Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man

An 83 year old white man with atrial fibrillation was admitted to hospital after a cerebral infarct. Echocardiography was characteristic of cardiac amyloid deposition and subsequent tests confirmed amyloidosis of transthyretin (TTR) type, in association with the Ile122 mutation of the TTR gene; this has only been reported previously in African Americans in whom it occurs with an allele frequency of 2%. Haplotype analysis did not suggest a different founder than for the African Ile122 mutation. Cardiac amyloidosis should be considered among elderly patients presenting with cardiac failure and/or arrhythmia, particularly if they are resistant to conventional treatment; if confirmed, it should be followed by precise characterisation of amyloid fibril type. The prevalence of autosomal dominant cardiac TTR amyloidosis in elderly white people is unknown but early diagnosis and supportive treatment may prevent complications among affected family members.


Keywords: amyloid; amyloidosis; transthyretin; hereditary amyloidosis; stroke     

April 1999--44 year old man with a bleeding intracerebral tumor.

A 44 year-old man presented with a three month history of increasing headache and evolving left sided hemiparesis that culminated in an haemorrhage into an intracerebral tumour which was partially resected. Histologic, immunohistochemical, electron microscopic and molecular studies are supportive of a diagnosis of primary embryonal rhabdomyosarcoma. While primary rhabdomyosarcoma of the central nervous system is rare, and 72% of previously reported cases are in the paediatric population, there appears to be subset of these tumours occurring supratentorially in the adult.     

Unusual appearance of thromboembolism on perfusion lung imaging.

A 46-year-old woman with advanced ovarian carcinoma had progressive dyspnea and was evaluated with ventilation and perfusion lung imaging. A characteristic pattern of multiple branching perfusion defects of a segmental nature on the perfusion scan suggested tumor microembolism and lymphangitic carcinomatosis. However, in this case, this pattern was associated with pulmonary thromboembolism and was documented by the post mortem examination. Pulmonary thromboembolism should be included among the differential diagnoses in a patient with clinical symptoms and a perfusion scan that reveals multiple branching perfusion defects.     

Clinical, radiological and serum amyloid P component scintigraphic features of beta2-microglobulin amyloidosis associated with continuous ambulatory peritoneal dialysis.

BACKGROUND: Beta2-Microglobulin (beta2M) amyloidosis occurs in patients with end-stage renal failure (ESRF) who undergo long-term continuous ambulatory peritoneal dialysis (CAPD), but its prevalence in patients treated exclusively by CAPD is unknown. In addition, its features may differ from those of haemodialysis-associated beta2M amyloidosis because CAPD is more biocompatible. METHODS: We performed serum amyloid P component (SAP) scintigraphy, a specific technique for imaging amyloid deposits, in 13 consecutive patients with ESRF who had been dialysed for >5 years, at least 80% of the time by CAPD. Clinical and radiological features of beta2M amyloidosis were sought and compared with the results of SAP scintigraphy. RESULTS: SAP scans showed articular amyloid deposits in seven patients, all of whom had evidence of carpal tunnel syndrome and four of whom had arthralgia characteristic of dialysis amyloidosis. Typical radiographic bone cysts were present in only one case who had been dialysed for >17 years. The remaining six patients had no clinical, radiological or scintigraphic evidence of beta2M amyloidosis. CONCLUSIONS: The prevalence of beta2M amyloidosis in this study was comparable with that in reported haemodialysis populations. Many of the amyloid deposits demonstrated by SAP scintigraphy were not associated with symptoms, but larger and longer term studies are required to determine whether CAPD favourably influences their clinical expression.     

Rapid detection and serotyping of adenovirus by direct immunofluorescence

Four fluorescent antibody reagents were evaluated for their suitability for the identification of adenovirus isolates by immunofluorescence. The antibodies used in the reagents consist of monoclonal antibodies against adenovirus type 3 (Ad3), Ad4, Ad8, and adenoviruses of subgroup C (Ad1,2,5,6), serotypes known to occur in outbreaks of disease. Most of the monoclonal antibodies employed were reactive against type-specific antigens found on the hexon protein. Reagents employing two noncompeting anti-hexon antibodies were more sensitive than reagents prepared with only one monoclonal antibody, although both types of reagents exhibited a high degree of specificity. Five hundred and seventeen adenovirus isolates (359 of which had previously been typed by other methods) and 46 nonadenovirus isolates were examined with all four type-specific reagents in parallel with an adenovirus group-specific reagent. The results indicate that direct typing of adenovirus isolates is feasible, leading to significant savings in time compared to other typing methods and should contribute to the management of certain adenovirus infections, particularly during outbreaks. J. Med. Virol. 51:198–201, 1997. © 1997 Wiley-Liss, Inc.     

Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high‐grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non‐dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real‐time spectroscopy and ensures spot‐on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy‐to‐use endoscopic tool during BE surveillance. We aimed to develop a tissue‐differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non‐suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross‐validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low‐grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low‐grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non‐neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe‐based spectroscopy techniques may be integrated in this optical biopsy forceps system.