects maintained on cardiopulmonary bypass simulating cardiac surgery.     

Postoperative mortality after nontraumatic lower extremity amputation in patients with renal insufficiency

Mortality rates after lower extremity amputation are extremely high among dialysis patients. However, the impact of milder degrees of renal insufficiency on death rates after lower extremity amputation has not been carefully examined. In this study, the authors used data from the Department of Veterans Affairs' National Surgical Quality Improvement Program (NSQIP) to measure the association between renal dysfunction and 30-d mortality after nontraumatic amputation adjusted for confounders. The study population consisted of 16,994 patients undergoing their first NSQIP recorded amputation from January 1, 1994 through September 30, 2001. Thirty-five percent of all cohort patients had at least moderate renal insufficiency, and 52% of all postoperative deaths occurred in this group. Postoperative mortality was 9% in patients with moderate renal insufficiency, 15% in patients with severe renal insufficiency, and 16% in dialysis patients, compared with 6% in patients with normal or mildly reduced renal function. Renal insufficiency remained associated with death after adjustment for confounders (adjusted odds ratio [OR] 3.36, 95% confidence interval [CI] 2.75 to 4.10 [dialysis patients]; OR 2.54, CI 2.06 to 3.14 [severe renal insufficiency]; and OR 1.52, CI 1.32 to 1.76 [moderate renal insufficiency]). In conclusion, even moderate renal insufficiency is independently associated with postoperative death after lower extremity amputation. This finding highlights the need for a targeted approach to improving the care of patients with renal insufficiency undergoing lower extremity amputation.     

Incidence of serious complications after uvulopalatopharyngoplasty

OBJECTIVES: Uvulopalatopharyngoplasty (UPPP) is the most common surgical treatment for obstructive sleep apnea (OSA). Anatomic and physiologic abnormalities associated with OSA can make perioperative management difficult. Only single-site case series provide current estimates of the incidence of perioperative complications, with a pooled crude serious complication rate of 3.5% and a crude mortality rate of 0.4%. The primary objective of this study was to calculate the incidence of perioperative morbidity and mortality in a large, multisite cohort of UPPP patients. STUDY DESIGN: Prospective cohort study of adults undergoing inpatient UPPP with or without other concurrent procedures METHODS: The serious complication and 30-day mortality rates were calculated from the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program database of prospectively collected outcomes of all VA inpatient surgeries nationally 1991 to 2001. Serious complications were defined by 15 specific life-threatening complications. Deaths were captured whether the patient was in the hospital or discharged. RESULTS: Veteran patients (n = 3130) had a mean age of 50 years and were predominantly male (97%). The serious nonfatal complication rate was 1.5% (47/3,130) (95% confidence interval [CI] 1.1%, 1.9%). The 30-day mortality rate was 0.2% (7/3130) (95% CI 0.1%, 0.4%). There was no significant effect of year of surgery or patient age on the risk of serious complication or death. CONCLUSION: The incidence of serious nonfatal complications and 30-day mortality after UPPP are 1.5% and 0.2%, respectively, in a large cohort of UPPP patients at veteran hospitals.     

A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status

BACKGROUND: Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1-3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5-fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1-2N2-3M0 NPC. METHODS: Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time-concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy. RESULTS: Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off-study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases. CONCLUSIONS: Although unlikely to be superior to cisplatin + 5-fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk-based approach examined in the current study merits further investigation.     

Sex differences in survival in non-small cell lung cancer patients 1974-1998

This study comprised a total of 7,553 patients with non-small cell lung cancer (2,660 women and 4,893 men) treated at a comprehensive cancer centre between 1974 and 1998. Significant differences in tumour histology were associated with gender (p < 0.001); adenocarcinoma was the most common diagnosis in both men (50.0%) and women (41.7%); squamous cell carcinoma was the second most prevalent diagnosis (21% and 31% in women and men, respectively); and bronchioalveolar tumours were more prevalent in men (3% compared with 7% in women). Frequency distributions with local, regional or distant disease at registration were similar between men and women (p = 0.906). In a multivariable Cox regression analysis the indications were that gender is an important risk factor for survival. Adjusting for age, stage, treatment received and ability to pay for care, a statistically significant interaction between gender and tumour histology (p = 0.043) was found, where, in relation to female sex and histologies other than squamous carcinoma, women who presented with squamous carcinoma had an increased risk of death (HR = 1.09, 95% CI 1.02-1.18) while men had an increased risk of death for all histologies (HR = 1.29, 95% CI 1.21-1.40, and HR = 1.15, 95% CI 1.07-1.24 for squamous and other histologies, respectively). This study confirms previous reports of strong gender-dependent differences in survival in patients with non-small cell lung cancer, including a histology-specific effect in women.