Developmental stages and estimated prevalence of coexisting mental health and neurodevelopmental conditions and service use in youth with intellectual disabilities, 2011-2012.

BACKGROUND: Few studies exist on mental health and neurodevelopmental conditions and service use among youth with intellectual disabilities (IDs), which makes it difficult to develop interventions for this population. The objective of the study is to (1) estimate and compare the prevalence of mental health and neurodevelopmental conditions in youth with and without ID across three developmental stages and (2) estimate and compare mental health service use in youth with and without ID across three developmental stages. METHODS: We conducted secondary data analysis using cross-sectional data collected from caregivers completing the 2011-2012 National Survey of Children's Health. The data set represents a nationally representative sample of youth (0-17 years) in the USA with one child from each household being randomly selected. Data were collected from caregivers in 50 states, Washington D.C. and the US Virgin Islands. We restricted the sample to parents of youth between 3-17 years (N = 81 510). RESULTS: Compared with youth without ID, youth ages 3-17 with ID had a statistically significantly higher prevalence of (1) mental health and neurodevelopmental conditions and (2) mental health care use and medication use for mental health and neurodevelopmental issues (other than attention deficit disorder/attention deficit hyperactivity disorder). Clinically significant differences in coexisting conditions and service use were also found across developmental stages. CONCLUSIONS: Youth with ID are at greater risk of having coexisting mental health and neurodevelopmental conditions than youth without ID and are more likely to receive treatment. Therefore, clinicians should consider mental health and neurodevelopmental conditions and the unique needs of youth by developmental stage when tailoring interventions for youth with ID.

Relation between mothers' types of labor, birth interventions, birth experiences and postpartum depression: A multicentre follow-up study.

AIM: This definitive and cross-sectional study was conducted to determine the relation between mothers' types of labor, birth interventions, birth experiences and postpartum depression. METHODS: A total of 1010 mothers who gave birth in four different provinces of Turkey were chosen to participate in the study via purposive sampling method Results: The Edinburgh Postpartum Depression Scale score was determined to be 13 and over in 36.4% of the women. In this study, it was determined that the Edinburgh Postpartum Depression Scale scores for women in the 18-24 age group who had a vaginal birth, did not have health insurance, experienced health problems during pregnancy and were not trained about type of labor during pregnancy were statistically higher. There was no significant correlation between the birth experiences and postpartum depression. The linear regression model showed that there was a statistically significant correlation between enema and amniotomy interventions practised during the birth and the Edinburgh Postpartum Depression Scale scores. CONCLUSION: In conclusion, it is thought that preparing the mothers for birth with birth preparation training in the antenatal period and imposing the necessary regulations in the delivery room for the mothers to have a positive birth experience are important in reducing postpartum depression risk.

A morphological study of uterine alterations in mice due to exposure to cadmium.

We investigated the morphologic and molecular effects of exposure to cadmium (Cd) for 30 and 60 days on the uteri of mice. We assessed uterine morphometric measurements, eosinophilia, mast cell numbers, endometrial apoptosis, proliferation and estrogen receptor alpha (ERα) immunoreactivity. We examined vaginal smears that reflected the hormonal alterations in the female reproductive tract. Because the female reproductive tract exhibits different morphology at each stage of the estrous cycle, we sacrificed all animals at estrus to make appropriate comparisons. Female BALB/c mice were exposed to 200 ppm Cd in their drinking water for either 30 or 60 days. Cd exposure caused significant decreases in endometrial thickness and number of glands in estrus phase uteri. The endometrial eosinophilia in the groups exposed to Cd also decreased compared to controls. Cd exposure increased the number of mast cells. Luminal and glandular epithelia were examined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and by immunostaining proliferating cell nuclear antigen (PCNA) and estrogen receptor α (ERα). Compared to controls, the apoptotic index increased with time in both Cd exposed groups, while the proliferation index decreased. ERα immunoreactivity was decreased in both Cd exposed groups compared to controls; the decrease was most apparent in the 30 day Cd group. We found that 60 day Cd exposure increased apoptosis in the endometrium, which may affect the receptivity of the uterus for implantation.

Validity of the activPAL3 activity monitor in people moderately affected by Multiple Sclerosis.

Walking is the primary form of physical activity performed by people with Multiple Sclerosis (MS), therefore it is important to ensure the validity of tools employed to measure walking activity. The aim of this study was to assess the criterion validity of the activPAL3 activity monitor during overground walking in people with MS. Validity of the activPAL3 accelerometer was compared to video observation in 20 people moderately affected by MS. Participants walked 20-30m twice along a straight quiet corridor at a comfortable speed. Inter-rater reliability of video observations was excellent (all intraclass correlations >0.99). The mean difference (activPAL3- mean of raters) was -4.70±9.09, -4.55s±10.76 and 1.11s±1.11 for steps taken, walking duration and upright duration respectively. These differences represented 8.7%, 10.0% and 1.8% of the mean for each measure respectively. The activPAL3 tended to underestimate steps taken and walking duration in those who walked at cadences of ≤38 steps/min by 60% and 47%, respectively. The activPAL3 is valid for measuring walking activity in people moderately affected by MS. It is accurate for upright duration regardless of cadence. In participants with slow walking cadences, outcomes of steps taken and walking duration should be interpreted with caution.

Isolated language impairment as the primary presentation of sporadic Creutzfeldt Jakob Disease.

OBJECTIVES: Sporadic Creutzfeldt Jakob Disease (sCJD) is a neurodegenerative disorder that typically presents as a rapidly progressive encephalopathy associated with various neurological features, culminating in akinetic mutism and death. Atypical cases, presenting with an isolated focal may cause diagnostic confusion. We described a series of patients with sCJD presenting with isolated language impairment. MATERIALS & METHODS: We report a patient with sCJD referred to the NCJDRSU, who presented with isolated language impairment and subsequently identified all cases of sporadic CJD on the NCJDRSU database (covering the years 1990-2012) with an isolated language impairment presentation. RESULTS: Nineteen patients (11 females) with sCJD (1.19% of all patients) had an isolated language disorder of at least 2 weeks duration as the first neurological symptom pattern. Mean age at onset was 68.28 years. No specific pattern of language affection was seen in these patients. Further progression usually affected more than one neurological domain, with all patients eventually developing cognitive decline and myoclonic jerks. The median duration of illness was 4 months. CSF 14.3.3 was positive and S100b level was elevated in all patients in whom it was performed. EEG and MRI showed typical features of sCJD in six patients each. Most patients showed MM genotype of PRNP codon 129. CONCLUSION: This study highlights the fact that isolated aphasia can be the first neurological symptom approximately in 1% of patients with sCJD. The diagnosis is usually made with appearance of other clinical features and investigation results, but in a small minority, these may not be apparent for relatively long periods.

Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs phenytoin.

OBJECTIVE: To evaluate the efficacy and tolerability of the treatment with valproic acid (VPA) in patients with status epilepticus (SE) or acute repetitive seizures (ARS) comparing it with phenytoin (PHT) treatment. MATERIALS AND METHODS: Patients with SE or ARS were treated in a consecutive manner with either VPA or PHT intravenously. The primary endpoint was defined as clinical seizure cessation; the secondary endpoint was evaluation of drug tolerability. RESULTS: Seventy-four adult patients with SE or ARS participated in the study, 49 with VPA i.v. and 25 PHT i.v. In 43 (87.8%) of the VPA patients, the seizures discontinued, and no rescue medication was needed. Similar results were found in the PHT group in which seizures of 22 (88%) patients were well controlled. Side effects were found in 12% of the PHT group, and in none of the VPA group. CONCLUSIONS: VPA i.v. seems to be effective and well tolerated in adult patients with SE or ARS.

Flight-associated headaches-prevalence and characteristics.

Environmental factors in airplanes may precipitate headaches. We conducted a questionnaire-based study among consecutive travellers to determine the rate, severity and duration of flight-associated headaches (FAHA). Of the 906 eligible travellers (mean age 33.3 +/- 13.8 years), 22.3% reported headaches at least once per month. FAHA occurred in 52 travellers (5.7%), of whom 34 were women (P = 0.0023 vs. none FAHA). The duration of pain was 4.0 +/- 10.2 h after takeoff and continued for 5.7 +/- 14.2 h after landing. Migraine was diagnosed in 19.2% of those with FAHA. The magnitude of headache was 6 +/- 2 (on a scale of 1-10). Among those who suffer from FAHA, 45.4% reported that their pain was unilateral, in contrast to 72.7% among those with 'non-flight' headaches (P = 0.019). Nine travellers had headaches when descending to -400 m below sea level, and nine upon climbing to high altitude. This preliminary observation indicates that FAHA is not uncommon and should be further investigated.

Two-year evaluation of restorations of a packable composite placed in UK general dental practices.

OBJECTIVE: The aim of this study was to assess the clinical performance at two years of 100 Solitaire 2 restorations placed in five United Kingdom dental practices by members of a practice-based research group. METHOD AND MATERIALS: Restorations were assessed after two years by a trained evaluator and the dental practitioner who had placed the material, for anatomic form, marginal adaptation, surface roughness, gingival condition and the presence or absence of secondary caries. In addition, the patients completed a questionnaire requesting details of the comfort and performance of the Solitaire 2 restoration(s). RESULTS: A total of 88 (58 Class II and 30 Class I) restorations of Solitaire 2 placed in 49 patients (mean age 43 years) were assessed. Twelve restorations could not be evaluated because of patient unavailability for the dates of the examinations. Two Class II restorations (2%) had failed by the time of the two-year evaluation and the remaining 86 restorations were found to be intact with no secondary caries. A high percentage of optimal scores were recorded for anatomic form and surface roughness. The colour match of two restorations (2%) was recorded as an obvious mismatch, but otherwise no unacceptable scores were recorded. CONCLUSIONS: After two years of clinical service a high proportion (96%) of the Solitaire 2 restorations that were available for re-examination, placed in general dental practice settings, were found to be performing satisfactorily.

Neck irradiation: a risk factor for occlusive carotid artery disease.

OBJECTIVES: to determine whether irradiation is an independent risk factor for carotid atherosclerosis, and propose guidelines for patient follow-up. DESIGN: a retrospective case control study. MATERIALS AND METHODS: two groups of patients with severe carotid artery stenosis (>70%) were compared: 30 post-neck irradiation patients, and a control group of 100 patients with no history of neck irradiation. Disease location and severity were assessed by duplex. The relationship between atherosclerotic risk factors, time since irradiation and carotid artery disease was examined. RESULTS: the average age of study group patients was 67 years (43-86) compared to 69 years (46-89) in the control group. The average interval from irradiation to diagnosis was 14 years (3-53) (median 12.5 years). The study group suffered less from diabetes, ischaemic heart disease, and peripheral vascular disease ( p<0.02). There were no significant differences among risk factors with respect to age, gender, smoking, hypertension, and hypercholesterolemia. Post-neck irradiation patients had a significantly higher prevalence of bilateral disease (p=0.02), and a higher rate of common carotid artery lesions (p<0.002). CONCLUSIONS: neck irradiation should be considered a risk factor for occlusive carotid artery disease. Preoperative angiographic study should be considered, due to frequent involvement of the common carotid artery.

Carotid endarterectomy in awake patients with contralateral carotid artery occlusion.

OBJECTIVES: Patients with severe stenosis of an internal carotid artery with contralateral occlusion (ICO) are at an increased risk for stroke, and therefore surgical treatment is usually recommended. Carotid endarterectomy (CEA) under regional anesthesia enables constant monitoring of neurologic status and selective shunting in cases of clinically evident cerebral ischemia. In this study, we assess the selective use of shunts based solely on changes in neurological status in awake patients with ICO undergoing CEA as well as their complication rates. METHODS: During 1996-1998, we studied intraoperative findings and results of CEA under regional anesthesia with clinical monitoring of neurological status in two groups: (1) patients with stenosis (> 70% by NASCET) and contralateral occlusion (n = 50) and (2) patients with stenosis and no contralateral occlusion (n = 94). RESULTS: Shunt insertion was required in 42% of group 1, and 6% in group 2. All of the patients in group 1 requiring shunts had stump pressures < 50 torr. The average stump pressure of group 1(40 torr) was significantly lower than that of group 2 (75 torr), and was also lower than that of patients with severe contralateral stenosis (35 patients, 76 torr). Perioperative stroke rates were identical in both groups (2.1%). CONCLUSION: Since ICO patients are at a high risk for brain ischemia during ICA clamping, they require shunt insertion frequently. Patients with no contralateral occlusion require shunting at a much lower rate - even in the presence of severe contralateral stenosis. Regional anesthesia allows for early detection of brain ischemia and therefore, the perioperative results in both groups are similar.

The epic project: developing national evidence-based guidelines for preventing healthcare associated infections. Phase I: Guidelines for preventing hospital-acquired infections. Department of Health (England).

In 1998, the Department of Health (England) commissioned the first phase of national evidence-based guidelines for preventing healthcare associated infections. These focused on developing a set of standard principles for preventing infections in hospitals together with guidelines for preventing hospital-acquired infections (HAI) associated with the use of short-term indwelling ureteral catheters in acute care and with central venous catheters in acute care. These guidelines are systematically developed broad statements (principles) of good practice that all practitioners can use and which can be incorporated into local protocols. A nurse-led, multi-professional team composed of infection prevention practitioners, clinical microbiologists/retrovirologist, epidemiologists, and researchers developed the guidelines. A rigorous guideline development process was used to inform the systematic reviews, the clinical and critical appraisal of relevant evidence, and linking that evidence to evolving guidelines. Both general and specialist clinical practitioners were involved in all stages of developing these guidelines, as were representatives from relevant Royal Colleges, learned societies, other professional organisations and key stakeholders. The introduction to these guidelines describes a robust and validated guideline development model that can be used by others to develop future guidelines. This model is described in more detail in the associated technical reports that can be found on the project web site http://www.epic.tvu.ac.uk. Locating and appropriately using good quality evidence to inform guideline development in this field is challenging. Evidence from rigorously conducted experimental studies was frequently limited and consequently a range of other types of evidence were systematically retrieved and carefully appraised. The concluding discussion on implementation highlights potential issues for clinical governance and areas for future research and suggests issues that need to be addressed to allow practitioners to successfully incorporate these guidelines into routine clinical practice.

Quantitation and localization of pulmonary manganese superoxide dismutase and tumor necrosis factor alpha following exposure to ozone and nitrogen dioxide.

Tumor necrosis factor a (TNFalpha) and manganese superoxide dismutase (MnSOD) are thought to play critical roles in the process of lung injury, repair, and disease. The induction of TNFalpha and MnSOD were examined in a model of progressive pulmonary fibrosis along the length of the alveolar duct in rats exposed for 1, 5, and 8 weeks to a combination of 0.8 ppm ozone and 14.4 ppm nitrogen dioxide. This oxidant injury model results in a triphasic response with an initial inflammatory stage during weeks 1-3, followed by a partial resolution at weeks 4-5, and a final stage of rapidly progressive fibrosis during weeks 6-8. Changes in TNFalpha and MnSOD labeling for the proximal and distal alveolar ducts of the lungs were quantified using immunohistochemistry and morphometric techniques at 1, 5, and 8 weeks of exposure. A significant elevation in MnSOD was noted in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following 8 weeks of exposure. Labeling for TNFalpha only in the proximal region of the alveolar duct, was significantly increased in alveolar macrophages after 1 and 8 weeks of exposure, while a significant increase in TNFalpha labeling of interstitial cells in proximal regions was noted at all time points. We conclude that MnSOD is elevated in areas of focal injury as well as the more distal protected areas of the lungs, while TNFalpha correlates strongly with both the temporal and spatial aspects of greatest cellular injury in the lungs.

Phenytoin-folic acid interaction: a lesson to be learned.

A case of a patient who developed symptomatic phenytoin-induced folic acid deficiency is reported. Folate supplementation of 5 mg/d was followed by a decrease of serum phenytoin concentration to a subtherapeutic level with a breakthrough seizure. Estimation of phenytoin's Km-Vmax Michaelis-Menten pharmacokinetic parameters in this patient demonstrated that folate supplements indeed caused a significant decrease in the Km value. This decrease correlates with a greater affinity of the metabolizing hepatic enzymes for the drug, and hence, with the resultant increase in phenytoin's metabolism and decrease of its serum concentration and anticonvulsive effect. In an era of increasing knowledge of folate's pivotal role in various diseases, we call attention to this drug-vitamin interaction, and to the previously suggested recommendation that folate supplementation should be initiated whenever phenytoin therapy commences. Because folic acid dosages as low as 1 mg/d may perturbate phenytoin's metabolism, smaller deficiency preventive doses may be the advisable allowance for phenytointreated patients with normal pretreatment folate levels. This suggestion must be confirmed by a prospective study in a large cohort of patients.

Myopathy with trabecular muscle fibers.

A systematic review of muscle biopsies over a 15 year period in a large neurological hospital revealed 21 cases (7% of the total of non-inflammatory myopathies) with a distinctive pattern of myopathology and a limb-girdle clinical phenotype. The muscle pathology was dominated by a large prevalence (20-90%) of trabecular or lobulated fibers in which maldistribution of intermyofibrillar mitochondria produced a lobulated pattern of oxidative enzyme activity on transverse sections. The clinical picture was characterized by adult onset, slowly progressive muscle weakness affecting mainly proximal limb musculature, although mild distal weakness was also present in 60% of the cases. The trabecular pattern of oxidative enzyme reaction reflects maldistribution of the intermyofibrillar mitochondria; this may be caused by malfunction of a putative anchoring mechanism. While trabecular fibers can occur as a nonspecific alteration of muscle fibers in many diverse myopathies, the high prevalence of trabecular fibers as the dominant pathology in trabecular fiber myopathy makes it a distinctive (though not necessarily etiologically homogeneous) clinico-pathological entity.

Dermatomyositis and nasopharyngeal carcinoma.

A nasopharyngeal carcinoma was diagnosed in a 37-year-old man with a two year history of dermatomyositis. The physical and laboratory examinations excluded further medical problems. To our knowledge, this is the first case of dermatomyositis associated with nasopharyngeal carcinoma in a white Israeli Jewish patient.

Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part XIII. A comparison of changes in the tracheobronchial epithelium and pulmonary acinus in male rats at 3 and 20 months.

A limitation of the NTP/HEI Collaborative Ozone Project conducted with F344/N rats at the Battelle Pacific North-west Laboratories in Richland, WA (1991-1993) was that the study used only one time point (20 months) to examine the chronic effects of exposure to ozone. Issues the design of that study could not address were (1) the status of cellular differentiation at earlier time points during the course of ozone exposure; (2) whether changes that appeared to be compensatory after 20 months of exposure were due to ozone, or were aspects of the natural aging process in rats; (3) the inability to define adequately which effects were related specifically to the prolonged duration of exposure; and (4) how and what changes brought about by the natural aging process may have overridden or confounded a clear definition of the effects of exposure to ozone at ambient concentrations (e.g., 0.12 parts per million [ppm]), which are of most concern with long-term exposure to this pollutant. The present study examined the effects of a 3-month exposure to ozone under conditions identical to those of the 20-month NTP/HEI Collaborative Ozone Project. In our facilities at the University of California, Davis, we exposed 42 male F344/N rats to either filtered air or 0.12 or 1.0 ppm ozone. After 3 months of exposure to 1.0 ppm ozone, changes in the distribution of superoxide dismutase (SOD) in the copper-zinc (Cu-Zn) form were shown by a pattern of reduced staining in terminal bronchioles and the centriacinar region; and the manganese (Mn) form of SOD was elevated within the centriacinar region. Further analysis by transmission electron microscopy and immunogold labeling confirmed that Mn SOD was elevated within epithelial type II cells immediately distal to the bronchiole-alveolar duct, junction (BADJ). The trachea, three major bronchi, and a short-length and long-length airway path relative to the trachea were examined by morphometric techniques. The pulmonary acini arising from each of these two paths were also examined morphometrically as a function of distance into the alveolar duct. Cellular changes occurring in each of these anatomical regions after 3 months of exposure were analyzed and compared to the changes noted after the 20-month ozone exposures. We found significant increases in the volume density of nonciliated epithelial cells lining the trachea and caudal bronchi as well as in the proximal and terminal bronchioles of the cranial region at a concentration of 1.0 ppm ozone after both 3 and 20 months of exposure. Remodeling of the centriacinar region, particularly within the cranial region of the lungs after exposure to 1.0 ppm ozone, was statistically significant at both 3 and 20 months. No statistically significant effects were noted following exposure to 0.12 ppm ozone for either 3 or 20 months. An important finding was that age did not influence the effect of ozone on the lungs of rats. We conclude that long-term exposure to ozone, rather than the effects of aging, lead to significant alterations of epithelial cell populations lining the airways and centriacinar region of the lung. Marked cellular changes were noted after exposure to 1.0 ppm ozone, but not to 0.12 ppm.

High association of anticardiolipin antibodies with psychosis.

BACKGROUND: Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are autoantibodies that can be detected in plasma or serum of patients with autoimmune-related diseases. The presence of these autoantibodies has been associated with recurrent arterial and/or venous thromboembolism as well as with recurrent fetal loss and thrombocytopenia. In recent years, other medical conditions such as dementia, chorea, psychosis, migraine, and peripheral neuropathy have been associated with these autoantibodies. An adverse response to neuroleptic treatment was reported to be associated with the presence of autoantibodies, but these patients rarely developed clinical vascular manifestations. METHOD: We conducted a study of 34 unmedicated patients admitted to the hospital with acute psychosis in whom aCL and LA were examined before and after neuroleptic treatment to determine the presence of antibodies relative to the treatment condition. RESULTS: 32% (11/34) of the unmedicated psychotic patients had antiphospholipid antibodies: we detected elevated titers of IgG-aCL isotype in 24% (8/34) of unmedicated patients (p < .02 compared with 20 normal controls, none of whom tested positive), and 9% (3/34) had LA. Twenty-two patients were followed up after medication; 31.8% (7/22) of these patients showed moderate titers of IgG-aCL (p < .28), and 18.2% (4/22) were LA positive. Altogether, antiphospholipid antibodies were detected in 40.9% (9/22) of the medicated patients. CONCLUSION: This study shows the increased incidence of LA and aCL antibodies in neuroleptic-treated psychotic patients and the possible association between psychosis and antiphospholipid antibodies.

[Diagnosis of cerebral embolism by transesophageal echocardiography].

Cerebrovascular events have high mortality and morbidity, especially in the elderly. Ischemia is the main cause and 30% of the ischemic events are embolic and of cardiac origin. The clinical picture is not always typical of the type of stroke, but diagnosis of the mechanism of the event determines treatment. Transesophageal echocardiography (TEE) is a sensitive procedure more appropriate for diagnosing emboli of cardiac origin than transthoracic echocardiography (TTE). We therefore compared TEE and TTE in the determination of the source of emboli in 65 patients with ischemic stroke but without significant atherosclerotic changes in their carotid arteries, and compared these findings with those in 50 patients without stroke. 68% of the patients had potential sources of emboli according to TEE, compared to only 15% according to TTE. In the control group only 24% had potential sources of emboli by TEE. The findings were: clots in the left atrium, severe aortic atheroma, patent foramen ovale with paradoxical shunt, spontaneous echocardiography contrast, vegetations and mitral valve prolapse. The study showed that TEE is better than TTE in detecting the etiology of embolic stroke in those with normal carotid arteries, thus determining appropriate management.

Site- and cell-specific alteration of lung copper/zinc and manganese superoxide dismutases by chronic ozone exposure.

The antioxidant enzymes copper/zinc (Cu-Zn) and manganese (Mn) superoxide dismutase (SOD) have been implicated in protection of the lungs from oxidant damage. Mn SOD in particular may be related to acquired tolerance in cells following chronic ozone exposure. In order to study these protective and adaptive phenomena in oxidant injury, the cellular location and relative abundance of Mn SOD and Cu-Zn SOD were examined in the lungs of Fischer 344 rats following exposure to 0.0 and 1.0 ppm ozone for up to 3 mo using immunolabeling and morphometric techniques. Cu-Zn SOD labeling was found to be markedly reduced following ozone exposure in epithelial cells within airways and parenchyma. In contrast, a significant increase was noted in Mn SOD labeling in the centriacinar regions of exposed lungs for both alveolar macrophages and epithelial type II cells. Mn SOD labeling per epithelial type II cell was significantly increased in alveoli 0-400 microm beyond the bronchiole-alveolar duct junction (BADJ), while type II cell Mn SOD labeling was similar to control values with greater distance down the alveolar duct. No induction of Mn SOD was noted in type I epithelial cells, fibroblasts, or Clara cells. Thus, alterations in Cu-Zn and Mn SOD are both site and cell specific in the lungs. The differential increase in Mn SOD in type II cells of the proximal alveolar duct may reflect the ability of these cells to acquire tolerance and to resist further injury to repeated ozone exposure.