Extensive Sclerosis Research Articles

Mechanisms underlying transition from acute glomerular injury to late glomerular sclerosis in a rat model of nephrotic syndrome.

Functional and morphologic measurements were performed in Munich-Wistar rats after a single central venous injection of puromycin aminonucleoside (PA) or saline vehicle (sham). During phase I, PA rats exhibited overt nephrotic syndrome and impaired glomerular filtration, primarily due to a reduction in the glomerular capillary ultrafiltration coefficient. The morphologic counterpart of the latter consisted of effacement of glomerular epithelial cell foot processes and decrease in the number of filtration slit diaphragms. Administration of the angiotensin I converting enzyme inhibitor (CEI) enalapril to PA rats did not ameliorate glomerular dysfunction. During phase II, PA rats exhibited spontaneous resolution of proteinuria, impaired function, and morphologic abnormalities. However, PA rats now demonstrated marked glomerular capillary hypertension and continued, albeit lesser, reductions in the ultrafiltration coefficient. Concurrent CEI administration modestly lowered systemic arterial pressure, and normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. Additional rats were studied during phase III, 70 wk after injection. In PA rats, prior glomerular hypertension was associated with development of recurrent proteinuria and extensive glomerular sclerosis, whereas concurrent CEI administration limited these parameters to values comparable to those in sham rats. Glomerular hypertension thus may explain the development of glomerular sclerosis and renal failure long after an episode of acute glomerular injury.

The mechanisms of proteinuria in aging rats

Aging is associated with the appearance of a selective proteinuria which cannot be attributed to any specific underlying renal disease. The present studies were conducted in conscious, chronically catheterized young (3–4 months), non-proteinuric male rats and old (22–25 months), proteinuric males to determine the mechanism(s) of the proteinuria. Compared with young males, old proteinuric rats had increased blood pressure, reduced glomerular filtration rate (GFR) and renal plasma flow and heavy proteinuria. Fractional clearance of neutral dextran (D) and anionic dextran sulfate (DS) were both significantly increased at the 36 Å molecular radius in old rats; the increase in DS fractional clearance being greater than the increase in D fractional clearance. The proteinuria of aging is therefore due to moderate increases in glomerular permeability and, more importantly, to loss of fixed glomerular polyanion. Striking glomerular morphologic changes were also evident in the old rats including thickening of the glomerular basement membrane and extensive glomerular sclerosis.

Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease

Serial changes in urine protein, blood chemistry, and histology of the kidney were investigated in rats for 28 weeks after injections of adriamycin (ADR). Massive proteinuria, hypoalbuminemia, and hyperlipidemia were observed at week 4 and throughout the experiment. Both BUN and serum creatinine began to increase at week 16 and reached the uremic level at week 28. Light microscopic study of the kidney demonstrated a normal appearance at week 4, vacuole formation in glomerular tuft at weeks 8 and 12, focal and segmental glomerular sclerosis at weeks 16 and 20, and extensive glomerular sclerosis with tubulointerstitial degenerations at weeks 24 and 28. Immunohistologically, IgM with a small amount of IgG and C3 appeared in the sclerosing glomeruli from week 16. Aggregated human IgG, injected intravenously at week 24, had accumulated mainly in the glomeruli. Electron microscopy revealed degenerative changes of glomerular epithelial cells with small vacuoles in the cytoplasm at week 4. Size of vacuoles increased at the later stage. In conclusion, ADR produced chronic, progressive glomerular changes in rats, which led to terminal renal failure. The segmental glomerular sclerosis and IgM-dominant glomerular deposition in these animals are similar to pathological characteristics of focal and segmental glomerular sclerosis seen clinically.

Sclerosteosis involving the temporal bone: Histopathologic aspects

Sclerosteosis is a rare, potentially lethal, autosomal recessive, progressive craniotubular sclerosing bone dysplasia with characteristic facial and skeletal features. The temporal bone changes include a marked increase in overall size, extensive sclerosis, narrowing of the external auditory canal, and severe constriction of the internal auditory meatus, fallopian canal, eustachian tube, and middle ear cleft. Attenuation of the bony canals of the 9th, 10th, and 11th cranial nerves, reduction in size of the internal carotid artery, and severe obliteration of the sigmoid sinus and jugular bulb also occur. Loss of hearing, generally bilateral, is a frequent symptom. It often manifests in early childhood and initially is expressed as sound conduction impairment. Later, a sensorineural hearing loss and loss of vestibular nerve function often develop. Impairment of facial nerve function is another feature occasionally present at birth. In the beginning, a unilateral intermittent facial weakness may occur which eventually progresses to a bilateral permanent facial paresis. The histologic examination of the temporal bones from a patient with sclerosteosis explains the mechanisms involved in the progressive impairment of sound conduction and loss of cochlear, vestibular, and facial nerve function. There is a decrease of the arterial blood supply to the brain and an obstruction of the venous drainage from it. The histopathology reveals the obstacles to decompression of the middle ear cleft, ossicular chain, internal auditory and facial canals, and the risks, and in many instances the contraindications, to such procedures. On the other hand, decompression of the sigmoid sinus and jugular bulb should be considered as an additional life-saving procedure in conjunction with the prophylactic craniotomy recommended in all adult patients.

Rapidly progressive renal deterioration in partially nephrectomized rats with experimental membranous nephropathy.

The effects of nephron loss on the clinical and histological picture of experimental membranous nephropathy were examined for 18 weeks in five-sixths nephrectomized rats with Heymann nephritis (HN-5/6N group). Heymann nephritis-induced rats without nephrectomy (HN group), normal rats with 5/6 nephrectomy (5/6N group) and normal rats without nephrectomy (control group) were also examined for comparison. A rapidly progressive increase in urinary protein, BUN and serum creatinine was observed after renal ablation in the HN-5/6N group. Light microscopic study revealed global or segmental sclerosis in most of the glomeruli, crescent formation in some of the glomeruli and marked tubulointerstitial changes. Electron microscopic study demonstrated vacuolation and necrosis of podocytes, detachment of podocytes from the glomerular basement membrane (GBM) and fibrin exudation into Bowman's space. Proteinuria was also marked but renal function was not impaired in the HN group. In the 5/6N group, proteinuria was mild and elevation in BUN and serum creatinine was apparent but not progressive. There were no differences in the depositions of IgG, C3 and electron-dense materials on GBM between the HN-5/6N group and the HN group. In conclusion, renal mass reduction associated with high flow and pressure to the remnant glomeruli could lead to extensive glomerular sclerosis and to a deterioration in renal function, in the case of pre-existing nephritic lesions.

Erosive temporomandibular joint disease as a feature of the spondyloarthropathy of ulcerative colitis

A patient with ankylosing spondylitis associated with ulcerative colitis developed bilateral temporomandibular joint pain and severe restriction of jaw motion. Conventional radiographs did not show structural abnormality of the temporomandibular joints, but corrected axis tomography revealed erosions in both mandibular condyles with extensive reactive sclerosis in the subchondral bone. These findings suggest that the temporomandibular joint disease in this case was a feature of the patient's spondylitis rather than a manifestation of the peripheral joint arthritis which commonly occurs in patients with ulcerative colitis.

Extensive sclerosis of the base of the skull due to primary nasal tuberculosis

An 8 year old black male is presented as a primary nasal tuberculous granuloma whose roentgenograms of the skull revealed extensive sclerosis of the periorbital region involving the frontal, sphenoid, and petrous bones. The tuberculous meningitis and the osseous sclerosis at the base of the skull were cured with anti-tuberculous therapy.

Hypertension in the Elderly

The available data indicate that classical hypertension, defined here as a diastolic blood pressure greater than or equal to 95 mm Hg, is a widely prevalent and as important a risk factor for the cardiovascular diseases in those aged 65 and over as it is in those under 65. The limited available data also indicate that pure systolic hypertension, defined here as a systolic blood pressure exceeding 160 mm Hg with a diastolic pressure under 95 mm Hg, also very common at age 65 and over, is also related to excess cardiovascular morbidity and mortality in the elderly. However, it is not clear whether this latter relationship is indicative of cause and effect, or merely reflects the fact that in the elderly pure systolic hypertension is a sign of extensive sclerosis of large arteries. The results of Veterans Administration studies on antihypertensive therapy indicate that the elderly patient with classical hypertension is amenable to effective treatment, and that the benefits of such treatment significantly outweigh the risks. Great care is needed in the use of drugs for the management of hypertension in elderly patients, especially to minimize risk of hypotensive episodes and their possible harmful consequences; but with judicious and careful therapy, hypertension of this type can be controlled with reduction in excess risk of morbidity and mortality, at least for those with average diastolic pressures greater than or equal to 105 mm Hg. The lack of data on the benefits of treatment for those with pure systolic hypertension precludes any recommendations in regard to pharmacologic treatment of this condition.

Some observations on Corynebacterium pyogenes infection of the bovine uterus.

Throughout the non-gravid period, bacteriological samples and endometrial biopsy specimens were taken repetitively from the uteri of 93 cows in 9 dairy herds. The genital organs of 7 of the 14 cows which developed chronic purulent endometritis or pyometra were examined at slaughter 8 to 9 months after parturition. C. pyogenes was recovered at least once from 61 (65.6 per cent.) of the cows. The highest rate of infection was found during the second week post-partum. Intrauterine infection with C. pyogenes invariably induced endometritis. The severity of the endometrial reaction was determined by the duration of the infection but the lesions never progressed to the “gland site mass” lesions and extensive stromal sclerosis which have been described as the “significant lesions” in endometritis. The duration of the infection also determined the effect of C. pyogenes on fertility. Transient infection during the puerperium did not affect fertility; transient infection at a later period reduced fertility to one service, rarely to a second or third service; persistent infection induced chronic purulent endometritis or pyometra accompanied initially by functional anoestrum and, after some months, by organic anoestrum. The factors which determined the duration of the intrauterine infection with C. pyogenes were not identified.

Pathophysiology of aortic baroreceptors in rabbits with vitamin D sclerosis and hypertension.

Calciferol (vitamin D 2 ) (50,000-100,000 IU) and calcium lactate (1 g) were added to the normal diet of 22 rabbits for 7-11 days. When mean arterial blood pressure had risen from a control value of 87.2 ± 3.7 mm Hg to an experimental value of 137.8 ± 5.7 mm Hg (11-145 weeks), the aortic arch of 9 of these rabbits was isolated and perfused with Krebs-Henseleit solution. The impulse activity in 75 aortic baroreceptor fibers from the left aortic nerve was studied during nonpulsatile perfusion at different pressures and was compared with the impulse activity in 29 fibers from 17 normal rabbits. The threshold pressures and the pressure at the point of inflection of the curves were lower in these fibers than they were with fibers from normal rabbits. The gradient of the curves relating baroreceptor impulse frequency to aortic pressure was depressed from a normal mean value of 1.19 impulses/sec mm Hg -1 to 0.61 impulses/sec mm Hg -1 ( P < 0.001). A similar depression of the gradient was found in 7 baroreceptor fibers from the right aortic nerve. The change in the sensitivity of the baroreceptors was more closely related to the time interval after the calciferol treatment ( r =-0.95) than it was to the mean arterial blood pressure ( r = -0.76). The pressure-volume curves show that it was also related to the decreased distensibility of the aortic arch region. Histologically, the aortic arch region had extensive medial sclerosis with calcification.

Nephronophthisis. Report of 8 cases from Britain.

Eight Scottish children with nephronophthisis are described. The typical clinical picture is thirst and polyuria associated with severe anaemia, progressive impairment of renal function, and dwarfism. Isosthenuria and gross enlargement of the bladder are usually present. Systemic hypertension is usually absent until the terminal stages. Five of these children are dead and the kidneys have been examined at necropsy. Percutaneous renal biopsy has been carried out on the remainder. The typical morbid anatomical feature is the presence of medullary cysts in small uniformly contracted kidneys. Histologically, the kidney is diffusely affected with extensive sclerosis of glomeruli, periglomerular fibrosis, and obvious hyaline thickening of the tubular basement membrane. The disease progresses inexorably and renal transplantation offers the only longterm solution.

Abel Ayerza (1861-1918), "black cardiacs".

Ayerza's syndrome, one of the few familiar eponymic terms honoring a South American clinician, lacks a published communication by the original observer. This deficiency is one of several items which surrounds the inexactness of the clinicopathological description. In 1901, Abel Ayerza studied a case of intractable dusky cyanosis which showed extensive sclerosis of the pulmonary vessels on postmortem examination. His observations, reported verbally at the time, were duly recorded and published in detail by his pupil Arrillaga¹a decade later. In the meantime, Marty associated the cardinal features of the unusual protocol with Ayerza's name.² Ayerza, son of a physician, was born in Buenos Aires, received his secondary education in Colegio del Salvador, studied humanities, and obtained his bachelor's degree at the Jesuit College of San José In 1880, he registered in the Faculty of Medicine in the National University of Buenos Aires.³Ayerza served as an

Hodgkin's Disease in Bone

Hodgkin's disease is not exclusively a disease of the lymphatic system. Involvement of every organ system including the skeleton has been reported. The present discussion of Hodgkin's disease in bone is based on a review of the literature and a study of 94 previously unreported cases from the Veterans Administration Research Hospital, Chicago, and the Evanston Hospital (Evanston, Ill.) of which 11 showed osseous involvement. Askanazy (2) described the pathologic aspects of osseous involvement in 1920, some twenty years after the clear definition of Hodgkin's disease as an entity by Reed and Sternberg. Grossman and Weis (6) first recorded the radiographic features of the bony lesions in 1922. Incidence The reported incidence of Hodgkin's disease in bone varies widely with the diagnostic criteria. A distinction must be made between medullary and cortical lesions. In the spongiosa the disease may be widespread without giving rise to symptoms or radiographic signs. The true incidence cannot be determined because of the limitations of the average postmortem examination. The more diligent the search of the bone marrow, the greater the apparent incidence (13). Ewing (5) believed that it approached 100 per cent in patients dying of the disease. Only when there is extensive destruction or sclerosis are the lesions discoverable radio-graphically. Cortical involvement is more readily detectable; radiographic evidence may be found antemortem in approximately 15 per cent of all cases of Hodgkin's disease (Table I), and Uehlinger (14) states that in an additional 10 per cent cortical lesions will be discovered only at autopsy. The mean age of occurrence of Hodgkin's disease is the fourth decade, and the peak incidence is in the third decade (8, 14, 15). These data correspond closely to cases with bone involvement. Although Uehlinger states that osseous lesions are a late and prognostically grave sign, the work of Vieta, Friedell, and Craver (15) and the new cases reviewed here do not substantiate this conclusion. Bone involvement occurs throughout the course of the disease, and its appearance does not affect the prognosis significantly. In this respect Hodgkin's disease differs from most metastatic tumors. The sex ratio is approximately equal. Signs and Symptoms Hodgkin's disease in cortical bone usually gives some indication of its presence, although large lesions are often found which have produced no signs or symptoms. The most common manifestation is localized pain. This may be intermittent or persistent and may occur in any phase of the disease. Negative radiographs may obscure its origin. Jackson and Parker (8) found that in 13 per cent of their cases symptoms were present for two to twelve months before positive radiographic findings were obtained. Occasionally pain without significant adenopathy directs attention to the disease.

Jacksonian seizures in infancy and childhood

Jacksonian seizures in infancy and childhood

Chest pain with inverted T waves, predominantly in precordial leads, as the only electrocardiographic abnormality.

Sixty-nine hospitalized patients, who gave a history of "coronary" type chest pain appearing at rest and lasting at least 15 minutes, and whose electrocardiographic changes were limited to deeply inverted T waves predominantly in the precordial leads, were selected from a large series of patients. The hospital course and electrocardiographic changes of these patients were studied. After an average follow-up period of 4 years, approximately half the patients were still able to work. Postmortem studies on 11 patients revealed extensive sclerosis of the coronary arteries in all.

Juvenile type of werner's syndrome: Progressive musculocutaneous dystrophy observed for eighteen years

Summary A puzzling case is reported of extensive atrophy and sclerosis of the skin, fibrous tissue, muscle and bone, the dystrophy beginning at the age of one week and progressing for eighteen years to a profoundly disabling disorder at the present time. The difficulties of diagnostic classification are discussed.

POLIODYSTROPHIA CEREBRI PROGRESSIVA (INFANTILIS)

DURING the last thirty years, cases of hereditary disease have occurred in which the white matter of the brain was extensively destroyed and the cerebral cortex and the gray matter were on the whole preserved. Originally, this condition was called diffuse sclerosis of the brain. The name is inappropriate, for two reasons: First, it is more natural to name a disease after its initial stage than after its cicatrizing, terminal, stage. Second, the name diffuse sclerosis of the brain is not explicit, for it has been used to designate very different conditions: Schilder's disease,1which is probably a chronic virus infection; extensive syphilitic sclerosis of the brain; certain forms of glioblastoma, and, finally, three types of hereditary diseases: the acute early infantile type,2the subchronic infantile type of Scholz3and the chronic juvenile type of Pelizaeus and Merzbacher.4Bielschowsky5proposed the designation leukodystrophia cerebri progressiva

Multiple Tuberculous Lesions of the Spine

The great difficulties in differentiating tuberculous from pyogenic infection in the spine are briefly emphasized. The statement that increased density of bone occurs in pyogenic infections only is not accepted, and a report of a case illustrating extensive sclerosis in multiple tuberculous lesions of the spine is discussed. The condition of the spine was observed at various stages over a period of eighteen months and ended up in generalised miliary dissemination involving almost the whole body, which was confirmed by the post-mortem examination. The importance of the radiological investigation of the pathological specimen and its comparison with the films of the living subject is stressed.

CONCERNING THE CORRELATION OF THE PATHOLOGY AND SYMPTOMS OF CORONARY ARTERY DISEASE

Article1 July 1940CONCERNING THE CORRELATION OF THE PATHOLOGY AND SYMPTOMS OF CORONARY ARTERY DISEASEFRED M. SMITH, M.D., F.A.C.P.FRED M. SMITH, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-1-65 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe fact that it is often difficult or perhaps impossible to correlate the pathology and symptoms of coronary artery disease has led to a great deal of discussion and numerous explanations have been proposed. Developments during recent years, however, have contributed much to better understanding of the problem.Certain aspects of the pathology have a particular bearing on the diverse symptoms. In the first place, it is generally known that the heart may be normal in size in the presence of extensive sclerosis of the coronary arteries. Thus, in 113 cases analyzed by Nathanson,1selected because they presented advanced stage...

Parenteral use of carotene in the treatment of vitamin A deficiency in albino rats

L T H O U G H it has been well known tha t ke ra toma lac i a is due to deficiency of v i t amin A in the diet, the oral t r e a t m e n t of the eye condit ion wi th substances showing v i t amin A po tency has not. p roved to be un i fo rmly effective. Among the fac tors which m a y in te r fe re wi th the efficacy of v i t amin A w h e a admin is te red oral ly m a y be mentioned d iar rhea l diseases, diseases of liver, gal lbladder and pancreas, occlusioa of the bile ducts, and other disorders which resul t i a a f au l t y metabol ism of fat.. Both I-Isa ~ and Weech 2 ment ioned the associat ion of ke ra toma lac i a wi th d ia r rhea and dysentery . Bloch 8 r epo r t ed a case of x e r o p h t h a l m i a in which periodic a t t acks of d ia r rhea were accompanied by a g g r a v a t i o n of the eye symptoms. W a g n e r ~ discussed the re la t ion of l iver funct io~ and xe roph tha lmia in a series of cases. In a clinical pa thologic repor t , Higgins and 1V[allory '~ presented the case of an infant in which keratomalacia was associatec~ with fat intoleraace and chronic pancreatitis. Particularly in patients with bi]iary occlusion, evidence has been brought forward by Parsons 7 to show that a very small amount of the ingested fat is absorbed; that is, only about 30 per cent of the fat intake, as compared to 98 per cer~t in the normal, is utilized in these subjects. In a recent article by B l a c k f a n and Wolbach G it has been po in ted out t ha t histologie changes charac ter i s t ic of ~ i tamin A deficiency were found in a number of infants, in whom congenital obl i tera t ion of the bile ducts, extensive sclerosis of the pancreas , or acute general ized infect ion were p rominen t features . F r o m exper imenta l evidence, Rownt ree 8 conclv~ded tha t the loss of ~ i tamin A runs para l le l to the e l iminat ion of fa t t h rough excre t ioa b y the bowels. F r o m these clinical da ta and exper imenta l evidence, it can be deduced tha t a n y mechanism which in te r fe res wi th the no rma l absorpt ion of fat , whe the r mechanica l ly or funct ional ly , m a y h inder the p rope r ut i l iza t ion of v i t amin A when given by mouth. The oral use of cod l iver oil dur ing ihe advaaced s tage of kera tomalac ia has been discouraging. In the experience of the wri ter , large doses, as much as 15 c.c. given three t imes a day, have fai led to check the progress of the des t ruc t ive eye lesions. I n view of the fa i lure of oral methods of t r ea tment , admin is t ra t ion by the pa ren t e r a l rou te is na tu ra l l y suggested.