Chronobiological circadian aspects of serum lactate dehydrogenase and serum thymidine kinase in monitoring multiple myeloma.
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Biomedical subjects
Publications and source records attributed to R Casale.
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A retrospective study was conducted in 285 cases of monoclonal gammopathy of undetermined significance (MGUS) and in 570 sex- and age-matched hospital controls in order to investigate the possible association between socioeconomic status, residence, alcohol and tobacco habits, occupation, occupational exposure to toxic substances, chronic antigenic stimulation, and risk of MGUS. Significant associations with the risk of MGUS were found for farmers (P < 0.005) and for workers in industry (P < 0.025). Occupational exposure to asbestos, fertilizers, mineral oils and petroleum, paints and related products, pesticides, and radiation was significantly (P < 0.05) associated with an increase in risk of MGUS. Chronic immune-stimulating conditions, when considered as a group, presented a significant (P < 0.025) association with the risk of MGUS, but no specific disease has been found to be significantly associated. These data are in agreement with the previous reports on multiple myeloma, suggesting that these factors may play an important role in the development of monoclonal gammopathies. However, these findings need to be confirmed in prospective larger population-based studies.
The diurnal rhythm in the circulating serum levels of erythropoietin (EPO) were determined in a group of 20 adult clinically-healthy subjects, in a group of 10 patients with myeloma without renal impairment and 10 patients with myeloma and renal failure. Venous blood samples were drawn during the span of a whole day and every 4 hr, starting from midnight, for the measurement of serum EPO levels by radioimmunoassay (RIA). Statistical analysis was carried out by means of the "cosinor" method. Results show that the controls and the myeloma patients without renal insufficiency present significant (P < 0.05) circadian rhythms in serum EPO levels; no rhythm (P < 0.05) was detected in patients with myeloma and renal failure. Patients with myeloma and renal failure have significant (P < 0.05) lower mean daily levels and diurnal fluctuations of EPO than the other groups, whereas the patients with myeloma without renal involvement present higher (P < 0.05) mean daily levels and lower (P < 0.05) diurnal variations of EPO than controls; no differences (P > 0.05) exist between the groups regarding peaks of rhythms. These data confirm the existence of a physiological circadian rhythm in serum EPO concentrations, with maximum in the afternoon, and they suggest that renal failure is an important cause of anemia and loss of EPO circadian rhythm in patients with myeloma.
The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.
The involvement of the nervous system in SSc is well recognized today. Different pathogenetic mechanisms are suggested that may alternatively explain the multiform appearance of the clinical spectrum (mononeuritis, mononeuritis multiplex, carpal tunnel syndrome, and so forth). It is now clear that the ANS is the earliest structure targeted by the disease in the gastrointestinal tract. The importance of this observation has not yet been adequately interpreted but may, together with the increasing evidence of the nervous system involvement in SSc, become a leading factor in understanding of the importance of the nervous system in the onset, development, and maintenance of the disease.
Both decreased and increased sympathetic nerve activity has been suggested as a possible underlying mechanism in inflammatory skin lesions. Modulation of sympathetic function has been proposed in the treatment of dermatitis. This case report describes the investigation strategy and normal findings in a case of dermatitis strictly confined to the median nerve territory, illustrating the need for specific tests of sympathetic function when pharmacological as well as physical sympatho-modulatory therapies are considered.
OBJECTIVE: Plasma-cell leukemia (PCL) is considered the leukemic variant of multiple myeloma. The diagnosis is based on plasmocytosis exceeding 2,000/mm3 and any evidence of clonal plasma cell proliferation. There are two forms of PCL: the primary form occurring in patients without preceding multiple myeloma or monoclonal gammopathy of undetermined significance, and the secondary form arising as a late manifestation in patients with multiple myeloma. Aim of the study was to describe our series of PCL and to report the main clinical and laboratory findings from the largest series in the literature. METHODS: Review of all cases of PCL observed from 1976 to 1994 in our Medical Divisions. Med-line research of the largest (more than 5 cases reports) series of PCL from 1969 to 1994. RESULTS: Eleven cases of PCL were identified. We diagnosed 6 cases with primary PCL out of a total of 512 patients with monoclonal gammopathy (incidence, 1.2%), 4 cases of secondary PCL as terminal phase out of 220 patients with multiple myeloma (incidence, 1.8%), and 1 case of secondary PCL as evolution of monoclonal gammopathy of undertermined significance out of 226 cases (incidence, 0.4%). From our and literature review, that identified 203 cases of primary PCL and 157 cases of secondary PCL, the clinical and the laboratory features did not significantly differ between primary and secondary forms of PCL, whereas significant differences exist between the two forms regarding response to therapy and median survival. In our series, the mean survival was 14 months for primary PCL and 6.8 months for secondary PCL. Two of the 6 patients with primary PCL obtained a complete remission, with a duration of 28 and 23 months, respectively; only 1 patient with secondary PCL had a response to chemotherapy, with a remission of 6 months. CONCLUSION: Our observation and literature data indicate that PCL, both primary and secondary, is a very poor prognosis disease, that the response rate is higher with combination chemotherapy than single agents, and that primary PCL has a relatively better survival, since secondary plasma PCL usually shows resistance to any type of chemotherapy.
Spasticity is one of the major problems affecting the outcome of rehabilitation in paraplegic patients. Orphenadrine citrate possesses an effective muscle relaxant action in many pathologies. Nevertheless, despite a recognized central site of action, no controlled data are available on its use in the treatment of spastic hypertonia in patients with spinal cord injuries. Therefore, the effect of intravenous administration of 60mg of orphenadrine citrate versus placebo on spastic hypertonia after spinal cord injury was studied in 11 patients. The threshold of the flexion reflex of the lower limb was studied as a neurophysiological correlate of spastic hypertonia. Clinical assessment was made using the Ashworth Spasticity Scale. The threshold, expressed in mAmp, was studied for 60 minutes after the treatment. A significant difference was found using the active drug compared with placebo (p < 0.0001). In 9 patients, the reduction of the abnormal flexion responses after orphenadrine appeared to begin only after 30 minutes. In one patient the onset of the therapeutic effect was early but weak. One patient with severe spastic hypertonia leading to triple flexion when the limb was manipulated did not gain any relief with orphenadrine. The clinical and neurophysiological results suggest an efficacy of orphenadrine citrate in the control of spastic hypertonia in paraplegics. This could be relevant in the rehabilitation strategy, although further studies are needed on the duration of its action.
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In order to assess the diagnostic value of serum gamma-glutamyl-transpeptidase (GGT) and mean corpuscular volume (MCV) as markers of alcoholism in chronic liver diseases, 107 patients with non-alcoholic chronic liver disease and 192 patients with alcoholic liver disèases have been compared. GGT and MCV values were checked two times: the day of admission to hospital and 10 days after complete withdrawal from alcohol. The patients with alcoholic liver diseases present significantly higher values of GGT and MCV in respect with patients with non-alcoholic liver diseases. A significant (p < 0.05) decrease of about 50% in serum GGT levels and of about 3% in MCV was observed after alcohol withdrawal only in the group of alcoholic liver diseases whereas no changes were found in the other group of patients: For the diagnosis of alcoholism in chronic liver diseases, while the sensitivity and the specificity of the several markers vary from 50% to 86%, the positive predictive values of GGT and MCV at admission were 92.2% and 73.4%, and the negative predictive values were 40.2% and 75.7%, respectively. Moreover, the positive predictive values of GGT and MCV after 10 days of alcohol withdrawal were 95.3% and 85.9% and the negative predictive values were 31.8% and 46.7%, respectively. The contemporary decrease in GGT and MCV values does not seem to offer better informations than GGT decrease. These data suggest that, even if GGT and MCV do appear per se as weak indicators of alcoholism during chronic liver diseases, the early decrease in their values, especially in serum GGT, are good and specific markers of alcohol abuse and, consequently, of the alcoholic etiology of liver disease.
Peripheral arterial disease (PAD) patients are commonly classified on the basis of subjective evaluations of pain and fatigue. Surface electromyography (EMG) is an objective method for studying peripheral muscle fatigue. Fifteen patients with PAD and 15 healthy volunteers matched for age and sex were studied. Surface EMG was recorded over the medial gastrocnemius during 100 seconds at 60% of maximal effort. EMG traces were analyzed off-line to obtain the power spectrum. The median frequency was calculated in the first 30 seconds (T0) and between 70 and 100 seconds (T1). Significantly lower T1 values, compared with T0, were found in both the PAD and the control groups (p < .005; p < .05). T0 values were not different between group, whereas T1 values were significantly lower in PAD patients (p < .01). EMG frequency analysis can be considered an easy, painless method providing objective information on muscular performance and fatigue in PAD patients.
The use of tert-butylphenoxyacetyl for N-protection of nucleoside bases during oligonucleotide synthesis facilitates its removal under mild conditions. This protecting group reduces depurination of deoxyadenosine residues, and minimizes premature desilylation resulting in chain degradation during post-synthesis workup of synthetic RNA.
It has been suggested that immunosuppression with cyclosporine induces marked sympathetic neural hyperactivity in heart transplant recipients. In the present study, the resting level of sympathetic nerve activity was investigated with intraneural recording in nine patients with severe chronic heart failure (NYHA class III-IV despite ongoing therapy), in nine heart-transplanted patients with previous heart failure (NYHA class III-IV) receiving standard low-dose triple-drug immunosuppression and in six age-matched controls without cardiovascular disease. Compared to the control group, resting sympathetic nerve discharge was markedly increased in heart failure patients (92 +/- 2 vs 60 +/- 6 B/100 b, P < 0.01), sympathetic nerve activity was lower in the majority of heart failure patients after heart transplantation, and mean burst incidence was significantly lower than in the cardiac failure group (70 +/- 7, P < 0.01). The difference between transplanted patients and the control group was not statistically significant. Thus, heart transplant recipients may reduce the augmented central sympathetic drive associated with cardiac failure despite ongoing cyclosporine treatment.
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Intraneural recording in skin fascicles of the left ulnar nerve was performed in a 51 year old patient with reflex sympathetic dystrophy (allodynia, marked vasoconstriction in the ulnar part of the left hand) following Vth finger amputation. Skin sympathetic activity showed normal characteristics with a weak discharge at rest whereas bursts of impulses could be evoked by sympatho-excitatory stimuli. Sympathetic bursts induced by painful stimuli were few, also during long-lasting allodynic pain. Sympathetic bursts induced by inspiratory gasps were not associated with excacerbation of pain. The discrepancy between the marked skin vasoconstriction and the low resting sympathetic discharge underlines the fact that sympathetic effector organ hyperactivity (i.e. vasoconstriction and/or hyperhidrosis) cannot be taken as evidence for increased sympathetic discharge. In the present case, the neuropathic pain syndrome cannot be considered as maintained by an increased sympathetic neural discharge to the symptomatic limb.
BACKGROUND: Because airway calibre shows a circadian rhythm and since exposure to passive smoking reduced lung function this study was undertaken to investigate whether passive smoking affects the circadian rhythm of peak expiratory flow (PEF) in schoolchildren. METHODS: Twenty schoolchildren (12 boys and 8 girls, aged 10-11 years) exposed to passive smoking were matched for sex, age, and height with 20 children who had not been exposed to cigarette smoke. Exposure to passive smoking was assessed by questionnaire and by urinary cotinine concentrations. A portable spirometer was used to measure PEF at 16:00, 20:00, 22:00, 06:00, 08:00, and 12:00 hours on a consecutive Saturday and Sunday. The circadian changes in PEF were measured by the cosinor method. RESULTS: Both groups showed diurnal fluctuation in PEF values with a noticeable circadian rhythm. PEF peaks were the same in the two groups and occurred around 15:00 hours. The cosinor mean was approximately 10% lower in children exposed to passive smoking and the amplitude was approximately 60% higher than in the unexposed children. CONCLUSION: Passive smoking in children is associated with a reduction in the cosinor mean and an increase in the amplitude of the normal circadian rhythm of airway calibre. This increased PEF rhythm amplitude may be considered as an early indication of airway obstruction.
The prognostic value of the Plasma Cell Synthesis Score (PCSS) has been tested in a group of 140 patients with multiple myeloma followed up from diagnosis to death. Calculation of PCSS, based on the regression coefficients obtained by multivariate regression analysis according to Cox's model, was performed according to the formula: [formula: see text] Substratification into three risk groups was performed as follows: low risk = PCSS more than 70; moderate risk = PCSS between 50 and 70; high risk = PCSS less than 50. Significant differences were found among the three stages regarding median survivals (p less than 0.005), survival curves (p less than 0.000000001), and response to therapy (p less than 0.00001). A positive significant relationship was demonstrated between calculated PCSS and survival in the whole group (p less than 0.000001). PCSS could be a good estimation of bone marrow plasma cell differentiation, and therefore could be a useful prognostic parameter in multiple myeloma.
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