A retrospective study of the Framingham cardiovascular risk scores in a liver transplant population.

OBJECTIVE: Evaluate the relationship between Framingham cardiovascular risk scores (FRS) and transplant-related factors, particularly renal function, in a stable liver transplant population. METHODS: Single-center retrospective study of 54 post-liver transplant patients followed in one outpatient clinic. Demographics and laboratory data were assessed using the modified FRS (2009). Standard statistical analyses were performed between FRS and transplant-related factors; patient demographics, new-onset diabetes after transplant (NODAT), immunosuppressives, and estimated glomerular filtration rate (eGFR) measured by isotope dilution mass spectrometry (IDMS) and Cockcroft-Gault (CG) equations. RESULTS: Forty percent of patients were classified as low FRS, 29.6% as moderate FRS, and 29.6% as high FRS (of whom 50% had NODAT). Immunosuppressant use was similar between the high- and low-risk groups. FRS inversely correlated with eGFR (P = .0001) measured by either equation. eGFR measured by IDMS in the high-risk group (60.4 ± 22.1 mL/min/1.73 m(2)) was significantly lower than that in the low-risk group (97.1 ± 54 mL/min/1.73 m(2); P = .0001). In the multivariate analysis, age, eGFR and NODAT were significantly different between the low- and high-risk FRS groups. Receiving operational characteristic (ROC) analysis identified eGFR measured by IDMS at 42.7 mL/min/1.73 m(2) with a sensitivity of 92%, specificity of 19%, and positive predictive value of 72% to identify high-risk patients. Box-plot analysis of variance between eGFRs in the three risk groups showed a P value of .001. CONCLUSIONS: In this study one-third of liver transplant patients had a high FRS, and 14.8% had an eGFR below 40 mL/min/1.73 m(2). Low eGFR predicts those with high FRS. Liver transplant patients particularly those with NODAT, with low eGFR should undergo close management of cardiovascular risk factors.

Collagenous colitis and microscopic colitis: the watery diarrhea-colitis syndrome.

Nine patients (seven females, two males) with chronic watery diarrhea and nonspecific colonic mucosal inflammation followed for 1-5 yr are presented. Eight were diagnosed as having collagenous colitis on the basis of marked thickening of the subepithelial collagen layer in at least one set of biopsies. The thickness of the collagen table varied with time in all eight cases. When thickening was minimal, morphological features were indistinguishable from microscopic colitis, signifying that, in most cases, collagenous colitis and microscopic colitis are part of the same spectrum of colonic mucosal response. One of the eight patients had documented collagenous colitis and gluten-associated enteropathy for 12 yr. The colitis and duodenal histology improved synchronously when a gluten-free diet and corticosteroids were administered. The ninth patient had microscopic colitis and enteropathy which did not respond to gluten withdrawal. This patient never exhibited thickening of subepithelial collagen in repeated biopsies over 5 yr, suggesting that an entity of microscopic colitis may exist independent of collagenous colitis. Duodenal mucosal biopsies showed normal histology in four other patients with collagenous colitis. The histological variability of collagenization and inflammation during the course of collagenous colitis and microscopic colitis and the clinical feature of watery diarrhea suggest that these two entities be grouped together as the watery diarrhea-colitis syndrome.

A novel enteropathy with partial villous atrophy, microscopic colitis, and pemphigoid change.

Microscopic colitis associated with gluten-resistant partial villous atrophy was documented in a 21-year-old woman with chronic nonbloody diarrhea. Electron microscopic examination of the colonic and duodenal biopsies showed focal separations of basal lamina from cryptal epithelial cells forming subepithelial blebs in which were mast cells and fibroblasts. These morphologic features have not been previously described in any inflammatory bowel disease and are reminiscent of bullous pemphigoid of the skin. The findings suggest that not all cases of microscopic colitis lie within the spectrum of collagenous colitis.

Gallbladder function during gallstone dissolution. Effect of bile acid therapy in patients with gallstones.

Impaired gallbladder emptying has been associated with gallstone disease but any effect on or from bile acid therapy for gallstone dissolution is unknown. We evaluated gallbladder filling and emptying with low-dose cholecystokinin infusion (0.02 U/kg.h) by computer-assisted cholescintigraphy in 52 controls versus 31 gallstone patients: 17 treated with 12-15 mg/kg.day of chenodeoxycholic acid and 14 with 8-10 mg/kg.day of ursodeoxycholic acid. Thirteen of 31 patients with complete dissolution had four scans: before, after 3 mo of therapy, after stone dissolution, and after discontinuation of bile acids. The 18 failures had three scans: before and after 3 and 15-18 mo of therapy. Before therapy, the 31 gallstone patients had significantly impaired gallbladder emptying compared with controls, but filling was not decreased. Bile acids significantly decreased emptying in both treatment groups after 3 mo of therapy. In the dissolution group, emptying improved once the stones had dissolved and increased further upon discontinuing the bile acids. In the failures, impaired emptying persisted for up to 15-18 mo. Gallbladder filling in the 31 gallstone patients was also significantly decreased after 3 mo of bile acid therapy, particularly in the failure patients, 5 of whom exhibited zero filling. No differences were detected between ursodeoxycholic acid and chenodeoxycholic acid for either gallbladder function or efficiency of dissolution. Thus, bile acid therapy impairs gallbladder filling and emptying in gallstone patients. Gallstone dissolution improves emptying, which is further enhanced when bile acids are discontinued.

Leiomyosarcoma of the inferior vena cava presenting as Budd-Chiari syndrome.

A case of a 72-year-old male with a leiomyosarcoma of the inferior vena cava causing Budd-Chiari syndrome is described. Percutaneous decompression of the portal system was attempted but with no success. At autopsy, a large tumor arising from and completely obstructing the inferior vena cava was found, histologically proven to be a leiomyosarcoma. Over 50 cases of leiomyosarcoma of the inferior vena cava have been reported in the literature, the majority of which occurred in women and 1/3 of which were associated with the Budd-Chiari syndrome. Histologically up to two mitotic figures per 10 high power fields have been scored. This case indicates the unreliability of a low mitotic index as an indicator of benign behavior of smooth muscle neoplasms of the venous system.

Comparison of purine degradative enzymes and terminal deoxynucleotidyl transferase in T cell leukaemias and in normal thymic and post-thymic T cells.

Adenosine deaminase (ADA), ecto 5' nucleotidase (5'NT), purine nucleoside phosphorylase (PNP) and terminal deoxynucleotidyl transferase (TdT) were measured in the cells of patients with acute or chronic T cell leukaemia and compared with normal putative prothymocytes (large, blast-like cortical thymocytes), cortical and medullary thymocytes and peripheral blood T lymphocytes. Distinct patterns of enzyme activities were found in the individual types of T cell leukaemia. Mean ADA, TdT and 5'NT activities in thymic acute lymphoblastic leukaemia (Thy-ALL) were 41.9 u/10(8) cells, 31.1 u/10(8) cells and 4.7 u/10(6) cells respectively; in chronic T cell leukaemia they were 7.1 u/10(8) cells, 0.6 u/10(8) cells and 18.1 u/10(6) cells respectively. Mean PNP activity was similar between these two groups of leukaemia (68.6 u/10(6)cells in Thy-ALL and 77.9 u/10(6) cells in chronic T cell leukaemia). The activities of these four enzymes in OKT4+ chronic T cell leukaemia did not differ significantly from those in the OKT8+ chronic T cell leukaemia cases. The activities of TdT, ADA, PNP and 5'NT in Thy-ALL closely resembled those in normal immature thymocytes, and in the chronic T cell leukaemias showed a similar pattern of enzyme activities to that of mature T lymphocytes. These findings are consistent with surface phenotypic studies of T cell malignancies which suggest that different T cell leukaemias represent malignant proliferation of T cell clones arrested at different stages of T cell differentiation. They also demonstrate the value of biochemical markers in defining the different subtypes of acute and chronic leukaemia.

The role of purine metabolic enzymes and terminal deoxynucleotidyl transferase in intrathymic T-cell differentiation.

Most cortical thymocytes die within the thymus. It is proposed here that lethally high intracellular levels of deoxynucleosides are the cause of death. Developing thymocytes appropriately equipped for self-recognition are protected because contact with stromal cells prevents the lethal accumulation of deoxynucleosides.

Enzymes of purine metabolism in human peripheral lymphocyte subpopulations.

Ecto-5'nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and deoxycytidine (CdR), deoxyguanosine (GdR), deoxyadenosine (AdR) and adenosine (AR) kinases have been measured in subpopulations of peripheral blood lymphocytes of eight healthy volunteers. The separation of B, T, T helper/inducer and T suppressor/cytotoxic cells was performed by means of density gradient centrifugation, E rosetting, passage through a nylon-wool column and antibody affinity chromatography utilising OKT8 and OKT4 monoclonal antibodies. ADA was significantly higher in T lymphocytes and 5'NT in B lymphocytes. Among T cell subpopulations, 5'NT activity was significantly higher (P less than 0 . 01) in T suppressor/cytotoxic (OKT8+) cells (32 . 9 units/10(6) cells than in T helper/inducer (OKT4+) cells (9 . 7 units/10(6) cells). Indeed, the 5'NT activity in T suppressor cells was similar to that in B cells. T helper cells tended, however, to have higher PNP and ADA activities than T suppressor cells but the differences were not statistically significant. No major differences were noted in kinase activities between any of the lymphocyte subpopulations.

Nucleoside incorporation into DNA and RNA in acute leukaemia: differences between the various leukaemia sub-types.

The incorporation of the labelled deoxyribonucleosides 3H-deoxythymidine (3H-TdR), H3-deoxycytidine (3H-CdR), 3H-deoxyadenosine (3H-AdR), 3H-deoxyguanosine (3G-GdR), 3H-deoxyuridine (3H-UdR) and of labelled uridine (3H-UR) into DNA and RNA was studied in bone marrow (BM) and peripheral blood (PB) cells from 10 normal donors and 11 patients with acute myeloblastic leukaemia, 13 with acute non-T non-B common ALL (c-ALL) and seven with thymic acute lymphoblastic leukaemia. 3H-TdR incorporation was highest into the DNA of normal BM cells, 3H-CdR into DNA in Thy-All and 3H-UdR into DNA of c-ALL cells. Purine deoxynucleoside (3H-AdR and 3H-GdR) incorporation was highest in AML cells and they were incorporated mainly into RNA indicating that before utilization they are partially degraded from the deoxyribose to the corresponding ribose form. In all but three leukaemia samples, the 3H-UdR/3H-TdR incorporation ratio was above the range found in normal bone marrow, suggesting the leukaemic cells are more dependent than a normal mixed marrow cell population on the de novo pathway of thymidylate synthesis. The incorporation of nucleosides by peripheral blood cells was usually much lower than by the corresponding bone marrow cells, irrespective of blast percentage.

Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes.

Terminal deoxynucleotidyl transferase (TdT) and purine metabolic enzymes were examined in subsets of human infant thymocytes (defined by surface cell antigens) and normal peripheral T lymphocytes. Putative prothymocytes (RFB-1+, HTA-1+/- large blast-like cells), medium and high density cortical thymocytes (RFB-1+, HTA-1+), and medullary thymocytes (RFB-1-, HTA-1-, OKT3+) were isolated by density gradient centrifugation, monoclonal antibody and complement-mediated cytolysis, and cell-antibody affinity chromatography. Peripheral T lymphocytes were isolated from normal adult mononuclear cells using nylon fiber technique. Adenosine deaminase (ADA) and TdT were highest in prothymocytes 48.8 +/- 14.7 mumol/hr/10(8) cells (mean +/- SE) and 22.9 +/- 1.4 U/10(8) cells, respectively. Both enzymes decreased progressively down the maturation pathway. In peripheral T lymphocytes, ADA was 3.9 +/- 1.5 mumol/hr/10(8) cells, and TdT was undetectable. Purine nucleoside phosphorylase (PNP) and ecto-5'nucleotidase (5'NT) were lowest in cortical thymocytes (27.5 +/- 11.0 nmol/hr/10(6) cells and 2.8 +/- 1.3 nmol/hr/10(6) cells, respectively) and increased with T cell maturation. The PNP level was 124.9 +/- 17.2 nmol/hr/10(6) cells and 5'NT was 30.1 +/- 3.9 nmol/hr/10(6) cells in peripheral T lymphocytes. The deoxynucleoside kinases (deoxyguanosine, deoxyadenosine, and deoxycytidine kinases) paralleled the changes in ADA and TdT activity among the different T subsets. The proliferative activity (labeling index) was highest in the prothymocyte fraction and lowest in peripheral T cells. Variation in the distribution of these enzymes in T cell subsets may explain their different sensitivities to deoxyadenosine and deoxyguanosine toxicity and the different effects on T cell development of ADA or PNP deficiency.

The effect of deoxycoformycin and deoxyadenosine on deoxyribonucleotide concentrations in leukaemic cells.

Intracellular deoxynucleoside triphosphate pools of normal bone marrow, thymocytes and cells from patients with ALL and AML were measured after 2 h incubation with deoxycoformycin (dCF) 10(-5) M and deoxyadenosine (AdR) 10(-4) M in vitro and after another 30 min incubation in the absence of dCF and AdR ('chase' experiment). Incubation with dCF and AdR resulted in a significant rise of dATP concentrations in all groups (the highest rises occurring in the leukaemic groups particularly in AML and Thy-ALL). The concentrations of the other three deoxyribonucleoside triphosphates fell in all groups. The dATP level fell during the 'chase' period but in Thy-ALL and thymocytes this fall was insignificant and slower than in the other groups. This suggests that not only intracellular build-up of dATP but also the capacity of the cell to degrade dATP is important for in vivo cytotoxicity of dCF treatment. These results help to explain the differences in response to dCF of the different leukaemias.

5'nucleotidase, adenosine deaminase and purine nucleoside phosphorylase activities in acute leukaemia.

Three enzymes concerned in purine degradation, 5'nucleotidase (5'NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been measured biochemically in the bone marrow or peripheral blood blasts from 75 patients with acute leukaemia, from 18 patients with blast crisis of chronic granulocytic leukaemia and in the bone marrow and peripheral blood lymphocytes from 14 normal donors. Characteristic patterns among the different sub-types of acute leukaemia have been detected, with high ADA, low 5'NT and PNP in Thy-ALL, high 5'NT and ADA in c-ALL, high PNP and low ADA in AML. The cells in CGL blast transformation resembled the enzymatic pattern of either AML or c-ALL respectively. However, no significant correlation was found between any pair of enzymes in any group of leukaemia, normal bone marrow or peripheral blood lymphocytes studied here.

The results of prolonged treatment of autoimmune haemolytic anaemia.

Ninety-seven patients with autoimmune haemolytic anaemia were observed in the period between 1965 and 1979. Corticosteroids were found to be more effective in the acute phase of haemolysis (68.6%) than in the prolonged treatment (35%). Favourable results with combined treatment (corticosteroids plus azathioprine or cyclophosphamide) were achieved in 60.5% of patients, while the therapeutic potency of corticosteroids alone was 18.6%. Splenectomy was effective in 81% of the patients. No correlation between postsplenectomy results and spleen to liver radioactivity ratio was observed.

[Effect of platelet concentrate transfusions on the thrombopoietic activity in rats]. / Wplyw przetaczan koncentratów plytkowych na aktywnosc trombocytopoetyczna u szczurów.

Rats were given selected doses of rabbit antiplatelet serum (APS) inducing after 6 hours thrombocytopenia at the level of 14% of the initial platelet count followed by a gradual rise in this count (after 12, 24 and 48 hours). Eight hours after APS administration the rats were given transfusion of a concentrate containing 1-2 X 10(9) fresh allogenic platelets (group A) or the same number of previously frozen platelets (group B). Rats receiving no concentrate after APS administration (group C) and rats receiving neither APS nor concentrate (group D) served as controls. Using a bioassay on mice the serum thrombocytopoietic activity (ATS) was determined in the rats and the platelet count was measured by the direct method. These determinations were done before and 24 and 48 hours after the experiment. It was shown that after 24 hours the values of the platelets (p less than 0.1) and ATS (p less than 0.001) were lower in group B than in the remaining groups. This suggests an inhibitory effect of the frozen concentrate on the ATS. After 24 hours the platelet count was highest in group A, and after 48 hours in group C, which suggests that transfusion of fresh concentrate has an immediate effect but in a later phase it inhibits spontaneous mechanisms effacing the thrombocytopenic effect.

Preliminary evaluation of immunotherapy in patients with Hodgkin's disease.

The clinical course of 38 patients with Hodgkin's disease in the stage of remission was evaluated. The material consisted of two groups of patients: 1. submitted to immunotherapy and 2. control group. In 16 cases immunostimulation was performed with BCG vaccine, including four cases treated with BCG vaccine and levamisole and 3 patients were given levamisole only. In some patients, immunotherapy restored normal immunologic reactivity, as shown by the reversion of negative tests of delayed hypersensitivity. In all patients treated with levamisole caused normal blastic transformation of PHA-stimulated lymphocytes. In the group of patients treated with immunotherapy relapses of malignant lymphogranulomatosis were observed in 10.6% of cases, and in the control group--in 15.7%. The patients of both groups remain under continuous clinical surveillance.

[Effect of splenectomy on blood serum thrombopoietic activity (ATS) in patients with hematopoietic diseases]. / WPlyw splenektomii u chorych z chorobami ukladu krwiotwórczego na aktywnosc trombocytopoetyczna surowic (ATS).

Thrombocytopoietic activity (ATS) was determined in tests on mice on the day before and on the 1st, 7th, and 14th days after splenectomy in 18 patients (13 with idiopathic thrombocytopenia, 5 with haemolytic anaemia). It was found that in patients with ITP and high-grade splenic destruction of platelets ATS increased on the first days after splenectomy. On the other hand, in ITP patients with low-grade splenic platelet destruction splenectomy decreased the value of ATS immediately after the operation. Splenectomy performed in cases with normal platelet count caused no greater changes in ATS in the first week. These observations suggest that in patients with increased splenic destruction of platelets ATS may be inhibited and this inhibition may be removed after splenectomy. Absent correlation between ATS and platelet count may indicate that the value of ATS is not of decisive importance in thrombocytopenia regression following splenectomy.