Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021

Immunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis. Overlooking the diagnosis of light chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Herein we provide a review of established and investigational treatments for patients with AL amyloidosis and provide algorithms for workup and management of these patients.Subject terms: Myeloma, Chemotherapy     

Atypical cutaneous γδ T cell proliferation with morphologic features of lymphoma but with clinical features and course of PLEVA or lymphomatoid papulosis

Reactive lymphoid infiltrates of the skin composed predominantly of gamma‐delta (γδ) T cells are not well described in the literature. Herein we report a case of an otherwise healthy 4‐year‐old male who presented with a waxing and waning papular rash characterized by small, discrete crusted papules spread across his trunk, face and extremities. Clinical evaluation revealed no evidence of systemic disease. Microscopic examination revealed a dermal, perivascular infiltrate of highly atypical lymphocytes with a γδ T cell phenotype, worrisome for primary cutaneous γδ T cell lymphoma. The clinical course, however, was that of a reactive condition and prompted consideration of a diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP). In many ways, this case defies current classification schemes and seems to expand the spectrum of reactive γδ T cell infiltrates of the skin.     

High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase

The enzyme O6-methylguanine-DNA methyltransferase repairs alkylation- induced DNA damage, O6-methylguanine and O4-methylthymine, the former being formed more frequently. Previously, by means of gene targeting, we generated mice in which alleles for methyltransferase were disrupted. We now use these mouse lines, which are totally deficient in methyltransferase activity, to examine protective effects of the enzyme against tumor formation. In gene-targeted female mice given an i.p. injection of 5 mg/kg of dimethylnitrosamine, a larger number of liver and lung tumors occurred, as compared with normal female mice treated in the same manner. In male mice given a lower dose of carcinogen, the difference between normal and gene-targeted mice was statistically insignificant although more tumors did form in the gene-targeted mice. Methyltransferase apparently afforded protection from nitrosamine- induced tumorigenesis.      

Novel benzamides as selective and potent gastric prokinetic agents. 1. Synthesis and structure-activity relationships of N-[(2-morpholinyl)alkyl]benzamides

With the purpose of obtaining more potent and selective gastric prokinetic than metoclopramide (1), a new series of N-[(2-morpholinyl)alkyl]benzamides (17-52) were synthesized and their gastric prokinetic activity was evaluated by determining effects on the gastric emptying of phenol red semisolid meal and of resin pellets solid meal in rats and mice. The morpholinyl moiety was newly designed after consideration of the side-chain structure of cisapride (2) and produced the desired activity when coupled with the 4-amino-5-chloro-2-methoxybenzoyl group of both metoclopramide and cisapride. Modification of the substituents of the benzoyl group markedly influenced the activity. In particular, 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2-methoxybenzamide (17) and the 4-(dimethylamino) and 2-ethoxy analogues (25 and 29) of 17 showed potent and selective gastric prokinetic activity along with a weak dopamine D2 receptor antagonistic activity.     

Detection of proteinous toxins using the Bio-Threat Alert system, part 3: effects of heat pretreatment and interfering substances

We previously reported that the Guardian Bio-Threat Alert (BTA) system could detect (detection limit: about 0.1 μg/ml) staphylococcal enterotoxin B (SEB), botulinum toxins (BTX) A and B, and ricin, with no interference by white-powdered materials or colored matrices. In this study, the capability of the BTA system was further assessed. With 10 min of preheating at 60°C, all toxins could be detected, but with preheating at 80°C, BTX A and B and ricin became undetectable. About 20% SEB could be detected after heating at 80°C, but this detection ability was completely removed after heating at 100°C. The effects of chemicals usually used for decontamination, such as sodium hypochlorite, hydrogen peroxide, formaldehyde, and sodium nitrite, on the detectability of SEB, BTX A, or ricin in the BTA system were also tested. The concentrations giving 50% line intensity for SEB, BTX A, and ricin were 3.1, 11, and 15 μM for sodium hypochlorite and 88, 210, and 60 mM for formaldehyde, respectively. The addition of hydrogen peroxide or sodium nitrite did not decrease the detectability even when used at high concentrations.     

Clinical usefulness of the frontal assessment battery (FAB) for elderly in memory clinic]

To investigate the usefulness of the frontal assessment battery (FAB) as a brief assessment for diagnosis in patients with dementia, we examined cognitive function using the FAB, Mini-mental state examination (MMSE), Kana-hiroi test, and Raven's colored progressive matrices (RCPM). Subjects were 82 senile patients having amnesia as a complaint including 28 Alzheimer's disease (AD), 14 frontotemporal dementia (FTD), 17 vascular dementia (VD), 13 mild cognitive impairment (MCI), and 10 healthy persons. We discussed the difference of scores in different types of dementia. In the FAB, the scores of healthy persons and MCI were much higher compared with the scores of all types of dementia. There were high correlation between FAB and MMSE, Kana-hiroi test, and RCPM. Although some subjects showed normal score in MMSE and/or RCPM, they showed low score in FAB. Based on this, FAB is efficient for the differential diagnosis of dementia as brief screening tool.     

Behavioral analysis of internal memory states using cooling-induced retrograde amnesia in Limax flavus.

Temporal evolution of internal memory states in a terrestrial mollusk, Limax flavus, was studied using cooling-induced retrograde amnesia. The slug was conditioned to avoid carrot odor by temporally correlated presentation of carrot juice and a bitter-taste stimulus of quinidine sulfate. We could induce retrograde amnesia by cooling of the conditioned slug immediately after the training trial. Thus, we studied the memory states in the slug using the retrograde amnesia according to strategies used in the studies of memory states in mammals or insects. In the early process of memory acquisition, at least two distinctive memory states were observed, short-term memory and long-term memory (LTM). For LTM, two states were also observed. One was a reactivated state of LTM, which was sensitive to the cooling used to induce the amnesia. The other was a so-called resting state of LTM, which was insensitive to cooling. A few days after memory acquisition, further evolution was observed in that the amnesia could not be induced even if the memory trace was reactivated. The results obtained in Limax flavus was comparable with those obtained in a variety of animals.