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Biomedical subjects

J Krieger

Publications and source records attributed to J Krieger.

At least 55 records · Page 3Linked to original sources
PubMed1999

Identification of a cyclic nucleotide- and voltage-activated ion channel from insect antennae.

From an antennal cDNA library of Heliothis virescens a clone has been isolated encoding a polypeptide of 678 amino acids. Data base comparisons and primary structure analysis of the deduced protein sequence (HvCNG) indicated significant homology to cyclic nucleotide and voltage-activated ion channels including six putative membrane spanning domains, a putative cyclic nucleotide binding site, a pore region and a voltage-sensor motif. Heterologous expression of the cloned cDNA in Sf9 cells resulted in a polypeptide of the predicted molecular mass. Patch clamp analysis allowed to record the activity of the identified HvCNG channels; they were activated by cAMP but also by hyperpolarization. The channel displayed in potassium solution a conductance of 30 pS; the ion selectivity was calculated as PK/PNa approximately 3. Northern blot analysis revealed that the channel is highly expressed in the antennae; weaker signal were detected in heads and legs. In situ hybridization of tissue sections through the antennae showed a spatial distribution of reactive cells; they are located beneath sensillar hairs. Thus, a novel channel type has been identified which may play an important role in antennal cells.

Amino Acid Sequence↗
PubMed1999

Daytime hypoventilation in obstructive sleep apnoea syndrome.

Chronic alveolar hypoventilation is a classic feature of the "pickwickian syndrome" (i.e. obesity-hypoventilation syndrome) but in fact hypercapnia is observed in a minority of obstructive sleep apnoea syndrome (OSAS) patients. Most recent studies having included large numbers of unselected, consecutive OSAS patients agree on a prevalence of 10-20% of alveolar hypoventilation. The mechanisms of hypercapnia in OSAS are not fully understood but the determining factors of daytime respiratory insufficiency are probably the presence of a marked obesity, leading to the obesity hypoventilation syndrome and, principally, the association of OSAS with chronic obstructive pulmonary disease. This association (the so-called "overlap syndrome") is observed in >10% of OSAS patients. Bronchial obstruction is generally mild to moderate and may be asymptomatic. The severity of the nocturnal events (apnoeas, hypopnoeas) and a (possible) diminished chemosensitivity to hypercapnic and hypoxic stimuli do not appear to be determining factors of hypercapnia. The most important consequence of chronic alveolar hypoventilation is pulmonary hypertension which is only observed in patients with daytime arterial blood gases disturbances, and which can lead to right heart failure. When nasal continuous positive airway pressure fails to correct sleep-related hypoxaemia, supplementary O, must be given or another way of assisted ventilation (BIPAP) must be considered. In the most severe patients (diurnal PaO(2) <55 mmHg) conventional O(2) therapy (>or=16h/24h) is required in addition to nocturnal ventilation.

Journal Article↗
PubMed1999

Therapeutic use of auto-CPAP.

Auto-CPAP is a new technology by which a continuous positive airway pressure (CPAP) device automatically adjusts the level of mask pressure to the patient's requirements. It has been proposed with two different goals: (1) to improve treatment and (2) to perform automatic titration. The improvement of treatment involves two aspects: (a) improving treatment efficacy and (b) improving compliance with treatment. The rationale behind better treatment efficacy is that the patients' requirements vary over both the short and long term. However, there are few data in the literature showing that this is true, let alone concerning its importance and impact. Published studies fail to demonstrate better treatment efficacy with auto-CPAP compared with manually titrated conventional CPAP. The rationale behind improved compliance with treatment is that auto-CPAP should achieve the same treatment efficacy with lower nasal pressures, and thus reduce side effects and improve compliance. Again, the postulate that higher nasal pressures cause lower compliance is not supported. Published studies show variable results both on the level of pressure delivered with an auto-CPAP device (as compared with the optimal pressure used with conventional fixed pressure, but this probably depends on the definition of optimal fixed pressure) and on observed compliance with auto-CPAP. The main problem here is that most studies were not double-blinded which is critical as the end-point (i.e., patient compliance), heavily depends on the relationship between the medical staff and the patient. The aim of titration with auto-CPAP is to save on costs, as patients are treated with fixed conventional CPAP once the titration procedure is accomplished. Auto-titration can be performed either in the sleep laboratory (then the auto-titrating devices can be sophisticated and cumbersome) or in the patients' home. Published studies suggest that auto-titration can be accurately performed, but given the additional cost of the device, the necessity of supervision (albeit a less qualified supervision than with manual titration) and the failure rate, the cost-effectiveness of auto-titration remains to be established.

Journal Article↗
PubMed1999

Prognostic value of lung function and pulmonary haemodynamics in OSA patients treated with CPAP.

The aim of the present study was to determine survival rates of obstructive sleep apnoea patients treated with continuous positive airway pressure (CPAP) and to investigate the prognostic value of pretreatment lung function and pulmonary haemodynamics. Two hundred and ninety-six patients, exhibiting > or = 20 apnoeas plus hypopnoeas per hour of sleep, were included. Patients were treated with nasal CPAP and regularly followed up. The cumulative survival rates were 0.96 (95% confidence interval (CI): 0.94-0.99) at 3 yrs and 0.93 (95% CI: 0.91-0.97) at 5 yrs. Most patients died from cardiovascular disease. Apart from age, covariates associated with a lower survival were the presence of a heavy smoking history, a low vital capacity, a low forced expiratory volume in one second (FEV1) and a high mean pulmonary artery pressure. Only three covariates were included by forward stepwise selection in the multivariate analysis, smoking habit (>30 pack-yrs), age and FEV1. The observed survival rates of the group as a whole were similar to those of the general population matched in terms of age, sex and smoking habit, except for patients between 50 and 60 yrs old who had reduced survival. This difference disappeared when patients of the present study with an associated chronic obstructive pulmonary disease were excluded from the comparison. In conclusion, survival of obstructive sleep apnoea patients treated with nasal continuous positive airway pressure is near to that of the general population. The prognosis is worse in subgroups of patients with a history of heavy smoking and with an associated chronic obstructive pulmonary disease.

Female↗
PubMed1999

In vivo migration and function of transferred HIV-1-specific cytotoxic T cells.

The persistence of HIV replication in infected individuals may reflect an inadequate host HIV-specific CD8+ cytotoxic T lymphocyte (CTL) response. The functional activity of HIV-specific CTLs and the ability of these effector cells to migrate in vivo to sites of infection was directly assessed by expanding autologous HIV-1 Gag-specific CD8+ CTL clones in vitro and adoptively transferring these CTLs to HIV-infected individuals. The transferred CTLs retained lytic function in vivo, accumulated adjacent to HIV-infected cells in lymph nodes and transiently reduced the levels of circulating productively infected CD4+ T cells. These results provide direct evidence that HIV-specific CTLs target sites of HIV replication and mediate antiviral activity, and indicate that the development of immunotherapeutic approaches to sustain a strong CTL response to HIV may be a useful adjunct to treatment of HIV infection.

Adoptive Transfer↗
PubMed1999

Periodic limb movements and obstructive sleep apneas before and after continuous positive airway pressure treatment.

Periodic limb movements during sleep (PLMS) and obstructive sleep apnea syndrome (OSAS) are two common sleep disorders. The similarity in periodicity of periodic limb movements (PLMs) and obstructive sleep apneas (OSAs) led us to hypothesize the existence of a common central generator responsible for the periodicity of both OSAs and PLMs. In order to test this hypothesis, we compared apnea periodicity before continuous positive airway pressure (CPAP) treatment with PLMs periodicity during CPAP treatment in 26 OSA patients, consecutively recorded and treated in our sleep laboratory. The investigation on CPAP was performed twice, once during the initial evaluation and once during a follow-up evaluation after 3 months of home treatment with CPAP. Our results showed that, in this sample, 16 patients out of 26 had an association of OSAS and PLMS, defined as the occurrence of at least 5 PLMs per hour of sleep. The mean apnea interval - measured as the time between the beginning of two successive apneas - was 43.1 s (+/-15.2, SD) and the mean PLM interval - calculated in the same way - was 29.6 s (+/-15.2) during the baseline night, 28.5 s (+/-15.7) during the first CPAP night, and 29.8 s (+/-14.8) during the second CPAP night. Thus, the periodicity of the two phenomena (apneas and PLMs) was different, both before and after CPAP treatment (P< 0.05). When considering the interval between the end of an event (apnea or PLM) and the beginning of the next one the mean apnea interval was 19.5 s (+/-11. 6), and the mean PLM interval was 28.1 s (+/-15.3) during the untreated night, 26.6 s (+/-16) during the first CPAP night and 27.9 s (+/-15) during the second CPAP night. The shortening of apnea intervals with this method of measuring intervals reflects the longer duration of apneas as compared to PLMs. Again the intervals between PLMs were not different between each other but the intervals between apneas were different from the intervals between PLMs (P< 0. 05) These results show that the periodicity of PLMs is different from that of OSAs, suggesting that sleep apneas and PLMs are not generated by a common central generator.

Adult↗
PubMed1999

Actigraphy and leg movements during sleep: a validation study.

A study comparing actigraphy and polysomnography in the detection of leg movements was performed in a group of 35 patients with sleep disorders. Visual scoring used epochs of 5-second duration, and in each epoch, electromyographic activity of tibialis anterior muscle was classified in eight types on the basis of its duration and amplitude. Activity levels of the actigraphic data were logged in 5-second intervals and stored in memory for computer retrieval. To assess the reproducibility of actigraphic detection scoring, in 10 patients actigraphic and polysomnographic data were compared during two consecutive nights. Despite a high correlation between polysomnography and actigraphy in the detection of muscular activity (r = 0.78; P = 0.001), no agreement was obtained between the two analyses according to the Bland and Altman method of concordance (mean bias: -117.5). The greater agreement was found for electromyographic activity lasting more than 3 seconds and with an amplitude of more than 50 microV. In the group of patients examined during two consecutive nights the scoring error did not differ significantly. The results demonstrated that (1) despite a significant correlation between actigraphic and polysomnographic data, actigraphy substantially underestimated leg electromyographic activity and therefore could not be used routinely for diagnostic purposes; and (2) because error scoring did not undergo significant changes across the two nights, actigraphy may be used for follow-up evaluation.

Adult↗
PubMed1999

Pharyngeal critical pressure in patients with obstructive sleep apnea syndrome. Clinical implications.

Current evidence suggests that patients with obstructive sleep apnea (OSA) may have greater pharyngeal critical pressure (Pcrit), which reflects the increase in upper airway collapsibility. The contribution of Pcrit to the severity of OSA and to the efficacious continuous positive pressure (nCPAPeff) therapy has never been extensively described and no data are available about the interaction of Pcrit, age, and anthropometric variables. To determine the relationship between Pcrit, severity of the disease, nCPAPeff, and anthropometric variables we measured Pcrit in a group of 106 patients with OSA. Pharyngeal critical pressure was derived from the relationship between maximal inspiratory flow and nasal pressure, Pcrit representing the extrapolated pressure at zero flow. Upper airway resistance (Rus) was determined as the reciprocal of the slope (DeltaPn/DeltaVImax cm H2O/L/s) in the regression equation. In a subgroup of 68 patients, during the diagnostic night, we measured as indices of respiratory effort, the maximal inspiratory esophageal pressure (Pes) at the end of apnea (Pesmax), the overall increase from the minimum to the maximum (DeltaPes), and the rate of increase of Pes during apnea (RPes). As a group, the mean Pcrit was 2.09 +/- 0.1 cm H2O (range, 0 to 4.5) and the mean Rus was 11.1 +/- 0.5 cm H2O/L/s. Although men have greater Pcrit, pharyngeal collapsibility was influenced neither by neck size nor by body mass index (BMI). Although there was a significant relationship between Pcrit and apnea plus hypopnea index (AHI) (r = 0.23, p = 0.02), neck circumference was the stronger predictor of apnea frequency, with Pcrit contributing only to the 3% of the variance. In the group of patients as a whole, a model including AHI, BMI, Rus, and Pcrit explained the 36% of the variance in nCPAPeff, with a greater contribution of AHI, Pcrit accounting for only 3% of the variation. In patients for whom the measure of respiratory effort was obtained, 42% of the variance in nCPAPeff was explained by RPes (33%) and BMI. From these results we conclude that Pcrit alone does not yield a diagnostically accurate estimation of OSA severity and nCPAPeff. Although individual collapsibility may predispose to pharyngeal collapse, upper airway occlusion may require the combination of several factors, including obesity, upper airway structure, and abnormalities in muscle control.

Anthropometry↗
PubMed1999

Effective compliance during the first 3 months of continuous positive airway pressure. A European prospective study of 121 patients.

Effective compliance (time spent at the effective pressure) with nasal CPAP in obstructive sleep apnea has been reported to be poor. The aim of our study was to evaluate effective compliance in a large European multicenter study. One hundred twenty-one consecutive newly treated patients (initial apnea-hypopnea index [AHI] = 62.0 +/- 29. 5/h, AHI under CPAP = 6.4 +/- 8.1/h, CPAP pressure = 8.7 +/- 2.6 cm H(2)O, BMI = 33.1 +/- 6.8 kg/m(2)) were randomly allocated to a group with (MC(+)) (n = 58) or without (MC(-)) (n = 63) a control unit measuring effective compliance at 1, 2, and 3 mo, which was compared with the built-in time counter data. MC(+) data were 94 +/- 10, 98 +/- 5, and 96 +/- 9% of counter data at 1, 2, and 3 mo, respectively. Using criteria of regular use already reported in the literature (at least 4 h of nCPAP per day of use and nCPAP administered more than 70% of the days) we found 77, 82, and 79% compliant patients at 1, 2, and 3 mo, respectively, 79% of the patients meeting these criteria each month. Although there were no pulmonary functions or polysomnographic differences between the two subgroups, the compliant patients did report a greater improvement in minor symptoms. We found a close correlation between effective use of CPAP and the machine run time. The main result of our study was a higher effective compliance than previously reported, approximately 80% of the patients being regular users versus 46% in a previously published study. This may result from different technical and medical follow-up.

Female↗
PubMed1999

Linking community-based blood pressure measurement to clinical care: a randomized controlled trial of outreach and tracking by community health workers.

OBJECTIVES: This study assessed the effectiveness of enhanced tracking and follow-up services provided by community health workers in promoting medical follow-up of persons whose elevated blood pressures were detected during blood pressure measurement at urban community sites. METHODS: In a randomized controlled trial, 421 participants received either enhanced or usual referrals to care. Participants were 18 years or older, were either Black or White, and had blood pressure greater than or equal to 140/90 mm Hg and income equal to or less than 200% of poverty. The primary outcome measure was completion of a medical follow-up visit within 90 days of referral. RESULTS: The enhanced intervention increased follow-up by 39.4% (95% confidence interval [CI] = 14%, 71%; P = .001) relative to usual care. Follow-up visits were completed by 65.1% of participants in the intervention group, compared with 46.7% of those in the usual-care group. The number needed to treat was 5 clients (95% CI = 3, 13) per additional follow-up visit realized. CONCLUSIONS: Enhanced tracking and outreach increased the proportion of persons with elevated blood pressure detected during community measurement who followed up with medical care.

Adolescent↗
PubMed1999

Prostatitis unplugged? Prostatic massage revisited.

Repetitive prostatic massage is not a new tool in the urologists' armatarium. Once the most popular therapeutic maneuver used to treat prostatitis, it was abandoned as primary therapy almost 3 decades ago. Based on experience reported outside North America and anecdotal experiences of some patients and their physicians, it may be making a comeback. Unfortunately, there are almost no prospective data that would substantiate a claim as to its effectiveness. This article discusses the historic aspects of prostatic massage, suggests possible mechanisms of action, and describes the opinions of North American urologists who are associated with academic clinical research centers and are universally acknowledged as experts in the diagnosis and treatment of prostatitis. At this time, the science of prostatic massage must rely on anecdotal experiences, small, uncontrolled studies, and perhaps somewhat biased opinions of the major thought leaders in the field of chronic prostatitis/chronic pelvic pain syndrome.

Chronic Disease↗
PubMed1998

Expression and functional analysis of olfactory receptors.

The olfactory system recognizes and discriminates myriads of odorants of diverse molecular structure. This task is supposed to be accomplished by a large array of seven-transmembrane domain receptors encoded by a multigene family. Although circumstantial evidence suggests that the identified genes encode odorant receptors, unequivocal proof requires demonstration that the resulting proteins should be able to interact with odorous molecules and couple via G proteins onto second messenger cascades. This goal can be achieved by heterologous expression of receptor proteins in surrogate eucaryotic cells, although the task is complicated by the diversity of putative odorous ligands and the large size of the receptor family. Employing the baculovirus/Sf9 cell system it was found that receptor proteins can be expressed at high levels. Stimulating receptor-expressing Sf9 cells with a mixture of numerous odorous compounds elicited a significant and dose-dependent second messenger response, which was never observed in control cells. Assaying a large panel of odorous compounds, including representatives of different odor classes and compounds of different chemical classes revealed that distinct receptor subtypes respond to certain odorants but not to others. Graded responses to only a subset of odorants indicate that the heterologous expressed receptor types have a selective but relatively broad ligand specificity. The easily manipulated bacterial system was employed to produce olfactory receptor proteins in large quantities. It was solubilized from inclusion bodies and upon reconstitution in liposomes displayed specific interaction with odor ligands.

Animals↗
PubMed1998

[Hypersomnia. Investigational strategy for evaluating hypersomnia].

CLINIC AND HISTORY: Expression of hypersomnia can take on several forms: long period of nocturnal sleep, excessive diurnal somnolence or both. History taking is essential. Useful tools include standardized questionnaires and a diary of sleeping habits. Not only do they provide evidence of the hypersomnia, but also information on possible eccentric origin(s). A pathological hypothesis can then be put forward: sleep apnea syndrome, narcolepsy, idiopathic hypersomnia, or periodic movements during sleep. POLYGRAPHY: Different recording protocols have been designed to determine sleep patterns, often depending on the clinical setting. The goal is to obtain an objective confirmation of hypersomnia and demonstrate a cause. The type of recording (hour and duration of the recording, parameters monitored) depends on the information desired. Because captors themselves sometimes perturb sleep, polygraphic explorations must be adapted to each individual situation.

Diagnosis, Differential↗
PubMed1998

Subtypes of odorant-binding proteins--heterologous expression and ligand binding.

Odorant-binding proteins (OBP) in the mucus of the olfactory epithelium are thought to transfer the hydrophobic odorous compounds through the aqueous barrier towards the chemo-sensory cells. To evaluate their binding properties, two distinct OBP subtypes of the rat were expressed as N-terminal His-tagged fusion proteins in Escherichia coli, thus allowing an efficient purification. Based on gel chromatography and CD spectroscopy analysis the recombinant OBP subtypes seem to share several structural features with other members of the lipocalin family. Approaches to elucidate whether heterologous expressed OBPs interact with odorous compounds revealed that OBP1 specifically binds 2-[3H]-isobutyl-3-methoxypyrazine whereas OBP2 did not shown any specific binding to this compound. In contrast, the chromophore 1-anilinonaphthalene 8-sulfonic acid (1,8-ANS) specifically interacted with OBP2 but not with OBP1. Displacement experiments monitored by the relative fluorescence intensity revealed that fatty acids with appropriate chain length act as efficient competitors. Some odorous compounds, notably lilial (p-tert-butyl-alpha-methyl dihydrocinnamic aldehyde) and citralva (3,7-dimethyl-2,6-octadienenitrile), also displaced efficiently the chromophore, whereas pyrazine derivatives including 2-isobutyl-3-methoxypyrazine and other odorants did not. These results indicate that rat OBPs have distinct ligand specificities.

Anilino Naphthalenesulfonates↗
PubMed1998

Cloning and expression of odorant-binding proteins Ia and Ib from mouse nasal tissue.

We had previously reported the purification and partial characterisation of four distinct odorant-binding proteins from male mouse nasal epithelium. One of these, named OBP-I appeared to be a heterodimer, whose subunits, Ia and Ib showed significant similarity in their N-terminal amino acid sequences with hamster aphrodisin. In this paper, we report the complete amino acid sequences of these two polypeptide chains, as deduced from nucleotide sequences of their relative cDNA. These data confirm the high similarity of both proteins with hamster aphrodisin. A comparison with the sequences of other known OBPs indicate that they are more closely related to members of class I, including bovine OBP, rat OBP-I and pig OBP-I. A putative odorant-binding site is indicated by the presence of amino acid residues conserved with respect to the bovine protein, whose three-dimensional structure has been recently resolved. In-situ hybridisation has revealed identical expression patterns for the two proteins, further supporting the heterodimeric structure of these proteins in the nasal mucus.

Amino Acid Sequence↗