The Prevalence of Frailty Using Three Different Frailty Measurements in Two Finnish Cohorts Born Before and After the Second World War.

OBJECTIVES: To study the prevalence of frailty and its relationship to mortality in cohorts born before and after the Second World War using three different frailty measures. METHODS: Cross-sectional data from two cohorts born in 1935 (n=593) and 1945 (n=714) were studied for frailty at the mean age of 70.7 (SD 1.8) years. Frailty was measured using the Frailty Phenotype (FP), the Frail Scale (FS) and the 74-item Frailty Index (FI>0.21 denoted frailty). Information on socioeconomic factors was obtained via a study questionnaire and the data on mortality were obtained from the Population Information System. RESULTS: The prevalence of frailty by FI was more common in the older 1935 cohort than in the 1945 cohort (p<0.001). The percentage of robust subjects was higher in both sexes in the 1945 cohort using both FI and FS. After adjusting for sociodemographic factors, the difference in the prevalence of frailty between the cohorts remained significant in women only (OR 1.9 (95% CI 1.3-2.9), p=0.001). The FI classified people as frail more often (30.2% in the 1935 cohort and 17.5% in the 1945 cohort) than the FS (13.1% and 8.8%) or FP (1.8% and 1.6%). Low financial satisfaction was associated significantly with frailty in both sexes. Low level of education was associated with frailty in women and being unmarried or divorced in men. Frailty was associated to increased mortality using all frailty definitions in the 1935 cohort with a longer follow-up time. CONCLUSIONS: Improved living conditions and health care may have resulted in the lower prevalence of frailty in the 1945 cohort. The present study further strengthens the association between frailty and mortality and poor economic status and frailty. Frailty definitions are in need of further study.

CD4 and CD8 expression of large granular lymphocytes after bone marrow transplantation and its effect on lymphocyte CD4/CD8 ratio.

Peripheral blood lymphocytes from 33 allogeneic bone marrow transplant recipients were studied. The number of large granular lymphocytes (LGL) in circulation increased rapidly after bone marrow transplantation (BMT). Their proportion of lymphoid cells exceeded 40% during the first month and was highest, 57%, one to three months after BMT. The CD4 and CD8 expression of LGL differed at different times after BMT. The CD4 positivity decreased from the pre-BMT value of 9.2 +/- 3.3% to 2.5 +/- 0.3% (p < 0.05) at 31-90 days post-BMT. The expression of CD8, on the other hand, was lowest during the first 30 days, 17.1 +/- 1.7%, and increased thereafter to reach its highest level, 49.2 +/- 4.3%, after three months. The low CD4 and high CD8 positivity together with a high proportion of LGL in lymphoid cells after the first month post-BMT inverted the CD4/CD8 ratio of lymphocytes for more than a year after BMT.

Immunohistology of skin and rectum biopsies in bone marrow transplant recipients.

We have studied histological and immunohistological specimens of 39 skin biopsies from 21, and 30 rectal biopsies from 17 bone marrow transplant recipients. The biopsies were taken before transplantation, during acute and chronic graft-versus-host disease (GVHD), and at times with no GVHD. In biopsies taken during cutaneous aGVHD grade I to III, epithelial changes were seen in 16/23 biopsies. The cutaneous infiltrates during aGVHD consisted of CD2-, CD4-, CD8- and FMC-33-positive cells both in the epithelium and in the dermis. CD57-positive NK cells were also detected in most biopsies. During chronic GVHD the cutaneous cellular infiltrates were similar to those seen in moderate aGVHD, i.e. both CD4- and CD8-positive lymphoid cells were present. When the biopsy was taken after the beginning of corticosteroid treatment for aGVHD, or at times when the patient did not have GVHD symptoms, the cellular infiltrates were considerably smaller in the dermis. During clinical intestinal aGVHD mucosal epithelial changes were relatively uncommon; instead, increased numbers of both CD4- and CD8-positive lymphocytes in the lamina propria (LP) were seen in 11/13 samples. During chronic GVHD the number of CD4-positive cells exceeded that of CD8-positive cells in the LP, and the large lymphoid infiltrates also reached the muscularis mucosae. In rectal biopsies the differences were not so prominent because most of the pretransplant biopsies showed CD2-, CD4-, CD8- and CD57-positive lymphocytes both in the lamina propria and epithelium.

Serum amyloid A levels in acute graft-versus-host disease in bone marrow transplant recipients.

We studied serum amyloid A levels of 31 bone marrow transplant recipients with and without acute graft-versus-host disease. Before transplantation the mean SAA concentration was 5.1 +/- 0.8 mg/l (mean +/- SEM). It remained low in patients with no signs of aGVHD but increased significantly during aGVHD to 54.0 +/- 8.2 mg/l (p less than 0.001 compared to pre-BMT value). Severe infections also induced high SAA levels.

Use of bronchoalveolar lavage cytology and determination of protein contents in pulmonary complications of bone marrow transplant recipients.

Bronchoalveolar lavage (BAL) cytology and immunoglobulin components of lavage fluid were studied during non-bacterial/non-fungal interstitial pneumonitis, bacterial/fungal pneumonia, and Pneumocystis carinii infection. Lavages done before bone marrow transplantation and in asymptomatic phases were used as controls. The total cell recovery was increased during lung processes of any aetiology. Non-bacterial/non-fungal pneumonitis caused a significant increase in the number of lymphocytes; the number of neutrophils increased particularly during bacterial pneumonia. In Pneumocystis carinii pneumonia the typical cell picture was an increased percentage of lymphocytes together with blasts. During acute graft-versus-host disease without respiratory symptoms the cytology in lavage fluids did not differ from the controls. Cytomegalovirus (CMV) isolation was frequently positive in lavage fluids regardless of the presence or absence of pulmonary symptoms, but most of the symptom-free CMV-positive patients did not have any marked changes in BAL cytology. The albumin content of BAL fluid increased during infectious and immunological processes in lungs.

A subset of systemic lupus erythematosus with progressive cystic bone lesions.

Clinical and serological findings of 16 patients with systemic lupus erythematosus (SLE) who had progressive cystic bone lesions were compared with a control group of 19 patients with SLE without radiological evidence of bone cysts. Central nervous system manifestations, synovitis, and other radiologically observed skeletal abnormalities were more prevalent in the patients with cysts than in the control group. Higher concentrations of C reactive protein, and a greater incidence of rheumatoid factor positivity were seen in the patients with cysts than in the control patients, but no other serological differences were found. It is suggested that patients with SLE with progressive cystic lesions form a subgroup of the syndrome characterised by an increased acute phase reaction.

Monitoring of bone marrow transplant recipient liver by fine-needle aspiration biopsy.

Acute graft-versus-host disease (aGVHD) of the liver was studied with fine-needle aspiration biopsies of thirty-four bone marrow transplant recipients. White cell differentials of liver FNABs and simultaneously taken blood samples were performed, and the increment and corrected increment methods were used to quantitate the inflammatory reaction in the liver. Biopsies taken before transplantation were used as the baseline. During aGVHD, the percentage of lymphoid cells and monocytes increased in the liver. The appearance of immunological blasts, together with a high proportion of activated lymphocytes in the FNABs, were typical findings during aGVHD. In patients with apparent prolonged liver graft-versus-host disease small lymphocytes were the predominating cell type. After initiating corticosteroid treatment, the number of blasts and the proportion of activated lymphocytes decreased. There was no significant difference in the proportions of CD4- and CD8-positive lymphoid cells in FNABs during or after aGVHD.

Immunoglobulin kappa and lambda light chain dual genotype rearrangement in a patient with kappa-secreting B-CLL.

The cytogenetics, immunophenotype and immunoglobulin gene rearrangements were analysed in a consecutive series of 56 patients with lymphoma or lymphatic leukaemia. One patient with B-CLL showed monoclonal rearrangements of the constant mu, kappa and lambda genes. The immunophenotype was kappa-secreting indicating expression of one immunoglobulin light kappa allele. Clones of kappa producing B-cells usually show germline lambda genes. The present case may thus be interpreted as a failure of the mechanisms controlling isotypic exclusion at the gene level. Further studies are needed to determine the frequency of such events and whether the patients show distinct clinical or other features.

Monocytic involvement by monosomy 7 preceded acute myelomonocytic leukemia in a patient with myelodysplastic syndrome.

Novel techniques were used to detect which cell lineages were affected by monosomy 7 in a patient who had myelodysplastic syndrome and later developed acute leukemia. The patient had had paroxysmal nocturnal hemoglobinuria for 20 years before developing refractory anemia with excess of blasts. Cytogenetic analysis at the myelodysplastic stage disclosed monosomy 7 in bone marrow mitoses. Restriction fragment length polymorphism analysis of fractionated white blood cells with the chromosome 7-specific probes MetH and MetD revealed that blood monocytes and most bone marrow erythroblasts but not blood granulocytes or lymphocytes were affected by monosomy 7. The patient later developed acute myelomonocytic leukemia with blast cells positive for markers of the myelomonocytic lineage but negative for granulocytic markers in a standard surface marker analysis. The leukemic blast cells had monosomy 7 as determined by direct cytogenetic investigation. Thus, the monocytes were found to be affected by monosomy 7 in this patient 8 months before her myelodysplastic syndrome progressed to acute myelomonocytic leukemia, and the affected cells had the same biologic markers at both stages of the disease.

Chromosome abnormalities in peripheral T-cell lymphoma.

We have studied neoplastic lymph nodes from six patients histologically, immunologically and cytogenetically. Histologically all the cases were classified as peripheral T-cell lymphomas. These were subclassified as T-zone lymphomas in three, large cell 'pale cell' variant in one, large cell immunoblastic in one, and small cell, mycosis fungoides in one. Two had features of angioimmunoblastic lymphadenopathy (AILD). Immunologically all cases expressed CD2 (OKT11) and CD4 (T4). All six cases had clonal chromosome abnormalities, although in four cases the majority of cells were chromosomally normal. Chromosome 3 was most often involved in abnormalities, occurring in five patients. The most common single chromosome abnormality, trisomy 3, was seen in all three cases classified as T-zone lymphoma and in no other cases. In the two cases with features of AILD only numerical abnormalities were seen, whereas in the other cases complicated structural rearrangements were present. Recurring structural abnormalities involved bands 1p12or13, 1q32, 3p25 and 14q11. Our data suggest that cytogenetic analysis may assist in diagnosis and classification of the peripheral T-cell lymphomas.

Trisomy 12 in B cells of patients with B-cell chronic lymphocytic leukemia.

Trisomy 12 is the most frequently reported chromosome abnormality in patients with B-cell chronic lymphocytic leukemia, but only normal karyotypes are found in one third of patients with that disorder. Moreover, samples from patients with trisomy 12 also have many normal metaphases. To identify immunologically the cells in which both the trisomy 12 and the normal karyotypes occur, we studied two patients with B-cell chronic lymphocytic leukemia--one whose neoplastic cells demonstrated lambda light-chain clonality and one whose cells had kappa light-chain clonality. We used a recently developed cytogenetic method that allows simultaneous analysis of cell morphology, immunologic phenotype, and karyotype in the same mitotic cell. In cultures of blood cells stimulated with pokeweed mitogen and tetradecanoylphorbol acetate, all the mitotic cells with either the lambda or the kappa immunoglobulin had trisomy 12, whereas all the cells that lacked these light chains or that had T-cell markers (OKT8 or OKT4) had normal karyotypes. These results show that trisomy 12 in B-cell chronic lymphocytic leukemia occurs in the neoplastic B cells, but not in the T cells, and they thus provide an explanation for the common finding of mitoses with normal karyotypes in patients with B-cell chronic lymphocytic leukemia.

Topographical distribution of inflammatory leukocyte subsets in acute cellular rejection of a kidney allograft.

The topographical distribution of different mononuclear inflammatory cell subsets in acute cellular rejection of human renal allograft was analyzed. Marker antibodies to T cells (OKT11), T helper cells (T4), T suppressor/killer cells (OKT8), B cells (B-1), monocytes (OKM1) and mononuclear phagocytes at different stages (FMC17, FMC33) and the indirect immunoperoxidase method were employed. At early stages of rejection, T lymphocytes were mostly confined to the perivascular areas and there was a T helper (Th) cell predominance over T suppressor/killer (Tsk) cells in the inflammatory infiltrate. Very few T cells and monocytes were found to infiltrate the arterial wall. Mononuclear phagocytes dominated over T lymphoid cells in the intertubular areas. Later during rejection, the Th/Tsk ratio became inverted, inflammatory T cells invaded also the intertubular areas, and infiltration of the arterial wall by T cells and mononuclear phagocytes became evident. Granulocytes were associated with the late events in the graft, and their appearance coincided with beginning necrosis. These non-random features in the distribution of the inflammatory cells were most pronounced during early stages of acute cellular rejection; later on, the differences seemed to disappear.

t(11;19)(q23;p11) in a child with acute T-cell leukemia.

A translocation, t(11;19)(q23;p11), is reported in a child with T-cell leukemia. Our case indicates that the t(11;19) may not be restricted to the monocytic leukemias, as earlier reported, but may occur in other malignancies.

Bone lesions in systemic lupus erythematosus.

Routine joint radiographs of 125 patients with systemic lupus erythematosus were studied. A total of 121 patients had a clinical history of articular symptoms. Cystic bone lesions were found in 51 patients (41%). The lesions, which were typically located subchondrally in the small joints of hands and feet, appeared as well-defined radiolucent areas surrounded by either normal bone or a narrow sclerotic zone. Nutritional disturbance in the bones, caused by the vasculitis associated with systemic lupus erythematosus, is proposed as a possible pathogenetic mechanism of the cystic lesions.

Immunological monitoring of bone marrow transplant recipients. I. Major leucocyte subclasses in the blood.

In the recipients of an allogeneic HLA-identical sibling transplant the blood leucocytes were reconstituted within 3 to 4 weeks but the level of lymphocytes remained low throughout the observation period of 20 weeks. Of the different lymphoid cell subsets, the large granular lymphocytes (LGL) reconstituted fastest, followed by DR-expressing lymphocytes. The reconstitution was accompanied by a significant lymphoid blastogenesis in the blood. The frequency of OKT4 and OKT8 lymphocytes was initially low; the number of OKT8-positive lymphocytes reached normal levels by the 6-8th week whereas the number of OKT4-positive lymphocytes and, consequently, the OKT4/8 ratio remained low. The responses to the T mitogens, phytohaemmagglutinin and concanavalin A, were strongly suppressed. Only a few significant changes were observed before and during acute graft-versus-host disease (aGVHD): the frequency of LGL, lymphoid blasts and OKT8-expressing lymphocytes was depressed before aGVHD and the frequency of lymphoid blasts remained depressed throughout the episode. We conclude that reproducible changes occur in the leucocyte subset frequencies during reconstitution, but the characteristic changes prior to and during aGVHD are not particularly prominent and hardly of diagnostic use.