Lesion-associated microglia and macrophages mediate corralling and react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion.

Neuroinflammation contributes to neuronal degeneration in Parkinson's disease (PD). However, how brain inflammatory factors mediate the progression of neurodegeneration is still poorly understood. Experimental models of PD have shed light on the understanding of this phenomenon, but the exploration of inflammation-driven models is necessary to better characterize this aspect of the disorder. The use of lipopolysaccharide (LPS) to induce a neuroinflammation-mediated neuronal loss is useful to induce reliable elimination of dopaminergic neurons. Nevertheless, how this model parallels the PD-like neuroinflammation is uncertain. In the present work, we used the direct LPS injection as a model inductor to eliminate dopaminergic neurons of the substantia nigra pars compacta (SNpc) in rats and reevaluated the inflammatory reaction. High-resolution 3D histological examination revealed that, although LPS induced a reliable elimination of SNpc dopaminergic neurons, it also generated a massive inflammatory response. This inflammation-mediated injury was characterized by corralling, a damaged parenchyma occupied by a vast population of lesion-associated microglia and macrophages (LAMMs) undertaking wound compaction and scar formation, surrounded by highly reactive astrocytes. LAMMs tiled the entire lesion and engaged in long-standing phagocytic activity to resolve the injury. Additionally, modeling LPS inflammation in a cell culture system helped to understand the role of phagocytosis and cytotoxicity in the initial phases of dopaminergic degeneration and indicated that LAMM-mediated toxicity and phagocytosis coexist during LPS-mediated dopaminergic elimination. However, this type of severe inflammatory-mediated injury, and subsequent resolution appear to be different from the ageing-related PD scenario where the architectural structure of the parenchyma is mostly preserved. Thus, the necessity to explore new experimental models to properly mimic the inflammatory compound observed in PD degeneration.

The high risk patient after recovery from myocardial infarction: recognition and management.

Patients at high risk for recurrent myocardial infarction or death can be identified after recovery from an acute myocardial infarction. Predictors of high risk at the time of initial hospital discharge may vary in different localities depending on the underlying baseline characteristics of the patient cohort. The medical records were analyzed of 139 patients discharged from San Francisco General Hospital after recovery from an acute myocardial infarction between July 1978 and September 1981. Multivariate stepwise discriminant analysis of 20 variables contributing to sudden and total death identified complex ventricular ectopic rhythm as the most important variable, followed by age. Failure to receive chronic long-acting nitrates was an independent variable contributing to total mortality but not to sudden death, while the presence of an initial anterior myocardial infarction and impaired left ventricular function were independent variables contributing to sudden death but not to total mortality. Routine 24 hour ambulatory monitoring, radionuclide ventriculography and submaximal stress tests performed during the second week after recovery from an acute myocardial infarction provide identification of a high risk cohort for subsequent recurrent myocardial infarction or death and permit appropriate interventions designed to lessen risk to be undertaken.

Magnetic resonance imaging of bone after radiation.

Magnetic resonance imaging (MRI) was performed in 22 patients at various times (0-3) years) following radiation therapy to the spine. T1 and T2 weighted images were obtained at 0.5 Tesla. Increased signal was seen after 800-6000 rads (8-60 Gy). Marrow effects corresponded to radiation ports. Recurrent tumor was clearly separated from fatty replacement. This was much better seen on T1 weighted images. Five patients that had MRI during their course of radiotherapy (XRT) did not have increased signal on T1 images of the bone marrow. The earliest fatty marrow change was seen nine days following completion of 3000 rads (30 Gy) XRT over one month's duration. One patient who received 800 rads (8 Gy) to the upper thoracic spine for eosinophilic granuloma had no radiation effects on MRI when imaged 16 days following completion of XRT given over five days. Fatty marrow change was seen in this patient on MRI six months later. MRI was particularly useful in defining the extent of prior radiation effects when repeat therapy was needed.

Hepatic amebic abscess: cholescintigraphic rim enhancement.

Cholescintigrams of 17 amebic liver abscesses (ALAs) in 13 patients were studied retrospectively. Rim enhancement around a photopenic defect was seen in nine (53%) of 17 abscesses. Most of the ALAs were solitary, in the right lobe, and ovoid. All were contiguous with the liver capsule. Ultrasonograms, obtained in 11 of 13 patients, showed the ALAs to be predominantly hypoechoic, with low-level echoes on high-gain settings. No sonographic finding could be identified to correlate with rim enhancement. Cholescintigraphic rim enhancement may allow early diagnosis of ALA in patients with right-upper-quadrant pain, facilitating early institution of specific therapy while definitive serologic confirmation of ALA is awaited.

Effects of antiarrhythmic drugs on atrioventricular conduction in patients with acute myocardial infarction.

Three hundred fifty-eight of 429 (83%) consecutive patients with acute myocardial infarction (MI) and a normal PR interval received various antiarrhythmic drugs (AD), including lidocaine and/or procainamide, quinidine, digoxin, propranolol or disopyramide. There was no significant difference in the incidence of progression to any degree of atrioventricular (AV) block or to higher degrees of AV block (Mobitz II or third-degree AV block) between those treated and not treated with AD: 38 of 358 (11%) and six of 358 (1.7%) with AD vs 11 of 71 (15%) and two of 71 (2.8%) in the untreated group, respectively. Similarly, there was no significant difference in progression between treated and untreated patients with anterior MI, 14 of 144 (10%) vs five of 32 (16%); inferior MI, 21 of 111 (19%) vs five of 26 (19%), or subendocardial MI, three of 103 (3%) vs one of 12 (8%). Bundle branch block (BBB) (without AV block) was initially present in 89 of 249 (21%). The incidence of AV block (seven of 24, 30%) was higher in treated patients with newly acquired BBB (27 patients) than in the untreated patients (none of three, p less than 0.05). The commonly used ADs did not adversely affect AV conduction in patients with acute MI with narrow QRS and either normal, first-degree, or Mobitz I AV block. Moreover, no subset of patients grouped by infarct location, specific AD used, or BBB (except perhaps for those with newly acquired BBB) appeared to be at risk of development of AV block during AD therapy.