The effects of early or direct admission to a specialised spinal injury unit on outcomes after acute traumatic spinal cord injury.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: For acute traumatic spinal cord injury (ATSCI), this study aimed to determine differences in outcomes between patient groups stratified by admission time (⩽24 vs >24 h) to the Spinal Injury Unit (SIU) and by the nature of the admission (direct admission to the SIU vs indirect admission via another hospital). We also aimed to measure the effect on time to admission of a 'non-refusal' policy that triggered immediate acceptance of ATSCI cases to the SIU. SETTING: New South Wales, Australia. METHODS: Study population was all adult SCI patients admitted to the Prince of Wales SIU from 1 January 2001 to 31 December 2012. Patients admitted with chronic-stage SCI or with incomplete data for the duration of their stay were excluded. Comparison of outcomes was made between groups according to the setting of admission. Time to admission before and after initiation (2009) of the 'non-refusal' policy was compared. The prevalence of complications, lengths of stay (LOSs) and time to admission were compared by Mann-Whitney non-parametric methods. Count modelling was used to control for confounders of age and gender. RESULTS: A total of 460 cases were identified and 76 were excluded. The early group had fewer pressure areas (41.8% vs 63.2%; P<0.001) and shorter LOS (136 vs 172 days; P<0.001) than the late group. The direct group had fewer pressure areas (35.2% vs 54.9%, P<0.001), deep vein thrombosis (9.9% vs 24.6%, P=0.003) and shorter LOS (124 vs 158 days, P=0.007) than those admitted indirectly. Time to admission was reduced after introduction of the 'non-refusal' policy (1.53 vs 0.63 days; P=0.001). CONCLUSIONS: Early and direct admission to SIU reduced complication rates and LOS. A non-refusal policy reduced time to admission.

Spinal cord and related injuries after attempted suicide: psychiatric diagnosis and long-term follow-up.

STUDY DESIGN: Retrospective analysis of acute spinal cord injuries (ASCI). OBJECTIVES: Determine incidence of ASCI due to suicide attempt from 1970 to 2000. Describe demographics, injuries, mental illness, functional outcomes and nature of subsequent deaths. SETTING: State spinal cord injury services, New South Wales, Australia. METHODS: Retrospective record review and follow-up interview. RESULTS: Of 2752 ASCI admissions, 56 were because of attempted suicide (55 falls, one gun-shot wound). Thirty-six males and 20 females. Median age 30 years (15-74). Most common levels of vertebral injury were C5 and L1. Twenty-three had complete spinal cord injury. Thirty-two had an Injury Severity Score of >15. Forty had more than one major injury. There was a significant rise in the incidence of ASCI following self-harm over time (Poisson regression, P=0.004). There was a significant change in scene of injury away from hospitals over time (chi (2) test, df=1, P=0.0001). Psychiatric diagnoses were personality disorder 27; schizophrenia 16; depression 14; chronic alcohol abuse 10; mood disorder 10; chronic substance abuse 10; other four. Follow-up was available in 47 cases (84%) at an average of 8 years. Four subsequent deaths were by suicide. Domiciliary arrangements were: home 28; hospital five; nursing home three; group home/hostel four. CONCLUSIONS: Community placement outcomes for survivors were good. Subsequent death by suicide was high. There was a significant rise in cases and a change in injury scene away from hospitals over time.

A novel, resorbable suture anchor: pullout strength from the human cadaver greater tuberosity.

The pullout strength of a collagen bone anchor that creates interference fixation as the result of radial swelling on hydration was compared with a Mitek rotator cuff anchor after insertion into the greater tuberosity of human cadaver humeri. Bones were fully hydrated at 37 degrees C. Stiffness, peak load, and the mode of failure were recorded. Real and apparent bone densities were measured. Peak load for the collagen anchor at 15 minutes (121.0N +/- 81.3N) was greater than at 2 minutes (60.5N +/- 38.5N) after insertion (P <.05). At between 5 and 60 minutes after insertion, peak loads for the Mitek and the collagen anchors did not differ. After 30 minutes from insertion, the mode of failure of the collagen anchor changed from pullout with minor body damage to pullout with major body damage. Peak load at pullout correlated with bone density for the Mitek (P <.05, r = 0.516) but for the collagen bone anchor appeared unaffected by bone density.

Monoaminergic effects of high-dose corticotropin in corticotropin-responsive pediatric opsoclonus-myoclonus.

Children with the opsoclonus-myoclonus syndrome (OMS) usually respond to corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of benefit is unknown. We previously showed that both cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations are low in pediatric OMS. In this study, we measured levels of CSF Dopa, catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5-HIAA in eight patients before and during treatment with ACTH. All the children were ACTH-responsive with 50-70% improvement in multiple clinical features of OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21% (p < 0.001). Treatment with ACTH was associated with significant correlations between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and Dopa. There were no significant changes in the CSF concentrations of the noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG), or the serotonergic marker 5-HIAA. The only child with a marked inflammatory pattern in CSF, which was reversed by ACTH, was atypical for a large increase in NE and decrease in 5-HIAA during ACTH treatment. Beneficial effects of ACTH in OMS are not associated with normalization of HVA or 5-HIAA levels. The pattern of decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal uptake of catecholamines (which steroids inhibit) or decreased 0-methylation of catecholamines in nonneuronal cells.

Mild emphysema is associated with reduced elastic recoil and increased lung size but not with air-flow limitation.

Thirty-nine excised human lungs were examined to identify early changes in the small airways, their size distribution, and their elastic recoil in relation to mild degrees of emphysema. Elastic recoil measurement, single-breath nitrogen (SBN2) tests, and FEV1 were obtained from 18 lungs with no emphysema and 21 emphysematous lungs with no greater than Grade 5 emphysema score. The mean number of alveolar attachments per brochiole was determined from all the bronchioles cut in cross section. When the 2 groups of lungs were compared, the percentage of predicted elastic recoil of the nonemphysematous lungs was significantly greater at 50, 70, 80, and 90% of TLC than in the mildly emphysematous lungs. The TLC of the emphysematous lungs (% of predicted) was also significantly greater than in the nonemphysematous lungs. Pigment of the small airways was the only pathologic feature that was significantly greater in the emphysematous lungs than in the nonemphysematous lungs. Size distribution in the small airways was similar except for the airways zero to 0.2 mm, which were more frequent in the emphysematous lungs. When data from both groups were combined, elastic recoil was shown to be related to both the number of alveolar attachments (p less than 0.03) and the mean diameter of the small airways (p less than 0.01). We conclude that structural and functional changes in lungs with mild emphysema include reduced elastic recoil, increased lung size, and some size distribution changes in the small airways. Mild emphysema is not associated with air-flow limitation.

Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.

Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar lavage fluid neutrophils increase after corticosteroid therapy in smokers with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are often cigarette smokers and are often being treated with corticosteroids at the time of bronchoalveolar lavage. We addressed the question of whether or not the bronchoalveolar lavage fluid (BALF) neutrophil content of patients with IPF undergoes changes in smokers different from those in nonsmokers after institution of corticosteroids. Eighteen patients were studied (10 smokers and 8 nonsmokers). Fourteen patients (6 smokers and 8 nonsmokers) were treated orally with prednisone. The histologic assessment of alveolar inflammation and inflammatory small airways disease was no different in smokers than in nonsmokers. None of the smokers treated with prednisone had pathologic evidence of emphysema in addition to IPF. Five of 6 smokers showed an increase in BALF neutrophils after 3 months of prednisone (p less than 0.05), whereas the nonsmokers' BALF neutrophils decreased or remained unchanged. This increase in BALF neutrophils in smokers was not associated with concomitant or subsequent clinical deterioration but, in fact, with clinical improvement after 3 months of therapy. These data indicate that the combination of cigarette smoking and corticosteroid therapy influences the BALF neutrophil content in patients with IPF and suggest that interval changes in BALF neutrophil content may not reflect the status of the inflammatory process or structural derangements in the lungs of some patients with IPF.

Radial traction and small airways disease in excised human lungs.

We studied 47 excised human lungs in order to examine the relationship between the number of alveolar attachments surrounding bronchioles 2 mm or less in diameter and the presence of small airways disease and overall lung function. Expiratory pressure-volume curves, the FEV1, and the single-breath nitrogen washout were obtained from 11 lungs without emphysema and 36 lungs with various degrees of emphysema. The lungs were subsequently inflation-fixed at 20 cm H2O. Gough sections were used to measure emphysema. Six to 10 blocks of tissue were cut at random from a midsagittal slice of lung tissue for the small airways and alveolar attachment study. We measured the inside diameters of all nonrespiratory bronchioles (2 mm or less in diameter) and made corrections for shrinkage during processing. The number of alveolar attachments on the outside wall of the bronchioles cut in cross section were obtained from all the sections observed. The mean number of alveolar attachments per bronchiole was determined for each lung. The histopathologic features of the bronchioles were evaluated by the method of Cosio and coworkers (2). We found a positive correlation between the number of alveolar attachments and the percentage of predicted FEV1 (r = 0.328, p less than 0.03) and the percentage of predicted closing capacity (r = 0.553, p less than 0.01). There was a negative correlation of the mean number of alveolar attachments and the small airways fibrosis score (r = -0.344, p less than 0.02). A correlation also existed between the number of alveolar attachments and the mean internal bronchiolar diameter (r = 0.561, p less than 0.001). We conclude that the alveolar attachments and elastic recoil are related to the size and function of the small airways.

A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis.

In order to develop a reproducible, quantifiable means of assessment of the clinical status of patients with idiopathic pulmonary fibrosis (IPF), a composite clinical-radiographic-physiologic (CRP) scoring system was devised, using 7 variables: dyspnea, chest radiograph, spirometry, lung volume, diffusion capacity, resting alveolar-arterial PO2, and exercise O2 saturation. To assess this scoring system, we examined the relationships between CRP scores and histopathologic findings, including a cellular pathology score composed of abnormalities deemed to be potentially reversible, a fibrotic pathology score based on abnormalities felt to be essentially irreversible, and an index of overall pathologic derangement (total pathology score), derived from the sum of the cellular and fibrotic scores. The initial CRP determination at the time of open lung biopsy correlated significantly with the total pathology score (r = 0.61, p less than 0.001). The CRP score determined after 6 months of corticosteroid therapy showed a significant correlation with the fibrotic pathology score present on open lung biopsy (r = 0.76, p less than 0.001). The change in CRP after 6 months of corticosteroid therapy tended to reflect the cellular histopathologic component of the open lung biopsy (r = -0.43, p less than 0.10). Moreover, in none of these relationships did any individual component of the CRP score correlate better with the respective histopathologic index than did the CRP score itself. These data suggest that this CRP score is useful for the estimation of the severity of underlying pathologic derangement and for the longitudinal quantitative assessment of clinical impairment in patients with IPF.

Small airway disease is associated with elastic recoil changes in excised human lungs.

We studied 54 excised human lungs, 15 with no emphysema and 39 with varying degrees of emphysema, to examine the relationship of small airway disease and elastic recoil. We found a negative correlation between the total small airway pathology score and the mean internal bronchiolar diameter (r = -0.309, p = less than 0.03), as well as with other measurements of small airway size. The internal bronchiolar diameter correlated well with both the elastic recoil expressed as a percentage of predicted values at 70% of total lung capacity (r = 0.533, p less than 0.001) and elastic recoil expressed as an exponential constant k (r = -0.370, p less than 0.01). Fibrosis of the small airways was associated with a reduced internal bronchiolar diameter (r = 0.460, p less than 0.001), as well as the percentage of predicted elastic recoil at 70% of total lung capacity (r = -0.382, p less than 0.01) and elastic recoil expressed as an exponential constant k (r = 0.348, p less than 0.02). We have concluded that changes in elastic recoil seen in these lungs and fibrosis of small airways may be related by a common inflammatory process.

Chronic sclerosing tracheobronchitis.

We report a child with wheezing and respiratory distress of 53 months duration which was undiagnosed and unresponsive to treatment. Necropsy examination of trachea and bronchi showed narrowing by chronic inflammation and fibrosis of mucosa and submucosa. Despite intensive investigations, the aetiology and pathogenesis remained undetermined.

Adenocarcinoma developing in a patient with midline granuloma.

A 51-year-old man with midline granuloma was treated successfully with a combination of local radiation and oral cyclophosphamide. Six years after therapy, adenocarcinoma of the lung developed. Possible relationships between these two diseases are discussed.

Bronchiolitis obliterans. Report of three cases with detailed physiologic studies.

We describe three patients with bronchiolitis obliterans seen at our hospital during the last two years. Their ages were 25, 49 and 69 years. One developed the disease secondary to a probable viral infection, another inhaled fumes, and the third was exposed to unknown precipitating factors. Lung biopsy showed changes compatible with bronchiolitis obliterans in the first two, while in the third, changes were compatible with bronchiolitis obliterans and interstitial pneumonitis. Pulmonary function tests of patient 1 showed severe airflow limitation, increased total lung capacity, a shift of the pressure-volume curve upward with a normal slope, and an elevation of upstream resistance. In patient 3 (bronchiolitis obliterans with interstitial pneumonitis) total lung capacity was normal, the pressure volume curve was shifted slightly to the right and upstream resistance was increased. After treatment with steroids, clinical improvement was observed along with normalization of the pressure-volume curve and a decline in the upstream resistance.

The morphology and morphometry of small airways disease (relevance to chronic obstructive pulmonary disease).

The morphologic and morphometric characteristics of the small airways of the lung and their relationship to airflow as measured by forced expiratory volume in one second (FEV1) were determined in 37 excised human lungs. After fixation the lungs were graded as to the degree of emphysema and the degree of small airway pathology. The internal diameters of the small airways were measured and corrected for shrinkage during processing. The mean bronchiolar diameter was positively correlated with the % predicted FEV1 (p less than 0.001) and negatively correlated with the small airway fibrosis (p less than 0.01). We conclude that fibrosis of the small airways of the lung is associated with a decrease in airway dimension which is in turn correlated with decreased FEV1 in excised human lungs.

Ultrastructure of congenital cystic adenomatoid malformation of the lung.

Four cases of congenital cystic adenomatoid malformation of the lung are presented with ultrastructural analysis. In some of the cases the ultrastructure is similar to that described in normal fetal airways during the early embryonic phase of lung development. Varying degrees of differentiation are noted, confirming what has previously been observed ultrastructurally in this lesion. One new finding is the presence of tonofilaments in one of our cases, which may represent a metaplastic change. Although the exact nature of the insult is unknown, there may be a developmental defect affecting epithelial differentiation as well as the interaction between the developing pulmonary mesenchyme and distal respiratory units.

Small airway dimension and size distribution in human lungs with an increased closing capacity.

Pulmonary function tests were obtained in 7 emphysema-free and 27 emphysematous lungs with minimal small airway disease. The lungs were divided into 2 groups on the basis of whether they had a small or large, i.e., increased closing capacity. The lungs were subsequently fixed and the small airways (less than or equal to 2.00 mm) from 6 to 10 blocks of tissue were counted and inside diameters were measured. There was a significant increase in the number of airways measuring 0.40 mm or less (p less than 0.03) and a decrease of airways measuring 0.81 to 1.0 mm (p less than 0.03) in the lungs that had larger closing capacities. When the data of both groups were combined there was a negative correlation between the mean bronchiole inside diameter as a function of the percentage of predicted closing capacity (r = -0.381, p less than 0.03) and a positive correlation between small airway inside diameter and the forced expiratory volume in one second (r = 0.595, p less than 0.001) and the maximal mid-expiratory flow rate (r = 0.527, p less than 0.01). We conclude that in lungs that are normal or involved with minimal lung disease, function can be related to the caliber of the small airways.

Functional correlations with mild and moderate emphysema in excised human lungs.

The relation between mold to moderate emphysema and lung function tests, including tests reported to identify "early" or mild disease, were examined using 24 excised human lungs, 5 with no emphysema, 11 with grade 5 or less emphysema, and 8 with as much as grade 50 emphysema. Static pressure volume curves, single breath nitrogen (SBN2) tests, maximal exemphysema. Static pressure volume curves, single breath nitrogen (SBN2) tests, maximal expiratory flow volume (MEFV) curves with air and a mixture of 80% He and 20% O22, and forced expiratory volume in one second (FEV1) were measured in all lungs. Negative correlations were found (r - -0.489, p less than 0.02) between the emphysema grade and the per cent predicted static lung recoil at 50% of total lung capacity and the emphysema grade and the per cent predicted FEV1 (r = 0.428, p less than 0.05). There was no significant correlation between the grade of emphysema and the SBN2, or MEFV test. Negative correlations were found between the elastic recoil, expressed as per cent predicted slope of Phase III (r = 0.482 p less than 0.02), and the per cent predicted FEV1 (r = -0.619, p less than 0.01). We concluded that mild to moderate degrees of emphysema are not correlated with single breath nitrogen test or flow volume curves using air or helium, but are better related to loss of elastic recoil in excised human lungs.

Gastrointestinal involvement in leukocytoclastic vasculitis and polyarteritis nodosa.

The records of 106 consecutive patients referred to the University of Colorado Medical Center (UCMC) vasculitis study group during a 5-yr period were evaluated for gastrointestinal (GI) manifestations attributable to vasculitis. There were 3 groups: 18 with leukocytoclastic vasculitis (LCV) on skin biopsy younger than 16 yr of age; 75 with LCV older than 16 yr of age; and 13 with polyarteritis nodosa (PAN). Significant GI manifestations at presentation or exacerbation of vasculitis occurred in 38 of 106 (36%) patients. These were more frequent in LCV patients younger than 16 yr (66%), than older LCV patients (26%) or PAN patients (46%). The commonest complaint was abdominal pain (79%), followed by nausea (63%), vomiting (37%) and diarrhea (23%). GI bleeding was present in 52% and acute abdomen in 21% of patients. No consistent radiologic findings were noted. Duodenal and peritoneal biopsies suggested vasculitis in 6 LCV patients. Seven exploratory laparotomies were performed in 4 LCV and 3 PAN patients. Intestinal infarction was found in 3 patients with PAN, but in one of the LCV patients. Two patients with LCV with an acute abdomen were not explored and responded promptly to iv corticosteroids. Thus, systemic vasculitis frequently involves the GI tract. In patients with LCV, recognition of this association and treatment with corticosteroids can avoid surgery. In our patients with PAN, however, acute abdominal signs indicated infarction requiring surgery and resection.

A model of immune complex-mediated pleuropulmonary injury; evidence of deposition of circulating immune complexes in the lung.

Severe acute, diffuse lung inflammation was induced in rabbits immunized to bovine serum albumin (BSA) and subsequently challenged with BSA intrapleurally. Evidence suggesting involvement of circulating immune complexes in the pathogenesis of lung injury in these rabbits include 1) positive lung immunofluorescence, 2) a fall in serum hemolytic complement, 3) diffuse bilateral involvement despite unilateral antigen challenge, and 4) absence of these findings in control rabbits. Further investigation with this model may provide insight into the processes involved in the deposition of immune complexes in the lung and the mechanisms of lung injury provoked by immune complex deposition.