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Cerebral amyloid angiopathy with dementia: clinicopathological studies of 17 cases.

OBJECTIVES: To study clinicopathologically 17 cases of cerebral amyloid angiopathy (CAA) with dementia and to investigate the possible neuropathology of this disorder. METHODS: Of 362 autopsy cases, 17 who had had dementia with proved CAA were studied. Hematoxylin and eosin, Congo red, Bodian and beta/A4 protein immunohistochemical stain were used. Brain sections were observed under light microscopy and polarized light microscopy. The amyloid was confirmed by positive Congo red stain with apple-green birefringence under polarized light and positive beta/A4 immunohistochemical stain. The severity of amyloid deposit was graded as slight, moderate and severe. RESULTS: In the 17 cases of CAA associated with dementia, Alzheimer's disease was found in 3 cases, Pick's disease in 1, multi-infarct dementia in 6, multi-hemorrhage dementia in 4, and pure CAA in 3. CONCLUSIONS: CAA not only is closely related to Alzheimer's disease, but also causes cortical multiple small infarcts and hemorrhagic lesions, which lead to dementia. Moreover, pure CAA may produce dementia through hypoperfusion of the cortex by CAA-related hyalinization and stenosis of the arteries, which lead to the loss of cortical neurons.

Aged↗

AL-amyloidosis in monoclonal gammopathies.

Sixty-two patients affected by MGUS underwent fat tissue aspirate examination for diagnosis of AL amyloidosis. Nine out of the 62 were found to be Congo red positive. MGUS had already been diagnosed for quite a long time in about 60% of these patients, while this prevalence decreased to 24% among the Congo red negative patients. The follow-up of the positive patients is reported.

Amyloidosis↗

Laparoscopic anterior extended seromyotomy with posterior truncal vagotomy: an experimental study.

We describe a new laparoscopic modification of parietal cell vagotomy. The laparoscopic anterior extended seromyotomy with posterior truncal vagotomy was performed in five pigs weighing 21 to 25 kg each. Congo-red and pH tests were undertaken 2 weeks later by open gastrotomy. The photographs of the stained gastric mucosa made at the 5-min interval after Congo-red administration were analyzed with a computer-driven area calculation program. Preoperative and postoperative weights were taken for all animals. The experimental parietal cell vagotomy group was compared with the sham group and showed a minimal amount of nondenervated parietal cell mass (0.9 +/- 0.4% versus 28.2 +/- 3.9%, p < 0.05). The pH values showed an inhibition of gastric acid secretion (7.8 +/- 0.7 versus 2.2 +/- 0.4, p < 0.05). During postoperative follow-up, no significant difference in the weight increase of the experimental and the sham control group was noticed (1.6 +/- 0.6 kg versus 2.0 +/- 0.1 kg, p < 0.27). The laparoscopic anterior extended seromyotomy with posterior truncal vagotomy efficiently suppresses gastric acid secretion, preserving the motility of the antrum and pylorus and diminishing the risk of residual areas of innervation. This procedure avoids dissection of the esophagus and can provide an easier but equally effective operative treatment of ulcer disease compared with other types of parietal cell vagotomy.

Animals↗

Differentiation of amyloid fibril proteins in tissue sections. Two simple and reliable histological methods applied to fifty-one cases of systemic amyloidosis.

The potassium permanganate method and the unlabeled immunoperoxidase (PAP) method were applied for distinguishing different types of amyloid fibril proteins in conventionally fixed, paraffin-embedded tissue sections obtained from fifty-one autopsied cases of systemic amyloidosis and three control cases of well-analysed fibril proteins. All of the eighteen cases "sensitive" to permanganate treatment, whose amyloid deposits lost completely their affinity to Congo red and birefringence under polarized light, were shown to have AA antigenic determinants by the PAP method. Meanwhile, all of the remaining thirty-three "resistant" cases, where Congo red affinity and birefringence were retained at various degree even only in minimal areas, were negative for AA antigenicity. This indicated the feasibility of potassium permanganate method for the identification of AA protein based on this criterion of "sensitivity". Twenty-eight cases were classified as AA, A lambda, A kappa or AA+[A kappa] the remaining twenty-three cases were unclassified, and there were some discrepancies between the preliminary clinicopathological classification and the protein nature of the amyloid. It is important to differentiate the types of amyloid fibril protein of individual patients because the expedience of selective therapeutic approaches had been suggested. The two methods applied herein are handy and useful for this purpose.

Adult↗

Unsuitable value of abdominal fat tissue aspirate examination for the diagnosis of amyloidosis in long-term hemodialysis patients.

Abdominal fat tissue aspiration was used in 22 long-term hemodialysis patients (5-17 years). Fourteen of these patients had carpal tunnel syndrome and amyloid deposits of beta 2-microglobulin in the synovium. One patient had a spontaneous rupture of the spleen with amyloid deposits in spleen vessels. Seven other patients presented carpal tunnel syndrome and/or articular pains, and radiological lytic lesions in bone, strongly suggesting an amyloid origin. As a control group, in 22 patients with biopsy-proven amyloidosis, abdominal fat tissue aspirates were performed and were studied under the same conditions: by light microscopy these tissues were stained with Congo red and examined with a polarizing microscope; these specimens were also studied by electron microscopy. In all hemodialyzed patients, no amyloid deposit was present in fat tissue with Congo red staining and by electron microscopy. On the contrary, amyloid was observed in 17 of 22 cases in other types of amyloidosis. It seems that this method which has been proved to be simple and sensitive for the diagnosis of systemic amyloidosis is not a good marker for the presence of amyloid in long-term hemodialysis patients.

Abdominal Muscles↗

Crystalline light-chain deposition and amyloidosis in the thyroid gland and kidneys of a patient with myeloma.

A 48-year-old Japanese woman died of multiple myeloma (lambda light-chain type) with chronic renal failure. Histological examination revealed deposition of a homogeneous substance and crystals in the kidneys and thyroid gland. The homogeneous substance was stained with Congo red after permanganate treatment but did not stain with antibody to amyloid A protein, and it was recognized as AL-type amyloid. Crystals were not stained with Congo red, but crystals were stained with antibody to the lambda light chain. Since AL-type amyloid is considered to be derived from a myeloma light chain, the present case showed two different types of deposition, both of which were derived from the same myeloma protein.

Amyloid↗

Ocular amyloid deposition in familial amyloidosis, Finnish: an analysis of native and variant gelsolin in Meretoja's syndrome.

PURPOSE: To analyze the deposition of amyloid and its precursors in eyes of patients with familial amyloidosis, Finnish (FAF; Meretoja's syndrome), a hereditary systemic amyloidosis. METHODS: Autopsy eyes from three patients with FAF and ten control eyes were studied by Congo red staining and with antibodies to the nonmutated part of gelsolin (GS-2C4), the mutated gelsolin Asn-187 fragment (AGel), and amyloid-P component (AP). RESULTS: Congo red and antisera to AP and AGel bound to amyloid deposits in the cornea and conjunctiva, the sclera, the perineurium of ciliary nerves, the walls of ciliary vessels, the optic nerve sheaths, the stroma of the ciliary body, and along the choriocapillaris. mAb GS-2C4 bound weakly and focally to most deposits and strongly around the choriocapillaris. It labeled the corneal epithelium and endothelium, keratocytes, scleral fibroblasts, trabecular and lens epithelial cells, the ciliary muscle and epithelium, the iris sphincter and dilator, and stromal cells of the conjunctiva and uveal tract. CONCLUSIONS: Local production, especially in the cornea, conjunctiva, sclera, and ciliary muscle, and systemic deposition, particularly in blood vessles and in the sclera, may contribute to amyloid deposits in FAF. To explain the complex pattern of deposition, microenvironmental factors such as lamellar architecture of the cornea and sclera, altered processing of gelsolin, or blood-tissue barriers must be invoked. In addition to corneal lattice dystrophy type II, the observed deposits help to explain glaucoma in patients with FAF.

Aged↗

A Japanese family with a variant of Gerstmann-Sträussler-Scheinker disease.

OBJECTIVE: A new variant of Gerstmann-Sträussler-Scheinker disease (GSS) was reported, which had a substitution of glutamate to lysine at codon 219 (E219K) in addition to a P102L mutation on the same allele of the PrP gene. However, clinical features were not detailed and pathological studies were not done. Unusual clinical, neuroradiological, and pathological findings are reported for these patients. METHODS AND RESULTS: Clinical presentations of the patients in the same family were variable; progressive dementia with minimal ataxia in some patients but ataxia without dementia in others. PET studies with 18F-2-fluoro-2-deoxyglucose (FDG) disclosed a relative decrease of FDG uptake in bilateral temporoparietal cortices of a patient with dementia, but in the cerebellar cortices in a patient with ataxia. At necropsy, a patient with dementia had multicentric and diffuse plaques stained with PrP antiserum, but not with haematoxylin and eosin or Congo red, in the cerebral and cerebellar cortices. CONCLUSION: Neurological and neuropathological features in the patients were atypical of the classic form of GSS with P102L mutation. The absence of Congo red staining prion protein plaques is probably attributable to E219K polymorphism on the same allele of the PrP gene.

Adult↗

[A case of nephrotic syndrome associated with minimal renal amyloidosis--a four-year follow-up].

A 61-year-old male had nephrotic syndrome in association with minimal renal amyloidosis. The amyloid deposits were inconspicuous and had been initially overlooked, and the biopsy specimen was thought to show minimal glomerular changes. Accordingly he was diagnosed as having minimal change nephrotic syndrome (MCNS). Thereafter, administration of 40 mg/day of prednisolone was started. A few weeks after treatment, proteinuria decreased, but did not disappear. Four years later, he was readmitted for the treatment of the nephrotic syndrome. The second biopsy at 65 years of age revealed typical renal amyloidosis by light microscopy. Congo red staining and electron microscopy confirmed the presence of amyloid deposits. The serum A protein (SAA) level was 328 micrograms/ml. Furthermore, the first biopsy specimen revealed minimal renal amyloidosis by Congo red staining. At the time, 40 mg/day of prednisolone proved ineffective for the proteinuria. However, after methylprednisolone pulse therapy, the proteinuria decreased and the nephrotic syndrome improved. After discharge, administration of 20 mg/day of prednisolone was maintained. One year later, the patient showed no evidence of recurrence of the nephrotic syndrome and the SAA level decreased (from 328 micrograms/ml to 74.4 micrograms/ml). Prednisolone proved to have a beneficial effect on the reduction of proteinuria and SAA levels. We strongly recommend careful examination for amyloid deposits in all kidney biopsy specimens with the appearance of MCNS on older patients whose proteinuria does not respond to the administration of prednisolone.

Amyloidosis↗

[Pleural amyloidosis].

OBJECTIVE: To evaluate the clinical significance of systemic amyloidosis in the differential diagnosis of pleural effusion. METHOD: Retrospective analysis of the incidence and the characteristics of pleural effusion in systemic amyloidosis. RESULTS: Seven (47%) of 15 cases of systemic amyloidosis were complicated with pleural effusion, of them 4 cases were confirmed by positive Congo red stain of percutaneous pleural biopsies specimens. CONCLUSIONS: Systemic amyloidosis involving pleura was not rare. Pleural amyloidosis should be suspected in pleural effusion complicated by multiorgan disease. Percutaneous pleural biopsy with Congo red stain can confirm the diagnosis.

Adult↗

Eradication of Helicobacter pylori has no effect on gastric acidity in duodenal ulcer patients--evaluation of 24-h pH monitoring.

It is accepted that eradication of Helicobacter pylori leads to healing of chronic active gastritis facilitates ulcer healing and prevents ulcer recurrence in duodenal ulcer (DU) patients. However, it is not entirely known whether the eradication of the bacteria normalizes gastric acid secretion and abolishes dyspeptic symptoms after ulcer healing. This study was aimed to evaluate the intragastric acidity and dyspeptic complaints before, and 3 months after, eradication in 18 endoscopically proven H. pylori positive DU patients. Gastric pH was measured by 24-h continuous intraluminal recording, serum gastrin measurements and Congo-red tests were also performed. Dyspeptic complaints and antacid consumptions were recorded in diary cards, antisecretory therapy was not allowed after the cessation of eradication therapy. Endoscopy, H. pylori status and Congo-red tests were controlled at the 6th and 12th week, while pH measurements and serum gastrin tests were performed at inclusion and 3 months later. Three patients dropped out and in 14 out of the remaining subjects healing of DUs and successful eradication was achieved by the 6th and 12th week controls. The 24-h median pH and the percentage of 24-h pH readings under pH 3 were not changing significantly by the 3-month controls (from 1.9+/-0.5 to 1.8+/-0.4 and from 52.6+/-5.5% to 58.6+/-5%, respectively). Similarly, no significant changes were observed in serum gastrin levels and dyspeptic symptom scores (from 72+/-7 pg/ml to 56.7+/-8 pg/ml and from 2.69+/-0.4 to 1.26+/-0.3, respectively). The antacid consumption was almost stable when compared with the pre- and post-eradication periods. It was concluded that despite successful H. pylori eradication and healing of DU, intragastric acidity does not change significantly at least 3 months after the therapy. The persisting dyspeptic symptoms and the need for antacid consumption suggest that some healed ulcer patients require antisecretory therapy in the post-eradication period.

Adult↗

Vagal dysfunction following endoscopic variceal sclerotherapy.

BACKGROUND: Sclerotherapy is associated with complications which involve adjacent structures like the pleura. The effect of sclerotherapy on function of the vagus nerve, which lies in close proximity to the thoracic esophagus, is not clear. AIM: To study gastric acid secretion as a marker of vagal function in portal hypertensive patients who have undergone sclerotherapy. METHODS: Portal hypertensive patients who had undergone at least three sessions of sclerotherapy were evaluated by mapping gastric acid-secreting mucosa by the Congo red test and by estimating gastric acid secretion using the modified sham feeding test. Patients with portal hypertension who had never been subjected to endoscopic sclerotherapy were recruited as controls. RESULTS: On Congo red test, complete or substantial reduction in acid-secreting mucosa was observed in eight patients in comparison to none of the controls. Significantly lower acid secretion on modified sham feeding test was observed in these eight patients. CONCLUSION: A lower gastric acid secretion, probably secondary to vagal dysfunction, is seen in patients who have undergone multiple sessions of sclerotherapy; vagus nerve involvement may be secondary to periesophageal inflammation.

Adult↗

Incidence and characterization of age related amyloid deposits in the human anterior pituitary gland.

To identify amyloid deposits in the anterior pituitary gland, we have immunohistochemical, histochemical and alkaline Congo red staining. The anti-human P component reacted positively with these amyloid deposits, while antisera against prealbumin, AA type amyloid fibril protein and various anterior pituitary hormones were negative. A combination of Congo red and anti-human P component staining was most sensitive and reliable for detection of amyloid in the anterior pituitary glands of 300 randomly autopsied patients. Amyloid deposits increased in parallel with the age of the patients, however, they appeared earlier and more frequently than heretofore reported. Deposition of amyloid was seen initially in the 3rd decade and the positivity rate of amyloid deposits was 73% in the 5th decade. The histochemical characteristics of these pituitary amyloid deposits differed from those of cerebral and systemic deposits, particularly those found in the amyloid of senile systemic amyloidosis.

Adolescent↗

Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates.

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of transthyretin (TTR) amyloid fibrils, particularly in the peripheral nervous system. No systematic immunohistochemical data exists relating TTR deposition with FAP progression. We assessed nerves from FAP patients in different stages of disease progression (FAP 0 to FAP 3) for TTR deposition by immunohistochemistry, and for the presence of amyloid fibrils by Congo Red staining. The nature of the deposited material was further studied by electron microscopy. We observed that early in FAP (FAP 0), TTR is already deposited in an aggregated nonfibrillar form, negative by Congo Red staining. This suggested that in vivo, preamyloidogenic forms of TTR exist in the nerve, in a stage before fibril formation. Cytotoxicity of nonfibrillar TTR was assessed in nerves of different FAP stages by immunohistochemistry for macrophage colony-stimulating factor. FAP 0 patients already presented increased axonal expression of macrophage colony-stimulating factor that was maintained in all other stages, in sites related to TTR deposition. Toxicity of synthetic TTR fibrils formed in vitro at physiological pH was studied on a Schwannoma cell line by caspase-3 activation assays and showed that early aggregates but not mature fibrils are toxic to cells. Taken together, these results show that nonfibrillar cytotoxic deposits occur in early stages of FAP.

Adolescent↗

Renal amyloidosis and other fibrillar glomerular diseases.

Fibrillar glomerular diseases are defined by the ultrastructural accumulation of glomerular extracellular microfibrils or microtubules. The deposits have compositions particular to specific diseases, and it is important to distinguish among these clinical pathologic entities and their differing clinical implications. Amyloidosis and immunotactoid glomerulopathy are two examples of fibrillar glomerular diseases. Amyloidosis is a systemic disease in which the fibrils stain with Congo red and contain various biochemically distinct proteins that identify diseases with differing prognostic and therapeutic implications. Immunotactoid glomerulopathy is a primary glomerular disease, and the deposits contain immunoglobulins that do not stain with Congo red. In contrast to amyloidosis, division of immunotactoid glomerulopathy based on the immunoglobulin content or ultrastructural appearance of the deposits has no clinical relevance.

Amyloidosis↗

A study of the morphology and distribution of amyloid beta protein immunoreactive plaque and related lesions in the brains of Alzheimer's disease and adult Down's syndrome.

An immunohistochemical study was carried out on the brains of 20 cases with Alzheimer's disease and the same number of non-Alzheimer's controls using a monoclonal antibody to amyloid beta protein. The morphology and distribution of immunoreactive plaque-like lesions and the sensitivity of immunostaining were assessed both with and without formic acid pretreatment of the sections, and these results were compared with those obtained from conventional Congo red and silver impregnation staining methods. The brains of 8 cases with Down's syndrome (ages 18 to 62) were also studied using similar staining techniques. In the cases with Alzheimer's disease Congo red and immunostaining without formic acid pretreatment mainly stained the core deposits of amyloid in compact plaques, whereas the silver stain could also detect numerous diffuse plaques. Immunostaining with formic acid pretreatment was the most sensitive technique, and this showed many additional immunoreactive lesions of faint granular staining with little evidence of amyloid deposition or degenerating neurites. Similar ill-defined, faintly immunoreactive areas were the only neocortical lesions observed in the two cases aged 31 and 38 years respectively, and in addition to these lesions, older cases of Down's syndrome revealed extensive and numerous discrete senile plaques with amyloid deposition. Far fewer immunoreactive lesions were observed in the non-Alzheimer's controls. The ill-defined, beta protein immunoreactive regions mentioned above, therefore, are presumed to be very early stages in senile plaque development, and it is concluded that an extensive appearance of beta protein immunoreactive plaque lesions throughout the cortex and subcortical gray matter structures is typical of Alzheimer's disease.

Adolescent↗

A new method to classify amyloid fibril proteins.

The permanganate method, the immunoperoxidase method, and a newly developed autoclave method were used to distinguish different types of amyloid fibril proteins in formalin-fixed, paraffin-embedded tissue sections. All tissues from permanganate-sensitive cases (AA type) lost the affinity of Congo red and green birefringence under polarized light after incubation with special autoclave treatment. AL type systemic amyloidosis and amyloid plaques of CJD and GSS were permanganate-resistant, but decreased markedly the affinity of Congo red after prolonged autoclaving. On the other hand, prealbumin type systemic amyloidosis and senile plaques of SDAT were resistant to both permanganate oxidation and prolonged autoclaving. Thus, amyloid plaques of CJD and GSS are identical to AL type in systemic amyloidosis, and senile plaques are similar to the prealbumin type. However, anti-prealbumin antiserum did not stain senile plaque amyloid. The anti-human P component stained positively systemic amyloids and cerebral amyloid plaques of SSE, but failed to stain senile plaques of SDAT. Therefore, the amyloid fibril protein of senile plaques is apparently different from other types of amyloid depositions. Amyloid plaques of SSE are different from senile plaques not only with regard to fibril proteins, but also to globular protein in the amyloid.

Adolescent↗

[A case of primary amyloidosis associated with giant cell infiltration within a Bowman's capsule].

A 67-year-old man was hospitalized with a diagnosis of nephrotic syndrome. Physical findings at admission were generalized edema and macroglossia. Urinalysis showed massive proteinuria, + +occult blood, and granular and broad casts. Ig A lambda monoclonal gammopathy was noted in the serum. There was no evidence of myeloma in the bone marrow aspirate, scintigram or X-ray of the bone. A biopsy specimen of the kidney showed massive deposits of structureless material in the glomeruli. Marked cell infiltration was also observed in the interstitium. Multinucleated giant cells were occasionally seen in the Bowman's capsules and the interstitium. There were reactive changes in the Bowman's capsule adjacent to the giant cell. The deposits were proved to be amyloid by positive staining with Congo red and apple-green birefringence by polarized light. In addition, microfibrills seen on electron microscopy displayed deposits. Amyloid depositions were observed in other tissues such as gingiva, skin and tongue. Staining of amyloid with Congo red was resistant to potassium permanganate, and amyloid was positively stained with lambda-light chain of immunoglobulin. These findings indicated that the patient had primary amyloidosis. Infiltration of the multinucleated giant cell has been reported only in patients with familial amyloidosis and secondary amyloidosis associated with rheumatoid arthritis. To our knowledge the present case is a first report of the giant cell infiltration in a Bowman's capsule in primary amyloidosis.

Aged↗