Late pulmonary impairment following allogeneic bone marrow transplantation

The pulmonary function of 88 consecutive leukemic patients who had undergone allogeneic bone marrow transplantation (BMT) was studied beforehand, at 3 months, at 6 months, and annually thereafter until 5 years after grafting. The parameters for function which are indicative for obstructive and restrictive lung disease deteriorated in all patient groups during the first 3 to 6 months after BMT but partially recovered within one year. Long-term decline in lung function was similar in all patient groups, and neither the onset nor the magnitude of pulmonary dysfunction was related to the occurrence of pulmonary impairment within 6 months after grafting. Multivariate analysis was then employed to assess predictors for long-term pulmonary disease. Despite the obvious effect of chronic graft versus host disease on the course of lung function, it was in itself not a significant predictor of long-term pulmonary outcome. Rather, the conditioning regimen turned out to be indicative; compared with busulfan, fractionated total body irradiation was demonstrated to be clearly superior with a lower incidence of both restrictive and obstructive long-term lung impairment. Our data indicate a previously unknown long-term side effect of busulfan conditioning.     

Expert statement and assessment of medical impairment in work-related pulmonary disease

The Norwegian Societies of Thoracic Medicine and Occupational Medicine established a working group to standardise diagnostic procedures and evaluation of work-related respiratory disorders. In cases of suspected work-related diseases the physician may be asked by the National Insurance Administration or an insurance company to make a statement which will be one of the documents used to decide the patient's right to compensation benefit. We discuss the role of the physician as an independent expert. This is different from his role as clinician. The statement should include a balanced presentation of information from different sources, including health and occupational history, and the employer's information about the work environment (quantitative and qualitative exposure data). The statement must also include the results of a clinical examination and an assessment of functional status based on objective tests. The paper contains recommendations for evaluation of permanent impairment in light of the present Norwegian laws and regulations.     

Effect of exercise on natural cytotoxicity and pulmonary tumor metastases in mice

Exercise has been demonstrated to reduce experimental tumor formation in rodents when the exercise is present during the tumor initiation or promotion phases. This study evaluated whether exercise influenced the process of tumor metastasis and subsequent growth in a secondary implant site. Male C3H mice remained sedentary, were given free access to running wheels, ran on a treadmill (15 m.min-1, 30 min.d-1), or walked on a treadmill (5 m.min-1, 5 min.d-1)(N = 20/group). Following 9 wk of this protocol, exercise was discontinued. At this time all animals received a tumor cell dose (CIRAS 1, 3 x 10(5)) i.v., and remained sedentary until sacrificed 3 wk later. Splenic natural killer (NK) cell activity was elevated in the wheel running mice compared with sedentary controls 3 wk after cessation of exercise (F(3,74) = 6.266, P < 0.002). Exercised mice displayed lower tumor cell retention in the lungs relative to nonexercised mice (F(1,37) = 6.593, P < 0.02). Tumor incidence was not different across activity groups whereas tumor multiplicity was higher in mice that had been previously exposed to exercise. (However, it should be noted that the significant exercise-tumor effect was due to a small number of exercised mice with extreme multiplicity, > 200 foci/lung.) More extensive tumor colony formation was present in wheel-trained mice that displayed the greatest volumes of daily running. The results from this study suggest that exercise was able to augment natural immune cytotoxic function for up to 3 wk after cessation of activity. However, this augmentation of natural immune function was not associated with reduced tumor incidence in the exercised animals.     

Indomethacin enhances the cytotoxicity of VCR and ADR in human pulmonary adenocarcinoma cells

Conscious sedation has become an important component of practice for many ambulatory procedures. Important factors to maintain the safety of this technique are proper patient selection, slow titration of the medication, continuous patient monitoring, proper education of the individuals administering the medication and monitoring the patient, and appropriate policies and guidelines in place in the ambulatory setting. When patient safety is the number one priority, conscious sedation can be a very effective, practical, and safe technique used in the ambulatory setting.     

Cholesterol protects PC12 cells from beta-amyloid induced calcium disordering and cytotoxicity

THE neurotoxic action of beta-amyloid seems to play an important role in the pathogenesis of Alzheimer's disease. The disruption of calcium homeostasis by beta-amyloid has been suspected to be the mechanism of its neurotoxicity. We found that beta-amyloid 25-35 induces a rapid increase in cytosolic calcium of PC12 cells, and subsequently, a dramatic decrease in cell viability. The increase in cytosolic calcium induced by beta-amyloid is effectively blocked by cholesterol in a dose-dependent manner. Furthermore, pretreatment of PC12 cells with cholesterol also significantly attenuates the neurotoxicity induced by beta-amyloid. These findings suggest that extracellular free cholesterol can protect neurones from beta-amyloid neurotoxicity mediated by the disruption of calcium homeostasis.     

Amiodarone induced pulmonary fibrosis in infancy

We report a case of pulmonary fibrosis in an infant receiving amiodarone for treatment of intractable atrioventricular reentrant tachycardia secondary to Wolff-Parkinson-White syndrome. At 9 months, a screening chest radiograph showed a diffuse interstitial infiltrate in an asymptomatic, thriving infant. Amiodarone was discontinued and the pulmonary fibrosis resolved gradually over 6 months. This case documents the first report of amiodarone induced pulmonary fibrosis in the pediatric age group. We speculate that as amiodarone is used more frequently to manage pediatric arrhythmias, pulmonary fibrosis, a known complication of this antiarrhythmia in adults may be seen with increasing frequency in children.     

Relationship of child loss to psychiatric and functional impairment in resettled Cambodian refugees

One hundred sixty eight respondents, recruited from a community of resettled Cambodian refugees in Massachusetts, were interviewed for a study of trauma, physical and emotional health, and functioning. Of the 161 respondents who have ever had any children, 70 parents (43%) reported the death of between one and six of their children. Child loss was positively associated with health-related concerns, a variety of somatic symptoms, and culture-bound conditions of emotional distress. No relationship was found with conventional psychiatric symptoms of depression and posttraumatic stress disorder. Parents whose children died were performing most routine daily activities and participating in social activities to a similar and even greater extent than were parents who did not lose children. Nevertheless, child loss was strongly associated with a perception of health-related limitation in both physical functioning and social activities. Further research on the prevalence of child loss and its impact on long-term adjustment in survivors of mass trauma is indicated.     

Long-term effect of botulinum toxin on impairment and functional health in cervical dystonia

Two methods for genotyping hepatitis C virus (DNA enzyme immunoassay [DEIA] and line probe assay [Inno-LiPA HCV I and II]) were compared on 120 samples and of these 87% were assigned to the same subtype by both assays. There were 15 subtyping discrepancies which involved 5% of type 1 isolates and 90% of type 2 isolates. Amplified products from the core and 5' untranslated regions (UTR) were sequenced to resolve conflicts. Type 1 discordant samples had a guanosine at position -99 in the 5' UTR, a characteristic of genotype 1b, and a core region typical of subtype 1a. The eight isolates classified as 2a/2c by LiPA and as subtype 2c by DEIA belonged to type 2.     

Relationship of physical disease and functional impairment to depression in older people.

Physical disease is commonly considered a risk factor for depression among older adults. However, this pattern is not consistently supported, and a theoretical framework for understanding such a relationship has not been articulated. P. M. Lewinsohn, H. Hoberman, L. Teri, and M. Hautzinger's (1985) integrative model of depression predicts that disease will be a risk factor for depression only when disease results in functional impairment, and that impairment in the absence of disease is also a risk factor for depression. The authors tested these predictions in a community-based sample of older adults followed longitudinally and found that functional impairment was a significant risk factor for depression, regardless of disease status. Disease was not a significant predictor of major depression, nor did it interact with impairment to predict depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Minor depressive disorder and subsyndromal depressive symptoms: functional impairment and response to treatment

BACKGROUND: This study quantifies functional impairment and depressive symptomatology in patients with minor depressive disorder (MinD) and subsyndromal depressive symptomatology (SSD) before and after 8 weeks of treatment with fluvoxamine. Study patients were compared and contrasted with archival data from a sample of the general population measured by the Medical Outcome Survey Short Form 36. METHOD: Fifteen patients with MinD and 15 patients with SSD were identified from primary care clinics, referrals and newspaper advertisements. Patients signed informed consent and were offered open label treatment with fluvoxamine 25-100 mg/day. Patients were seen biweekly and measures of functional impairment and depressive symptomatology were gathered systematically. RESULTS: MinD and SSD were associated with dysfunction and disability when compared to archival normative data from the general population. Eight week treatment with fluvoxamine was associated with a substantial decrease in depressive symptomatology and a normalization of psychosocial functioning. CONCLUSION: This is the first study to quantify functional impairment and the severity of depressive symptomatology in a clinical sample of patients with MinD and SSD, and to demonstrate that treatment with a selective serotonin reuptake inhibitor decreases depressive symptomatology and improves psychosocial functioning. Placebo-controlled double-blind confirmation of these preliminary observations seems warranted.     

Mechanism of mitochondrial dysfunction and cytotoxicity induced by tropolones in isolated rat hepatocytes

The hair cell orientation patterns present on the saccules of fishes may be important for encoding the direction of a sound source. This study was conducted to determine whether primary afferent projections to the medulla are organized by the best directions for the hair cells they innervate. The toadfish saccule has hair cells oriented primarily in the vertical plane: both the rostral and the caudal saccule have hair cell orientations sweeping from 0 degrees to 45 degrees, and the middle saccule has hair cells oriented at 90 degrees. Fluorescent dextran amines were used singly and in combination to label regions of the saccular nerve innervating rostral, middle, and caudal saccule. The projections of those afferents were examined in detail in the anterior and descending octaval nuclei, which are auditory nuclei in this species. There was no evidence of topographic projections based on location along the length of the saccule or based on hair cell orientation. There was some evidence that parallel inputs are present from each region of the saccule examined, which may be based on the 180 degrees opposition of hair cells found throughout the saccule; however, afferents from the rostral, middle, and caudal saccule appear to have overlapping projections to the anterior and descending octaval nuclei. These data suggest that in toadfish, calculations of the direction of the sound source may begin in either of these primary auditory nuclei by comparing afferent input from along the saccule.     

Protection of PC12 cells glutathione peroxidase in L-DOPA induced cytotoxicity

L-DOPA may cause side-effects during the treatment of Parkinson's disease. We investigated the role of glutathione peroxidase (GSHPx) in cellular defense against L-DOPA cytotoxicity. A line of PC12 cells overexpressing GSHPx with plasmid pRc/CMV-GSHPx was established and stable transfectants overexpressing GSHPx were used for this study. GSHPx activity was found to be 1.5-fold higher in GSHPx-transfectants than in mock-controlled transfectants. Transfectants over expressing GSHPx were also significantly more resistant to exposure to either L-DOPA or t-butyl hydroperoxide than mock-transfected cells. Results suggested that L-DOPA may cause neuronal cell death by an oxidative pathway and GSHPx may play an important role in cellular defense against oxidative stress.     

Influence of cadmium on cartilage and bone formation induced by bone morphogenetic protein

OBJECTIVE: To explore the therapeutic mechanism of Salvia miltiorrhize, ligustrazine and Panax notoginseng in treating late hemorrhagic shock in rabbit. METHODS: Rabbit hemorrhagic shock models (MPA 5.3 kPa) were set up according to Wiggers' method and administrated Salvia miltiorrhiza, ligustrazine, Panax notoginseng. The values of blood RBC superoxide dismutase (SOD) and blood lactate (BL), plasma malondialdehyde (MDA) and magnesium (Mg++) were continuously monitored before shock, 120 minutes after shock, 60 and 120 minutes after hydraulic dilatation. RESULTS: (1) In 120 minutes after shock, the level of SOD decreased and the concentrations of MDA, BL, Mg++ were markedly increased, which indicated that the cell membrane damage caused by oxygen free radicals in rabbit hemorrhagic shock. (2) Salvia miltiorrhiza, Ligustrazine or Panax notoginseng could alleviate lipidperoxidation injury to tissue. Compared with the single drug administration groups, the effects of oxygen free radicals scavangers by combined administration with half dose of 2 drugs were better than the single drug with full dose alone and the side effects such as depression of blood pressure and heart rates would be alleviated. CONCLUSION: Combined administration of Salvia miltiorrhiza, ligustrazine and Panax notoginseng would half the dosage, the blood pressure depression and heart rate reduction alleviated and better result obtained.     

Herbimycin-A attenuates ischaemia-reperfusion induced pulmonary neutrophil infiltration

OBJECTIVES: To determine whether pharmacological induction of heat shock proteins (HSPs) by herbimycin-A (a tyrosine-kinase inhibitor) would protect against neutrophil-mediated lung injury in an animal model of lower torso ischaemia-reperfusion. MATERIALS AND METHODS: Sprague-Dawley rats were randomised into three groups: the control group underwent midline laparotomy only; the ischaemia-reperfusion (IR) group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; the third group (HerbIR) was pretreated with herbimycin-A 18 h prior to IR insult. Wet to dry lung weight ratio (W:D), bronchoalveolar lavage protein concentration (BALprot), tissue myeloperoxidase activity (MPO) and bronchoalveolar lavage neutrophil count (BALPMN) were measured. Heat shock protein 72 (HSP72) expression in lung, intestine, mesentery and liver was measured using Western immunoblotting. RESULTS: IR resulted in acute lung injury with tissue oedema (W:D) and neutrophil infiltration (PMO, BALPMN). Herbimycin-A, in vivo, induced HSP expression and attenuated neutrophil infiltration (MPO, BALPMN). CONCLUSION: These data indicate that herbimycin-A protects against ischaemia-reperfusion induced pulmonary neutrophil infiltration, possibly by increasing the expression of heat shock proteins.     

Various pulmonary lesions induced by high-pressure oxygen

Hyperbaric oxygen may provoke lesions in various organs and tissues depending on the dose and application time. The toxic action mechanisms of oxygen are manifold. The pulmonary lesions that occur in mice submitted to various oxygen pressures are investigated. Anatomo-pathological examination revealed numerous alterations of various kinds depending on pressure used. Emphysema, pulmonary oedema and enormous inflammatory processes in the lung are the most frequent findings encountered in research.     

Lead exposure causes generation of reactive oxygen species and functional impairment in rat sperm

The relationships between blood lead, sperm lead, sperm reactive oxygen species (ROS) level, and sperm fertile capability were investigated to understand the effects of lead exposure on sperm function and the mechanism of these effects. Male Sprague-Dawley rats, 7 weeks old, were randomly divided into control group and lead-treated group. The controls and lead-treated animals received intraperitoneal injection of 10 mg sodium acetate and 10 mg lead acetate/kg body weight, respectively, weekly for 6 or 9 weeks. The blood lead and epididymal sperm lead were analyzed by graphite furnace atomic absorption spectrophotometer. Chemiluminescence was measured to evaluate the generation of sperm ROS. Sperm-oocyte penetration rate (SOPR) was measured to evaluate sperm function. After 6 weeks of lead exposure, the rats had average blood lead levels of 32 microg/dl, sperm lead levels of 0.67 +/- 0.11 microg/10(9) sperm, unchanged epididymal sperm counts, percent of motile sperms, and motile epididymal sperm counts compared with control animals. However, after 9 weeks of lead exposure, the rats had average blood lead levels of 48.0 +/- 4.3 microg/dl, sperm lead levels of 0.88 +/- 0.16 microg/10(9) sperm, statistically lower epididymal sperm counts, and lower motile epididymal sperm counts. There was a good correlation between the blood lead and sperm lead(r2 = 0.946, P < 0.001). The sperms of lead-exposed rats produced significantly higher counts ofchemiluminescence than did those from the control rats (P < 0.001). The chemiluminescence counts were positively associated with sperm lead level (r2 = 0.613, P < 0.001). Epididymal sperm counts, motility and motile epididymal sperm counts were negatively associated with sperm chemiluminescence (r2 = 0.255, 0.152, and 0.299; P < 0.01, 0.05, and 0.01, respectively). The SOPR were positively associated with epididymal sperm counts, motility and motile epididymal sperm counts (r2 = 0.136, 0.285, and 0.264; P < 0.05, 0.01, and 0.001, respectively). The sperm chemiluminescence was negatively associated with SOPR (r2 = 0.519, P < 0.001). It is concluded that lead exposure probably affected the sperm function by activating one of the pathways of ROS generation.     

Na-H exchange inhibition with cariporide limits functional impairment caused by repetitive ischemia

Intracellular calcium ([Ca]i) overload on reperfusion may be one of the mechanisms responsible for ischemia-induced regional myocardial dysfunction. Because inhibiting the Na-H exchanger (NHE) limits intracellular sodium ([Na]i) and subsequent [Ca]i accumulation, we hypothesized that NHE inhibition would attenuate regional dysfunction in response to 25 cycles of ischemia (I, 2-min) and reperfusion (R, 8-min) of the left circumflex coronary artery (LCx) in conscious swine. Six animals were instrumented to measure arterial pressure, regional myocardial blood flow (colored microspheres), systolic wall thickening (WTh) in the normally perfused (left anterior descending, LAD) and LCx regions (sonomicrometry), LCx blood flow velocity (Doppler), and to reversibly occlude the LCx (hydraulic occluder). Each animal completed three protocols separated by 7 days: ISC, 25 I/R cycles; CAR, 25 I/R cycles + NHE inhibition (cariporide); and VEH, vehicle administration for 4.2 h. Regional myocardial blood flow was measured during LCx occlusion in the first protocol and 10 min after I/R 25 in all protocols. Systemic hemodynamics were similar among and within each protocol. Blood flow measured during LCx occlusion confirmed that perfusion was reduced (p < 0.05) to this compared with the LAD region. During ISC, LCx WTh was reduced (p < 0.05) after five IR cycles, and a stable reduction (approximately 55% of baseline; p < 0.05) was present after 20 I/R cycles. During CAR, LCx systolic WTh was reduced (p < 0.05) only after 15 and 25 I/R cycles (approximately 80 and 72%, respectively). The decrease in LCx WTh was greater in ISC than in CAR (p < 0.05). LCx WTh was not altered during VEH, while LAD WTh was similar within and among all protocols. Regional blood flow measured after 25 I/R cycles was not different among protocols. Our results indicate that NHE inhibition delays the onset and limits the degree of regional dysfunction in response to repeated bouts of ischemia and reperfusion.