Relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease in psoriasis: Findings from a longitudinal observational cohort study.

BACKGROUND AND AIMS: Amygdalar 18F-fluorodeoxyglucose (FDG) uptake represents chronic stress-related neural activity and associates with coronary artery disease by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic physiological stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease, we studied the association between amygdalar FDG uptake, allostatic load score and subclinical non-calcified coronary artery burden (NCB) in psoriasis. METHODS: Consecutive psoriasis patients (n = 275 at baseline and n = 205 at one-year follow-up) underwent CCTA for assessment of NCB (QAngio, Medis). Amygdalar FDG uptake and allostatic load score were determined using established methods. RESULTS: Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity. Allostatic load score associated with psoriasis severity (ß = 0.17, p = 0.01), GlycA (a systemic marker of inflammation, ß = 0.49, p < 0.001), amygdalar activity (ß = 0.30, p < 0.001), and NCB (ß = 0.39; p < 0.001). Moreover, NCB associated with amygdalar activity in participants with high allostatic load score (ß = 0.27; p < 0.001) but not in those with low allostatic load score (ß = 0.07; p = 0.34). Finally, in patients with an improvement in allostatic load score at one year, there was an 8% reduction in amygdalar FDG uptake (p < 0.001) and a 6% reduction in NCB (p = 0.02). CONCLUSIONS: In psoriasis, allostatic load score represents physiological dysregulation and may capture pathways by which chronic stress-related neural activity associates with coronary artery disease, emphasizing the need to further study stress-induced physiological dysregulation in inflammatory disease states.

Glomerulonephritis for the generalist.

Glomerulonephritis is a common renal disorder, and a leading cause of end-stage renal disease. Glomerulonephritis can present in protean ways, with general features including proteinuria, hematuria, renal failure, and hypertension. Recent advances in our knowledge of glomerulonephritis have indicated that in many cases early therapeutic intervention can lead to improvement in renal function, long-term preservation of renal function, or slowing of the progression to end-stage renal failure. The goal of this review is to describe the method of evaluation of glomerulonephritis, stress the importance of general measures to preserve renal function or slow the rate of progression of disease, and finally to familiarize the reader with distinct categories of disease and their treatment.

Microscopic polyangiitis in a pediatric patient.

Microscopic polyangiitis (MPA), previously called hypersensitivity angiitis, is a systemic necrotizing vasculitis that involves many organ systems including the skin, joints, kidneys, and lungs. Microscopic polyangiitis most commonly affects adults in the fourth and fifth decades of life, with only a few cases reported in children. We describe a pediatric patient with microscopic polyangiitis. Arch Fam Med. 2000;9:1189-1192

Interferon-alpha-associated focal segmental glomerulosclerosis with massive proteinuria in patients with chronic myeloid leukemia following high dose chemotherapy.

BACKGROUND: Acute renal failure, with or without massive proteinuria, is a rare idiosyncratic toxicity of interferon (IFN)-alpha therapy. The authors sought to review their experience with this toxicity as well as the world literature on the subject. METHODS: The authors describe two patients with chronic myeloid leukemia treated with IFN-alpha following high dose chemotherapy who developed renal failure and proteinuria after 3 and 4 weeks of IFN-alpha therapy, respectively. Fifteen previously reported cases of renal failure and proteinuria associated with IFN-alpha therapy are also reviewed. RESULTS: Renal biopsies performed on the authors' two patients revealed focal segmental glomerulosclerosis. However, the other reported patients with IFN-alpha-associated renal failure and massive proteinuria had an assortment of pathologic findings. CONCLUSIONS: The specific renal pathology associated with proteinuria may be a consequence of the condition and not its cause; differences in renal pathology may be caused by other predisposing factors. Patients treated with IFN-alpha following high dose chemotherapy, with or without autologous transplantation, should be followed for the development of proteinuria and renal failure.

Periodic disklike structures of the adult human loop of Henle. Light and electron microscopic studies.

A total of 51 adult human kidneys was examined for the presence of the periodic disklike thickenings recently described by Belliveau in the basement membrane of the loop of Henle. These "Belliveau bodies" formed a PAS-positive rectangular lattice within the basement membrane and appeared limited to the loop of Henle. The bodies were seen in the medulla of every kidney examined but varied considerably in the frequency of their appearance from case to case. This variability did not correlate with predominant illness, organ weight, or time interval between death and autopsy. They averaged 9 to 14 micron in diameter with a horizontal and vertical periodicity of 12 and 16 micron, respectively. Although the bodies were PAS positive and diastase resistant, they did not stain with Congo red, mucicarmine, reticulin, or elastin staining techniques. Ultrastructurally, they consisted of multilaminated areas of basement membrane material. The constancy of their appearance in the material examined suggests that they are a normal anatomic feature or possibly an age-related change of the basement membrane of Henle's loop in the human kidney.

Gold-associated nephropathy.

Renal biopsy specimens from 11 cases of gold-associated nephropathy were studied by light, immunofluorescence, and electron microscopy. Seven biopsy specimens disclosed the typical glomerular lesions of membranous nephropathy. Four cases disclosed other patterns of glomerular injury, including minimal-change nephrotic syndrome. Although a membranous pattern of immune complex deposition is the most frequent type seen in gold nephropathy, our data indicate that other patterns of immune complex deposition may occur in renal biopsy specimens of patients receiving gold therapy.

The glomerular basement membrane in benign familial hematuria.

A total of nineteen children were studied because of asymptomatic hematuria. all had normal renal function, and immunologic and urologic studies. Renal tissue was obtained by percutaneous biopsy and examined by light, immunofluorescence and electron microscopy. On electron microscopy, thickness of the glomerular basement membrane (BGM) was found to distinguish benign familial hematuria (BFH - 10 cases) from non familial idiopathic recurrent hematuria (IRH - 9 cases). Measurements were taken in areas of peripheral glomerular capillary loops (minimum of five) where both cell membranes could be resolved to insure tht determinations were uniform and represented ideal cross sections. The mean thickness +/- SE of GBM in IRH of 303.3 +/- 16.9 nM was greater than that noted in BFH of 207.1 +/- 11.99 nM (P less than .002). The mean thickness +/- SE of the lamina densa in IRH of 236 +/- 15.36 nM was significantly greater than that observed in BFH of 128.5 +/- 11.7 nM (P less than .001). In both BFH and IRH the GBM and LD were uniform in thickness (CV = 20%) and qualitatively normal. The uniform attenuation observed in BFH can be used to distinguish this condition from IRH.

Test for C3 nephritic factor activity by immunofixation electrophoresis.

This report describes a relatively simple test for C3 nephritic factor (C3NeF) activity utilizing immunofixation electrophoresis to quantitate the production of the breakdown product C3c. Tests performed on plasmas from 22 control patients and 93 renal patients have biopsy diagnoses other than basement membrane dense deposit disease (BMDDD) yielded negative results for C3NeF activity. Tests performed on plasmas from three patients with BMDDD were positive for C3NeF activity, yielding values significantly higher than those for the control group and the patients with other renal diseases. The test can be performed on specimens collected in EDTA to prevent in vitro C3 degradation during storage or transport at ambient temperature.

Severe hypertension in a child with ganglioneuroblastoma.

A 26-month-old boy with Stage III abdominal ganglioneuroblastoma had tachycardia and hypertension. The hypertension increased following the institution of chemotherapy and necessitated the use of both alpha and beta adrenergic blocking agents to control the effects of the marked catecholamine production. After excision of the residual tumor, the blood pressure and urinary catecholamine excretion returned to normal. Histologic examination of this tissue under light microscopy revealed some sections of ganglioneuroblastoma as well as large areas of ganglioneuroma. Examination by electron microscopy demonstrated a moderate number of dense core neurosecretory-type granules in the cell bodies of the ganglion-like cells and an abundance of the same type of granules in the bundles of the interwoven cytoplasmic neural processes. To data, 32 months after diagnosis and 20 months off chemotherapy, the patient remains free of tumor and is in excellent general health. We postulate that the large number of secretory granules in this tumor permitted storage and release of markedly increased quantities of norepinephrine and resulted in a clinical profile similar to that associated with pheochromocytoma.

Variability of anti-GBM binding in hereditary nephritis.

Anti-GBM staining by indirect immunofluorescence microscopy was performed on renal biopsies from 64 patients with a variety of diseases in which no in vivo bound immunoglobulin or complement components were identified by direct immunofluorescence microscopy. The glomeruli of all of the entities examined bound anti-GBM antibodies except for four of nine cases of hereditary nephritis of the Alport-type. The absence of anti-GBM staining was found to correlate with the severity of GBM splitting identified by electron microscopy.

Skeletal muscle in polymyositis. Immunohistochemical study.

Thirty-two patients with adult-onset polymyositis uncomplicated by cancer or systemic connective tissue disease were studied. Muscle biopsy specimens were examined with direct immunofluorescence microscopy and results were compared with those in 94 control subjects. Sarcolemmal and sarcoplasmic staining were observed in both groups and considered to be nonspecific. Immune deposits in the muscle microvasculature were present in some cases of systemic lupus erythematosus and dermatomyositis but were not present in polymyositis. Our data suggest that the finding of vascular immunofluorescence excludes the diagnosis of adult polymyositis and implies that the pathogenesis of this disease and other idiopathic inflammatory myopathies may differ.

Alternative C3 pathway activiation in pneumococcal glomerulonephritis.

Glomerulonephritis following pneumococcal infection has been observed, but possible immunopathologic mechanisms have not been adequately explored. Multiple serologic studies as well as light, immunofluorescence and electron microscopic evaluation of kidney biopsy tissue from a 4 year old girl with pneumococcal glomerulonephritis were performed. Clinical studies at the onset of the disease showed normal serum C3 and C4 levels (third and fourth components of complement) with progression to selective C3 hypocomplementemia from days 2 to 58. A serum factor capable of breaking down C3 in normal human serum was present during the period of maximum C3 hypocomplementemia. Renal glomerular histology revealed a mesangial proliferative glomerulonephritis. Glomerular bound C3 and type 14 pneumococcal antigen were associated with similar, but less extensive, deposits of properdin. Minimal immunoglobulin M (IgM) and C4 were seen, but immunoglobulin G (IgG) and fibrinogen were absent. Ultrastructurally, subepithelial "humps" and intramembranous electron dense deposits were noted. It is hypothesized that the pneumococcal polysaccharide can activate the alternate complement pathway and may be responsible for a limited course of glomerulonephritis.