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Aortitis with dissection complicating systemic lupus erythematosus.

A 31 yr old female under treatment for systemic lupus erythematosus complained of episodes of atypical chest pain radiating to the back. Subsequently she suddenly collapsed and died. Post mortem revealed a well-defined, localized area of non-giant cell aortitis extending from the supra-aortic ridge of the aortic valve to the ligamentum arteriosum. Active arteritis with fibrinoid necrosis and obliterative endarteritis of vasa vasorum had resulted in multiple infarcts of differing ages with associated inflammation and disruption of the aortic wall, culminating in aortic dissection and cardiac tamponade.

Adult↗

Blood supply and vasculature of mycetoma.

The blood supply to the mycetoma lesion and its vasculature were studied in patients with various types of mycetoma using histological, ultrastructural, angiographic and sonographic techniques. The mycetoma lesion proved to be well vascularized. However, certain vascular abnormalities were demonstrated. In histological sections, the small arteries and arterioles showed medial muscular hypertrophy in 83%, intimal fibrosis in 33%, arteritis in 7% and endarteritis obliterans with narrowed lumen in 7% of the patients. No vascular occlusion, ischaemic changes or arteriovenous shunts were observed. These changes were confirmed ultrastructurally. Angiography of the lesion showed a brisk pathological circulation which was more evident in eumycetoma. The vascular Doppler study showed normal blood flow pattern in the affected limb. Regional intra-arterial chemotherapy for mycetoma is suggested as a possible treatment modality.

Arteries↗

Vascular pathology in hypertension.

The pathological changes in blood vessels observed in primary (essential hypertension) are similar to those seen in secondary hypertension due to renal disease or other causes. In benign hypertension, the major changes are in the small arteries and arterioles especially in the kidney. Interlobular arteries exhibit intimal thickening and duplication of the elastic lamina (elastosis) and there is hyaline change in the media of many arterioles. In some respects these changes are an accentuation of vessel ageing. Malignant hypertension usually presents in a younger age group (35--50 years) and is characterized pathologically by fibrous endarteritis in the interlobular arteries of the kidney and fibrinoid necrosis in the walls of a proportion of the efferent glomerular arterioles. Similar vessel changes are seen in other organs but many of the pathological changes in the heart and brain of patients with benign hypertension are related to the accentuation of arterosclerosis. There is an increased mortality from cardiac failure, myocardial infarction, cerebral haemorrhage and subarachnoid haemorrhage due to ruptured berry aneurysms in patients with benign hypertension. Although there is ischaemic damage to the kidneys in benign hypertension, death from renal failure is uncommon. Severe ischaemic damage to renal glomeruli and renal failure does, however, occur in malignant hypertension.

Aging↗

Syphilitic lymphadenopathy. Histology and human immunodeficiency virus status.

Few reports on syphilitic lymphadenopathy have appeared in 20 years, and none have compared findings in patients with and without human immunodeficiency virus (HIV) infection, despite the recent epidemic spread of syphilis and HIV. Twelve cases of syphilitic lymphadenopathy were studied and grouped according to HIV status. Patients were 21 to 62 years old (median, 29 years); 7 were men, 5 were women. Biopsy sites were cervical (7 cases), inguinal (4), and axillary (1) lymph nodes. All patients had evidence of syphilis. Rapid plasma reagin titers ranged from 1:32 to 1:512. Treponemal hemagglutination was positive in all cases tested. Spirochetes were found with Steiner staining in 2 cases. HIV testing was positive in 4, negative in 2, and unknown in 6 cases. Lymph nodes were enlarged and often fragmented due to capsular fibrosis and chronic inflammation, with focal obliteration of the subcapsular sinus. Follicular and interfollicular hyperplasia was seen in all cases and was usually marked, with prominent vascular proliferation, plasma cells, immuno-blasts, histiocytes, and occasional neutrophils. Follicle lysis and granulomas suggestive of unconfirmed toxoplasmosis were each seen in 1 case, and Kaposi sarcoma in 2, all in HIV-positive patients. Lymphoplasmacytic infiltration was marked, especially in interfollicular areas, with peri-vascular plasma cell cuffing in all cases and obliterative endarteritis in about half (7 of 12, 56%). Immunostaining for CD45RO (UCHL-1), CD20 (L26), kappa, lambda, and CD68 (Kp-1) revealed a mixed population of T cells, polyclonal B cells, and interfollicular histiocytes. Distribution of T and B cells (immunoarchitecture) was essentially normal and similar in all cases, regardless of HIV status. Syphilis produces essentially identical findings in lymph nodes in both HIV-positive and HIV-negative patients. The morphologic findings described should prompt evaluation for infection with Treponema pallidum and, in light of the current epidemic, HIV.

Adult↗

Coccidioidomycosis of the central nervous system: neuropathological and vasculopathic manifestations and clinical correlates.

Infection due to the fungus Coccidioides immitis, which is endemic to the southwestern United States, is currently occurring in epidemic proportions. Although it usually presents as a subclinical infection or a mild, self-limited pulmonary infection, disseminated infection can occur, especially in immunosuppressed patients. In patients with disseminated coccidioidomycosis, CNS spread is commonly responsible for significant morbidity and mortality. The neurological presentations of C. immitis infection of the CNS are variable. The spectrum of neuropathological change ranges from meningitis to meningoencephalitis and meningomyelitis with extensive parenchymal destruction, sometimes as a result of an associated endarteritis obliterans. We describe a patient with AIDS who developed CNS coccidioidomycosis, and we report the findings of a clinicopathological analysis of eight patients with fatal CNS coccidioidomycosis who were autopsied at UCLA Medical Center. CNS coccidioidomycosis should be considered in the differential diagnosis of patients with neurological symptoms, especially when they are immunosuppressed and live in regions where the disease is endemic.

AIDS-Related Opportunistic Infections↗

Invasive staphylococcal infections complicating percutaneous transluminal coronary angioplasty: three cases and review.

Infectious complications infrequently occur after percutaneous transluminal coronary angioplasty (PTCA) is performed. We recently treated three patients with invasive staphylococcal infections that developed after PTCA. Two patients had septic arthritis of the knee joint secondary to probable femoral endarteritis, and the third patient had an infected hematoma of the groin. Early reuse of the initial puncture site, prolonged retention of the femoral sheath, bleeding or hematoma at the femoral sheath insertion site and vascular complications such as pseudoaneurysm may predispose to infectious sequelae after PTCA. The clinician should be aware of these risks and the possibility that a patient may develop these potentially serious complications after PTCA.

Aged↗

Multicenter study of the clinical efficacy of imipenem/cilastatin for treatment of serious infections.

The efficacy and safety of imipenem/cilastatin was evaluated in a multicenter study. For 49 of the 78 patients with 79 infections entered into the study, the clinical and bacteriologic efficacy of therapy could be evaluated. Toxicity data were analyzed for all 79 infections. Overall, 35 of 49 infections were cured or improved: 10 of 11 cases of pneumonia; 8 of 15 cases of pyelonephritis; 4 of 5 cases of osteomyelitis; 3 of 4 intravascular infections; 6 of 9 soft tissue infections; and 4 of 5 miscellaneous infections. There were 13 bacteriologic failures; superinfections with resistant organisms (i.e., Candida albicans, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas maltophilia) occurred in three patients; reinfection with sensitive pathogens complicated one urinary tract infection; relapses developed of five urinary tract infections and of one case of endarteritis; and bacteriologic persistence occurred in three soft tissue infections. Infections with Pseudomonas aeruginosa were the most difficult to treat. In only six of 11 P. aeruginosa infections was both bacteriologic and clinical cure achieved. Adverse effects were minimal; no serious hematologic or hepatic toxicity and no adverse renal effects were noted.

Adult↗

A spectrum of clinicopathological features of nephropathy associated with POEMS syndrome.

BACKGROUND: In POEMS syndrome, substantial involvement of the kidney can occur and is reflected by proteinuria, haematuria, renal dysfunction, and renal failure requiring dialysis therapy. The mechanism by which renal dysfunction is induced and progresses to end-stage renal disease remains obscure. A pathogenic role of cytokines and growth factors has recently been implicated. METHODS: We reviewed cases of 52 Japanese patients with confirmed renal pathology who were reported in the literature, and personally analysed renal tissues from 22 subjects including nine patients of our own. Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were measured in our cases. RESULTS: Despite relatively mild renal symptomatology, about half of the cases had azotaemia with creatinine levels above 1.5 mg/dl and the BUN/creatinine ratio markedly raised by volume contraction or wasting. One-tenth of patients were placed on haemodialysis because of advanced or end-stage renal disease. Bilateral and unilateral contracted kidneys were found in four and two cases respectively. Pathological analyses disclosed two major changes: glomerular alterations and endarteritis-like lesions of renal small arteries. The former included glomerular enlargement, cellular proliferation, mesangiolysis and marked swelling of endothelial-mesangial cells. This structural disorganization led to a reduction in renal function to some degree by impairing the glomerular circulation. Vasculopathy of the small artery probably resulted in progressive renal damage and ultimately to kidney contraction. Serum IL-6 was elevated in about 40% of cases. IL-6 levels were found to be high in the ascites of three patients who were examined. In different studies, an increased level of VEGF was found in the peripheral blood (75-100%; overall 92.3%), but no apparent correlation with glomerular alterations was observed. CONCLUSION: POEMS nephropathy can be one cause of end-stage renal disease with variable intrarenal pathological changes of a microangiopathic nature which have differential influences on renal function. A pathogenic role for VEGF in POEMS syndrome appears to be likely, but its causal relation to the nephropathy awaits further investigation.

Adult↗

Inadvertent intraradial arterial injection of cocaine.

Injection of a chemical irritant into the radial artery at the wrist causes acute discoloration of the skin, edema, and pain in the hand. Subsequent damage due to vasospasm, endarteritis, particulate embolization, and vascular thrombosis may result in ischemic contractures, amputations, and other functional hand deficits. Injection of a street cocaine preparation into the radial artery of a 22-year-old man produced a constellation of signs and symptoms similar to that described for other irritants. Current thoughts with regard to the pathophysiology and treatment of these injuries are reviewed.

Adult↗

The neuromuscular pathology of the Eosinophilia-Myalgia syndrome.

The Eosinophilia-Myalgia Syndrome (EMS) is a recently reorganized disorder in patients ingesting pharmacologic doses of L-tryptophan. We studied the lesions of skeletal muscle, peripheral nerve and skin in 12 cases of EMS. Perimyositis was severe in four, moderate in two, mild in three and absent in three cases. The lesions contained many eosinophils, T-helper cells, mast cells and activated macrophages. Type 2 myofiber atrophy was present in five cases and in one, this was the only pathologic finding. Severe epineurial inflammation was seen in the three sural nerve biopsies. Indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs (two cases) and neurogenic atrophy (one case). Phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one. Fasciitis was present in three of four skin biopsies and dermal fibrosis in one.

Adult↗

Delayed neovascularization in free skin flap transfer to irradiated beds in rats.

A model for the study of neovascularization with a normal epigastric free flap set into an irradiated defect in the Fischer F344 rat is presented. In this model, both the administration of radiation and the flap transfer mimic the clinical situation. Significantly less tissue survives loss of the complete vascular pedicle at the second to fourth days following flap creation in rats with an irradiated bed. Later survival is not different from controls. Delayed neovascularization is proposed as the mechanism responsible for this effect during the period corresponding to the onset of the late phase of the response to skin radiation in rats. That neovascularization does occur, although delayed, suggests that the induced endarteritis may not be as important as previously suggested.

Animals↗

Cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis.

Vasculitis, inflammation of the vessel wall, can result in mural destruction with hemorrhage, aneurysm formation, and infarction, or intimal-medial hyperplasia and subsequent stenosis leading to tissue ischemia. The skin, in part due to its large vascular bed, exposure to cold temperatures, and frequent presence of stasis, is involved in many distinct as well as un-named vasculitic syndromes that vary from localized and self-limited to generalized and life-threatening with multi-organ disease. To exclude mimics of vasculitis, diagnosis of cutaneous vasculitis requires biopsy confirmation where its acute signs (fibrinoid necrosis), chronic signs (endarteritis obliterans), or past signs (acellular scar of healed arteritis) must be recognized and presence of extravascular findings such as patterned fibrosis or collagenolytic granulomas noted. Although vasculitis can be classified by etiology, many cases have no identifiable cause, and a single etiologic agent can elicit several distinct clinicopathologic expressions of vasculitis. Therefore, the classification of cutaneous vasculitis is best approached morphologically by determining vessel size and principal inflammatory response. These histologic patterns roughly correlate with pathogenic mechanisms that, when coupled with direct immunofluorescent examination, anti-neutrophil cytoplasmic antibody (ANCA) status, and findings from work-up for systemic disease, allow for specific diagnosis, and ultimately, more effective therapy. Herein, we review cutaneous vasculitis focusing on diagnostic criteria, classification, epidemiology, etiology, pathogenesis, and evaluation of the cutaneous vasculitis patient.

Humans↗

A portuguese isolate of Borrelia lusitaniae induces disease in C3H/HeN mice.

A low-passage, Portuguese isolate of Borrelia lusitaniae, strain PotiB2, was inoculated into C3H/HeN mice and disease was monitored by histopathology at 8 weeks after spirochaete challenge. Ear, heart, bladder, femoro-tibial joint, brain and spinal cord were examined. B. lusitaniae strain PotiB2 (6 of 10 mice) and B. burgdorferi sensu stricto strain N40 (9 of 10 mice) induced similar lesions in the bladder of infected mice characterised as a multifocal, lymphoid, interstitial cystitis. Moreover, both B. lusitaniae PotiB2 and B. burdorferi N40 induced lesions in the heart of infected mice. The lesions induced by B. lusitaniae PotiB2 (2 of 10 mice) were characterised as a severe, necrotising endarteritis of the aorta, with a minimal, mixed inflammatory infiltrate (neutrophils, macrophages and lymphoid cells) extending into the adjacent myocardium. In contrast, B. burgdorferi N40 induced a periarteritis of the pulmonary artery (7 of 10 mice), with no involvement of the endothelium and more extensive inflammation and subsequent necrosis of the adjacent myocardium. This infiltrate was composed entirely of mononuclear cells, predominantly mature lymphocytes and plasma cells. No lesions were noted in the joints or central nervous system with inoculation of strains N40 or PotiB2, and co-inoculation of either strain with Ixodes ricinus salivary gland lysate did not affect the resulting pathology. Serology, examined 8 weeks after inoculation, indicated a different reactivity in mice infected with B. lusitaniae PotiB2 compared with B. burgdorferi N40. Immunoblot analysis demonstrated that mice with lesions resulting from infection with B. lusitaniae PotiB2 reacted only to the flagellin protein (41 kDa) or to flagellin and OspC, whereas mice infected with B. burgdorferi N40 reacted with multiple high and low mol. wt proteins, including flagellin, p93, p39, OspA, OspB and OspC. These results indicate that B. lusitaniae PotiB2 induced pathology similar to B. burgdorferi N40 when inoculated into susceptible mice. Moreover, these results establish the first animal model of disease with B. lusitaniae. This mouse model can be used to characterise the immunopathogenesis of B. lusitaniae infection and to delineate the proteins responsible for disease induction in susceptible mice.

Animals↗

The microscopic features of inflammatory abdominal aortic aneurysms: discriminant analysis.

Up to 15% of abdominal aortic aneurysms are designated as inflammatory. They are characterized by marked fibrous thickening of the aneurysmal wall, with the fibrosis extending into the adjacent retroperitoneum. Thirty-five abdominal aortic aneurysms were studied, 15 inflammatory and 20 atherosclerotic. Of the inflammatory group, 10 were symptomatic and five asymptomatic. For each resection specimen, 59 microscopic features (variables) were scored semi-quantitatively. Discriminant function analysis showed that endarteritis obliterans, fibrosis around nerves or ganglia at the outer margin of mural fibrosis, and the thickness of the combined fibrotic media and adventitia gave a satisfactory high discrimination between atherosclerotic and inflammatory aneurysms. When these three variables are used together, a histological diagnosis of inflammatory aneurysm can be made with an expected accuracy in excess of 80%.

Aged↗

Neuropathology of acquired immunodeficiency syndrome.

The nervous system is involved in the acquired immunodeficiency syndrome (AIDS) by infections and infestations, by neoplasms, and by several diseases of uncertain pathogenesis. The most common pathological abnormalities are the changes associated with the HIV agent itself, the 'HIV subacute encephalitis'; the most specific change is demyelination with multinucleate giant cells. Cytomegalovirus (CMV) is the most common secondary virus, but progressive multifocal leucoencephalopathy (PML) is more frequently seen at biopsy. Toxoplasmosis is the most common cause of abscess formation, but fungal infections, especially by cryptococcus, are more often the cause of meningitis. Mycobacterial infections and other opportunistic organisms are relatively rarely seen in the CNS. A vacuolar myelopathy of unknown pathogenesis is seen in AIDS; it involves the dorsal and lateral columns and the thoracic spinal cord most prominently. Endarteritis of unknown cause with resultant infarction is seen in children. Primary CNS lymphoma accounts for a major percentage of the lymphomas seen in AIDS; they are high grade tumours, are most often multiple, and are of B-cell origin. Metastatic Kaposi's sarcoma is very rare. Several peripheral neuropathies occur in AIDS, and recently a myopathy with small rod bodies has been reported.

Acquired Immunodeficiency Syndrome↗

Subacute pulmonary hypertension due to carcinomatous microembolism.

A 43 year old female was admitted to hospital with severe pulmonary hypertension and cardiogenic shock. She had a two week history of dyspnea only. Resuscitative measures proved unsuccessful and she died ten hours after admission. Post mortem examination indicated that the pulmonary hypertension and right ventricular failure were due to endarteritis secondary to widespread carcinomatous microembolism from adenocarcinoma of the lung.

Adult↗

Coarctation of the aorta: a secondary cause of hypertension.

Coarctation of the aorta is a constriction of the aorta located near the ligamentum arteriosum and the origins of the left subclavian artery. This condition may be associated with other congenital disease. The mean age of death for persons with this condition is 34 years if untreated, and is usually due to heart failure, aortic dissection or rupture, endocarditis, endarteritis, cerebral hemorrhage, ischemic heart disease, or concomitant aortic valve disease in uncomplicated cases. Symptoms may not be present in adults. Diminished and delayed pulses in the right femoral artery compared with the right radial or brachial artery are an important clue to the presence of a coarctation of the aorta, as are the presence of a systolic murmur over the anterior chest,bruits over the back, and visible notching of the posterior ribs on a chest x-ray. In many cases a diagnosis can be made with these findings. Two-dimensional echocardiography with Doppler interrogation is used to confirm the diagnosis. Surgical repair and percutaneous intervention are used to repair the coarctation; however, hypertension may not abate. Because late complications including recoarctation, hypertension, aortic aneurysm formation and rupture, sudden death, ischemic heart disease, heart failure, and cerebrovascular accidents may occur, careful follow-up is required.

Adult↗

Both massive upper and lower gastrointestinal hemorrhage secondary to tuberculosis.

We report a case of gastrointestinal tuberculosis, presenting with both massive upper and lower gastrointestinal bleeding that required two emergency operations. Massive bleeding is rare in gastrointestinal tuberculosis because of associated obliterative endarteritis. Tuberculosis should be considered in the differential diagnosis of massive gastrointestinal bleeding in the appropriate clinical setting even in an immunocompetent patient.

Adult↗