Pump-probe quantum state tomography in a semiconductor optical amplifier.

Pump-probe quantum state tomography was applied to the transmission of a coherent state through an In(Ga)As based quantum dot optical amplifier during the interaction with an optical pump pulse. The Wigner function and the statistical moments of the field were extracted and used to determine the degree of population inversion and the signal-to-noise ratio in a sub-picosecond time window.

Interaction of a novel GDP exchange inhibitor with the Ras protein.

Mutated, tumorigenic Ras is present in a variety of human tumors. Compounds that inhibit tumorigenic Ras function may be useful in the treatment of Ras-related tumors. The interaction of a novel GDP exchange inhibitor (SCH-54292) with the Ras-GDP protein was studied by NMR spectroscopy. The binding of the inhibitor to the Ras protein was enhanced at low Mg2+ concentrations, which enabled the preparation of a stable complex for NMR study. To understand the enhanced inhibitor binding and the increased GDP dissociation rates of the Ras protein, the conformational changes of the Ras protein at low Mg2+ concentrations was investigated using two-dimensional 1H-15N HSQC experiments. The Ras protein existed in two conformations in slow exchange on the NMR time scale under such conditions. The conformational changes mainly occurred in the GDP binding pocket, in the switch I and the switch II regions, and were reversible. The Ras protein resumed its regular conformation after an excess amount of Mg2+ was added. A model of the inhibitor in complex with the Ras-GDP protein was derived from intra- and intermolecular NOE distance constraints, and revealed that the inhibitor bound to the critical switch II region of the Ras protein.

[Use of a new optoelectronic vision aid for highly visually handicapped patients]. / Anwendungen einer neuen optoelektronischen Sehhilfe für hochgradig Sehbehinderte (LVES).

UNLABELLED: A new low vision aid (LVA)-the Low Vision Enhancement System or LVES, which were as developed at the Johns Hopkins University in Baltimore, is now commercially available. This instrument allows a magnification up to 10 times with control of contrast and luminance while the field of view is very large: 60 x 40 degrees. We present first results concerning LVES in comparison to conventional LVAs. PATIENTS AND METHODS: 60 consecutive patients suffering from macular dystrophy, macular degeneration, optic atrophy, tapetoretinal degeneration, or diabetic retinopathy were included in this study. We compared visual acuity with glasses, with telescope and using LVES. Furthermore we compared contrast acuity by the use of the Pelli-Robson-charts as well as the subjective impression of the patients. RESULTS: Improvement of visual acuity with LVES compared to correction with glasses was 8 log steps on average and up to 3 steps as compared to the use of telescopes. More important is the improvement of contrast sensitivity (0-16 steps) and the reduced glare. Despite the subjective improvement of visual acuity and contrast sensitivity the majority of patients could not imagine to use LVES regularly. A significant improvement as compared to conventional low vision aids is possible for special applications such as office work, recognition of faces or images or for looking at a blackboard. CONCLUSION: In addition to traditional LVAs, the Low Vision Enhancement System opens up possibilities for a very small group of patients. Especially patients suffering from macular dystrophy or Lebers optic atrophy may benefit from this new system. The most important advantage of LVES is the improvement of contrast sensitivity and the significantly decreased glare sensitivity. Additionally the near working distance is changeable. The variable magnification allows an easier fitting to various tasks. Prior to the prescription of LVES a detailed and time consuming testing is necessary.

Nasal septal surgery as an out-patient procedure.

Sixty consecutive patients (48 males, 12 females; age range 16 to 57, mean age 35 years) underwent nasal septal surgery at our out-patient department for symptoms of nasal obstruction. The operations were performed under local anaesthesia supplemented with 2.5-5 mg intravenous midazolam. Only one surgeon and one nurse were needed for the procedure. The total time spent at the hospital averaged three hours. The preliminary short-term results of surgery are comparable to those at our day-care unit. The complication rate was negligible. Ninety-five per cent of these patients regarded the arrangements for their operation as safe. Our results show that nasal septal surgery can be performed with good cost-effectiveness, satisfactory quality and with good safety and patient satisfaction as an out-patient procedure.

[Fluconazole level in aqueous humor after oral drug administration in humans]. / Fluconazolspiegel im Kammerwasser nach oraler Wirkstoffgabe beim Menschen.

For 2 years fluconazole, a triazole antimycotic, has been available for treatment of systemic mycosis. Compared to amphotericin B fewer severe side effects have been reported. So far, no data have been published as to its penetration into the human eye. In the present study, 20 cataract patients were given 200 mg fluconazole (0.5 to 8 h preoperatively. During the cataract operation 0.1 ml of the aqueous was removed as well as 10 ml serum. With the help of high-pressure liquid chromatography (HPLC), the concentration of fluconazole in each of the samples was determine. If the aqueous humor was removed at least 2h after fluconazole application, concentrations between 2.7 and 5.4 micrograms/ml were reached (mean 3.7 +/- 2.17) In these cases the concentration in the aqueous humor was 80% of the concentration found in the serum at the same time. If the sample of the aqueous humor was collected only 1 h after application, 40% of the concentration in the serum was found in the aqueous humor. These data prove that fluconazole shows an extremely good penetration through the blood-aqueous barrier. After a single dose of 200 mg, a concentration is reached in the eye that surmounts the minimal inhibiting concentration found for Candida species sensitive to fluconazole. Therefore, fluconazole seems to be a good alternative to amphotericin B for the treatment of infections caused by such fungi.

Effect of local tranexamic acid gel in the treatment of epistaxis.

In patients with nosebleedings, the hemostatic effect of local application of tranexamic acid gel or placebo was compared in a randomized, double-blind, multicenter clinical trial with parallel groups. The times needed to arrest the initial bleeding were recorded, as well as any rebleedings within 10 days. The results showed no significant differences in any of the efficacy variables. Tranexamic acid was no better than placebo in the early treatment of nose bleedings, but the gel itself seemed to have a beneficial effect. The gel preparations were easy to insert into the nasal cavity and caused no discomfort to the patients.

Basic experimental studies of ostial patency and local metabolic environment of the maxillary sinus.

Experimental studies of human maxillary sinus gas exchange show that there is a balance between inflow of air through the maxillary ostium and local consumption as long as the functional size of the ostium is at least 5 mm2. Maxillary sinus mucosal blood flow is 30-40 ml/100 g tissue per minute, as measured in plethysmographic studies. This blood flow can bind and transport only half of the absorbed oxygen, the rest is consumed. Experimental histo- and biochemical studies of sinusitis show anaerobic mucosal metabolism with shortage of energy supply due to inadequate oxygen supply. There is no decrease in oxidative enzyme capacity of the mucosal epithelium. Analysis of organic acids in purulent secretion indicates that the high lactate and CO2 concentration found is mainly the result of leucocyte glycolysis with local lactic acidosis. Both ostial occlusion and the initiation of bacterial growth in serous sinusitis may be secondary to an initial inflammatory response, resulting in local tissue pathology and swelling of the ostiomeatal complex, as well as creating the appropriate redox potential for further bacterial growth in the secretions.

How the anti-(metal chelate) antibody CHA255 is specific for the metal ion of its antigen: X-ray structures for two Fab'/hapten complexes with different metals in the chelate.

Antibodies with bound metal-chelate haptens provide new means for exploiting the diverse properties of metallic elements. The murine monoclonal antibody CHA255 (IgG1 lambda) binds the metal-chelate hapten indium (III)-4-[N'-(2-hydroxyethyl)thioureido]-L-benzyl-EDTA (designated In-EOTUBE) with high affinity (K(a) = 1.1 x 10(10) M-1). Antibody binding is highly specific for the indium chelate; the affinity decreases as much as 10(4) with other metals, even those having ionic radii close to indium. To better understand this selectivity, the crystal structure of the antigen-binding fragment (Fab') of CHA255 complexed with its hapten, In(III)-EOTUBE, was determined by molecular replacement and refined at 2.2-A resolution. The structure of CHA255 Fab' complexed with Fe(III)-EOTUBE was also determined and refined at 2.8-A resolution. In both structures, the hapten's EDTA moiety is half-buried near the center of the complementarity-determining regions (CDR's). Five of the six CDR's on the Fab' interact with the hapten through protein side-chain atoms (but not main-chain atoms). A novel feature of the In-EOTUBE/Fab' complex is coordination of the indium by N epsilon of one histidine from the heavy chain's third CDR (distance = 2.4 A). The histidine coordination is not observed in the Fe-EOTUBE/Fab' complex, due mainly to a slightly different hapten conformation that reduces metal accessibility; this may partially explain the 20-fold lower affinity of CHA255 for iron hapten. An unexpected feature of the Fab' overall is an elbow angle of 193 degrees (the angle between the pseudodyad axes of the Fab's constant and variable domains).

The effect of Xylometazoline on the mucosa of human maxillary sinus.

A stuffy and running nose are two of the most expressed symptoms of acute rhinosinusitis and have made the use of decongestants very common. The medication, oral or nasal, gives relief from symptoms but its effect on the healing of the infection, positive or negative, is not clear. The effect of Xylometazoline on the blood flow, the pulse amplitude and the gas exchange in the antral mucosa of the maxillary sinus was studied in five healthy subjects. Our experiments show that the mucosal pulse amplitude and the blood flow are strongly reduced by insufflation of Xylometazoline but the gas exchange in the mucosa is only lowered to a minor extent. The reduction in gas exchange is not great enough to allow the gas mixture to be altered. The defence mechanisms in the antral mucosal lining, i.e. the mucociliary-, the immuno- and the phagocytotic mechanisms are all dependent on the blood flow and the gas exchange through narrow maxillary ostia of the pumping effect generated by the mucosal pulse wave. The reduction in blood flow and pulse amplitude in the maxillary mucosa caused by Xylometazoline leads us to consider that, although not harmful then it is at least not helpful, in healing rhinosinusitis. Since oral decongestants have almost the same effect on the mucosa as nasal decongestants, we do not think that any of the medicines faciliate the healing of infections in the upper airways even if they make the patient feel better during the infection.

Blood flow and pulse amplitude in the mucosa of the human maxillary sinus in relation to body posture.

The paranasal sinuses are non-collapsible ventilated gas pockets without any known function. They should, however, be adequately ventilated to stay healthy. Persons lying in a recumbent body position compared to persons sitting or standing upright have reduced antral mucosal blood flow, a reduction of 35%, and a congested mucosa which reduces both the mucosal gas exchange and the perostial ventilation, creating a more anaerobic antral gas mixture facilitating pathogenic bacterial growth and reduced ciliary activity. It is, therefore, recommendable for patients with sinusitis to treat themselves or be treated in an upright or semi-recumbent body position.

The effect of physical work on the mucosal blood flow and gas exchange in the human maxillary sinus.

The paranasal sinuses are lined with respiratory mucosa of principally the same structure as in the nasal mucosa but somewhat thinner. This mucosa has a rich blood flow and advanced system of blood vessels regulated mostly by the autonomous nervous system but also by other factors as acid/base balance and endocrine activity. The thickness of the nasal mucosa regulates the nasal breathing resistance and varies with among other factors, body activity. In this investigation we have studied the effect of physical work on the human maxillary sinus mucosa. The investigation shows that, as in the nose, the blood flow and the pulse amplitude are considerably reduced during physical work, in situations of heavy work falling to about half of the normal level, and probably result in the redistribution of blood from the respiratory mucosa. The gas exchange in the paranasal sinus is reduced only to a small extent, the reduction being too small to change the antral gas composition towards pathological conditions.

The relationship between body posture and pressure in occluded maxillary sinus of man.

One of the most common symptoms in sinusitis is pain over the infected cavity increasing when the patient is bending forward or lying down. It is commonly thought that this increase in pain is a result of increased pressure in the paranasal cavities when bending forward. In this investigation we have found that changing the body position from sitting to recumbent or even to "head between knees" gives a manometrical pressure rise in the sinus that is too small to cause a pressure-mediated pain. The pain is probably caused by a dilation in the blood vessels of the infected mucosa when the patient is bending forward or lying down.

The ultrastructure of the human antral mucosa as demonstrated by freeze-fracturing.

The fine structure of the normal mucous membrane in the human maxillary sinus was investigated by means of the freeze-fracture technique. Special interest was directed to membrane structures in the epithelial cells. The morphology of tight junctions could be analysed. According to morphological criteria these junctions might be classified as "very tight". So called ciliary necklaces were well distinguishable. Their morphology seemed to be in concordance with the structure reported in other mammalian respiratory epithelia. Abluminally the epithelial cells frequently displayed abundant caveolae or micropinocytotic vesicles. The present investigation was performed as a preface to later studies on pathologically altered antral mucosa.

Ventilatory effects of the pulse wave in the maxillary sinus.

The perostial ventilation of the human maxillary sinus is achieved via three main factors: diffusion, respiration wave and the mucosal pulse wave. The ventilatory factors have been studied with the help of a model sinus. The values used in the model are based upon in vivo human studies. Diffusion is responsible for the most important ventilatory effect in large ostia. Respiration has a ventilatory effect in all ostial sizes. The mucosal pulse has a ventilatory effect when the pulse volume exceeds the dead space of the ostium. When the ostial volume is diminished, the pulse-induced ventilation increases and keeps the total ventilation constant regardless of ostial size. In very small ostia, the mucosal pulse and respiration are the two important ventilatory factors.

Studies of the gas exchange and pressure in the maxillary sinuses in normal and infected humans.

The total gas pressure in experimentally occluded maxillary sinus was continuously recorded during 90 minutes on 7 healthy human subjects. PO2 and PCO2 were measured before and after the total pressure recording. In 3 cases the volume changes in the sinus were measured. The total gas pressure after an initial increase to about 35 mm H2O decreased to a steady state of about 70 mm H2O below atmospheric pressure. The volume changes in sinus showed a corresponding alteration. The gas measurements showed a decrease of PO2 of 25 mm Hg and a rise of PCO2 of 21 mm Hg. In 3 patients with acute purulent sinusitis there was seen a pressure of about 10 cm H2O above the atmospheric pressure.