Homocysteine measurements in geriatric patients.

OBJECTIVE: Homocysteine measurements may be relevant in geriatric medicine as homocysteine has been identified as an independent risk factor for prevalent disorders such as occlusive arterial vascular disease, cognitive impairment and dementia. The aim of the present study was to study diagnostic correlates of plasma total homocysteine (tHcy) in geriatric in-patients. MATERIAL AND METHODS: Blood samples for the analysis of tHcy and related factors like serum vitamin B12, serum folate, red blood cell folate and clinical data were collected from geriatric patients (n=114) in stable clinical condition. RESULTS: Almost 40% of the patients had tHcy values above 20 micromol/L. tHcy correlated significantly with serum folate, serum vitamin B12, serum creatinine and congestive heart failure, but not with red blood cell folate, cerebrovascular disease, coronary heart disease or cognitive impairment. CONCLUSIONS: Hyperhomocysteinaemia seems to be frequent in geriatric patients and might primarily be an indicator of low folate and high creatinine values.

Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study.

OBJECTIVE: Elevated levels of plasma total homocysteine (tHcy) are identified as independent risk factors for coronary heart disease and for fetal neural tube defects. tHcy levels are negatively associated with folic acid, pyridoxine and cobalamine, and positively associated with coffee consumption and smoking. A total of 600 ml of filtered coffee results in a tHcy increase that 200 mug of folic acid or 40 mg of pyridoxine supplementation might eliminate. DESIGN: Randomised, blinded study with two consecutive trial periods. SETTING: Free living population. Volunteers. SUBJECTS: A total of 121 healthy, nonsmoking men and women (78%) aged 29-65 y. INTERVENTIONS: (1) A coffee-free period of 3 weeks, (2) 600 ml coffee/day and a supplement of 200 mug folic acid/day or placebo for 4 weeks, (3) 3-week coffee-free period, (4) 600 ml coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks. MAIN OUTCOME MEASURES: The difference between the change in tHcy in the supplement group and the change in tHcy in the placebo group during the 4-week trial period. RESULTS: Coffee abstention resulted in a tHcy decrease of 1.04 mumol/l for the whole group. In the subsequent coffee period, a further decrease of 0.17 mumol/l was observed in the folic acid group whereas an increase of 1.26 mumol/l was observed in the placebo group, the difference was 1.43 mumol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no impact on tHcy levels. CONCLUSIONS: Supplementation of 200 mug folic acid/day eliminates the tHcy increasing effect of 600 ml filtered coffee in subjects not already on folic acid supplements. A supplement of 40 mg pyridoxine/day does not have the same effect.

Abstention from filtered coffee reduces the concentrations of plasma homocysteine and serum cholesterol--a randomized controlled trial.

BACKGROUND: Elevated concentrations of plasma total homocysteine (tHcy) and serum total cholesterol are risk factors for ischemic heart disease (IHD). Previous studies showed that the consumption of very high doses of unfiltered coffee increases tHcy and total cholesterol. OBJECTIVE: A prospective intervention study was performed to assess the effects of coffee consumption on the concentrations of tHcy and total cholesterol by using doses and brewing methods common in southeastern Norway. DESIGN: The study was an unblinded, controlled trial with 191 healthy, nonsmoking, coffee-drinking volunteers aged 24-69 y randomly assigned to 3 groups who were asked to consume for 6 consecutive weeks no coffee, 1-3 cups (approximately 175-525 mL)/d, or > or =4 cups (approximately 700 mL)/d prepared in the manner to which they were accustomed. Blood samples were drawn when the subjects were randomly assigned and at 3 and 6 wk of the trial. Dietary data were collected by questionnaire. RESULTS: Ninety-seven percent of the participants reported being regular consumers of caffeinated filtered coffee. Abstention from coffee for 6 wk was associated with a decrease in the tHcy concentration of 1.08 micromol/L and a decrease in the total cholesterol concentration of 0.28 mmol/L in participants who had been drinking on average 4 cups of filtered coffee daily for the past year. Adjustments for several possible confounders did not alter the results. CONCLUSION: Abstention from filtered coffee in doses that are commonly consumed was associated with lower concentrations of tHcy and total cholesterol.

Serum creatine kinase isoenzyme BB in mammalian osteopetrosis.

In mammalian osteopetrosis the different mutations exemplify reduced bone resorption leading to net accumulation of bone. Recently, high blood levels of creatine kinase-BB have been reported in some human forms, suggesting it as a marker of osteopetrosis. In the current study serum creatine kinase-BB was evaluated in relation to known osteoclastic pathophysiology in two human types of autosomal dominant osteopetrosis at baseline and after stimulation with triiodothyronine and in four different rodent mutations. Creatine kinase-BB was increased markedly in Type 2 autosomal dominant osteopetrosis and in the incisors absent rat, both characterized by large numbers of giant osteoclasts, and did not change significantly after stimulation. Although creatine kinase-BB was unchanged in Type 1 autosomal dominant osteopetrosis at baseline and after stimulation, the rodent counterparts characterized by small osteoclasts, microphthalmic and osteopetrotic mice and toothless rats, had significantly decreased levels. Similar differences were observed in both types of autosomal dominant osteopetrosis compared with controls concerning tartrate resistant acid phosphatase. Creatine kinase-BB in mammalian osteopetrosis is related to osteoclastic number and size, where it probably reflects the differentiation and maturation of inactive bone resorbing cells. The isoenzyme does not seem to be a valuable screening marker for osteopetrosis.

Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction.

High level of total homocysteine (tHcy) is a risk factor for coronary artery disease (CAD), but the mechanism is not known. The serum concentration of tHcy, total cholesterol, high density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (apo A-I) and the concentration of folate in whole blood were measured in 107 patients with first acute myocardial infarction (MI) and 103 controls. The level of whole blood folate was lower and that of tHcy higher in cases than in controls. An increase of 50 nmol/l whole blood folate was associated with an OR for MI of 0.75, and an increase of 5 micromol/l tHcy with an OR for MI of 1.57. Correlations were observed between the levels of whole blood folate and tHcy and between whole blood folate and alcohol intake, and in MI cases, between tHcy, HDL-C, and apo A-I as well as between HDL-C and alcohol intake. The number of cigarette smokers was higher among cases than controls. In smokers, the level of tHcy was higher and that of whole blood folate lower than in non-smokers. After adjustment for smoking, the whole blood folate and tHcy-associated risks of MI became non-significant. We conclude that smoking may affect folate status and tHcy level adversely. The risk of MI in smokers may at least partly be attributed to hyperhomocysteinemia or low folate.

[Laboratory operations in general practice--where do we stand, concerning quality assurance projects?]. / Laboratorievirksomheten i legepraksis--hvor står kvalitetssikringsprosjektet?

In 1992 a project was started by the Norwegian Medical Association to secure the quality of laboratory work performed on physicians' own premises in Norway. The project is now well established in all 19 counties and more than 90% of the practices participate on a voluntary basis. In each county a central clinical chemistry laboratory with a specially engaged laboratory adviser is responsible for assisting the general practitioners and specialists with the laboratory work performed on their own premises. The assistance includes visits, telephone contacts and education courses. An external quality control scheme is carried out by a national centre, which distributes samples of unknown concentrations to all the participants. The whole project is coordinated by a steering committee, which arranges national meetings annually. Working groups have been appointed to elucidate more complicated and time-consuming subjects, such as guidelines for internal quality control, evaluation of equipment and education programmes. A set of written manuals for all kinds of working procedures has recently been prepared and adjusted individually to each physician's premises.

[Use of laboratory examinations in the organized occupational health services]. / Bruken av laboratorieundersøkelser i den organiserte bedriftshelsetjeneste.

The extent of laboratory examinations in the health programmes of Norwegian companies was studied by questionnaire. From the reports (60% response) it can be calculated that less than 14% of the tests were requested to control employees at elevated occupational risk. Two thirds of the tests were carried out as part of programmes for screening of presumptive healthy individuals at no special risk. There were large variations in this service from company to company. About 75% of the analyses were performed at the occupational health service premises, usually by nurses without laboratory education. It is concluded that the use of laboratory examinations in occupational medicine should be critically evaluated.

The influence of fast and vegetarian diet on parameters of nutritional status in patients with rheumatoid arthritis.

Nutritional status was studied over a period of 13 months in 34 patients with rheumatoid arthritis (RA). Seventeen patients fasted for 7-10 days, were then transferred to a gluten-free vegan diet for 3.5 months and finally to a lactovegetarian diet for 9 months. The remaining 17 patients followed a "normal" diet. After one month, the values for body mass index (BMI) and triceps skinfold thickness (TSF) were significantly reduced in the diet group compared with the values at inclusion (p < 0.001), whereas upper arm muscle area (UAMA) was not significantly reduced. Evaluation of the whole study course revealed a significantly lower BMI (p = 0.04) and TSF (p < 0.01) in the diet group compared with the control group. The concentration of insulin-like growth factor 1 (IGF1) was significantly reduced in the diet group after one month compared with the value at inclusion (p = 0.01), but the overall difference between the two groups was not significant. There were no overall significant differences with regard to VAMA, concentration of serum albumin, haemoglobin, ferritin, zinc and copper between the two groups. Thus fast, followed by diet manipulations for one year, had a minor impact on nutritional status in patients with RA.

Cardiovascular risk factors: interactive effects of lipids, coagulation and fibrinolysis.

In western societies cardiovascular disease accounts for approximately one of every three deaths, and is a major contributor to chronic debiliation. During the last years our knowledge of factors that contribute to the development and progression of this disease has increased markedly. Elevated serum total cholesterol, hypertension and cigarette smoking are "traditional", well-known risk factors. In addition, low serum levels of high density lipoprotein (HDL) cholesterol predispose to development of disease, whereas in epidemiological studies the role of increased triglycerides is more controversial. During the last years derangements in several haemostatic components in persons who develop cardiovascular disease have been observed. Such alterations include increased plasma concentrations of fibrinogen, Factor VII coagulant activity and plasminogen activator inhibitor-1 (PAI-1). Furthermore, interactions between lipoproteins and haemostatic factors are gradually being disclosed. Serum triglycerides have been shown to correlate both to PAI-1 and to Factor VII. The lipoprotein (a), first described by Berg in 1963, also appears to be a link between lipoprotein metabolism and fibrinolytic function. In addition, linkages are observed between high triglycerides, low HDL cholesterol, reduced glucose tolerance, hyperinsulinemia, obesity, low physical activity, reduced fibrinolytic capacity and increased Factor VII. This clustering of risk factors has been suggested to be a coronary risk syndrome and has been called Reavens syndrome, syndrome X and insulin-resistance syndrome. A more descriptive name, athero-thrombogenic syndrome (ATS), has recently been suggested, thereby indicating that both atherosclerosis and thrombosis contribute to its development.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid immunometric measurement of C-reactive protein in whole blood.

We examined an instrument-free test for C-reactive protein (CRP) in whole blood. The NycoCard CRP Whole Blood test uses a cell-solubilizing dilution liquid, a membrane-bound antibody that binds CRP, and a gold-conjugated antibody for making visible the bound CRP. We obtained essentially identical dose-response curves in citrate-, heparin-, and EDTA-treated blood. CVs were 6.7-12.5% within series and 10.1-14.7% between series. The detection limit was 12 mg/L. Intralipid added to blood increased measured CRP by 10-20%, whereas no change was seen with added bilirubin, added serum amyloid P component, or the presence of rheumatoid factor. In 234 patients' blood samples the results of the NycoCard Whole Blood test correlated well (r = 0.96) with those of a turbidimetric serum method. The test allows reliable measurement of CRP from a small volume of whole blood (25 microL) without using expensive equipment; it should be useful for decentralized testing in hospital departments, emergency units, and primary health care centers.

[Which laboratory tests should be performed by general practitioners--and how to assure good analytical quality?]. / Hvilke laboratorieprøver bør allmennpraktikerne utføore--og hvordan sikre god analysekvalitet?

Near patient testing is increasing both in Norway and abroad. Having test results ready when the patient is present is beneficial in a number of clinical situations, as well as being efficient for both doctor and patient. However, the analytical quality in general practice has proved unstable and in many instances poor. Public expenditures to reimburse near patient tests are soaring. Therefore, high priority must be given to ensuring that the practitioner's laboratory is sound, both professionally and economically. The following items are considered important: All analytical work should be subjected to regular quality assessment. We list a number of constituents that are suitable for near patient analysis. The constituents are divided in two groups: those that all practices should be capable of analyzing, and constituents which should be analyzed in practices with doctors with a special interest in this field. We also suggest changes in the Norwegian public system of reimbursement for near patient testing.

[Abbot Vision. An interesting laboratory instrument for small hospitals]. / Abbott Vision. Et interessant laboratorieinstrument for mindre sykehus.

Abbott Vision is a technologically advanced chemistry analyzer developed for decentralized testing. About 30 different tests can be performed using disposable test packs containing wet reagents. The instrument was evaluated in a smaller hospital and (except for potassium) good results were obtained with respect to precision and conformity with results from a referral laboratory. The analyzer is considered to be of special advantage in cases of emergency and when there is no laboratory technician on duty. The cost per analysis is much higher, however, than with conventional techniques.

C-reactive protein: a new rapid assay for managing infectious disease in primary health care.

Quantitative C-reactive protein (CRP) measurement has become increasingly valuable as a test for rapid diagnosis of infections in hospital medicine. CRP has not obtained the same importance in primary health care. This has, at least partly, been due to methodological difficulties, with no simple or rapid tests with quantitative results available. A new immunometric semi-quantitative assay, NycoCard CRP, has recently been developed. CRP was analysed at the local health centres by the new assay in 288 consultations where patients came because of infections. Parallel CRP values were obtained by an established reference method. The two procedures had an acceptable correlation (r = 0.85). The primary care doctors also registered the clinical information they obtained from each CRP result. CRP was helpful in indicating the presence, or absence of bacterial infection in more than half the consultations due to new infections. CRP was thought to yield more clinical information than the erythrocyte sedimentation rate in almost every case.

A new case with hereditary xanthinuria: response to exercise.

The concentration of purines in plasma and urine from a 37-yr-old healthy man with a very low plasma urate concentration was measured by HPLC. A persistent increase in xanthine and a slight elevation of hypoxanthine was found. The metabolic response to intensive treadmill running and long distance running was investigated. The hypoxanthine concentration increased to about the same level as in healthy controls, but the elimination from plasma was considerably slower. The high xanthine level was practically unchanged by exercise.

Biochemical changes and endocrine responses in cystic fibrosis in relation to incremental maximal exhaustive exercise.

The purpose of this study was to compare biochemical changes and endocrine responses during an incremental maximal bicycle test in three well-trained 18-year-old patients with cystic fibrosis (CF) and in three healthy controls. Although the blood concentration at rest of the white cell count, haptoglobin, phosphorus, urea, creatinine, and uric acid were somewhat different in the two groups, the CF patients had similar biochemical changes in response to the exercise compared with the healthy men. The endocrine responses to exercise seemed to be different between the two groups with regard to changes in cortisol, growth hormone, and testosterone concentrations. The differences, however, were probably caused by differences in age, training situation, and psychological stress reaction rather than by pathological mechanisms.

Biochemical changes and endocrine responses in cystic fibrosis in relation to a marathon race.

Biochemical changes and endocrine responses during the New York Marathon (42195 m) were investigated in three 18-year-old male adolescents with cystic fibrosis (CF) and three healthy men who accompanied the CFs during the race. The ambient temperature was 20 degrees-28 degrees C and the relative humidity 98%-75% during the run. The CF patients, who had Shwachman scores of 60, 85 and 95 completed the run without major problems in 6.10, 4.42, and 4.32 h, respectively. Serum concentrations of Na and Cl decreased slightly, but the values were still within normal range. Na and Cl excretions in the urine decreased to very low levels in the CF adolescents during the run. All the other biochemical changes were similar to the changes in the controls. Aldosterone concentration increased to a higher level and maintained this increase for a longer time after the race in the CFs. Testosterone concentration decreased more in the CFs during the race compared with the controls. Growth hormone concentration showed individually varying changes in response to the exercise. This study demonstrates that patients with CF may participate in strenuous prolonged exercise even in humid and hot conditions, without untoward effects. The observed differences in hormonal responses to exercise might be explained by differences in age, training status, and relative exercise intensity rather than by hormonal or other disturbances in CF.

Vigorous exercise in a female with cystic fibrosis: spirometric, biochemical, and endocrine responses during four types of intensive exercise.

Spirometric, biochemical, and endocrine responses during a maximal ergometer cycle test and during three runs (10 km, 21.1 km, and 42.2 km) were investigated in one female with cystic fibrosis (CF) 27 years of age and in two healthy control females 26 and 29 years of age. One of the controls ran as a companion to the CF woman, while the other ran at her own speed. The CF woman has a chronic respiratory Pseudomonas aeruginosa infection, and her spirometric values were 50%-70% of predicted values at the time of the study. For the last years she has been training almost daily with aerobics, running, cycling, or skiing. She completed the four types of exercise without major problems. Her spirometric values increased transiently following the cycle test and for several hours following the three races (maximal 20%-30% increase of spirometric values), while the controls had transient decreases of the same variables in response to the runs. The biochemical and the hormonal changes were similar in the CF woman and the control who ran at her own speed, while the control who was a less stressed companion showed smaller changes. This study demonstrates that well-trained females with CF may participate in strenuous prolonged exercise without untoward effects.