Biomedical subjects
S Jovanovic
Publications and source records attributed to S Jovanovic.
[10 years of observation by public health offices in Baden-Württemberg--assessment of human biomonitoring for mercury due to dental amalgam fillings and other sources].
Since 1992, in Baden-Württemberg, ten-year old children have been surveyed in the project "Sentinel Health Departments" to study their exposure to environmental pollutants and possible health effects. In the four study areas 1200 children have been investigated every year initially, since 1996 every second year. The data for mercury in body fluids are reported here. The decrease in the body burden of mercury as a result of the declining usage of dental amalgam fillings, was been verified. In 1992/93, of all the children who had been surveyed, the 95 percentile for the body burden of mercury was 3.1 microg/l and in 2000/01 1.35 microg/l. Also to be discussed is the reason why mercury-based cosmetic ointments seriously exceed the HBM-II-intervention-value. Because of using these ointments, concentrations of mercury in urine up to 1400 microg/l were found. A study within the project "Sentinel Health Departments" compared the concentrations of mercury in the urine of adults with those in blood and salvia. The results support the opinion that mercury in urine is appropriate for estimating the mercury uptake from dental amalgam fillings. It can be assumed that these results reflect the situation in the entire Federal Republic of Germany. The ten years' experience confirms that the concept of the "Sentinel Health Departments" is excellently suited to obtain data relevant for environmental health of children. Environmental health protection and the essential gathering of data for future health observation in Baden-Württemberg.
[Exposition and sensitisation to indoor allergens, house dust mite allergen and cat allergens].
The study examined the exposure to biological indoor air agents and their possible role for allergies and respiratory tract illnesses of children. It was conducted as a case control study (atopic vs non-atopic children) at the four surveillance public health departments in Baden-Württemberg in the winter season 1999/2000 and included 379 children of the fourth class. The concentrations of the house dust mite antigens Der F1, Der p1, and Der Gr2 as well as cat allergen Fel d1 were determined in the children's bedrooms on the ground and in the mattress. Specific IgE-antibodies against allergens from house dust, mites and cat were determined in the serum of the children. For mite allergens the following medians ( micro g/g) were estimated in floor dust: Der p1 = 0.6, Der f1 = 2.3, Gr2 = 0.1; in mattresses: Der p1 = 1.2, Der f1 = 3.4, Gr2 = 0.3. The median of Fel d1 in floor dust was 0.2 microg/g, in mattresses 0.1 microg/g. Sensitisation to dust mite allergen was found to be more prevalent than sensitisation to cat. The distribution of sensitisation among the cases and controls is different. Among the cases, more subjects were sensitised to dust mites (32.9 %) and cat (13.1 %). Among the controls, 17.1 % were sensitised to dust mites and 4.1 % to cat. The results showed no direct association between the prevalence of allergies or respiratory tract illnesses and the indoor concentrations of the allergens. Possible reasons for these findings are discussed.
Hypoxic activation of an amiloride-sensitive cation conductance in alveolar epithelial cells.
Imposing hypoxia (P(O(2)) = 23 mmHg) upon A549 cells elicited increased G(amil) although previous work had predicted a fall in this parameter. G(amil) appeared to be dependent upon glucocorticoid-driven gene expression, a process inhibited by ERK, an enzyme activated by oxidative stress. However, hypoxia transiently activated this enzyme and the response was blocked by glucocorticoids, showing that the rise in G(amil) occurs only if ERK activation is suppressed. Fluorimetric assays showed that lowering P(O(2)) elicited H(2)O(2) formation indicating that this maneuver actually imposes oxidative stress, thus explaining how hypoxia can elicit responses normally associated with a rise in P(O(2)).
Delivery of genes encoding cardiac K(ATP) channel subunits in conjunction with pinacidil prevents membrane depolarization in cells exposed to chemical hypoxia-reoxygenation.
Metabolic injury is a complex process affecting various: tissues with membrane depolarisation recognised as a common trigger event leading to cell death. To examine whether, under metabolic challenge, membrane potential homeostasis can be maintained by an activator of channel proteins, we here delivered Kir6.2 and SUR2A genes, which encode cardiac K(ATP) channel subunits, into a somatic cell line lacking native K(ATP) channels (COS-7 cells). Chemical hypoxia-reoxygenation was simulated in COS-7 cells by addition and removal of the mitochondrial poison 2,4 dinitrophenol (DNP). The membrane potential of COS-7 cells at rest was -31 +/- 3 mV. This value did not change following 3 min-long exposure to DNP (-32 +/- 4 mV). In contrast, washout of DNP induced significant membrane depolarisation (-17 +/- 2 mV). Delivery of Kir6.2/SUR2A genes did not change cellular response to hypoxia-reoxygenation. Similarly, pinacidil, potassium channel opener, did not have effect on hypoxia-reoxygenation-induced membrane depolarisation in cells lacking recombinant K(ATP) channel subunits. However, gene delivery combined with pinacidil prevented membrane depolarisation induced by hypoxia-reoxygenation. This effect of pinacidil, in cells expressing Kir6.2/SUR2A, was observed regardless of whether pinacidil was added only during hypoxia or reoxygenation. The present study demonstrates that combined use of K(ATP) channel subunits gene delivery and pharmacological targeting of recombinant proteins can be used to efficiently control membrane potential under hypoxia-reoxygenation.
[The NEN (Nicolet Electronic Naviation System) ENT navigation system. Initial clinical application].
BACKGROUND: Intraoperative computer navigation will soon play an important role in procedures performed on the anterior and lateral skull base. Electromagnetic systems compared to optical systems offer some advantages such as small hardware dimension and free unimpaired mobility of the surgeon. PATIENTS AND METHODS: The NEN navigational system (Nicolet Electromagnetic Navigation System) was used in 22 patients who underwent microscopic/endoscopic surgery for polypoid rhinosinusitis. It is the prototype of a new system, which localizes the surgical probe via the measurement of pulsed electromagnetic DC fields. This system was modified for the needs of head and neck surgery. Preoperative imaging data consisted of an axially oriented spiral computed tomography (CT) resulting in a slice thickness of 1 mm with a radiation dose slightly higher than a routine coronary CT scan of the paranasal sinuses. RESULTS: The data acquired during clinical application was used to optimize navigation accuracy. The number and positions of the markers were gradually modified and improved. Six markers including the volume of the paranasal sinus system (three non-coplanar frontal markers, one on each of the mastoid processes and one median marker on parietooccipital junction) offered the best navigation precision. Additionally, all surgical instruments measured as ferromagnetic, i.e., nasal specula, were replaced by titanium instruments. An adapter affixed to the maxilla-designed to hold a second sensor used to track the patient's head was developed. With these modifications, it was possible to improve navigation accuracy to 1.5 mm in the plane of the sphenoid bone while retaining free head movement of the patient. CONCLUSION: For routine procedures such as microscopic/endoscopic endonasal sinus surgery, the systems have to be cost effective and easy to operate.
[Duration of middle ear ventilation after laser myringotomy with the CO2 laser otoscope Otoscan].
BACKGROUND: The most important principle in treating secretory otitis media (SOM) is ventilation of the tympanic cavity. CO2 laser myringotomy achieves this via a self-healing perforation whose diameter essentially determines the duration of transtympanic ventilation. PATIENTS, METHODS: In this study, laser myringotomy was performed with the CO2 laser otoscope Otoscan in a homogeneous patient collective comprising 81 children (159 ears) suffering from SOM. The tympanic intervention was combined with an adenoidectomy or a CO2 laser tonsillotomy and therefore performed under general insufflation anesthesia. In all ears, approximately 2 mm circular perforations were created in the lower anterior quadrants with a power of 12-15 W and a pulse duration of 180 ms. RESULTS: None of the children showed postoperative impairment of inner ear function. Otomicroscopic and videoendoscopic monitoring documented the healing process. The mean closure time was found to be 16.35 days (8-34 days). As a rule, an onion-skin-like membrane of keratinized material was seen in the former myringotomy perforations at the time of closure. At the follow-up 6 months later the laser myringotomy sites appeared normal and irritation-free. Two of the tympanic membranes (1.6%) examined showed atrophic scar formation, one (0.8%) a perforation with a diameter of 0.5 mm. In 19 ears (14.7%) there was a recurrence of SOM within the observation period. CONCLUSIONS: Laser myringotomy competes with ventilation tube insertion in the treatment of SOM. It may be an useful alternative in the surgical management of secretory otitis media.
Diadenosine tetraphosphate-gating of recombinant pancreatic ATP-sensitive K(+) channels.
Diadenosine tetraphosphate (Ap4A) has been recently discovered in the pancreatic beta cells where targets ATP-sensitive K(+) (K(ATP)) channels, depolarizes the cell membrane and induces insulin secretion. However, whether Ap4A inhibit pancreatic K(ATP) channels by targeting protein channel complex itself was unknown. Therefore, we coexpressed pancreatic K(ATP) channel subunits, Kir6.2 and SUR1, in COS-7 cells and examined the effect of Ap4A on the single channel behavior using the inside-out configuration of the patch-clamp technique. Ap4A inhibited channel opening in a concentration-dependent manner. Analysis of single channels demonstrated that Ap4A did not change intraburst kinetic behavior of K(ATP) channels, but rather decreased burst duration and increased between-burst duration. It is concluded that Ap4A antagonizes K(ATP) channel opening by targeting channel subunits themselves and by keeping channels longer in closed interburst states.
[Assessment of mould pollution in residences in southwest Germany].
Elevated levels of moulds in homes may represent a risk for development of allergies and respiratory diseases. Little is known about the levels of these biogenic contaminants in homes in South-West Germany. This paper presents the results of a study which was performed between November 1997 and May 1998 in the four Sentinel Health Departments in Baden-Württemberg (Stuttgart, Mannheim, Kehl and Aulendorf/Bad Waldsee). It included 377 households in which children of 10 years of age resided. Moulds were determined in indoor air, outdoor air, household dust from floors and mattresses. Specific home characteristics were assessed by questionnaire. The median value of the number of colony forming units (CFU) in indoor air was 135 CFU/m3 (range 5-17,000) and in outdoor air 145 CFU/m3 (range 15-2,900). The median value of CFU/g dust, collected from the floors, was 15,000 (range 0-700,000) and collected from mattresses was 28,000 (range 1,500-1,350,000). The data suggest that an indoor-outdoor difference exceeding the value of 500 CFU/m3 indicates an elevated mould concentration in indoor air compared to background. This value can be discussed as a temporary reference value for South-West Germany in the winter season. However, a health assessment can not be derived from this value.
Pinacidil prevents membrane depolarisation and intracellular Ca2+ loading in single cardiomyocytes exposed to severe metabolic stress.
Recently, it has been proposed that, besides sarcolemmal K(ATP) channels, the activation of mitochondrial K(ATP) channels may also contribute to the cardioprotective action of potassium channel openers. In this respect, use of drugs that target both mitochondrial and sarcolemmal K(ATP) channels, such as pinacidil, may be a promising therapeutic strategy against metabolic injury of the heart. Therefore, the main objective of the present study was to determine whether pinacidil could maintain the value of resting membrane potential and intracellular Ca2+ homeostasis in cardiac cells exposed to metabolic stress. Experiments were performed on isolated ventricular cardiomyocytes. The membrane potential was monitored during experiments using whole cell patch clamp electrophysiology and the intracellular Ca2+ concentration was measured by a digital epifluorescence imaging. Chemical hypoxia-reoxygenation was induced by application and removal of the mitochondrial poison 2,4 dinitrophenol (DNP). Under hypoxia-reoxygenation, membrane depolarisation and intracellular Ca2+ loading was induced by Ca2+ influx during hypoxia and release of Ca2+ from intracellular stores during reoxygenation. The K(ATP) channel activator, pinacidil, prevented intracellular Ca2+ loading and membrane depolarisation, irrespective of whether the channel opener was applied throughout the duration of hypoxia-reoxygenation or transiently during the hypoxic or reoxygenation stage. Thus, the present study provides evidence that pinacidil, a non-selective K(ATP) channel opener, can handle membrane potential and intracellular Ca2+ homeostasis in cardiomyocytes under hypoxia-reoxygenation irrespective of the stage of the metabolic insult. This provides further evidence, at the single cell level, that targeting K(ATP) channels may be a valuable approach to protect the myocardium against metabolic challenge.
Perioperative beta-blockade.
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Mechanical unloading versus neurohumoral stimulation on myocardial structure and endocrine function In vivo.
BACKGROUND-Mechanical load and humoral stimuli such as endothelin (ET) and angiotensin II (Ang II) are potent modulators of cardiac structure and endocrine function, specifically gene expression and production and release of atrial natriuretic peptide (ANP). We define the contribution of mechanical load compared with neurohumoral stimulation in vivo with specific focus on myocardial and circulating ANP during chronic myocardial unloading produced by thoracic inferior vena caval constriction (TIVCC). METHODS AND RESULTS-TIVCC was produced by banding the IVC for 10 days in 7 dogs, whereas in the 6 control dogs, the band was not constricted. TIVCC was characterized by a decrease in cardiac output, right atrial pressure, and left ventricular (LV) end-diastolic diameter and marked activation of ET and Ang II in plasma and atrial and ventricular myocardium. Despite neurohumoral stimulation, LV mass index and myocyte diameters in unloaded hearts decreased, reflecting myocyte atrophy. The total number of myocytes in the LV remained unchanged. Atrial stores of ANP increased, but plasma ANP did not change, in association with a trend toward ANP gene expression to decrease in unloaded hearts. CONCLUSIONS-Chronic mechanical unloading of the heart results in myocardial atrophy and lack of activation of ANP synthesis despite marked neurohumoral stimulation by the growth promoters ET and Ang II.
[Treatment of acute otitis media with the CO2 laser].
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[Enlarged ventricular sacculus in laryngeal carcinoma--in increased risk in tumor surgery].
The case of a 60-year-old female patient with a supraglottic larynx carcinoma (T3N2CM0) and bilateral enlargement of the laryngeal sacculus is presented. On one side, the sacculus opened atypically into the left vestibular fold. The sacculus is a physiologic part of the roof of Morgagni's ventricle, the size of which can vary greatly. These canal-like structures can be the point of origin of cysts, laryngoceles, mucoceles, and pyoceles. Laryngoceles are present in about 5% of larynx carcinomas; their cause is not precisely known. Frequently, a computer tomogram suggests the coincidence of larynx carcinoma and laryngoceles or a large laryngeal sacculus. In oral panendoscopy, these ventricular distensions are difficult to detect even using 70 degrees rigid endoscopes. A planned supraglottic partial resection must take into account early tumor growth along the performed canals in the preepiglottic space. In this patient, a laryngectomy was performed due to the bilateral involvement of the vocal process and the anterior commissure.
[Experimental and clinical experiences with the Er:YAG laser otoscope].
BACKGROUND AND OBJECTIVE: Laserotoscopes are suitable for low-pain outpatient surgery of otitis media with effusion (OME) under topical anesthesia. The myringotomy perforations should have a diameter greater than 2 mm to ventilate the middle ear for approximately 3 weeks. PATIENTS/METHODS: In this study, the clinical applicability of a prototype of an Er:YAG laserotoscope (Baasel Lasertechnik, Starnberg, Germany) was tested. Formalin-fixed human tympanic membranes yielded the parameters suitable for clinical application of an Er:YAG laserotoscope in patients. With a focussed laser beam (beam diameter 500 microns), one is able to achieve perforations of 50-micron diameter with one single laser pulse applying pulse energies of 70 mJ (energy density 36 J/cm2). The ablation rate, i.e., the tissue layer that is ablated per laser pulse, is 100 microns using pulse energies of 70 mJ. This means that formalin-fixed human tympanic membrane can be perforated with one single laser pulse. RESULTS: Ten patients with OME (otitis media with effusion) were treated under topical anesthesia of the tympanic membrane (8% tetracainbase in Isopropanol for 15 min) with focussed laser pulses (beam diameter 500 microns) with energies of 100 mJ (energy density 52 J/cm2). A sufficient perforation diameter of 2 mm could be achieved with an average of 15 juxtaposed laser applications. The enlargement of the perforations was made difficult by extruding middle ear secretions and slight bleeding of the tympanic membrane. Between laser applications, the target tissue had to be cleaned by suctioning using the operation microscope. The healing of the tympanic membrane was verified and compared in postoperative clinical follow-ups. With a perforation diameter of 2 mm, the Er:YAG laser myringotomies healed within 14 days. The used parameters did not generate side effects such as inner ear hearing loss. CONCLUSIONS: An effective, easy, and practical performance of laser myringotomy is not currently possible with the Er:YAG laserotoscope.
Influence of pulsed laser irradiation on the morphology and function of the guinea pig cochlea.
Recent experimental and clinical studies have demonstrated that several pulsed laser systems are also suitable for stapedotomy. The aim of the study was to investigate morphological and functional inner ear changes after irradiating the basal turn of the guinea pig cochlea with two pulsed laser systems of different wavelengths. The Er:YSGG (lambda=2.78 mcm) and Ho:YAG (lambda=2.1 mcm) lasers were used applying the laser energies necessary for perforating a human stapes footplate. The cochleas were removed 90 min, 1 day, 2 weeks, or 4 weeks after laser application. Acoustic evoked potentials (compound action potentials) were measured before and after laser application and at the above times immediately before removal of the cochleas. The organ of Corti was examined by scanning electron microscopy. Application of Er:YSGG laser parameters effective for stapedotomy had no adverse effects on Corti's organ in the guinea pig cochlea. On the other hand, effective Ho:YAG laser parameters cause damage to the outer hair cells with fusion of stereocilia and formation of giant cilia leading to partial or total cell loss. The inner hair cells and supporting cells were usually normal. These morphological data show a good correlation with the electrophysiological measurements. Our results clearly demonstrate that, besides achieving efficient bone management, the Er:YSGG laser has high application safety. On the other hand, the Ho:YAG laser is not well tolerated in our animal study. Its use in stapedotomy would be unreliable and dangerous for the inner ear.
Pregnancy is associated with altered response to neuropeptide Y in uterine artery.
Pregnancy is associated with a significant increase in uterine blood flow which contributes to optimal fetal development. Although neuropeptide Y (NPY) is considered to be an important regulator of uterine blood flow, it is not known whether: (i) products from the vascular endothelium modulate NPY action in the uterine artery; (ii) pregnancy changes the responsiveness of the uterine artery to NPY, or (iii) NPY interacts with noradrenaline and acetylcholine on the uterine artery, with pregnancy regulating this possible interaction. In the present study, NPY induced a concentration-dependent contraction of guinea pig uterine arterial rings both intact and denuded of endothelium. Pregnancy significantly decreased the potency of NPY to contract uterine artery with and without endothelium. In all preparations, addition of N(G)-monomethyl-l-arginine acetate (l-NMMA), indomethacin and diethylcarbamazine did not modify the effect of NPY. In the presence of NPY concentration-response curves for acetylcholine and noradrenaline were significantly shifted to the right and left respectively. This effect of NPY was independent of endothelial condition or pregnancy status. The receptor reserve (K(A)/EC(50)) for acetylcholine was decreased and for noradrenaline was increased in the presence of NPY, although no changes in the dissociation constants of the neurotransmitter-receptor complexes were observed. Thus, this study has shown that: (i) NPY induces contraction of guinea pig uterine arteries acting on receptors localized in smooth muscle; (ii) pregnancy alters the response of guinea pig uterine arteries to NPY in such a way as to promote vasorelaxation, and (iii) NPY modulates the effect of neurotransmitters on guinea pig uterine arteries, but pregnancy is not associated with the changes at the level of NPY-neurotransmitter interaction.
Pregnancy does not alter the response of uterine arteries to vasoactive intestinal polypeptide.
In order to provide sufficient nutrients for fetal development, pregnancy is associated with a significant increase in uterine blood flow. Although vasoactive intestinal polypeptide (VIP) is considered to be an important regulator of uterine blood flow it is not known whether endothelium-derived relaxing factors contribute to VIP action in the uterine artery, whether pregnancy alters the effect of VIP in the uterine artery and/or whether VIP interacts with noradrenaline and acetylcholine on the uterine artery and whether pregnancy regulates this possible interaction. In the present study, VIP induced a concentration-dependent relaxation of guinea pig uterine arterial rings, both intact and denuded of endothelium. Pregnancy did not alter the relaxation of uterine artery in response to VIP. In all preparations, addition of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin and diethylcarbamazine did not modify the effect of VIP in uterine arteries. The VIP-receptor complex dissociation constant did not differ significantly between studied vessels, and in all experimental groups the relationship between receptor occupancy and the response was linear, with the receptor reserve (K(A)/EC(50)) close to unity. VIP did not modulate acetylcholine-induced relaxation or noradrenaline-induced contraction in both non-pregnant and pregnant guinea pig uterine arteries. This study has shown that: (i) VIP induces relaxation of guinea pig uterine artery acting as a partial agonist on receptors localized in smooth muscle; (ii) pregnancy does not alter the response of guinea pig uterine arteries to VIP and does not change the receptor affinity for VIP, the efficiency of the receptor coupling or the VIP receptor density; and (iii) VIP does not modulate effects of neurotransmitters on guinea pig uterine arteries and pregnancy is not associated with the changes of VIP-neurotransmitter interaction.