A longitudinal study of the effects of tobacco smoking and other modifiable risk factors on ill health in middle-aged and old Americans: results from the Health and Retirement Study and Asset and Health Dynamics among the Oldest Old survey

BACKGROUND: While the effects of smoking and other modifiable risk factors on mortality and specific diseases are well established, their effects on ill health more generally are less known. Using two national, longitudinal surveys, the objective of this study was to analyze the effect of smoking and other modifiable risk factors on ill health, defined in a multidimensional fashion (i.e., disability, impaired mobility, health care utilization, and self-reported health). METHODS: The analyses were based on the Health and Retirement Study (HRS) (12,652 persons 50-60 years old surveyed in 1992, 1994, 1996, and 1998) and the Asset and Health Dynamics among the Oldest Old survey (8,124 persons 60-70 years old surveyed in 1993, 1996, and 1998). RESULTS: Smoking was strongly related to mortality and to ill health, with similar relative effects in the middle-aged and the elderly. There were consistent adverse dose-response relationships between smoking and ill health in the HRS. Persons who had quit smoking at least 15 years prior to the survey were no more likely than never smokers to experience ill health. A dose-response relationship was found between exercise and ill health. For body mass index and alcohol, there were U-shaped relationships with ill health. CONCLUSIONS: Public health efforts designed to encourage smoking cessation should emphasize improvements in ill health in addition to decreased mortality.     

Ascorbic acid enhances hydroxyl radical formation in iron-fortified infant cereals and infant formulas

Infant cereals and formulas are usually fortified with iron to prevent iron deficiency. To enhance iron bioavailability, supplemental ascorbic acid is recommended. Ascorbic acid is considered to be an antioxidant in vivo, but has pro-oxidant effects when exposed to non-protein-bound iron. We measured formation of free radicals in cereals and infant formulas after addition of ascorbic acid. The production of hydroxyl radicals was assessed by hydroxylation of salicylic acid to 2,5-dihydroxybenzoic acid (2,5-DHBA). Production of 2,5-DHBA increased with increasing ascorbic acid doses added. Addition of 0.8 mM ascorbic acid to breast milk produced less radicals (0.03 ± 0.05 μM) than addition of ascorbic acid to low-iron formula (0.13 ± 0.08 μM, P = 0.019), medium-iron formula (0.34 ± 0.12 μM, P < 0.0001) or high-iron formula (0.44 ± 0.08 μM, P < 0.0001). Even when iron content in breast milk was adjusted to a level comparable with that of formulas, production of 2,5-DHBA was lower. Breast milk seems to contain substances that reduce hydroxyl radical formation. Conclusion Supplemental ascorbic acid causes hydro-xyl radical formation in iron-fortified infant nutrients in vitro. Received: 30 March 1996 / Accepted in revised form: 10 December 1996     

Alpha-1-antitrypsin levels and clinical symptoms in forty-eight children with selective IgA deficiency

Previous studies in adult patients with selective IgA deficiency have pointed towards a possible connection between chombined IgA and alpha-1-antitrypsin deficiency and the development of bronchiectasis. Thus, investigation were conducted of serum alpha-1-antitrypsin levels and clinical symptoms in 48 children with selective IgA deficiency. However, alpha-1-antitrypsin deficiency was not found in this group of patients. Furthermore, radiographic signs of recurrent pneumonia restricted to certain fields of the lungs, suggestive of bronchiectasia, were not observed in the patients. Thus, although a highly selected group of children with selective IgA deficiency was studied, a connection between IgA deficiency and alpha-1-antitrypsin deficiency as not obvious.Abbreviations RAST radio-allergo-sorbent-test - AAT alpha-1-antitrypsin     

Physiologically based pharmacokinetic model for pralmorelin hydrochloride in rats.

Pralmorelin hydrochloride (pralmorelin), consisting of six amino acid residues, is a growth hormone-releasing peptide. The aim of this study is to analyze the pharmacokinetics of pralmorelin after intravenous bolus administration to rats, and to develop a physiologically based pharmacokinetic (PB-PK) model to describe and predict the concentrations of pralmorelin in blood and tissues. Pralmorelin (3 mg/kg) was administered intravenously to 24 Sprague-Dawley rats. Groups of three rats were sacrificed by decapitation at each designated time point (up to 4 h), and plasma and tissues (brain, lung, heart, liver, kidney, small intestine, muscle, adipose, and skin) were collected. Bile was also pooled until decapitation. The concentration of pralmorelin in samples was determined by liquid chromatography-tandem mass spectrometry. Plasma concentrations of pralmorelin declined rapidly in a biexponential manner. Biliary excretion of pralmorelin was so rapid that 80% of the dose was recovered unchanged in the bile within 1 h after administration. The distribution parameters in each tissue were obtained by using a hybrid model and an integration plot. They revealed that the distribution of pralmorelin into liver was blood flow-limited, and its distribution was permeability-limited in all other tissues. The PB-PK model developed in this study well described the time courses of pralmorelin concentration in the blood and tissues of rats.     

Long-term trial of 1-alpha-hydroxycholecalciferol in adults with chronic renal failure

Summary Twentytwo adult patients with chronic renal insufficiency received long-term treatment (mean 15.4 months) with 1-alpha-hydroxycholecalciferol (1(OH)D₃), a synthetic vitamin D analogue. Before treatment 73% of the patients were hypocalcemic, intestinal calcium absorption was reduced in 82%, serum immunoreactive parathyroid hormone (i-PTH) was increased in 86% and serum alkaline phosphatases were increased in 50% of them. Furthermore, 91% of the patients had generalized scintigraphic bone changes indicative of renal osteodystrophy, 59% had reduced bone mineral content (BMC), 32% had radiographic bone changes and 27% had clinical symptoms. During treatment all patients became normocalcemic within one month; intestinal calcium absorption increased to reach normal values; i-PTH declined significantly, but remained elevated in 50% of patients; serum alkaline phosphatases declined significantly and became normal in all except 2 patients; bone scintigraphy and/or radiography showed considerable improvement in 4 patients; the accelerated bone loss in uremia ceased and bone pain disappeared in 5 of the 6 patients who had had this symptom. Nineteen short-lasting acute hypercalcemic episodes were recorded during treatment. In all cases normocalcemia was re-established within 72 hours after discontinuing the drug. No side-effects were observed apart from hypercalcemia. The present data demonstrate the long-term beneficial effects of 1 (OH)D₃ in improving clinical symptoms and reversing several biochemical and skeletal abnormalities in patients with chronic renal failure.     

Endocarditis due toKingella kingae

Four cases of endocarditis due toKingella kingae are described in compromised patients. All had primary heart disease, and two had systemic lupus erythematosis and congenital heart defect respectively, in addition. Confirmation ofKingella kingae was made in one case at autopsy. The literature on 11 cases of endocarditis, 2 bacteremia, 4 osteomyelitis, 5 septic arthritis and 1 intervertebral disc infection, all caused byKingella kingae, is reviewed. Our findings confirm that the organism is of low pathogenicity. Children may be predisposed to infection withKingella kingae.     

Fluid balance in exercise dehydration and rehydration with different glucose-electrolyte drinks

Summary After exercise dehydration (3% of body weight) the restoration of water and electrolyte balance was followed in 6 male subjects. During a 2 h rest period after exercise, a drink of one of four solutions was given as 9×300 ml portions at 15 min intervals: control (C-drink), high potassium (K-drink), high sodium (Na-drink) or high sugar (S-drink). An exercise test (submaximal and supramaximal work) was performed before dehydration and after rehydration. Dehydration reduced plasma volume by 16%, a process reversed on resting even before fluid ingestion began, due to release of water accumulated in the muscles during exercise. After 2 h rehydration, plasma volume was above the initial resting value with all 4 drinks. The final plasma volumes after the Na-drink (+14%) and C-drink (+9%) were significantly higher than after the K- and S-drinks. The Na-drink favoured filling of the extracellular compartment, whereas the K- and S-drinks favoured intracellular rehydration. In spite of the higher than normal plasma volume after rehydration, mean heart rate during the submaximal test was 10 bpm higher after rest and rehydration than in the initial test, and was not different between the drinks. The amount of work which could be performed in the supramaximal test (105% ) was 20% less after exercise dehydration and subsequent rest and rehydration than before. This reduction was similar for all drinks, and may be due to a decreased muscle glycogen content (70% of initial) at the time of the second test. Danish National Institute of Occupational Health     

The application of various electron microscopic techniques for ultrastructural characterization of the human papillary heart muscle cell in biopsy material

Summary Various electron microscopical techniques have been applied to biopsy material obtained from patients suffering from mitral stenosis in order to characterize the subcellular organization of the hypertrophied papillary muscle. Small pieces of the same sample were processed for correlative transmission - (TEM) and scanning -(SEM) electron microscopical studies. TEM was carried out on conventionally fixed tissue with or withouten bloc staining with a Cu-Pb citrate solution, and on freeze fracture replicas, while cryofractured material was studied by SEM. Stereo electron micrographs of the Cu-Pb impregnated tissue and of the cryofractured material were especially useful for studying the spatial distribution and relationship between various cell organelles.The myofilaments of the hypertrophied cells were arranged in a normal hexagonal pattern. Regions with irregular orientation of the myofibrils were occasionally seen. Accumulations of interfilamentous glycogen particles adjacent to the Z-bands were characteristic patterns of the contracted muscle cells. The extensive nexuses frequently observed in the subsarcolemmal regions may reflect functional alterations of the intercommunication between hypertrophied cells. The T-tubules were relatively few and irregularly distributed, and the complexity of the sarcotubular system (SR) revealed regional variations. Excellent visualization of the interior couplings between the SR and the T-tubules was achieved by studying thick sections of Cu-Pb impregnated tissue in the TEM.The dense staining of the various intracellular membranes when compared with the almost unstained external membranes including the free cell surface, intercalated disc and T-system, strongly indicates differences in chemical and functional properties of the two membrane systems.En bloc staining resulted also in contrasted glycogen as well as components of the nucleolus and the heterochromatin. The biochemical basis for the selective staining remains obscure; it may be a result of binding of heavy metal ions to carboxyl groups of specific proteins, and/or it may represent deposits of lead phosphate.