Pathophysiology of nerve injury

The response to nerve injury is a complex and often poorly understood mechanism. An in-depth and current command of the relevant neuroanatomy, classifications systems, and responses to injury and regeneration are critical to current clinical success. Continued progress must be made in our current understanding of these varied physiologic mechanisms of neuro-regeneration if any significant progress in clinical treatments or outcome is to be expected in the future. Reconstructive surgeons have in many ways maximized the technical aspects of peripheral nerve repair. However, advances in functional recovery may be seen with improvements in sensory and motor rehabilitation after peripheral nerve surgery and with a combined understanding of the neurobiology and neurophysiology of nerve injury and regeneration.     

Effect of simultaneous blockade of AT1 and AT2 receptors on the NFkappaB pathway and renal inflammatory response

BACKGROUND: Angiotensin II (Ang II) is a cytokine that participates in the inflammatory response. The nuclear factor kappa B (NFkappaB) is involved in the regulation of many immune and inflammatory factors. Different works have shown that both angiotensin II receptor type 1 (AT1) and type 2 (AT2) receptors are involved in the NFkappaB pathway; however, some aspects remain mysterious. AT1 antagonists increased plasma Ang II levels that could bind to AT2, so understanding the clinical importance of AT2 stimulation or inhibition is an interesting unresolved point. METHODS: Experiments were done in wild-type (WT) and AT1a receptor knockout mice that received subcutaneous Ang II infusions (1000 ng/kg/min) for 3 days. Specific blockers of AT1 (losartan 10 mg/kg/day) and AT2 (PD123319 30 mg/kg/day) receptors were administered 1 day before and during Ang II infusion. NFkappaB activity was examined by electrophoretic mobility assay and inflammatory (monocyte/macrophage) cell infiltration by immunohistochemistry RESULTS: In WT mice, Ang II infusion caused renal NFkappaB activation that was partially diminished by either AT1 or AT2 antagonists. In AT1 knockout mice, Ang II also activated renal NFkappaB, which was only blocked by the AT2 antagonist. Both Ang II-infused WT and AT1 knockout mice showed inflammatory infiltration in tubulointerstitial areas that were suppressed by the AT2, but not AT1, antagonist. Combined therapy of both AT1 and AT2 antagonists blocked renal NFkappaB activation and inflammatory cell infiltration, both in WT and in AT1 knockout mice. CONCLUSION: Ang II, via AT1 and AT2 stimulation, leads to NFkappaB activation that was only blocked by combined therapy with both antagonists. The participation of AT2 receptors in the recruitment of inflammatory cells underscores the need of future studies that evaluate the clinical usefulness of this strategy.     

Inflammatory aneurysm in the infrarenal portion of thoracoabdominal aneurysms: an uncommon variant

INTRODUCTION: We present an unusual variant of type IV thoracoabdominal aneurysm with inflammatory changes in part of the aortic wall. MATERIAL AND METHODS: Between January 1990 and December 2000, 5 male patients (mean age, 68 years) with inflammatory aneurysms of 29 with type IV thoracoabdominal aneurysms (17.2%) underwent surgery. All five had arterial hypertension. The diagnosis of inflammatory aneurysm was made on the basis of clinical suspicion supported by characteristic features on CT scans. Endoaneurysmorraphy was performed in all cases; a tube graft was inserted in three cases, and bifurcation was performed in 2. The macroscopic appearance of periaortic fibrosis was detected at the infrarrenal portion of the aneurysm in the 5 patients, but no retroperitoneal fibrosis was found at the level of the distal thoracic aorta in any case. RESULTS: There was no operative mortality. Paraparesis was not detected in any patient. One patient had acute kidney failure, and another required an extended stay in the intensive care unit because of respiratory insufficiency. Pathologic examination confirmed the diagnosis of inflammatory aneurysm in all 5 patients, with characteristic adventitial thickening caused by lymphoplasmacytic infiltrate and fibrosis around the ganglionic and nerve structures. CONCLUSIONS: Type IV thoracoabdominal aneurysm with inflammatory changes can be treated at surgery with a retroperitoneal approach. Usually the fibrotic response is confined to the infrarenal portion of the aneurysm.     

Immunohistology of antigen-presenting cells in vivo: a novel method for serial observation of fluorescently labeled cells

PURPOSE: Dendritic cells and macrophages are phagocytic antigen-presenting cells that bridge the innate and acquired immune systems. The coexistence of subtypes of dendritic cells and macrophages with overlapping properties complicates resolution of their precise roles in an immune response within a given tissue. This report documents a method to identify and observe these cells over time in a living animal and thereby to visualize them during a dynamic immune response. METHODS: To label potential antigen-presenting cells, fluorescently tagged ovalbumin was injected into the anterior chambers of mouse eyes. Fluorescently tagged antibodies to cell surface proteins were injected to label specific cell types. Intravital fluorescence microscopy with digital image recording was used to visualize the labeled cells in the irises at various times after the injection. RESULTS: The pattern and density (116-148 cells/mm(2)) of cells labeled in vivo by fluorescent ovalbumin or F4/80 antibodies were similar to that identified by conventional wholemount immunostaining for macrophages and dendritic cells. Fluorescent antibodies specific for CD11b, CD11c, CD80, CD86, or major histocompatibility complex (MHC) class II protein each labeled selective populations of cells in vivo. In contrast to conventional histology, in vivo immunohistology permitted serial observations. The phenotype of cells labeled by fluorescent ovalbumin was not the same at 6 (95% CD11c(+)) and 24 hours (24% CD11c(+)) after injection. CONCLUSIONS: This method of in vivo immunohistology provides a tool for studying cell kinetics and dynamic interactions that cannot be assessed by conventional immunohistology. Furthermore, it avoids potential artifacts from tissue fixation and may work with antibodies that label cells poorly in vitro.     

Recombinant congenic strains of mice: a new tool for the genetic dissection of efficacy and toxicity of adjuvants

The efficacy of immunization of a vaccine depends on an antigen, an adjuvant, and on the expression of multiple genes in the host. The responsiveness of various strains of mice to adjuvants is therefore dependent on their genetic background present as a complex, multigenic trait similarly as in man. We have recently developed a gene-discovery platform, termed recombinant congenic strains (RCS), that greatly facilitates the dissection, localization and characterization of genes that mediate complex traits such as responsiveness to adjuvants. These recombinant congenic mice, which were constructed from two progenitor strains (A/J and C57BL/6) that are phenotypically different for several spontaneous or infectious diseases, were generated such that they carry 13.5% of the one genome in 85% of the other genome. The use of these RCS mice therefore enables a more efficient identification of genes that mediate the responsiveness of the adjuvant.     

Oral sex and HIV among men who have sex with men

Sexual transmission of the human immunodeficiency virus (HIV) continues to pose a public health problem worldwide. Men who have sex with men are still at differential risk of infection. Although there is evidence to claim that HIV can be transmitted by oral sex, the perception of this risk is ambiguous and relates paradoxically to behavior change. New models of risk perception must be developed in various areas of knowledge to obtain a fuller understanding of this phenomenon.     

Perioperative myocardial ischemia in patients undergoing sternectomy shortly after coronary artery bypass grafting

Coronary revascularization reduces cardiac complications associated with noncardiac surgery in patients with severe coronary disease. However, patients undergoing emergency noncardiac surgery soon after coronary bypass operations may still be vulnerable to ischemic myocardial events. We prospectively evaluated the incidence of myocardial ischemia in 82 consecutive patents scheduled for sternectomy in the first (Group 1; 35 patients) or second (Group 2; 47 patients) week after coronary artery bypass graft (CABG) surgery. The interval between CABG surgery and sternectomy in Groups 1 and 2 was 6 days (range, 4-7 days) and 11 days (range, 8-14 days), respectively. Electrocardiographic (ECG) changes consistent with myocardial ischemia were assessed with a two-channel Holter system for 48 h. There were no between-group differences in updated Acute Physiology and Chronic Health Evaluation score, use of beta-blockers, or perioperative hemodynamic changes. The incidence of ECG changes consistent with myocardial ischemia was fivefold more frequent in Group 1 (22.85% versus 4.25%; P < 0.05). Of the ischemic patients in Group 1, 25% experienced a perioperative acute myocardial infarction (one was fatal). There were no infarcts in Group 2. Thus, patients appear to be prone to coronary events during sternectomy performed early after CABG surgery. Although the incidence of ischemia did not differ from that previously reported after CABG surgery alone, further investigation is required to determine whether the findings obtained in this high-risk population are generalizable to patients undergoing noncardiac surgery soon after uneventful CABG surgery. IMPLICATIONS: This study demonstrates an increased incidence of myocardial ischemia when sternectomy for mediastinitis is performed within one week of coronary artery bypass graft surgery, and this ischemia is associated with a 25% incidence of myocardial infarction.     

Benign cystic mesothelioma with multiple recurrences: a clinical case

Benign multicystic mesothelioma is a rare disease with a high tendency to local recurrence, but with no tendency to malignancy. The correct diagnosis can be made by histopathological examination in conjunction with immunohistochemical and ultrastructural evaluations. A case of benign cystic mesothelioma recurring three times in a 48-year-old woman is reported, and the management of this disease and the importance of radical surgery are discussed.     

Cervico-mediastinal hematoma secondary to extracapsular hemorrhage of parathyroid carcinoma. Clinical case and review of the literature

Extracapsular parathyroid haemorrhage is a rare but ominous occurrence, which may cause cervico-mediastinal haematoma and a severe calcaemia imbalance. We identified only 23 cases reported in the literature and these were always secondary to adenoma, hyperplasia or cysts, and never to carcinoma. We describe a case of a 56-year-old man who was admitted to our Institute because of the sudden development of an anterior neck swelling, together with dysphagia, dyspnoea and hoarseness. Physical examination revealed a large ecchymosis extending from the anterior neck to the upper chest, while the early symptoms had disappeared. Laboratory studies, ultrasonography and 99mtTC-Sestamibi scintiscan demonstrated the presence of primary parathyroidism due to a right inferior parathyroid neoplasm. At operation, the parathyroid was excised en bloc with the right thyroid lobe because they were joined together by an extensive fibrous reaction. Histological examination showed a well-differentiated parathyroid carcinoma with evidence of recent haemorrhage. To the best of our knowledge this is the first case of extracapsular haemorrhage due to a parathyroid carcinoma. In summary, although parathyroid haemorrhage is a rare condition, it should always be suspected when a painful mass or diffuse swelling suddenly occurs in the anterior neck, with or without ecchymosis, especially when serum calcium and phosphorus are abnormal.