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Biomedical subjects

S Schmid

Publications and source records attributed to S Schmid.

At least 19 recordsLinked to original sources

Comparison of clinical diagnosis and standard laboratory and molecular methods for the diagnosis of genital ulcer disease in Lesotho: association with human immunodeficiency virus infection.

A multiplex polymerase chain reaction (M-PCR) assay for Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV) was compared with clinical and standard laboratory methods for the diagnosis of genital ulcer disease (GUD) in 105 patients; 36% were human immunodeficiency virus (HIV)-seropositive. Chancroid (80%), syphilis (8%), and genital herpes (8%) were the most frequent diagnoses. H. ducreyi and HSV were isolated from ulcers of 43% and 18% of patients, respectively; in 35%, all cultures were negative and the laboratory diagnosis indeterminate. M-PCR detected H. ducreyi, T. pallidum, and HSV in 56%, 23%, and 26% of patients, respectively; (no definitive diagnosis, 6%). The proportion of patients with more than one agent was 4% by culture and 17% by M-PCR (P = .002). Resolved sensitivities of M-PCR for H. ducreyi and HSV cultures were 95% and 93%, respectively. The sensitivities of H. ducreyi and HSV cultures were 75% and 60%, respectively. HSV, detected in 47% of specimens from HIV-infected versus 16% from HIV-uninfected patients (P < .001), may be emerging as a more frequent cause of GUD.

Adolescent

[Acute otitis media with effusion: an overview of the pathogenesis and recommendations for therapy].

Otitis media is one of the most common diseases in infants and young children. A combination of important factors contributes to the pathogenesis of acute otitis media and otitis media with effusion. These are poor tubal function, the degree of mastoid pneumatization, nasopharyngeal colonization with pathogenic bacteria and viruses, the ascending infectious pathway along the Eustachian tube, the immune status of the host, allergic and environmental factors, and genetic predisposition. Only correct diagnosis and understanding of they underlying pathophysiology enables the clinician to target treatment of the various forms of otitis media. We review the current concepts regarding evaluation and management of the diseased child and focus on the indication and selection of antibiotic therapy, bearing in mind the resistance rate within Switzerland. Most patients can be treated medically. "Otitis prone" individuals and children suffering from chronic otitis media with effusion with documented hearing loss clearly benefit from surgical intervention. We analyze the different treatment modalities and present a step-wise treatment algorithm. Newer vaccination trials indicate immunogenic effects even in young infants and show promising results in experimental and clinical studies.

Acute Disease

Two-fold effect of Angiotensin II on voltage-dependent calcium currents in rat retinal ganglion cells.

Angiotensin II (AngII) is one of the most important vasoconstrictive hormones but is also known to act as a neuromodulator in the central nervous system (CNS). Recently, AngII-containing neurons have been identified in the inner nuclear layer and the ganglion cell layer of the retina of various vertebrate species. The present study was undertaken to investigate the physiological effect of AngII on voltage-activated ion channels in retinal ganglion cells of the rat, Ion currents were recorded in freshly dissociated cells in the whole-cell configuration of the patch-clamp technique. AngII concentrations of 1 to 100 microM had no effect on sodium currents but modulated the influx through high voltage-activated (HVA) calcium channels in a 2-fold manner. AngII (100 microM) increased the HVA-calcium current by 15 to 65% in 41% of the cells, whereas a current reduction of 18 to 69% was observed in 59% of the cells. AngII effects were reversible within a few seconds of reperfusion with bath solution. Calcium-current kinetics and current-voltage relations remained unaffected.

Angiotensin II

Decrease in pacemaker incidence after orthotopic heart transplantation.

A decrease in sinus node dysfunction and pacemaker requirement after orthotopic heart transplantation was observed over a 6.5-year period, probably indicating the effect of a learning curve. Indirect evidence suggests a traumatic genesis of sinus node dysfunction after cardiac transplantation.

Arrhythmia, Sinus

Developmental regulation of voltage-activated Na+ and Ca2+ currents in rat retinal ganglion cells.

The developmental regulation of voltage-gated Na+ and Ca2+ current expression was investigated in rat retinal ganglion cells (RGCs) using whole cell patch clamp recordings. Experiments were performed on retinal whole mounts and slices from embryonic day 14 (E14), the developmental stage where RGCs start to differentiate from their precursor cells, to postnatal day 25 (P25) where the retina is fully differentiated and the animals have opened their eyes. No voltage-activated ion currents could be detected earlier than E17. From E17/18 on, small voltage-gated Na+ and Ca2+ currents could be measured which increased remarkably in amplitude until P16. Analysis of current kinetics and application of specific calcium channel antagonists revealed an alteration in the contribution of different Ca2+ current components to the voltage-activated whole cell Ca2+ current in RGCs during development.

Action Potentials

Douching and sexually transmitted diseases in pregnant women in Surabaya, Indonesia.

OBJECTIVE: Our purpose was to investigate the association between douching (douching agents and timing) and sexually transmitted disease. STUDY DESIGN: A cross-sectional survey of sexually transmitted diseases and habits of vaginal douching was performed on 599 pregnant women who visited a prenatal clinic in Surabaya, Indonesia. RESULTS: Of the 599 pregnant women, 115 (19.2%) had at least one sexually transmitted disease (gonorrhea, chlamydia, syphilis, trichomoniasis, or herpes simplex virus-2). Most women had douched with water (19%) or water and soap (63%) at least once in the preceding month. Approximately 10% of the women had douched in the preceding month with a commercial agent (2%) or betel leaf (8%). Douching with water alone after sex was not associated with sexually transmitted disease. Douching with water and soap or with a betel leaf or commercial agent after sex was associated with sexually transmitted disease; adjusted odds ratios were 2.6 (95% confidence interval 1.0 to 7.1) and 2.7 (95% confidence interval 0.5 to 14.5), respectively. The association was enhanced if the women douched before sex or both before and after sex; adjusted odds ratio were 2.7 (95% confidence interval 1.0 to 7.3) for douching with water and soap and 5.2 (95% confidence interval 1.6 to 16.7) for douching with betel leaf or a commercial agent. Compared with women who never douched, women who always douched with betel leaf or a commercial agent had a substantially increased risk for sexually transmitted disease (adjusted odds ratio 9.4, 95% confidence interval 1.8 to 50.3). CONCLUSIONS: We found a significant association between sexually transmitted disease and douching habits (douching with betel leaf, commercial agents, or water and soap). However, further prospective investigations are needed to evaluate the temporal relationship between douching and sexually transmitted disease.

Areca

Protease-antiprotease interactions and the rationale for therapeutic protease inhibitors.

A number of pancreatic enzymes have been suggested as the initiating factor for acute pancreatitis. In particular, the relationship between proteases and antiproteases has been examined extensively, based on the suspicion that an imbalance between them is the central factor in the pathogenesis of acute pancreatitis. Animal studies with antiproteolytic agents in models of acute pancreatitis have shown an improvement in outcome. However, more recently, prospective, randomized, multicentre trials treating human acute pancreatitis with antiproteolytic drugs (aprotinin, gabexate mesilate, and even fresh frozen plasma) have failed to show any benefit in the clinical setting. Thus, clinically, it seems likely that antiproteolytic therapy has no effect on the course of severe acute pancreatitis. Today, the mortality in severe acute pancreatitis is determined by septic complications due to infected pancreatic necroses in the late phase 2-3 weeks after the onset of the disease. Death in the early phase of the disease has become increasingly rare where an imbalance between proteases and antiproteases may be involved.

Acute Disease

Changes in Thy-1 antigen immunoreactivity in the rat retina during pre- and postnatal development.

Although Thy-1 is one of the most abundant surface glycoproteins in mammalian central neurons, its functional role is still not clarified. In this study we demonstrate that Thy-1 expression in the rat retina starts only at embryonic day 19 on both the cell somas and processes of retinal ganglion cells. Thy-1 immunoreactivity in the ganglion cell layer increases until postnatal day 14 and is paralleled by an increase in the thickness of the inner plexiform layer. Thus, the beginning of Thy-1 expression is correlated with a developmental stage when axonal elongation and neurite sprouting of ganglion cells has finished and refinement of synaptic structures in the colliculus superior begins. From postnatal day 9 on, Thy-1 immunoreactivity can also be observed on cell somas at the border of the inner plexiform/inner nuclear layer.

Animals

[Clinical aspects in oral, pharyngeal and laryngeal carcinoma--results of an overall Swiss cohort study].

Squamous cell carcinomas of the oral cavity, pharynx and larynx cause early symptoms and are fairly accessible. Nevertheless, in more than half of cases they are diagnosed at an advanced stage. This paper identifies patients at high risk of developing one of these carcinomas, describes the typical clinical findings and shows how, with a high index of suspicion and a proper examination technique, diagnosis at an earlier stage could be achieved. The study is based on the data of 636 patients with squamous cell carcinoma of the oral cavity (174 patients), oropharynx (177), hypopharynx (97), and larynx (188). 87% of the patients were male, and 90% were aged between 40 and 80 years. 85% of the patients smoked and drank alcohol regularly. The key symptoms were pain, dysphagia, hoarseness, a painless neck mass, or a visible ulcerating lesion. On average a 4-month period elapsed from the onset of symptoms to the histological diagnosis. The diagnostic delay was significantly shorter in patients with pain or visible organic changes (ulcerating lesions, neck masses) than in patients with functional symptoms (dysphagia and hoarseness).

Adult

Catabolic ornithine carbamoyltransferase of Pseudomonas aeruginosa. Changes of allosteric properties resulting from modifications at the C-terminus.

Ornithine carbamoyltransferases (OTCases) catalyse the formation of citrulline and phosphate from ornithine and carbamoylphosphate by a thermodynamically favoured reaction. In vivo, catabolic OTCase of Pseudomonas aeruginosa promotes the reverse reaction, the phosphorolysis of citrulline. Although the enzyme is assayed in vitro in the direction of citrulline synthesis, the enzyme cannot perform this reaction in vivo due to poor affinity for carbamoylphosphate and high cooperativity towards this substrate. Furthermore, the dodecameric catabolic OTCase is an allosteric enzyme; the enzyme is stimulated by nucleoside monophosphates and inhibited by polyamines (e.g. spermidine). A previous study showed that a modification of the C-terminus of the catabolic OTCase alters the homotropic cooperativity of the enzyme. We have now investigated the importance of the C-terminus for homotropic and heterotropic cooperativity by site-directed mutagenesis. Deletion of the C-terminal Ile335 residue strongly reduced cooperativity for carbamoylphosphate and sensitivity to spermidine. These properties were essentially restored when the two C-terminal amino acids (Asp334 and Ile335) were removed by deletion. However, in this variant enzyme, AMP failed to abolish carbamoylphosphate cooperativity completely, whereas the wild-type enzyme was rendered virtually non-cooperative by AMP. An extension of catabolic ornithine carbamoyltransferase by 15 amino acid residues interfered with both homotropic and heterotropic interactions and lowered the maximal velocity. All variant enzymes had the same dodecameric structure as the wild type and differed only slightly in affinity for the second substrate ornithine. A structural model of the dodecamer, at 0.3-nm resolution, suggests that the C-terminus could be involved in trimer/trimer interaction. We propose that modifications at the C-terminus alter the trimer/trimer interface and, in addition, removes the salt bridge His5-Ile335 within a monomer. These changes profoundly and indirectly modify the allosteric transition and consequently the interactions of the dodecamer with carbamoylphosphate and effectors.

Adenosine Monophosphate

p53 gene mutations in oropharyngeal carcinomas: a comparison of solitary and multiple primary tumours and lymph-node metastases.

Despite the steadily increasing number of patients suffering from squamous-cell carcinomas of the oropharyngeal region, little is known about the molecular steps involved in the induction of these neoplasms. We investigated oropharyngeal cancers from 38 patients for mutations in the p53 tumour-suppressor gene. The majority of patients (74%) had a history of tobacco and alcohol abuse. Five had lymph-node metastases, 3 had multiple primary carcinomas and 2 presented with multiple primary tumours and lymph-node metastases. Exons 5 through 8 of the p53 gene were screened by single-strand conformation polymorphism analysis followed by direct DNA sequencing. A total of 16 tumours (42%) contained point mutations which were scattered throughout exons 5 to 8. Most mutations (56%) were transitions, predominantly G-->A. Among the transversions, G-->T mutations prevailed; these have also been found in smoking-related lung cancer. One carcinoma of the soft palate showed a mutation which was retained in a lymph-node metastasis. In another patient, 2 primary carcinomas had different mutations, indicating that they had developed independently. Similar results were obtained in a case with a p53 mutation in the third of 3 primary tongue carcinomas which developed over a period of 23 years. One lymph-node metastasis had a 12-bp deletion which was not detected in any of the primary malignancies. The frequent occurrence of p53 mutations in oropharyngeal carcinomas supports the view that they play a role in the initiation or progression of the malignant phenotype.

Adult

In vitro identification of retinal ganglion cells in culture without the need of dye labeling.

We here describe a method for the identification of a distinct neuronal phenotype at all stages of development in culture without the need of any staining procedure. Based purely on a size criterion we can rapidly select vital retinal ganglion cells (RGCs) for further studies out of a mixed culture of rat retinal cells. In order to establish a size criterion for retinal cells of various age, RGCs were first labeled immunocytochemically with antibody against the ganglion cell-specific surface glycoprotein Thy-1. Soma diameters were then determined for labeled and unlabeled cells between embryonic day 16 (E16) and postnatal day 90 (P90). Unlabeled neurons of all ages had soma diameters between 3.6 microns and 12 microns (mean diameter: 6.3 microns). In contrast, soma diameters of RGCs ranged from 8.4 microns to 28 microns and the number of RGCs with large soma diameters increased with age. Thus, in a mixed retinal cell culture only RGCs are larger than 12 microns and can be selected solely based on their size. The validity of the size criterion during the whole period of retinal cell differentiation offers the possibility to study the development of cellular functions and ion channel properties in a distinct type of cell without the risk of artifacts introduced by staining.

Animals

Sinus node dysfunction after orthotopic heart transplantation: the Vienna experience 1987-1993.

In the present study, the annual incidence of postoperative sinus node dysfunction and the type of sinus node abnormality after cardiac transplantation were followed over a 6 1/2-year period in 185 patients. Each year the sinus node function was systematically characterized by rhythm and corrected sinus node recovery time in a significant number of patients. Over the entire study period, there were 131 patients with normal sinus node function (corrected sinus node recovery time 318 +/- 55 msec) while 54 patients had latent (n = 24, sinus rhythm, corrected sinus node recovery time 8,053 +/- 2,198 msec) or manifest (n = 30, absence of sinus rhythm or pacemaker dependence) sinus node dysfunction. Twenty-nine patients had pacemaker placement. The incidence of sinus node dysfunction declined in absolute terms and when indexed by the actual number of patients transplanted per year (index 1987: 38.5; 1998: 17.6; 1989: 23.2; 1990: 29.1; 1991: 10.4; 1992: 7.5; 1993: 2.2). Among those with sinus node dysfunction, the annual percentage of patients presenting with prolonged recovery time, escape rhythm, and those reverting back to sinus rhythm until discharge did not change significantly over the study period (P = 0.22). On multivariate analysis, only the date of transplantation was significantly associated with the occurrence of postoperative sinus node deficiency (P = 0.0007) while age of recipient (P = 0.85) or donor (P = 0.96), the type of cardioplegia used (P = 0.09) and ischemic time (P = 0.09) were insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The adenovirus E4-6/7 protein transactivates the E2 promoter by inducing dimerization of a heteromeric E2F complex.

Binding of the mammalian transcription factor E2F to the adenovirus E2a early promoter is modulated through interaction with the viral E4-6/7 protein. E4-6/7 induces the cooperative and stable binding of E2F in vitro to two correctly spaced and inverted E2F binding sites in the E2a promoter (E2F induction) by physical interaction in the protein-DNA complex. The E2a promoter is transactivated in vivo by the E4-6/7 product. The C-terminal 70 amino acids of E4-6/7 are necessary and sufficient for induction of E2F binding and for transactivation. To assess the mechanism(s) of E2a transactivation and the induction of cooperative E2F binding by the E4-6/7 protein, we have analyzed a series of point mutants in the functional C-terminal domain of E4-6/7. Two distinct segments of E4-6/7 are required for interaction with E2F. Additionally, and E4-6/7 mutant with a phenylalanine-to-proline substitution at amino acid 125 (F-125-P) efficiently interacts with E2F but does not induce E2F binding to the E2a promoter and is defective for transactivation. Induction of E2F stable complex formation at the E2a promoter by the F-125-P mutant protein is restored by divalent E4-6/7-specific monoclonal antibodies, but not a monovalent Fab fragment, or by appending a heterologous dimerization domain to the N terminus of the mutant protein. These and other data support the involvement of E4-6/7 dimerization in the induction of cooperative and stable E2F binding and transactivation of the E2a promoter. We present evidence that at least two cellular components are involved in E2F DNA binding activity and that both are required for E2F induction by the E4-6/7 product. The recently cloned E2F-related activities E2F-1 and DP-1 individually bind to an E2F binding site weakly, but when combined generate an activity that is indistinguishable from endogenous cellular E2F. Recombinant E2F-1, DP-1, and E4-6/7 are sufficient to form the induced E2F complex at the E2a promoter.

Adenovirus E2 Proteins

p53 mutations in oropharyngeal carcinomas: a comparison of solitary and multiple primary tumours and lymph node metastases.

Despite the steadily increasing number of patients suffering from squamous cell carcinomas of the oropharyngeal region, little is known about the molecular steps involved in the induction of these neoplasms. The aim of this study was to determine the incidence and type of p53 mutations in oropharyngeal squamous cell carcinomas. Five of 38 patients had lymph node metastases, three patients had multiple primary carcinomas and two patients presented with multiple primary tumours and lymph node metastases. Exons 5 through 8 of the p53 gene were screened by single-strand conformation polymorphism analysis followed by direct DNA sequencing. A total of 16 tumours (42%) contained point mutations scattered throughout exons 5 to 8. Most mutations (56%) were transitions, predominantly G-->A. G-->T mutations prevailed among the transversions that have also been found in smoking-related lung cancer. One carcinoma of the soft palate showed a mutation which was retained in a lymph node metastasis. The status of p53 differed in primary carcinomas of patients with multiple tumours indicating an independent generation of these neoplasms. The frequent occurrence of p53 mutations in oropharyngeal carcinomas supports the view that this gene plays a role in initiation or progression of the malignant phenotype.

Base Sequence

Total reconstruction of the ossicular chain.

The footplate only situation remains the greatest challenge of ossicular reconstruction. This article discusses the long term results obtained with a new type of columella, the Spandrel, which combines the rigidity necessary for sound transmission with the flexibility required to comply with the dynamic movements of the neotympanum.

Audiometry, Pure-Tone