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Biomedical subjects

L Hesse

Publications and source records attributed to L Hesse.

At least 19 recordsLinked to original sources
PubMed2004

Bilateral congenital dacryocystocele as a cause of respiratory distress in a newborn.

Newborns with respiratory distress and nasal obstruction must be examined for congenital dacryocystocele. This disease is caused by a stenosis in the proximal and distal area of the nasolacrimal duct and leads to a cystic dilatation of this duct. A case of a newborn with bilateral dacryocystocele and dyspnoea is presented. The otorhinolaryngologic as well as the paediatric examination could only reveal in the rhinoscopic examination a tumor of the left nasal cavity that partly obstructed the endonasal space. No other pathologic findings were detected. To clarify the origin and the localization of the tumor as well as to exclude an intracranial relation, a magnetic resonance imaging of the middle face and the frontal skull base was performed. After probe and rinsing of the lacrimal ducts the symptoms improved rapidly. In newborns with nasal obstruction a bilateral rhinoscopy of the lower nasal meatus is required to exclude the existence of a dacryocystocele.

Humans↗
PubMed2002

Exploiting current understanding of antibiotic action for discovery of new drugs.

The introduction of antibiotics for the chemotherapy of bacterial infections has been one of the most important medical achievements of the past 50 years. However, the emergence of bacterial resistance to antibiotics undermines the therapeutic utility of existing agents, creating a requirement for the discovery of new antibacterial drugs. Several drug discovery strategies have emerged, including incremental improvements to existing antibiotics by chemical manipulation and the search for novel drug targets based on genomic approaches. An alternative strategy seeks to exploit opportunities for drug discovery arising from an understanding of the mode of action of existing antibiotics. Thus biochemical pathways or processes inhibited by antibiotics already in clinical use may nevertheless contain key functions that represent unexploited targets for further drug discovery. A major benefit of employing pathways or processes that are already known to contain drug targets is that proof of principle for drug intervention is already established. This approach to drug discovery is illustrated by reviewing target sites for existing antibiotics and considering how this information might be applied for the discovery of new agents inhibiting peptidoglycan synthesis, tRNA synthesis, transcription and DNA replication

Anti-Bacterial Agents↗
PubMed2002

Exploiting current understanding of antibiotic action for discovery of new drugs.

The introduction of antibiotics for the chemotherapy of bacterial infections has been one of the most important medical achievements of the past 50 years. However, the emergence of bacterial resistance to antibiotics undermines the therapeutic utility of existing agents, creating a requirement for the discovery of new antibacterial drugs. Several drug discovery strategies have emerged, including incremental improvements to existing antibiotics by chemical manipulation and the search for novel drug targets based on genomic approaches. An alternative strategy seeks to exploit opportunities for drug discovery arising from an understanding of the mode of action of existing antibiotics. Thus biochemical pathways or processes inhibited by antibiotics already in clinical use may nevertheless contain key functions that represent unexploited targets for further drug discovery. A major benefit of employing pathways or processes that are already known to contain drug targets is that proof of principle for drug intervention is already established. This approach to drug discovery is illustrated by reviewing target sites for existing antibiotics and considering how this information might be applied for the discovery of new agents inhibiting peptidoglycan synthesis, tRNA synthesis, transcription and DNA replication.

Anti-Bacterial Agents↗
PubMed2001

Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease.

We reported previously that the carbohydrate domain of the amyloid precursor protein is involved in amyloid precursor protein (APP)-APP interactions. Functional in vitro studies suggested that this interaction occurs through the collagen binding site of APP. The physiological significance remained unknown, because it is not understood whether and how APP dimerization occurs in vivo. Here we report that cellular APP exists as homodimers matching best with a two-site model. Consistent with our published crystallographic data, we show that a deletion of the entire sequence after the kunitz protease inhibitor domain did not abolish APP homodimerization, suggesting that two domains are critically involved but that neither is essential for homodimerization. Finally, we generated stabilized dimers by expressing mutant APP with a single cysteine in the ectodomain juxtamembrane region. Mutation of Lys(624) to cysteine produced approximately 6-8-fold more A beta than cells expressing normal APP. Our results suggest that amyloid A beta production can in principle be positively regulated by dimerization in vivo. We suggest that dimerization could be a physiologically important mechanism for regulating the proposed signal activity of APP.

Alzheimer Disease↗
PubMed2001

[Using enzymes in the posterior eye segment. Current status and future possibilities].

The first investigations to treat diseases of the posterior segment enzymatically started 40 years ago. To treat acute subretinal hemorrhage a pneumatic displacement through intravitreally injected gas after enzymatically induced subretinal fibrinolysis (TPA) is recommended. Recent morphometric analysis clearly demonstrated a subretinal fibrinolytic effect after intravitreal injection of TPA. Obviously TPA crosses the retina through microlesions that develop through elevation of the retina during acute bleeding. For the first time pars plana vitrectomy was superseded by a simple and gentle enzymatic therapy combined with pneumatic displacement by intravitreally injected gas. Increasing experience with pars plana vitrectomy demonstrated that a complete removal of the vitreous body has beneficial effects on the course of vasoproliferative vitreoretinal diseases. Therefore enzymes were tested to either liquefy the vitreous body (collagenase or hyaluronidase) or to cleave the posterior vitreous cortex and the retina (dispase, plasmin, tissue plasminogen-activator or chondroitinase). At present only tissue-plasminogen activator (TPA), plasmin and hyaluronidase were used in small clinical studies. Recent developments in the understanding of vasoproliferative vitreoretinal disorders offers new therapeutical approaches like enzymatical destruction of growth factors (VEGF) or extracellular adhesive proteins (fibronectin). From this point of view future therapies may include enzymatic cleaning of the vitreous body to prevent proliferative diabetic vitreoretinopathy.

Animals↗
PubMed2001

[Population-based study of diabetic retinopathy in Wolfsburg].

INTRODUCTION: Since November 1997 the complete documentation of an ophthalmological examination of diabetics has been annually subsidized by the Volkswagen Corporation Health Maintenance Organization (VW-HMO). METHODS: The results of an annual ophthalmological examination were recorded in a standardised history sheet developed by the Initiative Group for Early Detection of Diabetic Eye Diseases. These data included visual acuity, intraocular pressure, lens status and a description of fundus abnormalities. RESULTS: Within 26 months ophthalmological examinations of 2,801 patients were completed which represented 4.5% of all VW-HMO insured patients. On average, patients suffered from diabetes for 9.6 years (SD +/- 8.3), artificial intraocular lenses were present in 357 eyes (6.4%) and 1,216 eyes (12.0%) were diagnosed with cataract or posterior capsule opacification impairing visual acuity. Out of 263 patients younger than 40 years old, 18.8% had a mild or moderate and 3.3% a severe non-proliferative diabetic retinopathy (NPDR). A proliferative diabetic retinopathy (PDR) was found in 2.2% of the younger patients. Of 2,228 patients aged 40 years and older, 11.9% had a mild or moderate and 2.6% a severe NPDR. In 0.9% of this group PDR was diagnosed. CONCLUSIONS: An annual ophthalmological screening based on a survey sheet of the Initiative Group was successfully introduced. For the first time a population-based evaluation on the prevalence of diabetic retinopathy was carried out for inhabitants of a German city. The prevalence of PDR was found to be lower than previously published in comparable studied.

Adolescent↗
PubMed2001

[Physiological functional evaluation of retinal implants in animal models].

Retinal implants can--by electrical stimulation--create visual impressions in people with certain kinds of degenerative retinal diseases (e.g. Retinitis Pigmentosa). Electrically evoked potentials in the retina must be transferred into the visual cortex in an orderly manner, a prerequisite for any kind of form- and movement-perception. In the current developmental stage the difficult investigations are performed in various animal models: isolated retinae of intact chicken and of RCS-rats (a model for Retinitis Pigmentosa), as well as in anesthetised rabbits, pigs and cats with intact retinae. Our investigations show that spatially selective ganglion-cell responses can be recorded following focal electrical stimulation, in healthy and as well in degenerated retinae. Registration of activities in area 17 of the visual cortex demonstrate that electrical retinal stimulation can indeed activate it.

Animals↗
PubMed2001

[Histopathology of 8 corneal buttons after penetrating keratoplasty in silicone oil-associated keratopathy].

BACKGROUND: In the literature there is only a limited number of morphological reports on clinically diagnosed silicone oil associated keratopathy describing different histological changes. The purpose of the present study was to evaluate the most common histopathological features of this disorder. MATERIAL AND METHODS: We reviewed the registry of the ophthalmopathological laboratory at the University of Marburg with respect to the following histopathological diagnoses: "bullous keratopathy", "endothelial-epithelial corneal decompensation", "band keratopathy" and "endothelial degeneration". These specimens were cross-checked with appropriate medical records. Eight specimens with a clinical diagnosis of silicone oil induced keratopathy were identified. All specimens were examined by light microscopy. RESULTS: Histologically, a long-standing bullous keratopathy was seen in 5 out of 8 specimens. A descemetocele was present in two other corneas. One case displayed band keratopathy. A posterior collagenous layer (PCL) between Descemet's membrane and the endothelium was identified in 7 out of 8 specimens examined. This layer was of a fibrillar type in 2 corneal buttons and of a fibrocellular type in all remaining specimens with PCL. PCL was associated with endothelial cell loss and degeneration. The endothelial cell density varied between 0 and 5 cells per high power field. CONCLUSION: Posterior collagenous layer associated with degenerating endothelium appears to be the most frequent histopathological feature in silicone oil induced keratopathy. The variety of PCL in this condition makes a firm histopathological diagnosis of "Silicone oil induced keratopathy" rather difficult.

Adolescent↗
PubMed2000

Induction of posterior vitreous detachment in rabbits by intravitreal injection of tissue plasminogen activator following cryopexy.

The purpose of this study was to generate intravitreal plasmin after intravitreal injection of tissue plasminogen activator (TPA) and cryopexy, and to assess its proteolytic effect on the vitreoretinal border region.Twenty-four hr after a mild cryopexy, 25 microg recombinant tissue plasminogen activator (TPA) was injected into the vitreous cavity, the fellow eye received an intravitreal injection of the same volume of buffered salt solution. Light, scanning and transmission electron microscopy was performed in 24 eyes that underwent vitrectomy 1 week later. Plasmin was measured prior and 2 hr after intravitreal TPA injection (4 eyes). Hyaluronic acid (8 eyes) and vitronectin (4 eyes) were measured 1 week after TPA- or BSS-injection and compared to untreated controls. In all eyes treated with TPA, histopathologic examination by scanning and transmission electron microscopy demonstrated a complete detachment of the vitreous from the surface of the retina as well as from the posterior surface of the lens. After BSS-injection, vitreous cortex attachment to the retina was demonstrated in all eyes. Two hr after TPA-injection, plasmin increased to 9.75 mU ml(-1)(s.d.+/-2.3). Neither a decrease of hyaluronic acid nor an increase of transglutaminase, that might alter the vitreous structure leading to a collapse of the vitreous, were detected in treated eyes. There was no increase of vitronectin indicating proliferative activity.A temporary breakdown of the blood-retinal barrier by cryopexy combined with intravitreal injection of TPA is a sufficient technique to induce a posterior vitreous detachment enzymatically. The method may be useful prior to mechanical vitrectomy.

Animals↗
PubMed2000

Implantation of retina stimulation electrodes and recording of electrical stimulation responses in the visual cortex of the cat.

BACKGROUND: Simple basic visual perception may be restored by epiretinal electrical stimulation in patients that are blind due to photoreceptor loss. To stimulate ganglion cells, epiretinally flat platinum microelectrodes embedded in thin polyimide film were developed and tested in the cat. METHODS: After removal of the lens and the vitreous body a thin microfilm electrode array was implanted through a corneoscleral incision in the cat eye (n = 4). In two eyes no further attempt was made to fixate the tip of the electrode, which was pressed onto the retinal surface due to the tension of the curved polyimide film. In two eyes the tip of the electrode was fixed with cyanoacrylate adhesive. The exterior part of the microelectrode film was directed under the skin towards the forehead which allowed fixation of the microplug to a head fixation bolt. Retinal stimulation experiments were performed within 1 week after implantation. Success of stimulation was assessed by recording neuronal activities from areas 17 and 18. Retinal microelectrodes were removed 2 weeks or longer after implantation. RESULTS: Intraocular inflammation or retinal detachment were not observed after implantation of the microelectrode film. In two eyes the tip of the microelectrodes dislocated spontaneously within the first few days. The lowest threshold of electrical stimulation was 35 microA, corresponding to a charge transfer of 14 nC per phase. These values were ten times higher than those obtained by needle electrodes used in prior experiments. CONCLUSIONS: Intraocular implanted flat microelectrodes made of platinum and polyimide were well tolerated. Because of the flat configuration of the microelectrodes higher stimulation thresholds than for needle electrodes were found, indicating insufficient contact to the retinal surface. An alternative shape and fixation technique is required to minimise electrodes' threshold of stimulation.

Animals↗
PubMed2000

Chondroitin sulphate inhibits connective tissue mast cells.

1. Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly inflammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and specific antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-inflammatory molecules that include histamine, cytokines and proteolytic enzymes. 2. Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory effect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell 'stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed off, while the effect of cromolyn was limited by rapid tachyphylaxis. 3. Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this effect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo- and monosaccharides were not as effective as the polysaccharides. 4. Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes. 5. Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications.

Animals↗
PubMed2000

Quantitative effect of intravitreally injected tissue plasminogen activator and gas on subretinal hemorrhage.

PURPOSE: To quantify the effect of intravitreally injected tissue plasminogen activator (TPA) and an expanding gas on freshly formed subretinal hemorrhage (SRH). PATIENTS AND METHODS: Thirteen patients with acute (1 week or less) SRH due to age-related macular degeneration (ARMD) were treated with an intravitreal injection of 50 microg TPA, and 24 hours later, with an expanding gas. Fundus photographs taken before and 24 hours after each injection were digitized and calibrated. Area, geometric center, and shift of the SRH were measured at each time point using NIH image analysis software. Elevation of the SRH was assessed by echography. RESULTS: Compared to the preoperative size, SRH enlarged significantly 24 hours after TPA injection (P < 0.001). A significant shift of the geometric center toward the inferior retinal periphery out of the macula was found after gas injection (P < 0.001). Significant horizontal displacement of the SRH was not noted after TPA or gas injection. More elevated subretinal blood clots showed a larger increase in size after TPA injection than flat clots (P < 0.05). CONCLUSION: Enlargement of SRH in a gravity-dependent manner indicates subretinal liquefaction of the clot after TPA treatment. An intravitreal injection of gas 24 hours later can significantly displace the SRH inferiorly.

Acute Disease↗