Ophthalmologic techniques to assess the severity of hyperviscosity syndrome and the effect of plasmapheresis in patients with Waldenström's macroglobulinemia

BACKGROUND: The aim of this study is to determine the serum immunoglobulin (Ig) M and serum viscosity (SV) levels at which retinal changes associated with hyperviscosity syndrome (HVS) as a result of Waldenström's macroglobulinemia (WM) occur. In addition, the effect of plasmapheresis on HVS-related retinopathy was tested. PATIENTS AND METHODS: A total of 46 patients with WM received indirect ophthalmoscopy, laser Doppler retinal blood flow measurements, serum IgM, and SV determinations. A total of 9 patients with HVS were studied before and after plasmapheresis. RESULTS: Mean IgM and SV levels of patients with the earliest retinal changes were 5442 mg/dL and 3.1 cp, respectively. Plasmapheresis improved retinopathy, decreased serum IgM (46.5 +/- 18%; P = .0009), SV (44.7 +/- 17.3%; P = .002), retinal venous diameter (15.3 +/- 5.8%; P = .0001), and increased venous blood speed by +55.2 +/- 22.5% (P = .0004). CONCLUSION: Examination of the retina is useful in identifying the symptomatic threshold of plasma viscosity levels in patients with HVS and can be used to gauge the effectiveness of plasmapheresis treatment.

Effects of adjunct electroacupuncture on severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease

OBJECTIVE: To compare severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease treated with a combination of conventional analgesics and electroacupuncture (EAP) or with conventional analgesics alone. DESIGN: Controlled clinical trial. ANIMALS: 15 dogs undergoing surgery because of acute thoracolumbar disk disease. PROCEDURES: Dogs were alternately assigned to treatment (conventional analgesics and adjunct EAP) and control (conventional analgesics alone) groups. Analgesic treatment was adjusted as necessary by the attending clinician, who was not aware of group assignment. Pain scores were assigned 1, 3, and 12 hours after surgery and every 12 hours thereafter for 72 hours by the same individual who performed acupuncture treatments. RESULTS: Total dose of fentanyl administered during the first 12 hours after surgery was significantly lower in the treatment group than in the control group, but dosages of analgesics administered from 12 through 72 hours after surgery did not differ between groups. Pain score was significantly lower in the treatment group than in the control group 36 hours after surgery, but did not differ significantly between groups at any other time. CONCLUSIONS AND CLINICAL RELEVANCE: Results provided equivocal evidence that adjunct EAP might provide some mild benefit in regard to severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease.

Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease

The outcome of spinal surgery in dogs with absent voluntary motor function and nociception following intervertebral disc (IVD) herniation is highly variable, which likely attests to differences in the severity of spinal cord damage. This retrospective study evaluated the extent to which neurological signs correlated with histologically detected spinal cord damage in 60 dogs that were euthanased because of thoracolumbar IVD herniation. Clinical neurological grades correlated significantly with the extent of white matter damage (P<0.001). However, loss of nociception also occurred in 6/31 (19%) dogs with relatively mild histological changes. The duration of clinical signs, Schiff-Sherrington posture, loss of reflexes and pain on spinal palpation were not significantly associated with the severity of spinal cord damage. Although clinical-pathological correlation was generally good, some clinical signs frequently thought to indicate severe cord injury did not always correlate with the degree of cord damage, suggesting functional rather than structural impairment in some cases.

Antibiotic Susceptibility of Mycoplasma bovis Strains Recovered From Mycoplasmal Pneumonia and Arthritis in Feedlot Cattle

Mycoplasmal pneumonia and arthritis is a problem of increasing significance in Midwestern feedlots. The disease presentation cannot be prevented by vaccination or successfully treated with antimicrobials. Due to the reported difficulty in treating these outbreaks, in-vitro antimicrobial susceptibility was tested on isolates of Mycoplasma bovis recovered from cases of pneumonia or pneumonia and arthritis where the mycoplasma was involved as a causative agent. Using a broth microdilution method, 36 M. bovis isolates from cases of pneumonia and 9 from cases of pneumonia and arthritis were tested for susceptibility to antimicrobials currently used in cattle with respiratory disease (ampicillin, tilmycosin, spectinomycin, tylosin, lincomycin, tetracycline, ceftiofur, and erythromycin). Among the isolates from cases with pneumonia, resistance to more antimicrobials was shown in recent isolates than in isolates from earlier years. Tetracycline and lincomycin were the drugs of choice for these isolates, although 3 of 36 isolates were resistant to all drugs tested. Isolates from cases of pneumonia and arthritis were from recent accessions. A majority of these isolates (5/9) were resistant to all antimicrobials tested. Lincomycin, spectinomycin, and tetracycline were antibiotics usable with 4/9 of the isolates. Overall, the results indicate that antimicrobial therapy in cases of mycoplasmal feedlot pneumonia and arthritis may be unrewarding.

Isothermal loop-mediated amplification (LAMP) for diagnosis of contagious bovine pleuro-pneumonia.

BACKGROUND Contagious Bovine Pleuropneumonia (CBPP) is the most important chronic pulmonary disease of cattle on the African continent causing severe economic losses. The disease, caused by infection with Mycoplasma mycoides subsp. mycoides is transmitted by animal contact and develops slowly into a chronic form preventing an early clinical diagnosis. Because available vaccines confer a low protection rate and short-lived immunity, the rapid diagnosis of infected animals combined with traditional curbing measures is seen as the best way to control the disease. While traditional labour-intensive bacteriological methods for the detection of M. mycoides subsp. mycoides have been replaced by molecular genetic techniques in the last two decades, these latter approaches require well-equipped laboratories and specialized personnel for the diagnosis. This is a handicap in areas where CBPP is endemic and early diagnosis is essential. RESULTS We present a rapid, sensitive and specific diagnostic tool for M. mycoides subsp. mycoides detection based on isothermal loop-mediated amplification (LAMP) that is applicable to field conditions. The primer set developed is highly specific and sensitive enough to diagnose clinical cases without prior cultivation of the organism. The LAMP assay detects M. mycoides subsp. mycoides DNA directly from crude samples of pulmonary/pleural fluids and serum/plasma within an hour using a simple dilution protocol. A photometric detection of LAMP products allows the real-time visualisation of the amplification curve and the application of a melting curve/re-association analysis presents a means of quality assurance based on the predetermined strand-inherent temperature profile supporting the diagnosis. CONCLUSION The CBPP LAMP developed in a robust kit format can be run on a battery-driven mobile device to rapidly detect M. mycoides subsp. mycoides infections from clinical or post mortem samples. The stringent innate quality control allows a conclusive on-site diagnosis of CBPP such as during farm or slaughter house inspections.

Terrorists Among Us: Effects of a Suspect's Group Membership, Terrorist Past, and Knowledge on Lay Persons' Interrogation Severity Recommendations

Support among US citizens for severe interrogation has been recognized as drawing upon utilitarian as well as on retributive motivation (Carlsmith & Sood, 2009). Two studies were conducted to expand on these findings in a Swiss sample. In Study 1, participants rated the severity of different interrogation techniques, which were scaled to provide an alternative measure of interrogation severity. In Study 2, retributive motivation was manipulated by varying the terrorist past of a male suspect, and utilitarian motivation was manipulated by varying the probability that the suspect could provide valuable information. Additionally, we manipulated the suspect’s group membership. The results of the vignette study suggest that the number and severity of recommended interrogation techniques is mainly influenced by whether the suspect might provide valuable information. Whether the suspect had a terrorist past was an additional influence that, however, was primarily attributable to the suspect’s group membership: If the suspect belonged to the ingroup, participants’ harsher interrogation recommendations were affected by that person’s past, whereas recommendations were not significantly influenced by a terrorist past if the suspect was an outgroup member.

HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic

BACKGROUND Pulmonary fibrosis may result from abnormal alveolar wound repair after injury. Hepatocyte growth factor (HGF) improves alveolar epithelial wound repair in the lung. Stem cells were shown to play a major role in lung injury, repair and fibrosis. We studied the presence, origin and antifibrotic properties of HGF-expressing stem cells in usual interstitial pneumonia. METHODS Immunohistochemistry was performed in lung tissue sections and primary alveolar epithelial cells obtained from patients with usual interstitial pneumonia (UIP, n = 7). Bone marrow derived stromal cells (BMSC) from adult male rats were transfected with HGF, instilled intratracheally into bleomycin injured rat lungs and analyzed 7 and 14 days later. RESULTS In UIP, HGF was expressed in specific cells mainly located in fibrotic areas close to the hyperplastic alveolar epithelium. HGF-positive cells showed strong co-staining for the mesenchymal stem cell markers CD44, CD29, CD105 and CD90, indicating stem cell origin. HGF-positive cells also co-stained for CXCR4 (HGF+/CXCR4+) indicating that they originate from the bone marrow. The stem cell characteristics were confirmed in HGF secreting cells isolated from UIP lung biopsies. In vivo experiments showed that HGF-expressing BMSC attenuated bleomycin induced pulmonary fibrosis in the rat, indicating a beneficial role of bone marrow derived, HGF secreting stem cells in lung fibrosis. CONCLUSIONS HGF-positive stem cells are present in human fibrotic lung tissue (UIP) and originate from the bone marrow. Since HGF-transfected BMSC reduce bleomycin induced lung fibrosis in the bleomycin lung injury and fibrosis model, we assume that HGF-expressing, bone-marrow derived stem cells in UIP have antifibrotic properties.

The severity of neural invasion is associated with shortened survival in colon cancer

PURPOSE Neural invasion (NI) is a histopathologic feature of colon cancer that receives little consideration. Therefore, we conducted a morphologic and functional characterization of NI in colon cancer. EXPERIMENTAL DESIGN NI was investigated in 673 patients with colon cancer. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the in vitro three-dimensional (3D)-neural-migration assay and analyzed via live-cell imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic-chemoattractant factors Artemin and nerve growth factor (NGF), was quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of newborn rats were exposed to supernatants of colon cancer, rectal cancer, and pancreatic cancer cells and neurite density was determined. RESULTS NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in colon cancer. In the 3D migration assay, colon cancer and rectal cancer cells showed much less neurite-targeted migration when compared with pancreatic cancer cells. Supernatants of pancreatic cancer and rectal cancer cells induced a much higher neurite density than those of colon cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in nerves in pancreatic cancer than in colon cancer. CONCLUSION NI is not an independent prognostic factor in colon cancer. The lack of a considerable biologic affinity between colon cancer cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in colon cancer may explain the low prevalence and impact of NI in colon cancer.

TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions. While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens, excessive production of cytokines and oxygen radicals can also severely harm the host. Studies addressing the pathogenic role of TREM-1 during endotoxin-induced shock or microbial sepsis have so far mostly relied on the administration of TREM-1 fusion proteins or peptides representing part of the extracellular domain of TREM-1. However, binding of these agents to the yet unidentified TREM-1 ligand could also impact signaling through alternative receptors. More importantly, controversial results have been obtained regarding the requirement of TREM-1 for microbial control. To unambiguously investigate the role of TREM-1 in homeostasis and disease, we have generated mice deficient in Trem1. Trem1(-/-) mice are viable, fertile and show no altered hematopoietic compartment. In CD4(+) T cell- and dextran sodium sulfate-induced models of colitis, Trem1(-/-) mice displayed significantly attenuated disease that was associated with reduced inflammatory infiltrates and diminished expression of pro-inflammatory cytokines. Trem1(-/-) mice also exhibited reduced neutrophilic infiltration and decreased lesion size upon infection with Leishmania major. Furthermore, reduced morbidity was observed for influenza virus-infected Trem1(-/-) mice. Importantly, while immune-associated pathologies were significantly reduced, Trem1(-/-) mice were equally capable of controlling infections with L. major, influenza virus, but also Legionella pneumophila as Trem1(+/+) controls. Our results not only demonstrate an unanticipated pathogenic impact of TREM-1 during a viral and parasitic infection, but also indicate that therapeutic blocking of TREM-1 in distinct inflammatory disorders holds considerable promise by blunting excessive inflammation while preserving the capacity for microbial control.

Injuries in agriculture-injury severity and mortality

PRINCIPALS Accidents in agriculture are a problem of global importance. The hazards of working in agriculture are manifold (machines, animals, heights). We therefore assessed injury severity and mortality from accidents in farming. METHODS We retrospectively analysed all farming accidents treated over a 12-year period in the emergency department (ED) of our level I trauma centre. RESULTS Out of 815 patients 96.3% were male and 3.7% female (p <0.0001). A total of 70 patients (8.6%, 70/815) were severely injured. Patients with injuries to the chest were most likely to suffer from severe injuries (odds ratio [OR] 9.45, 95% confidence interval [CI] 5.59-16.00, p <0.0001), followed by patients with injuries to the abdomen (OR 7.06, 95% CI 3.22-15.43, p <0.0001) and patients with injuries to the head (OR 5.03, 95% CI 2.99-8.66, p <0.0001). Hospitalisation was associated with machine- and fall-related injuries (OR 22.39, 95% CI 1.95-4.14, p <0.0001 and OR 2.84 95% CI 1.68-3.41 p <0.001, respectively). Patients suffering from a fall and patients with severe injury were more likely to die than others (OR 3.32, 95% CI 1.07-10.29, p <0.037 and OR 9.17, 95% CI 6.20-13.56, p <0.0001, respectively). Fall height correlated positively with the injury severity score , hospitalisation and mortality (all p <0.0001). CONCLUSION Injuries in agriculture are accompanied by substantial morbidity and mortality, and range from minor injuries to severe multiple injuries. Additional prospective studies should be conducted on injury severity, long-term disability and mortality.

Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severity.

Preeclampsia (PE), a syndrome affecting 5% of pregnancies, characterized by hypertension and proteinuria, is a leading cause of maternal and fetal morbidity and mortality. The condition is often accompanied by the presence of a circulating maternal autoantibody, the angiotensin II type I receptor agonistic autoantibody (AT(1)-AA). However, the prevalence of AT(1)-AA in PE remains unknown, and the correlation of AT(1)-AA titers with the severity of the disease remains undetermined. We used a sensitive and high-throughput luciferase bioassay to detect AT(1)-AA levels in the serum of 30 normal, 37 preeclamptic (10 mild and 27 severe), and 23 gestational hypertensive individuals. Here we report that AT(1)-AA is highly prevalent in PE ( approximately 95%). Next, by comparing the levels of AT(1)-AA among women with mild and severe PE, we found that the titer of AT(1)-AA is proportional to the severity of the disease. Intriguingly, among severe preeclamptic patients, we discovered that the titer of AT(1)-AA is significantly correlated with the clinical features of PE: systolic blood pressure (r=0.56), proteinuria (r=0.70), and soluble fms-like tyrosine kinase-1 level (r=0.71), respectively. Notably, only AT(1)-AA, and not soluble fms-like tyrosine kinase-1, levels are elevated in gestational hypertensive patients. These data serve as compelling clinical evidence that AT(1)-AA is highly prevalent in PE, and its titer is strongly correlated to the severity of the disease.

Less structured movement patterns predict severity of positive syndrome, excitement, and disorganization

Disorganized behavior is a key symptom of schizophrenia. The objective assessment of disorganized behavior is particularly challenging. Actigraphy has enabled the objective assessment of motor behavior in various settings. Reduced motor activity was associated with negative syndrome scores, but simple motor activity analyses were not informative on other symptom dimensions. The analysis of movement patterns, however, could be more informative for assessing schizophrenia symptom dimensions. Here, we use time series analyses on actigraphic data of 100 schizophrenia spectrum disorder patients. Actigraphy recording intervals were set at 2 s. Data from 2 defined 60-min periods were analyzed, and partial autocorrelations of the actigraphy time series indicated predictability of movements in each individual. Increased positive syndrome scores were associated with reduced predictability of movements but not with the overall amount of movement. Negative syndrome scores were associated with low activity levels but unrelated with predictability of movement. The factors disorganization and excitement were related to movement predictability but emotional distress was not. Thus, the predictability of objectively assessed motor behavior may be a marker of positive symptoms and disorganized behavior. This behavior could become relevant for translational research.