Clinical response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn

We observed clinical response to inhaled nitric oxide (iNO) in 12 neonates with persistent pulmonary hypertension of the newborn (PPHN). Clinical response was defined as a decrease in oxygenation index (OI) by 40%. Ten of 12 neonates had response to iNO showing decrease OI from 46.1+/-7.6 to 14.4+/-6.8 at 1 hour after inhalation. Sustained improvement of OI was achieved in 8 neonates and two neonates were relapsed. In the group of neonates who had OI above 40 (n=7), 6 of them showed the decrease of OI from 66.1+/-4.8 to 18.3+/-8.0 at 1 hour. In two groups, one had OI of 40 or greater, and the other OI of 40 or less, there were no differences in pattern of response and early death rate. The response rates according to underlying diseases were as follows; idiopathic PPHN 100%, respiratory distress syndrome 100%, and diaphragmatic hernia 66.7%. Relapse was observed in one neonate with sepsis caused by pneumonia and in one infant with meconium aspiration syndrome. Two infants showed no response to iNO (one diaphragmatic hernia and one suspected pulmonary hypoplasia). We conclude that iNO therapy could improve oxygenation in high percentage of newborn infants with severe PPHN of various underlying conditions except pulmonary hypoplasia.     

High expression of leptin by human bone marrow adipocytes in primary culture

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10-80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45+/-20 vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age > or =34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants.     

Epithelial repair in asthma. Do the benefits of house dust mite avoidance result from proteinase avoidance?

OBJECTIVE: To describe the timing of recovery of lung function after severe acute hypoxemic respiratory failure (AHRF) in children. DESIGN: A serial observational follow-up study of clinical and lung function measurements up to 53 months after acute illness. SETTING: University pediatric intensive care unit in a national children's hospital. PATIENTS: Five critically ill children aged 5-14 years. INTERVENTIONS: None RESULTS: Clinical recovery: each patient required a 3-5 month convalescence before being able to attend full-time school because of lethargy and dyspnea. All patients developed wheeze 3-12 months after illness and four received long-term bronchodilator therapy. Lung function recovery: for both the forced vital capacity (FVC) and forced vital capacity in the first second (FEV1) four patients had abnormally low values, regaining only 60-70% of predicted values for their height and sex, and all of this improvement had occurred by 6-12 months after illness. Beyond this interval, patients remained on their same FVC and FEV1 centile. FEV1/FVC ratios were consistently within the normal range, indicating a predominantly restrictive defect. Changes in peak expiratory flow exhibited a time course of improvement similar to the other lung function tests. CONCLUSION: In children, pulmonary recovery after severe AHRF may occur for 6-12 months. A 1-year follow-up could offer a rational single point for assessment of outcome and long-term counselling of child and parents.     

Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. The NO Almitrine Study Group

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.     

The antibody response to 27-, 17-, and 15-kDa Cryptosporidium antigens following experimental infection in humans

STUDY OBJECTIVE: Data concerning inhaled nitric oxide (iNO) on pediatric ARDS is rare. We investigated the effects of iNO on pediatric ARDS in order to examine the ability to predict a response to iNO, the optimal concentration of iNO, the effects of < or = 1 ppm nitric oxide (NO), and the effect of iNO on PaCO2. SETTING: ICU at Kumamoto (Japan) University Hospital. PATIENTS AND INTERVENTIONS: Seven children with ARDS. The initial responses to 16 ppm NO and the dose-response effects of 0.13 to 16 ppm NO were assessed. MEASUREMENTS AND RESULTS: Sixteen ppm of iNO improved oxygenation in all seven children. The use of iNO significantly increased the ratio of arterial oxygen tension to the fraction of inspired oxygen (PaO2/FIO2). A correlation between the NO-induced increase in PaO2/FIO2 and the baseline PaO2/FIO2 was observed (r=0.93, p<0.01). Dose-response tests showed that the optimal concentration of iNO was < or = 4 ppm, improvements in PaO2/FIO2 could be observed with concentrations of < or = 1 ppm NO, and iNO induced a slight decrease in PaCO2. CONCLUSIONS: In children with ARDS, iNO frequently improves oxygenation and induces a slight decrease in PaCO2, with the baseline PaO2/FIO2 functioning as a predictor of all NO response. Improvements of PaO2 and PaCO2 were observed with concentrations of iNO of < or = 1 ppm, a level in which the risk of a toxic reaction in children is minimal. Effects on outcome need verification in larger controlled trials.     

Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic significance of slow early response to induction chemotherapy for children and adolescents with acute lymphoblastic leukemia and unfavorable presenting features: a report from the Children's Cancer Group

PURPOSE: Compared with previous Children's Cancer Group (CCG) acute lymphoblastic leukemia (ALL) trials, therapy based on the Berlin-Frankfurt-Munster (BFM) 76 trial has effected an improvement in event-free survival (EFS). In an attempt to improve EFS further, CCG investigators formulated an augmented BFM (A-BFM) regimen that provides prolonged, intensified postinduction chemotherapy relative to the CCG-modified BFM regimen. PATIENTS AND METHODS: We tested A-BFM in 101 patients with ALL and unfavorable presenting features that showed slow early response (SER) to induction therapy who attained remission on day 28. Their outcome was compared with that of 251 concurrent patients with unfavorable presenting features, a rapid early response to therapy (RER), and remission by day 28, treated with CCG-BFM with or without cranial radiation (CRT). RESULTS: The 4-year EFS rate from the end of induction for SER patients treated with A-BFM was 70.8% +/- 4.6%. Seventeen patients remain in continuous remission beyond 5 years. Vincristine (VCR) neurotoxicity developed in 50% of patients, but was rarely debilitating. Allergies to Escherichia coli L-asparaginase (L-ASP) occurred in 35% of patients. Avascular necrosis of bone (AVN) developed in 9% of patients. In comparison, a concurrent RER group treated with standard BFM +/- CRT had a 4-year EFS rate of 73.1% +/- 4.6%. CONCLUSION: The toxicity of A-BFM is significant, but acceptable. Compared with historical control SER patients treated with CCG-modified BFM, A-BFM therapy appears to produce a significant improvement in EFS. This is the first study to show that intensive chemotherapy, as given in the A-BFM regimen, can abrogate the adverse prognostic significance of SER.     

Response to inhaled nitric oxide in acute lung injury depends on distribution of pulmonary blood flow prior to its administration

Responses to inhaled nitric oxide (iNO) in acute lung injury (ALI), as evidenced by improvements in oxygenation, are variable. We hypothesized that the effect of iNO may be related to the pre-iNO distribution of pulmonary blood flow (PBF). In the present study we evaluated the effect of iNO on PBF in normal healthy dogs and in a canine model of ALI induced by oleic acid (OA). In Group "OA only" (n = 5), ALI was induced by central venous injection of 0.08 ml/kg OA. In Group "E+OA" (n = 5), hypoxic pulmonary vasoconstriction after ALI was blocked with low-dose endotoxin (15 microg/kg of Escherichia coli endotoxin) administered 30 min before giving the same dose of OA. Measurements of regional PBF and lung water concentration (LWC) using positron emission tomography (PET) and H215O were performed before and after OA or placebo, and then again at concentrations of 10, 40, and 0 ppm iNO. One hundred twenty minutes after OA injury, PaO2/FIO2 fell significantly in Group OA only, from 567 +/- 32 to 437 +/- 67 mm Hg. In these animals, PBF redistributed from the dorsal edematous regions of the lungs to the nondependent zones, thus partially preserving normal ventilation/ perfusion relationships. As in the normal animals, in Group OA only, iNO did not significantly change either PBF or oxygenation. In Group E+OA, the administration of low-dose endotoxin eliminated perfusion redistribution from the dorsal edematous lung regions. As a result, PaO2/FIO2 fell from 558 +/- 70 to 119 +/- 53 mm Hg, a decrease that was significantly greater than that in Group OA only. In Group E+OA, administration of iNO restored perfusion redistribution to a similar level as in Group OA only, which was associated with a significant improvement in PaO2/FIO2, from 119 +/- 53 to 251 +/- 159 (10 ppm iNO), and 259 +/- 165 mm Hg (40 ppm iNO). We conclude that the effect of iNO on oxygenation after ALI depends on the pre-iNO perfusion pattern, which may help explain the variable response to iNO often observed in patients with acute respiratory distress syndrome.     

Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids

BACKGROUND: The histologic appearance of esophageal eosinophils has been correlated with esophagitis and gastroesophageal reflux disease in children. Esophageal eosinophilia that persists despite traditional antireflux therapy may not represent treatment failure, but instead may portray early eosinophilic gastroenteritis or allergic esophagitis. In this study, a series of pediatric patients with severe esophageal eosinophilia who were unresponsive to aggressive antireflux therapy were examined and their clinical and histologic response to oral corticosteroid therapy assessed. METHODS: Of 1809 patients evaluated prospectively over 2.5 years for symptoms of gastroesophageal reflux, 20 had persistent symptoms and esophageal eosinophilia, despite aggressive therapy with omeprazole and cisapride. These patients were treated with 1.5 mg/kg oral methylprednisolone per day, divided into twice-daily doses for 4 weeks. All patients underwent clinical, laboratory, and histologic evaluation before and after treatment. RESULTS: Histologic findings in examination of specimens obtained in pretreatment esophageal biopsies in children with primary eosinophilic esophagitis indicated significantly greater eosinophilia (34.2+/-9.6 eosinophils/high-power field [HPF]) compared with that in children with gastroesophageal reflux disease who responded to medical therapy (2.26+/-1.16 eosinophils/HPF; p < 0.001). After corticosteroid therapy, all but one patient with primary eosinophilic esophagitis had dramatic clinical improvement, supported by histologic examination (1.5 +/-0.9 eosinophils/HPF, p < 0.0001). CONCLUSIONS: Pediatric patients in a series with marked esophageal eosinophilia and chronic symptoms of gastroesophageal reflux disease unresponsive to aggressive medical antire-flux therapy had both clinical and histologic improvement after oral corticosteroid therapy.     

Escalating health care costs: costs of litigation

Fifty children with head injury were evaluated in an attempt to establish a correlation between post-traumatic hyperglycaemia and long-term outcome. In all the patients, the blood glucose level was measured on admission and on the days following the trauma (threshold of normal value set at 150 mg/dl). Hyperglycaemia was seen more frequently in children with severe head injury than in those with mild and moderate head injury. It was present in 87.5% of the patients with a Glasgow Coma Score (GCS) < or =8 (the average blood glucose level on admission was 237.8+/-92 mg/dl), in 60% of the patients with a GCS of 9-12 (178+/-78.7 mg/dl) and only in 25% of those with a GCS of 13-15 (131.5+/-39 mg/dl). A close correlation was also seen between the outcome and the blood glucose level. In fact, the blood glucose on admission was higher in the patients with a poor outcome, i.e. in those having a Glasgow Outcome Score (GOS) of 2 or 3 and in those who died (GOS 1), than in the patients with a good outcome (GOS of 4 or 5). Finally, hyperglycaemia persisted beyond the first 24 h after trauma in all the children who died or who survived with a poor outcome. Hyperglycaemia, and especially its persistence over time, appears to be an important negative prognostic factor in children with head injury.     

Incremental threading optimization (TITO) to help alignment and modelling of remote homologues

OBJECTIVE: To evaluate the role of thyroid hormones in maintaining early pregnancy and to examine the association between thyroid physiological functions and immunological parameters. METHODS: Forty-five pregnant women with a clinical diagnosis of threatened abortion and a live fetus and 30 normal pregnant women were included in the study. Blood samples were taken on admission to the hospital. The patients were divided retrospectively into two groups on the basis of outcome: 1) 31 women who did not miscarry (positive outcome) and 2) 14 women who miscarried (negative outcome). Plasma TSH, free triiodothyronine (fT3), free thyroxine (fT4), hCG, immunoglobulin (Ig) G and IgM concentrations and blood counts were determined in each patient. RESULTS: Human chorionic gonadotropin was significantly higher in women who did not abort (39.4 +/- 16.9 IU/mL) than in women who miscarried (17.6 +/- 14.8 IU/mL, P < .001). Free thyroxine but not fT3 was lower in patients with negative outcome (1.25 +/- 0.26 ng/mL compared with 1.98 +/- 0.22 ng/mL, P < .001) and IgG and IgM plasma levels were higher (780 +/- 500 ng/mL compared with 470 +/- 300 ng/mL and 930 +/- 400 ng/mL compared with 650 +/- 280 ng/mL, respectively, P < .05). Plasma TSH levels were higher in patients with negative outcomes (1.72 +/- 0.84 mIU/mL compared to 1.01 +/- 0.41 mIU/mL, P < .001). Plasma concentrations of hCG and thyroid hormones were significantly correlated with peripheral blood lymphocyte and neutrophil counts only in the group of women who aborted. CONCLUSION: Our results indicate that maternal immune response, trophoblast function, and maternal thyroid function are somehow correlated. The presence of low concentrations of hCG and fT4 and high levels of TSH and gamma globulins in women with threatened abortion suggests a negative outcome for the pregnancy.     

Severe head injury in children--analyzing the better outcome over a decade and the role of major improvements in intensive care

We suggest a few possible explanations, including improvement of intensive care, as the main cause, for the improved outcome after severe head injury in children and present the predictors of outcome observed in a contemporary series. From January 1984 to June 1988 we saw 117 children (ages 0-14) with postresuscitation GCS (Glasgow Come Scale) scores of 3-8. The more recent cohort of children seen in 1994-1996 was made up of 152 patients. Apart from standard statistics we used a segmentation method called CHAID (SSPS software). Previously known predictors of outcome are found still to apply in our series. Although in the recent period there was a lower proportion of patients with GCS 3-4 (11% versus 32%), a higher percentage had suffered multiple trauma (56% versus 33%). The rates of craniotomy and of ICP monitoring were similar (66% and 61%). Comparison of the two cohorts for outcome at discharge and through 1 year shows that mortality fell from 33% to 10% and the proportion achieving improvement of neurological status increased from 24% to 56%. CHAID analysis showed that the mortality rates of patients within specific groups declined significantly over the two periods: (1) a significant reduction in mortality was seen in patients with GCS 5-7, especially those with diffuse axonal injury (DAI) (17.3% to 0%); (2) no child admitted in shock survived in the earlier period, whereas 7 with GCS 4-6 survived during the recent period. The best model for mortality prediction includes GCS, and in the GCS 4-7 subgroup, the presence of subdural hematoma. It seems that the trend toward better immediate outcome is continuous, and this is the more striking when the severity of injury is taken into consideration. Our belief is that the modern medical and surgical techniques, although incurring higher costs and necessitating ongoing intensity, are well worth the effort.     

Trauma patients 75 years and older: long-term follow-up results justify aggressive management

BACKGROUND: Long-term survival rate and functional status after trauma for one of the fastest growing segments of the population, patients 75 years and older, is poorly documented. METHODS: Trauma patients 75 years and older who were discharged from our Level I trauma center between June 1988 and July 1992 (n = 279) were contacted by mail or phone. Public death records were used to identify patients who had died. A stepwise logistic regression analysis was performed to determine predictors of poor outcome (death within 6 months). Main outcome measures included mortality and self-assessed functional status. RESULTS: A minimum 4-year follow-up was obtained for 81% of the 279 study patients. The mean follow-up period was 5.4 +/- 1.1 years. Mean age at time of injury was 81 +/- 5 years (range, 75-101 years); mean Injury Severity Score was 9.4 +/- 7.7. At follow-up, 132 patients (47%) had died, 93 patients (33%) were contacted, and 54 patients (19%) could not be located. Twelve percent of patients survived less than 6 months after discharge. Poor survival was predicted by preexisting diseases (dementia, p = 0.001; hypertension, p = 0.02; and chronic obstructive pulmonary disease, p = 0.05) and not by age or severity of injury. The mean age of patients still living was 85 +/- 3.9 years (range, 79-99 years), and 77 of 93 patients were living in an independent setting (33 alone, 44 with spouse or family); of these, 57% reported no difficulties in performing 12 of 14 activities of daily living. CONCLUSION: Despite higher than expected mortality after discharge, aggressive management of trauma patients 75 years and older is justified by the favorable long-term outcome.     

Combination chemotherapy with doxorubicin, bleomycin, and vindesine for AIDS-related Kaposi's sarcoma

BACKGROUND: Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. METHODS: A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. RESULTS: Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. CONCLUSIONS: The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.     

Myocardial infarction in critically ill patients presenting with gastrointestinal hemorrhage: retrospective analysis of risks and outcomes

OBJECTIVES: To determine the frequency of and risk factors for myocardial infarction (MI) in patients admitted to an ICU with GI hemorrhage, and the effects of MI on mortality and length of stay. METHODS: A retrospective review of the medical records of patients admitted to our ICU with GI hemorrhage was conducted. Charts were reviewed for various demographic, laboratory, and outcome parameters. Patients were categorized as having MI, not having MI, or inadequate data to allow classification. RESULTS: Two hundred thirty admissions to the ICU for GI hemorrhage were reviewed. One hundred thirteen cases had serial creatine phosphokinase (CK) measurements with isoenzymes allowing diagnosis of MI. In these 113 cases, patients' mean age was 67.4+/-1.3 years and the mean APACHE II (acute physiology and chronic health evaluation) score was 10.9+/-0.6. The in-hospital mortality rate was 13/113 (11.5%). Patients who did not survive had a higher admission APACHE II score (15.8+/-2.0 vs 10.2+/-0.5; p = 0.02), lower initial systolic BP (104.5+/-4.4 vs 121.2+/-3.2 mm Hg; p = 0.005), and a longer length of ICU stay (8.3+/-1.8 vs 4.0+/-0.4 days; p = 0.04) than those who survived. Sixteen of 113 patients met enzymatic and ECG criteria for MI. One patient complained of chest pain and nine of 16 had shortness of breath and/or dizziness. Patients with MI had significantly more cardiac risk factors (2.4+/-0.2 vs 1.6+/-0.1; p = 0.006), lower presenting hematocrit (26.0+/-1.3 vs 30.5+/-0.8; p = 0.007), and lower lowest hematocrit in the first 48 h (22.3+/-0.9 vs 25.1+/-0.6; p = 0.01), and tended to have a longer ICU stays (7.9+/-2.2 vs 4.0+/-0.4 days; p = 0.09) than those without MI. Patients who had MI were not more likely to die during hospitalization (risk ratio = 1.8; 95% confidence interval, 0.6 to 5.8). CONCLUSIONS: Myocardial infarction occurs frequently in patients admitted to intensive care with GI hemorrhage. A clinical history of and multiple risk factors for coronary artery disease may help identify patients who are at increased risk of MI, which tends to be associated with a higher acuity of illness and in-hospital mortality. Prospective studies are required to further substantiate these associations.     

Diabetes insipidus revealing primary malignant non-Hodgkin''s lymphoma of bone]

Renal histology is increasingly used as a guide for therapy and prognosis in SLE but data in children are few and/or short-term. We assessed renal histological features in 19 children with SLE to determine whether these features are useful in predicting long-term outcome. Mean age at biopsy was 10 +/- 1.7 years old, male to female ratio was 1:2.8. Fourteen patients (73%) had diffuse proliferative lupus nephritis. Renal histology was evaluated using an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis and serum creatinine. Renal function at biopsy correlated well with AI (p < 0.001) but not CI. At short-term follow-up (30 months), 3 patients had died from sepsis and another 2 reached end-stage renal disease. CI predicted poor clinical outcome, i.e. death or renal failure (p < 0.005) but AI did not. At long-term follow-up (mean 92.1 +/- 26.8 months) only one more patient reached end-stage renal disease. In others renal function assessment showed improvement or were stable. Neither CI nor AI correlated with clinical outcome. We conclude that although AI correlates well with renal function at biopsy and CI with short-term prognosis, neither can predict long-term outcome. Treatment may have altered the natural course of disease in these patients.     

To tube or not to tube: do infants and children need post-laparotomy gastric decompression?

The purpose of this study was to evaluate the role of nasogastric (NG) decompression after laparotomy in pediatric surgical practice: 94 children who underwent abdominal surgery by a single surgeon were consecutively prospectively managed without postoperative NG tubes. Patients with either bowel obstruction or intra-abdominal infection were excluded from the study. These children were compared with 94 retrospective, matched controls who were routinely managed with postoperative NG decompression by the same surgeon. Data were analyzed with regard to patient, operative, and outcome variables. There was no difference in gender, age (3.8 +/- 0.5 vs 3.5 +/- 0.4 years, P > 0.7), or postoperative complications (P > 0.8) between the two groups. However, there was a higher incidence of postoperative vomiting (22% vs 11%, P > 0.05) in the children who did not have postoperative NG decompression. Nevertheless, a significant decrease in time to first feed, first stool, and discharge was noted in the group of patients managed without NG tubes (P < 0.05). NG decompression thus need not be routinely used in the pediatric patient undergoing abdominal surgery, as there is no difference in postoperative complications and the hospital stay is shortened.     

Carbon-11-thymidine and FDG to measure therapy response

This study was performed to determine if PET imaging with 11C-thymidine could measure tumor response to chemotherapy early after the initiation of treatment. Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine, was compared with measurements of tumor energetics, obtained by imaging with 18F-fluorodeoxyglucose (FDG). METHODS: We imaged four patients with small cell lung cancer and two with high-grade sarcoma both before and approximately 1 wk after the start of chemotherapy. Thymidine and FDG studies were done on the same day. Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions of interest placed on the most active part of the tumor. RESULTS: In the four patients with clinical response to treatment, both thymidine and FDG uptake markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR) declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient with metastatic small cell lung cancer who had disease progression, the thymidine SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and progressive disease, thymidine SUV was essentially unchanged (declined by 3%), whereas FDG SUV increased by 69%. CONCLUSION: Images show a decline in both cellular energetics and proliferative rate after successful chemotherapy. In the two patients with progressive disease, thymidine uptake was unchanged 1 wk after therapy. In our limited series, K(TdR) measurements showed a complete shutdown in tumor proliferation in patients in whom FDG showed a more limited decrease in glucose metabolism.     

Serum neuron-specific enolase as early predictor of outcome after cardiac arrest

OBJECTIVE: To examine the prognostic value of serum neuron-specific enolase for early prediction of outcome in patients at risk for anoxic encephalopathy after cardiac arrest. DESIGN: Prospective study. SETTING: Coronary intensive care unit of the University of Heidelberg. PATIENTS: Forty-three patients (66.8 +/- 12.7 [SD] yrs, range 33 to 85) who had had either primary or secondary cardiac arrest, followed by cardiopulmonary resuscitation (CPR). INTERVENTIONS: Serial blood samples and clinical examinations. MEASUREMENTS AND MAIN RESULTS: Serum neuron-specific enolase concentrations were determined after CPR on 7 consecutive days. Twenty-five patients remained comatose and subsequently died; 18 patients survived the first 3 months and had no relevant functional deficit at 3-month follow-up. Neuron-specific enolase concentrations were correlated with neurologic outcome. Concentrations of >33 ng/mL predicted persistent coma with a high specificity (100%) and a positive predictive value of 100%. Overall sensitivity was 80%, with a negative predictive value of 78%. Serum concentrations of neuron-specific enolase exceeded this cutoff value no more than 3 days after cardiac arrest in 95% of patients in whom these concentrations had exceeded 33 ng/mL. CONCLUSIONS: In patients who have been resuscitated after cardiac arrest, serum neuron-specific enolase concentrations of >33 ng/mL predict persistent coma with a high specificity. Values below this cutoff level do not necessarily indicate complete recovery, because this method has a sensitivity of 80%.     

Mortality in burned children with acute renal failure

BACKGROUND: During the past 13 years, mortality from acute renal failure in burned children has been on the decline. OBJECTIVE: To determine which new burn therapies contributed to the decrease in mortality. DESIGN: The medical records of burned children admitted from February 1966 to January 1997 were reviewed, and the outcome of changes in the treatment of burned children were compared. PATIENTS AND METHODS: Sixty children with acute renal failure were identified. These children were divided into those admitted from 1966 to 1983 (n=24) and those admitted from 1984 to 1997 (n=36). They were compared with matched control subjects from the same period without renal failure. Values are presented as means+/-SEMs. Statistical analysis was by the Student t test or chi2 analysis. RESULTS: Mortality rates in burned children with acute renal failure decreased from 100% before 1983 to 56% after 1984 (P<.001). The time between a burn injury and the initiation of intravenous fluid resuscitation was 8.6+/-1.7 hours before 1983 compared with 3.0+/-0.5 hours after 1984 (P<.005). The time between a burn injury and complete early wound excision decreased from 228+/-37 hours before 1983 to 40+/-7 hours after 1984 (P<.001). The incidence of sepsis decreased from 71% to 44% in these periods (P<.05). After 1984, survivors had a shorter time delay for fluid resuscitation than nonsurvivors (1.7+/-0.5 hours vs 4.8+/-0.9 hours; P<.005) and a lower incidence of sepsis (19% vs 60%; P<.05). From 1984 to 1997, burned children with acute renal failure who did not require dialysis had significantly shorter delays for fluid resuscitation (2.2+/-0.5 hours vs 4.4+/-0.9 hours) and complete wound excision (29+/-6 hours vs 49+/-7 hours) compared with those requiring dialysis (P<.05 for both). CONCLUSION: Early adequate fluid resuscitation, early wound excision, and better infection control may reduce mortality in burned children with acute renal failure.     

Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia

BACKGROUND: Switch therapy is defined as the early transition from intravenous to oral antibiotics during treatment of infection. This study was designed to evaluate the clinical outcome and length of stay of hospitalized patients with community-acquired pneumonia treated with an early switch from intravenous to oral third-generation cephalosporins. METHODS: Patients with a new roentgenographic pulmonary infiltrate and at least two symptoms (cough, fever, or leukocytosis) were enrolled in this study and treated with intravenous ceftizoxime sodium (1 g every 12 hours) or ceftriaxone sodium (1 g every 24 hours). Patients were switched to oral cefixime (400 mg every 24 hours) as soon as they met the following criteria: (1) resolution of fever; (2) improvement of cough and respiratory distress; (3) improvement of leukocytosis; and (4) presence of normal gastrointestinal tract absorption. RESULTS: Of the 120 patients enrolled, 75 (62%) had clinical data evaluated. Long-term follow-up showed that 74 patients (99%) were cured; one patient required readmission for further intravenous therapy. Mean duration of hospital stay was 4 days. CONCLUSIONS: This investigation demonstrated that an early switch to oral cefixime may be reasonable in hospitalized patients with community-acquired pneumonia who have already shown a good clinical and laboratory response to therapy with intravenous third-generation cephalosporins. This approach is clinically effective and minimizes hospital stay.