Alvar Svanborg

Blood haemoglobin declines in the elderly: implications for reference intervals fromage 70 to 88

Abstract: 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.

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

Abstract: 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 < 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.

The ovarian hormone deficiency-induced hypercholesterolemia is reversed by soy protein and the synthetic isoflavone, ipriflavone

The purpose of this study was to compare the effects of soy protein isolate with normal isoflavone content (soy) and with reduced isoflavone content (soy-), ipriflavone (IP), a synthetic isoflavone; and 17β-estradiol (E2) on lipid metabolism in ovariectomized (ovx) rats. Seventy-two 95-day old Sprague-Dawley rats were assigned to six groups: sham operated (sham), ovx, ovx+soy, ovx+soy-, ovx+IP, and ovx+E2. Rats in the sham, ovx, ovx+IP, and ovx+E2 groups were fed a casein-based diet, whereas the soy and soy- groups were fed diets in which casein was replaced with soy or soy-. Animals were pair-fed to the mean food intake of ovx+E2 for 35 days. At the end of the study, animals were sacrificed in a nonfasted state and blood was collected via abdominal aorta. The ovx-induced increase in serum total cholesterol was reversed by all the treatments including ipriflavone and soy. Serum triglyceride levels were not significantly affected by any of the treatments. Liver cholesterol (μmol/g) in animals receiving IP or fed soy were significantly (p<0.01) lower than the ovx, ovx+soy-, and ovx+E2 groups. Liver lipids (mg/g) were significantly (p<0.05) lower in the animals that received E2 or fed soy, but not those which were fed soy- or given IP. The ovx-induced increase in abdominal fat was completely reversed by soy and E2 treatments but not by soy- or ipriflavone treatments. Soy, soy-, and IP had no uterotrophic activity as compared to E2. Ovariectomy significantly increased body weight gains which were not suppressed by any of the treatments except E2. These data indicate that ipriflavone is effective in preventing the unfavorable changes in serum and liver cholesterol associated with ovarian hormone deficiency in this animal model. Moreover, the consumption of synthetic or natural isoflavones may offer a potential alternative therapy in the treatment of hypercholesterolemia in ovarian hormone-deficient women.

Age-Related Changes in Cardiac Physiology Can They be Postponed or Treated by Drugs?

SummaryThe basic mechanisms that cause aging are still poorly understood. Longitudinal prospective population studies using noninvasive examination techniques have improved our ability to differentiate between aging and disease. This review describes some general morphological and functional aging-related changes of the heart that have clinical relevance, and considers the possibility of drug treatment for the manifestations of aging per se.Digitalis has not been shown to improve the aging-related decline in myocardial strength and contractility. During aging, heart tissue stiffens and the speed and extent of diastolic filling decline. The latter is a limiting functional factor, particularly during increases in heart rate. Lowering peripheral vascular resistance, which is often increased in older people, might indirectly improve heart function. However, no drug has been shown to improve myocardial strength or lower tissue stiffness via a direct effect on the heart. It has been claimed, however, that calcium antagonists might improve diastolic filling.Morphological changes during aging are dominated by some left ventricular wall and septal hypertrophy, and left atrial and ventricular widening. Recent findings have suggested that angiotensin II might act as a growth stimulating factor, promoting cardiac hypertrophy. This has led to speculation that ACE inhibitors might contribute to the restructuring of the heart, not only in hypertension but also in patients with the common combination of slightly elevated blood pressure and aging-related myocardial hypertrophy.At present, it appears that improving exogenous factors (e.g. lifestyle, living circumstances and access to adequate medical care) offers greater opportunities for postponing cardiac aging than drugs that directly interfere with the physiological aging of the heart.

High Anti-phosphorylcholine Antibody Levels and Mortality Associated with Pneumonia

Phosphorylcholine is an immunodominant determinant of pneumococcal teichoic acids. Antibodies to phosphorylcholine are naturally occurring in man and decline in amount with age. Since antibodies to phosphorylcholine are markers of the immune responsiveness to polysaccharides and since anti-polysaccharide antibodies are highly protective against most bacterial pneumonia we expected a higher rate of pneumonia in elderly individuals with low levels of antibodies to phosphorylcholine. The relationship between the levels of antibodies to phosphorylcholine and mortality was analyzed prospectively in a representative sample of elderly individuals. A significant anti-phosphorylcholine antibody response occurred in a subgroup of the probands. There was a strong association (p less than 0.0001) between high levels of antibodies to phosphorylcholine in the serum at 70 years of age and pneumonia related death up to 14 years later. A similarly strong association was not observed between mortality and the antibody titer to another naturally occurring polysaccharide antigen: the blood group B antigen. Furthermore, there was no association between mortality due to diseases other than pneumonia and the levels of antibodies to phosphorylcholine. The association between antibody levels and subsequent fatal pneumonia provides a means of detecting individuals at risk for pneumonia-related death.

Low Natural Killer Cell Function in Disseminated Aspergillosis

We investigated whether immune deficiency was associated with a fatal case of invasive cerebral aspergillosis due to Aspergillus fumigatus infection. The lymphocyte proliferative capacity to T- and B-cell mitogens was comparable to that of healthy controls. However, the natural killer (NK) cell activity of the patient was 2-6-fold lower than the activity expressed by a paired control and age-sex matched healthy controls (n = 20). No specific abnormalities were evident in the capacity to transduce either proliferative signals or cytokine (interleukin 2) secretory capacity of in vitro activated lymphocytes from the patient. The specific reduction in NK cell activity might either indicate that she was a low NK responder, or that the low NK cell activity was primarily or secondarily associated with the fungal infection caused by Aspergillus fumigatus in humans.

Salicylate Intoxication Presenting with “Pseudoexacerbation” of a Focal Neurologic Deficit

The patient had been discharged from the hospital 10 days before and had done well at home for about 1 week. She then began to complain of disturbed sleep. Her daughter discontinued her triazolam and held off on several doses of salsalate prescribed on the previous admission. The day before admission, the daughter noted increasing daytime agitation and that her mother was seeing and speaking to people who were not there. She had developed left-sided weakness and slurred speech. A chemstick blood sugar that morning was 17 mg/dL. Her daughter held her tolbutamide and administered orange juice with sugar. Later that day the patient vomited clear mucous. The daughter called and was instructed to bring her mother to the clinic. The patient’s recent medical history was remarkable for four admissions over the past 2 months for hypoglycemia due to an insulin overdose, falling, dehydration, hemorrhagic cystitis, shortness of breath, and atrial fibrillation. Her past medical history included a nephrectomy 27 years earlier for renal carcinoma, a femoral head prosthesis, bilateral cataract extraction, pernicious anemia, and a right-sided cerebrovascular accident in 1982 with left-sided weakness and slurred speech, both of which resolved without sequelae. The patient had adult-onset diabetes mellitus complicated by sensory neuropathy, retinopathy, and neurogenic bladder requiring intermittent catheterization. She suffered numerous urinary