Lung Transplant Metalloproteinase Levels Are Elevated Prior to Bronchiolitis Obliterans Syndrome

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.     

The Usefulness of Magnetic Resonance Imaging in the Diagnosis of Anterolateral Impingement of the Ankle

The purpose of this study is to assess the sensitivity and specificity of magnetic resonance imaging (MRI) in the diagnosis of anterolateral impingement of the ankle and to assess the most helpful sequence in making the diagnosis. Twenty-four patients who had undergone ankle arthroscopy were chosen. Twelve patients had arthroscopically documented anterolateral impingement, and 12 patients with no impingement on arthroscopy served as controls. Two musculoskeletal radiologists and an orthopedic surgeon, blinded to the operative diagnosis, retrospectively reviewed selective MRI images in the sagittal, axial, and coronal planes. The sensitivities and specificities were calculated for all 3 reviewers. The Kendall coefficient of concordance was calculated for overall agreement among reviewers. Sensitivities varied from 0.75 to 0.83, whereas specificities varied from 0.75 to 1.00. Using the Fisher exact test of contingency, the sensitivities and specificities showed that all reviewers' interpretations were statistically significant with P = .039, .001, and .012, respectively. The axial images were felt to be most helpful in making the diagnosis. The physicians felt that the sagittal images were helpful in 67%, 83%, and 100%, respectively. MRI is a useful tool that can aid the clinician in the diagnosis of anterolateral impingement of the ankle. T1 sagittal images demonstrating displacement of the normal fat signal anterior to the fibula by scar can be useful and help to confirm the diagnosis.     

Behavioral treatment of bisexual aggression of an adult with developmental disabilities

This case study describes the use of a behavioral intervention to treat bisexual aggression of an adult with developmental disabilities. Treatment involved the suppression of deviant sexual behavior and enhancement of appropriate social interactions. Implementation of the intervention resulted in an immediate reduction in sexual aggression. Long-term follow-up indicated no further occurrences of the behavior.Discussion focuses on the limited data regarding the assessment and treatment of persons who are developmentally disabled and engage in deviant sexual behavior, determination of consenting sexual relations, and development of behavioral interventions.The comments of Lew Lewin are appreciated. Reprints can be obtained by contacting Duane Lundervold at LINC Behavioral Services, 1430 Willamette, Suite 363, Eugene, Oregon 97401.     

Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

Brain Death Further Promotes Ischemic Reperfusion Injury of the Rabbit Myocardium

Background. Little is known about preload-dependent cardiac function after brain death (BD) and subsequent graft preservation.

Methods. A validated model of BD in rabbits was developed and myocardial performance was studied after BD induction and 1 hour of subsequent global hypothermic ischemia using a validated rabbit model and an isolated work-performing heart preparation.

Results. Significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed 2 hours after BD. After global hypothermic ischemia, significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed in the BD group compared with controls. Cardiac output and coronary flow were also significantly decreased in BD hearts compared with controls. Creatine kinase release was increased by 32.5% in BD hearts compared with controls.

Conclusions. In a rabbit model, BD combined with global hypothermic ischemia causes a significant decrease in left ventricular function compared with global hypothermic ischemia. This dysfunction may be attributed to a significant decrease in coronary flows in BD hearts.     

Physical status score and trends in anesthetic complications

Since deaths due to anesthesia have now become rare, emphasis in quality assurance of anesthetic care must focus on morbidity rather than only on mortality. To facilitate comparisons of outcomes, data from a large anesthesia follow-up program (N = 112,000 anesthetics) were used to evaluate the usefulness of the American Society of Anesthesiologists' Physical Status score (PS) as an independent predictor of nonfatal adverse anesthetic complications. For each patient, the anesthesiologist filled out a form containing information about the patient, the anesthetic, the operative procedure, and outcomes in the operating and recovery rooms. Postoperative complications were assessed by a designated anesthesia follow-up nurse. We calculated the PS-specific complication rate by dividing the number of complications to patients in each PS category by the number of anesthetics given to patients in the same category. We found that PS-specific complication rates increased with increasing PS scores for most complications sought. For intraoperative and recovery room complications, the PS-specific rates increased from 1978-80 and 1981-83 as compared to 1975-77. However, there was no increase over time in the rate of postoperative major complications. After adjusting for patient, anesthesia, and surgery-related variables by multiple logistic regression, the relative odds of having an intraoperative or postoperative major complication were increased for patients classified PS2, PS3 and PS4 & 5 as compared to PS1. However, those in higher PS categories were less likely to have a recovery room complication than PS1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

INTERACTIONS BETWEEN THE CIRCULATORY EFFECTS OF CENTRAL HYPOVOLAEMIA AND ARTERIAL HYPOXIA IN CONSCIOUS RABBITS

1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval-cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min. 2. Caval-cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O₂, with and without the addition of 3–4% CO₂, in randomized order. 3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased. 4. During Phase I, there were independent linear relationships between Pao₂ (but not Pao₂) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of Pao₂, the greater was the rate of fall of SVCI and the less the rate of fall of MAP. 5. There was an inverted U-shaped effect of Pao₂, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O₂), Phase II occurred later than during normoxia (21% O₂); and (b) across the normoxic and hypoxic gas mixtures (21–8% O₂, with and without added CO₂), there was an independent linear relationship between Pao₂ (but not Pao₂ or Pao₂×Pao₂) and the level of CI at which Phase II occurred. That is, the lower the level of Pao₂, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.     

The effects of population density and malnutrition on the dynamics of whooping cough.

Liverpool, a seaport in NW England, suffered severely from lethal infectious diseases in the second half of the 19th century: the population was densely crowded and malnourished and life expectancy was low. Time-series analysis shows that the epidemics of whooping cough (i) had an interepidemic interval of 2.9 years, 1863-85, which lengthened to 3.4 years, 1885-1900 (ii) were strongly coherent with wheat prices (P < 0.001) and (iii) also correlated with cycles of seasonal weather conditions. It is suggested from mathematical modelling that the epidemics in this compromised population were maintained (i.e. the system was driven) by an oscillation of malnutrition and by seasonal weather conditions. A model that incorporates both the dynamics of whooping cough and the demographic characteristics of the population is presented. It has been shown to replicate the dynamics of the epidemics and has been used to predict the changes with time of (i) the force of the infection and (ii) the proportion of those infected with whooping cough who died.