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Biomedical subjects

K Geiger

Publications and source records attributed to K Geiger.

At least 73 records · Page 4Linked to original sources
PubMed1995

Inhaled nitric oxide reduces pulmonary transvascular albumin flux in patients with acute lung injury.

BACKGROUND: In acute lung injury, when pulmonary microvascular permeability is enhanced, transvascular fluid filtration mainly depends on pulmonary capillary pressure. Inhaled nitric oxide has been shown to decrease pulmonary capillary pressure. Therefore, the effect of inhaled nitric oxide at a concentration of 40 ppm on pulmonary transvascular albumin flux was studied in nine patients with acute lung injury. METHODS: Transvascular albumin flux was measured by a double radioisotope method using 99mTc-labeled albumin and 51Cr-labeled autologous red blood cells. Radioactivity of both isotopes was externally measured over the right lung by a gamma scanner and simultaneously in arterial blood. The normalized ratio of 99mTc/51Cr lung to 99mTc/51Cr blood (normalized index) was calculated. The normalized slope index which is the slope of the regression line of the normalized index versus time represents the accumulation rate of albumin in the interstitial space of the lungs. Normalized slope index and pulmonary capillary pressure were determined before, during, and after inhalation of 40 ppm nitric oxide. Pulmonary capillary pressure was estimated using the visual analysis of the pressure decay curve after pulmonary artery occlusion. RESULTS: Normalized slope index decreased from 0.0077 +/- 0.0054 min-1 (SD) off nitric oxide to -0.0055 +/- 0.0049 min-1 (P < 0.01) during nitric oxide and increased to 0.0041 +/- 0.0135 min-1 after nitric oxide. Pulmonary capillary pressure declined from 24 +/- 4 mmHg off nitric oxide to 21 +/- 4 mmHg during nitric oxide (P < 0.01), whereas pulmonary artery wedge pressure and cardiac output did not change. CONCLUSIONS: It is concluded that 40 ppm inhaled nitric oxide decreases pulmonary transvascular albumin flux in patients with acute lung injury. This effect may be the result of the decrease in pulmonary capillary pressure.

Acute Disease↗
PubMed1995

Differential effects of dobutamine, dopamine, and noradrenaline on splanchnic haemodynamics and oxygenation in the pig.

Supranormal oxygen (O2) transport may benefit critically ill patients. Catecholamines are clinically employed for this purpose. However, their effects on splanchnic haemodynamics and oxygenation are now well defined. The effects of dobutamine (DOBU), dopamine (DOPA), and noradrenaline (NA) on splanchnic blood flows electromagnetic flow probes), O2 deliveries and uptakes (catheterisation of portal and hepatic veins) were studied in nine anaesthetised (ketamine/flunitrazepam), ventilated, paralysed, and laparotomised pigs. All three catecholamines (DOPA at 15 micrograms.kg-1.min-1, DOBU at 13 micrograms.kg-1.min-1, NA at 0.4 micrograms.kg-1.min-1) significantly (P < 0.05) increased cardiac output and systemic O2 delivery. Only DOPA increased small intestinal and total hepatic blood flows, and O2 deliveries, and decreased O2 extractions. The same parameters did not change during DOBU. During NA, total hepatic blood flow and O2 delivery decreased, and hepatic O2 extraction increased. During all three catecholamines, small intestinal and total hepatic O2 uptakes did not change significantly. Whereas hepatic arterial blood flow decreased during both DOPA and NE, portal venous flow increased during DOPA. These data suggest that in the experimental model used splanchnic O2 supply and O2 reserve capacity appear improved by DOPA, unaffected by DOBU, and impaired by NA.

Adrenergic beta-Agonists↗
PubMed1994

Local production of IFN-gamma abrogates the intraocular immune privilege in transgenic mice and prevents the induction of ACAID.

The eye represents an immunologically privileged site with specific properties mediated by immunosuppressive constituents of the intraocular fluids. This system, termed ACAID (anterior chamber-associated immune deviation), was originally attributed to the anterior chamber of the eye, and is characterized by impairment of the cellular immune response, including a lack of delayed type hypersensitivity (DTH) reaction in response to intraocularly presented Ag and decreased cytotoxicity of T cells. We created a transgenic mouse with ectopic expression of IFN-gamma in the photoreceptors of the retina to study the effects of this cytokine on the immunosuppressive properties of the eye with special regard to the posterior chamber. BALB/c-derived transgenic and nontransgenic mice were challenged intravitreally either with allogeneic splenocytes from C57Bl/6 mice or with BSA, in IFA, and tested for the delayed type hypersensitivity reaction to BSA by intrapinnal injection of the same Ag in the ear 7 days later. Pathologic changes of the eyes were evaluated by histology and immunohistochemistry. We found that transgenic mice developed an increased amount of ocular inflammation in response to both Ags compared with the nontransgenic controls. Furthermore, transgenic mice showed a marked DTH reaction to BSA, whereas nontransgenic mice did not. Our results indicate that local IFN-gamma production disturbs the immunosuppressive properties of the eye and prevents the induction of ACAID in response to intraocularly presented Ag. The data confirm the extension of the intraocular immune privilege to the posterior chamber of the eye.

Animals↗
PubMed1994

Inhaled nitric oxide lowers pulmonary capillary pressure and changes longitudinal distribution of pulmonary vascular resistance in patients with acute lung injury.

In acute lung injury (ALI), where pulmonary microvascular permeability is increased, transvascular fluid filtration depends mainly on the hydrostatic capillary pressure. In the presence of intrapulmonary vasoconstriction pulmonary capillary pressure (PCP) may increase thereby promoting transvascular fluid filtration and lung oedema formation. We studied the effect of 40 ppm inhaled nitric oxide (NO) on PCP and longitudinal distribution of pulmonary vascular resistance (PVR) in 18 patients with ALI. PCP was estimated by visual analysis of the pressure decay profile following pulmonary artery balloon inflation. Contribution of venous pulmonary resistance to total PVR was calculated as the percentage of the pressure gradient in the pulmonary venous system to the total pressure gradient across the lung. Inhalation of 40 ppm NO produced a prompt decrease in mean pulmonary artery pressure (PAP) from 34.1 +/- 6.8 to 29.6 +/- 5.7 (s.d.) mmHg; (P < 0.0001). PCP declined from 24.8 +/- 6.2 to 21.6 +/- 5.2 mmHg; (P < 0.0001) while pulmonary artery wedge pressure (PAWP) did not change. PVR decreased from 166 +/- 73 to 128 +/- 50 dyn.sec.cm-5; (P < 0.0001). Pulmonary venous resistance (PVRven) decreased to a greater extent (from 76 +/- 41 to 50 +/- 28 dyn.sec.cm-5; (P < 0.001) than pulmonary arterial resistance (PVRart) (from 90 +/- 36 to 79 +/- 29 dyn.sec.cm-5; (P < 0.01). The contribution of PVRven to PVR fell from 44.3 +/- 10.8 to 37.8 +/- 11.9%; (P < 0.01). Cardiac output (CO) remained constant. The findings demonstrate that NO has a predominant vasodilating effect on pulmonary venous vasculature thereby lowering PCP in patients with ALI.

Administration, Inhalation↗
PubMed1994

Ectopic expression of gamma interferon in the eye protects transgenic mice from intraocular herpes simplex virus type 1 infections.

Transgenic (rho gamma) mice provide a model for studying the influence of gamma interferon (IFN-gamma) produced in the eye on ocular and cerebral viral infection. To establish this model, we injected BALB/c- and C57BL/6-derived transgenic and nontransgenic mice of different ages intravitreally with herpes simplex virus type 1 (HSV-1) strain F. Eye and brain tissues of these mice were assessed for pathological and immunocytochemical changes. HSV-1 infection induced severe retinitis of the injected eyes and infection of the brain in all mice. In transgenic mice inoculated with HSV-1, the left, nontreated eyes were protected from retinitis, whereas nontransgenic mice developed bilateral retinitis. Additional intravitreal injection of IFN-gamma with the virus protected the noninoculated eyes of nontransgenic mice. Three-week-old nontransgenic mice died from HSV-1 infection, whereas transgenic mice of the same age and nontransgenic mice intravitreally treated with IFN-gamma survived. Ocular IFN-gamma production increased the extent of inflammation in transgenic mice but did not have a significant influence on the growth of HSV-1 until day 3 after inoculation and did not influence the neuroinvasion of this virus. Thus, the effects of IFN-gamma were not caused by an early block of viral replication. Possible mechanisms of IFN-gamma action include activation of the immune response, alteration of the properties of the virus, and direct protection of neurons.

Animals↗
PubMed1994

Paraffin induced sclerosing lipogranuloma of eyelids and anterior orbit following endonasal sinus surgery.

During the past 5 years we have seen 10 patients who had developed sclerosing lipogranuloma of the lid and orbit after endonasal sinus surgery with subsequent ipsilateral monocular haematoma. The histopathological examination of all and the additional nuclear magnetic resonance spectroscopic examination of four surgical specimens in combination with the typical clinical course led to the conclusion that the granulomas were caused by small paraffin droplets. These in turn stemmed from the ointment plugs applied to the sinuses at the end of the operation, and were washed out into the surrounding tissues by the postoperative haemorrhage. As the chronic and recurring granulomas can lead to considerable cosmetic and functional impairment, the application of ointment plugs at the end of sinus surgery should be abandoned, especially when peri- or postoperative bleeding occurs.

Adult↗
PubMed1994

Relationship of plasma epinephrine and circulating eosinophils to nocturnal asthma.

The mechanisms of nighttime airway obstruction are not fully established, but include circadian fluctuations in epinephrine and cortisol. To evaluate the relationship of circadian patterns in epinephrine and cortisol to nighttime airflow obstruction, 10 young adult asthma patients (ages 19 to 25 yr) were admitted to a hospital clinical research unit for a 3-day study during which plasma concentrations of epinephrine, cortisol, and histamine were determined along with white blood cell and eosinophil counts every 6 h (1600, 2200, 0400, and 1000 h). Six of the 10 patients experienced at least one episode of nocturnal asthma (defined by more than a 15% decrease in antemeridian (A.M.) to postmeridian (P.M.) FEV1 values). Plasma epinephrine levels (pg/ml) showed a circadian pattern, and the concentration at 2200 h was significantly (p = 0.039) different for the nocturnal and non-nocturnal asthma groups. Circulating eosinophil numbers were greater in subjects who had more frequent episodes of nocturnal asthma, and correlated with the frequency of nocturnal asthma (r = 0.732, p = 0.02, Spearman rank correlation) and average percent decrease in FEV1 (r = 0.667, p = 0.035). Plasma cortisol concentrations also showed circadian patterns, but no direct association with nocturnal asthma; plasma histamine concentrations showed no circadian patterns and no association with nocturnal asthma. Our findings indicate that changes in plasma epinephrine precede the development of nocturnal airway obstruction and contribute to the likelihood of nighttime airflow obstruction.

Adult↗
PubMed1994

[Long term course of catecholaminergic polymorphic ventricular tachycardia in children. Apropos of 20 cases with an 8 year-follow-up].

BACKGROUND: Primary ventricular arrhythmias are rarely seen in children. Some of them have a poor prognosis; they should be diagnosed because adequate treatment can prevent sudden death. POPULATION AND METHODS: Twenty children (11 male, nine female), aged 3 to 16 years (mean: 7.7 +/- 4), with apparently normal hearts and normal QTc intervals were referred for stress or emotion-induced syncope. Primary ventricular arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvos eventually degenerating into ventricular fibrillation, was reproducibly induced by physical exertion. The syncopal events and "torsades de pointe" disappeared with beta-blocking therapy. A total of four syncopal events and two sudden deaths occurred during a mean follow-up of 8 years, probably due to discontinuation of treatment. DISCUSSION: Fifty-four-cases of stress-induced severe polymorphous ventricular arrhythmia have been reported in the literature. There were four sudden deaths in 37 patients on beta-blocking therapy, and ten sudden deaths in 21 untreated patients. CONCLUSION: Clinically close to the congenital long QT syndrome, this primary ventricular arrhythmia must be looked for in cases of stress or emotion-induced syncope. The diagnosis relies on Holter monitoring and a stress test. Life-long beta blocker therapy is required.

Adolescent↗
PubMed1994

Transgenic mice expressing IFN-gamma in the retina develop inflammation of the eye and photoreceptor loss.

PURPOSE: Inflammatory mediators such as interferon-gamma (IFN-gamma) are thought to play a role in ocular disease. Although IFN-gamma was found in the vitreous of mice with experimentally induced autoimmune uveitis, intracameral injection of this cytokine did not induce intraocular inflammation in mice. Therefore, the authors created a transgenic mouse line using the rhodopsin promoter to direct the expression of IFN-gamma in the photoreceptor cells of the retina. These mice, designated rho gamma, enabled them to model intraocular inflammatory disease. METHODS: The authors fused a 2.1 kb 5' Hind III fragment from the murine rhodopsin gene to the IFN-gamma gene and introduced the DNA construct into fertilized zygotes. These were implanted into pseudopregnant C57BL/6 mice, and the resulting progeny were crossed back to balb/c mice. The transgene was identified by Southern blot hybridization. Eyes from the rho gamma mice were either fixed in zinc formalin and stained with hematoxylin and eosin or were frozen in OCT compound and processed for immunostaining using the indirect immunoperoxidase method with DAB as a chromogen. RESULTS: The rho gamma transgenic mice developed intraocular disease, manifested as intraocular cellular infiltration, loss of photoreceptors, corneal clouding, cataract formation, and epithelial and microglial proliferation. Additionally, rho gamma mice exhibited antigenic changes, comprising GFAP expression on Müller cells, accumulation of neurofilament on photoreceptors, and expression of MHC class I and class II molecules on retinal cells. CONCLUSIONS: IFN-gamma alters the antigenic properties of intraocular tissue and induces intraocular inflammation in mice. The results suggest a key position of IFN-gamma in the development of pathologic conditions related to intraocular inflammation and provide a useful animal model for the further study of inflammatory disorders, including autoimmune diseases.

Animals↗