Surfactant treatment in the neonate with severe respiratory distress syndrome

Eighteen preterm infants severely ill with respiratory distress syndrome who required assisted ventilaton were given modified natural surfactant (Survanta) endotracheally. They had a mean +/- SEM gestational age of 31.2 +/- 0.4 weeks (range 28-34) and a mean +/- SEM birthweight of 1562 +/- 71 g (range 1160-2010). Average time of initial surfactant administration was 15 +/- 1.7 hour (range 5-24). No significant side effects were found during surfactant instillation. Post surfactant, the air entry was improved, oxygenation and arterial/alveolar gradients increased, and the levels of inspired oxygen could be reduced. Some of the radiological abnormalities were resolved. In 13 infants, patent ductus arteriosus became clinically evident, seven of whom received Indomethacin. There were 4 cases of pulmonary air leak, 5 cases of pulmonary hemorrhage and 8 cases of bronchopulmonary dysplasia. Four infants expired, two were due to severe asphyxia/shock and two died of unrelated causes. Among the 14 survivors who came for follow-up, two cases of retinopathy of prematurity had gradually regressed, one had cerebral palsy and delayed development. Surfactant rescue therapy is a supplemental beneficial treatment for severe respiratory distress syndrome while newborn intensive care concept is necessary for efficient diagnosis and treatment of RDS.     

Surfactant inhibits cationic liposome-mediated gene transfer

We have demonstrated that tracheal insufflation of recombinant plasmid DNA results in transfection of rat lungs to the same extent as insufflation of plasmid-cationic liposome complex. To understand this observation better, we investigated the in vitro gene transfer of plasmid DNA in the presence and absence of cationic liposome and the effect of surfactant on gene transfer. The chloramphenicol acetyltransferase (CAT) expression plasmids pBL-CAT and pSV-CAT were studied in three cell types: rat fetal lung fibroblast (RFL-6), calf pulmonary artery endothelial cell (CPAE), and rat type II alveolar epithelial cell (type II AE). Three cationic liposomes were tested: DDAB (dimethyl-dioctadecyl ammonium bromide)-liposome, DOTAP (dioleoyltrimethyl ammonium propane)-liposome, and lipofectin. The results revealed that (i) plasmid DNA alone caused a dose-dependent, low-level transfection, most efficiently in RFL-6 followed by CPAE and type II AE, (ii) DDAB-liposome markedly enhanced gene transfer, most efficiently in RFL-6 followed by CPAE and type II AE, (iii) Survanta, a naturally derived surfactant preparation, and Exosurf, a synthetic surfactant, while having no effect on in vitro gene transfer by plasmid DNA alone, markedly inhibited cationic liposome-mediated gene transfer, (iv) dipalmitoyl phosphatidylcholine was responsible for the inhibitory effect of Exosurf, and (v) inhibition of cationic liposome-mediated gene transfer by Exosurf was not due to inhibition of plasmid DNA-cationic liposome complex uptake or interference with the promoter and enhancer. The observed inhibition of cationic liposome-mediated gene transfer by surfactant may in part explain our previous observation that tracheal insufflation of plasmid DNA and plasmid-cationic liposome complex results in equal lung gene transfer.     

Effect of surfactant replacement therapy on the outcome of premature infants with respiratory distress syndrome

Lung surfactant replacement has been tested clinically in recent years. In this study the outcome of 31 premature infants with moderate to severe neonatal respiratory distress syndrome (RDS) treated with surfactant was compared to that of 74 prematures with RDS treated conventionally by positive pressure ventilation and supportive care. The groups were well matched for gestational age, birthweight, sex, and Apgar scores at 1 and 5 min. Surfactant treatment resulted in a significant decrease in mortality--from 36.6% in the untreated group to 12.9% in the surfactant-treated group (P < 0.04). This improvement in survival was seen also in prematures with a birthweight < 1,000 g; in the untreated group mortality was 57.6% compared to 23.5% in the treated group (P < 0.05). The incidence of pneumothorax was lower in the treated group--42% vs. 13% (P < 0.01). Surfactant treatment resulted in a trend of more survivors without bronchopulmonary dysplasia or intraventricular hemorrhage, even though surfactant therapy did not change the incidence of either.     

The effect of synthetic surfactant Exosurf on gene transfer in mouse lung in vivo

Gene transfer in the lung holds promise for the treatment of diseases such as pulmonary fibrosis, cystic fibrosis and asthma. Pulmonary surfactant has been reported to enhance expression from endobronchial, adenovirus-mediated gene transfer in experimental animals. This study examines the effect of exogenous synthetic surfactant (Exosurf) on gene expression from naked plasmid DNA administered endobronchially to adult mice. Transfection efficiency was evaluated by quantifying the expression of chloramphenicol acetyltransferase (CAT) and luciferase (Luc) genes in the lung. Endobronchial administration of either CAT or Luc expression plasmid DNA resulted in detectable concentrations of each reporter protein. CAT expression from plasmid DNA was monitored after endobronchial administration with the maximal expression observed at 3-5 days after administration and decreasing for 5 days thereafter. When DNA was delivered in a 50% suspension of Exosurf, the expression of either CAT or Luc was significantly reduced by 89.6 +/- 1.4% and 82.7 +/- 10.5%, respectively. The decrease in Luc expression was closely correlated (r = 0.99, P < 0.001) to log concentration of surfactant in the plasmid buffer solution (IC50 = 8.6%). CAT expression was not altered when surfactant was administered either 2 h before or after plasmid DNA instillation. Examination of the components of Exosurf revealed that two compounds, DPPC and tyloxapol, showed inhibitory effects on CAT expression. However, the inhibition caused by Exosurf appeared greater than that of either component. Our results suggest that the lung surfactant is a barrier to transfection of the endobronchial airway and may be partly responsible for the low expression of exogenous DNA in vivo in the bronchial tree.     

Cell yield. ThinPrep vs. cytocentrifuge

The results of treatment of severe respiratory distress syndrome in premature infants with gestational age < or = 32 weeks are reported. During the two-year period 1991-92, the department participated in both the Osiris study (Exosurf) and the Curosurf 4 study (Curosurf). Five of the 23 infants treated with Exosurf died and 16 survived without major sequelae. 14 of the 25 infants treated with Curosurf died and six survived without major sequelae. Four of the infants treated with Curosurf developed severe retinopathy of prematurity. During the study period this complication occurred in one additional patient who was not eligible for inclusion in the study. The results show the need to study differences in the physiological effects of surfactants more closely, in order both to improve the basis for selection of surfactant for individual patients, and to define the indications for treatment. The results raise the question of whether such studies should continue to include control patients.     

Comparison of rSP-C surfactant with natural and synthetic surfactants after late treatment in a rat model of the acute respiratory distress syndrome

1. In a previous paper we showed that an SP-C containing surfactant preparation has similar activity as bovine-derived surfactants in a rat lung lavage model of the adult respiratory distress syndrome. In this study surfactant was given ten minutes after the last lavage (early treatment). In the present investigation we were interested how different surfactant preparations behave when they are administered 1 h after the last lavage (late treatment). 2. Four protein containing surfactants (rSP-C surfactant, bLES, Infasurf and Survanta) were compared with three protein-free surfactants (ALEC, Exosurf and the phospholipid (PL) mixture of the rSP-C surfactant termed PL surfactant) with respect to their ability to improve gas exchange in this more stringent model when surfactant is given one hour after the last lavage. For better comparison of the surfactants the doses were related to phospholipids. The surfactants were given at doses of 25, 50 and 100 mg kg(-1) body weight. The surfactants were compared to an untreated control group that was only ventilated for the whole experimental period. 3. Tracheotomized rats (8-12 per dose and surfactant) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min(-1), inspiration expiration ratio of 1:2, peak inspiratory pressure of 28 cmH2O at positive endexpiratory pressure (PEEP) of 8 cmH2O. Animals were ventilated for one hour after the last lavage and thereafter the surfactants were intratracheally instilled. During the whole experimental period the ventilation was not changed. 4. Partial arterial oxygen pressures (PaO2, mmHg) at 30 min and 120 min after treatment were used for statistical comparison. All protein containing surfactants caused a dose-dependent increase of the reduced PaO2 values at 30 min after treatment. The protein-free surfactants showed only weak dose-dependent increase in PaO2 values at this time. This difference between the protein-containing and the protein-free surfactants was even more pronounced when comparing the PaO2 values at 120 min after treatment. Only rSP-C surfactant, bLES and Infasurf showed a dose-dependent increase in PaO2 at this time. 5. With this animal model of late treatment it is possible even to differentiate between bovine derived surfactants. The differences between protein-containing and protein-free surfactants become even more pronounced. From the comparison of rSP-C surfactant with bovine-derived surfactants and the PL surfactant without rSP-C, it can be concluded that addition of rSP-C is sufficient to achieve the same activity as that of natural surfactants.     

Treatment of neonatal respiratory distress syndrome with Alveofact--results of a prospective observational study

AIM: After registration of the bovine Surfactant Alveofact (Fa. Thomae) for treatment of neonatal respiratory distress syndrome (RDS) an observational study was performed in 47 german neonatal departments to register indication, effectivity, mode of administration and unexpected side effects. METHODS: 680 ventilated preterm infants (gestational weeks 29.5 +/- 2.9; birth weight 1359 +/- 507 g) were enrolled in an uncontrolled clinical study with study-protocol, prospectively defined outcomes and covariates, manual of operation, central control system, biometrical control. RESULTS: Surfactant was applicated at a postnatal age of 2 hours 56 minutes (median). Only 2.9% of newborn infants got the first surfactant doses < 6 min postnatally, 19.4% between 6 ... 60 min and 77.7% > 60 min postnatally. Following 1338 instillations in 76% an improved lung function, in 21% no change and in 3% a worsening was observed. During the study the total dose of surfactant increased. Safety considerations determined by the rate of pulmonary and extrapulmonary complications were similar to data of the literature: pneumothorax 12%, pulmonary interstitial emphysema 11.6%, secondary pneumonia 20.4%, broncho-pulmonary dysplasia 27%, pulmonary hemorrhage 2.1%, peri/intraventricular hemorrhage (degree III/IV) 27.9%, ductus arteriosus persistens 24.4%, sepsis/meningitis 12.4%. During the study the mortality reduces from 31% (first period) to 18% (third period) the mean was 20%. In 44 infants (6.5%) a disturbed ventilation (airway obstruction, overdystension of pulmonary areas, atelectasis) after surfactant administration was observed. CONCLUSION: In RDS the surfactant Alveofact is preferably used therapeutically (rescue mode), it is effective but not free of risk. Its administration needs for a clear indication. New unknown side effects of Alveofact were not observed.     

Viral carcinogenesis of brain (author''s transl)

To test the hypothesis that intarpartum acidosis has a role in the etiology of hyaline membrane disease (HMD), blood was collected from the umbilical artery (UA) at birth from 110 premature infants and analyzed for hydrogen ion concentration ([H+]), PCO2, standard bicarbonate, and lactic acid. The infants were followed until a definite diagnosis was made of HMD (33 infants), type II respiratory distress syndrome (16 infants) or the absence of respiratory distress (61 infants). In general, infants with HMD were more premature and had lower Apgar scores than nondistressed infants; however, there were no significant differences between the two groups in any acid-base measurement. Only in those patients of 32 to 37 weeks' gestational age was it possible to detect a significant increase in UA [H+] in infants with HMD compared to those without respiratory distress. There was evidence that the reduced Apgar score of infants with HMD may be due to immaturity and abnormal pulmonary function secondary to lung disease. It is concluded that acidosis at birth is not a factor in the development of HMD except possibly in more mature infants.     

Surfactant treatment may accelerate epithelial cell regeneration in hyaline membrane disease of the newborn

Previous studies of histologic changes in the lungs of infants with hyaline membrane (HMD) disease of the newborn treated with surfactant have focused on the occurrence of hemorrhage and bronchopulmonary dysplasia (BPD). Observations in autopsied infants with HMD suggested a possible acceleration of epithelial cell regeneration in those receiving surfactant. We studied lungs of the 11 autopsied infants with HMD treated with surfactant, who survived less than 1 week, and compared them to 22 infants with HMD not given surfactant. Epithelial cell regeneration, BPD, and airway and interstitial hemorrhage were graded on a 0-to-3 scale. Treated infants showed significantly more epithelial cell regeneration (p<0.05) and airway hemorrhage (p<0.05). Also, treated infants showed recognizable epithelial regeneration 1 day earlier than the nontreated group. The study supports the observation that regeneration of the necrotic respiratory epithelium of HMD is accelerated in infants treated with surfactant.     

Plasma arginine vasopressin and motor activity in major depression

The aim of this study was to test whether the effect of surfactant treatment on lung function in a surfactant-deficient animal model can be influenced by the rate at which surfactant is administered. Surfactant deficiency was induced in 18 New Zealand white rabbits (weighing approx. 1 kg each) by lung lavage with normal saline. The arterial/alveolar oxygen ratio (a/A ratio), functional residual capacity (FRC), dynamic compliance of the respiratory system (Crs), tidal volume (V(T)), alveolar portion of the tidal volume (V(A)) and arterial P(CO2) (P(a,CO2)) were measured before and after lavage and 15, 30, 60, 90, and 120 min after administration of a single dose of surfactant (Survanta, 100 mg/kg). Two surfactant administration protocols were compared over a 2-h interval: an infusion lasting 4 min and an infusion over 2 min. Both administrations were given during continuous mechanical ventilation. The six lung function and gas exchange parameters improved significantly following surfactant administration over 2 min compared with a control group. However, only the a/A ratio and V(A) improved following the 4-min protocol. Comparison of the two intervention protocols yielded significantly differences in V(A) and P(a,CO2), favoring the shorter administration. These results support the hypothesis that fast (2 min) administration of surfactant will improve its distribution to formerly collapsed alveoli and results in better lung function, improved ventilation, and (to a lesser extent) better oxygenation than prolonged infusions (4 min).     

Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ

Treatments available to improve compliance in surfactant-deficient states include exogenous surfactant (ES) and either partial (PLV) or total liquid ventilation (TLV) with perfluorochemical (PFC). Because of the additional air-lung and air-PFC interfaces introduced during PLV compared with TLV, we hypothesized that compliance would be worse during PLV than during TLV. Because surfactant is able to reduce interfacial tension between air and lung as well as between PFC and lung, we further hypothesized that compliance would improve with surfactant treatment before PLV. In excised preterm lamb lungs, we used Survanta for surfactant replacement and perflubron as the PFC. Compliance during PLV was intermediate between TLV and gas inflation, both with and without surfactant. Surfactant improved compliance during PLV, compared with PLV alone. Because of the force-balance equation governing the behavior of immiscible droplets on liquid surfaces, we predict that PFC droplets spread during PLV to cover the alveolar surface in surfactant-deficient lungs during most of lung inflation and deflation but that the PFC would retract into droplets in surfactant-sufficient lungs, except at end inspiration.     

Urinary tract infection in adult women: morbidity without mortality

The effectiveness of aminophylline in the treatment of apnea of prematurity was evaluated in 13 premature infants (mean birthweight, 1.13 kg; mean gestational age, 29 weeks). Apnea was recorded by direct observation in combination with impedance monitoring. Rectal suppositories of aminophylline (5 mg) were given at six-hour intervals. The average dose was 4.1 mg/kg. No toxicity or complications were noted. The parents became free of apneic episodes during therapy. The response for each eight-hour interval of treatment over 72 hours when compared to pretreatment was significant (P less than .01; paired t-test), after the first eight hours. Only one patient required mechanical ventilation for apnea. Treatment was continued for 2 to 14 days (mean, 5 days). A recurrence of apnea was noted in nine patients after discontinuing aminophylline. All patients except one survived. No change in Po2, Pco2, pH, mean heart and respiratory rates, and blood pressure was noted. A direct effect on the respiratory center is postulated.     

Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants

AIMS: To compare the effects of a single dose of frusemide administered either intravenously or by nebulisation on pulmonary mechanics in premature infants with evolving chronic lung disease. METHODS: The effect of frusemide on pulmonary mechanics was studied at a median postnatal age of 23 (range 14-52) days in 19 premature infants at 24 to 30 weeks gestational age, who had been dependent on mechanical ventilation since birth. Frusemide (1 mg/kg/body weight) was administered, in random order, intravenously and by nebulisation, on two separate occasions 24 hours apart. Pulmonary function studies were performed before and at 30, 60, and 120 minutes after administration of frusemide. Urine was collected for six hours immediately before and for six hours after administration of frusemide. RESULTS: Nebulised frusemide increased the tidal volume 31 (SE 11.5)% and compliance 34 (SE 12)% after two hours, whereas no change in either was noted for up to two hours after intravenous frusemide administration. Neither intravenous nor nebulised frusemide had any effect on airway resistance. Six hour urine output increased from a mean (SE) of 3.3 (0.4) ml/kg/hour to 5.9 (0.8) ml/kg/hour following intravenous frusemide administration while nebulised frusemide had no effect on urine output. Urinary sodium, potassium, and chloride losses were also significantly higher after intravenous frusemide, whereas nebulised frusemide did not increase urinary electrolyte losses. CONCLUSION: Single dose nebulised frusemide improves pulmonary function in premature infants with evolving chronic lung disease without adverse effects on fluid and electrolyte balance.     

Junctional tachycardia during radiofrequency ablation of the slow pathway in patients with AV nodal reentrant tachycardia: effects of autonomic blockade

BACKGROUND: Exogenous surfactant treatment of hyaline membrane disease is known to modify the pattern of radiological changes on the chest radiograph. OBJECTIVES: To analyse and attempt to explain the radiological changes observed after exogenous surfactant treatment. Materials and methods. Thirty-nine premature infants with typical hyaline membrane disease. RESULTS: Transient asymmetrical clearing with better aeration of the right lung in the absence of malposition of the tip of the endotracheal tube was observed in nine cases (23 %). This asymmetry was patchy in one case. It was due to a complication of mechanical ventilation in three cases [pneumothorax (n = 2) and pneumomediastinum (n = 1)]. In the other six cases, asymmetrical clearing could be related to the anatomical position of the right main bronchus, which facilitates distribution of surfactant to the right lung. However, the course of these premature infants was similar to that of infants with symmetrical chest radiological findings after treatment. CONCLUSIONS: Asymmetrical clearing of chest radiographs, sometimes patchy, after surfactant treatment requires exclusion of pneumothorax or infection but has no influence on clinical outcome.     

Cardiac effects of short course dexamethasone in preterm infants

AIM: To examine the incidence and natural history of left ventricular hypertrophy (LVH) associated with the shorter 2-3 week course of dexamethasone, now more usual, for chronic lung disease. METHOD: Thirty one infants, gestational age 23-34 (median 26) weeks, birthweight 500-2054 (median 815)g, received dexamethasone, starting at 0.4-0.6 mg/kg/day, at a median of 11 days of age (range 2-34), weaning over a period of 2-3 weeks. Eighteen preterm neonates were studied as controls over a similar time period. Serial echocardiographic measurements of end diastolic interventricular septum (IVSd) and left ventricular posterior wall (LVPWd) thicknesses were taken before, and up to 48 days after, starting dexamethasone. Maximum Doppler blood flow velocities from the left ventricular outflow tract (LVOT) were measured. RESULTS: Left ventricular hypertrophy (LVH) occurred in 29 babies (94%). Median hypertrophy of the IVSd in those receiving dexamethasone was 67% and LVPWd 56% of baseline measurements, significantly greater than control infants (p < 0.001). LVH appeared by a median of three days, peaking by a median of 10 days. All resolved by a median of 27 days. LVOT obstruction was not seen. There was no significant correlation with birthweight, gestation, blood pressure, or glucose tolerance. CONCLUSIONS: LVH developed in almost all preterm neonates receiving a 2-3 week course of dexamethasone, but was of little clinical importance and always resolved. Echocardiography is probably not required routinely in infants receiving such short course dexamethasone for chronic lung disease.     

Surfactant improves lung function and mitigates bacterial growth in immature ventilated rabbits with experimentally induced neonatal group B streptococcal pneumonia

AIMS: To study the influence of surfactant on lung function and bacterial proliferation in immature newborn rabbits with experimental group B streptococcal (GBS) pneumonia. METHODS: Preterm rabbit fetuses (gestational age 28 days) underwent tracheotomy and were mechanically ventilated in a warmed body plethysmograph that permitted measurement of lung-thorax compliance. Fifteen minutes after the onset of ventilation the animals received either GBS or saline intratracheally; at 30 minutes, a bolus of saline or 200 mg/kg of a porcine surfactant (Curosurf) was administered via the airway. Bacterial proliferation was evaluated in lung homogenate at the end of the experiments and the results expressed as mean log10 cfu/g lung (SD). Animals receiving only saline (n = 20) or saline and surfactant (n = 20) served as controls. RESULTS: The average survival time was about three hours in all groups. Infected animals receiving surfactant (n = 22) had significantly less bacterial growth (9.09 (0.45) vs 9.76 (0.91)) and improved lung function (compliance: 0.61 (0.14) vs 0.34 (0.19) ml/kg. cm H2O) than infected rabbits receiving saline at 30 minutes (n = 22). CONCLUSION: Surfactant improves lung function and mitigates bacterial growth in preterm rabbits infected with group B streptococci.     

Transcriptional regulation of the rat poly(ADP-ribose) polymerase gene by Sp1

BACKGROUND: Exogenous surfactant therapy of lung donors improves the preservation of normal canine grafts. The current study was designed to determine whether exogenous surfactant can mitigate the damage in lung grafts induced by mechanical ventilation before procurement. METHODS AND RESULTS: Five donor dogs were subjected to 8 hours of mechanical ventilation (tidal volume 45 ml/kg). This produced a significant decrease in oxygen tension (p = 0.007) and significant increases in bronchoscopic lavage fluid neutrophil count (p = 0.05), protein concentration (p = 0.002), and the ratio of poorly functioning small surfactant aggregates to superiorly functioning large aggregates (p = 0.02). Five other animals given instilled bovine lipid extract surfactant and undergoing mechanical ventilation in the same manner demonstrated no significant change in oxygen tension values, lavage fluid protein concentration, or the ratio of small to large aggregates. All 10 lung grafts were then stored for 17 hours at 4 degrees C. Left lungs were transplanted and reperfused for 6 hours. After 6 hours of reperfusion the ratio of oxygen tension to inspired oxygen fraction was 307 +/- 63 mm Hg in lung grafts administered surfactant versus 73 +/- 14 mm Hg in untreated grafts (p = 0.007). Furthermore, peak inspired pressure was significantly (p < 0.05) lower in treated animals from 90 to 360 minutes of reperfusion. Analysis of lavage fluid of transplanted grafts after reperfusion revealed small to large aggregate ratios of 0.17 +/- 0.04 and 0.77 +/- 0.17 in treated versus untreated grafts, respectively (p = 0.009). CONCLUSIONS: Instillation of surfactant before mechanical ventilation reduced protein leak, maintained a low surfactant small to large aggregate ratio, and prevented a decrease of oxygen tension in donor animals. After transplantation, surfactant-treated grafts had superior oxygen tension values and a higher proportion of superiorly functioning surfactant aggregate forms in the air space than untreated grafts. Exogenous surfactant therapy can protect lung grafts from ventilation-induced injury and may offer a promising means to expand the donor pool.     

Pulmonary surfactant concentration during transition from high frequency oscillation to conventional mechanical ventilation

OBJECTIVE: To test the hypothesis that conventional mechanical ventilation (CV) provides a greater stimulus to secretion of pulmonary surfactant than high frequency oscillatory ventilation (HFO). METHODOLOGY: Sequential examination of surfactant indices in lung lavage fluid in a group of six infants with severe lung disease (group 1), ventilated with HFO and then converted back to CV as their lung disease recovered. A similar group of 10 infants (group 2) ventilated conventionally throughout the course of their illness were studied for comparison. In groups 1 and 2, two sequential tracheal aspirate samples were taken, the first once lung disease was noted to be improving, and the second 48-72 h later. Group 1 infants had converted from HFO to CV during this time. RESULTS: A marked increase in concentration of total surfactant phospholipid (PL) and disaturated phosphatidylcholine (DSPC) was seen in group 1 after transition from HFO to CV; the magnitude of this increase was significantly greater than that sequentially observed in group II (total PL: 9.4-fold increase in group 1 vs 1.8-fold in group 2, P = 0.006; DSPC: group 1 6.4-fold increase vs. group 2 1.7-fold, P = 0.02). CONCLUSION: These findings suggest that intermittent lung inflation during CV produces more secretion of surfactant phospholipid than continuous alveolar distension on HFO, and raise the possibility that conservation and additional maturation of surfactant elements may occur when the injured lung is ventilated with HFO.     

Sperm cytology in azoospermia

BACKGROUND: To progress the clinical treatment of neonates, especially in the management of respiration, we have to be able to measure their pulmonary function appropriately. Various methods have been developed, but little is known about the pulmonary function of very low birthweight infants (VLBWI) because of the difficulty in taking their measurements with existing equipment. We have developed a very low dead space pneumotachograph to measure lung function in VLBWI. METHODS AND RESULTS: We used our pneumotachograph on 30 infants each weighing less than 1500 g at birth. The infants were intubated with endotracheal tubes of 2.5 or 2.0 mm diameter to measure tidal volume and minute ventilation in the prone and supine position. The tidal volume in the supine position was 6.99 +/- 0.42 mL/kg and 7.58 +/- 0.38 mL/kg in the prone position (mean +/- SE). The tidal volume was significantly larger in the prone than the supine position (P < 0.05). However, no significant difference was observed in minute ventilation and respiratory rates. CONCLUSION: The tidal volume significantly increased in the prone position in VBLWI, confirming the previous observation of larger healthy infants is also applicable to the very low birthweight infants.     

Treatment Investigational New Drug experience with Survanta (beractant)

From September 1989 through July 1991, before commercial availability, Survanta (beractant intratracheal suspension), a modified bovine-derived surfactant used for prevention and treatment of neonatal respiratory distress syndrome, was made available to 231 neonatal intensive care units in the United States and Canada under a Treatment Investigational New Drug protocol. Results of this open clinical experience are reported. Investigators could give one dose of Survanta soon after birth to neonates weighing 600 to 1250 g (prevention strategy). Neonates weighing 600 to 1750 g who were not treated at birth could begin Survanta therapy if respiratory distress syndrome developed within 8 hours of birth (rescue strategy). All neonates could receive up to three more doses over the first 48 hours of life at minimum intervals of 6 hours if they met retreatment criteria. Qualifications for enrollment closely matched those used in previous randomized controlled clinical trials. This report includes results from 8168 neonates who completed the study. Treatment Investigational New Drug rates for intracranial hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, pulmonary air leaks, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, pulmonary interstitial emphysema, pretreatment sepsis, and posttreatment sepsis were less than for treated neonates in the controlled trials and survival was equivalent across studies. Problems with treatment administration were reported with 30.4% of doses, while adverse events were reported in 0.5% of neonates. The results of the Treatment Investigational New Drug protocol revealed no new safety concerns associated with the widespread use of Survanta and confirmed the safety profile established in earlier controlled trials.