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Biomedical subjects

A Gerber

Publications and source records attributed to A Gerber.

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

Dual chamber pacing with a single-lead DDD pacing system.

The successful application of single-lead VDD pacing during the last few years has generated the idea of single-lead DDD pacing. Preliminary data from several single-lead VDD studies attempting to pace the atrium by a floating atrial dipole are unsatisfactory, causing an unacceptably high current drain of the device. We studied the feasibility as well as the short- and long-term stability of atrioventricular sequential pacing, using a new single-pass, tined DDD lead. In eight consecutive patients (age 73+/-16 years) with symptomatic higher degree AV block and intact sinus node function, this new single-pass DDD lead was implanted in combination with a DDDR pacemaker. Correct VDD and DDD function was studied at implantation; at discharge; and at 1, 3, and 6 months of follow-up. At implant, the atrial stimulation threshold was 0.6+/-0.1 V/0.5 ms. During follow-up, the atrial pacing thresholds in different every day positions averaged 2.1+/-0.5 V at discharge, 2.9+/-0.5 V at 1 month, 3.8+/-0.4 V at 3 months, and 3.4+/-0.4 V at 6 months (pulse width always 0.5 ms). The measured P wave amplitude at implantation was 4.5+/-2.2 mV; during follow-up the telemetered atrial sensitivity thresholds averaged 2.1+/-0.3 mV. Phrenic nerve stimulation at high output pacing (5.0 V/0.5 ms) was observed in three (38%) patients at discharge and in one (13%) patient during follow-up; an intermittent unmeasurable atrial lead impedance at 3 and 6 months follow-up was documented in one (13%) patient. This study confirms the possibility of short- and long-term DDD pacing using a single-pass DDD lead. Since atrial stimulation thresholds are still relatively high compared to conventional dual-lead DDD pacing, further improvements of the atrial electrodes are desirable, enabling lower pacing thresholds and optimizing energy requirements as well as minimizing the potential disadvantage of phrenic nerve stimulation.

Aged↗
PubMed1999

Hospital transfer for primary coronary angioplasty in high risk patients with acute myocardial infarction.

OBJECTIVE: To investigate the feasibility, safety, and associated time delays of interhospital transfer in patients with acute myocardial infarction for primary percutaneous transluminal coronary angioplasty (PTCA). DESIGN AND PATIENTS: Prospective observational study with group comparison in a single centre. 68 consecutive patients with acute myocardial infarction transferred for primary PTCA from other hospitals (group A) were compared with 78 patients admitted directly to the referral centre (group B). MAIN OUTCOME MEASURES: Patient groups were analysed with regard to baseline characteristics, time intervals from onset of chest pain to balloon angioplasty, hospital stay, and follow up outcome. RESULTS: Patients in group A presented with a higher rate of cardiogenic shock initially than patients in group B (25% v 6%, p = 0.01) and had been resuscitated more frequently before PTCA (22% v 5%, p = 0.01). No deaths or other serious complications occurred during interhospital transfer. Median transfer time was 63 (range 40-115) minutes for helicopter transport (median 42 (28-122) km, n = 14), and 50 (18-110) minutes by ground ambulance (median 8 (5-68) km, n = 54). The median time interval from the decision to perform coronary arteriography to balloon inflation was 96 (45-243) minutes in group A and 52 (17-214) minutes in group B (p = 0.0001). In transferred patients (group A) the transportation associated delay and the longer in-hospital median decision time (50 (10-1120) minutes in group A v 15 (0-210) minutes in group B, p = 0.002) concurred with a longer total period of ischaemia (239 (114-1307) minutes in group A v 182 (75-1025) minutes in group B, p = 0.02) since the beginning of chest pain. Success of PTCA (TIMI 3 flow in 95% of all patients), in-hospital mortality (7% v 9%, mortality for patients not in cardiogenic shock 0% v 4%), and follow up after median 235 days was similarly favourable in groups A and B, respectively. Only one hospital survivor (group A) died during follow up. CONCLUSION: Interhospital transport for primary PTCA in high risk patients with acute myocardial infarction is safe and feasible within a reasonable period of time. Short and medium term outcome is favourable. Optimising the decision process and transport logistics may further improve outcome by reducing the total time of ischaemia.

Aged↗
PubMed1999

Expression of cathepsin K in lung epithelial cells.

Alveolar and bronchial epithelial cells have been shown to have regulatory functions in the maintenance of lung structure and function. Recent evidence supports the premise that these cells can synthesize a variety of extracellular matrix components in vitro, suggesting an active participation in connective tissue remodeling. Their possible role in extracellular matrix degradation, however, is less clear. This study addresses the question of whether alveolar and bronchial epithelial cells express the highly collagenolytic and elastinolytic cysteine proteinase cathepsin K, which has recently been newly described. We provide evidence that the epithelial cell lines A549 and BEAS-2B are capable of expressing cathepsin K messenger RNA. Furthermore, we show that cathepsin K is expressed in normal bronchial epithelial cells. Western blot analyses of human lung-tissue lysates revealed specific immunoreactivity at molecular weights of 46 and 27 kD, corresponding to the procathepsin and the mature cathepsin K. Immunohistochemical analyses showed a pronounced staining of bronchial epithelial cells and in single alveolar epithelial cells. Using a specific fluorogenic cytochemical assay, the intracellular activity of the enzyme was localized. These findings demonstrate that bronchial and alveolar epithelial cells are capable of expressing cathepsin K, which could be of considerable importance for remodeling processes of the extracellular matrix in the lung.

Bronchi↗
PubMed1999

Emotional and behavioural problems in adolescents/young adults receiving treatment at a community-based psychotherapy centre for young people: a preliminary study of the correspondence among adolescent/young adult and significant other reports.

The present study examined the correspondence among adolescent/young adult and parental figure, professional, peer and partner reports, in their rating of emotional and behavioural problems of 195 young people aged between 12 and 25 years who attended a community-based psychotherapy centre. Data from young people were obtained at intake by participants completing the Youth Self Report Form and from significant others by them completing the Significant Other version of the Teacher's Report Form. Professionals rated internalizing (emotional) problems lower than peers, partners or parental figures. Externalizing (disruptive) problems were rated lowest by professionals, highest by partners with parental figures and peers in between. Agreement for internalizing problems was highest between self and professionals and lowest for partners and peers; parental figures were in between these two extremes. For externalizing problems, agreement was highest between self and friends but very low for partners. Professionals' ratings of internalizing problems showed a strong association with clinicians' assessment of global functioning and there was a strong association between partner ratings of total problems and clinicians' ratings of global functioning. The study showed the value of using a wider range of informants for assessing emotional and behavioural problems presented by young people seeking treatment than used in the assessment of pre-adolescents.

Adolescent↗
PubMed1999

[Cathepsin cysteine proteinases in the lung].

Proteolytic enzymes play an important role during remodeling and digestion of extracellular matrix proteins. An overproduction of extracellular matrix or insufficient extracellular matrix digestion may result in fibrosis. Enhanced proteolytic activity or an insufficient inhibitory potential could be followed by emphysema development. Since the first reports showed an emphysema induction in rats after intratracheal application of the cysteine protease papain, a number of proteolytic enzymes involved in the remodeling of the extracellular matrix of the lung were discovered. Most of them are cysteine-, metallo-, serine- or aspartic proteases. In this paper some new findings concerning the expression, function and regulation of the activity of papain-like cysteine proteases in the process of tissue destruction and remodeling in the lung are reviewed. The functional relationship between cathepsins and other proteolytic enzymes are discussed.

Animals↗
PubMed1998

[Sedation and analgesia in childhood].

As a rule the indication for sedation should be broad. Any child who is, or could be, frightened by an intervention should have the benefit of sedation. Correspondingly, an analgesic should be chosen if the intervention is painful. The sedatives of choice are midazolam and chloral hydrate, and possibly a neuroleptic for interventions which require the child to be motionless. Any physician who sedates a child must be aware of the side effects of the sedation and be well versed in countermeasures, including resuscitation. The dangers of sedation arise from wrong selection of patients and also from postsedation and combination of sedatives and analgesics; both should be left to experienced physicians or specialists. If sedation or analgesia is planned with the rest of the intervention and the described guidelines are followed, the patient's safety is ensured. Despite all efforts a small proportion of patients show an inadequate response to the chosen medication. In young children and in sick children the specific physiological and anatomical features will overtax the therapist. In such cases the help and advice of a specialist trained in paediatric anaesthesia can and should be sought.

Analgesia↗
PubMed1998

Tad1p, a yeast tRNA-specific adenosine deaminase, is related to the mammalian pre-mRNA editing enzymes ADAR1 and ADAR2.

We have identified an RNA-specific adenosine deaminase (termed Tad1p/scADAT1) from Saccharomyces cerevisiae that selectively converts adenosine at position 37 of eukaryotic tRNAAla to inosine. The activity of purified recombinant Tad1p depends on the conformation of its tRNA substrate and the enzyme was found to be inactive on all other types of RNA tested. Mutant strains in which the TAD1 gene is disrupted are viable but lack Tad1p enzyme activity and their tRNAAla is not modified at position A37. Transformation of the mutant cells with the TAD1 gene restored enzyme activity. Tad1p has significant sequence similarity with the mammalian editing enzymes which act on specific precursor-mRNAs and on long double-stranded RNA. These findings suggest an evolutionary link between pre-mRNA editing and tRNA modification.

Adenosine Deaminase↗
PubMed1998

Purification of native and recombinant double-stranded RNA-specific adenosine deaminases.

ADAR1 and ADAR2 are members of a family of enzymes that catalyze the conversion of adenosine to inosine in double-stranded RNA. Unlike the other types of RNA editing that involve multiprotein editing complexes, the site-specific deamination of an adenosine to inosine is catalyzed by single enzymes. ADAR1 and ADAR2 have been purified and the genes cloned from various sources. Each gene encodes multiple splice variants. As it is crucial to have an adequate supply of pure protein to investigate this type of RNA editing, we describe in this article methods for both the purification and the overexpression of either full-length or partial ADAR1 and ADAR2 isoforms.

Adenosine Deaminase↗
PubMed1998

Combined internal and external osteosynthesis a biological approach to the treatment of complex fractures of the proximal tibia.

Lateral plating was combined with external fixation to treat 18 complex, proximal, tibial fractures with severe soft tissue injury. All patients were followed up until functional restoration of the limb had been achieved. In 15 cases, bone healing was uneventful. One deep infection without knee joint arthritis, one delayed union and one malunion necessitated revision. Pin track complications were negligible and soft tissue breakdown was not observed. The short-term results regarding the functional outcome showed a painless condition and good function in all patients. The method of fixation described is more invasive than the currently proposed minimally invasive combined fixation techniques, but can be regarded as an optimization of the mechanical and biological advantages of the implants.

Adult↗
PubMed1998

The relationship of serum-eosinophil cationic protein and eosinophil count to disease activity in children with bronchial asthma.

BACKGROUND: The serum-eosinophil cationic protein level (S-ECP) has been promoted as a biomarker of asthma that reflects the degree of bronchial eosinophilic inflammation. PATIENTS AND METHODS: To investigate whether S-ECP is indeed a clinically useful objective parameter, especially in mild or moderate chronic childhood asthma, we studied 100 outpatient children with chronic asthma symptoms (63 boys and 37 girls, aged three to 15 years, median of age eight) and 25 controls (12 boys and 13 girls aged three to 15 years, median of age eight). Symptom scores, lung function parameters and atopy were compared with S-ECP determined by commercially available tests and eosinophils measured by an autoanalyser. RESULTS: Asthma symptom scores in the patient group ranged between one and 13 (median of 8), S-ECP between 2.1 and 75.6 microg/l (median of 13.3 microg/ l), and eosinophils between 30/microl and 2002/microl (median of 314). Symptom scores and S-ECP were correlated significantly (P < 0.001) as were symptom scores and eosinophils (P = 0.001). S-ECPs were significantly higher in children with chronic asthma symptoms compared with non-asthmatic, non-atopic children (P = 0.005 for non-atopic chronic asthmatics and P < 0.001 for atopic asthmatics); similar results were found comparing eosinophils in these groups. There was no difference in S-ECP between atopic and non-atopic asthmatic children, but the 25 polysensitised asthmatic children especially with sensitisations to mite, pollen and pet allergens were found to have significantly higher S-ECP compared to 15 monosensitised children (P = 0.002). Similar results were found when correlating eosinophil numbers with atopy. Polysensitised (mite, pollen, pet) asthmatics had significantly higher eosinophil counts compared with monosensitised (pollen) asthmatics (P = 0.01); there was, however, a better discrimination between atopic and non-atopic asthmatics (P = 0.001). Non-asthmatic, non-atopic controls had significantly lower eosinophil counts compared with asthmatics (P < 0.001 for both non-atopic and atopic asthmatics). No correlation between S-ECP or eosinophils and any of the lung function parameters measured (FEV1, FEV1/FVC, MEF50, airway resistance and ITGV) was found. SUMMARY: Our data thus indicate that 1) S-ECP is higher than normal in children with asthma symptoms and correlates with asthma symptom score. 2) S-ECP is better correlated to symptom score than to lung function parameters especially in children with mild and moderate asthma symptoms. 3) Raised S-ECP appears to reflect the extent of allergen sensitivity and may also reflect current allergen exposure. 4) Similar correlations were seen when measuring eosinophil number by an autoanalyser instead of S-ECP. CONCLUSIONS: Although S-ECP and eosinophils are not diagnostic of asthma they are useful inflammation markers especially in the context of clinical studies. However, both methods are not yet suitable for use in daily practice because they require extensive procedures and special equipment.

Adolescent↗
PubMed1998

Adolescents who drop out of psychotherapy at a community-based psychotherapy centre: a preliminary investigation of the characteristics of early drop-outs, late drop-outs and those who continue treatment.

The present study examined the difference between young people who terminated treatment prematurely and who continued in treatment. One hundred and thirty-four young people (ages 12 to 24 years) who attended a community-based psychotherapy centre for psychoanalytic psychotherapy between 1 April 1993 and 31 March 1996 comprised the sample. It was predicted that drop-outs would consist of younger adolescents who were referred, who show a high score for externalizing problems such as aggression and delinquency and a low score for internalizing problems such as anxiety and depression. It was also predicted that continuers would be older, self-referred and show a high score for internalizing problems and a low score for externalizing problems. The results indicated significant differences between drop-outs and continuers: drop-outs were younger, had greater externalizing problems, school problems and presented with moderate to severe hyperkinetic or conduct disorder. Continuers were older, had fewer externalizing problems, were self-referred and were likely to be treated by supportive therapists. Since age was the most significant predictor of attendance, the sample was separated into younger adolescents and older adolescents and the same analyses repeated. In the younger group ethnic minority status, and being treated by a supportive therapist predicted continuing in treatment and a diagnosis of conduct disorder predicted premature termination. The clinical implications of the present findings for the delivery of psychotherapy services to young people are discussed.

Adolescent↗
PubMed1997

Purification of human double-stranded RNA-specific editase 1 (hRED1) involved in editing of brain glutamate receptor B pre-mRNA.

RNAs encoding subunits of glutamate-gated ion channel receptors are posttranscriptionally modified by RNA editing and alternative splicing. The change in amino acid sequence caused by RNA editing can affect both the kinetics and the permeability of the ion channel receptors to cations. Here, we report the purification of a 90-kDa double-stranded RNA-specific adenosine deaminase from HeLa cell nuclear extract that specifically edits the glutamine codon at position 586 in the pre-mRNA of the glutamate receptor B subunit. Site-specific deamination of an adenosine to an inosine converts the glutamine codon to that of arginine. Recently, a gene encoding a double-stranded-specific editase (RED1) was cloned from a rat brain cDNA library. Antibodies generated against the deaminase domain of its human homolog specifically recognized and inhibited the activity of the 90-kDa enzyme, indicating that we have purified hRED1 the human homolog of rat RED1. This enzyme is distinct from double-stranded RNA-specific adenosine deaminase which we and others have previously purified and cloned.

Adenosine Deaminase↗
PubMed1997

Effects of retinoids on the generation of neutrophil-derived reactive oxygen species studied by EPR spin trapping techniques.

OBJECTIVE: To study the potential efficacy of retinoids on granulocytes with regard to their role in inflammatory dermatoses. METHODS: We investigated the in vitro effect of acitretin and isotretinoin on the generation of reactive oxygen species (ROS) by stimulated human neutrophils using EPR spin trapping techniques. RESULTS: The effects of the two retinoids on ROS generation by neutrophils were different. Acitretin increased the generation of hydroxyl radicals, whereas isotretinoin showed an antioxidant activity against the superoxide anion. CONCLUSIONS: Our study demonstrates retinoid type-dependent effects on ROS production by stimulated neutrophils.

Acitretin↗
PubMed1997

Protection against UVA damage and effects on neutrophil-derived reactive oxygen species by beta-carotene.

OBJECTIVE: Phagocyte-derived reactive oxygen species (ROS) are involved in microbicidal activities as well as in tissue damage at sites of inflammation. Carotenoids play an important function in protecting cells from oxidant damage. We investigated the in vitro and in vivo effect of 13-cis and 9-cis-beta-carotene on human neutrophils. METHODS: Neutrophils from healthy donors in the presence of 0.25 mumol/L-1 mumol/l beta-carotene and from subjects under beta-carotene supplementation and UVA or UVA/B exposure were stimulated by opsonized zymosan and the generation of ROS was measured by electron spin resonance spectroscopy. RESULTS: Our in vitro results show different effects of the two isomers on stimulated neutrophils. 9-cis-beta-carotene did not produce any change, whereas 13-cis-beta-carotene significantly and concentration-dependent inhibited the ROS generation by stimulated neutrophils. Further, in a controlled study, we were able to demonstrate an in vivo protective effect of beta-carotene on neutrophils against UVA damage by beta-carotene supplemented subjects.

Electron Spin Resonance Spectroscopy↗
PubMed1997

[Cellular and humoral functions in acute pancreatitis].

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.

Acute Disease↗
PubMed1997

Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by the insertion of an Alu cassette.

The double-stranded RNA-specific editase 1 (RED1/ADAR2) is implicated in the editing of precursor-mRNAs (pre-mRNA) encoding subunits of glutamate receptors (GluRs) in brain. Site-specific deamination of adenosine to inosine alters the codon at the Q/R site in GluR-B rendering the heteromeric receptor impermeable to Ca2+ ions. We cloned human RED1 (hRED1/hADAR2) cDNAs from a brain cDNA library. The human enzyme is 95% identical to the rat homologue. We characterized two alternatively spliced forms that differed by the presence of an Alu-J cassette in the deaminase domain. For the long form containing the Alu cassette, we isolated cDNA clones with an alternative C-terminus and 3'-UTR. An 8.8-kb transcript of hRED1 is most abundant in brain and heart, and lower levels are detected in other tissues. In vitro editing assays with purified recombinant hRED1 containing or lacking the Alu-J cassette revealed that both forms of the protein have the same substrate specificity, but differ in their catalytic activity.

Adenosine Deaminase↗