Integrating advanced practice nurses into inpatient care.
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Biomedical subjects
Publications and source records attributed to S Suter.
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To determine whether junctional communication between pancreatic acinar cells contributes to their secretory function in vivo, we have compared wild-type mice, which express the gap junctional proteins connexin32 (Cx32) and connexin26, to mice deficient for the Cx32 gene. Pancreatic acinar cells from Cx32 (-/-) mice failed to express Cx32 as evidenced by reverse transcription-PCR and immunolabeling and showed a marked reduction (4.8- and 25-fold, respectively) in the number and size of gap junctions. Dye transfer studies showed that the extent of intercellular communication was inhibited in Cx32 (-/-) acini. However, electrical coupling was detected by dual patch clamp recording in Cx32 (-/-) acinar cell pairs. Although wild-type and Cx32 (-/-) acini were similarly stimulated to release amylase by carbamylcholine, Cx32 (-/-) acini showed a twofold increase of their basal secretion. This effect was caused by an increase in the proportion of secreting acini, as detected with a reverse hemolytic plaque assay. Blood measurements further revealed that Cx32 (-/-) mice had elevated basal levels of circulating amylase. The results, which demonstrate an inverse relationship between the extent of acinar cell coupling and basal amylase secretion in vivo, support the view that the physiological recruitment of secretory acinar cells is regulated by gap junction mediated intercellular communication.
To understand chronic neutrophil attraction into cystic fibrosis airways, both global chemotactic activity and individual chemotactic factors were studied in bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients, collected on the first day of admission for antibiotic treatment, showed a high chemotactic index (19.4 +/- 5.7, n = 8). Fractionation by gel filtration of bronchial secretions resulted in three chemotactic fractions. The first factor corresponded to interleukin-8, and the second activated neutrophils via the FMLP receptor. The third factor, which was of lower molecular weight, did not activate FMLP or leukotriene B4 receptors, and its nature is still under investigation. Treating patients with antibiotics reduced global chemotactic activity, mainly by reducing the activity due to stimulation of the FMLP receptor.
Erectile dysfunction has an incidence of 2-9% and it is seen often in general practice. But the more recent treatment methods such as intracavernous drug injections and vacuum constriction devices are not known by general practitioners and normally used drug treatment has no efficacy. The management of impotence of the general practitioner should concentrate upon internistic conditions like diabetes, hypertension, hypercholesteremia and different drugs causing impotence. The symptomatic treatment of erectile dysfunction has to be done by a specialist, who is able to offer all therapeutic options.
Nocturnal penile tumescence monitoring (NPT) is a non-invasive method to differentiate between organic and psychogenic impotence. The routine use of NPT monitoring in the evaluation of impotence is not effective due to its moderate sensitivity and specificity with small therapeutic benefit and relatively high costs. Patient's selection by intracavernous pharmacotest can improve the efficiency of the investigation, so the method can help to secure the diagnosis of a psychogenic impotence and then take effect on adequate therapy.
Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children's Hospital (Rotterdam, the Netherlands), but as more benign infections in others such as the Geneva Children's Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994-5) and retrospectively (1993-4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v 23.9%), the rate of admission to the intensive care unit (3.6 v 28.1%), mechanical ventilation (0 v 7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8 v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1 v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.
Phagocytosis represents a powerful stress for the phagocytic cells. Phagocytosis of Staphylococcus aureus induces a stress response associated with the synthesis of specific heat shock/stress proteins (HSP). Here we investigated the stress response of human monocyte-macrophages (m phi) to Pseudomonas aeruginosa, a bacterium found, as for S. aureus, in the airways of patients suffering cystic fibrosis. P. aeruginosa activated in m phi the production of both extra- and intracellular O2-; increased Interleukin-1 beta and actin, but failed to induce host HSP. Neither S. aureus' exotoxins nor the scavenging property of P. aeruginosa's alginate, but the lower toxicity of P. aeruginosa and/or differential activation of proteine kinase C (PKC) by the two bacteria, might explain their differences in host HSP induction. While O2- is insufficient to induce HSP synthesis in m phi, hydroxyl radicals, generated in the presence of exogenous iron, is a likely additional signal, along with PKC activation, for HSP induction during bacterial phagocytosis.
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In cystic fibrosis (CF), large amounts of free leucocyte proteases are present in bronchial secretions, contributing to progressive lung damage. Recombinant, human deoxyribonuclease (rhDNase) is a new therapeutic agent that decreases sputum viscosity. However, deoxyribonuclease has been shown, in vitro, to release cationic enzymes from complexes with deoxyribonucleic acid (DNA). The present study was conducted to assess this effect in vivo. Free human leucocyte elastase (HLE), human leucocyte cathepsin G (HCG), total chemotactic activity, and interleukin-8 (IL-8) were determined in sputum from eight patients before, during and after rhDNase treatment. After 15 days of treatment, HLE activity increased by 81+/-44% (NS), and HCG by 189+/-70% (p<0.05). One week after stopping a 4-6 months treatment, HLE activity decreased by 35+/-18% (p<0.05), and HCG by 43+/-11% (p<0.05). Sputum bacterial density, chemotactic activity, and IL-8 concentration did not change. Thus, treatment with rhDNase can indeed increase the activity of HLE and HCG in the bronchial secretions of CF patients, and this effect is still detectable after several months of treatment. If this can be shown to be clinically relevant, combination therapy of recombinant human deoxyribonuclease with protease inhibitors should be considered as an approach to the problem.
Lung inflammation in cystic fibrosis (CF) is associated with an increased release from activated neutrophils of oxidants and proteinases. Free radical generation is not efficiently neutralized, and the major anti-proteinase, alpha 1-proteinase inhibitor (alpha 1-PI) is thought to be oxidatively inactivated. We hypothesized that enhanced antioxidant protection could represent an additional long-term strategy to attentuate the host inflammatory response. The effect on plasma neutrophil elastase/alpha 1-PI (NE/alpha 1-PI) complex levels (as a marker of lung inflammation) and plasma malondialdehyde concentrations (as a marker of lipid peroxidation) of additional oral beta-carotene supplementation was studied in 33 CF patients who had already received long-term vitamin E supplementation. In the presence of a more than 10-fold increase in plasma beta-carotene concentrations (mean +/- SEM) (0.09 +/- 0.01 to 1.07 +/- 0.19 mumol/L; p < 0.0001), a small increase in plasma alpha-tocopherol concentrations (23.8 +/- 1.31 to 28.4 +/- 1.81 mumol/L; p = 0.02), and a more than 50% decrease in plasma malondialdehyde concentrations (1.00 +/- 0.07 to 0.46 +/- 0.03 mumol/L; p < 0.0001), plasma NE/alpha 1-PI complex levels decreased from 102.2 +/- 16.0 to 83.0 +/- 10.4 micrograms/L; (p = 0.02). Plasma retinol concentrations increased (1.05 +/- 0.06 to 1.23 +/- 0.07 mumol/L; p = 0.0001) due to conversion of beta-carotene to retinol, which could have contributed to the decrease in NE/alpha 1-PI complex levels. Based on these results, we speculate that efficient antioxidant supplementation could attenuate lung inflammation in CF.
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The first part of this paper reviews: (1) the spectrum of clinical features of congenital toxoplasmosis; (2) the natural course of fetal infection; (3) the influence of antitoxoplasma therapy on the course of the disease; (4) methods for diagnosing the toxoplasma infection and assessing the severity of the disease; (5) currently used antitoxoplasma drugs and different therapeutic regimens. The second part suggests a practical approach to the problem of congenital toxoplasma infection, including diagnostic work-up, drug therapy, and follow-up. This practical approach is modulated according to the clinical syndrome in the infant and diagnostic and therapeutic considerations in the mother.
Penicillin therapy has considerably reduced the occurrence of serious late complications of streptococcal pharyngotonsillitis. However, treatment failure with this antibiotic is currently reported in up to 30% of the cases. Beta-lactamase production by the commensal flora of the tonsils, and poor compliance of patients have been implicated as the main causes of treatment failure. Cefetamet pivoxil is a new oral cephalosporin with a twice daily dosage and striking stability against beta-lactamases. We are conducting a prospective, randomized study in 120 children, comparing the efficacy of cefetamet pivoxil 10 mg/kg bid for 5 and 10 days and phenoxymethyl penicillin 25,000 U/kg tid for 10 days in the treatment of group A beta-hemolytic streptococcus (GABHS) pharyngotonsillitis. Children are enrolled after the positive culture of a throat swab and randomly assigned to one of the three groups. A follow-up check-up is performed at the end of the therapy (clinical check-up) and 3 to 5 days later (bacteriological check-up). The preliminary analysis of 55 cases shows that in 88.9%, 100% and 87.5% of children GABHS was eradicated by 5 days or 10 days of cefetamet pivoxil, or 10 days of penicillin respectively (p = NS). Side effect were mild and transient in cefetamet pivoxil-treated patients, but required cessation of treatment in 2 children treated with penicillin. These results suggest that cefetamet pivoxil therapy for 5 days eradicates GABHS from the throat in streptococcal pharyngotonsillitis as efficiently as cefetamet pivoxil or phenoxymethyl penicillin for 10 days.
A 28-year-old turkish patient was admitted to hospital several times within the last years because of acute abdominal and thoracic pain. On each admission laboratory parameters indicative of an acute inflammatory process were initially found to be slightly increased; however, the cause for the complaints remained undetected. During a recent episode of acute abdominal pain a short increase of these laboratory parameters (particularly of CRP) could be documented, and since no other diagnostic sign indicative of an other disease was found, familial mediterranean fever was diagnosed. A basic therapy with colchicine was initiated, and since five months the patient remained mostly free of symptoms.
Neurotransmitter transporters determine the intensity and duration of signal transduction by controlling the rapid removal of transmitter molecules from the synaptic cleft. The importance of their function is further reflected by the medical and social implications of compounds that inhibit their activity such as the antidepressants and cocaine. Molecular characterization of these transporters has revealed that they are members of a large family of membrane proteins with 12 putative transmembrane domains. However, little information exists as to whether discrete domains of these proteins mediate the various defined functions of these transporters. In this study, we constructed a series of chimeras between two structurally related but pharmacologically distinct transporters, the dopamine and norepinephrine transporters. The properties of these chimeric transporters suggest that distinct regions of these molecules determine these individual functions. Regions from the amino-terminal through the first five transmembrane domains are likely to be involved in the uptake mechanisms and ionic dependence. Regions within transmembrane domains 6-8 determine tricyclic antidepressant binding and cocaine interactions, whereas the carboxyl-terminal region encompassing transmembrane domain 9 through the COOH-terminal tail appears to be responsible for the stereoselectivity and high affinity for substrates. The dissociation of the substrate uptake and cocaine binding properties of these transporters further raises the possibility that antagonists of cocaine action devoid of uptake blockade activity might be developed for the clinical management of cocaine addiction.
In the past 40 years, the mean survival of patients with cystic fibrosis (CF) has increased from less than 1 year to 30 years. The identification of the gene mutated in CF in 1989 has already been followed by the first phase of somatic gene therapy in 1993. The target organ of somatic gene therapy is the respiratory epithelium, which is progressively damaged by the chronic infection and inflammation characteristic of the disease. Since in the future, more patients may benefit from somatic gene therapy, the understanding of the mechanisms leading to chronic infection and inflammation becomes increasingly important. In the future, current therapeutic measures to protect the respiratory epithelium from damage, such as intravenous antimicrobial treatment, will be improved by the additional delivery of new drugs to the bronchial tree by aerosol. Amiloride and recombinant human DNAse administered by this route have the potential to improve mucociliary clearance. Antibiotics as well as protease inhibitors delivered by aerosol should contribute to prevent damage by infection and inflammation in order to increase the probability of successful somatic gene therapy in this disease.