Oxygen consumption in normally grown, small-for-dates and large-for-dates new-born infants

1. Serial measurements of minimal oxygen consumption (V(O2)) have been obtained from nineteen healthy new-born infants in order to find out how body weight, gestational age and age after birth affected V(O2). The first measurement of V(O2) was done within 12 hr of birth, and further measurements were made at intervals until the baby left hospital.2. The majority of the infants (seventeen) weighed less than 2.5 kg at birth, and were ;premature' according to international definition. Gestational age, calculated from the mother's last menstrual period, was corroborated by clinical data and obstetrical history. The babies were divided into four groups according to birth weight and gestational age combined (see Table 1). Babies in the first two groups were the appropriate weight for dates (i.e. normally grown), babies in the other two groups were either small-for-dates or large-for-dates.3. At birth minimal V(O2) was closely correlated with birth weight in all babies and appeared to be directly proportional to it. The value for V(O2)/kg was similar in all groups. V(O2) was not related to gestational age per se. However, in the two normally grown groups V(O2) was roughly related to gestational age because birth weight was related to gestational age.4. In all babies minimal V(O2) rose progressively with increasing age after birth; a marked increase in V(O2) occured in the first week of life, despite a small decline in body weight.5. At a given age after birth differences in V(O2)/kg between the four groups were mostly less than 10%, and in general the differences were not statistically significant.Values for minimal V(O2) in all four groups were roughly:5 ml. O(2)/kg.min at < 12 hr of age.7 ml. O(2)/kg.min at 7-14 days of age.9 ml. O(3)/kg.min at about 2 months of age.6. It is concluded that:(a) At birth minimal V(O2) is largely determined by birth weight. V(O2)/kg is little affected by either rate of growth in utero or gestational age.(b) Minimal V(O2) is a function of age after birth as well as of body weight, and the value for V(O2)/kg increases as the baby gets older.     

Evaporative water loss in the new-born baby

1. Measurements of total evaporative water loss (EWL) were made on sixty-three premature and full-term babies 0-65 days after birth within a closed Perspex chamber under varied environmental conditions by measuring the flow and absolute humidity of air entering and leaving the chamber. Control experiments suggested that the method underestimated loss by about 5%. Measurements of O(2) consumption were made concurrently by recording the volume change of the closed gas circuit.2. The total basal EWL averaged 10.8 g H(2)O/m(2).hr in infants 2-10 days old when ambient water vapour pressure (P(H2O)) was 18 mm Hg; basal EWL was correlated with basal metabolic rate at all ages studied and evaporative heat loss accounted for approximately 23% of basal heat production.3. Respiratory water loss was measured by detecting the water added to air at 33 degrees C passed across the face of eight infants in a trunk plethysmograph. Respiratory water loss was inversely related to the water vapour content of the inspired air; gas appeared to leave the nose approximately 95% sat. at 35.6 degrees C.4. Measurements of total EWL were obtained when humidity was varied and skin loss was calculated by subtracting estimated respiratory loss from total loss; changing P(H2O) from 7 to 25 mm Hg appeared to decrease basal skin water loss by only 1.5 g/m(2).hr.5. No consistent changes in EWL were obtained when environmental temperature (T(E)) was varied between 28 and 34 degrees C. Active sweating occurred in infants 0-10 days old born within 3 weeks of term when T(E) exceeded 34-35 degrees C and rectal temperature (T(R)) rose above 37.2 degrees C. The threshold rectal temperature at which sweating was detected fell significantly in the first 10 days of life; EWL increased two to fourfold when T(R) rose to between 37.5 and 37.8 degrees C.6. In infants of less than 215 days post-conceptual age (term approximately 268 days) EWL increased less than 50% at T(R) 37.7-37.8 degrees C; it is concluded that the sweating mechanism is defective in these infants.     

The post-natal changes in minimal metabolic rate in the pig

1. Minimal metabolic rate was measured as oxygen consumption in new-born pigs when environmental temperature was rising and passing through thermal neutrality.2. Three different periods were observed in 20 days after birth. The first period included the time from birth to 82 hr and was characterized by a continuous rise in minimal metabolic rate from 9.4 to 16.0 ml. O(2)/kg.min (70% increase). The second period extended from 82 hr to 9.5 days with values near to 16 ml. O(2)/kg.min. The third period beginning on the eleventh day lasted until observations ceased on the twentieth day and was characterized by a 25-30% fall in minimal metabolic rate when compared with the second period.3. Minimal metabolic rates from the second and third period were proportional to body weight and not to the surface area. Exponential factors for body weight were 0.93 and 0.96 for the second and third periods respectively.4. Rectal temperature rose from 38.6 degrees C on the first day to 39.3 degrees C on the second and 39.5 degrees C on the fourth day after birth.5. Environmental temperature associated with minimal metabolic rate showed a general tendency to fall from 36.5 in the first 4 days to between 33 and 34 degrees C in the following days.6. Age rather than body weight is the decisive factor influencing changes in minimal metabolic rate in the new-born pig.     

Oxygen consumption during pouch development of the macropod marsupial Setonix brachyurus

1. Measurements of O(2) consumption at 9 or 10 temperatures in the 20-40 degrees C ambient temperature range were made on joeys with ages selected to cover the 180-day period of pouch occupancy.2. The rate of O(2) consumption of joeys younger than 100 days increased directly with ambient temperature.3. After 100 days of age the O(2) consumption rate at low temperatures rose and at about 140 days of age a constant rate was maintained over the full ambient temperature range.4. Heat transfer from joey to mother commenced after 100 days of age.5. At 150-180 days of age the rate of O(2) consumption at 20 degrees C was approximately 12 times greater than at ages less than 100 days. A thermal neutral zone was established in the range 32-36 degrees C by joeys older than 150 days.6. At the usual pouch temperature of 36.5 degrees C, O(2) consumption per unit wet body weight rose from 12 ml./kg.min at birth to 17 ml./kg.min at the end of pouch life. On a unit dry body weight basis it fell from 120 to 56 ml./kg.min. This decline parallels the decrease in growth rate.     

New uses of intravenous immune globulin in newborn infants

Preterm infants are hypogammaglobulinemic at birth, a condition that worsens during the first several weeks of life. It has been postulated that periodic infusions of intravenous immune globulin in preterm infants might prevent systemic infections after age 7 days, but clinical trials have been inconclusive. To test this hypothesis in neonates weighing 500 to 1750 g at birth, a multicenter, randomized, double-blind, placebo-controlled trial was initiated. Either intravenous immune globulin (500 mg/kg) (284 infants) or placebo (5% albumin-normal saline, 10 ml/kg) (293 infants) was infused periodically for 8 weeks. Infusions were well tolerated. Mortality (4%) was similar in both groups. However, the incidence of systemic infection was significantly reduced in the treatment group, but only in those weighing less than 1500 g. More than 80% of infections were bacterial; half were caused by staphylococci. Standard use of intravenous immune globulin in preterm infants looks promising but must await full analysis of data from this and another ongoing multicenter trial.     

Comparison of thermoregulatory responses to exercise in dry heat among prepubertal boys, young adults and older males

The purpose of this investigation was to compare the thermoregulatory responses during exercise in a hot climate among three age categories. Eight prepubertal (PP), eight young adult (Y) and eight elderly (O) male subjects cycled at an intensity of 50 +/- 1% of their maximum oxygen uptake (V(O2peak)) for 85 min (three 20 min bouts with three 7 min rest periods) in hot and dry conditions (41 +/- 0.67 degrees C, 21 +/- 1% relative humidity). During the exercise-in-heat protocol, rectal temperature (T(re)) skin temperatures (T(sk)), heart rate (HR), V(O2), V(CO2) V(E), RER, sweat rate, and the number of heat activated sweat glands (HASG) were determined. Despite highest and lowest end-exposure T(re) in the Y and O groups, respectively, the rise in rectal temperature (accounting for differences in baseline T(re)) was similar in all age groups. Changes in body heat storage (DeltaS), both absolute and relative to body mass, were highest in the Y and O groups and lowest in the PP group. While end-session as well as changes in mean skin temperature were similar in all three age groups, HR (absolute and percentage of maximum) was significantly lower for the O compared with the PP and Y groups. Total body as well as per body surface sweating rate was significantly lower for the PP group, while body mass-related net metabolic heat production ((M -- W) kg(-1)) and heat gained from the environment were highest in the PP and lowest in the O group. Since mass-related evaporative cooling (E(sk) kg(-1)) and sweating efficiency (E(sk)/M(sw) kg(-1)) were highest in the PP and lowest in the O group, the mass-dependent heat stored in the body (DeltaS kg(-1)) was lowest in the PP (1.87 +/- 0.03 W kg(-1)) and highest in Y and O groups (2.19 +/- 0.08 and 1.97 +/- 0.11 W kg(-1), respectively). Furthermore, it was calculated that while the O group required only 4.1 +/- 0.5 W of heat energy to raise their body core temperature by 1 degrees C, and the Y group needed 6.9 +/- 0.9 W (1 degrees C)(-1), the PP group required as much as 12.3 +/- 0.7 W to heat up their body core temperature by 1 degrees C. These results suggest that in conditions similar to those imposed during this study, age and age-related characteristics affect the overall rate of heat gain as well as the mechanisms through which this heat is being dissipated. While prepubertal boys seem to be the most efficient thermoregulators, the elderly subjects appear to be the least efficient thermoregulators.     

The total thermal insulation of the new-born baby

1. One hundred and seventeen healthy new-born babies weighing between 0.9 and 4.8 kg at delivery have been studied during the first ten days of life, and sixteen of these babies have been studied serially for 6 weeks after birth. The babies lay supine in a draught-free environment (air speed 4-5 cm/sec) of moderate humidity. The operative temperature was between 26 and 38 degrees C for the babies who were studied naked.2. Total non-evaporative heat loss was calculated from simultaneous measurements of oxygen consumption, evaporative water loss and the concomitant change in mean body temperature.3. Approximately 10% of the total body surface area was in contact with the mattress or floor. Conductive heat loss accounted for only about 5% of all non-evaporative heat loss when the naked baby was lying on a thick foam mattress, but for as much as 25% when the baby was lying in a water-jacketed chamber with a floor of clear plastic approximately 5 mm thick.4. Insulation to heat loss by convection and radiation varied with environmental temperature. Total specific insulation was low in a warm environment when the naked baby vasodilated, and rose by between 16 and 25% to a maximum in an environment of 31 degrees C. It decreased significantly when the baby became physically active in environments with a temperature less than this.5. Total specific insulation in an environment of 31 degrees C varied with body size: it averaged 0.156 degrees C.m(2).hr/kcal in seven naked babies weighing 0.9-1.2 kg, rose to 0.190 degrees C.m(2).hr/kcal in twelve babies weighing 1.8-2.2 kg, and averaged 0.201 degrees C.m(2).hr/kcal in the thirty-four babies who weighed over 3 kg. Tissue insulation accounted for 23% of this total specific insulation in the smaller babies, and about 28% of the total in babies weighing over 3 kg.6. Clothing ten babies in a vest, napkin and long cotton nightdress increased the total specific insulation by an average of 0.23 degrees C.m(2).hr/kcal.     

Anatomic fit assessment for the Penn State pediatric ventricular assist device

This investigation determined the ages and weights of children that could be supported with 12 and 25 ml Penn State pediatric ventricular assist devices (PVADs) using 6, 8, and 10 mm outlet cannulas and grafts. Future patients will be matched to devices based on cardiac output (CO) and ascending aortic diameter (AA). These were calculated for children 0-10 years with regression formulas given as clinical standards [<5 kg, CO = 0.2171(kg) + 0.0703], [>5 kg, CO = 3.06 (m2) + 0.37], [AA = -0.0427 + 14.54 (m2)1/2]. The 12 ml PVAD will be useful for patients from approximately birth to 3-8 months, weighing 2-7 kg, and having 0.5-1.4 L/min CO; the 25 ml PVAD will be for children 2-6 months to 5-9 years old, weighing 6-23 kg, and having 1.3-3.0 L/min of CO. The 6 mm outlet graft will fit children from 0 to 12 months, weighing 2-8 kg; the 8 mm graft from 0 to 47 months, weighing 4-14 kg; and the 10 mm graft for children 4 months to 8 years, weighing 8-21 kg.     

The relation between body size and maximum and minimum metabolic rates in the new-born pig

1. Measurements of rates of oxygen consumption were made on a total of sixty-two Large White pigs aged between 1 hr and 6 days, with a range of body weight from 0.75 to 2.40 kg.2. The maximum rate was determined from the continuous estimation of oxygen consumption as the environmental temperature fell past the point at which the maximum occurred.3. The minimum rate was determined both as the environmental temperature rose through the zone of thermal neutrality, and from measurements at thermal neutrality.4. In animals aged 1-6 days the mean maximum rate was 49.0 ml. O(2)/kg.min, and the mean minimum was 15.3 ml. O(2)/kg.min. Both rates were proportional to body weight and not to surface area.5. Pigs less than 1 day old exhibited lower maximum and minimum rates than the older pigs.     

Changes in breathing pattern and thoracoabdominal motion after bariatric surgery: a longitudinal study

This study evaluated the breathing pattern of 30 obese patients [32 ± 9 years old; body mass index (BMI): 42.72 ± 4.10 kg/m(2)] before and after bariatric surgery and compared them with 30 control individuals (31 ± 8 years old, BMI: 21.99 ± 2.22 kg/m(2)). Measurements were performed using calibrated respiratory inductive plethysmography. Six months after bariatric surgery, obese patients exhibited a significant reduction in tidal volume (V(T)), minute ventilation (V(E)) and inspiratory duty cycle (T(I)/T(TOT)) compared with pre-surgical values. The control group had a higher breathing frequency, V(E) and phase angle (PhAng). There were no significant differences in V(T)/T(I), percentage of rib cage motion (%RC) or abdominal motion (%AB). Obese patients exhibited changes in their breathing pattern and asynchrony after bariatric surgery without any changes in thoracoabdominal motion. Certain aspects of the breathing pattern of obese patients became more similar to those of the controls after surgery.     

Cardiopulmonary exercise testing (CPET) in pulmonary emphysema

In patients affected by chronic obstructive pulmonary disease (COPD), cardiopulmonary response to exercise was never related to the severity of emphysema (E) measured by high resolution computed tomography (HRCT). Sixteen patients (age=65±8 yrs; FEV(1)=54±18%pred; RV=160±28%pred) with moderate to severe E (quantified by lung HRCT as % voxels <-910 HU) were exercised on a cycle-ergometer to exhaustion. Oxygen uptake (V˙(O2)), carbon dioxide output (V˙(CO2)), ventilation (V˙(E)), tidal volume (V(T)), and end-tidal P(CO2) (PET(CO2)) derived variables were measured breath-by-breath. The % of E correlated with: (1) the ratio V(Tpeak) (r=0.74; p=0.001); (2) the V˙(E)/V˙(CO2) slope (r=-0.77; p=0.0004); (3) PET(CO2) values at peak exercise (r=0.80; p=0.0001). Also, the %E was strongly predicted by the following exercise equation: %E(EST) = 58.1 + 11.9 × ΔV˙(E)/V˙(CO2) (r=0.94; p<0.0001). A V(Tpeak)/FEV1 ratio>1 is typically observed in severe E patients; furthermore, the V˙(E)/V˙(CO2) slope and the PET(CO2peak) values decrease and increase respectively as more as the emphysema is severe.     

Correlations between the circadian patterns of body temperature, metabolism and breathing in rats

It had been demonstrated previously that the circadian patterns of activity and state of arousal are not essential for the manifestation of the daily patterns of pulmonary ventilation (V(E)), tidal volume (V(T)) and breathing frequency (f). In this study we investigated the extent of the linkage between the circadian pattern of breathing and those of body temperature (T(b)) and metabolic rate (oxygen consumption, V(O2), and carbon dioxide production, V(CO2)). Rats were instrumented for measurements of T(b) (by telemetry), and placed in a chamber for continuous 13-day period of measurement of breathing (by a modification of the barometric methodology), and of V(O2) and V(CO2) (by an open flow method). After the first 4 days in control conditions under a 12 h light:12 h dark (L:D) cycle, a perturbation was introduced on day 4, with an L-phase prolongation of 12 h, and on day 9, with an D-phase prolongation of 12 h. During the control days 1-4, all variables had daily oscillations (higher values in D), in phase with each other. During the perturbations (days 4-13), changes in T(b), V(O2) and V(CO2), averaged over the whole period, correlated significantly better with f than with V(T). Day-by-day X-Y loops indicated that V (E), V(T) and f could lead significantly the changes of T(b), V(O2) and V(CO2), and that these relations changed throughout the perturbation period. In addition, f and V(T) did not change necessarily in phase with each other. It is concluded that neither the oscillation in T(b) nor that in metabolism can be considered the direct cause of the daily oscillation of breathing. Presumably, the circadian pattern of breathing reflects the interplay of the daily patterns of many variables, none acting as the primary guide of the breathing daily rhythm.     

No effect of trans sodium crocetinate on maximal O(2) conductance or V(O(2),max) in moderate hypoxia

The lumped parameter describing skeletal muscle diffusional conductance for O(2), DM(O(2)), reflects all of the resistances for O(2) in moving from red cell to muscle fiber mitochondria. The purpose of our study was to determine if the carotenoid compound, trans sodium crocetinate (TSC), which has been reported to increase the diffusivity of O(2) in plasma, improves DM(O(2)) and thus, V(O(2),max) in maximally contracting in situ skeletal muscle. V(O(2),max) was measured in the isolated perfused canine gastrocnemius (n=5) during 3 min of isometric tetanic contractions at 1 Hz, while the animal was breathing 12% O(2) (PA(O(2))=32+/-2 Torr, mean+/-S.E.) under two experimental conditions. The first was a control contraction period and the second (following 60 min recovery) was performed within 5 min after infusion of a 0.1 mg x ml(-1) solution of TSC (total dose 100 microg kg(-1)). There were no significant differences in convective O(2) delivery (11.9+/-2.3 vs. 12.1+/-2.2 ml x min(-1) x 100 g(-1)), V(O(2),max) (9.5+/-1.5 vs. 9.6+/-1.5 ml x min(-1) x 100 g(-1)) or calculated DM(O(2)) (0.37+/-0.03 vs. 0.37+/-0.04 ml x min(-1) x 100 g(-1) x Torr(-1)) between contraction periods. As such, our results show that TSC does not improve performance in maximally contracting canine gastrocnemius muscle in situ under moderately hypoxic conditions, suggesting either that TSC in this situation does not increase plasma O(2) diffusivity or that this step in O(2) diffusion from red cell to myocyte does not constrain DM(O(2)).     

Ventilation- and carotid chemoreceptor discharge-response to hypoxia during induced hypothermia in halothane anesthetized rat

It has been hypothesized that respiratory "gain" to hypoxic stimulus is not depressed in hypothermic animals though ventilation and that metabolic O(2) demand (Vo(2)) decreases with reduction in body temperature. The present study addressed this hypothesis by quantitative analysis of ventilatory and carotid chemoreceptor responsiveness to hypoxia during induced hypothermia in halothane anesthetized and spontaneously breathing rats. Rectal temperature was lowered from 37 degrees C (normothermia) to 30 and 25 degrees C by cooling body surface at comparable anesthetic depth without inducing shivering. Ventilation (V(E)), V(O2), PaO(2) and carotid chemoreceptor afferent discharges were measured during hyperoxic and hypoxic gas breathing. PaO(2) values at the same Fi(O2) (range 0. 35-0.08) decreased progressively as rectal temperature decreased. Both the V(E)/V(O2)- and chemoreceptor discharge-response curves shifted toward a lower PaO(2) range with a slight increase in the response slopes during hypothermia. The results indicated that the sensitivity of carotid chemoreceptor and ventilatory responses to hypoxia did not decrease at reduced body temperature. It is concluded that carotid chemoreceptor mediated regulation of ventilation is tightly coupled to changes in PaO(2 )range in halothane anesthetized rats during induced hypothermia.     

Muscimol dialysis into the caudal aspect of the Nucleus tractus solitarii of conscious rats inhibits chemoreception

We studied the effects on chemoreception of bilateral focal inhibition of the caudal Nucleus tractus solitarii (cNTS) by microdialysis of muscimol (0.5 mM) in rats during wakefulness and NREM sleep at two temperatures, 24 degrees C and 30 degrees C, just below and within the thermoneutral zone, respectively. Body temperature and VO2 did not differ at these two temperatures. The CO2 response (% increase in V(E)/VO2) did not differ at 24 degrees C vs. 30 degrees C and muscimol inhibited the CO2 response equally at both temperatures. In contrast, the hypoxic response (% increase in V(E)/VO2) was greater at 30 degrees C than at 24 degrees C and muscimol inhibited it only at 30 degrees C. These effects were similar in wakefulness and NREM sleep. We conclude that: (1) ambient temperature can affect the V(E)/VO2 response to hypoxia but not hypercapnia and (2) at 24 degrees C muscimol in the cNTS affects the CO2 response but not the hypoxic response providing indirect support for the presence of chemoreception within the NTS.     

Prenatal and neonatal testosterone exposure interact to affect differentiation of sexual behavior and partner preference in female ferrets

Implanting testosterone (T) subcutaneously over Postnatal Days 5-20 masculinized sexual behavior, reduced proceptive responsiveness, and shifted sexual preference more readily in male than in female ferrets gonadectomized on Day 5. This enhanced sensitivity of males to neonatal T was best duplicated in females exposed transplacentally to T over Embryonic Days (E) 27-39 (41-day gestation) and injected at birth with T (2.5 micrograms sc in oil: 10% ethanol). Extended exposure of male ferrets to high levels of T, beginning shortly after the onset of testicular steroidogenesis (E25) and continuing for several hours after birth (E41) normally sensitizes their brains to the subsequent organizational effects on coital performance and sexual motivation of the relatively low levels of T that circulate in male ferrets during the first 3 postnatal weeks.     

Shivering and non-shivering thermogenesis during summit metabolism in young lambs

1. Summit metabolism of lambs declined steadily from about 3.5 l. O(2)/kg.hr during the first day of life, to about 2.0 l. O(2)/kg.hr at 2 months of age.2. The contributions of shivering and non-shivering thermogenesis to these changes were estimated by three independent methods; non-shivering thermogenesis was stimulated by catecholamines in a thermoneutral environment, shivering was suppressed by curariform drugs during summit metabolism, and an attempt was made to suppress non-shivering thermogenesis during summit metabolism by use of the sympatholytic drugs phentolamine and propranolol. Drugs were given by intravenous infusion during measurement of oxygen consumption in a closed circuit respiration chamber.3. ;Resting' metabolic rate of lambs during the first day of life was increased two to three-fold, from 1 l. O(2)/kg.hr, by either adrenaline or noradrenaline infused at 1-10 mug/kg.min. The increase declined with increasing age of lamb and was virtually absent by 3 weeks. The response to catecholamines appeared maximal at the dose levels used.4. Muscular paralysis induced by suxamethonium or gallamine reduced summit metabolism by about 2 l. O(2)/kg.hr in all lambs examined within the first 2 months of life. The residual metabolic rate, and the metabolic response to catecholamines under thermoneutral conditions, declined with age in the same manner, and their magnitudes were similar.5. Summit metabolism in lambs aged up to 2 months was depressed to varying degrees by the sympathetic inhibitors phentolamine, propranolol and hexamethonium. The depression with propranolol was greater, and the decline with age clearer, than with phentolamine. Hexamethonium and phentolamine depressed blood pressure, propranolol decreased heart rate and phentolamine and propranolol each suppressed shivering in some experiments.6. In 1 day-old lambs estimates of non-shivering thermogenesis, by the various methods, ranged from 0.8 to 1.4 l. O(2)/kg.hr (mean 1.1 l. or 31% of summit metabolism), and the estimates of shivering ranged from 1.3 to 1.9 l. O(2)/kg.hr (mean 1.6 l. or 46% of summit metabolism). However, in lambs 1-month old, estimates of non-shivering thermogenesis from sympathetic inhibition (0.6 and 0.8 l. O(2)/kg.hr) were considerably higher than estimates from muscular paralysis or stimulation by catecholamines (0.2 and 0.1 l. O(2)/kg.hr). It is suggested that the depression of summit metabolism by the sympathetic inhibitors is not solely due to specific inhibition of non-shivering thermogenesis, at least in the older lambs.7. The possession of a non-shivering thermogenic mechanism in addition to shivering is of clear survival value to new-born lambs.     

On the crucial ventilatory setting adjustment from two- to one-lung ventilation

Lung mechanics, histology, oxygenation and type-III procollagen (PCIII) mRNA were studied aiming to evaluate the need to readjust ventilatory pattern when going from two- to one-lung ventilation (OLV). Wistar rats were assigned to three groups: the left lung was not ventilated while the right lung received: (1) tidal volume (V(T))=5 ml/kg and positive end-expiratory pressure (PEEP)=2 cm H(2)O (V5P2), (2) V(T)=10 ml/kg and PEEP=2 cm H(2)O (V10P2), and (3) V(T)=5 ml/kg and PEEP=5 cm H(2)O (V5P5). At 1-h ventilation, V5P2 showed hypoxemia, alveolar collapse and impaired lung function. Higher PEEP minimized these changes and prevented hypoxemia. Although high V(T) prevented hypoxemia and maintained a higher specific compliance than V5P2, a morphologically inhomogeneous parenchyma and higher PCIII expression resulted. In conclusion, the association of low V(T) and an adequate PEEP level could be useful to maintain arterial oxygenation without inducing a possible inflammatory/remodeling response.     

Safety and trough concentrations of nevirapine prophylaxis given daily, twice weekly, or weekly in breast-feeding infants from birth to 6 months

Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV-1 transmission, postpartum transmission through breast milk remains a problem. Antiretroviral administration to the infant during the period of breast-feeding could protect against postnatal transmission. An open-label phase 1/2 study was designed to assess the safety and trough concentrations of nevirapine (NVP) given once weekly (OW), twice weekly (TW), or once daily (OD) to HIV-exposed breast-feeding infants for 24 weeks. Following maternal dosing with 200 mg NVP orally at onset of labor, breast-feeding infants were randomized within 48 hours of birth to 1 of 3 regimens: arm 1, NVP given OW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg from 15 days to 24 weeks), arm 2, NVP given TW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg from 15 days to 24 weeks), and arm 3, NVP given OD (2 mg/kg from birth to 14 days, upward arrow to 4 mg/kg from 15 days to 24 weeks). Trough NVP concentrations and clinical and laboratory abnormalities were monitored. Of the 75 infants randomized (26 to OW, 25 to TW, and 24 to OD dosing), 63 completed the 32-week follow-up visit. No severe skin, hepatic, or renal toxicity related to NVP was observed. Neutropenia occurred in 8 infants. Trough NVP levels were lower than the therapeutic target (100 ng/mL) in 48 of 75 (64.0%) samples from infants in the OW arm, 3 of 65 (4.6%) samples in the TW arm, and 0 of 72 samples in the OD arm. Median (range) trough NVP concentrations were 64 ng/mL (range: <25-1519 ng/mL) with OW dosing; 459 (range: <25-1386 ng/mL) with TW dosing; and 1348 (range: 108-4843 ng/ml) with OD dosing. Our data indicate that NVP prophylaxis for 6 months was safe and well tolerated in infants. OD NVP dosing resulted in all infants with trough concentration greater than the therapeutic target and maintenance of high drug concentrations. A phase 3 study is planned to assess the efficacy of OD infant NVP regimen to prevent breast-feeding HIV-1 transmission.