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Biomedical subjects

M Herrmann

Publications and source records attributed to M Herrmann.

At least 109 records · Page 6Linked to original sources

[Puerperal sepsis caused by streptococcus group A with a severe form of progression like "toxic shock-like syndrome"].

HISTORY AND CLINICAL FINDINGS: A previously healthy 32-year-old woman was admitted with shock symptoms 5 days after an uneventful home delivery. She developed a fever up to 39.5 degrees C during the days after delivery with sore throat, diarrhoea and muscle aches in all limbs. On physical examination there were swellings of the arms and lower legs as well as macular and vesicular erythrodermia, especially of the trunk. INVESTIGATIONS: Abnormal laboratory findings were thrombocytopenia (20,000/microliters), increased serum concentrations of fibrin breakdown products (102 mg/dl) and of C-reactive protein (> 200 mg/dl), increased creatine kinase (5700 U/l), transaminases (GOT 220 U/l, GPT 52 U/l), creatinine (2.0 mg/dl) and urea (114 mg/dl). Streptococcus pyogenes was grown on blood culture and from vaginal smear. Sonography, echocardiography and radiological examinations failed to demonstrate a septic focus. TREATMENT AND COURSE: Mechanical ventilation was required for 7 days because of respiratory failure and shock symptoms (toxic shock-like syndrome, TSLS). Penicillin G and tobramycin were given after the bacteriological diagnosis. Severe consumption coagulopathy was successfully treated with antithrombin III and platelet concentrates. After extubation she was found to have a flaccid tetraparesis, especially of the right and of the legs, due to soft-tissue necrosis and damage to peripheral nerves. An embolic occlusion of the right brachial artery 4 weeks after onset of the disease required upper-arm amputation. CONCLUSION: One of the decisive factors for the prognosis of TSLS is early antibiotic treatment. The prodromal symptoms in this case underline the necessity of early recognition and treatment to prevent a full-blown picture of the syndrome.

Adult↗

Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus.

OBJECTIVE: To investigate whether the established impaired phagocyte function in systemic lupus erythematosus (SLE) patients also affects apoptotic cell clearance. Accumulation of apoptotic waste as a source for autoantigens that induce and maintain autoimmune responses is discussed. METHODS: Apoptosis was detected by morphology and propidium iodide staining. In vitro phagocytosis of autologous apoptotic cells in cultured peripheral blood mononuclear cells was evaluated microscopically. Cross-feeding experiments were performed to investigate phagocytosis of heterologous apoptotic cells by in vitro-differentiated macrophages. Furthermore, the effect of annexin V on the phagocytosis of apoptotic cells was investigated. RESULTS: Reduced clearance of apoptotic cells in SLE patients was observed. The defective clearance appeared to reflect phagocyte dysfunction and not an abnormal execution of apoptosis. A similar picture was seen when in vitro-differentiated macrophages from control populations were treated with annexin V. CONCLUSION: Noninflammatory engulfment phagocytosis of apoptotic cells is decreased in SLE patients. Persistently circulating apoptotic waste may encounter inflammatory removal pathways and serve as immunogen for the induction of autoreactive lymphocytes and as antigen for immune complex formation.

Annexin A5↗

[Prevention of catheter-related infections, The official American guidelines--from the Centers for Disease Control].

The official German guidelines for prevention of intravascular-device-associated infections were published by the Bundes-gesundheitsamt, now called the Robert-Koch-Institut, 12 years ago. The recently published official "Guidelines for Prevention of Intravascular-Device Associated Infections" of the Centers for Disease Control and Prevention (CDC) are categorized according to scientific evidence. The American guidelines are very detailed and differ in some aspects from the official German guidelines. The purpose of the present paper is to inform the German-speaking anaesthesiologist about the official CDC guidelines and to provide an update on the prevention of intravascular-device-associated infections.

Catheterization↗

[The official American guidelines for prevention of nosocomial pneumonia. U. S. Centers for Disease Control].

The official German guidelines for prevention of nosocomial pneumonia were published by the Bundesgesundheitsamt, now called Robert-Koch-Institut, twelve years ago. The recently published official "guidelines for prevention of nosocomial pneumonia" of the Centers for Disease Control and Prevention (CDC) are categorized according to scientific evidence. The American guidelines are very detailed and differ in some aspects from the official German guidelines. The purpose of the present paper is to inform the German anaesthesiologist about the official CDC guidelines and to provide a renewed background for the prevention of nosocomial pneumonia.

Cross Infection↗

[Gene therapy in rheumatoid arthritis--an already feasible therapeutic principle?].

Based upon our increasing knowledge of mechanisms underlying tissue destruction in RA patients, new therapeutic principles have been developed, aimed at blocking proinflammatory cytokines or using antiinflammatory cytokines. Both principles, however, have proven to be very effective. In addition, the availability of the methodology to transduce cells with genes has initiated first experiments in animal models to test whether gene therapy for arthritis is suitable, followed by a first, very carefully formulated protocol for human RA. Gene therapy for RA has to still be considered as an experimental form of therapy in a very early stage, not allowing even now any serious treatment offer to RA patients. Several problems, such as the question of a suitable vector system have not yet been solved. With more experiments this therapeutic principle might become available and might prove effective even in a disease with a systemic character like RA in the coming years.

Animals↗

Enhanced antigenicity of a four-contact-residue epitope of the measles virus hemagglutinin protein by phage display libraries: evidence of a helical structure in the putative active site.

Antigenicity and conformational propensities of synthetic peptides corresponding to the sequential epitope H236-255 of the measles virus hemagglutinin protein were investigated. This epitope corresponds to the neutralising and protective monoclonal antibody BH129 and includes Arg243, implicated in CD46-down-regulation and Arg253 that has been mapped to the putative enzymatic site. Fine mapping with truncation-, elongation-, Gly- and Ala-substitution analogues defined EL-QL as the critical residues of the minimal epitope S244ELSQL249. CD spectra of peptides, comparison with the 3D-structure of homologous sequences, and prediction algorithms suggested a helical structure with the contact residues E245L-QL249 located on the protein surface. Mimotopes obtained with a 6-mer phage display library contained a consensus Pro (important for binding) instead of Ser247 of the wild-type sequence (irrelevant for binding). The kink induced by Pro seemed to be essential to bring the 4 contact-residues in the mimotopes and in the corresponding short peptides together. CD analysis and prediction algorithms suggested that non-helical conformations of the phage insert and of the peptides may favourably mimic the antigenic helical turns of the wild-type sequence, resulting in an up to 135 times higher antigenicity of the mAb towards the mimotope peptides.

Animals↗

Rest-activity rhythm of the blind mole rat Spalax ehrenbergi under different lighting conditions.

The mole rat is a solitary, subterranean and photoperiodic rodent. We investigated its rest activity behavior under several lighting conditions, complemented our observations with light-induced c-fos expression, and compared the activity behavior of two chromosomal forms (2n = 58 and 60). The 26 mole rats had a clear overall preference for activity in the light or dark period, but prolonged recordings in five individuals showed that the initial preference was not stable in the nocturnal animals, they became diurnal. A 6-h advance of the light-dark (LD) cycle induced a shift of activity and the previous LD preference was reestablished. The large daily variability of activity onset did not allow this study to determine whether the animals were entrained to the LD cycle upon release into constant darkness (DD) or whether activity had been masked by light. The period of the motor activity rhythm in DD free ran in more than 50% of the animals. No differences in activity were observed between the two karyotypes. Immunohistochemistry for c-fos expression in the nucleus suprachiasmaticus at different circadian times showed that c-fos was induced only in animals exposed to a 1-h light pulse during the subjective night, but not during the subjective day or in control animals in the absence of a light pulse. The large intra- and inter-individual variability in daily motor activity both in LD and in DD suggest only a weak photic entrainment of the circadian clock to light of approximately 100 lux, and possibly a weak regulation of behavior by the circadian clock.

Animals↗

Increased spontaneous in vitro apoptosis in double negative T cells of humans with a fas/apo-1 mutation.

We describe a 17 year old patient suffering from Canale-Smith syndrome (CSS) including chronic lymphadenopathy, splenomegaly, hypergammaglobulinemia and recurrent Coombs positive hemolytic crises. The parents are not consanguine, all other family members including two brothers are healthy. Peripheral blood mononuclear cells of the patient showed an increased rate of CD3 positive, CD4/CD8 double negative T-lymphocytes. In vitro assays showed these cells to have an increased rate of spontaneous apoptosis. Though expression of Fas/Apo-1 (CD95) and Fas-ligand (FasL) was detected on RNA- and protein level we found Fas/Apo-1 mediated apoptosis being significantly reduced. Sequencing of the fas/apo-1 gene proved the patient RT and his father to carry a point mutation at position 804 located in exon 9 (death domain) leading to an amino acid substitution. For developing of CSS, a fas/apo-1 mutation seems to be necessary but not sufficient. An additional independent mechanism must be involved in the pathogenesis of human lpr<-phenotype.

Adolescent↗

Induction of apoptosis reduces immunogenicity of human T-cell lines in mice.

Apoptotic cells, e.g. postinflammatory neutrophils, were reported to be engulfed by phagocytes without induction of an inflammatory response. We investigated the humoral immune response of BALB/c mice after repeated injection of viable or apoptotic human T cells. Following interleukin-2 (IL-2) deprivation, phytohaemagglutinin (PHA)/IL-2 expanded human T-cell lines were irradiated with UV-B light to induce apoptosis, confirmed by propidium iodide staining of Triton X-100-lysed cells. Indirect immunofluorescence was used to detect antilymphocyte antibodies 7 days after each injection. We found high levels of antilymphocyte antibodies in all animals immunized with viable T cells, whereas animals injected with apoptotic cells showed a significantly reduced humoral immune response. We conclude that apoptotic cells induce poor xenoreactive T-cell responses when compared with viable cells.

Animals↗

Microbiological examinations and in-vitro testing of different antibiotics in therapeutic endoscopy of the biliary system.

BACKGROUND AND STUDY AIMS: Prior to endoscopic therapeutic procedures, no antibiotic prophylaxis is administered routinely. Because of the reported incidence of infectious complications, which may reach up to 10%, a prospective study was undertaken to investigate the effects of a prophylactic dose of cefuroxime on the incidence of bacteremia and clinical signs of infection, but no significant effects could be demonstrated. In addition to this published work, blood and bile cultures obtained in this trial were also investigated, and the in-vitro susceptibility to several antibiotics was tested in order to recommend the appropriate substances. PATIENTS AND METHODS: Ninety-nine consecutive patients (51 men, 48 women; mean age 61.4 +/- 17 years) with biliary obstruction who underwent an endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography with drainage (PTCD) were included. Sequential blood cultures were taken before and up to 60 minutes after the endoscopic intervention. Bile cultures were obtained in 56 patients with biliary drainage. Aerobic and anaerobic cultures were prepared from all obtained specimens and the isolated organisms were identified. In the case of positive cultures, an in-vitro resistance test for 15 different antibiotics was performed. RESULTS: The incidence of bacteremia was 11.1% (n = 11), and 16 bacteria were isolated. Twelve different microorganisms were detected, with Escherichia coli found in four cases. From 41 positive out of 56 prepared bile cultures (73.2%), 91 isolates were found with 25 different species. A single agent was detected in eight cases (19.5%), while a mixed growth, with pathogens ranging from two to six species, was found in 33 cases (80.5%). The seven most frequently isolated germs were E. coli and Enterococcus (each n = 19), Klebsiella (n = 10), Streptococcus viridans (n = 9), Staphylococcus epidermidis (n = 5), Morganella morganii (n = 4), and Bacteroides fragilis (n = 3), representing 76% of all agents. Examination for fungal infection revealed positive cultures of Candida albicans in 16.1% of bile cultures (nine of 56). Interestingly, the use of proton-pump inhibitors (PPIs), with a consequent rise in the gastric pH value, led to an increase in the rate of bacteremia to 26.2% (five of 19) compared to the other patients not on PPIs (n = 80), who developed bacteremia in only six cases (7.5%; p = 0.02). In-vitro testing of different antibiotics was carried out in 73 isolates. Imipenem showed the best antimicrobial activity (98.4%), followed by trimethoprim and sulfamethoxazole (90%), amoxicillin plus clavulanic acid (87.3%), vancomycin (82.4%), and ofloxacin (76.9%). CONCLUSIONS: Escherichia coli was found to be the pathogen most frequently detected in blood and bile following endoscopic interventions in the biliary tract. Enterococci, Klebsiella and Streptococcus viridans were found in bile cultures with an incidence exceeding 10%. In view of the in-vitro test results, possible side effects, and contraindications, amoxicillin plus beta-lactamase inhibitors or quinolones are considered to be suitable antibiotics for the prophylaxis of biliary infections.

Adult↗

[Neuropsychological and psychopathologic changes following cardiac surgical procedures].

Neuropsychological and neuropsychiatric disorders following open heart surgery are estimated to occur in as many as 80 per cent of all patients. They have been recognised from the very beginning of modern heart surgery. Despite a huge amount of scientific literature, data concerning incidence, the phenomenology and duration of symptoms diverge. This finding may be explained by heterogeneous aetiopathogenetic concepts and methodological and terminological problems associated with the investigation of postoperative delirium or neuropsychological and psychopathological sequelae of cardiac surgery. Nowadays, most authors agree in respect of a multifactorial pathogenesis of cognitive deficits following cardiac surgery. Factors influencing the psychopathological and neuropsychological outcome of cardiac surgery can be divided into pre-, intra- and postoperative variables. Advanced age, degree of cardiovascular impairment and other case histories, as well as history of drug abuse, are those preoperative variables that may be responsible for a postoperative cognitive decline. The predictive value of personality traits (depression and/or anxiety), however, is most controversial. Among the intraoperative variables related to the postoperative cognitive state, are e.g. the type of operation and technical procedure (micro-/macroembolism due to the way of oxygenation, pulsatile/-non-pulsatile flow) and duration of extracorporeal circulation. In the postoperative period, the duration of intubation or ICU stay and related variables (like sleep or sensory deprivation/hyperstimulation) were identified as significant predictors of neuropsychological and psychopathological alterations. Modern research focusses on neurobiochemical markers of brain injury which may serve as early predictors of a postoperative cognitive decrease. These parameters may indicate an early postoperative diagnosis and neuroprotective treatment in patients at risk.

Cardiac Surgical Procedures↗

Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis.

In a 34-month prospective study to determine the prevalence of Staphylococcus aureus small colony variants (SCVs) in cystic fibrosis (CF) patients, S. aureus SCVs or SCVs plus normal S. aureus were recovered from 26 of 78 patients; 27 patients harbored only normal S. aureus. By pulsed-field gel electrophoresis, clonal identity was demonstrated of SCV and normal strains isolated at the same time and of multiple S. aureus SCV and normal strains in consecutive specimens from individual patients. All S. aureus SCVs were resistant to antifolate antibiotics, while the corresponding parent strains were susceptible, and in 11 of 12 SCV/normal pairs, gentamicin was less active against S. aureus with the SCV phenotype than against the normal isolate. Analysis of the underlying auxotrophism of SCVs revealed hemin, thymidine, and/or menadione dependencies. Thus, S. aureus SCVs are highly prevalent in respiratory secretions of CF patients, persist over extended periods, and may contribute to S. aureus persistence in CF patients.

Adolescent↗

Retrovirus-associated rheumatic syndromes.

The influence of environmental factors in the initiation of autoimmune rheumatic diseases is still under debate. Infections with viruses (e.g., retroviruses) or expression of gene products encoded by endogenous retroviruses are believed to contribute to both loss of tolerance for autoantigens and immunosuppression. In various rheumatic disorders the detection of retroviral antibodies provides evidence for retroviral gene expression and suggests a role in the etiopathogenesis. Molecular mimicry, defects in apoptosis, altered autoantigens, and alterations of monocyte or macrophage as well as dendritic cell functions may contribute to the molecular mechanisms causing the loss of tolerance. On the other hand, destruction of lymphocytes during lytic retrovirus infections as well as envelope gene-env derived immunosuppressive retroviral gene products may prevent chronic inflammatory diseases and tissue destruction. Furthermore, retrovirus encoded super-antigens with the potency to skew the T-cell repertoire may seriously modify the host's immune system.

Acquired Immunodeficiency Syndrome↗

High levels of circulating early apoptic peripheral blood mononuclear cells in systemic lupus erythematosus.

Increased in vitro apoptosis and altered expression of apoptosis-related molecules have been reported in systemic lupus erythematosus (SLE). It was speculated that autoantigens released from apoptizing cells may contribute to the etiopathogenesis of SLE by both activation of autoreactive lymphocytes and the formation of immune complexes. Conflicting data about the level of cellular apoptosis from animal models for SLE and human SLE indicate different pathomechanisms. In the present study we analysed the count of circulating early apoptotic cells and its correlation with the clinical activity in SLE compared with the amount in primary systemic vasculitis (PSV). The percentage of early apoptotic cells determined by Annexin V-FITC binding cells was significantly increased in peripheral blood of SLE patients compared with normal healthy donors (NHD) and PSV (NHD 5.62%, SLE 13.68%, PSV 8.69%). Analysis of lymphocytes revealed significantly increased counts in the T cell populations (NHD 5.15%, SLE 12.22%, PSV 10.01%), whereas the increase in B cells did not reach significance level (NHD 9.20%, SLE 18.95%, PSV 16.59%). Apoptotic cell count revealed no correlation to SLAM-Score or to immunosuppressive therapy, corticosteroid-dosage or absolute lymphocyte count. The general increase of circulating apoptotic cells may indicate an impaired clearance in SLE patients, independent of clinical activity or therapeutic interventions. Autoantigens from apoptotic cells may contribute to both activation of autoreactive lymphocytes and formation of immune complexes.

Activities of Daily Living↗

Left ventricular assist device infection is associated with increased mortality but is not a contraindication to transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a bridge to transplantation. Infection is a frequent and major complication associated with the use of these devices, however, the correlation of infection and outcome has not yet been evaluated in a prospective fashion. METHODS AND RESULTS: Twenty-five patients (24 male, 1 female) with end-stage cardiac failure and resulting organ dysfunction were included. Patients were bridged with the Novacor N100 portable LVAD (median duration of support, 55 days) and were evaluated prospectively by device surface cultures on explantation, molecular typing of isolates, and correlation of infection with survival to transplant. Twelve (48%) of 25 patients had LVAD infection as defined by recovery of multiple isolates of identical genotype from the device surface. Whereas only 5 (42%) of 12 patients with LVAD infection survived until transplantation, 11 (85%) of 13 patients without infection were successfully transplanted (P < .05). Death of the 7 patients with proven LVAD infection was associated with multiple organ failure or other signs of acute infection. CONCLUSIONS: LVAD infection is associated with a significantly decreased survival probability. It does not preclude successful bridging but rather may pose an indication for urgent transplantation.

Adult↗

In vitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases.

OBJECTIVE: To analyze factors related to apoptosis in systemic lupus erythematosus (SLE) peripheral blood mononuclear cells (PBMC) and to compare the findings in SLE PBMC with those in normal donor PBMC or PBMC from patients with other autoimmune diseases. METHODS: PBMC from normal healthy donors or patients with SLE, mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), or various vasculitides were isolated. The percentage of apoptosis after activation through different signaling pathways was quantified using propidium iodide staining. Protein expression of Fas/APO-1 or bcl-2, and messenger RNA (mRNA) expression of bcl-2, bcl-xL, bax, bak, Fas/APO-1, Fas ligand (Fas-L), c-myc, mad, or max were determined. RESULTS: We confirmed previous findings of increased numbers of apoptotic cells in SLE PBMC compared with normal donor cells after in vitro incubation. After activation of PBMC with CD28 monoclonal antibody plus phorbol myristate acetate (CD28 MAb/ PMA), staphylococcal enterotoxin B (SEB), or phytohemagglutinin (PHA), the percentage of apoptotic cells was unchanged (SEB) or diminished (CD28 MAb/PMA, PHA) in SLE cells, and the difference between normal donor and SLE cells was less pronounced. On the mRNA level, expression of apoptosis-related gene products did not differ between SLE cells and normal donor cells. Expression of Fas/APO-1 protein was increased in freshly isolated SLE T lymphocytes compared with normal donor T lymphocytes, whereas bcl-2 protein was up-regulated after a 3-day culture period. Cellular activation further increased bcl-2 protein levels, eliminating differences between normal donors and SLE patients. In RA cells, the percentage of apoptosis was similar to that in normal donor PBMC, whereas results using cells from patients with other autoimmune diseases (MCTD, Wegener's granulomatosis, Takayasu arteritis, polyarteritis nodosa) were comparable with those found using SLE PBMC. Addition of growth factors such as interleukin-2 (IL-2), IL-4, or IL-15 to culture medium decreased the percentage of in vitro apoptosis in both normal donor and SLE cells. CONCLUSION: Based on these data, we conclude that accelerated in vitro apoptosis and increased Fas/ APO-1 and bcl-2 protein expression in SLE are nonspecific for the disease, and might be explained at least in part by the increased in vivo activation levels of PBMC from patients with SLE, MCTD, or autoimmune vasculitides combined with in vitro incubation under "noninflammatory" conditions and growth factor withdrawal.

Apoptosis↗