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Biomedical subjects

R J Falk

Publications and source records attributed to R J Falk.

At least 73 records · Page 4Linked to original sources
PubMed1994

Antineutrophil cytoplasmic autoantibody-positive crescentic glomerulonephritis as a complication of treatment with propylthiouracil in children.

Propylthiouracil, which is commonly used in the treatment of hyperthyroidism, has been associated in adults with antineutrophil cytoplasmic autoantibody, a serologic marker of vasculitis. Severe renal disease has not been reported as a complication of therapy with this drug. We report severe antineutrophil cytoplasmic autoantibody-positive vasculitis in children receiving propylthiouracil, as well as rapidly progressive crescentic glomerulonephritis after administration of this drug.

Adolescent↗
PubMed1994

The pathology of vasculitis involving the kidney.

The kidneys are frequently affected by systemic vasculitides. This is not surprising given the numerous vessels within the renal parenchyma. The kidneys are most often involved by small vessel vasculitides, such as microscopic polyangiitis (microscopic polyarteritis), Wegener's granulomatosis, Henoch-Schönlein purpura, and cryoglobulinemic vasculitis. These vasculitides cause renal dysfunction predominantly by inducing glomerular inflammation with resultant nephritis and renal failure. Microscopic polyangiitis (microscopic polyarteritis) and Wegener's granulomatosis are associated with and may be caused by antineutrophil cytoplasmic autoantibodies. Henoch-Schönlein purpura is caused by immunoglobulin (Ig) A-dominant immune complex localization in small vessels. Cryoglobulinemic vasculitis is sometimes induced by hepatitis C infection. Necrotizing medium-sized vessel vasculitides, such as classic polyarteritis nodosa and Kawasaki's disease, are less frequent causes of renal disease. They cause infarction secondary to thrombosis of inflamed major extrarenal and intrarenal arteries, and may lead to life-threatening hemorrhage from rupture of aneurysms. Large vessel vasculitides, such as giant cell (temporal) arteritis and Takayasu arteritis, only rarely injure the kidneys, usually by ischemia secondary to vasculitic involvement of the renal arteries or abdominal aorta. This ischemia can cause renovascular hypertension.

Animals↗
PubMed1994

Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis.

Sixteen patients with renal biopsy findings of extensive focal glomerular capillary collapse, visceral epithelial cell hypertrophy and hyperplasia, and variable degrees of tubulointerstitial injury in the absence of evidence for human immunodeficiency virus (HIV) infection or intravenous drug abuse were prospectively identified by renal biopsy. The pathologic process was designated collapsing glomerulopathy to distinguish it from other patterns of focal glomerular sclerosis. The clinical and pathologic characteristics of these 16 patients were analyzed and compared to a group of 25 patients with noncollapsing focal segmental glomerulosclerosis (FSGS). Thirteen of 16 patients with collapsing glomerulopathy were black as compared with 11 of 25 with FSGS (P = 0.018). The most common findings at presentation were hypertension and manifestations of the nephrotic syndrome. Although the duration of symptoms prior to presentation was no longer in the collapsing glomerulopathy group, the presenting mean serum creatinine was higher in patients with collapsing glomerulopathy than in those with noncollapsing FSGS (3.5 +/- 3.4 mg/dl vs. 1.3 0.6 mg/dl, P = 0.001). Twenty-four-hour urine protein excretion was also higher in the collapsing glomerulopathy group (13.2 +/- 7.7 g/day vs. 4.6 +/- 4.5 g/day FSGS, P = 0.005). The collapsing glomerulopathy patients had a mean age of 41.4 +/- 19.1 (range 19 to 81), a male-to-female ratio of 11:5 and a black-to-white ratio of 13:3. Renal survival, evaluated by life-table analysis, was markedly worse in collapsing glomerulopathy patients than in FSGS patients (P = 0.0004). It is proposed that collapsing glomerulopathy is a distinct entity characterized by black racial predominance, massive proteinuria, relatively rapidly progressive renal insufficiency, and distinctive pathologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Immune complex glomerulonephritis is induced in rats immunized with heterologous myeloperoxidase.

Anti-neutrophil cytoplasmic antibodies (ANCA), including anti-myeloperoxidase (MPO) antibodies, are associated with pauci-immune necrotizing small vessel vasculitis or glomerulonephritis. In order to substantiate a pathogenic role for ANCA, an animal model of pauci-immune ANCA-induced glomerulonephritis or vasculitis is required. Brouwer et al. reported pauci-immune glomerulonephritis in rats immunized with human MPO followed by perfusion of kidneys with lysosomal enzyme extract combined with H2O2, and suggested that this could serve as a model of ANCA-induced disease. We repeated these studies in spontaneously hypertensive rats (SHR) and Brown Norway rats (BNR). We immunized rats with human MPO. When circulating anti-MPO antibodies were detectable by indirect immunofluorescence microscopy and ELISA, blood pressure was measured, then perfusion of the left kidney of each rat was done via the renal artery in a closed, blood-free circuit with either MPO + H2O2, MPO, H2O2 alone or MPO + H2O2 + neutral protease. Rats were killed on day 4 or day 10 after perfusion, and specimens were examined by light and immunofluorescence microscopy. Pathological lesions and deposits of IgG, C3, and MPO were found in immunized rats perfused with MPO + H2O2 with or without neutral protease, or MPO alone, in both rat strains and on both day 4 and day 10. The degree of histologic injury was proportional in intensity to the amount of IgG immune deposits. Spontaneously hypertensive rats sustained more damage and higher blood pressure than Brown Norway rats. No lesion was observed in immunized rats perfused with H2O2 or in the non-perfused right kidneys. Some of the non-immunized rats perfused with MPO + H2O2 developed pathological lesions. In conclusion, these rat models are examples of immune complex-mediated glomerulonephritis, and therefore are not similar to human ANCA-associated disease.

Animals↗
PubMed1994

Vasculitis affecting the skin. A review.

Although cutaneous purpura and nodules are important clinical manifestations of vasculitis, many other cutaneous expressions of injury also can be caused by vasculitis. Once cutaneous vasculitis is recognized, patient evaluation should center on identifying causative agents, pathogenic mechanisms and extracutaneous organ system involvement, and diagnostic categorization of the disease. Once identified, some causative agents, such as an infectious pathogen, drug, or neoplasm, can be eliminated leading to resolution of the vasculitis. Recognition of the pathogenic category, such as immune complex-mediated vasculitis or ANCA-associated vasculitis, will narrow the differential diagnosis and suggest the likelihood and pattern of extracutaneous disease. Accurate diagnostic categorization, which will direct prognostication and treatment, usually requires integration of clinical, pathologic, and serologic data.

Humans↗
PubMed1993

A nephrological view of the classification of vasculitis.

From the nephrologic perspective, a nomenclature system has been proposed that is clinically useful for diagnosis, classification and therapy. This nomenclature allows the nephrologist to consider the best approach to ANCA positive patients with necrotizing and crescentic glomerulonephritis. It allows for better understanding of the extra-renal manifestations of disease especially those with pulmonary-renal syndrome. The classification system allows for the rapid introduction of immunosuppressive therapy in individuals without repetitive search for specific pathological features on biopsy. This classification system allows for the possibility that all of these conditions are pathogenically related. As such, it separates this group of diseases from those which are attributable to immune complex disease or direct antibody binding. For this nomenclature system to stand the test of time it must be simple, logical and clinically usefully. While not yet perfected, the working nomenclature for ANCA-associated diseases is a step forward.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

The clinical, serologic, and immunopathologic heterogeneity of cutaneous leukocytoclastic angiitis.

Histologically identical cutaneous leukocytoclastic angiitis occurs in patients with different serologic markers for vasculitis. When categorized on the basis of serologic analysis for antineutrophil cytoplasmic autoantibodies and IgA fibronectin aggregates, categories of leukocytoclastic angiitis have many overlapping features; however, there are distinctive clinical and immunopathologic trends among the categories. When both serologic tests are negative, there is a low probability that systemic vasculitis is present. The presence of either serologic marker indicates a strong probability for the presence of extracutaneous vasculitis and/or glomerulonephritis.

Adolescent↗
PubMed1993

Immunoglobulin A-fibronectin aggregate levels in children and adults with immunoglobulin A nephropathy.

Immunoglobulin A-fibronectin aggregates (IgAFNs) may be demonstrable in the serum of patients with IgA nephropathy. Initial reports suggested that IgAFN could be a marker for IgA nephropathy with clinical utility in differentiating IgA nephropathy from non-IgA glomerulonephritis. Serum IgAFN concentration was determined in 105 samples from 52 patients with IgA nephropathy who were followed in Kentucky or Tennessee. On at least one occasion, IgAFN was positive (significantly elevated) for 25 of the 52 patients (48%). Thirty-eight percent of the 105 samples were positive. Pediatric and adult patients had a similar incidence of positive IgAFN. A small but nonsignificant increase in the incidence of positive IgAFN was shown for patients who had or subsequently developed chronic renal insufficiency. Weak but significant correlations were found between IgAFN concentration and serum IgA concentration and C3 activation. In the present study, IgAFN concentration was significantly higher for the patients with IgA nephropathy as compared with the patients with non-IgA glomerulonephritis from our previous study. While IgAFN may be clinically useful in differentiating IgA nephropathy from non-IgA nephropathy, the present assay cannot be used to diagnose IgA nephropathy.

Adult↗
PubMed1993

Hematometra associated with estrogen replacement therapy.

We have described two cases of hematometra occurring after initiation of estrogen replacement therapy. In both cases, cervical stenosis had developed during a prolonged period of hypoestrogenism. After initiation of sequential estrogen/progestin therapy, the stenosis prevented menstrual flow, and sonography revealed an asymptomatic hematometra in both cases. Based on these cases, we recommend doing a baseline evaluation of cervical patency before initiating estrogen replacement therapy in women who have been menopausal for a substantial length of time.

Aged↗
PubMed1993

Do antineutrophil cytoplasmic autoantibodies cause Wegener's granulomatosis and other forms of necrotizing vasculitis?

The in vitro experimental observations support the theoretical pathogenic scenario depicted in Figure 14. A similar scenario could be portrayed for monocytes. ANCA in the circulation are unable to interact with unprimed neutrophils because the target antigens are within the cytoplasm (Fig. 14A). Synergistic priming of neutrophils, e.g., by an infection, causes small amounts of target antigens to be released at the cell surface (Fig. 14B) where they can interact with ANCA (Fig. 14C). ANCA-activated neutrophils then adhere to endothelial cells via adhesion molecule interactions that may require prior priming of the endothelial cells (Fig. 14C). These activated and adherent neutrophils then injure endothelial cells (and eventually underlying vessel wall structures) by releasing granule enzymes and toxic oxygen metabolites (Fig. 14D). Although many research groups throughout the world have been attempting to create an animal model of ANCA-induced disease based on the theoretical paradigm proposed in Figure 14, as well as on other paradigms, no one has reported complete success. Until this is accomplished, the role of ANCA in the pathogenesis of Wegener's granulomatosis and other forms of ANCA-associated vasculitides will remain conjectural.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Nephropathology consultation via digitized images.

Investigations into a digitized image communications system were prompted by a need to bring expert consultation to physicians in community practice. Pathologists desired the capability to concomitantly view, annotate, and discuss images with referring physicians at distant sites. Methods included evaluation of the human and procedural domain into which the system was to be integrated. The GDCN computer consultation system has the consultant nephropathologist first evaluate the processed biopsy slides, digitize representative images, transmit them with the diagnosis to referring nephrologist, and, finally, conduct an interactive consultation and review of the biopsy and case. Image resolution and compression variables must be set for each individual medical consulting application. For the GDCN, it was found that the 640 x 496 x unlimited color with compression ratios not exceeding 1:32 are acceptable. An obvious improvement of this computerized system over the noncomputerized review sessions is the ability to immediately share and discuss a new image that had not been previously sent. In the old noncomputerized consultation, only images that had been mailed could be discussed. The computerized sessions allow transmission (10 sec) of a new image that the consultation might demand. The computerized sessions also provide the ability to show the referring nephrologist an area of biopsy interest that the pathologist had not previously transmitted. Biopsy slides can be viewed during the consultation, an area digitized, and that image transmitted to the nephrologist during the consultation. Hardware and costs for the sending station were: [table: see text] This system far exceeds the requirements for this particular application; however, it is sufficient to support future, higher-technology computer applications. If necessary, this same system could be used with a less expensive computer, a less expensive camera, software compression, and a single monitor. These alterations could lessen the expenditures by some $8000 and result in a total cost of $10,000. Hardware and costs for the receiving station were: [table: see text] Cost of the receiving station could be reduced by using a less expensive computer and a single monitor system, thereby saving up to $5000 and resulting in a total cost of $7,400. DCCEC and GDCN have elected to use the more expensive, user-friendly and more rapid image transmission system SEND-->IT, rather than the less expensive system mainly because of experience with incorporating the system into the daily activities of the GDCN. SEND-->IT best met the essentials for GDCN.(ABSTRACT TRUNCATED AT 400 WORDS)

Biopsy↗
PubMed1992

Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme.

BACKGROUND: Nephropathy may develop in patients with sickle cell disease. We determined the prevalence of proteinuria and renal insufficiency in a group of patients with sickle cell disease and investigated the renal pathologic changes and the effects of an angiotensin-converting-enzyme inhibitor (enalapril) on protein excretion in patients found to have nephropathy. METHODS: We prospectively screened 381 patients with sickle cell disease for the presence of proteinuria and renal insufficiency. Renal biopsy and measurements of glomerular filtration rate, effective renal plasma flow, and urinary protein excretion were performed in 10 patients with mild nephropathy before and after the administration of enalapril, and again two to three weeks after its discontinuation. RESULTS: Of the 381 patients with sickle cell disease, 26 (7 percent) had serum creatinine concentrations above the normal range and 101 (26 percent) had proteinuria of at least 1+. The renal lesions in the 10 patients who had biopsies consisted of glomerular enlargement and perihilar focal segmental glomerulosclerosis. The mean (+/- SD) glomerular area in these patients was 28.7 +/- 4.1 x 10(3) micron 2, as compared with 15.8 +/- 4.3 x 10(3) micron 2 in 10 control patients without renal disease who had died of trauma (P less than 0.0001). During the administration of enalapril, the mean 24-hour urinary protein excretion decreased 57 percent (range, 23 to 79 percent) below the base-line value (P less than 0.001), and it increased to 25 percent below the base-line value after enalapril was discontinued. The glomerular filtration rate and effective renal plasma flow did not change significantly. CONCLUSIONS: Approximately 25 percent of patients with sickle cell disease have proteinuria. Treatment with enalapril reduces the degree of proteinuria in these patients, suggesting that glomerular capillary hypertension may be a pathogenic factor in sickle cell nephropathy.

Adult↗