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PubMed1995

Prediction of long-term survival by preoperative exercise testing in patients with depressed ejection fraction undergoing myocardial revascularization.

Ejection fraction is a major determinant of morbidity and mortality for patients with ischemic heart disease. Patients with an ejection fraction of 0.40 or less are generally recognized as having a poorer prognosis than those patients with an ejection fraction of 0.50 or better and remain a heterogeneous group. It would be useful if patients with a favorable surgical prognosis could be identified preoperatively. Fifty-five patients who underwent coronary artery bypass grafting and had an ejection fraction less than 0.40 (mean of 0.23 +/- 0.07 standard deviation) were studied by catheter measurement of pulmonary arterial pressure and radionuclide left ventriculography. Heart rate, systemic blood pressure, pulmonary artery pressures, cardiac output, and ejection fraction were measured, at rest, after nitroglycerin was given intravenously and with supine bicycle exercise. Forty-seven patients who had follow-up longer than 4 years were divided into two groups according to their life status (alive or dead) 4 years after operation. Measured variables of exercise stress tests and clinical characteristics were entered into factor analysis to obtain a cardiac function factor score for predicting the life status after 4 years. The cardiac function factor score was highly loaded by stroke index (rest, nitroglycerin), cardiac index (exercise), systemic vascular resistance index (exercise), and history of congestive heart failure. The cardiac function factor provided a predictive value superior to that of any individual variable. By dividing the patients into two groups by cardiac function factor score, the actuarial 5-year survival was 72% versus 17% for good and poor prognosis groups, respectively (p < 0.0001). Preoperative exercise stress testing data integrated by factor analysis provide a predictive tool for patients with a low ejection fraction.

Adult↗
PubMed2003

Control of immunoglobulin isotype production by porcine B-cells cultured with cytokines.

Cytokines regulate immunoglobulin (Ig) isotype production following the Th1/Th2 paradigm, derived from studies of inbred mice. In pigs, it is not known which, if any, Ig isotypes may reflect a Th1/Th2 response. To evaluate this, purified porcine CD21(+) B-cells were co-cultured with Staphylococcus aureus Cowan strain 1 or Escherichia coli lipopolysaccharide as B-cell mitogens together with recombinant human IL-2, and recombinant porcine (rp) interferon (IFN)-gamma, IL-12 or IL-10. While the mitogens increased B-cell proliferation, cytokines had no additional effect. A quantitative competitive enzyme-immuno assay was used to measure concentrations of porcine IgM, IgG(1) and IgG(2) in B-cell culture supernatants. In vitro, porcine B-cells produced IgG(2), 106 +/- 17.3 microg/ml; IgG(1) 107 +/- 38.3 microg/ml and IgM 25.6 +/- 8.45 microg/ml. In some individuals, Th1 cytokines such as rpIFN-gamma and IL-12, enhanced IgG(2) in the face of low concentrations of IgG(1). Furthermore, individual responses, in some cases, tended to be diametrically opposed, reminiscent of previously documented categorical immune responses in pigs such that some individuals produced high concentrations of IgG(1) in response to the various doses of rp cytokines, while others produced lower concentrations. Pigs may generate a high IgG(1):IgG(2) ratio in response to rpIL-10, and possibly to other Th2-associated cytokines. However, B-cell response to rp cytokines in vitro exhibits marked variation by pig, a feature that is likely a function of highly variable individual genotypes and their interaction with complex environments.

Animals↗
PubMed2005

Genotype-phenotype correlation between the polymorphic UGT2B17 gene deletion and NNAL glucuronidation activities in human liver microsomes.

The nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is one of the most potent and abundant procarcinogens found in tobacco and tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), is an important mechanism for NNK detoxification. In cigarette smokers and tobacco chewers, there is a wide variation in the urinary levels of the ratio of NNAL to NNAL glucuronide (NNAL-Gluc). To determine whether genetic variation plays a potential role in this inter-individual variability, NNAL-glucuronidating activities were analysed in a series of human liver microsomal specimens and compared with UGT2B17 deletion genotypes in the same subjects. Assays performed in vitro demonstrated that over-expressed UGT2B17 exhibits high O-glucuronidating activity against NNAL. When stratifying subjects by UGT2B17 genotype, a significant or near-significant decrease in NNAL-O-Gluc formation was observed in liver microsomes from individuals who were either heterozygous [(+/0), P=0.07] or homozygous [(0/0), P=0.016] for the UGT2B17 deletion compared to liver microsomes from individuals with intact UGT2B17 alleles [(+/+)]. There was a significant (P<0.01) association between the level of liver microsomal NNAL-O-glucuronide formation and increasing numbers of the UGT2B17 null alleles in the liver microsomal specimens examined in this study, and a significant decrease in NNAL-O-Gluc formation was observed when comparing liver microsomes from individuals who had at least one UGT2B17 allele deleted [(+/0)+(0/0)] versus microsomes from UGT2B17 (+/+) subjects (P=0.004). When stratifying by the median value of NNAL-O-Gluc formation activity, a significantly (P=0.015) higher number of subjects with liver microsomes having low NNAL-O-Gluc formation activity contained the UGT2B17 null genotype compared to subjects with liver microsomes exhibiting high NNAL-O-Gluc formation activity. When stratifying by UGT2B7/UGT2B17 haplotypes, the association between the level of liver microsomal NNAL-O-glucuronide formation and increasing numbers of the UGT2B17 null allele was at the level of statistical significance for subjects with the UGT2B7 (*1/*2) (P=0.05) or UGT2B7 (*2/*2) (P<0.02) genotypes. These data suggest that the UGT2B17 deletion polymorphism is associated with a reduced rate of NNAL detoxification in vivo and may increase individual susceptibility to tobacco-related cancers.

Base Sequence↗
PubMed2005

Social dynamics of health inequalities: a growth curve analysis of aging and self assessed health in the British household panel survey 1991-2001.

OBJECTIVES: To study how social inequalities change as people age, this paper presents a growth curve model of self assessed health, which accommodates changes in occupational class and individual health with age. DESIGN: Nationally representative interview based longitudinal survey of adults in Great Britain. SETTING: Representative members of private households of Great Britain in 1991. PARTICIPANTS: Survey respondents (n = 6705), aged 21-59 years in 1991 and followed up annually until 2001. MAIN OUTCOME MEASURE: Self assessed health. RESULTS: On average, self assessed health declines slowly from early adulthood to retirement age. No significant class differences in health were observed at age 21. Health inequalities emerged later in life with the gap between mean levels of self assessed health of those in managerial and professional occupations and routine occupations widening approaching retirement. Individual variability in health trajectories increased between ages 40 and 59 years so that this widening of mean differences between occupational classes was not significant. When the analysis is confined to people whose occupational class remained constant over time, a far greater difference in health trajectories between occupational classes was seen. CONCLUSIONS: The understanding of social inequalities in health at the population level is enriched by an analysis of individual variation in age related declines by social position.

Adult↗
PubMed2006

Biomechanics of lower limb raising from the supine position.

AIM: This study analyses the kinematics of the lower limb raising movement from the supine position and the electromyography activity of the muscles involved. METHODS: Twenty healthy right hand subjects performed the right lower limb raising from the supine position, starting from the clinical bed plane and up to a 70 degrees inclination of the thigh over the horizontal plane, while the knee was kept flexed at 120 degrees by a soft splint. The same exercise was executed with no resistance and with 2 kg and 8 kg respectively applied to the ankle. The kinematics was recorded utilising an optoelectronic system, whereas the electromyography activity was recorded by a surface electromyography (EMG) applied to the following muscles: right rectus femoris, left biceps femoris, rectus abominalis from both sides and dorsal major from both sides. RESULTS: In all the cases the pelvis performed a backwards rotation retroversion. The highest increase of EMG activation was recorded on the right rectus femoris as well as on the left biceps femoris; the increase was lower in the right rectus abdominis and in the right dorsal major, whereas it was minimum in the left rectus abdominis and in the left dorsal major. A great variability in the activation times was reported in the various muscles of the different subjects, regardless of the trials. The only muscle anticipating the right rectus femoris activation was the left biceps femoris. CONCLUSIONS: The research has shown how the simple movement under study is more complex than what is usually described by the text books, both in regard to the kinematics and to muscles' actions. Even the individual variability in utilising the agonist and stabilisation muscles can be of relevance for a more rational utilisation of the physical exercise in motor re-education.

Adult↗
PubMed2006

Parkinson's disease: premotor clinico-pathological correlations.

Parkinsonism is a clinical syndrome characterized by bradykinesia, hypo-/ akinesia, muscular rigidity, and resting tremor, mainly caused by Parkinson's disease (PD). Progressive loss of nigral neurons with Lewy bodies is considered an essential neuropathological feature. Recent studies, however, indicate that nigral degeneration is only a part of this synucleinopathy, and clinical symptoms go far beyond motor parkinsonism. Olfactory disturbances, autonomic dysfunction, pain, sleep fragmentation, depression, and dementia with or without psychosis are frequently seen. The variability in the expression of these signs and symptoms suggests multiple causes and/or pathogeneses within the present diagnostic disease entity. In this article, a recently proposed staging of PD-related brain pathology will be correlated with the various clinical expressions. It will be argued that the specific topographical sequence of the pathology, depending on the extent and progression of the degenerative process at defined sites, may explain the individually variable expression of this disease.

Disease Progression↗
PubMed1998

Estimation of the accuracy of a surface matching technique for registration of EEG and MRI data.

OBJECTIVES: We developed a method to register EEG and MRI data used for the source reconstruction of electric brain activity. METHODS: The method is based on matching of the head surfaces as obtained by 3D scanning after the EEG recording, and by segmentation of MRI data. The registration accuracy was estimated by calculating the residual error of the surface matching and its intra-individual and inter-individual variability. In addition, the test-retest reliability concerning the transformation of electrode positions was studied, to estimate how inaccuracies resulting from the 3D scanning of the head surface translate into registration uncertainty. RESULTS: For 61 measurements, performed on 20 subjects, the average root mean square of the Euclidean distances between the 3D-scanned and the MRI-derived head surfaces amounted to 3.4 mm. An inter-individual standard deviation of 0.24 mm, and an intraindividual standard deviation of 0.003-0.31 mm proved a high inter- and intra-subject stability of the surface matching technique. The variation of transformation results when studying the test-retest reliability amounted to 1.6 mm on average. The maximum error of transformation was smaller than the diameter of the electrodes. CONCLUSIONS: The findings suggest that the surface matching technique is a precise method for determination of the transformation of electrode positions and MRI data into a single co-ordinate system and can successfully be used in a routine laboratory setting.

Brain↗
PubMed1990

Educational and psychosocial needs of patients with chronic disease. A survey of preferences of patients with rheumatoid arthritis.

There is increasing interest in better defining and meeting the nonmedical needs of patients with chronic diseases, such as rheumatoid arthritis (RA). We surveyed patients with RA about the importance of eight psychosocial and eight educational issues, and asked patients from what source they preferred to get help with these issues and which sources they would not use. We also looked at individual variables, including sex, age, disease duration, and disease severity, to see if they affected patients' choices. The issues rated most important by patients included communicating with the doctor, understanding medication, dealing with pain, and the effects of arthritis on energy level, the future, and work. Most patients preferred to seek help from their physicians, although up to 75% were willing to attend groups, and 68% were willing to see individual counselors for some issues.

Adaptation, Psychological↗
PubMed1989

Long-term intra-individual variation of platelet parameters.

Mean platelet volume, platelet count and platelet distribution width were determined in eight male subjects at monthly intervals over a 4-6 month period. Measurements were made on a Coulter S Plus VTM exactly 15 min and 2 h after blood collection. Long-term intra-individual variability for mean platelet volume showed a mean coefficient of variation (CV) of 1.60% at 15 min and 2.01% at 2 h after blood collection; for platelet count a mean CV of 3.18% at 15 min and 2.40% at 2 h; and for platelet distribution width a mean CV of 7.3% at 15 min and 6.5% at 2 h. Platelet parameters are stable over time in the normal male individual.

Adult↗
PubMed1981

[Certain anatomical explanations for the symptoms of Costen's syndrome].

An attempt is made to explain certain variability for display of Costen's syndrome. For this purpose, in 20 macerated skulls of mature persons certain structural peculiarities of separate elements of the temporomandibular joint (distance from the center of recess of the articular fossa up to the anterior area of the petrotympanic fissure, thickness of the tympanic part at the beginning of the fissure, its length and width at either side) have been studied. An essential individual variability of diameters is noted. In the group of persons where the measurements are taken from the right side, a greater right-sided variability for the length of the fissure is noted, and for the distance from the center of the recess of the articular fossa up to the petrotympanic fissure-the least absolute size is noted.

Humans↗
PubMed2000

[Variability of the level of thermoresistance as an indicator of the functional status of a cell].

Effect of acclimating temperature on the thermoresistance of isolated ciliated gill epithelium of Anodonta anatina was studied. One strip of gills from each mussel was used to determine the initial level of thermoresistance (survival time at 40 degrees C). Other strips were kept at 24 degrees C until their death, and their thermoresistance and fluorescence after Ethidium bromide staining were determined at different time intervals. After a short exposure at 24 degrees C the mean level of thermoresistance of the epithelium increased. The individual shift in the value and direction of cell thermoresistance in different mussels negatively correlated with its initial level. It resulted in narrowing the extent of individual variability of the level of thermoresistance. The prolongation of exposure at 24 degrees C decreased the mean level of thermoresistance, disturbed the negative correlation, and increased the variability of thermoresistance level. The value of cell fluorescence remained constant within 48 h. The increase in fluorescence was observed 12 h after reducing the mean thermoresistance level. Hence, the dynamics of variability in the thermoresistance level is a most sensitive indication of the cell functional state.

Animals↗
PubMed2007

Population pharmacokinetics of mefloquine in military personnel for prophylaxis against malaria infection during field deployment.

OBJECTIVE: The purpose of this study was to determine the population pharmacokinetics of mefloquine in healthy military personnel during prophylaxis for malaria infections. METHODS: The subjects were 1,111 Australian soldiers participating in two studies: a randomised double-blinded study (group A, 161 subjects) and an open-label study (group B, 950 subjects). Following a loading dose (250 mg mefloquine base daily, 3 days), subjects received an oral weekly maintenance dose of 250 mg over 6 months. Blood was collected after the last split loading dose then at weeks 4, 8 and 16 for group A, and at weeks 13 and 26 for group B. Plasma mefloquine concentrations were measured by high-performance liquid chromatography (HPLC). Pharmacokinetic modelling was performed using NONMEM. RESULTS: A two-compartment model with inter-occasion variability (IOV) for clearance satisfactorily described the pharmacokinetics. Typical values were clearance (CL/F, 2.09 l/h), central volume of distribution (V1/F, 528 l), absorption rate constant (KA, 0.24 h(-1)), inter-compartmental clearance (Q/F, 12.5 l/h), peripheral volume of distribution (V2/F, 483 l) and elimination half-life (t (1/2), 14.0 days). Weight had a positive influence on central volume but was insufficient to warrant dosage adjustments. The inter-individual variability (coefficient of variation, CV%) for CL/F and V1/F was 24.4% and 29.6%, respectively. The IOV for CL/F was 17.8%. The proportional residual error (CV%) for groups A and B was 11.5% and 19.5%, respectively, and the additive error standard deviation (SD) was 57 ng/ml and 149 ng/ml, respectively. CONCLUSION: The typical parameter values were comparable with those estimated in much smaller cohorts of healthy subjects and in malaria patients treated with single-dose mefloquine. The lower unexplained variability in the blinded study suggested these subjects may have been more compliant in taking their medication than soldiers in the open-label study.

Adolescent↗
PubMed2006

Validity of preoperative demand matching as an indicator of activity after TKA.

We questioned whether our current preoperative demand matching accurately predicted patient activity after TKA. From a prospective database we reviewed 511 patients who had unilateral, primary TKA from 1994 to 1999 and who were preoperatively assessed for five patient characteristics: age, weight, expected postoperative activity, health status, and bone stock. We assigned each knee to one of four demand categories. Knee implant selection was based on the patient's demand category. Other preoperative patient characteristics that could be associated with postoperative activity were recorded. The reported postoperative patient activity after TKA was determined, and was correlated with each patient variable and the demand category. Five hundred eleven TKAs were distributed among four demand categories: 39 (7.6%) demand I (high); 156 (30.5%) demand II; 294 (57.5%) demand III; and 22 (4.3%) demand IV (low). Age, gender, expected postoperative activity, bone stock, health status, preoperative activity, Knee Society Function Score, and the Hospital for Special Surgery Knee Score correlated with postoperative patient activity. The demand category was more predictive than any individual variable. The data suggest preoperative demand matching a valid approach to predict patient reported activity after TKA. Because patient activity is correlated with wear, implant selection and resource allocation can be targeted to those patients who may benefit from presumed improvements in implant technology.

Adult↗
PubMedDate not supplied

[Latex allergy. Diagnosis and therapeutic aspects].

In the last two decades of the 20th century, latex allergy has reached epidemic proportions. Epidemiological studies demonstrate that 3-25 % of health personnel is allergic to latex. The main risk groups are health workers, machine operators in latex factories, and children with spina bifida and urogenital anomalies. From the allergenic point of view, latex contains 240 peptides but approximately 50 are able to react to IgE. Latex elongation factor Hevdl is the relevant allergen in patients with spina bifida. Prohevein (hev B6) behaves as a major allergen, since it reacts to IgE in most of the sera of patients with latex allergy. The nature of latex is complex; it is an allergenic mixture that depends on chemical, immunological and epidemiological variables. Latex proteins show strong cross reactivity with several proteins from fruit and vegetable grains such as avocado, potato, banana, tomato, chestnut, and kiwi. In vivo studies have shown that class I chitinase from avocado and chestnut behave as major allergens in allergic patients with latex-fruit syndrome. The clinical manifestations related to the use of latex products depend on the type of exposure, the amount of the allergen, and individual variability. The most useful diagnostic method is the skin prick test. Several perioperative guidelines are recommended in patients sensitized to latex as well as various alternatives to rubber gloves. An increasing number of studies describe the efficacy of etiological treatment (immunotherapy), using different guidelines and routes of administration. These preliminary data encourage the hope that in the near future immunomodulatory therapy will be available to mitigate against the latex allergy epidemic.

Adult↗
PubMed2003

[Difficulties in controlled inhalation of alpha 1-protease inhibitor].

In this paper a number of studies will be summarized which were designed to improve the inhalation of alpha 1 -protease inhibitor in patients with alpha 1-protease inhibitor deficiency. A pilot study has shown that the high inter-individual variability of drug deposition in the lungs is due to heterogeneous breathing patterns of the patients. Controlling the breathing pattern led to a significantly decreased variability. Then it was studied which particle size and breathing pattern resulted in highest peripheral lung deposition in patients with emphysema. It was found that for 3 - 4 microm particles and slow inhalation flow rate the peripheral deposition increases with increasing inhalation volume. After the development of an inhalation device which allows to perform controlled inhalations in clinical practice it was shown that this device, in combination with a breathing pattern individually normalized to the patients lung function, allows to deposit nearly 60 % of the drug into the patients lung periphery.

Administration, Inhalation↗
PubMed1993

Quantitation and three-dimensional reconstruction of Ch4 nucleus in the human basal forebrain.

The basal nucleus of Meynert, incorporating the Ch4 group of cholinergic neurons, was examined in six patients with no signs of neurological abnormalities. The ages of the patients ranged from 20 to 80 years. Despite a number of descriptions of these neurons, few age-related studies have been dedicated to the analysis of the entire anteroposterior extent of the nucleus. Staining with cresyl violet and acetylcholinesterase histochemistry, alone or in combination, was used to identify the cytoarchitectural organization of the Ch4. Computer-assisted morphometry was used for three-dimensional visualization and quantitation. The three-dimensional computer reconstructions revealed a continuous ribbon of neurons with a highly variable density. Four distinct subregions could be clearly identified in all cases by their cytoarchitecture and cellular morphology, although these subgroups were different to those previously described. There were no quantitative differences between the hemispheres in volume, density or cell number of the Ch4, although equivalent levels varied in area and density. The measures were similar in all cases with the exception of the case aged 80 years old. The data demonstrate individual variability in three dimensions and confirm previous studies that found only a mild decline of the Ch4 in old age.

Acetylcholinesterase↗
PubMed2005

Attention modulates perception of transparent motion.

Human observers can extract a given motion direction from sets of random dots moving simultaneously in two or more directions in the same region of the visual field, a phenomenon referred to as motion transparency. As a necessary condition for separating transparent motion directions, low level encoding of local motion signals must generate frequency distributions of local directions with separable peaks corresponding to these directions--this process would be constrained by local stimulus attributes and the properties of local motion detectors. Furthermore, a representation of multiple directions is needed for simultaneous retrieval of several directions in a psychophysical task--this operation would be limited by higher level processes, such as attention selecting a particular direction to rise into awareness. Preliminary observations suggest that the number of directions that can be seen simultaneously is rather limited and the question arises whether this could be related to limitations of low-level encoding or higher level representations. To study specifically the effect of attention on transparent motion perception, observers were presented with sets of dots moving coherently in a variable number of directions, and were asked after the presentation whether one particular direction was present in the set. When the direction of motion was not known before stimulus onset (uncued condition), observers detected a particular motion direction among no more than 3 other directions. When direction of motion was indicated prior to stimulus onset (precued condition), however, this limit increased up to 6 directions. This attentional effect showed some inter-individual variability and appeared to benefit from spatiotemporal integration of the motion signals. A corresponding effect became apparent when observers were tested in the same paradigm whether they could separate two motion directions with variable angular difference between them. In the precued condition a typical minimum direction difference was about 60 degrees, whereas in the uncued condition this was about 120 degrees, suggesting that the performance in detecting one direction in a multiple direction stimulus might be limited by the ability to separate adjacent motion directions. This pattern of results suggests that attention can reliably improve transparent motion processing by affecting the separability of directional signals in low level encoding mechanisms.

Attention↗
PubMed1998

Spatiotemporal stability of lip movements in older adult speakers.

Although the intelligibility of healthy older adults normally seems unimpaired, age-related changes occur in sensorimotor components of the speech system and in such global parameters as speech rate. In order to clarify the effect of these changes on the variability of speech movements, we examined oral peripheral abilities, speech rate, and speech kinematics in a group of 10 adults age 76-83, compared to a group of 10 young adults. Participants repeated a short phrase 15 times at habitual, fast, and slow rates. The resulting lip displacement signals were time- and amplitude-normalized, and successive standard deviations along the movement waveforms were summed to produce a spatiotemporal index (STI) representing individual variability in movement pattern. Participants tended to show greatest variability at slow rate, less variability at fast rate, and least variability at habitual rate. For the older adults, STI at habitual rate was significantly higher (more variable) and speech durations were longer than those of young adults. Perioral strength and tactile acuity were poorer in these older adults than in young adults. We conclude that as sensorimotor abilities change in old age, speakers are less consistent in the spatiotemporal organization of speech movements, reflecting decreased stability of speech motor control.

Adult↗