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PubMedDate not supplied

[Myocardial electrolytes in "cardioplegic" myocardosis (author's transl)].

Changes of the mineral concentrations of the heart muscle can point at disturbances of myocardial metabolism. Disturbances of heart muscle with functional loss and without coronary or inflammatory heart disease are called myocardosis, especially cardioplegic myocardosis after open-heart surgery with extracorporal bypass. 30 dogs were examined in three groups varying the method of induced cardiac arrest: 1. ischemic cardiac arrest by clamping the ascending aorta, 2. functional cardiac arrest by electrically induced fibrillation and 3. ischemic cardiac arrest and in addition injection of a Mg-aspartate-procain-solution. Sodium, potassium, magnesium, calcium, copper and zinc were analyzed by atomic absorption spectrophotometry. Specimens from the left and right ventricular wall were examined before and after extracorporal circulation. After a recovery period for one hour the dogs were killed and specimens from the right and left ventricular wall and from the basis and apex of the interventricular septum were taken and reduced to ashes with mineral acids. In all animals changes of the mineral content were most marked after the recovery period. In all forms of cardiac arrest mineral metabolism showed monotone reactions: water content increased, potassium and magnesium decreased. Variations of mineral concentrations were more expressed in the right ventricular wall than in the left. Animals with cardiac arrest by electrically induced fibrillation indicated the smallest deviations from the basic values. The comparison of the values of dogs with sufficient circulation at the end of the experiments and those dogs with medicamentally or mechanically supported circulation at this time showed a more increased water content and simultaneously a decrease of all cations in the group with supported circulation. The decrease of the osmolality of the cations seems to be the metabolic answer to the increased cardioplegic damage of heart muscle.

Animals↗

PubMed1992

Interaction of click intensity and cochlear hearing loss on auditory brain stem response wave V latency.

Auditory brain stem responses (ABRs) to 95, 80, 60, 40, and 30 dB nHL clicks were retrospectively studied from 103 patients (194 ears) with various degrees of cochlear impairment. Hearing loss and sample size were balanced across gender. Results indicate that the slope of the wave V latency versus 4000 Hz hearing loss function doubles as click intensity is decreased from 80 (0.01 msec/dB HL) to 60 nHL (0.02 msec/dB HL). Overall results indicate a slope increase of 0.0004 msec for each decibel decrease in click intensity from 95 to 30 dB nHL. Intersubject variability increased with increased hearing loss and/or decreased stimulus intensity. The effects of hearing loss on wave V latency are minimal, and intersubject variability is less if high-intensity clicks (greater than or equal to 95 dB nHL) are used. No differences in the effects of hearing loss on wave V latency were seen between males and females. Latency corrections for cochlear hearing loss should, therefore, consider stimulus intensity.

Acoustic Stimulation↗

PubMed2006

An in-depth review of the evidence linking dietary salt intake and progression of chronic kidney disease.

BACKGROUND: Dietary salt has been debated for decades as having a potentially deleterious influence on human health. OBJECTIVES: To determine the quality of research and the relationship between dietary salt and markers for progression of kidney disease. METHODS: Data sources included 7 electronic databases comprehensively searched for literature published between January 1, 1966, and August 31, 2004, and a manual search of bibliographies of relevant papers, and consultation with experts in the field. Differences between the paired reviewers were reconciled through consensus or by a content expert. RESULTS: Sixteen studies met the inclusion-exclusion criteria and were identified for review; however, the study methodologies were extremely heterogeneous. Conclusions commonly cited in the studies include: variations in salt consumption are directly correlated with albuminuria, and an increase in salt consumption is associated with an acute increase in glomerular filtration rate, while a reduction in salt consumption may slow the rate of renal function loss. CONCLUSIONS: The available published information, while highly variable in methods and quality, suggests that variations in dietary salt consumption directly influence albuminuria, with increasing salt intake associated with worsening albuminuria; however, results are inadequate and conflicting on the effects of dietary salt consumption on renal function, especially over a prolonged time. There was no evidence of a detrimental effect of reduced salt intake. On the other hand, there is consistent experimental evidence to link increased salt exposure with kidney tissue injury. On the basis of these data, we believe that dietary salt restriction should be considered in patients with chronic kidney disease.

Comorbidity↗

PubMed2005

Functional connectivity in elderly controls and AD patients using resting state fMRI: a pilot study.

Conventionally, Alzheimer's disease (AD) and other dementias are diagnosed using clinical assessment, neuropsychology and also structural neuroimaging, showing neuronal degeneration starting in the hippocampal regions. However, there is an increasing need for a new method that is more sensitive to early AD identification than currently possible. A new promising technique that may be used for this is to measure local brain activation using functional magnetic resonance imaging (fMRI), since functional loss predates structural loss of brain tissue. A new method to apply fMRI is to study connectivity between brain regions during a resting state without application of a task. Recent data suggest that connectivity within memory systems during such a resting state is associated with the level of memory function. Here we explain how we will study healthy elderly controls, patients with a mild cognitive impairment (MCI, considered to be a transitional stage between normal condition and AD), and AD patients using resting state connectivity fMRI. If resting state connectivity is sensitive to cognitive decline, this will be of great importance for noninvasive dementia research, offering a tool to easily study functional networks in the brain without the requirement of a memory task, and perhaps offering a tool sensitive for early diagnostics.

Aged↗

PubMedDate not supplied

Meniscal allograft replacement: a 1-year to 6-year experience.

PURPOSE: Progressive degenerative arthritis leading to premature pain and functional loss in the postmeniscectomy state is a well- recognized and debilitating condition. Meniscal allograft replacement may be a suitable, early treatment alternative for this population at risk. The purpose of this study was to examine the potential benefits of meniscal allograft replacement on relieving pain and restoring function. TYPE OF STUDY: Retrospective clinical review. METHODS: From 1993 to 1999, 29 menisci were implanted in 28 patients. Of these, 25 patients (26 menisci) were available for review. All patients had a minimum of 12 months of follow-up, with an average of 33 months. Study participants included 17 men and 8 women with primary symptoms of pain or instability at study onset. Eighteen patients had grades I through III Outerbridge chondromalacia changes and 7 demonstrated grade IV changes in the affected compartment. Data were collected using the International Knee Documentation Committee (IKDC), Lysholm II, and Tegner scoring systems as well as a visual analogue scale (VAS) for pain measurement. RESULTS: Our findings revealed that following meniscal allograft replacement, pain was significantly reduced and function was improved (P <.001). In addition, IKDC scores for activity were reported as normal or nearly normal in 17 subjects and abnormal in 8 participants. Outerbridge grade had a significant impact on final outcome; only 3 of 7 with grade IV changes achieved normal or nearly normal scores versus 14 of 18 in those with lesser Outerbridge changes. Isolated implants fared the same as those combined with an ACL reconstruction. Overall satisfaction reported by the subjects averaged 83%. Ten second-look procedures revealed 5 normal menisci, 3 with shrinkage, and 2 with recurrent tears. CONCLUSIONS: Earlier results from this population of patients indicated substantial pain relief and improved function. The durability of these early results has not met the test of time for those with exposed subchondral bone. However, statistically significant early and midterm improvements in pain, symptoms, and functional status continue to be noteworthy in the properly selected patient.

Female↗

PubMed1990

The 'healthy smoker': a phenomenon of health selection?

The detrimental effects of smoking on lung function have been recognized for several decades. Evidence comes from cross-sectional studies which emphasize that damage, certainly at the level of the small airways, may be detectable after a relatively short smoking history, and from longitudinal studies which show that smoking is associated with an increased rate of function loss over time. Implicit in most published evaluations of the evidence has been the concept that smoking is a habit taken up at random by the general population, and that those who do and do not take up the habit start out with similar levels of lung function. Published material was reviewed for evidence to the contrary, consistent with a health selection process similar to that shown in relation to workplace exposures and labeled the 'healthy worker' effect. Despite the wealth of published data on the topic of lung function in relation to the smoking habit, much is presented in a way which does not permit the concept of the 'healthy smoker' to be addressed. Nevertheless, this review revealed sufficient evidence from cross-sectional studies, as well as evidence from one longitudinal study to support the concept of the 'healthy smoker' as an individual who takes up the habit because his/her lungs are relatively resistant to the effects of smoking. If correct, this means that previous studies, particularly those which were cross-sectional in design and focussed on younger persons, are likely to have underestimated the consequences of smoking on lung function. The concept of the 'healthy smoker' may also throw light on characteristics which identify the 'susceptible smoker'.

Adolescent↗

PubMed2006

A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment.

The gamma-actin gene (ACTG1) encodes a major cytoskeletal protein of the sensory hair cells of the cochlea. Recently, mutations in ACTG1 were found to cause autosomal dominant, progressive, sensorineural hearing impairment linked to the DFNA20/26 locus on chromosome 17q25.3 in four American families and in one Dutch family. We report here the linkage of autosomal dominant, progressive, sensorineural hearing impairment in a large Norwegian family to the DFNA20/26 locus. Sequencing of ACTG1 identified a novel missense mutation (c.1109T>C; p.V370A) segregating with the hearing loss. Functional analysis in yeast showed that the p.V370A mutation restricts cell growth at elevated temperature or under hyperosmolar stress. Molecular modelling suggested that the p.V370A mutation modestly alters a site for protein-protein interaction in gamma-actin and thereby modestly alters gamma-actin-based cytoskeletal structures. Nineteen Norwegian and Danish families with autosomal, dominant hearing impairment were analyzed for mutations in ACTG1 by sequencing, but no disease-associated mutations were identified. Finally, a long-term follow-up of the hearing loss progression associated with the p.V370A mutation in ACTG1 is provided. The present study expands our understanding of the genotype-phenotype relationship of this deafness gene and provides a sensitive and simple functional assay for missense mutations in this gene, which may assist future molecular diagnosis of autosomal-dominant hearing impairment. Finally, the present results do not indicate that mutations in ACTG1 are a frequent cause of autosomal-dominant postlingual sensorineural hearing impairment in Norway nor Denmark.

Actins↗

PubMed1991

Somatosensory evoked potentials following stimulation of median and tibial nerves in patients with localized intracerebral hemorrhage: correlations with clinical and CT findings.

Median and tibial somatosensory evoked potentials (SEPs) were performed on 38 patients with localized intracerebral hemorrhage, 23 with thalamic hemorrhage and 15 with putaminal hemorrhage. Of 65 arms and 62 legs examined, cerebral evoked responses of 60 arms and 50 legs were diagnosed as abnormal. The abnormal findings in scalp-recorded SEPs consisted of a reduction in amplitude, loss of waves and delay in peak latencies. The SEP abnormalities were not indicative of location of hemorrhage. Absence of SEPs was more frequently observed in large hemorrhages and at the early stage. Substantial improvement in SEPs was observed over several months after stroke in many limbs. Motor function as evaluated with Brunnstrom staging of the upper limbs whose SEPs were absent was lower than that whose SEPs were evoked, but that was not observed in the lower limbs because in some cases absence of SEPs coexisted with good motor function. Loss of SEP waves had a significant correlation with disturbed deep sensation. The median and tibial SEPs provided an excellent clinical correlation with the patients' improvement over several months.

Adult↗

PubMed1999

Improvement of visual function in an adult amblyope.

PURPOSE: In this case report, the efficacy of occlusion therapy was investigated in a strabismic amblyope above the currently accepted age for treatment. Success was assessed not simply by a change in visual acuity, but by examining a number of parameters which relate to both sensory and motor aspects of visual function. METHODS: As well as routine orthoptic and optometric evaluation, additional tests were administered as follows: high and low contrast LogMAR Crowded Acuity, repeat letter acuity, and hyperacuity measurements. RESULTS: A functional loss in each of the tests used was demonstrated, and occlusion therapy appeared to improve all aspects of the amblyopia, with a significant difference in pre- and post-therapy results. CONCLUSIONS: The results of this study suggest that: (1) occlusion therapy can produce substantial improvements in visual function in adult amblyopia; (2) many aspects of visual function can improve beyond the traditional critical periods for development in amblyopia; and (3) with good patient compliance and cooperation, age should not be the critical factor in the initiation of treatment for amblyopia.

Adult↗

PubMed1976

Management of facial lacerations.

The prevention of unsightly scars and functional loss after facial lacerations is accomplished by early, meticulous repair in layers without tension on the suture line. The interrupted subcuticular suture applied with a small full-curved cutting needle and with the aid of a skin hook is recommended to reach the goal of aesthetic and functional restoration.

Cicatrix↗

PubMed2005

A disintegrin and metalloprotease 33 polymorphisms and lung function decline in the general population.

RATIONALE: A disintegrin and metalloprotease 33 (ADAM33) has been identified as a susceptibility gene for asthma and single nucleotide polymorphisms (SNPs) in this gene have been associated with excessive decline of lung function in individuals with asthma. OBJECTIVES: To assess whether SNPs in ADAM33 are associated with accelerated lung function loss in the general population and with chronic obstructive pulmonary disease (COPD). METHODS: DNA was collected from subjects of the Vlagtwedde-Vlaardingen cohort participating in the last survey in 1989-1990 after a follow-up of 25 years. Information was collected every 3 years, including lung function measurements. We defined COPD as GOLD stage 2 or higher at the last survey. A total of 1,390 subjects from the cohort was genotyped for the following SNPs in ADAM33: F+1, Q-1, S_1, S_2, T_1, T_2, V_4, and ST+5. Differences in prevalence of SNPs were analyzed with chi(2) tests. Linear mixed effects models were used to analyze FEV(1) decline according to genotype. MEASUREMENTS AND MAIN RESULTS: In the whole population, mean adjusted decline was 18.7 and 12.7 ml/year in females and males, respectively. Individuals homozygous for minor alleles of SNPs S_2 and Q-1 and heterozygous for SNP S_1 had a significantly accelerated decline in FEV(1) of, respectively, 4.9, 9.6, and 3.6 ml/year compared with wild type. We found a significantly higher prevalence of SNPs F+1, S_1, S_2, and T_2 in subjects with COPD. CONCLUSIONS: We demonstrated that SNPs in ADAM33 are associated with accelerated lung function decline in the general population. These SNPs are also risk factors for COPD.

ADAM Proteins↗

PubMed1985

[Morphologic and functional changes in the pancreas following acute necrotizing pancreatitis].

Acute necrotizing pancreatitis according to the presented results leads to definite endo- and/or exocrine functional loss in 57% of the patients (n = 21, pancreatic necrosis ascertained by laparotomy) evaluated by orale glucose tolerance test, secretin-ceruletide-test and fluorescein-dilaurate-test. Morphological alterations developed in 76% of patients, predominantly cicatricial ductal lesions shown by ERCP. The finding of a normal pancreatic function after extended necrosis in 43% of the patients can be explained by the enormous functional reserve of the pancreatic gland.

Acute Disease↗

PubMed1996

Analysis of chromosome 17p13 (p53 locus) alterations in gastric carcinoma cells by dual-color fluorescence in situ hybridization.

Chromosome 17 and p53 gene locus alterations were determined on 67 gastric carcinomas by dual-color fluorescence in situ hybridization, using probes for centromere 17 and the 17p13.1 (p53 locus). The results were compared with loss of heterozygosity (LOH) at 17p13.3, direct sequencing of exons 5 to 9 of p53, and nuclear overexpression of p53 protein. Deletion of p53 was found in 26 of 67 tumors (39%). All 26 also showed LOH at 17p13.3, frequently overexpressed p53 protein, and had polysomy 17. The functional loss of p53 gene in these tumors, 85% of which were of intestinal type, appears to be caused by both deletion of 17p13.1 and missense mutation of the remaining allele. There were 9 tumors that had neither deletion nor LOH but had a large proportion of cancer cells that overexpressed p53 election. Despite evidence of LOH, there was no p53 deletion in 11 tumors. Finally, 21 tumors, mostly of diffuse type, showed neither deletions, LOH, nor p53 overexpression. Our data suggest that in gastric cancer, deletion of 17p is principally responsible for the allelic loss at the p53 gene and that analysis of deletions by the dual-color fluorescence in situ hybridization is a sensitive and useful approach to clarify chromosomal aberrations.

Carcinoma↗

PubMed2006

Loss of invariant chain protects nonobese diabetic mice against type 1 diabetes.

The invariant (Ii) chain acts as an essential chaperone to promote MHC class II surface expression, Ag presentation, and selection of CD4(+) T cells. We have examined its role in the development of type 1 diabetes in NOD mice and show that Ii chain-deficient NOD mice fail to develop type 1 diabetes. Surprisingly, Ii chain functional loss fails to disrupt in vitro presentation of islet Ags, in the context of NOD I-A(g7) molecules. Moreover, pathogenic effector cells could be shown to be present in Ii chain-deficient NOD mice because they were able to transfer diabetes to NOD.scid recipients. The ability of these cells to transfer diabetes was markedly enhanced by depletion of CD25 cells coupled with in vivo anti-CD25 treatment of recipient mice. The numbers of CD4(+)CD25(+)Foxp3(+) T cells in thymus and periphery of Ii chain-deficient NOD mice were similar to those found in normal NOD mice, in contrast to conventional CD4(+) T cells whose numbers were reduced. This suggests that regulatory T cells are unaffected in their selection and survival by the absence of Ii chain and that an alteration in the balance of effector to regulatory T cells contributes to diabetes prevention.

Adoptive Transfer↗

PubMed2005

Repositioning-dependent fate of duplicate genes.

Gene duplication is the main source of evolutionary novelties. However, the problem with duplicates is that the purifying selection overlooks deleterious mutations in the redundant sequence, which therefore, instead of gaining a new function, often degrades into a functionless pseudogene. This risk of functional loss instead of gain is much higher for small populations of higher organisms with a slow and complex development. We propose that it is the epigenetic tissue/stage-complementary silencing of duplicates that makes them exposable to the purifying selection, thus saving them from pseudogenization and opening the way towards new function(s). Our genome-wide analyses of gene duplicates in several eukaryotic species combined with the phylogenetic comparison of vertebrate alpha- and beta-globin gene clusters strongly support this epigenetic complementation (EC) model. The distinctive condition for a new duplicate to survive by the EC mechanism seems to be its repositioning to an ectopic site, which is accompanied by changes in the rate and direction of mutagenesis. The most distinguished in this respect is the human genome. In this review, we extend and discuss the data on the EC- and repositioning-dependent fate of gene duplicates with the special emphasis on the problem of detecting brief postduplication period of adaptive evolution driven by positive selection. Accordingly, we propose a new CpG-focused measure of selection that is insensitive to translocation-caused biases in mutagenesis.

Animals↗

PubMed2002

Combining several screening tests: optimality of the risk score.

The development of biomarkers for cancer screening is an active area of research. While several biomarkers exist, none is sufficiently sensitive and specific on its own for population screening. It is likely that successful screening programs will require combinations of multiple markers. We consider how to combine multiple disease markers for optimal performance of a screening program. We show that the risk score, defined as the probability of disease given data on multiple markers, is the optimal function in the sense that the receiver operating characteristic (ROC) curve is maximized at every point. Arguments draw on the Neyman-Pearson lemma. This contrasts with the corresponding optimality result of classic decision theory, which is set in a Bayesian framework and is based on minimizing an expected loss function associated with decision errors. Ours is an optimality result defined from a strictly frequentist point of view and does not rely on the notion of associating costs with misclassifications. The implication for data analysis is that binary regression methods can be used to yield appropriate relative weightings of different biomarkers, at least in large samples. We propose some modifications to standard binary regression methods for application to the disease screening problem. A flexible biologically motivated simulation model for cancer biomarkers is presented and we evaluate our methods by application to it. An application to real data concerning two ovarian cancer biomarkers is also presented. Our results are equally relevant to the more general medical diagnostic testing problem, where results of multiple tests or predictors are combined to yield a composite diagnostic test. Moreover, our methods justify the development of clinical prediction scores based on binary regression.

Bayes Theorem↗

PubMed1990

Segregation of discrete GS alpha-mediated responses that accompany homologous or heterologous desensitization in two related somatic hybrids.

1. Prostacyclin and adenosine A2 receptors activate adenylate cyclase in the neuroblastoma hybrid cell lines NG108-15 and NCB-20. Prolonged exposure of NG108-15 cells to iloprost (a stable analogue of prostacyclin) results in a subsequent reduction in the capacity for adenylate cyclase activation by iloprost, the adenosine analogue 5'-(N-ethyl)-carboxamidoadenosine (NECA) or NaF. In contrast prolonged exposure of NCB-20 cells to iloprost results only in the loss of iloprost responsiveness. 2. Iloprost pretreatment of NG108-15 cells also magnified the morphine-dependent inhibition of iloprost-stimulated adenylate cyclase activity from 36 to 48%. This change was not due to lower iloprost stimulation following desensitization, since the % inhibition of adenylate cyclase activity by morphine in control cells was constant irrespective of enzyme activity. 3. These heterologous effects observed in NG108-15 cells following iloprost pretreatment may involve changes in the GS alpha protein, since there was a reduction of about 30% in the cholera toxin-induced [32P]-ADP-ribosylation of a 45 kDa protein from cell membranes (corresponding to the extent of loss of NECA or NaF responsiveness). A similar reduction was not observed in NCB-20 cells. 4. These results indicate that iloprost pretreatment induces different forms of desensitization in NG108-15 and NCB-20 cell lines. The heterologous desensitization in the former may, like the human platelet, involve a functional loss of GS alpha from the cell membrane. Changes in the activity of GS alpha may also account for the heterologous effects on receptors that mediate inhibition of adenylate cyclase.

Adenosine↗

PubMed1991

Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms.

In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury. The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects include early hemorrhagic necrosis leading to major infarction at the injury site. These posttraumatic vascular effects can be treated. Systemic normotension can be restored with volume expansion or vasopressors, and spinal cord blood flow can be improved with dopamine, steroids, nimodipine, or volume expansion. The combination of nimodipine and volume expansion improves posttraumatic spinal cord blood flow and spinal cord function measured by evoked potentials. These results provide strong evidence that posttraumatic ischemia is an important secondary mechanism of injury, and that it can be counteracted.

Animals↗