Multistate case-control study of maternal risk factors for neonatal group B streptococcal disease. The Active Surveillance Study Group

Risk factors for early onset disease (EOD) caused by Group B streptococci (GBS) that are the foundation of prevention guidelines were identified in studies conducted in a few hospital centers. We investigated cases of EOD identified through laboratory-based active surveillance during 1991 and 1992 in a multistate population of 17 million. Ninety-nine cases were compared with 253 controls matched for hospital, date of birth and birth weight. Prematurity (< 37 weeks of gestation) was present in 28% of cases; 53% of case mothers had rupture of membranes > 12 hours; and 48% reported intrapartum fever. The incidence of EOD in each surveillance area was higher among blacks. By multivariate analysis, case mothers were more likely than controls to have rupture of membranes before labor onset (adjusted odds ratio 8.7, P < 0.001), intrapartum fever (adjusted odds ratio 11.9, P < 0.001), and history of urinary infection during pregnancy (adjusted odds ratio 4.3, P < 0.05). Young maternal age was also associated with risk of disease. Three-fourths of case mothers had intrapartum fever, < 37 weeks of gestation and/or prolonged rupture of membranes, indicators previously used to select high risk women for intrapartum chemoprophylaxis. Our findings extend data from single hospitals and suggest prenatal screening and selective intrapartum chemoprophylaxis of high-risk mothers could potentially prevent the majority of EOD in the United States.     

Case-control study of intrapartum care, cerebral palsy, and perinatal death

OBJECTIVE: To investigate the relation between suboptimal intrapartum obstetric care and cerebral palsy or death. DESIGN: Case-control study. SETTING: Oxford Regional Health Authority. SUBJECTS: 141 babies who subsequently developed cerebral palsy and 62 who died intrapartum or neonatally, 1984-7. All subjects were born at term of singleton pregnancies and had no congenital anomaly. Two controls, matched for place and time of birth, were selected for each index case. MAIN OUTCOME MEASURES: Adverse antenatal factors and suboptimal intrapartum care (by using predefined criteria). RESULTS: Failure to respond to signs of severe fetal distress was more common in cases of cerebral palsy (odds ratio 4.5; 95% confidence interval 2.4 to 8.4) and in cases of death (26.1; 6.2 to 109.7) than among controls. This association persisted even after adjustment for increased incidence of a complicated obstetric history in cases of cerebral palsy. Neonatal encephalopathy is regarded as the best clinical indicator of birth asphyxia; only two thirds (23/33) of the children with cerebral palsy in whom there had been a suboptimal response to fetal distress, however, had evidence of neonatal encephalopathy; these 23 formed 6.8% of all children with cerebral palsy born to residents of the region in the four years studied. CONCLUSION: There is an association between quality of intrapartum care and death. The findings also suggest an association between suboptimal care and cerebral palsy, but this seems to have a role in only a small proportion of all cases of cerebral palsy. The contribution of adverse antenatal factors in the origin of cerebral palsy needs further study.     

A new collection method for the evaluation of nasal mucus proteins

BACKGROUND: Although it is generally recognized that poverty and depression can coexist among single parents receiving social assistance, there is insufficient research on this topic. The goals of this study therefore were to investigate the prevalence, correlates and health care expenditures associated with depression among sole-support parents receiving social assistance. METHODS: Sole-support parents who had applied for social assistance in 2 regions of southwestern Ontario were included in the study. Depression was diagnosed with the 1994 University of Michigan Composite International Diagnostic Interview short forms. RESULTS: The 12-month prevalence rate of depressive disorder among the parents interviewed was 45.4% (345/760). A total of 247 (32.5%) had major depressive disorder alone, 19 (2.5%) had dysthymia, and 79 (10.4%) had both major depressive disorder and dysthymia ("double depression"). Those with major depressive disorder, particularly double depression, had significantly higher rates of coexisting psychiatric disorder than those without depressive disorders. Parents with depression reported higher rates of developmental delay and behaviour problems in their children than parents without depression. Expenditures for health care services were higher for parents with depression and for their children than for parents without depressive disorder and their children. INTERPRETATION: Single parents receiving social assistance have high rates of depression. Such parents with depression also have higher rates of other psychiatric disorders and higher expenditures for health care services, and their children have higher rates of developmental delay and behaviour problems.     

Surveillance of developmental disabilities with an emphasis on special studies

The developing central nervous system seems to be particularly vulnerable to chemical insults. A model for developmental disabilities surveillance is presented that provides a reasonable framework for monitoring the prevalence of various developmental abnormalities in human populations. Effective monitoring will not only increase the likelihood of detecting the adverse effects of new physical or chemical agents in the environment but will provide a readily available case series for specially directed case-control studies. A specific example is provided of a large case-control study of cerebral palsy and intrapartum magnesium exposure among very low birth weight children, which is being conducted within the framework of a developmental disabilities surveillance program.     

Prevention of parasitic infections (excluding toxoplasmosis) in immunocompromised patients

Fracture frequency was studied in 107 hypopituitary patients with GH deficiency (GHD) (69 men, mean age 53 years, range 18-74 and 38 women, mean age 54 years, range 31-73). Routine hormonal replacement therapy was given, except GH. Five male patients and 15 female patients with untreated hypogonadism were allocated to a separate group. The mean duration of hypopituitarism was 13.4 years. The prevalence of a history of fractures was assessed using questionnaires. A subsample of the G?teborg WHO MONICA Project was used as a reference population (n = 323). The total fracture frequency was threefold higher (P < 0.001) in patients (24.1%) compared with controls (8.7%) (odds ratio 3.49) (1.85-6.56; 95% confidence intervals). In men (n = 64) the fracture frequency was 25.0%, compared with 7.8% among the controls (P < 0.001). In women (n = 23) the fracture frequency was 21.7%, compared with 9.5% among the controls (P = 0.08). The odds ratios for fracture frequency were 3.97 (1.81-8.40; 95% confidence intervals) and 2.64 (0.89-7.81; 95% confidence intervals) in men and women respectively. In conclusion, adult hypopituitary patients with GHD had a threefold increased fracture frequency compared with controls. Further studies are needed to ascertain whether long-term recombinant human GH treatment can reduce the fracture rate in hypopituitary patients with GHD.     

Low birthweight and neuromotor development: a population based, controlled study

The aims of the study were to investigate: (a) the relationship between low birthweight (LBW) and pre-school neuromotor development; and (b) the predictive value of various pre-, peri-, and neonatal factors for neuromotor development in LBW pre-school children. A population based sample of 144 5-year-old LBW children (birthweight < 2000 g) with no major handicaps was compared with a random sample of 163 normal birthweight term controls. Using the Peabody Developmental Motor Scales, impaired performance on the balance scale was seen more often in LBW boys than in controls (odds ratio 5.5, 95% CI 1.5-20.3), while performance on the eye-hand coordination and locomotor scales was comparable for the two groups. LBW girls were comparable to controls on all these scales. On neurological examination, an increased frequency of minor neurological signs was found in LBW boys, while increased ankle tone and/or leg hyperreflexia was more common in LBW girls compared to controls. Small head circumference at birth was associated with an increased frequency of minor neurological signs in LBW boys, and lack of breastmilk in the neonatal period with impaired balance in LBW boys. None of the other pre-, peri- or neonatal factors were predictive of neuromotor development. We conclude that motor functions essential for daily activities are intact in most LBW preschoolers.     

The psychological development of children of epileptic parents. II. The differential impact of intrauterine exposure to anticonvulsant drugs and further influential factors

After obtaining evidence that tetratogenic effects were operant in a sample of children born to epileptic mothers, we analyzed the effects of type of medication and further influential factors. Children with prenatal exposure to polytherapy had significantly lower scores than controls for a large number of psychological tests. In addition to polytherapy, there were even stronger effects of socioeconomic status and sex was found to be less influential than polytherapy. Among further epilepsy variables, only seizure frequency of the mother during pregnancy had a modest impact on the child's developmental outcome, whereas a score of obstetric abnormality was less effective in predicting developmental outcome, as measured and defined by various standardized psychological tests.     

Physical disability, physical attractiveness, and social outcomes in children's small groups.

Examined the sociometric status of children with obvious physical handicaps in an integrated (approximately 70% Black, 20% Puerto Rican, and 10% White) summer camp setting containing 61 girls (aged 7.5–14 yrs) and 60 boys (aged 7.75–14 yrs). 23% of Ss had obvious physical handicaps (e.g., spinal injuries, limb deformities), and 33% had some form of chronic illness or physical condition (e.g., sickle cell anemia, pulmonary insufficiency). Ss were interviewed during the 3rd wk of camp on questions concerning who they liked best in their groups and how they made friends. In addition, 12 male and 12 female children from neighboring camps were shown full-body photographs of all Ss and asked to rate them for attractiveness. Results indicate that handicapped Ss were less preferred as friends than their able-bodied peers. Physical attractiveness was also related to sociometric standing, as well as to the presence or absence of a physical handicap. An analysis of the relationship between physical attractiveness and social status for Ss alone indicated that these variables were significantly related for this group. Significant differences were found between obviously handicapped and able-bodied Ss on a knowledge-of-friend-making task; but among the latter group, role-play scores did not differentiate high- from low-status Ss. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternal zinc indices and small babies

Recent studies have shown that the persistence of the cavum septi pellucidi beyond the neonatal period is a marker of cerebral dysgenesis. It has been suggested that the finding of a persistent cavum vergae is also a marker of disturbed brain development. In order to investigate this hypothesis we reviewed 161 brain magnetic resonance imaging scans from normal individuals for the presence of cavum septi pellucidi or cavum vergae, or both. In the 34 prospectively obtained normal adults, there were no individuals with either a cavum septi pellucidi or cavum vergae. In the "defined" normal subjects 3 of 127 individuals (2.4%) had a cavum septi pellucidi whereas a cavum vergae was noted in 26 of 127 (20.5%). We next reviewed the neuroimaging studies of 249 children and adults evaluated for mental retardation or developmental delay. A cavum septi pellucidi was found in 38 of 249 (15.3%) and a cavum vergae in 48 of 249 (19.3%) of these patients. A cavum septi pellucidi and cavum vergae were found together in 19 of 249 (7.6%). We interpret these data as showing that the cavum septi pellucidi is rarely seen in normal individuals although the cavum vergae is seen with the same frequency in normal and retarded populations. Thus we conclude that the cavum septi pellucidi serves as a significant marker of cerebral dysfunction manifested by neurodevelopmental abnormalities while the cavum vergae alone does not identify individuals at risk for cognitive delays.     

Prevalence of intracranial lesions in children initially diagnosed with disconjugate nystagmus (spasmus nutans)

A small number of children who develop disconjugate nystagmus, torticollis, and head titubation (spasmus nutans) have been found to have optic chiasm or third ventricle gliomas. However, the prevalence of glioma or other developmental abnormalities in this disorder is unknown because no large series of spasmus nutans cases has previously been reported. A reviewer of the records of 67 consecutive children initially diagnosed with spasmus nutans and followed for an average of 3.3 years at the St Louis Children's Hospital revealed the following: 61% had a history of prematurity, developmental delay, or other systemic abnormality; strabismus, most commonly infantile esotropia, developed in 55%; 43% had neuroimaging studies; and 0% had evidence of a glioma or showed signs of tumor on follow-up examinations. From this consecutive patient series, we estimate the prevalence of tumor in spasmus nutans to be less than 1.4%. Without other evidence of an intracranial mass lesion, neuroimaging of infants initially diagnosed with spasmus nutans may not be immediately warranted.     

The molecular basis of beta thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated alpha-globin loci

We have analysed 201 beta-thalassaemia (beta-thal) genes from natives of the Punjab (156) and Maharashtra states of India and found the causative mutation in 200 of them. The most common beta-globin gene mutations differed significantly between these two groups and between these groups and Indian immigrants in the U.S.A. and the U.K. In the Punjabi Indians the IVS-1, nt 1 (G-T) mutation accounted for nearly one-quarter of beta-thal genes, whereas it was 5% or less in the other groups. Likewise, the cap + 1 mutation was much more prevalent in the Punjabis, whereas the nonsense codon 15 allele had a higher frequency in the Maharashtrans of the Bombay region. The common IVS-1, nt5 allele had a frequency of 60% of beta-thal genes in the Maharastrans, 35% in North American immigrants, and only 23% in the Punjabis. Two-thirds of all beta-thal genes in Punjab were found in the merchant caste (Khatri-Arora), whereas the menial caste (Shudra) was highly represented among those with beta-thal genes in Maharashtra. Two novel beta-globin alleles were each found once; a frameshift codon 55 (+A) in Maharashtrans and a frameshift codons 47-48 (+ATCT) in Punjabis. Of three Punjabi patients with beta-thal intermedia in whom only a single severe beta-globin gene mutation was found, two had six alpha-globin genes (homozygosity for a triplicated alpha-globin locus) instead of the normal alpha-globin gene number of four. Thus, these two individuals had a multilocus aetiology of beta-thal and their parents have the unusual recurrence risk of 1 in 8 for conceiving a third with beta-thal intermedia. Since 15% of 126 alpha-globin clusters studies in Punjabis contained either single (10%) or triplicated (5%) alpha-globin genes, the alpha-globin gene number is a frequent modifier of the phenotype of beta-thal in this ethnic group.     

Procedural memory system supports single cue trace eyeblink conditioning in medial temporal lobe amnesia.

A number of studies investigating trace eyeblink conditioning have found impaired, but not eliminated, acquisition of conditioned responses (CRs) in both animals and humans with hippocampal removal or damage. The underlying mechanism of this residual learning is unclear. The present study investigated whether the impaired level of learning is the product of residual hippocampal function or whether it is mediated by another memory system that has been shown to function normally in delay eyeblink conditioning. Performance of bilateral medial temporal lobe amnesic patients who had a prior history of participating in eyeblink conditioning studies was compared to a control group with a similar training history and to an untrained control group in a series of single cue trace conditioning tasks with 500 ms, 250 ms, and 0 ms trace intervals. Overall, patients acquired CRs to a level similar to the untrained controls, but were significantly impaired compared to the trained controls. The pattern of acquisition suggests that amnesic patients may be relying on the expression of previously acquired, likely cerebellar based, procedural memory representations in trace conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Current status of neonatal screening for congenital adrenal hyperplasia

Randomized trials are the optimal approach for evaluations of treatment efficacy but may not always be feasible. We study the adequacy of the case-control design in evaluating efficacy in a situation where the investigated therapy, namely the administration of magnesium sulfate for the prevention of eclampsia in patients with preeclampsia, has a suspected strong protective effect. A total of 66 cases of eclampsia were ascertained from among deliveries occurring between 1977 and 1992 at two hospitals in Houston, Texas. Randomly selected preeclamptic controls were matched to cases based on hospital and month of delivery. Magnesium sulfate administration prior to seizure occurrence had a strong protective effect against eclampsia in patients with preeclampsia (OR, 0.02; 95% CI, 0.01-0.05). This protective effect remained when controls were stratified by the degree of severity of preeclampsia (mild-to-moderate OR, 0.03, 95% CI, 0.01-0.09 and severe OR, 0.005; 95% CI, 0.0005-0.04) and when cases were stratified by the timing of the first seizure (antepartum and intrapartum seizures OR, 0.01; 95% CI, 0.003-0.05 and postpartum seizures OR, 0.03; 95% CI, 0.005-0.15). The effect also remained after adjustment for other important predictors in a multivariate logistic regression model (OR, 0.11; 95% CI, 0.03-0.38). The results of this study are in support of a recent randomized trial on the efficacy of magnesium sulfate as a prophylactic agent against eclampsia. Although there are serious potential sources of bias in this study, the magnitude of the protective effect of magnesium sulfate minimizes the likelihood that this effect can be explained by bias. Observational studies could be appropriate complements or alternatives to randomized trials in situations where a strong treatment effect is expected.     

High prevalence of bihemispheric structural and functional defects in Sturge-Weber syndrome

Abnormal cerebral venous drainage is associated with hypoxia and glucose deprivation, which can account for progressive neurologic deterioration in Sturge-Weber syndrome. Although developmental delay is common in Sturge-Weber syndrome, bihemispheric calcification is uncommon. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to study the neuroanatomy, while single photon emission computed tomography (SPECT) was used concurrently to evaluate perfusion and glucose metabolism using 99mTc hexamethylpropyleneamine oxime (HMPAO) and [18F] fluorodeoxyglucose (FDG), respectively. Ten patients (10 to 22 years of age) with previously diagnosed Sturge-Weber syndrome, port-wine nevi, and clinical evidence of seizures or stroke-like episodes were studied. Five children with onset of seizures in the first year of life had overall clinical severity comparable to that of children with later-onset seizures. Calcification was present in both hemispheres in one patient; six additional patients had other radiologic evidence of bihemispheric disease; SPECT studies detected bihemispheric disease in four cases. Our study is the first to concurrently evaluate structure, perfusion, and glucose metabolism in Sturge-Weber syndrome and to show a mismatch between functional and structural brain imaging in both cerebral hemispheres. Widespread abnormalities of cerebral perfusion and glucose metabolism might explain the high prevalence of developmental delay associated with Sturge-Weber syndrome. Longitudinal studies are needed to define better the natural history of neurologic deterioration and radiologic progression that relates to central nervous system circulatory dysfunction in Sturge-Weber syndrome.     

What do we know about children who fail to thrive?

It is the aim of this article to provide an overview of difficulties in children with poor growth enrolled in an intensive community intervention trial for failure to thrive (FTT). Children were assessed for developmental delay (Bayley test), inadequate diet, iron deficiency, eating and other behavioural problems, and maternal anxiety and depression (HAD Scales). Sixty-three children aged 6 months to 2 1/2 years were studied. The majority of children were from families living in poverty with many from divorced, separated or single families. On developmental testing (Bayley Developmental Scales) 55% were delayed, 27% severely. Seventy-seven per cent had caloric intakes below the expected average requirement (EAR) with 19% reported at less than 50% of requirements. Iron intakes were similarly low and one-third had iron deficiency anaemia on testing. Sixty per cent of children were reported to have eating difficulties, principally in terms of responding negatively to food. Eating difficulties had commonly presented within the first weeks of life. Other behavioural and sleeping difficulties were also common. Children identified as failing to thrive in the community are likely to have associated developmental, dietary and behavioural problems which may not be immediately evident and to an extent which may require intensive multidisciplinary involvement.     

Repeated administration of alpha-hederin results in alterations in maternal zinc status and adverse developmental outcome in the rat

The administration of alpha-hederin, an inducer of metallothionein, results in a secondary zinc deficiency that may be an important maternally mediated mechanism of developmental toxicity. Previous studies have shown adverse developmental outcome with a single administration of alpha-hederin to rats on gestation day (GD) 8 or 11. The objective of this study was to determine whether dosing of alpha-hederin throughout organogenesis would result in a sustained elevation of maternal hepatic metallothionein and subsequent developmental abnormalities. Rats were administered dosage levels of 0 (vehicle only), 20, or 30 mumol/kg from GD 6-15. Maternal hepatic metallothionein levels were 10-fold higher on GD 16 in the treatment groups than the controls. Consequently, liver zinc concentrations increased 60% and 54%, whereas plasma levels decreased 23% and 33% in the 20 and 30 mumol/kg treatment groups, respectively. At GD 20, mean fetal weights of the treatment litters were 11% less than control litters. The administration of alpha-hederin resulted in a threefold increase in the number of offspring that exhibited developmental abnormalities, including visceral and skeletal malformations. Following an oral pulse of 65Zn subsequent to treatment with 0 or 20 mumol/kg of alpha-hederin, the distribution of 65Zn to the liver of treated dams was twice that of controls, whereas the radiolabeled zinc apportioned to the decidua and uterus decreased by 44%. Furthermore, the 65Zn detected in the embryos from treated dams was 70% lower than in embryos from control dams. In conclusion, low doses of a metallothionein inducer administered to the dam from GD 6-15 resulted in a sustained elevation of hepatic metallothionein and a subsequent redistribution of zinc leading to a decrease in the zinc available to the embryo and ultimately to adverse development of the offspring. Repeated dosing throughout organogenesis, as required in regulated safety assessment testing, increased the severity of the effects previously observed with single large dosages of the toxicant administered during midgestation.     

Penile trauma: an etiologic factor in Peyronie's disease and erectile dysfunction

PURPOSE: It has been postulated that trauma to either the partially or fully erect penis is a potential cause of Peyronie's disease. In addition, it has been proposed that engaging in sexual relations with a partial erection due to mild impotence is a risk factor for the development of Peyronie's disease. This study was performed to determine whether patients with either Peyronie's disease or non-Peyronie's disease impotence had an increased rate of penile trauma compared with potent controls. MATERIALS AND METHODS: We mailed surveys to 207 men who had been seen for management of Peyronie's disease, 250 impotent men without Peyronie's disease, and 275 age-matched urologic patients without a history of either impotence or Peyronie's disease. The survey inquired whether the individual had a history of penile trauma to the flaccid or erect phallus or injury during sexual intercourse. In addition, patients were questioned whether they had been engaging in sexual relations with a partial erection. RESULTS: The mean age of the impotent patients was slightly less than both the Peyronie's disease patients and controls. A similar response rate to the survey was found among the 3 groups. The mean duration of illness was 6 years for Peyronie's disease and 10 years for impotence. The frequency of penile trauma of any kind was significantly greater in both the Peyronie's disease (40%) and impotence (37%) patients than in the controls (11%). There was no significant difference between the Peyronie's disease and impotence groups. However, the Peyronie's disease patients had a lower frequency of attempting sexual relations with a partial erection than the 2 other groups. CONCLUSIONS: The results of this survey demonstrate a significantly higher incidence of penile trauma in both impotent patients and patients with Peyronie's disease compared with controls. This study demonstrates an association between penile trauma and both Peyronie's disease and impotence. The reduced incidence of engaging in sexual relations with a partial erection among the Peyronie's disease patients implies that partial impotence is not a predisposing factor for Peyronie's disease.     

Cardiac performance during insulin clamp: its evaluation by bioimpedance measurement

OBJECTIVE: The objective of this study was to know the most common organisms causing neonatal meningitis in a defined region of southern Madrid, the developmental outcome of these babies and the risk factors associated with the prognosis. PATIENTS AND METHODS: This was an observational study of 56 cases of meningitis diagnosed in our Neonatal Service between 1988 and 1994. In order to study the handicaps of these babies, only those who were born before May 1993 were considered so that they had a corrected age of at least 2 years when the neurological evaluations were done. RESULTS: The most common causative organisms were group B Streptococcus (27%), E. coli (11%) and enteroviruses (9%). In the premature infants the leading organisms were E. coli and Candida albicans. The age at diagnosis was 8 +/- 6 days in the group of preterm infants (p = 0.002). The mortality was associated with the prematurity (risk ratio: 17.8), the isolation of a gram-negative organism in the cerebral fluid (RR: 3.3) and the presence of abnormal findings in cerebral ultrasound studies (RR: 12.7). Sequelae were associated with the presence of abnormal findings in cerebral ultrasound studies (RR: 24.7) or in the neurologic examination (R: 7) and with the presence of previous cerebral lesions (RR: 5.7). CONCLUSIONS: Neonatal ultrasound examination, as well as the gestational age, the causative organisms, the presence of a previous cerebral lesion and the neurological examination, seem to be very important in predicting the prognosis of these babies.     

Increasing hypnotic susceptibility by brain wave feedback.

Presents a reanalysis of earlier studies by D. R. Engstrom et al (1970) as well as additional findings which show that successful training to increase alpha rhythm duration raises people's hypnotic susceptibility. Ss in the previous studies were 30 volunteers who had low to moderate hypnotic susceptibility and low alpha production. It was found, subsequent to publication, that some Ss had had previous exposure to alpha training. When they were eliminated in reanalysis, the previous findings were still confirmed; alpha training was more effective for experimental than for control Ss, and hypnotic susceptibility accordingly increased more among experimentals than among controls. In addition, base-rate alpha production in each training session was correlated with feedback alpha output among experimental Ss but not among controls. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tissue specificity of spontaneous point mutations in lambda supF transgenic mice

Abuse of nitrite inhalants, widespread among male homosexuals, has been identified by epidemiological studies as an independent risk factor for AIDS and for Kaposi's sarcoma. Subchronic exposure of mice to inhaled isobutyl nitrite was previously found to impair the tumoricidal activity of peritoneal macrophages. Because inhalants would be expected to have the greatest effects on cells in the lung, alveolar macrophages from exposed mice were examined in this study. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 min/day for 14 days. Following this treatment, the lungs of exposed mice had large increases in cellularity, both in the alveolar septa and within the alveoli. Bronchoalveolar lavages also contained increased numbers of cells. Alveolar macrophages collected from treated mice had increased tumoricidal activity compared with controls and produced higher levels of inducible nitric oxide and tumor necrosis factor-alpha (TNF-alpha). The frequency of alveolar cells secreting TNF-alpha was increased ninefold in mice exposed to the inhalant. Cell influx into the lung, as indicated by the presence of red blood cells in lung lavages, was evident after only a single 45-min exposure to inhaled isobutyl nitrite at doses as low as 300 ppm.