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In vivo assessment of anticoagulation.

All methods of assessing anticoagulation rely on in vitro techniques. Although these may reflect the clotting tendency in a specimen of blood accurately, they do not necessarily indicate the effectiveness of the anticoagulant in the body where stasis, acidosis, catecholamines, endotoxin, and exposed collagen may alter the coagulability of blood locally. We have utilized autologous 125I-labelled fibrinogen to assess fibrinogen half-life in normal subjects and in patients with clotting complications before and after the administration of anticoagulants. Fibrinogen half-life has varied from normal (104 hours) to markedly abbreviated (13 hours) in patients apparently fully anticoagulated, utilizing standard laboratory parameters. Although there are many potential causes of the shortening of fibrinogen half-life, including fibrinogenolysis and extravascular losses into the interstitial space and wounds, we have been able to establish whether the disappearance of the radioactive-labelled fibrinogen is due to these causes or to clotting by increasing the levels of anticoagulation. Plateauing of fibrinogen half-life values despite increased doses of heparin, or return of the half-life to normal, indicates full anticoagulation. This has permitted determination and administration of the theoretically optimal dose of heparin. In situations involving life-threatening clotting complications, such as massive pulmonary embolism, the use of 125I-labelled fibrinogen provides a means for controlling anticoagulant therapy in a rational fashion by this technique of assessing clotting.

Adult↗

Treatment with sisomicin of complicated urinary tract infections in patients with varying degrees of renal function impairment, pharmacokinetics and dosage adjustment.

The efficacy, tolerance and pharmacokinetics of the new aminoglycoside antibiotic sisomicin, have been studied in 29 elderly male patients with varying degrees of renal function impairment and suffering from complicated urinary tract infections. The antibiotic was equally effective in patients with normal and impaired renal function and a cure (negative urine culture at one week follow-up) of 56% was obtained. There was little apparent toxicity with the dosage regimens used, although serum creatinine values were statistically but not clinically significantly increased in some patients following treatment. Serum half-lives of sisomicin were prolonged in cases of impaired renal function but accumulation of antibiotic could be prevented by varying dosing intervals between 8 and 24 hours based on serum creatinine values. There was good correlation between serum creatinine and sisomicin serum half-life values and a practical method is described for dose adjustment based on the relationship between serum half-lives and serum creatinine concentrations.

Aged↗

Review of the pharmacokinetics and dose dependency of azlocillin in normal subjects and patients with renal insufficiency.

Cross-over studies on volunteers with several doses of azlocillin ranging from 1.0 to 5.0 g have shown that azlocillin is subject to dose dependent pharmacokinetics, the area under the serum curve becoming larger than expected as doses increase. There was also a tendency towards longer serum half-life values and excretion of more unchanged compound as the doses increase. The serum half-life varied between 0.9 h after 1.0 g increasing to 1.5 h after intravenous doses of 5.0 g given to adults. In neonates, values around 2.6 h have been observed, and they were slightly longer in premature babies at approximately twice the value in adults receiving similar doses per kg body weight. In normal adults protein binding lies between 35 and 40% for therapeutic concentrations. Approximately 60-75% of the dose appears as unchanged azlocillin in the urine, increasing with higher doses. Reduced renal function lowers urinary excretion, but concentrations are always above the break point for sensitivity of 32 mg/l in patients with creatinine clearances above 10 ml/min. In anephric subjects T1/2 of 2.5-6 h is observed. Dosage modifications only to one-third of normal are needed for a renal clearance of 10-25 ml/min. The concentrations of active compound are high in the bile in subjects with normal liver function.

Azlocillin↗

Values clarification and the post-myocardial infarction patient.

Marked changes in an individual's attitudes and actions are frequently due to severe or prolonged conditions of stress. A stress encountered by the myocardial infarction patient is the anxiety or depression induced by the forced reduction of activities. Values clarification may be utilized to assist the patient to sort out those activities that are truly important, thus decreasing tension and anxiety. Values, developed and subsequently modified by a person's on-going experiences, give direction to life. Values clarification assists in developing an awareness of those entities a person considers important. It rests on a specific method of reponding to what an individual says or does. The clarifying response is non-judgmental and encourages the individual to examine and to think about his life and ideas. The responsibility is placed on the individual to make a decision as to what he wants. Understanding a patient's values provides the nursing staff with a rational basis for his care and support.

Adult↗

Is life of infinite value?

It is possible and necessary to compare stretches of human life with other goods, such as the good of conserving resources for others. A minute of human life is not of infinite value; all else being equal, a minute of life is less valuable than 10 years of the same life. Nevertheless, this ability to evaluate human life does not necessarily lead to total commodification of human life.

Adult↗

Laboratory studies on formation of bound residues and degradation of propiconazole in soils.

Laboratory studies on the formation of bound residues and on the degradation of the triazole fungicide propiconazole were conducted in two different soils. Soils treated with 14C-propiconazole were incubated at 22 degrees C and extracted exhaustively with a solvent at each sampling date until no further propiconazole was extracted. The solvent-extractable residues were used to measure propiconazole remaining in the soil, and the extracted soils were used to investigate bound residues of propiconazole. Mineralization of propiconazole was investigated by measuring [14C]carbon dioxide evolved from the soil samples. Formation of bound residues of propiconazole was higher in silty clay loam soil than in sandy loam soil, giving approximately 38 and 23% of the applied 14C, respectively. In contrast, the rates of degradation and mineralization of propiconazole were lower in silty clay loam soil than in sandy loam soil. Decreased extractability of the 14C residues with incubation time was observed with increased formation of bound residues. When the propiconazole remaining in the solvent-extractable residues was quantitatively measured by high-pressure liquid chromatographic analysis, the half-life value in sandy loam soil was about 315 days, while the half-life in silty clay loam soil exceeded the duration of the 1 year experimental period. Increased formation of bound residues was observed as propiconazole degraded with incubation time, suggesting that degradation products are involved in the formation of bound residues. Our study suggests that the formation of bound residues of propiconazole contributes to the persistence of this fungicide in soil.

Carbon Radioisotopes↗

Modeling the growth of long-stay populations in public mental hospitals.

Long-stay, chronic patients have been a problematic subpopulation in public mental hospitals for over a century. Despite three decades of deinstitutionalization and a major shift toward shorter episodes of hospitalization, there continues to exist a group of patients who experience lengthy hospital stays. As the number of such patients increases in a facility, its ability to provide acute care may be compromised, and the size of this subpopulation must therefore be anticipated. This paper examines the length-of-stay patterns of a sample of public mental hospital admissions through the use of life table analysis, and develops a dynamic modeling algorithm using sample survival function values. Life table analysis revealed a declining hazard function, indicating a diminishing probability of discharge with increased hospital stay. The dynamic model showed that, after 2 years of operation of a hypothetical facility, current length-of-stay patterns would generate an inpatient population 40% of which had been hospitalized for over 6 months. Goodness-of-fit tests comparing the algorithm's forecast with actual hospital utilization data showed its predictions to be reliable. The authors discuss the use of this methodology to anticipate the effects of programmatic or other types of changes in mental hospitals, and also suggest other types of settings where such modeling techniques might profitably be applied.

Algorithms↗

Life, illness and death--existential reflections of a Swedish sample of patients who have undergone curative treatment for breast or prostatic cancer.

The aim of this study is to describe cancer patients' existential reflections and how these reflections were met by the nursing staff. A qualitative method of data collection was used. Ten patients with breast- or prostate cancer who had completed curative treatment were interviewed. The results showed that the cancer diagnosis resulted in existential reflections in some of the patients. These reflections concerned the meaning of life, God/a higher power, health, work, relations and sexuality. Reflections on the cancer consisted in beliefs about the causes of cancer, treatment and cancer and sexuality. It could also be seen that loss of important life values, such as health and sexuality could lead to loss of meaning of life. Explicit reflections on sexuality were only made by two of the men in the study. The patients reported a need of existential support as well as obstacles for giving such support. Obstacles could be lack of time and lack of continuity, as well as lack of knowledge resulting in an inability to identify existential issues. Some of the patients had wanted existential support from nurses, while others received the support they needed from family and friends.

Adaptation, Psychological↗

The networking between hospital and health centre.

Health care providers, purchasers, and insurers try to manage the costs while maintaining the quality of the care. In the Hospital District of Central Finland we based our plans on the following values: life worth living, justice, truth, responsibility, equality, relationship, and commitment. Most of these values mean responsibility for the patient. At the same time they tell of the ethical basis of our regional networking between hospitals and health centres.

Computer Communication Networks↗

Evaluation of treatment responses in late Lyme borreliosis on the basis of antibody decrease during the follow-up period.

The purpose of this study was to identify a serological marker of successful treatment as distinct from treatment failure in late Lyme borreliosis. Consecutive serum samples from 68 treated patients with late Lyme borreliosis were analyzed during a 1-2 year follow-up period after the start of treatment. End-point enzyme immunoassay titres of IgG1, IgG2, IgG3, and combined IgG1+3 subclasses against a sonicate antigen of Borrelia burgdorferi were determined and compared to the IgG antibody response against Borrelia burgdorferi flagella. Individual half-lives of the antibody levels were calculated for each patient. The half-life values were compared to the patients' clinical outcome in order to find a serological marker of remaining disease activity or relapse. The levels of combined IgG1+3 subclass antibodies against the sonicate antigen and the individual levels of IgG1, IgG2, and IgG3 antibodies did not change significantly after treatment. In contrast, antibodies to flagella decreased markedly after successful treatment, with a half-life of 112+/-92 days (arithmetic mean value +/- SD). This was significantly shorter than the half-life after unsuccessful treatment (271+/-151 days), (P<0.0001). The decrease was observed mainly in IgG1 and IgG4 responses to flagella, less so for IgG2 or IgG3. The results suggest that a rapid decrease in flagella antibodies can serve as a marker for a successful treatment of Lyme borreliosis.

Animals↗

The half-life of 218Po.

Direct observation of the 218Po alpha-peak decay with a microcomputer-controlled alpha-spectrometer yielded a mean half-life value of 3.040 +/- 0.008 min, where the error quoted represents twice the standard deviation of the means from 38 separate decay measurements. The 1912 and 1924 218Po half-life measurements, which provided the 3.05-min value listed in nuclear tables for the past 60 y, are critically reviewed. Two more recent experiments, which yielded longer values of 3.11 min (Van Hise et al. 1982) and 3.093 min (Potapov and Soloshenkov 1986), are also discussed.

Half-Life↗

Cost effectiveness of perindopril in reducing cardiovascular events in patients with stable coronary artery disease using data from the EUROPA study.

BACKGROUND: The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported. OBJECTIVE: To assess the cost effectiveness of perindopril in stable coronary heart disease in the UK. METHODS: Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health-related quality of life values were taken from published sources. A cost-effectiveness analysis is presented as a function of the risk of a primary event (non-fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money. RESULTS: The median incremental cost of perindopril for each quality-adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as 9700 pounds(interquartile range 6400-14,200 pounds). Overall, 88% of the EUROPA population had an estimated cost per QALY below 20,000 pounds and 97% below 30,000 pounds. For a threshold value of cost effectiveness of 30,000 pounds per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care. CONCLUSIONS: Whether the use of perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.

Angiotensin-Converting Enzyme Inhibitors↗

Pharmacokinetics of phenylethylmalonamide (PEMA) in elderly men.

The pharmacokinetics of phenylethylmalonamide (PEMA) were studied in 6 elderly men after oral administration of a single 400 mg dose. Peak PEMA serum levels were obtained within 4 h of intake, half-life values ranged from 30.7-57.9 h in these elderly men. The elimination half-life was twice as long when compared to a study previously performed in young volunteers.

Aged↗

Normalization rate and cellular localization of phosphatidylethanol in whole blood from chronic alcoholics.

Phosphatidylethanol (PEth) is an abnormal phospholipid which is formed in the presence of ethanol, via the action of phospholipase D (PLD). PEth in blood is a potential marker of alcohol abuse. The present study was made to determine the compartmentalization and the elimination rate of PEth in human whole blood. PEth was assayed by an improved HPLC technique, with evaporative light-scattering detection. Blood from six alcoholic males was separated into different blood cell fractions. The PEth concentration in whole blood was 2.5+/-0.9 and 1.9+/-1.1 micromol/l in erythrocytes. Only one subject had detectable PEth in the mononuclear cells. Fifteen patients (13 men, two women) with chronic alcoholism, were followed as inpatients, after admission to an alcohol detoxification clinic. PEth, carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) were measured on days 1, 3, 5 and 7 after admission. Linear regression analysis of logarithmic PEth values in individuals, with measurable PEth at day 1, gave a good fit (P<0.001) with the one-compartment elimination model. The half-life was calculated as 4.0+/-0.7 days. A weak significance (P<0.05) was observed in the correlation of PEth at day 1 and half-life values of the same subjects.

Alcoholism↗

Observations on lithium disposition in the elderly.

The disposition kinetics of lithium were studied in six elderly women who had been maintained on this medication for several years. Lithium administration was stopped abruptly. Plasma, whole blood, and erythrocyte half-lives were then measured, as well as renal plasma clearance and distribution volume. Half-life values in whole blood and in its components were found to be similar. The plasma lithium half-life approximated that in younger schizophrenics, but appeared prolonged when compared with half-lives reported for young normal volunteers. Renal plasma clearance and distribution volume of lithium appeared substantially reduced when compared with published values. The data are consistent with altered lithium disposition in the aged.

Affective Symptoms↗

Marker half-life analysis as a prognostic tool in testicular cancer.

In a retrospective study we compared the actual half-life of the serum tumor markers alphafetoprotein and human chorionic gonadotropin to the clinical course of patients who underwent an operation or chemotherapy for germ cell cancer. Of the 7 patients with residual disease postoperatively 5 had abnormal half-life values and in 3 this knowledge would have been of clinical value. Only 1 of 10 patients with a complete response to chemotherapy had an unfavorable actual half-life compared to 17 of 19 with a less than complete response. Prolonged marker decay rates during the first month of chemotherapy reflected ineffective chemotherapy and appeared to be independent of tumor bulk. Postoperatively, actual half-lives probably are useful prognostically only if the values are abnormal. Similar calculation may be of prognostic value early in the course of induction chemotherapy.

Chorionic Gonadotropin↗

Respiratory cartridge efficiency studies: VIII. summary and conclusions.

The theory of solvent vapor adsorption of activated carbon is reviewed. Calculated and experimental cartridge service life values are compared using various breathing rates, relative humidities, concentrations and solvent vapors. Cartridge service life (the 10% breakthrough time) can be estimated from the emperical expression: t 10% = 2.4 X 10(6) WC (A + BT)/C 2/3 MQ Carbon weight (wc), relative solvent volatility (a, b and t) concentration (C), molecular weight (M) and breathing rate (Q) all play a vital role in cartridge performance predictions.

Adsorption↗

Bromide kinetics and distribution in the rat. I. Biokinetics of 82Br-bromide.

Biological half-lives of bromine in 15 different organs and tissues of the rat, in addition to the whole-body half-life, were determined by measuring the radioactive concentration of 82Br-bromide in samples of tissues collected at the time intervals of 12-396 h from animals that continuously (up to 17 d) received 82Br-labeled bromide in their drinking water. The half-life values, calculated from the experimental data by the method of gradual estimates of the parameters in question with the SPSS statistical program, ranged from 94.3+/-14.6 h in the thyroid gland to 235.0+/-88.9 h in liver. In most of the studied tissues, the biological half-lives of bromine were shorter than in the whole body, in which it equaled 197.8+/-22.2 h. Significant correlation between the values of the steady-state concentration of bromide and of the biological half-life was found for most tissues (except for liver). The steady-state concentrations of 82Br in tissues are probably proportional to the magnitude of bromide space, and, consequently, of chloride space.

Animals↗