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H Nilsson-Ehle

Publications and source records attributed to H Nilsson-Ehle.

At least 19 recordsLinked to original sources
PubMed2007

Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly.

OBJECTIVES: To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. DESIGN AND SETTING: Population-based study of 209 community-dwelling subjects, mean age 76 years. INTERVENTIONS: Four months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo. MAIN OUTCOME MEASURES: Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex. RESULTS: Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B(12)- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%). CONCLUSIONS: The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.

Aged↗
PubMed2003

Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial.

OBJECTIVES: To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B(12)/folate deficiency on the basis of different decision limits. DESIGN: Double-blind placebo-controlled intervention study. SETTING: Outpatient clinic. SUBJECTS: A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y. INTERVENTION: Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6). RESULTS: High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B(12) and age. CONCLUSIONS: Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.

Aged↗
PubMed2003

No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease.

In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels </=9.5 microkat/l, bone marrow cellularity </=70%, and WBC counts <4.0 x 10(9)/l, but S-LDH was the only variable independently associated with response by logistic regression analysis. Cox's regression analysis identified four significant prognostic factors for survival: bone marrow cellularity, S-LDH, cytogenetic risk group (International Prognostic Scoring System), and age. Only bone marrow cellularity (P=0.01) and S-LDH (P=0.0003) retained statistical significance in the log-rank test. Severe adverse events were significantly more common in the GM-TAD arm (P=0.01). Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects. We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.

Acute Disease↗
PubMed2002

Trofosfamide as salvage therapy for anaplastic large cell lymphoma relapsing after high-dose chemotherapy.

Patients with relapsed aggressive lymphoma after high dose chemotherapy have a very poor prognosis and long-term survival is rare. Most patients are not eligible for allogeneic stem cell transplantation in this setting and treatment, therefore, becomes palliative. A few studies have shown that trofosfamide, an oral alkylating agent, may be effective as palliative treatment in non-Hodgkin's lymphoma. Trofosfamide therapy is considered rather non-toxic with an overall response rate from 50 to 80%. Most responses are, however, partial and their duration is short. We report a patient with a very aggressive ALK + anaplastic large cell lymphoma (ALCL), relapsing shortly after high dose chemotherapy. Unrelated allogeneic transplantation was hot possible. After several radio/chemotherapy regimens trofosfamide was started as palliative treatment. This therapy resulted in a complete remission, still ongoing, 27 months after termination of intravenous cytotoxic therapy and 16 months after withdrawal of trofosfamide. Thus, in this particular case, trofosfamide turned out to be an unexpectedly effective salvage therapy for an otherwise very aggressive relapsing ALCL.

Adult↗
PubMed2000

Blood haemoglobin declines in the elderly: implications for reference intervals from age 70 to 88.

The objective was to determine whether Hb declines in healthy elderly men and women and if this influences health-related reference intervals. A representative population sample, comprising 30% of all 70-yr-old subjects in a Swedish city with 420,000 inhabitants (n = 1148, participation rate 85%), was followed at 1-5-yr intervals for 18 yr within a longitudinal population study. Age-related changes in Hb were calculated after exclusion of non-healthy probands and by multivariate analyses in the total study group. Mean Hb declined between age 70 and 88 from 149 to 138 g/L in men (annual decline 0.69 g/L, p = 0.000), and from 139 to 135 g/L in women (annual decline 0.06 g/L, n.s.). Healthy men declined from 152 to 141 g/L (annual decline 0.53 g/L, p = 0.038), for women from 140 to 138 g/L (annual decline 0.05 g/L, n.s.). Age and body mass index correlated, in multivariate analysis, independently to Hb in both men and women, as did variables indicating a non-healthy state. Epidemiological decision limits for anaemia declined for men from 128 to 116 g/L, for women from 118 to 114 g/L. Anaemia, thus defined, occurred in 3.2 to 9.7% of the subjects, whereas 28.3% of the 88-yr-old men had anaemia according to the WHO definition. In conclusion, there is a significant age-related decline in Hb from age 70 to 88 among healthy men, and a less pronounced decline among women. This justifies the use of lower epidemiological decision limits for anaemia of about 115 g/L for both men and women from age 80-82.

Age Factors↗
PubMed1998

Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients.

Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months. The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates.

Aged↗
PubMed1998

Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy.

Cobalamin (vitamin B12) deficiency is more common in the elderly than in younger patients. This is because of the increased prevalence of cobalamin malabsorption in this age group, which is mainly caused by (autoimmune) atrophic body gastritis. Cobalamin supplementation is affordable and nontoxic, and it may prevent irreversible neurological damage if started early. Elderly individuals with cobalamin deficiency may present with neuropsychiatric or metabolic deficiencies, without frank macrocytic anaemia. An investigation of symptoms and/or signs includes the diagnosis of deficiency as well as any underlying cause. Deficiency states can still exist even when serum cobalamin levels are higher than the traditional lower reference limit. Cobalamin-responsive elevations of serum methylmalonic acid (MMA) and homocysteine are helpful laboratory tools for the diagnosis. The health-related reference ranges for homocysteine and MMA appear to vary with age and gender. Atrophic body gastritis is indirectly diagnosed by measuring serum levels of gastrin and pepsinogens, and it may cause dietary cobalamin malabsorption despite a normal traditional Schilling's test. The use of gastroscopy may also be considered to diagnose dysplasia, bacterial overgrowth and intestinal villous atrophy in healthy patients with atrophic body gastritis or concomitant iron or folic acid deficiency. Elderly patients respond to cobalamin treatment as fully as younger patients, with complete haematological recovery and complete or good partial resolution of neurological deficits. Chronic dementia responds poorly but should, nevertheless, be treated if there is a metabolic deficiency (as indicated by elevated homocysteine and/or MMA levels). Patients who are at risk from cobalamin deficiency include those with a gastrointestinal predisposition (e.g. atrophic body gastritis or previous partial gastrectomy), autoimmune disorders [type 1 (insulin-dependent) diabetes mellitus and thyroid disorders], those receiving long term therapy with gastric acid inhibitors or biguanides, and those undergoing nitrous oxide anaesthesia. To date, inadequate cobalamin intake has not proven to be a major risk factor. Intervention trials of cobalamin, folic acid and pyridoxine (vitamin B6) in unselected elderly populations are currently under way.

Aged↗
PubMed1995

Bone marrow progenitor cell growth and karyotype changes in healthy 88-year-old subjects.

Previous studies have indicated a decline in bone marrow progenitor cell function in subjects aged 75-82 years, possibly causing lower Hb concentrations. We studied the bone marrow with in vitro colony assays and cytogenetic analysis in 24 apparently healthy 88-year-olds with Hb concentrations ranging from moderate anaemia to normal levels. Twenty-two healthy younger subjects, aged 21-57 years, were used as a control group. The 88-year-olds showed significantly lower numbers of myeloid bone marrow progenitors than the controls, and the elderly men had lower numbers of both erythroid and myeloid progenitors than the elderly women. There were no in vitro growth differences between elderly subjects with "low" or "normal" Hb concentrations. Ten out of 14 men had bone marrow cells with a missing Y-chromosome, which did not seem to have any relationship to the erythroid function. No morphological or other cytogenetic indications of a clonal progenitor cell disorder were found. A more rapid decline in Hb concentrations in healthy elderly men as compared to elderly women might be explained by differences in bone marrow progenitor cell function. However, progenitor cell abnormalities do not seem to explain differences in Hb concentrations within groups of apparently healthy men and women of advanced age.

Adult↗
PubMed1991

Serum cobalamins in the elderly: a longitudinal study of a representative population sample from age 70 to 81.

In a representative population sample (n = 973) born 1901-1902 and examined at the ages of 70, 75, 79, and 81, the change in serum cobalamins with increasing age was studied by trend analysis using values obtained in single individuals at all four examinations. In subsamples without definable disorders, the mean annual decline was: among men 3.4 pmol/l (p less than 0.05), among women 3.2 pmol/l (n.s.). The decline was possibly more pronounced among individuals with low and intermediate concentrations. The health-related lower reference limits (the 2.5 percentile values of subsamples without definable disorders) did not differ significantly between sexes and age groups, but low concentrations or ongoing cobalamin medication became more common with advancing age. The results indicate a slight fall in serum cobalamins between age 70 and 81 but do not call for age-related lower reference limits.

Aged↗
PubMed1990

Iron deficiency.

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Anemia, Hypochromic↗
PubMed1989

Low serum cobalamin levels in a population study of 70- and 75-year-old subjects. Gastrointestinal causes and hematological effects.

We examined causes and hematological consequences of low serum cobalamin (vitamin B12) concentration in two representative population samples of 70-year-old (N = 293) and 75-year-old subjects (N = 486). Subjects with values below 130 pmol/liter (4.8% and 5.6%, respectively) were investigated with Schilling test, upper gastrointestinal endoscopy, determination of serum gastrin and group I pepsinogens, and bone marrow examination. Gastrointestinal abnormalities of etiologic significance were found in 26 of the 32 examined subjects: atrophy of the gastric body mucosa (N = 16, with pernicious anemia in six), partial gastrectomy (N = 6), and intestinal malabsorption (N = 4). Megaloblastic hematopoiesis was found in 10 individuals, four of whom had macrocytic anemia. Our results indicate that low serum cobalamin concentration in the elderly is usually a consequence of disease rather than of high age per se and that gastric mucosal atrophy is a major etiologic factor.

Aged↗
PubMed1989

Decline of blood haemoglobin in the aged: a longitudinal study of an urban Swedish population from age 70 to 81.

Blood haemoglobin (Hb) and related components were determined in a representative sample (n = 973, 449 men and 524 women) of a 70-year-old population, reinvestigated at age 75, 79 and 81. At age 81, 145 men and 259 women remained in the study. Longitudinal analysis demonstrated a significant decline in Hb concentration with advancing age, in the total study groups as well as in subsamples remaining after exclusions due to disease. The mean annual decline from age 70 to 81 in a subsample without definable disorders was in men 0.063 g/dl, in women 0.035 g/dl. There was a similar decline among subjects with high, intermediate or low Hb concentrations during the study. Only part of the observed intraindividual variations could be explained by factors other than age.

Aged↗
PubMed1988

Haematological abnormalities in a 75-year-old population. Consequences for health-related reference intervals.

A representative sample (n = 486) of a 75-year-old population was studied, and probands with defined laboratory aberrations were re-investigated. Anaemia was present in 6% of the men and 3% of the women; in 17/22 anaemic subjects a cause was found. The prevalence of plasma cobalamin concentrations less than 130 pmol/l was 6%, of iron deficiency approximately 6%. Divergences in white blood cell and platelet counts were rare. The observed haematological aberrations were almost always caused by disease. Reference intervals for haematological components were calculated in the total study group and two reference sample groups after exclusions based on anamnestic and/or laboratory screening criteria or anamnestic criteria and/or verified disease. The lower reference limits for B-Hb and P-B12 in a group obtained after exclusions based on anamnestic and screening data were considered to be minimum values for healthy subjects. The WHO criteria for anaemia were applicable.

Aged↗
PubMed1988

Haematological abnormalities and reference intervals in the elderly. A cross-sectional comparative study of three urban Swedish population samples aged 70, 75 and 81 years.

We compared three representative population samples aged 70 (n = 312), 75 (n = 486) and 81 (n = 404) years. Anaemia defined either as blood haemoglobin concentration below the corresponding health-related lower reference limits or according to WHO was, in the total study groups, more common at age 81. Anaemia of unknown cause was rare, but somewhat more common at age 81. Mean blood haemoglobin concentrations in subsamples without definable disorders were significantly lower at age 81 than at ages 70 and 75, whereas the lower health-related reference limits did not differ significantly. White blood cell counts tended to be lower and iron deficiency was somewhat more common at age 81. No significant differences were found in platelet counts or in the prevalence of low plasma cobalamin concentrations. These results indicate a fall in blood haemoglobin with advancing age. The arbitrary WHO criteria for anaemia are clinically applicable at age 70-81.

Age Factors↗