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Biomedical subjects

J Carlson

Publications and source records attributed to J Carlson.

At least 91 records · Page 5Linked to original sources

Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea.

Pharmacologic enhancement of serotonergic transmission by serotonin uptake inhibition has been suggested as one approach to improve upper-airway patency and thus nocturnal breathing in patients with obstructive sleep apnea (OSA). To test this hypothesis, we performed a double-blind, randomized, placebo-controlled crossover study testing the effect of paroxetine (20 mg od) on polysomnographic and psychopathologic outcomes in 20 male OSA patients (mean age 52.1 years, mean BMI 28.7 kg/m2, mean oxygen desaturation index on a previous screening 25.4/hour). The two treatment periods of 6 weeks and the separating washout period of 4 weeks were completed by 17 patients. Paroxetine reduced the apnea index during NREM sleep (-35%, p = 0.003), but not during REM sleep. No significant effect on hypopnea indices was found. With the exception of a previously described REM-postponing effect (p = 0.05), sleep architecture was not significantly influenced by paroxetine. Similarly, the effect of paroxetine on apnea was not associated with a significant overall alleviation of psychopathologic symptoms as rated on the Comprehensive Psychopathological Rating Scale or OSA-related daytime complaints assessed by visual analog scales. We conclude that enhanced serotonergic transmission improves breathing during NREM sleep in OSA. This effect is poorly related to effects on sleep architecture or daytime symptoms.

Adult↗

Plasmodium falciparum: molecular background to strain-specific rosette disruption by glycosaminoglycans and sulfated glycoconjugates.

Rosetting, the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes, is a virulent parasite phenotype associated with the occurrence of severe malaria, e.g., cerebral malaria. Compounds with specific anti-rosetting activity are potential therapeutic agents. Glycosaminoglycans and sulfated glycoconjugates were found to disrupt rosettes in a strain- and isolate-specific manner. Rosette disruption was strongly connected to the presence of N-sulfate groups in heparin/heparan sulfate as demonstrated by modified heparin preparations. This finding was corroborated by the disruption of rosettes with mono- and disaccharides derived from heparin/heparan sulfate that contained N-sulfated glucosamine. Furthermore, heparinase III treatment of erythrocyte cultures infected by FCR3S1 (and to some extent TM 284) P. falciparum strains abolished rosetting. Heparinase III treatment of the uninfected erythrocytes prior to mixing with the infected culture impeded formation of rosettes, indicating that the rosetting receptors at least partially are of glycosaminoglycan nature.

Animals↗

Rouleaux-forming serum proteins are involved in the rosetting of Plasmodium falciparum-infected erythrocytes.

Excessive sequestration of Plasmodium falciparum-infected (pRBC) and uninfected erythrocytes (RBC) in the microvasculature, cytoadherence, and rosetting, have been suggested to be correlated with the development of cerebral malaria. P. falciparum erythrocyte membrane protein-1 (PfEMP1) is the parasite-derived adhesin which mediates rosetting. Herein we show that serum proteins are crucial for the rosette formation of four strains of parasites (FCR3S1, TM284, TM180, and R29), whereas the rosettes of a fifth strain (DD2) are serum independent. Some parasites, e.g., FCR3S1, can be depleted of all rosettes by washes in heparin and Na citrate and none of the rosettes remain when the parasite is grown in foetal calf serum or ALBUMAX. Rosettes of other parasites are less sensitive; e.g., 20% of TM180 and R29 and 70% of TM284 rosettes still prevail after cultivation. A serum fraction generated by ion-exchange chromatography and poly-ethylene-glycol precipitation restored 50% of FCR3S1 and approx 40 to 100% of TM180 rosettes. In FCR3S1, antibodies to fibrinogen reverted the effect of the serum fraction and stained fibrinogen bound to the pRBC surface in transmission electron microscopy. Normal, nonimmune IgM and/or IgG was also found attached to the pRBC of the four serum-dependent strains as seen by surface immunofluorescens. Our results suggest that serum proteins, known to participate in rouleaux formation of normal erythrocytes, produce stable rosettes in conjunction with the recently identified parasite-derived rosetting ligand PfEMP1.

Animals↗

The nurse parent support tool.

This report describes the development of an instrument, the Nurse-Parent Support Tool (NPST) designed to measure parents' perception of nursing support during their child's hospitalization. The NPST was based on the Nurse Parent Support Model developed from House's conceptualizations of four domains of support. Thus, the 21-item NPST assesses four dimensions of support: (1) supportive communication and provision of information related to the child's illness, treatments, care, and related issues; (2) parental esteem support focused on respecting, enhancing, and supporting the parental role; (3) emotional support to help the parents cope with their own emotional responses and needs related to the child's illness; and (4) caregiving support involving the quality of care provided to the child. Strong support for the content validity of the NPST derives from the steps used in constructing the instrument. This includes use of a conceptual framework, generating items from the literature, using data from interviews with parents of hospitalized children, and pilot testing with parents and experts. Factor analysis provides support for the underlying construct and significant correlations with another instrument measuring a similar construct provides support for the concurrent validity. The internal consistency reliability is very high. The NPST holds promise for use in nursing research and quality improvement programs in pediatric and neonatal in-patient settings.

Adult↗

Changing acute pain management to improve patient outcomes: an educational approach.

The United States Agency for Health Care Policy and Research (AHCPR) Acute Pain Management Guidelines were written to provide a scientific basis for practice. Educational programs designed to promote use of the guidelines may change practice in community hospitals. This article describes the development and implementation of an education program for nurses, physicians, and pharmacists in six community hospitals. Program content addressing the use of continuous quality improvement (CQI) teams, detailed pain histories, application of algorithms and dose calculation is described; direct and indirect outcome measures are reviewed. Six months after the program, all three experimental sites reported use of the AHCPR Guidelines in practice. Nurses reported that assessment and documentation of patients' duration of pain were perceived to be the most important caregiver behaviors providing benefit to patients: Across all respondents' reports of regularly performed activities, the activity performed by the largest proportion was assessing and documenting pain using a 0-10 rating scale.

Acute Disease↗

In vivo functional analysis of Drosophila Gap1: involvement of Ca2+ and IP4 regulation.

Control of Ras activity is crucial for normal cellular behavior such as fate determination during development. Although several GTPase activating proteins (GAPs) have been shown to act as negative regulators of Ras, the mechanisms involved in regulating their activity in vivo are poorly understood. Here we report the structural requirements for Gap1 activity in cone cell fate decisions during Drosophila eye development. The Gap1 catalytic domain alone is not sufficient for in vivo activity, indicating a requirement for the additional domains. An inositol-1,3,4, 5-tetrakisphosphate (IP4)-sensitive extended PH domain is essential for Gap1 activity, while Ca2+-sensitive C2 domains and a glutamine-rich region contribute equally to full activity in vivo. Furthermore, we find a strong positive genetic interaction between Gap1 and phospholipase Cgamma (PLCgamma), an enzyme which generates inositol-1,4,5-trisphosphate, a precursor for IP4 and a second messenger for intracellular Ca2+ release. These results suggest that Gap1 activity in vivo is stimulated under conditions of elevated intracellular Ca2+ and IP4. Since receptor tyrosine kinases (RTKs) trigger an increase in intracellular Ca2+ and IP4 concentration through stimulation of PLCgamma, RTKs may stimulate not only activation of Ras but also its deactivation by Gap1, thereby moderating the strength and duration of the Ras signal.

Amino Acids↗

Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients.

OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjögren's syndrome (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmö University Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with primary SS (according to the Copenhagen criteria). MAIN OUTCOME MEASURES: Cryoglobulins were analysed in all patients, while patients with primary SS were investigated with regard to markers of HCV infection, and HCV patients with objective tests of SS (Schirmer-1 test, break-up time, van Bijsterveld score, sialometry, labial salivary gland biopsy) and antibodies against nuclear antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small salivary glands from lower lip biopsies were detected by immunohistochemical analysis. RESULTS: Only one of the SS patients had detectable cryoprecipitates, while another was HCV-positive. None of the 21 HCV patients had cryoprecipitates. A total of 14/21 (67%) patients with HCV infection had at least one abnormal objective test suggestive of xerostomia or keratoconjunctivitis sicca, while eight (38%) had objective evidence of both eye and salivary gland involvement. HCV antigens were not detected in affected glands. Only two patients had clinical symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV-positive patients had detectable antibodies against SS-A, SS-B, RNP, Jo-1, PCNA or Scl-70, and the frequency of ANA/SMA/AMA was low. CONCLUSIONS: While involvement of salivary and lacrimal glands was common in Swedish patients with HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism responsible for glandular inflammation appears to be different from that in primary SS. HCV infection does not seem to be an aetiological factor for primary SS in this population. These observations suggest that viral, genetic or possibly environmental factors may be responsible for the reported high frequencies of systemic complications associated with chronic hepatitis C infection in southern Europe.

Adult↗

Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil.

AIMS: Electrical remodelling with shortening of the atrial refractory period and increased fibrillatory rate occurs after onset of atrial fibrillation and can be attenuated by pre-treatment with intravenous verapamil. The aim of the present study was to investigate whether already established fibrillatory-induced shortening of atrial fibrillatory cycle length could be reversed with oral verapamil. METHODS AND RESULTS: Thirteen patients (nine men; mean age 67 years) with chronic atrial fibrillation (CAF) were studied. The dominant atrial cycle length (DACL) was estimated non-invasively using the frequency analysis of fibrillatory ECG (FAF-ECG) method. Measurements were repeated following treatment with slow release oral verapamil. DACL increased from 147 +/- 13 ms to 156 +/- 21 ms after 1 day (P=0.02), to 164 +/- 18 ms after 5 days (P=0.005) and finally to 160 +/- 16 ms after 6 weeks (P=0.008). CONCLUSION: Long-term oral treatment with verapamil increases the DACL significantly in patients with CAF. The prolongation is evident after 1 day and is further developed during the first 5 days of treatment. Since DACL is believed to be an index of refractoriness, the findings of the present study suggest that this treatment increases the atrial refractory period in patients with CAF.

Aged↗

Treatment of sleep apnoea with continuous positive airway pressure in children with craniofacial malformations.

We conducted sleep studies in a consecutive series of 21 children with craniofacial malformations and suspected obstructive sleep apnoea. Thirteen had sleep apnoea, and one patient with a tracheostomy could not be tested. Twelve children were admitted for initiation of treatment with nasal continuous positive airway pressure (nCPAP). Ten patients accepted nCPAP, two did not. Seven children use home treatment successfully. Obstructive sleep apnoea in most children is completely eliminated with nCPAP. The treatment is safe, effective, and leads to a reduction in the number of operations done for children with craniofacial malformations. Aesthetic operations can be delayed until facial growth is complete.

Child↗

Increased prevalence of apolipoprotein E3/E4 genotype among Swedish renal transplant recipients.

There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the epsilon4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of epsilon2 (0.044), epsilon3 (0.716), and epsilon4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0. 078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the epsilon4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.

Adult↗

Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial.

200 adult respiratory distress syndrome patients were included in a prospective multicenter randomized trial to determine the efficacy of computerized decision support. The study was done in 10 medical centers across the United States. There was no significant difference in survival between the two treatment groups (mean 2 = 0.49 p = 0.49) or in ICU length of stay between the two treatment groups when controlling for survival (F(1df) = 0.88, p = 0.37.) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group (F(1df) = 4.1, p = 0.04) as well as significantly lower incidence and severity of overdistension lung injury (F(1df) = 45.2, p < 0.001). We rejected the null hypothesis. Efficacy was best for the protocol group. Protocols were used for 32,055 hours (15 staff person years, 3.7 patient years or 1335 patient days). Protocols were active 96% of the time. 38,546 instructions were generated. 94% were followed. This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical settings and significantly improve patient morbidity.

Adult↗

Gonococcal invasion of epithelial cells driven by P.IA, a bacterial ion channel with GTP binding properties.

The neisserial porin P.I is a GTP binding protein that forms a voltage-gated channel that translocates into mammalian cell membranes and modulates host cell signaling events. Here, we report that P.I confers invasion of the bacterial pathogen Neisseria gonorrhoeae into Chang epithelial cells and that this event is controlled by GTP, as well as other phosphorus-containing compounds. Bacterial invasion was observed only for strains carrying the P.IA subtype of porin, which is typically associated with the development of disseminated neisserial disease, and did not require opacity outer membrane proteins, previously recognized as gonococcal invasins. Allelic replacement studies showed that bacterial invasiveness cotransferred with the P.IA (por1A) gene. Mutation of the P.I-associated protein Rmp did not alter the invasive properties. Cross-linking of labeled GTP to the porin revealed more efficient GTP binding to the P.IA than P.IB porin subtype. GTP binding was inhibited by an excess of unlabeled GTP, ATP, and GDP, as well as inorganic phosphate, but not by UTP or beta-glycerophosphate, fully in line with the respective invasion-inhibitory activities observed for these compounds. The P.IA-mediated cellular invasion may explain the more invasive behavior of P.IA strains in the natural infection and may broaden the basis for the development of a P.I-based gonococcal vaccine.

Alleles↗

Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum.

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum-infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1-glutathione S transferase; Duffy binding-like-1-GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate-like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.

Amino Acid Sequence↗

Modification of intrinsic AV-nodal properties by magnesium in combination with glucose, insulin, and potassium (GIK) during chronic atrial fibrillation.

OBJECTIVE: To explore the effects of MgSO4 in combination with glucose, insulin, and potassium (GIK) on intrinsic AV-nodal properties during chronic atrial fibrillation. METHODS: The study included two patient groups--(a) control and intervention and (b) intervention--with different infusion times and concentrations of MgSO4. Ambulatory electrocardiographic recordings were analyzed using modified heart-rate stratified histogram (HRSH) analysis allowing detailed observation of the RR distribution at different average heart rate levels. The two RR-interval populations observed in most patients were characterized by analyzing the relationship between the summits of the peaks of the bimodal histograms. RESULTS: A bimodal RR distribution with a shorter and a longer RR-interval population was observed in 9 of 11 (control), 9 of 11 (intervention) in group (a), and 11 of 13 in group (b) patients. No significant changes in the two RR populations were seen in the control registration (group a). There were, however, indications of a conduction delay in the longer RR intervals in group (a), which received a low concentration of MgSO4, when control was compared with intervention recordings. In group (b), receiving a high MgSO4 concentration, a conduction delay was seen in both the shorter and longer RR populations, being most pronounced for the longer RR population. CONCLUSION: High MgSO4 levels caused a delay in both the shorter and longer RR intervals. The conduction delay in the longer RR population was most pronounced, indicating that MgSO4 differently affected the two corresponding AV-nodal pathways.

Aged↗