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PubMed2002

Individualizing insulin management. Three practical cases, rules for regimen adjustment.

Many patients with diabetes become frustrated by the tedium of inflexible insulin instructions and unpalatable dietary restrictions. They lose confidence when their blood glucose levels fluctuate widely, and they may begin to think of themselves as "bad diabetics." Therefore, choosing the appropriate insulin and injection regimen for each patient is essential. Coordinated efforts by a concerned team of diabetes educators, dietitians, and physicians enhance the effectiveness of treatment. Patients should be taught how to count carbohydrates, select foods with a low glycemic index, and adjust their insulin regimen by using sliding scales based on the 1500 or 1800 rule. Regular exercise and solid emotional support from family and friends also are helpful. By teaching patients the rules for insulin management, physicians can empower them to be much more actively involved in their own care and to lead healthier lives.

Blood Glucose↗
PubMed1976

Studies on the biodegradation of nonionic surfactants applied in the polyester fiber industry. II. Effect of activated sludge load on microorganisms.

The effect of selected nonionic surfactants Cirrasol FP, Cirrasol SF 200 and Cirrasol TCS on activated sludge organisms purifying wastes from the polyestre fibre industry was studied. The toxic effect of the mentioned surfactants towards bacteria, protozoa, rotifera and nematoda occurred at loads exceeding 0.32 mg surfactant/mg d.w./day and in periods of large fluctuations of the employed loads. Morphological changes of activated sludge flocs are also observed in similar conditions.

Adaptation, Physiological↗
PubMed2001

Distortion-product otoacoustic emissions and glycerol testing in endolymphatic hydrops.

OBJECTIVES/HYPOTHESIS: Aural fullness is a frequent symptom of endolymphatic hydrops. Its evaluation may provide valuable information on the initial stage of development of endolymphatic hydrops. STUDY DESIGN: The present investigation was specifically designed to ascertain the ability of the glycerol test, combined with pure tone audiometry and distortion product otoacoustic emissions (DPOAEs) testing, to diagnose endolymphatic hydrops early and to identify patients who may evolve toward Meniere's disease. For these purposes, patients who complained about aural fullness as their only audiologic symptom were selected. METHODS: This investigation consisted of 19 consecutive patients with unilateral or bilateral aural fullness who received no treatment. Each patient underwent glycerol testing measured with conventional pure tone audiometry and with both DPOAEs. For the traditional pure-tone glycerol test, a hearing improvement of at least 10 dB, at the lower two or three frequencies (125, 250, and 500 Hz), was judged as a positive result. For the DPOAE glycerol test, a smaller positive difference (5 dB) for at least three frequencies was interpreted as an ameliorative fluctuation. RESULTS: The outcomes of the glycerol tests (24 ears examined) showed variable patterns. Seven ears showed no significant changes of either the pure-tone audiogram or DPOAE. In seven other ears, the comparison of the traditional glycerol test and the DPOAE glycerol test indicated an improvement in both measures. Another seven ears showed negative glycerol tests, whereas DPOAE responses gradually recovered reaching levels significantly higher than those recorded before glycerol administration. The three remaining ears showed contrasting results. CONCLUSIONS: Patients with aural fullness in the absence of other associated symptoms may potentially be in the initial stages of Meniere's disease. This notion is confirmed by the present findings showing a high rate (58%) of positive glycerol tests in the selected patients. The importance of DPOAE testing is supported by their ability to detect minimal dysfunction, possibly representing endolymphatic hydrops that goes undetected by routine pure-tone audiometry.

Adult↗
PubMed2003

Model assessment and model building in fMRI.

Model quality is rarely assessed in fMRI data analyses and less often reported. This may have contributed to several shortcomings in the current fMRI data analyses, including: (1) Model mis-specification, leading to incorrect inference about the activation-maps, SPM[t] and SPM[F]; (2) Improper model selection based on the number of activated voxels, rather than on model quality; (3) Under-utilization of systematic model building, resulting in the common but suboptimal practice of using only a single, pre-specified, usually over-simplified model; (4) Spatially homogenous modeling, neglecting the spatial heterogeneity of fMRI signal fluctuations; and (5) Lack of standards for formal model comparison, contributing to the high variability of fMRI results across studies and centers. To overcome these shortcomings, it is essential to assess and report the quality of the models used in the analysis. In this study, we applied images of the Durbin-Watson statistic (DW-map) and the coefficient of multiple determination (R(2)-map) as complementary tools to assess the validity as well as goodness of fit, i.e., quality, of models in fMRI data analysis. Higher quality models were built upon reduced models using classic model building. While inclusion of an appropriate variable in the model improved the quality of the model, inclusion of an inappropriate variable, i.e., model mis-specification, adversely affected it. Higher quality models, however, occasionally decreased the number of activated voxels, whereas lower quality or inappropriate models occasionally increased the number of activated voxels, indicating that the conventional approach to fMRI data analysis may yield sub-optimal or incorrect results. We propose that model quality maps become part of a broader package of maps for quality assessment in fMRI, facilitating validation, optimization, and standardization of fMRI result across studies and centers. Hum. Brain Mapping 20:227-238, 2003.

Brain↗
PubMed1986

The sensitivity of liquid sensor, ion-selective microelectrodes to changes in temperature and solution level.

Current procedures for the manufacture of ion-selective microelectrodes using liquid ion sensors result in two kinds of electrode, one with a short (10-100 micron) column of sensor at the tip and one with a long column (greater than 1 mm). We report here that the signal from a long-column microelectrode is very sensitive to small fluctuations in bath temperature and solution level when a recording is made above room temperature. This sensitivity is explained by the effects of temperature on the potentials developed at the interfaces between the ion sensor and the bordering aqueous solutions (the internal filling solution of the electrode and the test solution). If the temperature at the two interfaces is changed by different amounts, these interfacial potentials will also change by different amounts resulting in a change in the output of the electrode. Such an effect occurs for long-column electrodes because the column of sensor is usually not completely immersed in the heated test solution. Hence fluctuations in solution temperature and level will induce fluctuations in temperature along the column of sensor producing variations in the electrical signal from the electrode. In contrast, sensitivity to temperature and solution level is virtually absent in short-column microelectrodes since their column of sensor is fully immersed in the test solution and thereby at uniform temperature. In conclusion, in order to produce noise-free recordings of ion activities, the use of short-column microelectrodes is recommended for experiments performed above (or below) room temperature.

Electrophysiology↗
PubMed1987

Kinetics of drug metabolism inhibition: use of metabolite concentration-time profiles.

A simple model simulating the kinetics of drug metabolism inhibition interaction is investigated. The relative sensitivity of drug and metabolite concentration-time profiles as indices of inhibition is assessed. Under steady-state conditions where inhibitor concentrations are maintained constant, the determination of metabolite in addition to drug kinetics provides little additional information when inhibition is nonselective in nature. However metabolite profiles do offer increased sensitivity when parallel routes of metabolism exist and there is selectivity of inhibitory action. Non-steady-state conditions are also investigated as they often apply in inhibition studies; the inhibitor is often administered as a single dose or as a multiple dosing regimen rather than by a constant rate intravenous infusion. Under the former conditions, when inhibitor concentrations in the body fluctuate during the study, metabolite kinetics can be more useful than drug kinetics. The changes evident in the metabolite concentration-time profiles are substantial due to both the inhibition per se and the nonlinearity in the system arising from inhibitor elimination. It is concluded that metabolite kinetics provide a useful aid in the detection of drug metabolism inhibition interactions.

Drug Interactions↗
PubMed1992

Balbiani ring 1 gene in Chironomus tentans. Sequence organization and dynamics of a coding minisatellite.

Balbiani ring (BR) genes in diptera encode large secretory proteins and are classical model systems for studies of gene expression. In Chironomus tentans, four closely related BR genes, BR 1, BR 2.1, BR 2.2 and BR 6 form a gene family. The BR genes have been partially characterized and are known to contain long arrays of tandemly arranged repeat units with an hierarchical repeat organization. Here, we report the sequence organization of the complete transcribed part of the BR 1 gene in C. tentans. The gene contains five exons and four introns. Three of the introns are located at the 5' end and the fourth at the 3' end of the gene. Exon 4 is approximately 35,000 bases long and is built completely from tandemly organized repeats. We show that this long repeat block contains two types of related repeat units, beta and gamma. Each type forms a large uninterrupted array, a 5' beta array and a 3' gamma array with a sharp border between them. In the hierarchical repeat structure in each repeat array, all repeats are virtually identical at one level of repetition, but shown differences at the next level. The whole repeat block in the BR 1 gene fluctuates in size between different alleles, but not by more than 10%. In contrast, within the block, the beta and gamma arrays vary in length between 8000 and 29,000 bases in an inverse fashion, together keeping the overall length requirement. We propose that the length of exon 4 is conserved by selection of cross-over products of a given length, and that the internal hierarchical sequence organization in the BR 1 gene is a consequence of the combined action of several different sequence turnover mechanisms, all dependent on the unequal pairing of homologous sequences at different, competing levels of repetition.

Amino Acid Sequence↗
PubMed1986

Placental essential fatty acid transport and prostaglandin synthesis.

The studies reported here demonstrate two important aspects of placenta EFA transport and metabolism. (1) A mechanism exists within the placenta for the selective incorporation of 20:4 omega 6 into phosphoglycerides and the export of those phosphoglycerides to the fetal circulation. This mechanism allows the selective sequestering of 20:4 omega 6 in the fetoplacental unit and may provide the fetus with important performed structural membrane components. (2) Placental PG synthesis is directed mostly to the maternal circulation and stimulated placental PG synthesis is directed totally to the maternal circulation. This mechanism may protect the fetus from fluctuations in maternal and placental PG synthesis and may direct stimulated placental PG synthesis to a target organ, the myometrium. The perfused human placental model provides a valuable method for the study of a variety of biochemical phenomena in a whole human organ and its use may further elucidate the role of this tissue in the maintenance of pregnancy, the transport of EFA to the developing fetus and the involvement of placental PG synthesis in fetal development and parturition.

Biological Transport↗
PubMed2002

[Diffuse hair loss in women].

The complaint "Doctor, I am losing my hair" represents a particular challenge to the physician, and involves making a specific diagnosis, selecting an appropriate therapy, and expressing empathy for the patient's anxiety. Diffuse hair loss in women was formerly classified as an entity of its own. Since the identification of female pattern hair loss, most cases have been recognized to be due to androgenetic alopecia, often during phases of life characterized by fluctuations of sexual hormone levels or in connection with intake or cessation of hormonal therapy. The most difficult differential diagnosis includes androgenetic alopecia, chronic telogen effluvium, and psychogenic pseudo efflvuium. Androgenetic alopecia is due to androgen-induced, non-synchronized, progressive shortening of the hair growth cycle and gradually leads to thinning of the central scalp area. Idiopathic chronic telogen effluvium typically occurs in women, starting abruptly without a recognizable initiating factor, and involves the entire scalp area with increased shedding of telogen hair. It is believed to be due to synchronization phenomena of the cyclic hair growth. Psychogenic pseudo effluvium affects fashion-oriented, self-conscious women suffering of a discrepancy between the actual state of their hair and idealized expectations. Later the problem of age-related hair thinning oft becomes a surrogate for the more generalized problem of senescence. Rational therapy of androgenetic alopecia aims at blocking the androgen effect on hair follicles with estrogens and antiandrogens or at pharmacologically reversing vellus hair transformation with topical minoxidil. In contrast, women with idiopathic chronic telogen effluvium should be reassured that their problem is rather a state of exaggerated "hair shedding" than of actual "hair loss".

Adult↗
PubMed2005

Conduction through the inward rectifier potassium channel, Kir2.1, is increased by negatively charged extracellular residues.

Ion channel conductance can be influenced by electrostatic effects originating from fixed "surface" charges that are remote from the selectivity filter. To explore whether surface charges contribute to the conductance properties of Kir2.1 channels, unitary conductance was measured in cell-attached recordings of Chinese hamster ovary (CHO) cells transfected with Kir2.1 channels over a range of K+ activities (4.6-293.5 mM) using single-channel measurements as well as nonstationary fluctuation analysis for low K+ activities. K+ ion concentrations were shown to equilibrate across the cell membrane in our studies using the voltage-sensitive dye DiBAC4(5). The dependence of gamma on the K+ activity (a(K)) was fit well by a modified Langmuir binding isotherm, with a nonzero intercept as a(K) approaches 0 mM, suggesting electrostatic surface charge effects. Following the addition of 100 mM N-methyl-D-glucamine (NMG+), a nonpermeant, nonblocking cation or following pretreatment with 50 mM trimethyloxonium (TMO), a carboxylic acid esterifying agent, the gamma-a(K) relationship did not show nonzero intercepts, suggesting the presence of surface charges formed by glutamate or aspartate residues. Consistent with surface charges in Kir2.1 channels, the rates of current decay induced by Ba2+ block were slowed with the addition of NMG or TMO. Using a molecular model of Kir2.1 channels, three candidate negatively charged residues were identified near the extracellular mouth of the pore and mutated to cysteine (E125C, D152C, and E153C). E153C channels, but not E125C or D152C channels, showed hyperbolic gamma-a(K) relationships going through the origin. Moreover, the addition of MTSES to restore the negative charges in E53C channels reestablished wild-type conductance properties. Our results demonstrate that E153 contributes to the conductance properties of Kir2.1 channels by acting as a surface charge.

Animals↗
PubMed1987

Parkinson's disease. Cognitive changes in relation to treatment response.

Four groups of patients with Parkinson's disease matched for age, education and IQ were categorized by response to treatment and compared with a normal control group. The patient groups were (1) No Treatment (de novo); (2) Good Response (including minor fluctuations in symptoms); (3) Fluctuations (significant, including 'on-off' phenomena) and/or marked Abnormal Involuntary Movements (dyskinesias); and (4) Poor Response ('secondary treatment failure' characterized by significant deterioration over time in all major symptoms). As a previous investigation had established that neuropsychological tests thought to be sensitive to the functional integrity of the frontal lobes are selectively impaired in Parkinson's disease, the first phase of this study compared the five groups on five such tests and two tests of psychomotor ability. While all patient groups displayed deficits on the psychomotor tests and on several tests associated with frontal lobe function compared with normals, only the Poor Response group was impaired on all tasks. In a second phase, comprehensive testing of additional cognitive processes such as attention, mnemonic, and visuospatial functions, the latter two traditionally thought to depend primarily on posterior cortical regions, revealed no significant cognitive deficits in any patient group. Results are discussed with respect to the involvement of the nigrostriatal and mesocortical dopaminergic systems.

Aged↗
PubMed2001

Apomorphine in the treatment of Parkinson's disease.

Apomorphine is a potent, nonselective, direct-acting dopamine-receptor agonist. Given subcutaneously, it has a rapid onset of antiparkinsonian action qualitatively comparable to that of levodopa. Despite its long history, it was not until peripheral dopaminergic side effects could be controlled by oral domperidone that the clinical usefulness of apomorphine in Parkinson's disease began to be investigated thoroughly in the mid-1980s. Although several routes have been tried, subcutaneous administration, either as intermittent injections or continuous infusion, is so far the best and most applied in the treatment of advanced, fluctuating Parkinson's disease. Clinical trials have shown stable efficacy with markedly reduced time spent in "off" phases as well as, for infusion therapy, reduced levodopa requirements. In the most successful cases, motor fluctuations disappear and the need for oral medication is eliminated. Adverse events are usually mild and dominated by cutaneous reactions. Neuropsychiatric side effects occur, but the influence of apomorphine on these remains controversial. Controlled long-term clinical trials are highly warranted to reveal the full potentials of this treatment. Careful patient selection and follow-up, where the specialized movement disorder nurse has a crucial role, are paramount for a successful long-term outcome. Apomorphine warrants a wider application in the treatment of advanced Parkinson's disease and should be tried before more invasive interventions are considered.

Antiparkinson Agents↗
PubMed1994

Fluctuating asymmetry in gorilla canines: a sensitive indicator of environmental stress.

Populations of the western lowland gorilla (Gorilla gorilla gorilla) have decreased markedly as a result of human encroachment. The species is therefore likely to have been exposed to substantial environmental stress. Fluctuating asymmetry (FA) is one measure of environmental stress. We examined the expression of FA in the canines and second premolars of the upper jaw of western lowland gorillas. The canines had patterns of FA typical of secondary sexual characters, whereas the expression of premolar FA was typical of non-sexually selected traits. We found that FA in male canines was positively correlated with year of collection (YOC) or year of collection and acquisition (YOCA) of the specimen. This suggested a sustained environmental deterioration. However, there was no relation between FA and YOC, or FA and YOCA, in female canines. There was a correlation between FA and YOC in male premolars, but this was relatively weak and disappeared when FA and YOCA were considered. There was no correlation between FA and YOC or YOCA in the premolars of females. We conclude that these patterns of FA support the argument that sexually selected structures are sensitive to environmental stress but non-sexually selected structures are not.

Animals↗
PubMed1990

The interplay of population dynamics and the evolutionary process.

Long-term maintenance of genetic diversity is affected by ecological forces that are driven in turn by current levels of genetic variation. The strength of population regulation and the consequent patterns of population fluctuations determine the likelihood of genetic changes considered pivotal for rapid speciation. However, genetic diversity in the susceptibility to regulatory forces can reduce the magnitude of such fluctuations and minimize the likelihood of genetic revolutions. A group of populations that experiences local extinctions and recolonizations may hold lower levels of genetic diversity than in the absence of such extinctions, but local adaption, which provides enhanced genetic diversity, can reduce the likelihood of local extinctions. Tightly regulated populations experience different selection pressures than poorly regulated populations, although tighter regulation itself can evolve. When genotypic variation affects the outcome of interspecific interactions on a local scale, this effect, coupled with appropriate spatial variation, can enhance the resilience of the interactive system.

Animals↗
PubMed1996

Effect of phenylethanolamine N-methyltransferase inhibitor, CGS19281A, on the alpha-2-adrenoceptor function in the hypothalamus of rats in comparison with SKF29661, SKF64139 and yohimbine.

CGS19281A, a phenylethanolamine N-methyltransferase (PNMT) inhibitor, is reported not to inhibit alpha-2-adrenoceptor activity, in vitro. Effects of CGS19281A on the hypothalamic alpha-2-adrenoceptor function were studied in vivo in male Wistar rats. Agents used as controls were SKF29661, which is a selective peripheral PNMT inhibitor, SKF64139, a PNMT inhibitor that inhibits equally both alpha-2-adrenoceptor activity and PNMT, and yohimbine, an alpha-2-adrenoceptor inhibitor that does not inhibit PNMT. Following the administration of PNMT inhibitors, hypothalamic 3-methoxy 4-hydroxy phenylglycol (MHPG) was measured during micro brain dialysis to observe its fluctuations. Effects of PNMT inhibitors on growth hormone (GH) secretion caused by clonidine were examined in order to assess the effects of PNMT inhibitors on postsynaptic alpha-2-adrenoceptors in the hypothalamus. Neither saline nor the peripherally active PNMT inhibitor SKF29661 (50 mg/kg) increased hypothalamic MHPG. Both SKF64139 (50 mg/kg) and yohimbine (5 mg/kg) increased MHPG significantly when compared with SKF29661. There was no significant increase in MHPG after the administration of CGS19281A (20 mg/kg). Blood GH increased 30 min after clonidine was administered. While CGS19281A (20 mg/kg), SKF64139 (50 mg/kg) and yohimbine (5 mg/kg) inhibited GH secretion, the peripherally active PNMT inhibitor SKF29661 (50 mg/kg) did not. These results suggest that CGS19281A has an in vivo inhibitory effect on the clonidine induced GH secretion. This may be due to inhibition of adrenaline synthesis by this agent.

Animals↗
PubMed2001

Taciturn patients in health counseling at a hospital: passive recipients or active participators?

This study explored patients' taciturnity as observed on videotape during hospital health counseling situations with a nurse. Health counseling sessions, 38 in number, were videotaped, transcribed verbatim, and analyzed by using an adaptation of conversation analysis. The data analysis included information on 18 selected patients who spoke little and did not introduce new topics, but rather supported the discussion on the theme chosen by the nurse. When we examined nurses' and patients' speech word by word, we discovered four participation frames that produced taciturnity: in the hands of professionals, compliant, guilty, and polite. These could fluctuate during interaction. The findings indicate that there is a need for a more extensive description of taciturn, or silent, patients. What has been interpreted as passivity in the literature can be interpreted more constructively. This insight can be useful for developing health counseling practice in hospitals.

Adolescent↗
PubMed2000

Meniere's disease.

Meniere's disease is an idiopathic disorder of the inner ear characterized by the syndrome of endolymphatic hydrops, episodic vertigo, fluctuating hearing loss, tinnitus, and aural fullness. People with this disorder may be severely disabled. Medical therapy exists in the form of diuretics and dietary restriction of salt to minimize the fluid pressure in the labyrinth and cochlea. Treatment of allergies with desensitization and steroids has also shown to be effective in selected patients. Surgical therapies exist in two categories, conservative and ablative. Endolymphatic sac decompression with or without shunt placement remains highly effective and we feel that it should be the first line surgical therapy for patients who fail medical therapy. Ablative therapies include labyrinthectomy (medical or surgical) and vestibular neurectomy. Both of these procedures control the episodic vertigo by destroying vestibular function in the affected ear and should be reserved for patients who have persistent vertigo in spite of more conservative treatments.

Disease Progression↗
PubMed2000

[Physicochemical and biological characterization of the water quality in the Piedras Blancas basin, Antioquia, Colombia] [In Process Citation]

From April to December 1996 a limnological study was carried out in 17 streams near Medellin, in order to stablish their water quality. The area is located in Piedras Blancas Park (6 degrees 8' 20"N, 75 degrees 30' 20"W) SE of Medellin at 2,400 m altitude. Three sampling periods, encompasing wet and dry season were selected: April-May, August-September and October-December. For qualitative collection methods hand screen and D-net were used. Each station was intensively sampled to collect most macroinvertebrates in all types of habitat. The area sampled in each station was 6 m2. Physicochemical variables in general showed small fluctuations along the study; only conductivity and total dissolved solids exhibited significant changes, all related with high precipitation in the wet season. Macroinvertebrate community consisted of 113 genera, 63 families and seven phyla. Trichoptera was the most abundant group. The results indicate that the freshwater ecosystems in the study area present a high water quality corresponding to a oligo-mesotrophic system.

Journal Article↗