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Biomedical subjects

M F Kramer

Publications and source records attributed to M F Kramer.

At least 19 recordsLinked to original sources
PubMed2006

[Diagnosis of persistent rhinitis].

A total of 9923 patients with persistent rhinitis were characterized on the basis of their symptoms and in vitro data. The most bothersome symptom in these patients was nasal obstruction. "Post-nasal drip" proved to be untypical for allergic rhinitis. In all the diseases investigated, involvement of eosinophilic granulocytes and mast cells was found to vary. In addition to endoscopy and imaging procedures, the determination of selective in vivo and in vitro parameters represents an essential part of the diagnostic work-up of persistent rhinitis, which thus proves to be a domain of the allergological rhinologist.

Adult↗
PubMed2006

[Susac's syndrome. A rare microangiopathy of cochlea, retina, and brain].

Susac's syndrome is a rare disease characterized by encephalopathy, retinal artery occlusion, and a sensorineural hearing loss. Diagnosis may be difficult since most specialists are not familiar with this angiopathy. However, the typical symptom complex can mimic different pathologies, therefore requiring the attention of radiologists, ENT specialists, and ophthalmologists. We present a rare case of Susac's syndrome unveiled by audiometry results, MR imaging of the brain, and the ophthalmological findings..

Adult↗
PubMed2006

[Clinical symptoms and mediators in the allergic early and late phase reaction].

BACKGROUND: This examination focused on the allergic early and late phase reaction via nasal symptom scores, acoustic rhinometry, and the determination of mediators possibly involved in late phase eosinophilia. We examined nasal secretions for IL-5; the chemokines IL-8, MCP-1, and Eotaxin; the adhesion molecule sVCAM-1, and the leukotriene LTC4 for their suggested impacts on tissue eosinophilia. METHODS: 13 patients suffering from seasonal allergic rhinitis were challenged intranasally out of the natural pollen season by their specific allergen. In a time window of 8 h following the provocation, patients completed symptom questionnaires, and underwent acoustic rhinometry. Nasal secretions were gained by the cotton wool method over a time period of 8 h. Nasal secretions were analyzed for the above mentioned mediators. RESULTS: Individual evaluation of the acoustic rhinometry measurements revealed an early phase reaction in 100 % of the cases and a late phase reaction in 92 %. The need to sneeze and a runny nose were the strongest symptoms during the allergic early and late phase reaction. A typical late phase kinetic was observed for IL-5, MCP-1, Eotaxin, sVCAM-1, and LTC4. IL-8 was characteristic for early phase reaction but increased in late phase as well. CONCLUSIONS: The need to sneeze, a runny nose, and the overall quality of life were most apt to evaluate the allergic early and late phase reaction. Highly significant correlations between nasal obstruction and acoustic rhinometry measurements indicate a high sensitivity of visual analogue scales in the representation of minimal changes in nasal symptom scores during the allergic reaction. Our data point to a relevant role of the TH2 cytokine IL-5; of the chemokines IL-8, MCP-1, and Eotaxin; of the adhesion molecule sVCAM-1, and of the leukotriene LTC4 for the allergic late phase eosinophilia.

Adult↗
PubMed2006

[Lethal end of a group C streptococcal necrotizing fasciitis in a healthy female].

The necrotizing fasciitis (NF) is a life threatening, quickly progressive soft-tissue infection characterized by necrosis of the superficial fascia. It is very rare in the head and neck region. Usually this infection attacks weak patients with chronic diseases, such as diabetes or cancer. In adults the most common organisms implicated in craniocervical NF are Streptococcus pyogenes, Staphylococcus aureus, Streptococcus viridans and Peptostreptococci. The typical infectious entrance is a deep wound, after surgery or a peritonsillar abscess. We describe a very unusual case of a craniocervical NF with a deadly outcome in a sixty year old female. The patient had no chronic diseases and went to an ENT doctor with an acute tonsillitis for 3 days. Within the next three hours the general condition became dangerous to life. Therefore she was brought to us for immediate therapy. But despite fast and aggressive surgery of the neck, throat and thorax the patient died of a toxic schock syndrome on the intensive care unit within a few hours. The microbiology showed just group C Streptococcus. The postmortem examination confirmed the NF with starting point in the left tonsil after acute tonsillitis. Such a foudroyant course of a craniocervical NF with group C streptococci in a healthy patient is not published yet.

Acute Disease↗
PubMed2005

[Humoral mucosal immunity in allergic rhinitis].

BACKGROUND: Mucosa-immunologic aspects are gaining an increasing awareness in the pathophysiology of type I allergies. Humoral mucosal immune responses are dominated by secretory IgA, but there is evidence for a relevant role of IgG in nasal mucosa-associated lymphoid tissue. OBJECTIVE: was to measure allergen-specific immunoglobulins (IgA and IgG) in nasal secretions as an expression of a humoral mucosal immune response in allergic rhinitis. For tissue eosinophilia we studied nasal Eosinophilic Cationic Protein (ECP) and for mast cell activation nasal tryptase. METHODS: Nasal secretions of 40 patients suffering from allergic rhinitis were analyzed for allergen-specific IgA, IgG, and IgE, and for ECP and tryptase. Patients were highly sensitized against the major allergens of house dust mites, timothy, and birch pollen. 43 non-atopic individuals served as controls. In order to study possible effects of the actual pollen season on the studied parameter we secondly compared patients allergic to seasonal allergens co- (n = 28) and extra-seasonally (n = 41). In order to determine a possible influence of allergen-specific IgA in eosinophilic degranulation we additionally studied 5 patients after nasal allergen challenge. RESULTS: In allergic rhinitis we found significantly increased levels of allergen-specific immunoglobulins of all studied subclasses and allergens in nasal secretions. Comparison of nasal ECP and tryptase showed significantly increased concentrations in allergic individuals as well. Co-seasonally we found elevated allergen-specific IgE, ECP, and tryptase but lower concentrations of allergen-specific IgA and IgG. There was no association between late phase eosinophilia and IgA concentrations after local allergen challenge. CONCLUSIONS: The occurrence of allergen-specific immunoglobulins in nasal secretions is interpreted as a local humoral mucosal immune response. The physiologic role of local allergen-specific immunoglobulins is not clear to date. Involvement in degranulation of eosinophils or mast cells, like suggested before, seems unlikely.

Adult↗
PubMed2004

In vitro diagnosis of chronic nasal inflammation.

BACKGROUND: Differential diagnosis of chronic nasal inflammation is insufficient when based solely on clinical examination and radiography of paranasal sinuses. Patients complain about more or less similar symptoms. Activation of mast cells and eosinophils is pivotal in nasal inflammation. OBJECTIVE: To compare tryptase and eosinophilic cationic protein (ECP) in nasal secretions in different forms of chronic nasal inflammation and to establish norm values. METHODS: The study included 1710 patients presenting with nasal complaints. Nasal secretions were gained by the cotton wool method and analysed for tryptase, as a marker of mast cell activation, and for ECP, as a marker of tissue eosinophilia and activation. Patients were grouped according to their diagnosis: chronic, non-allergic rhinosinusitis (sinusitis, n=194), non-allergic nasal polyposis (polyposis, n=138), non-allergic rhinitis with eosinophilia syndrome (NARES, n=198), isolated perennial allergic rhinitis (AR) (n=126), isolated seasonal AR (n=132), and patients allergic to both, seasonal and perennial allergens (n=193). Seven hundred and twenty-nine patients with nasal complaints due to a deviated septum and without any nasal inflammation served as controls. RESULTS: Nasal tryptase was highly significantly (P<0.001) elevated in polyposis, NARES, and in AR. ECP was highly significantly (P<0.001) elevated in all groups of patients suffering from chronic nasal inflammation. Based on our data and method we established norm values (95% confidence interval of mean value) for nasal tryptase in healthy adults, ranging from 12.0 to 18.7 ng/mL and for ECP ranging from 84.4 to 102.6 ng/mL. CONCLUSION: Mast cells and eosinophils are involved in non-allergic and allergic forms of chronic nasal inflammation. We established an in vitro assay for tryptase and ECP in nasal secretions and defined norm values based on our data and method. In vitro measurement of biological markers in nasal secretions provides important information for differential diagnosis and therapeutic strategies of chronic nasal inflammation.

Adult↗
PubMed2004

Molecular confirmation of Enterococcus faecalis and E. faecium from clinical, faecal and environmental sources.

AIMS: The genus Enterococcus includes opportunistic pathogens such as E. faecalis and E. faecium, and is also used to assess water quality. Speciation of enterococci in environmental studies can be particularly problematic, therefore protocols for unambiguous, DNA-based analysis could receive wide use in applications ranging from water quality monitoring to microbial source tracking. The goal of this work was to investigate the usefulness of PCR for speciation of putative, biochemically identified E. faecalis and E. faecium isolated from water, faeces and sewage. METHODS AND RESULTS: Putative enterococci (n = 139) were isolated on mEI agar from dog, human, gull and cow faeces, and from sewage, freshwaters and marine waters. A total of 128 isolates passed standard physiological tests for the genus, and were speciated by the API 20 Strep (APIStrep) biochemical test system. 42.2% were identified as E. faecalis, and all were confirmed by PCR. 19.5% were biochemically identified as E. faecium, but only seven were PCR-positive. CONCLUSIONS: The 16S rDNA of PCR-positive and PCR-negative E. faecium, including isolates that were inconclusively identified by APIStrep, was sequenced. All formed a monophyletic clade with E. faecium sequences in Genbank. SIGNIFICANCE AND IMPACT OF THE STUDY: Biochemical identification of E. faecalis agreed 100% with PCR assays, therefore a simple protocol of isolation on mEI followed by PCR should be useful for environmental studies. Discrepancies among biochemical identification, PCR confirmation and DNA sequencing were noted for E. faecium, indicating that routine isolation/identification of E. faecium from environmental samples is a much more difficult task.

Anal Canal↗
PubMed2003

[The sinobronchial syndrome. Assessment of the influence of the upper on the lower airway diseases].

Epidemiological and clinical data are discussed dealing with a possible influence of inflammatory changes of the nasal and especially the paranasal tissue on lower airway disease like asthma, the so-called "sinobronchial syndrome". Even though there is clear evidence of an association of the upper with the lower airway diseases, a causal relationship and a possible work of action are still up for discussion. The literature has been reviewed, and different theories are discussed. Generally speaking, a branch of differently accentuated mechanisms seems to play a role.

Adult↗
PubMed2001

Immunohistological expression of interleukin 16 in human tonsils.

BACKGROUND: Interleukin 16 (IL-16) acts highly chemotactic on CD4-bearing cells. Besides chemotaxis, IL-16 has numerous immunomodulatory effects, and not only on T cells. OBJECTIVE: To determine IL-16 expression in human tonsils. METHODS: Tonsillar follicles were immunohistologically characterized to elicit a possible cellular source of IL-16 expression. RESULTS: The mantle zone of immature and mature B cells was CD22 immunoreactive (ir), whereas the germinal center of activated B cells was CD23-ir. Plasma cells that were CD38-ir were observed extrafollicularly beneath the epithelium and within the germinal center. T cells were found most frequently in the extrafollicular space, with a majority of CD4 cells. CD68-ir macrophages were predominantly found within the germinal center. Immunostaining of anti-IL-16 revealed strong cytoplasmatic reactivity of extrafollicular cells and of cells at the outer rim of the mantle zone. Numerous cells adherent to the stratified squamous epithelium were IL-16-ir as well. Double immunostaining identified CD4(+) T cells as the major cellular source of IL-16 expression. Furthermore, a population of CD22(+) B cells at the outer rim of the mantle zone expressed IL-16 as well. CONCLUSIONS: Interleukin 16 was mainly expressed in a typical CD4-like pattern in human tonsils. Our data strongly suggest that CD4(+) lymphocytes constitute the major cellular source for IL-16. We hypothesize that the double-immunostained CD4-ir and IL-16-ir cells represent activated T cells. Because CD22(+) B cells at the outer rim of the mantle zone expressed IL-16 as well, we conclude that this area might constitute the locus of IL-16-mediated B-cell differentiation.

Child↗
PubMed2001

Allergic rhinitis does not constitute a risk factor for obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a condition characterized by recurrent episodes of obstruction of the upper airway. The aim of this study was to evaluate whether nasal obstruction due to allergic rhinitis constitutes a risk factor for OSAS. Patients (n = 119) presenting typical symptoms of sleep apnea were tested for OSAS using polysomnography. Additionally all patients were tested in vivo and in vitro (including nasal eosinophilic cationic protein) for allergic rhinitis. Examination for allergic rhinitis revealed that 88.3% of all patients had no allergic rhinitis, whereas only 11.7% were diagnosed as allergic. No significant differences in sleeping parameters were observed between allergic and non-allergic patients. Comparison of parameters indicative of relevant OSAS (apnea-hypopnea index [AHI] > 10) revealed that 60% of non-allergic patients had relevant OSAS, compared to only 50% of allergic patients. Investigation of allergic subgroups revealed similar results: no significant differences in sleeping parameters or elevated rates of relevant OSAS parameters were observed, especially in perennial allergic rhinitis due to house dust mites. No elevated rates of allergic rhinitis were observed in the studied cohort of patients suffering from sleep apnea or OSAS. Furthermore, no significant differences in sleeping behavior or polysomnography parameters were found on comparing allergic and non-allergic patients. In summary, our data rule out allergic rhinitis as a major risk factor for OSAS.

Electroencephalography↗
PubMed2000

Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene.

5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway in mammalian cells. Separate genes encode the two isoforms: ubiquitously expressed ALAS (ALAS1) and erythroid-specific ALAS (ALAS2). Transcription of the ALAS2 gene is only activated during erythroid cell differentiation. This stimulation allows for the formation of hemoglobin-specific heme. The 5'-flanking region of the mouse ALAS2 gene was studied in order to define its erythroid-specific function in transcriptional activation. Putative binding sites for the erythroid-specific nuclear factors GATA-1, NF-E2, and EKLF were identified within the first 300bp region of the mouse ALAS2 5'-flanking region. However, this 300bp region alone did not efficiently activate transient expression in erythroid MEL and K562 cell lines. Additional DNA regulatory sequences found within 300-718bp upstream of the transcription start site were required for maximal transcriptional activation, even though these regions stimulated similar expression in the non-erythroid HeLa and NIH/3T3 cells. This suggests that cis-acting elements present in the 5'-flanking region are not responsible for maintenance of transcriptional silencing in non-erythroid cell lines and that tissue-specific regulation of ALAS2 depends on other regions of the gene or on chromatin remodeling. A putative hypoxia inducible factor 1 (HIF-1) response element was identified within the 300-718bp upstream region. Significantly, two proximal GATA-1-binding sites (-118/-113 and -98/-93) and a region located within -518 to -315bp of the mouse ALAS2 promoter were essential for transcriptional activation during chemically induced differentiation of MEL cells, implying their importance in conferring erythroid specificity to the ALAS2 transcriptional activation. This is the first study to delimit the cis-acting region responsible for activation of the ALAS2 promoter upon dimethyl-sulfoxide induction in MEL cells.

3T3 Cells↗
PubMed2000

Isolation of a somatic cell mutant resistant to the induction of apoptosis by oxidized low density lipoprotein.

Oxidized low density lipoprotein (oxLDL) induces apoptosis in macrophages, smooth muscle cells, and endothelial cells. To elucidate the molecular mechanism of oxLDL-induced cytotoxicity and determine its tissue specificity, we have used Chinese hamster ovary (CHO)-K1 cells expressing human CD36 (CHO/CD36). Expression of CD36 rendered these cells susceptible to killing by oxLDL. This cytotoxicity was due to the induction of apoptosis. Therefore, CD36 expression is the only requirement for oxLDL-induced apoptosis. Oxysterols apparently mediate the cytotoxicity of oxLDL in macrophage foam cells and endothelial cells. 25-Hydroxycholesterol, at concentrations higher than 1 microg/ml, killed CHO-K1 cells, by apoptosis, in medium supplemented with serum as a source of cholesterol. These effects were not seen in a 25-hydroxycholesterol-resistant CHO/CD36 mutant (OX(R)), which was otherwise capable of undergoing apoptosis in response to staurosporine. This mutant was also resistant to killing by oxLDL, suggesting that oxysterols are at least partially responsible for the toxic effects of oxLDL. Oxysterol-induced apoptosis did not involve regulation of sterol regulatory element-binding protein proteolysis or the cholesterol biosynthetic pathway. 25-Hydroxycholesterol stimulated calcium uptake by CHO-K1 cells within 2 min after addition. Treatment of CHO or THP-1 (macrophage) cells with the calcium channel blocker nifedipine prevented 25-hydroxycholesterol induction of apoptosis. OX(R) showed no enhanced calcium uptake in response to 25-hydroxycholesterol.

Animals↗
PubMed2000

[A new system for the classification of ethmoid polyposis. Effect of combined local and systemic steroid therapy].

BACKGROUND: Nasal polyps are a common disease with in the majority of cases unknown origin. Both the medical and surgical treatment of nasal polyps present a challenge in Otorhinolaryngology. METHODS: We developed a four-stage grading system for nasal polyps based on the endoscopic aspect of more than 300 patients. In a study of 37 patients, treated by systemically (Methylprednisolon 64 mg p.o., decreasing amounts for the first 11 days) and locally (Budesonid 400 micrograms intranasal) applied steroids for 90 days, this staging-system was tested. RESULTS: The mean stage of polyps decreased significantly (p < 0.01) from 2.8 at day 0 to 1.7 at day 7 and further to 1.2 and to 0.7 at day 28 and day 90 respectively. The mean nasal symptom score decreased equally from 1.14 on day 1 to 0.19 and to 0.14 on day 7 and day 28 respectively. To summarize, we observed a significant (p < 0.01) decrease in polyp stages of 75% respectively a significant (p < 0.01) reduction of symptom scores of 93%. CONCLUSIONS: Thus, we present a suitable new grading system for nasal polyps which we applied directly to assess the efficacy of combined local and systemic steroid therapy. It was shown that this treatment can reduce polyps and prevent their recurrence over the observed time.

Administration, Intranasal↗
PubMed2000

Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis.

OBJECTIVE: To compare concentrations of interleukin-5 (IL-5), immunoglobulin E (IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to obtain information about the pathogenesis of these diseases. METHODS: Nasal secretion and serum were analyzed by routine enzyme-linked immunosorbent assay techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis were included in the study. Eight healthy, nonallergic probands served as control subjects. RESULTS: Significantly elevated concentrations of IL-5 (5-fold, P < .05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 +/- 3.1 kU/L). There were no significant differences between patients with allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of ECP were significantly elevated (sixfold, P < .01) in patients with allergic rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas twofold higher concentrations (not significant) of ECP were observed in patients with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The elevated sICAM-1 nasal secretion values in this group correlated significantly (P < .05) to the serum values. CONCLUSIONS: Equally elevated concentrations of IL-5 and IgE in patients with allergic rhinitis and nonallergic nasal polyposis implicated similar pathogenic processes in both diseases. Whereas the pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue eosinophilia, which was confirmed by data in the present study. Elevated concentrations of ECP were suggested to result from tissue eosinophilia--a characteristic of both diseases. Elevated concentrations of sICAM-1 in patients with chronic nonallergic sinusitis pointed to its key role in the recruitment of neutrophils into the inflamed tissue, whereas an important role in eosinophil recruitment was ruled out.

Adult↗
PubMed2000

Construction, phenotypic analysis, and immunogenicity of a UL5/UL29 double deletion mutant of herpes simplex virus 2.

A number of studies have shown that replication-defective mutant strains of herpes simplex virus (HSV) can induce protective immunity in animal systems against wild-type HSV challenge. However, all of those studies used viruses with single mutations. Because multiple, stable mutations provide optimal levels of safety for live vaccines, we felt that additional mutations needed to be engineered into a candidate vaccine strain for HSV-2 and genital herpes. We therefore isolated an HSV-2 strain with deletion mutations in two viral DNA replication protein genes, UL5 and UL29. The resulting double deletion mutant virus strain, dl5-29, fails to form plaques or to give any detectable single cycle yields in normal monkey or human cells. Nevertheless, dl5-29 expresses nearly the same pattern of gene products as the wild-type virus or the single mutant viruses and induces antibody titers in mice that are equivalent to those induced by single deletion mutant viruses. Therefore, it is feasible to isolate a mutant HSV strain with two mutations in essential genes and with an increased level of safety but which is still highly immunogenic.

Animals↗
PubMed1998

Importance of the herpes simplex virus UL24 gene for productive ganglionic infection in mice.

The UL24 gene of herpes simplex virus overlaps the viral thymidine kinase (tk) gene. Most previous studies of UL24 have examined UL24 mutants that have also contained tk and sometimes other mutations. To address the importance of UL24 for viral replication in cell culture and in infections of a mammalian host, we constructed a mutant virus containing a UL24 nonsense mutation that does not affect TK activity and a second mutant that contains clustered point mutations in UL24 and a mutation in tk that does not by itself affect the ability of the virus to replicate acutely in mouse ganglia or to reactivate from latent infection following corneal inoculation of mice. Both mutant viruses replicated in cells in culture and in the mouse eye, albeit less efficiently than wild type or control viruses. Both mutants were much more severely impaired for acute replication in trigeminal ganglia and for reactivation from latency following explant of these ganglia. Viral DNA and latency-associated transcripts were present, albeit at lower levels in ganglia infected with the nonsense mutant. These results indicate that UL24 is especially important for productive infection of mouse sensory ganglia and may have implications for the behaviors of certain tk mutants in pathogenesis.

Amino Acid Sequence↗
PubMed1998

Occurrence of a terminal vascularisation after experimental myocardial infarction.

Physiological data indicate a residual vascularisation within ischemic myocardial regions where necrosis of most cells have been reported to occur after myocardial infarction. We therefore studied, by means of immunohistochemistry, computer-assisted morphometry, and electron microscopy, the terminal vascularisation in correlation to cardiomyocytes in ten canine hearts 1 and 3 weeks after occlusion of the left anterior descending (LAD) coronary artery. In comparison to non-infarcted myocardium we found the following alterations in infarcted myocardium: (1) the area density of cardiomyocytes decreased from 98% (control) to 7.9% (1 week after occlusion) and to 2.7% (3 weeks after occlusion); (2) the number of capillaries was diminished to 11.6% and to 2.6%; respectively; (3) smooth muscle alpha-actin was induced in endothelial (EC) cells of the microvessels; and (4) terminal resistance vessels increased 11-fold and 20-fold in number, respectively. Our findings confirm the necrosis of the vast majority of cardiomyocytes and capillaries within the first 3 weeks after myocardial infarction. Besides a small number of capillaries, many terminal resistance vessels, however, seem to persist in the scarring infarcted tissue. The occurrence of these microvessels is supposed to be important for the granulation tissue as well as for the control and regulation of a residual blood supply during scar formation.

Animals↗