Inhaled nitric oxide in congenital hypoplasia of the lungs due to diaphragmatic hernia or oligohydramnios

OBJECTIVE: We determined whether inhaled nitric oxide (NO) could improve systemic oxygenation in human neonates with hypoplastic lungs. METHODS: A multicenter nonrandomized investigation was performed to study the efficacy of short-term NO inhalation. Inhaled NO was administered at 80 ppm to nine neonates without evidence of structural cardiac disease by echocardiography. Lung hypoplasia was due to congenital diaphragmatic hernia (CDH) in eight patients and to oligohydramnios in one patient. A total of 15 trials of NO inhalation were performed in these nine patients. Eight trials in seven patients were performed before extracorporeal membrane oxygenation ((ECMO); one patient had two trials) and seven trials were performed in five patients after decannulation from ECMO (two patients had two trials each). RESULTS: NO inhalation before ECMO did not change postductal PaO2 (42 +/- 3 mmHg vs 42 +/- 4 mmHg), oxygen saturation (SpO2; 89% vs 88%) or oxygenation index (31 +/- 4 cm H2O/torr vs 31 +/- 4 cm H2O/torr) for the group. All patients required ECMO support, which lasted from 5 to 17 days (mean 9). After decannulation from ECMO, NO inhalation increased postductal PaO2 from a median of 56 mm Hg (range 41 to 94) to a median of 113 mm Hg (range 77 to 326), P < .05. It decreased the oxygenation index from a median of 23 cm H2O/torr (range 11 to 7) to a median of 11 cm H2O/torr (range 4 to 21), P < .05. It increased SpO2 from 91% to 96% (P < .05) and pH from 7.48 +/- .03 to 7.50 +/- .03. CONCLUSION: In our patients with hypoplastic lungs, inhaled NO was effective only after ECMO. This could be due to maturational changes such as activating the endogenous surfactant system. Inhaled NO may be effective in neonates with hypoplastic lungs who have recurrent episodes of pulmonary hypertension after ECMO, even if they were previously unresponsive.     

Transurethral balloon dilation of the external urinary sphincter: effectiveness in spinal cord-injured men with detrusor-external urethral sphincter dyssynergia

The authors investigated balloon dilation as a minimally invasive alternative to transurethral external sphincterotomy for the treatment of detrusor-external urethral sphincter dyssynergia (DESD). Seventeen spinal cord-injured men with voiding pressures greater than 60 cm H2O underwent balloon dilation of the external sphincter to 90 F at 4 atm of pressure for 10 minutes. The mean voiding pressures before and 12 months after dilation were 83 cm H2O +/- 35 and 37 cm H2O +/- 15, respectively (P = .008). There was a significant decrease in residual urine volume, from 163 mL +/- 162 to 68 mL +/- 59 (P = .05), whereas bladder capacity remained relatively unchanged at 253 mL +/- 181 and 230 mL +/- 97 (P = .30). Complications included one case of postoperative bleeding necessitating transfusion, two treatment failures, and one bulbous urethral stricture. Fourteen of the 17 patients (82%) now void without the aid of an indwelling catheter or alternative therapy. Balloon dilation has no detrimental effect on erectile function and may improve fertility.     

Clinical, physiological, and radiological study of a new purpose-designed artificial bowel sphincter

BACKGROUND: Studies of the use of artificial urinary sphincters for faecal incontinence have led to refinement and adaptation of such sphincters to the anatomy of the anal region. We aimed to test this new device. METHODS: Six women, median age 53 (range 32-58) years, who were unsuitable for sphincter repair, had an artificial bowel sphincter implanted as a one-stage procedure without colostomy cover. Clinical assessment, physiological testing, and endosonography were done before and after the operation. Plain radiography, three-dimensional endosonography, and magnetic-resonance imaging were done after the operation, to define its anatomical location. RESULTS: Median follow-up was 10 (range 5-13) months and the device was functional in five patients. In one patient, the device was removed after ulceration through the skin. Of the patients with intact devices, Wexner incontinence scores improved from a median of 19 (18-20) of 20 before the operation, to 3 (0-6) of 20 after the operation. Median anal pressure at rest significantly increased from 60 (range 30-80) cm H2O to 110 (100-120) cm H2O. Functional anal-canal length varied after the operation from 3.3 cm to 3.8 cm. There was no significant change in the maximum tolerated volume of the rectum (140 [80-230] vs 100 [75-250] mL), or rectal compliance (2.9 [2.8-6.0] cm H2O/mL vs 3.5 [2.3-7.3] cm H2O/mL). All the imaging techniques accurately located the implant relative to the anal canal and pelvic floor in each patient. INTERPRETATION: The new artificial bowel sphincter provided a good functional result in five of the six patients, the surgical procedure was straightforward, and the maximum resting anal pressure rose without affecting rectal function. The ease of visualisation of such implants in situ should aid simple management of complications, should they arise.     

Preoperative albendazole treatment for liver hydatid disease decreases the viability of the cyst

OBJECTIVE: Although in experimental models the efficacy of albendazole has been demonstrated, more clinical data are required. In this study, the effect of preoperative albendazole treatment was investigated in patients with liver hydatid cysts. DESIGN: This is a prospective non-randomized study. METHODS: In this study, the viability was assessed by the gross appearance of the cyst and intracystic pressure (ICP). The study consisted of 70 patients with 89 liver hydatid cysts in two groups. The patients in the first group (n = 29) received 10 mg/kg albendazole orally for 3 weeks before surgery. Thirty-five cysts were evaluated in this group. The second group (n = 41) with 54 liver hydatid cysts received no preoperative treatment. RESULTS: In the first group receiving preoperative albendazole, 20 cysts were viable and 15 non-viable. The median ICP was 21 (range 8-56) cm H2O in viable and 0 (range 0-8) cm H2O in non-viable cysts. In the second group, 43 cysts were viable and 11 non-viable. The median ICP was 35 (range 8-75) cm H2O in viable and 0 (range 0-2) cm H2O in non-viable cysts. The ICP values of viable cysts in the first group receiving preoperative albendazole were significantly lower (P < 0.05). The number of non-viable cysts was also significantly higher in the group treated with preoperative albendazole (P < 0.05). CONCLUSION: Albendazole in this study has proved to be effective in decreasing the viability of liver hydatid cysts when given for 3 weeks preoperatively.     

The effect of positive endexpiratory pressure, peak inspiratory pressure, and inspiratory time on functional residual capacity in mechanically ventilated preterm infants

In mechanical ventilation of preterm infants, positive endexpiratory pressure (PEEP) is widely used to prevent alveolar collapse, maintain functional residual capacity (FRC) and improve oxygenation. Prolongation of inspiratory time (ti) and increase of peak inspiratory pressure (PIP) are also used for this purpose. We investigated the effect of variations of PEEP, PIP and ti on FRC in ten infants with hyaline membrane disease and onset of bronchopulmonary dysplasia (BPD, n = 7), pulmonary hypertension (n = 1), pulmonary hypoplasia (n = 1) or severe BPD (n = 1) (gestational age 24-39 weeks, median 26 weeks; birth weight 590-2960 g, 785 g; chronological age 7 84 days, 19 days; weight 689-4650 g, 1185 g). FRC, measured using the sulphur hexafluoride washout technique, was between 6.2 and 48.3 ml/kg (median 21.5 ml/kg). PEEP was changed stepwise 2-5 times in each patient (median 3) and mean airway pressure (MAP) was modified independently of PEEP by changing PIP 0 2 times (median 1) and ti 0(2 times (median 2). Changes of FRC correlated well with modifications of PEEP in each patient (r = 0.90, range 0.71 0.99). The slope factors of linear correlations had a median value of 2.94 ml/cm H20 per kg, which was significantly different from zero (P < 0.01) and significantly higher than the slope factors of linear correlations between FRC and MAP after modifications of PIP or ti (P < 0.01). The latter two were statistically not different from zero. The quotients deltaFRC/deltaMAP were significantly higher after adjustments of PEEP than after adjustments of PIP or ti (P < 0.01). The time lag between the change of PEEP and the stabilization of FRC on a new level ranged from 2 to 14 min (median 5). CONCLUSION: FRC is mainly determined by PEEP but not by PIP or ti. Stabilization of FRC after a change of PEEP can last up to 14 min. Its duration is unpredictable and has to be waited for when testing pulmonary function in ventilated preterm infants.     

Auto-positive end-expiratory pressure during one-lung ventilation using a double-lumen endobronchial tube

The present study was undertaken to investigate the possible relationships between the magnitude of autopositive end-expiratory pressure (auto-PEEP) and measured PaO2 during one-lung ventilation (OLV). Forty-one adults received OLV anesthesia using a tidal volume of 8 mL/kg and a respiratory rate of 12 breaths/min. Auto-PEEP was quantified using an end-expiratory port occlusion method. During two-lung ventilation (2LV), auto-PEEP was observed in 18 of 41 patients and ranged from 0.5 to 2.5 cm H2O. During OLV, auto-PEEP was observed in 34 of 41 patients and ranged from 0.5 to 10 cm H2O. The mean (+/- SD) value of auto-PEEP was significantly higher during OLV than during 2LV (3.2 +/- 3.3 cm H2O versus 0.5 +/- 0.7 cm H2O, P < 0.0001). Auto-PEEP during OLV correlated inversely with preoperative forced expiratory volume in 1 s/forced vital capacity (y = 12.5 - 0.13x, r = -.05, P < 0.005). During OLV, there was no significant correlation between auto-PEEP and measured PaO2. These findings confirm that many patients do not exhale completely to functional residual capacity during OLV.     

Peripheral blood progenitor cell mobilization using stem cell factor in combination with filgrastim in breast cancer patients

The safety and optimal dose and schedule of stem cell factor (SCF) administered in combination with filgrastim for the mobilization of peripheral blood progenitor cells (PBPCs) was determined in 215 patients with high-risk breast cancer. Patients received either filgrastim alone (10 microg/kg/d for 7 days) or the combination of 10 microg/kg/d filgrastim and 5 to 30 microg/kg/d SCF for either 7, 10, or 13 days. SCF patients were premedicated with antiallergy prophylaxis. Leukapheresis was performed on the final 3 days of cytokine therapy and, after high-dose chemotherapy and infusion of PBPCs, patients received 10 microg/kg/d filgrastim until absolute neutrophil count recovery. The median number of CD34+ cells collected was greater for patients receiving the combination of filgrastim and SCF, at doses greater than 10 microg/kg/d, than for those receiving filgrastim alone (7.7 v 3.2 x 10(6)/kg, P < .05). There were significantly (P < .05) more CD34+ cells harvested for the 20 microg/kg/d SCF (median, 7.9 x 10(6)/kg) and 25 microg/kg/d SCF (median, 13.6 x 10(6)/kg) 7-day combination groups than for the filgrastim alone patients (median, 3.2 x 10(6)/kg). The duration of administration of SCF and filgrastim (7, 10, or 13 days) did not significantly affect CD34+ cell yield. Treatment groups mobilized with filgrastim alone or with the cytokine combination had similar hematopoietic engraftment and overall survival after PBPC infusion. In conclusion, the results of this study indicate that SCF therapy enhances CD34+ cell yield and is associated with manageable levels of toxicity when combined with filgrastim for PBPC mobilization. The combination of 20 microg/kg/d SCF and 10 microg/kg/d filgrastim with daily apheresis beginning on day 5 was selected as the optimal dose and schedule for the mobilization of PBPCs.     

Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever. PATIENTS AND METHODS: One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period). RESULTS: Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05). CONCLUSION: These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.     

High frequency oscillation for preterm infants with severe respiratory failure

High frequency oscillation (HFO) as rescue treatment for preterm infants with severe respiratory failure has been assessed and prognostic factors identified. Thirty six infants with a median gestational age of 27 weeks were studied. Immediately before transfer to HFO, the infants were receiving an inspired oxygen concentration of > or = 85% and/or a mean airway pressure of > or = 12 cm H2O and had a median alveolar-arterial oxygen gradient (A-aDO2) of 73.28 kPa (range 49.34-89.91). Seventeen infants subsequently died. Comparison of those 17 with the remaining 19 infants demonstrated that respiratory distress syndrome and persistent fetal circulation were associated with a significantly better outcome than pulmonary airleak. The A-aDO2 after two and six hours on HFO was significantly higher in those infants who survived compared with those who died. We conclude that a diagnosis of pulmonary airleak and failure to show early improvement in respiratory status indicate a poor prognosis when HFO is used as rescue treatment.     

Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary vascular mechanics and cardiac output in a pediatric swine model

OBJECTIVES: In a pediatric swine model, the effects of increasing tidal volumes and the subsequent development of pulmonary overdistention on cardiopulmonary interactions were studied. The objective was to test the hypothesis that increasing tidal volumes adversely affect pulmonary vascular mechanics and cardiac output. An additional goal was to determine whether the effects of pulmonary overdistention are dependent on delivered tidal volume and/or positive end-expiratory pressure (PEEP, end-expiratory lung volume). DESIGN: Prospective, randomized, controlled laboratory trial. SETTING: University research laboratory. SUBJECTS: Eleven 4- to 6-wk-old swine, weighing 8 to 12 kg. INTERVENTIONS: Piglets with normal lungs were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. MEASUREMENTS AND MAIN RESULTS: The swine were ventilated and data were collected with delivered tidal volumes of 10, 15, 20, and 25 mL/kg and PEEP settings of 5 and 10 cm H2O in a random order. Pulmonary overdistention was defined as a decrease in dynamic compliance of > or =20% when compared with a compliance measured at a baseline tidal volume of 10 mL/kg. At this baseline tidal volume, airway pressure-volume curves did not demonstrate pulmonary overdistention. Tidal volumes and airway pressures were measured by a pneumotachometer and the Pediatric Pulmonary Function Workstation. Inspiratory time (0.75 sec), FIO2 (0.3), and minute ventilation were held constant. We evaluated the pulmonary vascular and cardiac effects of the various tidal volume and PEEP settings by measuring pulmonary vascular resistance, pulmonary characteristic impedance, and cardiac output. When compared with a tidal volume of 10 mL/kg, a tidal volume of 20 mL/kg resulted in a significant decrease in dynamic compliance from 10.5 +/- 0.9 to 8.4 +/- 0.6 mL/cm H2O (p = .02) at a constant PEEP of 5 cm H2O. The decrease in dynamic compliance of 20% indicated the presence of pulmonary overdistention by definition. As the tidal volume was increased from 10 to 20 mL/kg, pulmonary vascular resistance (1351 +/- 94 vs. 2266 +/- 233 dyne x sec/cm5; p = .004) and characteristic impedance (167 +/- 12 vs. 219 +/- 22 dyne x sec/cm5; p = .02) significantly increased, while cardiac output significantly decreased (951 +/- 61 vs. 708 +/- 48 mL/min; p = .001). Each of these effects of pulmonary overdistention were further magnified when the tidal volume was increased to 25 mL/kg. The tidal volume-induced alterations in pulmonary vascular mechanics, characteristic impedance, and cardiac output occurred to a greater degree when the PEEP was increased to 10 cm H2O. Pulmonary vascular resistance and characteristic impedance were significantly increased and cardiac output significantly decreased for all tidal volumes studied at a PEEP of 10 cm H2O as compared with 5 cm H2O. CONCLUSIONS: Increasing tidal volumes, increasing PEEP levels, and the development of pulmonary overdistention had detrimental effects on the cardiovascular system by increasing pulmonary vascular resistance and characteristic impedance while significantly decreasing cardiac output. Delivered tidal volumes of >15 mL/kg should be utilized cautiously. Careful monitoring of respiratory mechanics and cardiac function, especially in neonatal and pediatric patients, is warranted.     

N-Glycosylation affects endoplasmic reticulum degradation of a mutated derivative of carboxypeptidase yscY in yeast

BACKGROUND: Reports of short- and medium-term evolution of Lung Function Tests (LFT) in infants with bronchopulmonary dysplasia (BPD) are still scarce. POPULATION AND METHODS: The results of the first (before 3 months of corrected age) and the second (between 3 and 9 months of corrected age) LFT in 22 premature infants with BPD (gestational age 31 +/- 2.5 weeks; birth weight: 1570 +/- 440 g; duration of mechanical ventilation: 46 +/- 24 days, total duration of oxygen therapy: 88 +/- 47 days) were compared to those obtained in 27 normal infants for the first LEF and 10 normal infants for the second LFT, similar to the patients for birth weight and corporeal index (CI). RESULTS: In the first LFT, major abnormalities were an increased thoracic gaz volume (TGV) (16.5 +/- 42 vs 122 +/- 24 mL; P < 0.001) and TGV CI ratio (1.25 +/- 0.31 vs 0.89 +/- 0.17 ml/kg/m2; P < 0.0001) a decreased pulmonary compliance (2.49 +/- 1.46 vs 11.60 +/- 4.50 mL/cmH2O; P < 0.0001) and specific pulmonary compliance (0.015 +/- 0.10 vs 0.100 +/- 0.042 mL/cmH2O/mL de TGV; P < 0.0001), an increased total pulmonary resistance (20.4 +/- 12.1 vs 10.5 +/- 5.3 cmH2O/L/s; P < 0.001). In the second LFT, an increased TGV (235 +/- 62 vs 166 +/- 28 mL; P < 0.01) and TGV CI ratio (1.64 +/- 0.65 vs 0.98 +/- 0.11 ml/kg/m2; P < 0.05), a decreased pulmonary compliance (2.68 +/- 2.0 vs 15.2 +/- 5.7 mL/cmH2O; P < 0.0001) and specific pulmonary compliance (0.013 +/- 0.010 vs 0.106 +/- 0.050 mL/cmH2O/mL de TGV; P < 0.0001), an increased total pulmonary resistance (17.1 +/- 9.6 vs 8.6 +/- 4.9 cmH2O/L/s; P < 0.05) were noted when compared with the control group results. Major abnormalities of the blood gases were hypoxemia (63 +/- 10 vs 85 +/- 20 mmHg; P < 0.05), hypercapnia (38.5 vs 31 +/- 4 mmHg; P < 0.0001) during the first LFT. Hypoxemia (77 +/- 14 vs 90 +/- 14 mmHg and hypercapnia (37 +/- 4 vs 29 +/- 5 mmHg) continued in the second LFT. Thoracic distention and total pulmonary resistances in infants with BPD did not improve but their pulmonary compliance (P < 0.0001) and PaO2 (P < 0.01) between the first and second LFT did it. Infants who had been ventilated for a hyaline membrane disease (HMD) were more hypoxic on the second LFT (P < 0.05) than those who had been ventilated for other causes. Statistically significant relationships were found between thoracic distention and duration of positive inspiratory pressure (P < 0.05; r = 0.43), duration of positive expiratory pressure (P < 0.05, r = 0.45) total oxygen therapy duration; between total pulmonary resistance and duration of mechanical ventilation with high frequency (P < 0.05; r = 0.52); between hypoxemia and duration of oxygen therapy with FiO2 > or = 60% (P < 0.05; r = 0.54). CONCLUSIONS: This study shows prolonged clinical and functional abnormalities of the respiratory functions requiring longer follow-up.     

A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation

The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) transplantation. Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation. Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant. Patients < or =70 kg received 300 microg/day and >70 kg 480 microg/day. All patients were reinfused with PBPCs with a CD34+ cell count >2.0 x 10(6)/kg. Baseline characteristics of age, sex and CD34+ cell count were similar between the two arms, the median CD34+ cell count being 5.87 x 10(6)/kg in the day +1 group and 7.70 x 10(6)/kg in the day +7 group (P=0.7). The median time to reach a neutrophil count of >0.5 x 10(9)/l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P=0.68). Similarly, there was no difference in median days to platelet recovery >20000 x 10(9)/l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P=0.83). There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P=0.7), intravenous antibiotic use (7 vs 8 days; P=0.54) or median number of red blood cell transfusions (4 vs 7 units; P=0.82) between the two arms. Median length of hospital stay was 11 days post-PBPC reinfusion in both groups. The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P < 0.0001). There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation. There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay. The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug costs. For patients with an adequately mobilized PBPC graft, the initiation of G-CSF can be delayed until day +7 post-PBPC reinfusion.     

Adult respiratory distress syndrome

In this article the authors present a case of successful treatment of a 54-year old male patient with non-insulin dependent diabetes mellitus (NIDDM) and triple-vessel coronary artery disease who underwent surgical myocardial revascularization and was reoperated on the same day because of excessive bleeding. The patient was given cca 5000 mL of whole blood and cca 3000 mL of blood derivatives. The first postoperative chest X-ray showed radiological signs of ARDS. The therapy was based upon authors' experience and was consisted of controlled mechanical ventilation (respiratory volume 12-15 mL/kg, 10-14 cycles/min, I/E ratio 1:2, FIO2 0.6, PEEP 2-5 cm H2O), daily bronchoscopies with bronchoaspiration, aggressive diuresis, negative fluid balance, specific antibiotic therapy, and last but not least, of prostaglandin E1 (PGE1) 0.5-20 micrograms/kg/min combined with dopamine inotropic support (2-5 micrograms/kg/h). Simple but careful clinical observation still remains a milestone for all therapeutic measures taken in ARDS patients.     

Reduced collagen accumulation after major surgery

The preoperative and postoperative wound-healing capacity of 23 patients undergoing elective major abdominal, thoracic or urological surgery was tested objectively by the subcutaneous accumulation of hydroxyproline and proline in an expanded polytetrafluoroethylene (ePTFE) tube. Before scheduled surgery two ePTFE tubes were implanted for removal after 5 and 10 days. This was repeated for each patient immediately after surgery. After 10 days a higher amount of hydroxyproline was measured before than after operation (median 2.91 (range 0.37-14.45) versus 1.45 (range 0.26-6.94) micrograms/cm, P = 0.01)). This decline was significantly higher in the six patients who had a postoperative infection (median 3.02 (range -0.06 to 6.14) versus 0.36 (range -1.56 to 12.60) micrograms/cm, P = 0.02). This study shows that major surgery is associated with impairment of subcutaneous collagen accumulation in a test wound, suggesting diminished systemic wound-healing capacity in such patients.     

Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells

The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m2 day 3, BCNU 60 mg/m2 day 3, etoposide 75 mg/m2 days 4-7, Ara-C 100 mg/m2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34+ cells: 32.5 x 10(4)/kg vs 31.3 x 10(4)/kg CFU-GM, and 7.6 x 10(6)/kg vs 5.6 x 10(6)/kg CD34+ cells, for G-CSF and GM-CSF, respectively (U test, P= 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4, BCNU 150 mg/m2 days 1-4, etoposide 400 mg/m2 days 1-4. All patients transplanted with more than 5 x 10(6) CD34+ cells/kg had a rapid platelet recovery (20 x 10(9)/l) between 6 and 11 days and neutrophil recovery (0.5 x 10(9)/1) between 9 and 16 days, while patients transplanted with less than 5 x 10(6)/kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.     

Laparoscopy improves outcomes for pediatric splenectomy

BACKGROUND: Pediatric laparoscopic splenectomy is a relatively new surgical procedure with a limited number of reports comparing its outcomes to that of the open procedure. The authors have minimized the invasiveness of our procedure by using only three ports and have described the technique as well as compared it with the open method. METHODS: A retrospective review of seven laparoscopic splenectomies (LS) using a three port technique were compared with seven open splenectomies (OS) performed for similar indications at a single children's hospital. RESULTS: The average age in the LS group was 8.7 years compared with 8.9 years for OS, (P value not significant), and the average weights were also similar. The indications for splenectomy were hereditary spherocytosis, idiopathic thrombocytopenic purpura, sickle cell anemia, and splenic cyst. All splenectomies were performed safely with an average estimated blood loss of 41 mL for LS and 34 mL for OS (P value not significant). Operative time averaged 147 minutes for LS and 86 minutes for OS (P < .05). LS patients recovered more rapidly and were discharged home on a median of postoperative day (POD) 2 versus POD 4 for OS (P < .05). LS patients received significantly less total amount of intravenous pain medication with an average of 0.18 mg/kg of morphine sulfate versus 0.8 mg/kg for OS (P< .05). Total hospital charges were higher for LS with an average of $10,899 versus $8,275 for OS (P < .05). CONCLUSIONS: Laparoscopic splenectomy currently is a safe procedure, offering better cosmesis, much less pain, and a shorter hospital stay compared with the traditional open procedure. The more sophisticated equipment and time needed to carry out the procedure led to a modestly increased hospital cost.     

High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral blood progenitor cell transplantation

Optimal numbers of CD34(+) cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34(+) cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 x 10(9)/L) and unsustained platelet recovery (>50 x 10(9)/L) were analyzed in three groups defined by the number of CD34(+) cells reinfused: a low group with less than or equal to 2.5 x 10(6) CD34(+) cells/kg, a high group with greater than 15 x 10(6) CD34(+) cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P < .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34(+) cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 x 10(6) CD34(+) cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.     

The need for inotropic support in a subgroup of infants with severe life-threatening respiratory syncytial viral infection

BACKGROUND: We experienced an unusual complication of life-threatening respiratory syncytial viral disease cardiovascular compromise. Life-threatening respiratory syncytial virus (RSV) infection has predominancy involved with ventilatory support for respiratory distress and/or failure. We performed a retrospective chart review of 20 consecutive infants admitted to the pediatric intensive care unit (PICU) for impending respiratory failure. METHODS: Seventeen required ventilatory support. As part of the infants' initial assessment, blood pressure, distal perfusion [capillary refill time (CRT) > or = 3 sec], decreased peripheral pulses, and peripheral mottling were used to determine cardiovascular compromise. These infants received volume resuscitation either at the referring facility or the PICU until euvolemia was obtained, as determined by central venous pressure (CVP) monitoring (between 3 to 7 cm H20). Nine of the 20 infants did not respond to volume resuscitation alone and required vasopressor support in the form of: Dopamine (7 patients, 5-10 micrograms/kg/min), Dobutamine (2 patients, 5-7 micrograms/kg/min), and one who expired required both Epinephrine (600 ng/kg/min) and Dopamine (10 micrograms/kg/min). The mean ages of these 9 patients were 6.2 +/- 3.4 weeks (range 3-12 weeks), the mean duration of ventilation was 7.2 +/- 4.1 days (range 4-12 days). The mean duration of pharmacologic support was 69.7 +/- 47 hours (range 14-168 hours). The mean ages of RSV+ infants not requiring inotropic support was 19.4 +/- 27.4 weeks (range 1-90 weeks), and mean duration of ventilation was 5.5 +/- 5.9 days (range 2-20 days). RESULTS: The inotrope treated patients were weaned from pharmacologic support prior to extubation, without any hemodynamic deficits. Our experience with this rather high incidence of hemodynamic complications during this RSV epidemic was unexpected. CONCLUSION: These results substantiate the fact that younger patients with RSV disease are at both greater risk for pulmonary complications and cardiovascular deterioration and may thus benefit from pharmacologic support.     

Differential regional hemodynamic effects of corticotropin in conscious sheep

The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 micrograms/kg per day) were examined in conscious sheep (n = 8). Mean arterial pressure increased from 81 +/- 2 to 93 +/- 3 mm Hg (P < .001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13 +/- 0.19 to 6.06 +/- 0.33 L/min (P < .01) because of an increase in stroke volume from 65 +/- 4 to 79 +/- 8 mL per beat (P < .01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8 +/- 0.2 to a minimum of 4.9 +/- 0.3 (mL/min)/mm Hg (P < .05), and renal conductance increased from 3.5 +/- 0.3 to 4.6 +/- 0.3 (mL/min)/mm Hg (P < .001). There was a small increase in iliac conductance (P < .05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278 +/- 18 to 403 +/- 23 mL/min (P < .001); mesenteric blood flow was unchanged; there was a small increase in iliac blood flow (P < .01); and coronary blood flow increased (P < .05), paralleling the change in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)