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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 127 records · Page 7Linked to original sources

[Dislocation of the cricoarytenoid joint: diagnosis and therapy].

BACKGROUND: Laryngeal joint injury or cricoarytenoid dislocation is a relatively rare laryngologic finding, according to the international medical literature. It may occur as a result of external neck trauma or more frequently as a result of intubation. Chief symptoms are hoarseness, vocal fatigue, and loss of voice control. PATIENTS: Between 1993 and 1997 we diagnosed an arytenoid dislocation in 2 female and 5 male patients, in every case the etiology was an intubation trauma. Videolaryngoscopic recording was the most useful aid in diagnosis. RESULTS: Six patients were treated with closed reduction surgery between 8 and 49 days after dislocations. Normal voice was restored in four patients, and in one patient as late as 49 days after the dislocation. One patient had an additional recurrent nerve paralysis. CONCLUSIONS: Our results suggest that a closed reduction of the arytenoid luxation can be successful even several weeks after the injury.

Adolescent↗

Prevalence of human papillomavirus in squamous cell carcinoma of the head and neck determined by polymerase chain reaction and Southern blot hybridization: proposal for optimized diagnostic requirements.

Human papillomaviruses (HPV) are discussed as cofactors in the carcinogenesis of squamous cell carcinoma of the head and neck (SCCHN). The prevalence of HPV infection in SCCHN is the subject of controversy since reported HPV prevalences range from less than 10% to almost 100%, depending mainly on the detection method employed. This study presents a realistic approximation to the real prevalence of HPV in SSCHN by applying polymerase chain reaction (PCR) and Southern blot hybridization (SBH), which are the most sensitive and specific HPV detection methods. Diagnostic procedures were optimized by applying a "hot-start" PCR protocol followed by a confirmatory SBH of the PCR products to reactions using both type-specific and consensus primers and probes. DNA of 75 tumour samples and 22 normal mucosa samples of the same patients were investigated. In 14 cases genomic SBH using complete HPV genomes as probes was performed additionally. HPV DNA was detected in 17/75 (22.7%) SCCHN specimens. HPV 16 was identified in four cases, HPV 45 in three cases, and HPV 6 and 18 in one case each. Hot-start PCR and SBH are the most reliable HPV detection methods, as they minimize both false-positive and false-negative results. With these methods, a HPV prevalence of 23% was achieved, which can be assumed to be representative for comparable study populations. The significant number of positives detected only by consensus primer PCR, along with the identification of HPV 45, indicate that further HPV types may play an important role in the genesis of SCCHN.

Adult↗

Several unsuccessful internal and external defibrillations during active can ICD implantation in a patient with pneumothorax.

During implantable cardioverter defibrillator (ICD) implantation of an active can ICD several defibrillations with 20 J and 34 J as well as 360 J externally were ineffective. The implant criteria were finally met with a second defibrillation lead and reversed polarity. A left-sided pneumothorax due to subclavian vein puncture was detected soon after ICD implantation. It is assumed that especially in the active can alignment the developing pneumothorax made defibrillation current flow more difficult. In case of several unsuccessful defibrillations during active can ICD implantation in which the subclavian vein was punctured, the possibility of a pneumothorax should be considered.

Defibrillators, Implantable↗

Molecular analysis of a gene encoding a cell-bound esterase from Streptomyces chrysomallus.

A gene (estA) encoding a 42-kDa cell-bound esterase, EstA, was found to be located 75 bp upstream of the cyclophilin A gene (cypA) of Streptomyces chrysomallus. Western blot analysis revealed the presence of EstA (42 kDa) in cell extracts of S. chrysomallus X2 and Streptomyces lividans. EstA specifically hydrolyzes short-chain p-nitrophenyl esters. EstA formation starts at the end of growth phase, and its activity level remains constant throughout stationary phase. Expression of estA from the melanin (mel) promoter in plasmid pIJ702 led to a substantial increase of total esterase activity in streptomycetes.

Amino Acid Sequence↗

Carotid endarterectomy after recent stroke--how soon? An interim analysis.

AIM: To determine whether timing of carotid endarterectomy (CEA) was significant in terms of morbidity and mortality for significant carotid stenosis in a prospectively evaluated cohort of patients with recent stroke. METHODS: A tailored protocol using contemporary neuro-imaging modalities including transcranial Doppler and non-invasive angiography. Standardised clinical scores, neurological deficit scores, an aetiopathogenic scale and disability stroke scales were used in the two group. Statistical analysis was done to compare differences in two groups: CEA done less than 6 weeks after stroke (group 1) and CEA done more than 6 weeks after stroke (group 2). RESULTS: Patients formed part of the Durban Stroke Data Bank (N = 655), with 26 patients in group 1 (CEA a mean of 16 days after stroke) and 34 in group 2. There were no statistically significantly differences between the two groups with regard to demographic factors, clinical scales, neurological deficit scores and investigate findings. There was 1 post-CEA stroke and 1 death in each group (P = 0.781), which was not significantly different. CONCLUSION: Timing of CEA after stroke may be unimportant with regard to mortality and morbidity in patients with relatively small stable neurological deficits. Other causative factors, as yet unclear, remain to be identified.

Algorithms↗

Costimulation of T cell proliferation by a chimeric B7-2 antibody fusion protein specifically targeted to cells expressing the erbB2 proto-oncogene.

T cells require at least two signals for activation and clonal expansion. The first signal conferring specificity is initiated by interaction of the T cell receptor with antigenic peptides in the context of MHC molecules. The second, costimulatory signal can be provided by cell surface molecules on APCs such as B7-1 (CD80) and B7-2 (CD86), which interact with their counter-receptors on T cells. The absence of costimulatory signals presents one possible mechanism for tumor cells to escape immune surveillance. In experimental models transfection of B7 genes into tumor cells can result in T cell-dependent tumor rejection. We have developed a novel approach to direct the costimulatory B7-2 molecule to the surface of target cells. Our approach is based on a chimeric fusion protein that consists of the extracellular domain of human B7-2 fused to a single-chain Ab domain (scFv) specific for the ErbB2 protein, a type I growth factor receptor overexpressed in a high percentage of human adenocarcinomas. This B7-2(225)-scFv(FRP5) molecule expressed in the yeast Pichia pastoris and purified from culture supernatants is functionally active and binds to B7 counter-receptors and to ErbB2. B7-2(225)-scFv(FRP5) localizes specifically to the surface of ErbB2-expressing target cells, thereby providing a costimulatory signal that results in enhanced proliferation of syngeneic T cells. Our results suggest that effective tumor vaccines for cancer immunotherapy could be created by targeting such chimeric ligands to the surface of tumor cells.

Abatacept↗

T cell tolerance and autoimmunity.

Many T cells with auto-aggressive potential are deleted in the thymus. Although some of these escape to the general circulation, they do not usually damage organs such as the pancreas. To investigate the mechanisms preventing autoimmunity, we generated transgenic mice expressing known genes under the control of various promoters. We found that the occurrence of autoaggression depended on factors such as the precursor frequency of responding T cells, their state of activation, their accessibility to the autoantigen, the physicochemical properties of the autoantigen, the possibility of priming by environmental antigens which mimic the target antigen, and some inflammatory reaction in the target site.

Animals↗

Constitutive and strong association of PAF53 with RNA polymerase I.

Mouse RNA polymerase I (Pol I) is composed of 14 polypeptides, 3 of which are thought to be loosely associated with, and may be dislodged from, Pol I. To find out whether these polymerase-associated factors (PAF53, 51, and 49) serve a role in growth-dependent control of rDNA transcription, we generated polyclonal antibodies against three subunits of murine Pol I, RPA116, RPA40 and PAF53, and used different experimental approaches, e.g. immunoblot analysis, immunoprecipitation and immunofluorescence studies, to compare the stoichiometry of individual subunits both in different Pol I preparations and in extracts from cells grown under different conditions. This comparative analysis reveals that the molar ratio of the second largest subunit RPA116 to PAF53 is the same, irrespective of whether crude extracts or highly purified Pol I fractions are analyzed. Significantly, the relative level of PAF53 was comparable in exponentially growing or growth-arrested cells, indicating that growth-dependent fluctuations in Pol I activity are not accompanied by alterations in the amount of PAF53. In addition, we show by high resolution immunofluorescence analysis that, under conditions of repressed rDNA transcription, including serum starvation, actinomycin treatment und during mitosis, PAF53 remains attached to the transcriptional machinery. The finding that the Mr 53,000 protein remains in the multiprotein complex under all experimental conditions tested indicates that PAF53 is not a loosely associated regulatory factor but a bona fide subunit of Pol I.

3T3 Cells↗

Yeast cycloheximide-resistant crl mutants are proteasome mutants defective in protein degradation.

In 1988 McCusker and Haber generated a series of mutants which are resistant to the minimum inhibitory concentration of the protein synthesis inhibitor cycloheximide. These cycloheximide-resistant, temperature-sensitive (crl) mutants, in addition, exhibited other pleiotropic phenotypes, e.g., incorrect response to starvation, hypersensitivity against amino acid analogues, and other protein synthesis inhibitors. Temperature sensitivity of one of these mutants, crl3-2, had been found to be suppressed by a mutation, SCL1-1, which resided in an alpha-type subunit of the 20S proteasome. We cloned the CRL3 gene by complementation and found CRL3 to be identical to the SUG1/CIM3 gene coding for a subunit of the 19S cap complex of the 26S proteasome. Another mutation, crl21, revealed to be allelic with the 20S proteasomal gene PRE3. crl3-2 and crl21 mutant cells show significant defects in proteasome-dependent proteolysis, whereas the SCL1-1 suppressor mutation causes partial restoration of crl3-2-induced proteolytic defects. Notably, cycloheximide resistance was also detected for other proteolytically deficient proteasome mutants (pre1-1, pre2-1, pre3-1, pre4-1). Moreover, proteasomal genes were found within genomic sequences of 9 of 13 chromosomal loci to which crl mutations had been mapped. We therefore assume that most if not all crl mutations reside in the proteasome and that phenotypes found are a result of defective protein degradation.

Adenosine Triphosphatases↗

Single photon emission and cerebral computerised tomographic scan and transcranial Doppler sonographic findings in eclampsia.

OBJECTIVE: To define more clearly the neuropathophysiology of eclampsia utilising single-photon emission computed tomography (SPECT), cerebral computerised tomography (CT) and transcranial Doppler (TCD) ultrasonography. DESIGN: A prospective study SETTING: The obstetric unit in King Edward VIII Hospital, a large tertiary referral centre in Kwa-Zulu Natal, South Africa. PARTICIPANTS: Sixty-five women with eclampsia. INTERVENTIONS: Imaging and ultrasonographic investigations were performed within 48 hours postpartum. Unenhanced cerebral CT scans were performed in all the women and SPECT scans were performed on 63 women using Technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) as a tracer of regional cerebral blood flow. Middle cerebral artery blood flow velocity waveforms were measured using 2 MHz pulsed Doppler ultrasound via the transtemporal approach. MAIN OUTCOME MEASURES: Abnormalities in SPECT scan, CT scan and TCD ultrasound findings. RESULTS: SPECT scanning revealed perfusion deficits in the watershed areas in all women, 75% of whom had concomitant deficits in the parieto-occipital areas of the brain. Hypodensities (cerebral oedema) were reported in 38 CT scans (58.5%), with parieto-occipital involvement in 97.4% of cases. Increased flow velocity measurements in the middle and posterior cerebral arteries were recorded in 36 (85.7%) women in whom TCD ultrasound was performed. CONCLUSION: The pathophysiological mechanism of eclamptic seizures is primary cerebral vasospasm with resultant ischaemia and cerebral oedema involving mainly the watershed areas and parieto-occipital lobes of the brain. SPECT scanning has been shown to be superior to CT scanning and TCD ultrasonography in detecting neuropathophysiologic alterations in eclampsia. However, each of the three investigative tools provide its own unique information and all three are necessary research techniques to improve our understanding of the neuropathophysiological mechanism of eclamptic seizures.

Adolescent↗

High incidence of antibiotic resistance among bacteria in 4 intensive care units at a university hospital in Sweden.

The frequency of antibiotic resistance among bacteria in 4 intensive care units (ICUs) at a university hospital in Sweden was investigated annually from 1993 to 1996. An increase in ampicillin-resistant enterococci from 1993 to 1995 was seen which was due to a shift from Enterococcus faecalis to Enterococcus faecium. After a special infection control programme was instituted, the rate of ampicillin resistance among enterococci and the number of E. faecium isolates declined during 1996. The oxacillin resistance rates for Staphylococcus aureus were < or = 2%, while most of the coagulase-negative staphylococci (CNS) were oxacillin resistant. No vancomycin-resistant enterococci or staphylococci were seen. The ciprofloxacin resistance rate for CNS and Enterococci spp. were high. Relatively, high levels of resistance to cefotaxime and piperacillin/tazobactam among Enterobacter spp. were also seen. During 1995 and 1996 Pseudomonas aeruginosa showed increasing resistance to ceftazidime, ciprofloxacin and piperacillin/tazobactam. This was due to an outbreak among rather few patients. The overall resistance rates for Gram-negative bacteria were low for aminoglycosides and imipenem. From 1993 to 1996 the total antibiotic consumption decreased by 27% in the whole hospital and 16.5% in the ICUs. However, the reduced antibiotic consumption was paralleled with a 23% decrease in the total number of patients treated in the hospital from 1993 to 1996. In contrast there was an 11.5% increase in the number of ICU patients treated during this period. The conclusion is that all ICUs within a hospital should have a programme for 'on-line' antibiotic resistance surveillance of drugs used in that unit in order to change the empiric treatment when there is an increase in antibiotic resistance. It is also important to survey the antibiotic consumption in the ICUs in order to avoid further selective pressure on bacteria showing increased resistance rates.

Anti-Bacterial Agents↗

[Do low-threshold detoxification units reach new groups of the drug dependent?].

The conventional form of detoxication for illicit drug users in German psychiatric hospitals is an inpatient treatment approach connected with high admission prerequisites. These demand a high stage of motivational compliance from of the patients, e.g. the determination to continue with long-term treatment aiming at a life free of drugs. This strategy is termed "high-threshold" approach. A new form of inpatient treatment is the "low-threshold" approach offering intervals of some days or weeks free of drugs to illicit drug users, supported by professional detoxication strategies. This study compares client characteristics of illicit drug users treated at "high-threshold" vs. "low-threshold" units. A new subpopulation of clients could be reached who are more advanced in their drug intake careers and less influenced by social pressure to enter treatment. The differences in clients treated can be explained rather by differences in admission prerequisites than by a more balanced distribution of sexes in the newly introduced detoxication programme.

Adult↗

Prospective study of extraction atherectomy in patients with acute myocardial infarction.

Although percutaneous transluminal coronary angioplasty (PTCA) has been an effective treatment for primary reperfusion in acute myocardial infarction, patients with thrombolytic ineligibility, thrombolytic failure, cardiogenic shock, and vein graft occlusion remain at high risk for complications with PTCA treatment. The transluminal extraction catheter may be useful for treatment for such patients owing to its ability to aspirate thrombus. At 2 clinical centers, extraction atherectomy was prospectively evaluated in 100 patients (age 62 +/- 10 years). High-risk features included thrombolytic failure in 40%, postinfarct angina in 28%, presence of angiographic thrombus in 66%, presence of cardiogenic shock in 11%, and a saphenous vein graft occlusion in 29%. Procedural success, defined as a final residual stenosis <50% and Thrombolysis in Myocardial Infarction 2 or 3 grade flow, was seen in 94%. Events during the hospitalization included death in 5%, bypass surgery in 4%, and blood transfusion in 18%. In a substudy, patients enrolled at William Beaumont Hospital (n = 65) underwent elective predischarge angiography, which revealed a patent infarct-related vessel in 95%. These patients were also followed for 6 months with angiographic follow-up in 60%. Target vessel revascularization was necessary in 38%, and 6-month mortality was 10%. Although long-term vessel patency was 90%, angiographic restenosis occurred in 68%. Acute myocardial infarction patients can be treated with extraction atherectomy with a high technical success rate and a low incidence of complication. Infarct artery patency at 1 week and 6 months was excellent; however, angiographic restenosis remains a problem. Extraction of thrombus in this high-risk group of patients is associated with low in-hospital mortality and a high rate of vessel patency at 6 months.

Angina Pectoris↗