Dietary interactions and INR variability: retrospective evaluation of patients couples on oral anticoagulant therapy.

AIM: The association between dietary vitamin K intake and International Normalized Ratio (INR) variability in patients on oral anticoagulants treatment (OAT) has been evaluated in several studies. Changes in diet composition are known to lead to INR variability. We evaluated INR over time in married couples on OAT and non-cohabitant couples on OAT, to assess clinical relevance of the diet. METHODS: Among outpatients receiving OAT we selected 31 married couples. Husbands and wives were then matched by demographic and clinical characteristics to 31 men and 31 women on OAT not married nor living together. We analyzed 6,357 INR measurements recorded from February 1998 to November 2009. RESULTS: We found similar average INR values within married couples and also within non-cohabitant couples. Using mixed models we confirmed INR differences between seasons and the slightly lower INR in non-cohabitant couples compared to married couples; although statistically significant, they were of marginal clinical significance. CONCLUSION: Within both married and non-cohabitant couples, we did not find statistically or clinically significant differences between men and women over time. The lack of INR differences over time within non-cohabitant couples indicates that diet is not an important determinant of INR over time. Also seasonal INR variations and differences between married and non-cohabitant couples were of little practical importance.

Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis.

Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in various neurological diseases. Cognitive impairment occurs early in multiple sclerosis (MS). Conflicting data have been reported regarding plasma total homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive impairment in MS is not known. This study investigated whether plasma total homocysteine levels are increased in MS and if HHcy is associated with cognitive impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy age-matched controls. We used a neuropsychological test battery that included the Raven's Coloured Progressive Matrices, the Visual Search Test, the Trail Making Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration, coexisting disease, smoking habit, and physical disability) and laboratory variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were evaluated for their ability to predict cognitive impairment. The mean tHcy was higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L, SD2.53; p < 0.001). Univariate analysis determined the following factors to be associated with cognitive impairment: higher age at observation, chronic progressive course of disease, longer disease duration,moderate or severe physical disability, and frequency of HHcy. With multivariate regression analysis, there remained a significant association only between frequency of HHcy and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are increased in MS and that HHcy is associated with cognitive impairment in this disease.

"In vitro" colony growth of blood T-lymphocytes from B-cell chronic lymphocytic leukemia.

T-lymphocyte colony formation in agar culture was investigated in 20 untreated B-cell Chronic Lymphocytic Leukemia (CLL) patients in stage O. As compared to the controls, colony growth was very poor when unseparated peripheral-blood lymphocytes from CLL-patients were seeded. The number of colonies was greatly higher when T-cell enriched fractions from CLL were plated; however, they failed to reach the normal range even in this experimental condition. The role of adherent cells in the colony growth was also investigated. Depletion of these cells resulted in impaired colony generation either in normals or in CLL-patients, which was subsequently restored by the addition of the same adherent cells. In the patients investigated in this study, an imbalance of T-subsets was found with increase of OKT8-positive cells (T-suppressors). When the number of colonies and the percentage of OKT8-positive cells were plotted, an inverse correlation was found. Conversely, a linear relationship was detected between the percentage of OKT4-positive cells (T-helpers) and the values of colonies. On the basis of the present experiments, it is suggested that the defective colony growth of T-cell fractions in B-cell CLL may be related to the low number of OKT4-positive cells plated, which are known to be mainly responsible for the colony generation in agar culture.

Multiple myeloma in husband and wife.

An instance of multiple myeloma (MM) in a married couple is discussed, since cases of MM in husband and wife have rarely been observed. The patients were aged 60 when the disease was discovered, and the interval between the diagnosis in the mates was 44 months. Genetic or environmental factors that could have explained the occurrence of myelomatosis were not found in these spouses. Therefore, on absence of a defined cause, our observation, like others previously reported in the literature, should be considered, although exceptional, a chance event.

In vitro proliferative response of chronic lymphocytic leukemia.

The peripheral blood lymphocytes of 13 previously untreated chronic lymphocytic leukemia (CLL) patients showed a decreased and delayed response in vitro to plant mitogens (PHA and PWM) and specific antigens (PPD and MLC). In addition, the serum of these patients inhibited the mitotic reactivity of both autologous and homologous normal lymphocytes. Since incubation with CLL serum did not affect the SRBC-rosetting capacity of normal lymphocytes, we believe that CLL serum interferes with some metabolic stage in blastogenesis rather than at the level of mitogen membrane interaction. The in vitro transformation of lymph node, bone marrow and peripheral blood lymphocytes in some of these patients was also investigated. Stimulation of peripheral blood cells with plant mitogens resulted in a more serious impairment of the response than that found with bone marrow and lymph node cells. This could be explained by the fact that, although CLL is a widespread lymphoproliferative disorder, some preferential homing of normally reactive cells in the bone marrow and lymph nodes cannot be excluded. Finally, since no stimulation was observed in mixed leukocyte cultures (MLC), our experiments provide evidence that no antigenic differences are detectable in CLL lymphoid populations.