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Biomedical subjects

G Merlini

Publications and source records attributed to G Merlini.

At least 109 records · Page 6Linked to original sources

A new improved clinical staging system for multiple myeloma based on analysis of 123 treated patients.

The effect of the presenting clinical features on survival time was evaluated in 173 patients of a population of 201 individuals with multiple myeloma observed at Malmö General Hospital during the 11-yr period 1960 to January 1, 1971. Complete follow-up was continued until December 1978. One-hundred and five of the patients came from the city of Malmö and constitute a complete nonselected myeloma population. Bivariate correlation and multivariate regression analyses showed that the survival (i.e., the prognosis) could be accurately predicted in IgG and pure Bence Jones myeloma patients from (A) serum creatinine level, (B) serum calcium level, and (C) bone marrow plasma cell percentage; and in IgA myeloma patients from (A) hemoglobin level, (B) serum calcium level, and (C) serum M-component level. The results were synthesized to produce a simple and reliable clinical staging system with three stages (i.e., risks of death). To facilitate the clinical application, multivariate regression equations were developed to optimally predict the prognosis, and graphs were constructed in order to make the staging of the myeloma patients easier and quicker. The comparison of the duration of survival between the three groups of staged patients confirmed the high reliability of the present staging system.

Aged↗

An IgM monoclonal protein with multiple serological specificities.

An IgM lambda M-component with a false Wasserman reaction and 'false' rheumatoid factor activity from a patient suffering from a well-differentiated lymphocytic lymphoma is presented. The monoclonal protein showed antibody activity against cardiolipin and cross-reacted with acryl particles, not with human IgG. Both these activities were found in the Fab fragment. The reduction of the 19S IgM to 7S IgM subunits was responsible for a strong decrease in activity. The importance of the IgM quaternary structure in determining antibody affinity is emphasized.

Acrylates↗

Long-term effects of parenteral dichloromethylene bisphosphonate (CL2MBP) on bone disease of myeloma patients treated with chemotherapy.

Data on the long-term treatment of myeloma bone disease with bisphosphonates are scanty. In a prospective pilot trial we evaluated the effect of long-term parenteral administration of dichloromethylene bisphosphonate (Clodronate), in addition to standard chemotherapy, in 30 patients with active myeloma bone disease. Patients were treated with a mean of 4 courses (range 2-8) of Clodronate: 300 mg/day i.v. for seven days followed by 100 mg/day i.m. for 10 days, administered at a mean interval of 4 months (range 3-6). The median follow-up was 24 months (range 8-36). Clodronate reduced bone pain rapidly and significantly, and reduced the mean values of the biochemical indices of bone resorption to within normal limits; these effects were maintained throughout the follow-up. In three hypercalcemic episodes serum calcium became normal after 2-5 days of treatment with Clodronate. No toxic or side effects were noticed. The occurrence of skeletal morbidity in patients treated with Clodronate was compared with that observed in the control group of myeloma patients (p less than 0.001) in severe bone pain as well as in the incidence of new osteolytic lesions and pathological fractures (p less than 0.001). Supportive Clodronate therapy contributes significantly in controlling the progression of myeloma bone disease.

Bone Diseases↗

Calcium antagonists and hormone release. IV. The role of calcium in glucose-stimulated early phase insulin release in vivo.

Extensive in vitro studies have demonstrated that an increase in the concentration of Ca2+ in the cytosol of the beta-cell of islets of Langherhans is essential for the glucose-stimulated insulin release. However, there are controversies as to whether both phases of insulin release are equally dependent upon glucose-stimulated uptake of extracellular calcium. Previous studies performed in vivo, have demonstrated an inhibitory effect of verapamil, an organic antagonist of calcium transport into cells, on the release of insulin induced by an oral glucose load. The present study was designed to investigate whether calcium antagonists are capable of inhibiting the rapid release of insulin that follows the iv infusion of glucose. Verapamil, infused into normal subjects for different periods of time before the iv administration of glucose was ineffective in inhibiting the rapid release of insulin, even when it was infused for 1 h before the glucose stimulus was applied. The present results obtained in vivo confirm some previous in vitro data showing that the first phase insulin release is not inhibited by calcium antagonist, agents known to block the uptake of calcium from extracellular sources.

Administration, Oral↗

Nodular macroglossia with combined light chain and beta-2 microglobulin deposition in a long-term dialysis patient.

We describe a case in which nodular macroglossia, a very rare type of tongue involvement, was associated with the co-deposition of lambda light chain and beta-2 microglobulin fibrils in the tongue. The combined presence of two different amyloid fibrils did not lead to a more unfavourable clinical outcome. We believe that both these features often remain underdiagnosed and are in fact more frequent than reported. A careful clinical examination of the tongue together with serum immunofixation should be routine in all patients with dialysis-related amyloidosis in order to investigate the prevalence and type of tongue involvement and to rule out other types of amyloidosis. In all cases of suspected mixed amyloidosis, immunohistochemical characterization of fibrils should be carried out by electron microscopy.

Amyloidosis↗

Gene expression of pyrogenic cytokines in Hodgkin's disease lymph nodes.

BACKGROUND: Inflammatory cytokines released by either the neoplastic or reactive cells in Hodgkin's disease (HD) might mediate its peculiar clinical and histopathological features. We investigated by Northern blotting the gene expressions of the pyrogenic and inflammation-associated cytokines IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta (lymphotoxin) and IL-6 in 14 HD lymph nodes and studied their relation to systemic symptoms (B symptoms). METHODS: Two ug of poly(A)+RNA from 14 HD lymph nodes (8 from symptomatic and 6 from asymptomatic patients, of different histological type and disease stage) were subjected to agarose electrophoresis, Northern blotted and hybridized to the various cytokine cDNA probes. RESULTS: The inflammatory cytokines were expressed very heterogenously in HD, even in lymph nodes with the same histological type and with similar stromal inflammatory reactions. IL-1 beta was increased about 2 to 10 times in 5 of 8 lymph nodes from patients with B symptoms, whereas the other cytokines were heterogenously expressed in both symptomatic and asymptomatic patients. Statistical analysis on densitometric values demonstrated that the difference in IL-1 beta expression between symptomatic and asymptomatic patients was significant (p less than 0.02). CONCLUSIONS: These results support the hypothesis of increased IL-1 levels in tumoral lymph nodes from symptomatic HD patients.

Cytokines↗

Immunochemical characteristics of a particular cryoglobulin. A new cryoglobulin subgroup?

In a patient (BAR) affected by chronic active hepatitis we isolated a cryoglobulin constituted of polyclonal IgM (k and lambda) and a monoclonal IgG3 lambda. The IgM represented the antibody of the cryoglobulin complex. This type of cryoglobulin, where the monoclonal component is the antigen and not the antibody, cannot be correctly classified using the nomenclature of Brouet et al. (1) currently in use. In this patient a two-year follow-up excluded any clinical signs of cryoglobulin toxicity. The immunochemical and clinical characterization of other cryoglobulins similar to BAR could establish a new homogeneous group.

Blotting, Western↗

Multiple myeloma.

Multiple myeloma (MM) originates from the malignant clonal expansion of transformed B-lymphocytes (in which c-myc and ras oncogenes are probably involved). MM cells have a hybrid phenotype (with coexpression of the markers for both early and late B-differentiation and, sometimes, of T-lymphocyte, myelomonocyte, erythroid and megakaryocyte markers), which accounts for the association between MM and myeloproliferative disorders and for cytokine production. Interleukin-6 and immunologic control mechanisms regulate proliferation and differentiation into plasma cells secreting a monoclonal component (MC). Overt MM is diagnosed 1-2 years following malignant transformation. At this time, several aneuploid clones with resistant phenotype have been selected, and a small pool of actively cycling cells produces the great bulk (over 90%) of non proliferating tumor cells. The clinical and laboratory signs of MM arise from both tumor proliferation and MC damage to organs and organ systems. Tumor proliferation is mainly responsible for bone disease (since MM cells produce cytokines that activate the osteoclasts), inhibition of hemopoiesis and the appearance of plasma cell tumors. The MC causes renal failure, neurological signs, hemorrhagic manifestations. The prognosis for multiple myeloma is probably best estimated by two parameters, serum beta-2-microglobulin and the bone marrow labeling index. Induction therapy is still based on the use of alkylating agents, melphalan and cyclophosphamide, combined with prednisone. Second line treatment consists of VAD polychemotherapy or high-dose pulsed glucocorticoids. Many investigational approaches have been proposed, but their effectiveness awaits confirmation. In the absence of a curative regimen, much effort should be dedicated to the quality of supportive care. In this respect, bisphosphonates represent a new effective tool for the control of myeloma bone disease.

Antineoplastic Agents↗