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PubMed1991

Pulmonary mechanics and outcome of neonates on ECMO.

Deciding when to wean neonates from extracorporal membrane oxygenation (ECMO) can be difficult. The usefulness of simple measurements of pulmonary mechanics e.g., dynamic compliance (Cdyn) has been questioned. We investigated the pulmonary mechanics of eight neonates using the interrupter technique, which allows the partitioning of pulmonary mechanics into compartments representing the conducting airways and more peripheral phenomena (viscoelastic properties and "pendelluft"). Three neonates required ECMO for a congenital diaphragmatic hernia (CDH), two for hyaline membrane disease (HMO), two for meconium aspiration syndrome (MAS), and one for pneumonia. All neonates with MAS, HMD, and pneumonia were successfully weaned from ECMO when their Cdyn was 0.3 mL/cmH2O/kg or greater [mean 0.34 +/- 0.06 (SEM)]. All three neonates with CDH died and their highest Cdyn was 0.21, 0.19, and 0.09 mL/cmH2O/kg respectively (mean, 0.16 +/- 0.037). The airway resistance (Raw) and the slower component of pressure change after interruption (delta Pdiff), a measure of the more peripheral phenomena of the lung, were not significantly different in those neonates who survived and those who did not. The values for delta Pdiff in all patients were higher than those in healthy neonates. However, the Raw was not different. This suggests that the major disturbance in pulmonary mechanics was distal to the conducting airways. Those neonates who were successfully weaned from ECMO had a significantly higher Cdyn 24-48 hours prior to decannulation. Considering the lung as a two-compartment model offers no advantages when compared to the one-compartment model for the prediction of the outcome of a neonate on ECMO.

Airway Resistance↗
PubMed1993

Human neonatal and adult vascular smooth muscle cells in culture.

Neonatal vascular smooth muscle cells (SMC) in culture have been demonstrated to be quite different from adult SMC and to be similar to intimal SMC in animal models. To characterize human neonatal vascular SMC in culture, cultures of arterial SMC were prepared by an explant method from the subclavian arteries of autopsied patients (10 adults and 6 neonates). The morphology and growth characteristics of these cells were compared. All cells were positively immunostained with HHF 35, a monoclonal antibody specific for muscle actin. Electron microscopically, both adult and neonatal SMC were of synthetic phenotype. SMC from neonates had a short population doubling time (PDT, 28.6 +/- 7.5 hr) and high saturation density (SD, 37.5 +/- 11.9 x 10(4) cells/cm2). They did not show hill and valley growth patterns. Among the SMC cultured from adult media, two subtypes were distinguished, based on their growth characteristics. Classical adult SMC (7 of 10 cases) grew in hill and valley patterns with long PDT and low SD values (61.7 +/- 28.8 hr, 6.5 +/- 1.9 x 10(4) cells/cm2, respectively). The second subtype (3 of 10 cases), neonatal-type adult SMC, had PDT and SD values (22.9 +/- 4.0 hr, 31.3 +/- 14.7 x 10(4) cells/cm2, respectively) similar to those of neonatal SMC. Intimal SMC became senescent in early phases of subculture. To test for the possible participation of autocrine growth factors in the heterogeneity of the growth patterns, Northern blot analysis was conducted for PDGF-A, TGF-beta, c-myc, and c-fos mRNA in three types of SMC. There was no significant difference in these mRNA levels between the SMC. We demonstrated that human neonatal vascular SMC in culture are quite different in their growth characteristics from classical adult SMC in culture and that neonatal-type SMC can be isolated from adult media.

Adult↗
PubMed1987

Acute renal failure in neonates: incidence, etiology and outcome.

Acute renal failure (ARF) occurs in as many as 8% of neonates admitted to neonatal intensive care units. Most often, ARF is recognized because of oliguria (urinary flow rate less than 1 ml/kg per hour) although nonoliguric neonatal ARF is being detected with increasing frequency. Among urinary indices utilized to differentiate oliguric neonatal ARF from prerenal oliguria, a fractional excretion of sodium greater than 3% or a renal failure index (RFI) greater than 3 are helpful in confirming ARF. Such indices must be viewed with caution in very premature infants who may have a physiologically high sodium excretion rate and in neonates with the nonoliguric form of ARF. The mortality of oliguric neonatal renal failure may be as high as 60% in medical ARF and even higher in neonates with congenital heart disease, or with anomalies of the genitourinary system. In contrast, nonoliguric renal failure in neonates has an excellent prognosis. Long-term abnormalities in glomerular filtration rate and in renal tubular function are common in survivors of neonatal ARF.

Acute Kidney Injury↗
PubMed1993

Value of measurement of neutrophil elastase-alpha 1 proteinase inhibitor levels in the early diagnosis of neonatal infection.

In a case-control study in 398 neonates the value of measuring the levels of neutrophil elastase-alpha 1 proteinase inhibitor (EPI) for early diagnosis of neonatal infection was studied in comparison to the commonly used parameters of leukocyte count, ratio of immature to total granulocytes and C-reactive protein levels. Investigations were performed on day 1 or day 6 of life. On the basis of the clinical findings patients were allocated to one of the three following groups: healthy neonates (group A), neonates with local infections such as pneumonia or skin infection (group B) or neonates with septicemia as demonstrated by a positive blood culture (group C). The median EPI levels (with range) measured on day 1 were: group A 40 (15-65) micrograms/l, group B 120 (80-260) micrograms/l, group C225 (140-355) micrograms/l. The levels on day 6 were: group A 27.5 (5-55) micrograms/l, group B 105 (65-370) micrograms/l, group C 182.5 (74-450) micrograms/l. EPI thus discriminated well between healthy neonates and neonates with infection, but not between neonates with infection and neonates with septicemia.

C-Reactive Protein↗
PubMed2002

Serum cortisol and thyroid hormone levels in neonates with sepsis.

OBJECTIVE: To evaluate the thyroid hormone and cortisol levels in neonates with sepsis in relation to the final outcome. It was hypothesized that the hormonal level could act as some prognostic guideline. METHODS: Forty nine neonates, aged 8- 28 days, diagnosed as neonatal sepsis were selected for the study. Neonates below 8 days of age, 35 weeks of gestation and 2000 g of birth weight were excluded from the study. Twenty FT-AGA neonates beyond day 7 of life served as control for the study. The hormones were estimated by radioimmunoassay. RESULTS: The neonates with sepsis had significantly higher mean serum cortisol and lower mean serum total T4 at admission as compared to healthy neonates. The mean serum total T3 level was also lower, but the difference was not statistically significant. The mean serum TSH levels were comparable in both groups. The levels normalised following recovery. Sixteen neonates succumbed to the disease process. The non-survivors had significantly lower mean total T3 and total T4 levels as compared to the survivors. CONCLUSION: The endocrinal abnormalities are of transient nature as a response to sepsis. Low total T3 and total T4 are the predictors of adverse outcome in neonates with sepsis.

Humans↗
PubMed2003

Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism.

OBJECTIVE: To investigate age-related differences in morphine requirements and metabolism in full-term neonates. DESIGN AND SETTING: Randomized double-blind study in the pediatric surgical intensive care unit. PATIENTS: Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery. INTERVENTIONS: After surgery patients were randomly assigned to continuous morphine (10 micro g/kg per hour) or intermittent morphine (30 micro g/kg per 3 hours). Additional morphine was administered on guidance of pain scores. MEASUREMENTS AND RESULTS: Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6-glucuronide (M6G) plasma concentrations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed significantly from the older neonates in morphine requirement (median 10 vs. 10.8 micro g/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ratio (0.6 vs. 1.5). Pain scores did not differ between age groups or morphine treatment groups. Neonates who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentrations than the spontaneously breathing neonates 12 and 24 h after surgery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Morphine plasma concentrations were not correlated with analgesia or respiratory depression. Five neonates (intermittent morphine) showed respiratory insufficiency; however, the difference between the groups was not significant. CONCLUSIONS: Neonates aged 7 days or younger require significantly less morphine postoperatively than older neonates. The two morphine regimens (continuous, intermittent) were equally effective and safe. Mechanical ventilation decreases morphine metabolism and clearance.

Age Factors↗
PubMed2003

The epidemiology of neonatal tumours. Report of an international working group.

Neonatal tumours occur every 12,500-27,500 live births and comprise 2% of childhood malignancies, but there is little clarity as to their real prevalence, sites of origin and pathological nature as reported series vary. As an entity, neonatal tumours provide a unique window of opportunity to study tumours in which minimal environmental interference has occurred. The majority of tumours present with a mass at birth (e.g., teratomas, neuroblastomas, mesoblastic nephroma, fibromatosis), which are not infrequently identified on antenatal ultrasound. Histologically, teratoma and neuroblastoma remain the two main tumour types encountered with soft tissue sarcoma, renal tumours, CNS tumours and leukaemia being the next most common tumour types identified. Malignant tumours are uncommon in the neonatal period per se and benign tumours may have malignant potential. A particular problem exists in clinical classification, as histological features of malignancy do not always correlate with clinical behaviour. Benign tumours may also be life threatening because of their size and location. Other tumours may demonstrate local invasiveness, but no metastatic potential, and tumours that are clearly malignant may demonstrate unpredictable or uncertain behaviour. Screening programmes have brought more tumours to light, but do not appear to affect the overall prognosis. They may provide clues to the stage at which tumours develop in foetu. The aetiology of cancer in children is multifactorial and includes both genetic and environmental factors. The association between congenital abnormalities and tumours is well established (15% of neonatal tumours). Genetic defects are highly likely in neonatal tumours and include those with a high risk of malignancy (e.g., retinoblastoma), but also genetically determined syndromes with an increased risk of malignancy and complex genetic rearrangements. Tumours are mostly genetically related at a cellular level and factors influencing cellular maturation or apoptosis within the developing foetus may continue to operate in the neonatal period. Cytogenetics of neonatal neoplasms appear to differ from neoplasms in older children, thus possibly explaining some of the observed differences in clinical behaviour. Certain constitutional chromosome anomalies, however, specifically favour tumours occurring in the foetal and neonatal period. In support of this hypothesis, certain cytogenetic anomalies appear to be specific to neonates, and a number of examples are explored. Other environmental associations include ionizing radiation, drugs taken during pregnancy, infections, tumours in the mother and environmental exposure.

Female↗
PubMed2004

Trans-placental exposure of neonates to acrylamide--a pilot study.

OBJECTIVES: Acrylamide (AA) (CAS No 79-06-1) has most recently been identified as a food-borne toxicant generated during the heating process of starch-containing foods. It was the aim of the present study to investigate the trans-placental exposure of newborn infants to this possible human carcinogen by analysis of the specific haemoglobin adduct of AA ( N-2-carbamoylethylvaline, AAV) in the blood of mothers and the corresponding umbilical cord blood of neonates as a parameter of biochemical effects. METHODS: We investigated the blood of 11 women advanced in pregnancy (one smoker, ten non-smokers) and the corresponding umbilical cord blood of neonates for the N-terminal haemoglobin adducts of AA (AAV) and the smoking-specific adduct of acrylonitrile (CAS No 107-13-1) ( N-cyanoethylvaline, CEV). The limit of detection (LOD) was 5 pmol/g globin for AAV and 4 pmol/g globin for CEV. RESULTS: AAV could be determined in all blood samples of the mothers (median 21 pmol/g globin, range 18-104 pmol/g globin) as well as in the umbilical cord blood of neonates (median 10 pmol/g globin, range 6-43 pmol/g globin). The highest values were detected in the blood of the smoking mother and her child. CEV was detected only in the blood of the smoking mother (185 pmol/g globin) and the corresponding umbilical cord blood (69 pmol/g globin). DISCUSSION: AAV adduct levels in non-smoking mothers and neonates showed a good correlation (r=0.859). The concentration of AA adducts in the blood of neonates is approximately 50% of the adduct level found in the blood of the mother. In view of the shorter life span of neonatal erythrocytes and the lower body weight of newborn infants, the relative internal dose of AA in neonates (in microgrammes per kilogramme body weight) must be assumed to be at least equal to that of the mother. Because of the high cell-replication rates during foetal development, trans-placental exposure of neonates to AA might raise concerns. Neonates of smoking mothers take up much higher doses of AA than those of non-smoking mothers.

Acrylamide↗
PubMed2006

Effect of culture conditions and mother's age on the sensitivity of Daphnia magna Straus 1820 (Cladocera) neonates to hexavalent chromium.

Daphnia magna is a freshwater cladoceran used worldwide as test organism in aquatic toxicity assays. In Mexico there is a test protocol for this species; nevertheless, some aspects of the controlled neonate production, as well as the possible consequences of the reproducers' culture conditions on the response of neonates to the toxic substance, are not completely known. In the present study, we evaluated the effect of temperature and photoperiod on the acute toxicity of CrVI in D. magna neonates, aimed at providing useful information on the Median Lethal Concentration (LC50) to this heavy metal, which is used as reference toxicant in some laboratories. D. magna was cultured at 20 and 25 degrees C, in combination with two photoperiod values: 16:8 and 12:12 (light:dark) during 40 days; the green microalga Ankistrodesmus falcatus (4x10(5) cells ml(-1)) was supplied as food. Once the reproduction began, the neonates were removed and acute toxicity bioassays at 20 and 25 degrees C were performed, by exposing them to hexavalent chromium. We also determined changes in neonates' size at 20 and 25 degrees C. Chromium toxicity increased along with increasing temperatures, and LC50 values were slightly lower for the first and last clutches in the observed period, but these findings are not conclusive because of the large variability recorded. The average LC50's were 0.2076+/-0.0164 mg l(-1) (at 20 degrees C) and 0.1544+/-0.0175 mg l(-1) (at 25 degrees C). The reproducers' culture temperature had no effect on neonates' sensitivity to chromium, in spite of performing the tests at temperatures either lower or higher than those at which the neonates had been obtained. The length of neonates produced during the first two clutches (<1.25 mm) was significantly lower than that measured in neonates of following reproductions (>1.3 mm), and were smaller at 25 degrees C; however, this did not seem to affect their sensitivity to chromium.

Animals↗
PubMed2002

Meningitis in the Neonate.

Group B beta-hemolytic streptococci and Escherichia coli strains account for approximately two thirds of all cases of neonatal meningitis, while bacteria that typically account for meningitis in older age groups (Haemophilus influenzae type B, Neisseria meningitidis, and Streptococcus pneumoniae) are infrequent causes of meningitis in the neonatal population. As with other medical problems in neonates, signs and symptoms of bacterial infection of the central nervous system are generally few in number and nonspecific in nature. Manifestations that can suggest meningitis, as well as other serious illnesses, include temperature instability, lethargy, respiratory distress, poor feeding, vomiting, and diarrhea. Signs suggestive of meningeal irritation, including stiff neck, bulging fontanelle, convulsions, and opisthotonus, occur only in a minority of neonates with bacterial meningitis and cannot be relied on solely to identify such patients. Ampicillin and either gentamicin or cefotaxime are recommended for initial empiric therapy of neonatal meningitis. When the results of the cerebrospinal fluid (CSF) culture and susceptibilities are known, therapy can be narrowed to cover the specific pathogen identified. In general, penicillin G or ampicillin is preferred for group B streptococcal meningitis, ampicillin for Listeria monocytogenes meningitis, and ampicillin plus either an aminoglycoside or cefotaxime for gram-negative meningitis. For the very low birth weight neonate who has been in the nursery for a prolonged period of time, organisms such as enterococci and gentamicin-resistant gram-negative enteric bacilli must also be considered. In patients with long-term vascular catheters, Staphylococcus aureus or coagulase-negative staphylococci must also be considered. Empiric combinations of antibiotics for such patients would include ampicillin or vancomycin, plus amikacin or cefotaxime. All neonates should undergo repeat CSF examination and culture at 48 to 72 hours after initiation of therapy. If organisms are observed on gram stain, modification of the therapeutic regimen should be considered, and neuroimaging should be performed. In general, therapy should be continued for 14 to 21 days for neonatal meningitis caused by group B streptococci or L. monocytogenes, and for at least 21 days for disease caused by gram-negative enteric bacilli. All patients with neonatal meningitis should have hearing and development monitored serially. The first audiologic evaluation should occur 4 to 6 weeks after resolution of the meningitis.

Journal Article↗
PubMed1988

Clinical and electrophysiologic features of fetal and neonatal paroxysmal atrial tachycardia resulting in congestive heart failure.

Those clinical and electrophysiologic features of paroxysmal atrial tachycardia (PAT) that appeared to be the cause of prenatal congestive heart failure (CHF) (hydrops fetalis) were evaluated in 12 neonates, ages 1 to 14 days, and compared with those occurring in 12 neonates, ages 2 to 34 days, who developed CHF from PAT diagnosed postnatally. Transesophageal electrophysiologic evaluation was performed after birth or at the time of PAT occurrence in the prenatal CHF group and at the time of CHF diagnosis in the postnatal CHF group. Before the electrophysiologic study, spontaneous PAT onset and termination were observed in all prenatal CHF neonates. In the postnatal CHF neonates, however, a single, prolonged episode of PAT was observed. During PAT, all neonates were observed to have a regular heart rate, normal QRS morphology and ventriculoatrial interval exceeding 80 ms. These findings suggested an orthodromic reciprocating tachycardia using an accessory atrioventricular connection as the tachycardia mechanism. In the 12 neonates with prenatal CHF, the PAT cycle length measured 243 +/- 30 ms, whereas in the 12 neonates with postnatal CHF it measured 208 +/- 19 ms (p less than 0.003). Neonates with prenatal CHF secondary to PAT appear to develop CHF from multiple PATs recurring at relatively long cycle lengths (slow heart rates), whereas postnatal CHF neonates develop heart failure symptoms during a sustained tachycardia episode with relatively short cycle lengths (fast heart rates).

Edema↗
PubMed1992

Myocardial protection of neonatal heart by cardioplegic solution with recombinant human superoxide dismutase.

The effectiveness of high-potassium cardioplegic solution in the neonatal heart remains controversial. Our previous study indicated that the protection afforded by a cardioplegic solution was inadequate in the neonatal heart. On the hypothesis that oxyradicals were responsible for the ineffectiveness of cardioplegic solution in neonatal heart, the effects of a cardioplegic solution (a modified St. Thomas' Hospital cardioplegic solution) with recombinant human superoxide dismutase on the isolated perfused neonatal guinea pig hearts (within 2 days after delivery, body weight of 60 to 120 g) were studied in comparison with those on the adult hearts (6 to 8 weeks after delivery, body weight of 300 to 500 g). After arrest induced by modified St. Thomas' Hospital cardioplegic solution, hearts were subjected to 120 min of ischemia at 20 degrees C, during which time the cardioplegic solution was injected every 30 minutes. Then the heart was reperfused for 60 minutes at 37 degrees C. Under this condition, the left ventricular developed pressure recovered to 84.4% +/- 4.0% of the preischemic value in the adult heart, whereas the recovery was only 68.1% +/- 3.1% in the neonatal heart. Thiobarbituric acid-reactive substance level, a parameter of lipid peroxidation by oxyradicals, significantly increased during ischemic arrest both in the adult and neonatal heart. However, the increase was much greater in the neonatal heart than in the adult. Cardioplegia with recombinant human superoxide dismutase (300 and 1,000 U/mL) significantly inhibited this accumulation of thiobarbituric acid-reactive substance in the neonatal heart; at 1,000 U/mL, the myocardial function of the reperfused neonatal heart recovered to the level of the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Neonatal myocardium resists reperfusion injury.

The response of neonatal myocardium to ischemia and reperfusion was observed in an isolated working heart model using neonatal rabbits and compared to that of the adult rabbit heart. Lipid peroxidation occurring during ischemia and that occurring during reperfusion were evaluated separately. Malondialdehyde (MDA) in heart tissue was measured as an index of lipid peroxidation, and the occurrence of oxygen free radical damage was assessed by the effects of the scavengers, superoxide dismutase and catalase, on MDA production. Baseline MDA levels were similar in neonatal and adult hearts, were changed little by treatment with normoxic cardioplegia, and were elevated in both groups by treatment with hyperoxic cardioplegia. Thus, the degree of lipid peroxidation during ischemia is similar in neonatal and adult hearts. After 10 min of retrograde reperfusion subsequent to treatment with anoxic cardioplegia, the MDA content of adult hearts was significantly greater than that of similarly treated neonatal hearts. Addition of free radical scavengers to the reperfusion medium lowered the MDA content of adult hearts significantly, but not to the level of neonatal hearts. After 60 min of reperfusion subsequent to hyperoxic cardioplegia, adult hearts had higher MDA than neonates; addition of scavengers to the cardioplegia did not lower the MDA significantly in either group. Only 5 of 12 adult hearts recovered function after hyperoxic cardioplegia, while all 12 neonatal hearts recovered. Our results indicate that neonatal myocardium suffers less damage from oxygen-centered free radicals during reperfusion than does adult myocardium.

Aging↗
PubMed1986

Comparison of respiratory effects of intravenous adenosine in neonatal and adult rabbits.

We administered adenosine by repeated intravenous bolus doses to 34 neonatal rabbits in a dose of 120 micrograms X kg-1 (which we had previously found to stimulate respiration in adult rabbits). In 13 neonatal animals adenosine produced transient respiratory depression. In 15 neonatal animals the change in respiration in response to adenosine did not reach statistical significance. In two animals a transient increase in respiration occurred in response to adenosine. In the neonatal group as a whole intravenous adenosine significantly depressed ventilation. In eleven of the animals studied as neonates, respiratory responses to adenosine were again studied in adulthood. In 10 animals respiratory stimulation occurred in response to adenosine. In the adult group adenosine significantly increased ventilation, in contrast to its effects in the neonatal group. The respiratory effects of intravenous adenosine have not been previously described in neonatal animals. Respiratory stimulation produced by intravenous adenosine in adult rabbits contrasts with the respiratory depression commonly seen in neonatal rabbits in this study. It is suggested that altered responses to adenosine may be involved in the difference between the ventilatory response to hypoxia in adult and neonatal animals.

Adenosine↗
PubMed1995

Term early-onset neonatal seizures: obstetric characteristics, etiologic classifications, and perinatal care.

OBJECTIVE: To describe obstetric characteristics and etiologic classifications and assess perinatal care in term neonates with early-onset seizures. METHODS: We performed a retrospective review of neonatal and obstetric records of neonates delivered at term with a diagnosis of early-onset seizures between January 1981 and December 1992 at Long Beach Memorial Medical Center. Data regarding obstetric characteristics and etiologic classifications of the seizures were abstracted from the medical records. Lack of antepartum testing in high-risk patients, delayed intervention with nonreassuring antepartum or intrapartum fetal heart rate patterns, birth trauma, and failure to use prophylactic antibiotics or treat infection were the criteria used for identifying seizures that were potentially preventable. RESULTS: Forty term neonates had early-onset seizures out of 60,712 live births (0.07%). These seizures were attributed to hypoxic events in 15 neonates (37.5%), cerebral malformations in seven (17.5%), cerebral infarcts in seven (17.5%), intracranial hemorrhage in five (12.5%), infection in three, and an unknown etiology in three. Twenty-three neonates had 5-minute Apgar scores of 7 or greater (cerebral malformations excluded). Seven of these neonates (30%) had cerebral infarcts. A review of all records identified nine cases (22.5%) of the early-onset seizures as potentially preventable. CONCLUSION: The majority of the term early-onset neonatal seizures identified did not appear to be preventable. Many of the neonates with 5-minute Apgar scores of 7 or greater had cerebral infarcts.

Adult↗
PubMed1996

Acyclovir prophylaxis in late pregnancy to prevent neonatal herpes: a cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of oral acyclovir prophylaxis in late pregnancy to the current strategy of cesarean delivery for genital herpes lesions in the prevention of neonatal herpes transmission from mothers with recurrent genital infections. METHODS: Decision analysis was used to evaluate the clinical outcomes and direct costs of a prevention program from the health care payer's perspective. Probabilities were obtained from the literature and experts. Cost data were based on hospital costs and a cohort of herpes-infected neonates. RESULTS: Acyclovir prophylaxis during late pregnancy followed by cesarean delivery for genital lesions at delivery in women with recurrent genital herpes requires 1818 women to follow this strategy to prevent one neonatal infection and 7.4 women to take acyclovir to prevent one outbreak of genital herpes at delivery, at a cost (above no intervention) of over $493,000 per neonatal infection prevented, $1.1 million per neonatal death or disability prevented, and $1444 per maternal outbreak prevented. Cesarean delivery for genital herpes lesions requires 386 women with recurrent herpes to undergo cesareans to prevent one neonatal infection, at a cost of more than $1.3 million per neonatal infection prevented and more than $3 million per neonatal death or disability prevented. If acyclovir is given and herpes lesions still occur, the incremental cost of requiring cesarean delivery for these women over vaginal delivery with culture and follow-up of exposed infants is more than $1.4 million per neonatal infection prevented. CONCLUSION: Oral acyclovir prophylaxis in late pregnancy for women with recurrent genital herpes is more cost-effective than the current strategy of cesarean delivery for all women presenting with genital herpes lesions.

Acyclovir↗
PubMed1993

Phorbol ester- and glutamate-sensitive phosphorylation of hippocampal membrane proteins from adult and neonatal rats.

The phosphoinositide (PI) second messenger system in the neonatal rat brain is differentially stimulated as compared to that of the adult by agonists such as glutamate. Among the factors that might contribute to the neonatal pattern is the nature of phosphorylated membrane-bound proteins which could regulate this receptor-mediated response. This study was undertaken to compare membrane protein phosphorylation under conditions that affect PI hydrolysis in neonatal and adult rat hippocampus. Two-dimensional gel analysis revealed enhanced basal phosphorylation of two membrane proteins (M(r): 46,000 and 80,000; pI: 4.4 and 4.2, respectively) in the neonatal hippocampus when compared to the adult. The former phosphoprotein is present only in neonatal hippocampus. Phosphorylation of a 48,000 M(r) protein with a pI of 4.5 is prominent in hippocampal membranes from both neonatal and adult rats. After incubation of neonatal hippocampal slices with an active phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), all three proteins show decreased post-hoc phosphorylation. Slices from neonatal rats incubated with glutamate demonstrated no alteration in the phosphorylation of any of these proteins, while those from adult rats produced a marked change in phosphorylation of the 80,000 M(r) protein. The data suggest that phosphorylation of this protein from neonates is not yet as efficiently coupled to receptor stimulation as that from the adult. Immunoblot analysis revealed that the 48,000 M(r) protein is the growth-associated protein B-50/GAP-43 and that the 80,000 M(r) protein is a membrane-associated form of the MARCKS protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat.

Effects of neonatal toluene exposure (80 ppm, day 1-7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using alpha-methyl-p-tyrosine methyl ester hydrochloride (alpha MT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the alpha MT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradrenaline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood.

Administration, Inhalation↗