Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 109 records · Page 6Linked to original sources

PubMed1999

[Direct coronary stent implantation without predilatation--a new therapeutic approach with a special balloon catheter design].

Stent implantation serves as the gold standard for proximal lesions of the coronary arteries with a diameter between 2.75-3.5 mm. Our new concept aims at a reduced procedure duration and fluoro-time as well as a decreased ischemic period during stent implantation. A new therapeutic concept of a direct stent implantation without predilatation was tested using a specially developed balloon catheter on which various 14-16 mm long "slotted-tube" stents are mounted between two conical, radiopaque markers. In 105 consecutive patients, who were scheduled for angioplasty, this method of direct stent implantation was performed. Six of the procedures were performed for acute myocardial infarction and 8 in so-called high-risk procedures. The direct stent implantation was successful in 88%. In 6%, predilatation of the lesion site was necessary before stent placement. In the remaining 6%, a stent could not be successfully implanted despite the availability of various other systems. Comparison of the direct stent implantation with conventional stent placement with predilatation revealed that 1) The fluoro-time for direct stent implantation, compared to the conventional method, was 8.4 +/- 4.9 min vs. 13.7 +/- 8.0 min; p < 0.05, respectively. Furthermore, there were less balloons used per lesion for direct stent implantation (1.4 +/- 0.4) compared to the conventional method (1.7 +/- 0.7), but there was not a significant difference. 2) If we compare those patients with successful direct stent implantation with those with the unsuccessful procedures, the latter group had a higher percent of angiographically visible calcification at the site of the lesion (80% vs. 18%; p < 0.01). In addition, these patients had an increased average age (72 +/- 7 vs. 61 +/- 11 yrs; p < 0.01). The success rate of direct stent implantation did not depend on lesion diameter stenosis before PTCA. Stent dislocation was observed in 3.8% of the procedures, and a single case of stent embolism was seen. In conclusion, the direct stent implantation offers the advantages of a shortened fluoro-time, the use of fewer balloons, and has the potential of less ischemic stress compared to the conventional method of stent implantation with predilatation, if old patients with calcified lesions are excluded. This should be proved on a large scale in future studies also considering a learning curve with regard to the new method. Whether this new approach also reduces the restenosis rate, warrants further studies.

Adult↗

PubMed1999

Cotranscription of the rpl5-rps14-cob gene cluster in pea mitochondria.

In pea mitochondria the rpl5, rpsl4 and cob ORFs are clustered in a unique genomic environment and are cotranscribed into a 4.7-kb primary transcript and several other polycistronic RNAs with sizes between 4.0 and 2.3 kb. All of the larger RNAs terminate at a common 3' end, 52 nucleotides downstream of the cob gene. Transcription is initiated at a promoter about 1.3 kb upstream of the rpl5 start codon. The promoter sequence 5'-AATAAGAGA-3' corresponds to the highly conserved 5'-CRTAAGAGA-3' motif often found in promoters in dicot plants. Functional analysis in a homologous in vitro transcription system showed the pea rpl5 promoter to be active, despite the presence of an altered base in first position of the promoter motif. In Oenothera, in contrast to pea, transcription of the rpl5 gene is driven by a promoter motif that conforms perfectly to the consensus sequence. Double inverted repeats located in the 3' flanking regions of the rpsl4 and cob ORFs in pea were investigated with respect to their possible role in defining transcript termini and their potential function in controlling exo- and endonucleolytic processing or transcript stabilization.

Base Sequence↗

PubMed1999

Time course of motion adaptation: motion-onset visual evoked potentials and subjective estimates.

The aim of this study was to quantitatively describe the dynamics of adaptation to visual motion with electrophysiological and psychophysical methods in man. We recorded visual evoked potentials (VEPs) to motion onset of random dot patterns from occipital and occipito-temporal electrodes during a succession of adaptation-recovery sequences. In these sequences the test stimulus was used to set the adaptation level: seven trials with 70% motion duty cycle (adaptation) followed by seven trials of 7% motion duty cycle (recovery). In a similar paradigm we determined the length of the perceptual motion after-effect to obtain a psychophysical measure of the time course of motion adaptation. Our results show a highly significant reduction of the N2 amplitude in the maximally compared to the minimally adapted condition (P < 0.001). Electrophysiological and psychophysical results both indicate that adaptation to visual motion is faster than recovery: The data were fit with an exponential model yielding adaptation and recovery time constants, respectively, of 2.5 and 10.2 s for the N2 amplitude (occipito temporal derivation) and of 7.7 and 16.7 s for the perceptual motion after-effect. Implications for the design of motion stimuli are discussed, e.g. a motion stimulus moving 10% of the time may lead to about 30% motion adaptation.

Adaptation, Ocular↗

PubMed1999

Guidelines for anti-emetic therapy: acute emesis.

Anti-emetic therapy has become integral to the management of patients with cancer. Goals related to complete emesis control include providing treatment that reduces hospitalisation and time in the ambulatory setting, care that is convenient for the patient and therapy that enhances patients' quality of life. A panel of clinical, health economic and basic scientists with expertise in various oncology disciplines reviewed published literature to develop evidence-based consensus guidelines for the prevention and treatment of chemotherapy-induced emesis. Currently, serotonin receptor antagonists and corticosteroids are the two categories of anti-emetics that are most effective, have the fewest side-effects and are convenient to use. These agents are recommended in combination for highly emetogenic chemotherapy regimens and as single agents or in combination for moderately to highly emetogenic chemotherapy. When possible, these agents may be given orally in single doses; current evidence does not support dose escalation for either category of anti-emetics. In special situations, such as the use of high-dose chemotherapy combination regimens, the most emetogenic component of the regimen should dictate the choice of anti-emetic. Appropriate anti-emetic use described in these guidelines represents both good medical practice and a sensible economic approach to care.

Acute Disease↗

PubMed1999

Positron emission tomography with fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) does not visualize extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type.

BACKGROUND: On the basis of promising data on the use of fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) whole body positron emission tomography (WB-FDG-PET) in the staging of patients with lymphoma, we initiated a pilot series to evaluate the role of WB-FDG-PET in the staging of extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. PATIENTS AND METHODS: We examined ten consecutive patients with histologically-verified MALT-type lymphomas of various origin before initiation of therapy. Nine patients had low-grade lymphomas (five cases of gastric lymphoma, two patients with lymphoma arising in the lung, one parotid and one lacrimal gland lymphoma), while one patient had a high-grade gastric lymphoma arising from a low-grade background. Two patients had stage EI, seven had stage EII disease, and one presented with stage EIII. WB-FDG-PET scans were performed 40 min following the injection of 300-380 MBq of F18-FDG. The PET scans were correlated with extensive conventional staging including ophthalmologic investigation, otolaryngologic examination, gastroscopy, endosonography, enteroclysis, colonoscopy, CT of thorax and abdomen, and bone marrow biopsy. RESULTS: WB-FDG-PET documented no lymphoma in any of the 10 patients studied, as no focal tracer uptake was demonstrated in either gastric or extragastric lesions or in involved lymph nodes, irrespective of histologic grading. In three patients the scan showed a false negative result with respect to the MALT lesions but showed focal tracer uptake indicating tumor spread, which, however, was ruled out by further follow-up and biopsy, respectively, and was thus rated false positive. Due to these results, the study was discontinued prematurely after the first ten patients. CONCLUSIONS: These discouraging results indicated that WB-FDG-PET is not useful for staging and follow-up of MALT-type lymphoma, and should therefore not be included in the clinical decision making process.

Aged↗

PubMed1999

Surveillance of antibiotic resistance in ICUs in southeastern Sweden. ICU Study Group of the South East of Sweden.

BACKGROUND: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs. METHODS: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores). RESULTS: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (approximately 70%), ciprofloxacin (approximately 50%), fucidic acid (approximately 50%) and netilmicin (approximately 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption. CONCLUSIONS: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

APACHE↗

PubMed1999

Platelet-reactive IgG antibodies cloned by phage display and panning with IVIG from three patients with autoimmune thrombocytopenia.

Autoimmune thrombocytopenic purpura (AITP) is a severe disease in children with a still unknown aetiology. It is not known why AITP can either be transient and self limiting or become chronic. The beneficial use of intravenous immunoglobulins (IVIG) in certain groups of AITP patients has been proven. It is, however, not clear how IVIG functions. To analyse patient-derived monoclonal IgG platelet autoantibodies that interact with IVIG in an anti-idiotypic manner, the combinatorial antibody phage display system was applied. From three different patients a large number of clones specifically reacting with IVIG molecules were derived. Many of these IVIG binders also reacted strongly with platelets in ELISA and FACS, in contrast to IVIG binders derived from a healthy individual. The heavy and light chain variable regions were sequenced and compared with each other and with databases. In all three AITP patients clones with a striking complementarity-determining region (CDR) sequence homology to each other and to many of the known anti-platelet antibodies were observed. Selected Fab-phages representing the characteristic variable regions that occurred in the investigated patients with AITP may now be used to clone potentially regulatory anti-idiotypes from healthy donors by phage display.

Adolescent↗

PubMed1999

Carotid endarterectomy after recent cerebral infarction.

OBJECTIVES: whether timing of carotid endarterectomy (CEA) was significant in terms of morbidity and mortality for significant carotid stenosis. DESIGN/MATERIALS: comparison was made of patients requiring CEA performed in less than 6 weeks or more than 6 weeks after their stroke. To enable quantification in terms of clinical presentation, aetiology and handicap, standardised scales were incorporated into the registry protocol. A postoperative event was considered to have occurred if a stroke or death from any cause took place within one month of surgery. RESULTS: patients with CEA (n=1005) and stroke numbered 232. Comparison was made of the early (n=86) and late surgery groups (n=121) in terms of demography, risk factors, clinical findings, quantitative neurological deficit, handicap and degree of carotid stenosis with no significant differences found except for race. There was no difference in morbidity and mortality (M+M) between the early and late surgery group. The relative risk (RR) of >6 week group was 1.90 (CI: 0.52-6. 94) with an odds ratio of 1.96 (CI: 0.45-9.63). There is, therefore, a trend of a two-fold risk of MM in the >6 week group. CONCLUSION: we propose that the historical 6-week wait period for CEA post stroke is outdated.

Aged↗

PubMed1999

Regional cerebral blood flow during temporal lobe seizures associated with ictal vomiting: an ictal SPECT study in two patients.

PURPOSE: Ictal vomiting represents a rare clinical manifestation during seizures originating from the temporal lobes of the nondominant hemisphere. The precise anatomic structures responsible for generation of ictal vomiting remain to be clarified. Ictal single photon emission computed tomography (SPECT), which allows one to visualize the three-dimensional dynamic changes of regional cerebral blood flow (rCBF) associated with the ongoing epileptic activity, should be useful to study the brain areas activated during ictal vomiting. METHODS: We performed ictal Tc-HMPAO SPECT scans in two patients with mesial temporal lobe epilepsy (MTLE) whose seizures were characterized by ictal retching and vomiting. MTLE was documented by typical clinical seizure semiology, interictal and ictal EEG findings, hippocampal atrophy on magnetic resonance imaging (MRI) scan, and a seizure-free outcome after selective amydalohippocampectomy. In both patients, seizures originated in the nondominant temporal lobe. We obtained accurate anatomic reference of rCBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. We used ictal SPECT studies in 10 patients with MTLE who had seizures without ictal vomiting as controls. RESULTS: In the two patients with ictal vomiting, we found a significant hyperperfusion of the nondominant temporal lobe (inferior, medial, and lateral superior) and of the occipital region on ictal SPECT. In patients without ictal vomiting, on the contrary, these brain regions never were hyperperfused simultaneously. CONCLUSIONS: Ictal SPECT provides further evidence that activation of a complex cortical network, including the medial and lateral superior aspects of the temporal lobe, and maybe the occipital lobes, is responsible for the generation of ictal vomiting.

Adult↗

PubMed1999

Impact of the ECG for detection of intraatrial conduction block after atrial flutter ablation.

Induction of complete bidirectional conduction block via the posterior isthmus of the right atrium is introduced as a standard endpoint for catheter ablation of atrial flutter. The present study sought to investigate the impact of changes in P wave duration and morphology detected by the surface ECG during coronary sinus and posterolateral right atrial stimulation as a marker for conduction block. Morphology and duration changes of the paced P wave before and after radiofrequency catheter (RFC) ablation were estimated in 22 patients referred for ablation of atrial flutter. We looked for a morphology change of the terminal portion in the 12-lead ECG and an increment of P wave duration. In 16 of 22 patients in whom atrial flutter ablation resulted in a complete bidirectional block, the conduction block was unidirectional in 4 patients and conduction times remained unchanged in 2 patients. After induction of complete bidirectional block a change of the terminal portion of the P wave towards a more positive morphology in one or more inferior leads was detected in 14 (88%) of 16 patients during coronary sinus stimulation and in 15 (94%) of 16 patients during posterolateral right atrial stimulation. These changes were predominantly observed in the inferior leads. Positive morphology changes of the terminal P wave portion in the inferior leads indicating conduction block with a sensitivity of 86% and a specificity of 100% were observed. An increment of 10 ms or more in P wave duration indicates conduction block with a specificity of 100% and a sensitivity of 67%. There was a significantly larger increment of P wave duration during coronary sinus (CS) stimulation compared to posterolateral right atrial stimulation (38 +/- 21 vs 16 +/- 21 ms). The analysis of P wave duration and morphology in the inferior leads of the surface ECG is a reliable tool to assess the intraatrial conduction after atrial flutter ablation. Different conduction during coronary sinus and posterolateral right atrial pacing may cause a different P wave duration after ablation.

Aged↗

PubMed1999

Atrial flutter ablation using a technique for detection of conduction block within the posterior isthmus.

Catheter ablation orientated on the induction of a functional intraatrial block within the posterior isthmus of the tricuspid annulus has been shown to effectively abolish atrial flutter. In order to improve and simplify the current technique, a strategy based on an electrode catheter for combined right atrial and coronary sinus mapping and stimulation was explored prospectively. Twenty-four consecutive patients referred for catheter ablation of recurrent type I atrial flutter were included. A steerable 7 Fr catheter (Medtronic/Cardiorhythm) composed of two segments with 20 electrodes was used for right atrial and coronary sinus activation mapping and stimulation. Multiple steering mechanisms allowing intubation and positioning of the distal part within the coronary sinus were incorporated into the device. Adequate positioning of the mapping catheter was achieved solely via a transfemoral approach in all patients after 7.7 +/- 4.6 minutes, providing stable electrogram recordings during the entire ablation procedure. Radiofrequency current ablation (16.3 +/- 9.6 pulses) caused a significant bidirectional increase of the mean intraatrial conduction times via the posterior isthmus irrespective to the stimulation interval. Significant changes of intraatrial conduction properties were induced during ablation in 22 of 24 patients (bidirectional block: n = 18, unidirectional block: n = 3, conduction delay: n = 1, unchanged conduction: n = 2). Following ablation atrial flutter was noninducible in all patients. Twenty-two of 24 patients (92%) remained free of atrial flutter episodes during a follow-up of 12.5 +/- 5.7 months. Two of six patients without a bidirectional conduction block had a recurrence of atrial flutter. Atrial flutter ablation guided by the induction of an intraatrial conduction block can be effectively performed with this novel strategy for combined mapping of the posterior tricuspid isthmus, including coronary sinus and right atrial free wall. This transfemoral approach has a high accuracy with respect to the detection of radiofrequency current-induced changes of intraatrial conduction patterns.

Atrial Flutter↗

PubMed1999

Efficacy and safety of simultaneous immunomagnetic CD34+ cell selection and breast cancer cell purging in peripheral blood progenitor cell samples used for hematopoietic rescue after high-dose therapy.

We have established a new simultaneous positive/negative selection procedure using the Baxter Isolex 300i system. We tested its tumor cell (TC) purging efficacy by tumor contamination tests ex vivo and its safety in a group of 17 breast cancer (BC) patients by measuring hematopoietic recovery after high-dose (HD) therapy and autologous stem cell rescue with the selected cells. Tumor contamination tests resulted in a TC depletion of 4.1-6.0 log steps. The CD34+ cell yield in this experimental setting was 38.9-91.5%, and the CD34+ cell purity was 86.0-96.0%. In a group of 17 BC patients (5 high-risk adjuvant, > or = 10 lymph nodes positive, and 12 metastatic), we processed leukapheresis products (LPs) by simultaneous positive/negative selection. In these clinical samples, the mean CD34+ cell yield was 56.2% (range, 14.0-80.1%), and the CD34+ cell purity was 94.5% (range, 69.0-99.8%). Additionally, we screened samples of the patients' LPs before and after the purging procedure for contaminating TC by immunocytochemistry. In 15 of 17 tested cases, TCs were detectable prior to the purging procedure. After the procedure, we could not detect residual TCs in 16 of 17 cases. In one case, we found a highly reduced number of TCs. Furthermore, we evaluated the times for hematopoietic reconstitution in a group of five BC patients in the high-risk adjuvant situation who underwent HD chemotherapy and hematopoietic rescue with positive/negative selected stem cells and compared it with our own data from 10 BC patients who, after identical HD therapy, received only positively selected CD34+ cells and 14 patients who, after identical HD therapy, received autografts purged by incubation with toxic ether lipids (ET-18-OCH3). In all groups, a leukocyte count of >2000 cells/microl was reached at day +10. A platelet count of > 50,000 cells/microl was reached at day +12 in the ET-18-OCH3 group and at day +14 in the other two groups. Furthermore, 12 patients with metastatic disease rescued with positive/negative selected stem cells after HD therapy also showed fast and comparable hematopoietic recovery. The new simultaneous immunomagnetic positive/negative selection using a closed system is effective and safe. Processing LPs leads to a similar CD34+ cell yield, a higher TC depletion compared to standard CD34+ cell selection, and no delay in hematopoietic recovery.

Antigens, CD34↗

PubMed1999

Molecular properties and signalling pathways of the histamine H1 receptor.

With cloning of the gene encoding the histamine H1 receptor, a new area of histamine research has become reality. Finally, it seems feasible to study the target of the therapeutically important clans of antihistamine. Expression of the genes in mammalian cells allows detailed investigations of the various signal transduction routes of the histamine H1 receptor. Moreover, using molecular biological techniques, it is now possible to investigate ligand receptor interaction at the molecular level. Studies with mutant H1 receptors have shown that H1 antagonists bind to a specific amino acid residues in TM3 and 5. It is expected that these new developments will provide much fundamental knowledge on the ligand interaction with the H1 receptor.

Amino Acid Sequence↗

PubMed1998

High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models.

GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and GT-2331 ((1R,2R)-4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole) were developed as new potent histamine H3 receptor antagonists. The functional activity of these ligands on the histamine H3 receptor-mediated inhibition of neurogenic contraction of the guinea-pig jejunum and histamine H3 receptor-mediated inhibition of norepinephrine release from guinea-pig heart synaptosomes were investigated. GT-2227 and GT-2331 both antagonized the inhibitory effects of (R)-alpha-methylhistamine on the contraction induced by electrical field stimulation in the guinea-pig jejunum with pA2 values of 7.9+/-0.1 and 8.5+/-0.03, respectively. In addition, GT-2227 and GT-2331 antagonized the inhibition of norepinephrine release in cardiac synaptosomes by GT-2203 ((1R,2R)-trans-2-(1H-imidazol-4-yl)cyclopropylamine), a histamine H3 receptor agonist. The current results demonstrate the antagonist activity for both GT-2227 and GT-2331 in two functional assays for histamine H3 receptors.

Animals↗

PubMed1998

Activation of EGF receptor family members suppresses the cytotoxic effects of tumor necrosis factor-alpha.

Tumor necrosis factor (TNF)-alpha has a broad range of biological activities, which depend heavily on cell type and physiological condition. In a panel of human tumor cell lines we analyzed expression of the receptor tyrosine kinases EGFR, ErbB2 and ErbB3, and the response to TNF-alpha. Among the cell lines tested those resistant to TNF-alpha were found to express high levels of either EGFR, or ErbB2 and ErbB3. In TNF-sensitive breast and cervical carcinoma cells activation of EGFR or ErbB2 by the exogenous growth factors EGF and heregulin beta1 resulted in a significant increase in the number of cells surviving TNF-alpha treatment. In contrast, inhibition of EGFR activation in TNF-resistant breast carcinoma cells by the novel antagonistic anti-EGFR antibody 14E1 sensitized the cells to the cytotoxic effects of TNF-alpha. A bacterially expressed fusion protein consisting of a 14E1 single-chain (sc) Fv antibody fragment linked to human TNF-alpha retained TNF-alpha activity. This scFv(14E1)-TNF-alpha molecule localized specifically to EGFR on the surface of tumor cells and activated the NF-kappaB pathway in co-cultured T cells, as demonstrated by electrophoretic mobility shift assays.

Animals↗

PubMed1998

Comparison of various in vitro susceptibility methods for testing Stenotrophomonas maltophilia.

A total of 57 clinical isolates were screened by disk diffusion for a related pharmacodynamic study. Testing was performed using National Committee for Clinical Laboratory Standards guidelines, except that results were interpreted at 16 to 18 h and 48 h. Of the 57 isolates, 19 were randomly chosen for additional comparative susceptibility testing of five methods (disk diffusion, Etest, Alamar colorimetric broth microdilution, Vitek, and MicroScan) and an in-house broth microdilution method. The two diffusion methods (disk and Etest) had the closest correlation. The commercial broth microdilution methods and the in-house microdilution method generated inconsistent results for all agents except trimethoprim-sulfamethoxazole. Vitek compared poorly with both diffusion and microbroth dilution methods. The most significant discrepancies were evident with all methods when the incubation period was extended to 48 h. When results were interpreted at 48 h, the incidence of resistance for all bactericidal agents was approximately double the resistance observed at 16 to 18 h. The bacteriostatic agents, trimethoprim-sulfamethoxazole and doxycycline, demonstrated the greatest in vitro activity and were least influenced by extended incubation with diffusion methods. Because correlative in vivo and in vitro studies have not revealed an effective therapeutic regimen for serious S. maltophilia infections, susceptibility results with all testing methods should be interpreted with caution when choosing therapy for patients with life-threatening infections. Susceptibility testing for this heterogeneous group remains controversial and routine testing, with the possible exception of doxycycline (or minocycline) and trimethoprim-sulfamethoxazole, should be avoided. Our data support that if testing is done with bactericidal agents, consideration should be given to interpretation after 48-h incubation.

Anti-Bacterial Agents↗

PubMed1998

Constitutive activity and structural instability of the wild-type human H2 receptor.

Stable expression of the human H2 receptor in Chinese hamster ovary cells resulted in an increase in basal cyclic AMP (cAMP) production, which was inhibited by the inverse agonists cimetidine, famotidine, and ranitidine with potencies similar to those found for the rat H2 receptor. Burimamide, a neutral antagonist at the rat H2 receptor, behaved as a weak partial agonist at the human H2 receptor. Burimamide competitively antagonized both the histamine-induced increase in cAMP and the cimetidine-induced reduction of the basal cAMP level with apparent K(B) values that were similar to its H2 receptor affinity. Investigation of the modulation of receptor expression after long-term drug treatment revealed that at low concentrations histamine induced a significant reduction in H2 receptor expression, whereas at high concentrations receptor expression was slightly increased. The partial agonist burimamide induced, like inverse agonists, an up-regulation of the human H2 receptor after prolonged treatment. These findings suggest a structural instability of the constitutively active human H2 receptor in transfected Chinese hamster ovary cells. Occupation of the H2 receptor by any ligand reduces the instability, thus resulting in higher cellular expression levels.

Animals↗

PubMed1998

[Clinical and molecular biology studies of respiratory papillomatosis].

BACKGROUND: Recurrent laryngeal papillomatosis is a benign neoplastic disease which is probably caused by but at least associated with the human papillomavirus. It can be of significant importance for the affected patients because of its recurrent clinical course. A great variety of therapeutic measures has been described including the surgical removal either with conventional instruments or using the laser. Development of malignancies from papillomas have been reported. PATIENTS: The clinical courses of all 95 patients who have been treated for laryngeal papillomatosis since 1960 were analysed retrospectively. The two most common forms of treatment, surgical removal either conventionally or with the use of the laser, were compared. "Hot start" polymerase chain reaction and Southern blot hybridization were used to detect HPV DNA. The case reports of all patients developing cancer of the larynx are included. RESULTS: Laryngeal papillomatosis is a disease of all ages, more often first diagnosed in the first and fourth decade. Puberty had no effect on the clinical course. The different forms of treatment did not affect the rate of recurrence. However, the rate of complications such as tracheostomy and glottic webs was significantly reduced after laser surgery. Since the introduction of this new form of therapy no more tracheostomies had to be performed on these patients. HPV DNA was found in four of five samples (HPV 6:3, HPV 11:1). Squamous cell carcinoma subsequently developed in four cases, three of which occurred almost simultaneously and were therefore not included. CONCLUSION: The term juvenile laryngeal papillomatosis should be replaced by recurrent respiratory papillomatosis. One could then distinguish according to the age of onset, i.e., in children below the age of 16 years and in adolescents and adults older than 15 years. The occurrence of squamous cell carcinomas in patients previously treated for papillomas underlines the need for repeated histological studies. The surgical treatment remains the mainstay in the management of laryngeal papillomatosis. The laser surgical technique is superior to conventional removal. Using the at present most sensitive and specific methods HPV DNA can be detected in a large percentage of laryngeal papillomas.

Adolescent↗